Acne

Dermatophyte infections, commonly referred to as tinea, involve the superficial epidermis and are caused by fungi belonging primarily to the genera Trichophyton, Epidermophyton, and Microsporum.¹ Malassezia are lipophilic yeasts found in the normal skin flora that can overgrow within hair follicles and trigger an inflammatory response. While both fungal infections are associated with several classic clinical features, they can demonstrate variable clinical morphology, especially when modified by previous topical treatments. In such cases, fungal infections may mimic other forms of inflammatory dermatitis and can be misdiagnosed.

Acne vulgaris is one of the most prevalent dermatologic conditions and typically is diagnosed clinically based on characteristic morphology and distribution. Despite their distinct etiologies, dermatophyte infections and acne vulgaris may manifest with overlapping features, particularly in acne-prone regions such as the face, chest, and back, which may result in diagnostic errors and inappropriate management. This review highlights dermatophyte infections as an underrecognized mimic of acne vulgaris, emphasizing key clinical distinguishing features, common diagnostic pitfalls, and a practical approach to evaluation.

Clinical Overlap of Dermatophyte Infections and Acne

Despite their fundamentally different etiologies, dermatophyte infections and acne may demonstrate overlapping clinical morphology and anatomic distribution, creating diagnostic challenges and increasing misdiagnosis risk. Clinically, acne is characterized by the presence of open and closed comedones as well as inflammatory papules, pustules, nodules, and occasionally cysts.² In contrast, dermatophyte infections classically manifest as annular erythematous plaques with peripheral scale and central clearing, primarily due to their superficial confinement to the stratum corneum; however, in certain cases the dermatophyte invades the hair follicle, which can lead to the formation of folliculocentric pustules.¹ This is known as dermatophyte folliculitis and may closely resemble the pustules observed in acne.

Follicular invasion by dermatophytes is more likely in cases in which infection has been misdiagnosed as a noninfectious inflammatory dermatosis, (eg, atopic dermatitis) and treated with topical corticosteroids. Corticosteroid-induced local immunosuppression facilitates deeper and more extensive proliferation of the invading fungus, including into the hair follicle. Topical corticosteroid use may further obscure the diagnosis of a dermatophyte infection by masking its hallmark features such as scale and annularity.³ This steroid-altered dermatophyte infection is referred to as tinea incognita and may be misdiagnosed as acne or another inflammatory dermatosis. When dermatophytes extend from the stratum corneum into the dermis due to local immunosuppression (eg, corticosteroid use), trauma, shaving, or occlusion, the resulting deep follicular infection is known as Majocchi granuloma.

Further complicating the diagnostic picture is the substantial anatomic and epidemiologic overlap between dermatophyte infections and acne vulgaris. Acne preferentially affects sebum-rich areas, including the face, chest, and back.² Dermatophytes, by contrast, thrive in keratinized tissue.¹ Because areas with a higher density of hair follicles contain abundant keratin, dermatophyte infections often involve the same sebum-rich regions affected by acne. Both acne and tinea are observed frequently in adolescents, possibly due to hormonal changes that increase sebum production and create an environment conducive to fungal growth.⁴

Pityrosporum Folliculitis Manifesting as Acne Vulgaris

Although it has been widely popularized in lay and social media, the term fungal acne is a misnomer; this entity more accurately represents a fungal folliculitis manifesting as an acneform eruption. In most cases, fungal acne refers to Malassezia folliculitis, also called pityrosporum folliculitis, which is caused by Malassezia species. Malassezia are not dermatophytes but rather lipophilic yeasts found in the normal skin flora. Whereas dermatophytes are drawn to highly keratinized tissue, Malassezia are drawn to lipid-rich environments of the skin. In these conditions, including sweating and hot or humid environments, Malassezia may proliferate to pathogenic levels within the hair follicle.⁵

Clinically, Malassezia folliculitis manifests as monomorphic, folliculocentric, dome-shaped papules and pustules with occasional progression to nodules or cysts in more severe cases.⁵ Lesions typically are intensely pruritic, a distinguishing feature that helps differentiate them from acne vulgaris.⁶ The eruption predominantly involves sebum-rich areas, including the face, hairline, chest, and upper back (Figure 1).⁵ Overall, the clinical presentation often more closely resembles steroid-induced acne than classic acne vulgaris. Antibiotic exposure is an important risk factor, potentially due to disruption of the normal skin microbiome and subsequent yeast overgrowth; for example, in a retrospective review of 110 patients (age range, 0-21 years) with Malassezia folliculitis, more than 75% had recently received antibiotics for treatment of acne.⁶ Additional predisposing factors include corticosteroid use and immunosuppression.⁵

Importantly, Malassezia folliculitis and acne vulgaris may coexist, further complicating diagnosis. In a study of 217 patients with acne vulgaris, cytologic evaluation demonstrated Malassezia overgrowth (defined as >6 spores per high-power field) in approximately 25% of patients, of whom 70% responded to antifungal therapy.⁷ Similarly, a study of 300 patients with newly diagnosed acne found a prevalence of Malassezia folliculitis of almost 30%. Patients with concurrent Malassezia folliculitis and acne were more likely to report pruritus and have involvement of the scalp, hairline, and upper back compared to those with acne alone.⁸

Tinea Faciei and Tinea Barbae Manifesting as Facial Acne

Tinea faciei describes a dermatophyte infection of the nonbearded area of the face, whereas infection of the beard-bearing region is known as tinea barbae. In North America, Trichophyton species are the leading cause of tinea faciei.¹ Clinically, tinea faciei manifests as one or more erythematous scaly plaques on the face, often associated with pruritus. Lesions often assume an annular shape with an advancing border along which pustules, vesicles, or crusting can be observed. In cases of inappropriate treatment with topical corticosteroids, lesions may lose their characteristic scale and annularity and instead become papular, mimicking the acneform eruptions of facial acne vulgaris (Figure 2).

Like tinea faciei, tinea barbae most commonly develops from infection with Trichophyton species but differs in its clinical presentation. While superficial scaly variants exist, tinea barbae more frequently manifests as a deep, papular, inflammatory folliculitis. This deeper form typically is caused by follicular infiltration by zoophilic dermatophytes such as Trichophyton verrucosum and Microsporum canis. Not surprisingly, infection by these zoophilic dermatophytes is associated with exposure to animals such as cattle, horses, dogs, and cats, and a history of agricultural work may offer a helpful clue to diagnosis.⁹ The tender, nodular, or nodulocystic lesions of severe tinea barbae infections may closely resemble nodulocystic acne.

Misdiagnosis, inappropriate treatment, and diagnostic delays are common in patients with tinea faciei and tinea barbae. In a retrospective study of 818 cases of tinea faciei, approximately 30% of patients had received prior corticosteroid treatment at the time of diagnosis.¹⁰ Similarly, a cross-sectional study of 7 adult patients with tinea barbae in a Portuguese hospital found that 3 cases initially were misdiagnosed and that in 2 cases potent topical steroids were previously applied.¹¹ Finally, in a retrospective review of 38 patients with mycologically confirmed tinea faciei, the mean duration from symptom onset to diagnosis was 3.4 months.¹⁰ Notably, nearly 60% of patients had concomitant dermatophyte infections at other body sites, most commonly involving the feet and toes, highlighting that recognition of dermatophyte infections elsewhere on physical examination may provide an important diagnostic clue.¹²

Tinea Corporis Manifesting as Truncal Acne

Tinea corporis refers to a dermatophyte infection involving the glabrous, or hairless, skin of the trunk and extremities. Trichophyton rubrum accounts for 80% to 90% of the pathogenic strains that cause tinea corporis.¹ As with other variants of superficial dermatophyte infections, tinea corporis classically manifests as annular erythematous plaques with peripheral scale and central clearing, distinguished by its involvement of the trunk. Pruritus of lesions is variable.¹

Inappropriate treatment of tinea corporis with topical corticosteroids may induce a morphologic change in the infection so that it resembles the lesions of truncal acne, which characteristically involves the chest, upper back, and shoulders, and less frequently the lower back and abdomen.² As in other forms of acne vulgaris, the lesions are characterized by a mixture of inflammatory papules, pustules, and comedones. When differentiating tinea corporis and truncal acne, consider the distribution and symmetry of the lesions. Dermatophyte infections often are localized to one area of the trunk and are asymmetric. In contrast, acne typically is generalized and manifests more symmetrically.

Additional clinical clues may aid in differentiation. An acneform eruption involving other seborrheic areas of the body (eg, the face) supports a diagnosis of truncal acne. Conversely, the presence of tinea elsewhere, particularly on the hands or feet, may suggest tinea corporis. Finally, although pustules can be seen with tinea corporis, the presence of true comedones is a key distinguishing factor favoring acne vulgaris.

Importantly, resistant dermatophyte infections have emerged as a growing concern among public health experts over the past decade. A recently described species, Trichophyton indotineae, has played a substantial role in driving these cases.¹³ While early US cases largely were limited to patients who had travelled to Bangladesh, infections now are increasingly reported in individuals without travel history.¹³ Trichophyton indotineae most commonly involves the trunk, extremities, and groin, which mirrors the distribution of truncal acne. Further complicating the clinical picture is the lack of response to standard antifungal therapies such as oral terbinafine in these patients.¹³ Failure to consider this diagnosis, particularly given its recent recognition, may lead physicians to empirically switch treatment to topical or systemic corticosteroids. This can further alter lesion morphology and increase the likelihood of misdiagnosis.

Helpful Bedside Diagnostic Tools

When clinical findings are equivocal, bedside diagnostic tools, including dermoscopy, a Wood lamp, potassium hydroxide (KOH) preparation, and histopathology, may be helpful in differentiating cutaneous fungal infections from acne.

Dermoscopy—In an observational study of 81 patients with fungal folliculitis, dermoscopy demonstrated a diagnostic accuracy of 76.5%.¹⁴ Dermoscopic findings in a cohort of 45 patients with KOH-confirmed Malassezia folliculitis included folliculocentric lesions and background erythema (100%); dotted, linear, or tortuous vessels (89%); fine white scale (78%); perifollicular hypopigmentation (64%); coiled or looped hairs (58%); and broken hairs (13%).¹⁵ Moreover, in a study comparing 36 microscopically confirmed tinea cases with 40 negative cases, peripheral scales (odds ratio [OR], 5.2; 95% CI, 2.0-13.5), moth-eaten scales (OR, 3.9; 95% CI, 1.9-8.1), broken hairs (OR, 5.8; 95% CI, 2.0-16.6), and outward-peeling scales (OR, 14.3; 95% CI, 1.3-155.2) were predictive of tinea.¹⁶ Dermoscopic findings in a cross-sectional study of 100 clinically diagnosed tinea cases included diffuse erythema with whitish scars (100.0%), follicular micropustules (36.7%), brown spots with a white-yellow halo (20.0%), wavy or broken hairs (13.0%), and Morse code– like vellus hairs (3.0%).¹⁷ In tinea incognito, features such as Morse code–like hairs, deformable translucent hairs, comma and corkscrew hairs, and perifollicular scaling may persist despite corticosteroid use.^18,19

Wood Lamp Examination—Wood lamp examination may be a helpful adjunctive tool for diagnosis of Malassezia folliculitis. In a study of 264 patients with folliculitis (49 of whom were diagnosed with Malassezia folliculitis), Wood lamp examination demonstrated yellow-green fluorescence in 66.7% of cases.²⁰ In contrast, this method has limited utility in diagnosing common dermatophyte infections, as only Microsporum and a small subset of Trichophyton species fluoresce.²¹ In a study of 50 pediatric patients with tinea capitis, Microsporum cases were identified via Wood lamp examination by bright green fluorescence. Wood lamp examination demonstrated 73% sensitivity and 100% specificity for Microsporum canis, confirmed by microscopy and culture, indicating that positive results are highly reliable for this genus, though false negatives may occur.²²

Some dermatoscopes incorporate a Wood lamp, enabling UV-induced fluorescence dermoscopy (UVFD). In a study of 208 patients with nonneoplastic dermatoses, UVFD of tinea showed light green hair shaft concretions in 27% (4/15) of patients and no fluorescence in 73% (11/15), whereas Malassezia folliculitis demonstrated blue follicular concretions in 85% (11/13) and acne showed disruption of uniform follicular red fluorescence in 81% (13/16).23 However, these dermatoscopes are not widely available.

KOH Preparation—While the aforementioned tests are useful and require minimal effort, the diagnostic test of choice for cutaneous fungal infections remains the KOH preparation, which is fast and inexpensive and offers immediate results, often while the patient is still in the office. The test should be performed by obtaining scale, ideally from an active lesion border, by gently scraping the stratum corneum, often with a #15 blade. For sampling of pustules or when there is concern for Malassezia folliculitis, optimal technique involves unroofing a pustule and transferring its contents onto a slide for KOH preparation. The specimen then is treated with KOH, a keratolytic agent that dissolves keratinocytes and facilitates visualization of fungal elements under light microscopy. Reported sensitivity and specificity of KOH preparation are approximately 73% and 78%, respectively.²⁴ Notably, sensitivity and specificity of KOH is highly dependent on expertise. A fungal culture also can be collected and sent for microbiologic analysis, although results often are delayed. In one pooled analysis of tinea pedis using clinical assessment as the reference standard, fungal culture demonstrated a sensitivity of 42% and specificity of 78%, though these estimates are highly dependent on study design and sampling technique.²⁴

Histopathology—Finally, histopathologic evaluation may be considered in diagnostically challenging cases. Histology of Malassezia folliculitis demonstrates fungal spores within the follicular lumen, while histology of acne shows irregular keratin plugging, nuclear debris within the follicular lumen, and intrafollicular inflammation. Notably, perifollicular inflammatory infiltrates are histologically similar in acne and Malassezia folliculitis.²⁵

Practical Diagnostic Approach to Differentiating Dermatophyte Infections from Acne

For physicians encountering papulopustular eruptions in acne-prone regions, distinguishing acne vulgaris from dermatophyte infection can be challenging. A stepwise approach incorporating history, morphology, and distribution can improve diagnostic accuracy and guide appropriate management.

First, obtain a thorough treatment history. Presumed acne that has failed to respond to appropriate acne therapies should prompt reconsideration of the diagnosis. Prior treatment with topical corticosteroids should be specifically assessed. Patients may not volunteer this history unless directly asked. Corticosteroid use can alter the clinical appearance of dermatophyte infections, leading to diagnostic confusion.

Second, use morphologic features and lesion distribution as diagnostic clues. The presence of comedones favors acne vulgaris, whereas their absence should raise suspicion for tinea. It is important to note, however, that certain dermatophyte infections may manifest with folliculocentric pustules, which can mimic closed comedones or inflammatory lesions seen in acne. Acne vulgaris also typically demonstrates a bilateral and relatively symmetric distribution, particularly on the face, chest, and upper back. In contrast, dermatophyte infections are more often asymmetric or localized, especially in early stages.

Patient-reported symptoms and a complete skin examination can further aid in differentiation. While acne may occasionally be pruritic, pain or tenderness is more commonly reported. In contrast, dermatophyte infections often will have prominent pruritus, which frequently is the patient’s primary complaint. The presence of tinea on the hands or feet supports a diagnosis of dermatophyte infection, whereas concurrent acneform lesions in classic seborrheic regions favor acne vulgaris. The Table outlines key clinical features that help distinguish dermatophyte infections from acne vulgaris.

When the diagnosis remains unclear after clinical assessment, physicians may utilize both bedside and laboratory tests, including dermoscopy, Wood lamp examination, in-office KOH preparation, and/or fungal culture, as discussed previously. In cases of diagnostic uncertainty, empiric antifungal therapy is preferred over topical corticosteroid therapy, as corticosteroids may exacerbate an underlying dermatophyte infection. In refractory or diagnostically challenging cases, skin biopsy with periodic acid–Schiff staining may be considered to confirm the presence of fungal organisms. Biopsy generally is reserved for cases that fail to respond to empiric therapy or when diagnostic confirmation is strongly desired. Figure 3 provides an algorithmic approach to distinguishing acne vulgaris from dermatophyte infection.

Final Thoughts

Dermatophyte infections are a common but often overlooked mimic of acne vulgaris. Clinically, acne is characterized by comedones, whereas dermatophyte infections typically demonstrate scale, though these features can be less apparent in modified presentations. In cases of diagnostic uncertainty, physicians should keep dermatophyte infections in mind and be comfortable performing bedside KOH preparations to support timely diagnosis. Early recognition is important to reduce morbidity and avoid inappropriate treatments, particularly corticosteroids, which can worsen the infection and delay improvement.

Dermatophyte infections, commonly referred to as tinea, involve the superficial epidermis and are caused by fungi belonging primarily to the genera Trichophyton, Epidermophyton, and Microsporum.¹ Malassezia are lipophilic yeasts found in the normal skin flora that can overgrow within hair follicles and trigger an inflammatory response. While both fungal infections are associated with several classic clinical features, they can demonstrate variable clinical morphology, especially when modified by previous topical treatments. In such cases, fungal infections may mimic other forms of inflammatory dermatitis and can be misdiagnosed.

Acne vulgaris is one of the most prevalent dermatologic conditions and typically is diagnosed clinically based on characteristic morphology and distribution. Despite their distinct etiologies, dermatophyte infections and acne vulgaris may manifest with overlapping features, particularly in acne-prone regions such as the face, chest, and back, which may result in diagnostic errors and inappropriate management. This review highlights dermatophyte infections as an underrecognized mimic of acne vulgaris, emphasizing key clinical distinguishing features, common diagnostic pitfalls, and a practical approach to evaluation.

Clinical Overlap of Dermatophyte Infections and Acne

Despite their fundamentally different etiologies, dermatophyte infections and acne may demonstrate overlapping clinical morphology and anatomic distribution, creating diagnostic challenges and increasing misdiagnosis risk. Clinically, acne is characterized by the presence of open and closed comedones as well as inflammatory papules, pustules, nodules, and occasionally cysts.² In contrast, dermatophyte infections classically manifest as annular erythematous plaques with peripheral scale and central clearing, primarily due to their superficial confinement to the stratum corneum; however, in certain cases the dermatophyte invades the hair follicle, which can lead to the formation of folliculocentric pustules.¹ This is known as dermatophyte folliculitis and may closely resemble the pustules observed in acne.

Follicular invasion by dermatophytes is more likely in cases in which infection has been misdiagnosed as a noninfectious inflammatory dermatosis, (eg, atopic dermatitis) and treated with topical corticosteroids. Corticosteroid-induced local immunosuppression facilitates deeper and more extensive proliferation of the invading fungus, including into the hair follicle. Topical corticosteroid use may further obscure the diagnosis of a dermatophyte infection by masking its hallmark features such as scale and annularity.³ This steroid-altered dermatophyte infection is referred to as tinea incognita and may be misdiagnosed as acne or another inflammatory dermatosis. When dermatophytes extend from the stratum corneum into the dermis due to local immunosuppression (eg, corticosteroid use), trauma, shaving, or occlusion, the resulting deep follicular infection is known as Majocchi granuloma.

Further complicating the diagnostic picture is the substantial anatomic and epidemiologic overlap between dermatophyte infections and acne vulgaris. Acne preferentially affects sebum-rich areas, including the face, chest, and back.² Dermatophytes, by contrast, thrive in keratinized tissue.¹ Because areas with a higher density of hair follicles contain abundant keratin, dermatophyte infections often involve the same sebum-rich regions affected by acne. Both acne and tinea are observed frequently in adolescents, possibly due to hormonal changes that increase sebum production and create an environment conducive to fungal growth.⁴

Pityrosporum Folliculitis Manifesting as Acne Vulgaris

Although it has been widely popularized in lay and social media, the term fungal acne is a misnomer; this entity more accurately represents a fungal folliculitis manifesting as an acneform eruption. In most cases, fungal acne refers to Malassezia folliculitis, also called pityrosporum folliculitis, which is caused by Malassezia species. Malassezia are not dermatophytes but rather lipophilic yeasts found in the normal skin flora. Whereas dermatophytes are drawn to highly keratinized tissue, Malassezia are drawn to lipid-rich environments of the skin. In these conditions, including sweating and hot or humid environments, Malassezia may proliferate to pathogenic levels within the hair follicle.⁵

Clinically, Malassezia folliculitis manifests as monomorphic, folliculocentric, dome-shaped papules and pustules with occasional progression to nodules or cysts in more severe cases.⁵ Lesions typically are intensely pruritic, a distinguishing feature that helps differentiate them from acne vulgaris.⁶ The eruption predominantly involves sebum-rich areas, including the face, hairline, chest, and upper back (Figure 1).⁵ Overall, the clinical presentation often more closely resembles steroid-induced acne than classic acne vulgaris. Antibiotic exposure is an important risk factor, potentially due to disruption of the normal skin microbiome and subsequent yeast overgrowth; for example, in a retrospective review of 110 patients (age range, 0-21 years) with Malassezia folliculitis, more than 75% had recently received antibiotics for treatment of acne.⁶ Additional predisposing factors include corticosteroid use and immunosuppression.⁵

Importantly, Malassezia folliculitis and acne vulgaris may coexist, further complicating diagnosis. In a study of 217 patients with acne vulgaris, cytologic evaluation demonstrated Malassezia overgrowth (defined as >6 spores per high-power field) in approximately 25% of patients, of whom 70% responded to antifungal therapy.⁷ Similarly, a study of 300 patients with newly diagnosed acne found a prevalence of Malassezia folliculitis of almost 30%. Patients with concurrent Malassezia folliculitis and acne were more likely to report pruritus and have involvement of the scalp, hairline, and upper back compared to those with acne alone.⁸

Tinea Faciei and Tinea Barbae Manifesting as Facial Acne

Tinea faciei describes a dermatophyte infection of the nonbearded area of the face, whereas infection of the beard-bearing region is known as tinea barbae. In North America, Trichophyton species are the leading cause of tinea faciei.¹ Clinically, tinea faciei manifests as one or more erythematous scaly plaques on the face, often associated with pruritus. Lesions often assume an annular shape with an advancing border along which pustules, vesicles, or crusting can be observed. In cases of inappropriate treatment with topical corticosteroids, lesions may lose their characteristic scale and annularity and instead become papular, mimicking the acneform eruptions of facial acne vulgaris (Figure 2).

Like tinea faciei, tinea barbae most commonly develops from infection with Trichophyton species but differs in its clinical presentation. While superficial scaly variants exist, tinea barbae more frequently manifests as a deep, papular, inflammatory folliculitis. This deeper form typically is caused by follicular infiltration by zoophilic dermatophytes such as Trichophyton verrucosum and Microsporum canis. Not surprisingly, infection by these zoophilic dermatophytes is associated with exposure to animals such as cattle, horses, dogs, and cats, and a history of agricultural work may offer a helpful clue to diagnosis.⁹ The tender, nodular, or nodulocystic lesions of severe tinea barbae infections may closely resemble nodulocystic acne.

Misdiagnosis, inappropriate treatment, and diagnostic delays are common in patients with tinea faciei and tinea barbae. In a retrospective study of 818 cases of tinea faciei, approximately 30% of patients had received prior corticosteroid treatment at the time of diagnosis.¹⁰ Similarly, a cross-sectional study of 7 adult patients with tinea barbae in a Portuguese hospital found that 3 cases initially were misdiagnosed and that in 2 cases potent topical steroids were previously applied.¹¹ Finally, in a retrospective review of 38 patients with mycologically confirmed tinea faciei, the mean duration from symptom onset to diagnosis was 3.4 months.¹⁰ Notably, nearly 60% of patients had concomitant dermatophyte infections at other body sites, most commonly involving the feet and toes, highlighting that recognition of dermatophyte infections elsewhere on physical examination may provide an important diagnostic clue.¹²

Tinea Corporis Manifesting as Truncal Acne

Tinea corporis refers to a dermatophyte infection involving the glabrous, or hairless, skin of the trunk and extremities. Trichophyton rubrum accounts for 80% to 90% of the pathogenic strains that cause tinea corporis.¹ As with other variants of superficial dermatophyte infections, tinea corporis classically manifests as annular erythematous plaques with peripheral scale and central clearing, distinguished by its involvement of the trunk. Pruritus of lesions is variable.¹

Inappropriate treatment of tinea corporis with topical corticosteroids may induce a morphologic change in the infection so that it resembles the lesions of truncal acne, which characteristically involves the chest, upper back, and shoulders, and less frequently the lower back and abdomen.² As in other forms of acne vulgaris, the lesions are characterized by a mixture of inflammatory papules, pustules, and comedones. When differentiating tinea corporis and truncal acne, consider the distribution and symmetry of the lesions. Dermatophyte infections often are localized to one area of the trunk and are asymmetric. In contrast, acne typically is generalized and manifests more symmetrically.

Additional clinical clues may aid in differentiation. An acneform eruption involving other seborrheic areas of the body (eg, the face) supports a diagnosis of truncal acne. Conversely, the presence of tinea elsewhere, particularly on the hands or feet, may suggest tinea corporis. Finally, although pustules can be seen with tinea corporis, the presence of true comedones is a key distinguishing factor favoring acne vulgaris.

Importantly, resistant dermatophyte infections have emerged as a growing concern among public health experts over the past decade. A recently described species, Trichophyton indotineae, has played a substantial role in driving these cases.¹³ While early US cases largely were limited to patients who had travelled to Bangladesh, infections now are increasingly reported in individuals without travel history.¹³ Trichophyton indotineae most commonly involves the trunk, extremities, and groin, which mirrors the distribution of truncal acne. Further complicating the clinical picture is the lack of response to standard antifungal therapies such as oral terbinafine in these patients.¹³ Failure to consider this diagnosis, particularly given its recent recognition, may lead physicians to empirically switch treatment to topical or systemic corticosteroids. This can further alter lesion morphology and increase the likelihood of misdiagnosis.

Helpful Bedside Diagnostic Tools

When clinical findings are equivocal, bedside diagnostic tools, including dermoscopy, a Wood lamp, potassium hydroxide (KOH) preparation, and histopathology, may be helpful in differentiating cutaneous fungal infections from acne.

Dermoscopy—In an observational study of 81 patients with fungal folliculitis, dermoscopy demonstrated a diagnostic accuracy of 76.5%.¹⁴ Dermoscopic findings in a cohort of 45 patients with KOH-confirmed Malassezia folliculitis included folliculocentric lesions and background erythema (100%); dotted, linear, or tortuous vessels (89%); fine white scale (78%); perifollicular hypopigmentation (64%); coiled or looped hairs (58%); and broken hairs (13%).¹⁵ Moreover, in a study comparing 36 microscopically confirmed tinea cases with 40 negative cases, peripheral scales (odds ratio [OR], 5.2; 95% CI, 2.0-13.5), moth-eaten scales (OR, 3.9; 95% CI, 1.9-8.1), broken hairs (OR, 5.8; 95% CI, 2.0-16.6), and outward-peeling scales (OR, 14.3; 95% CI, 1.3-155.2) were predictive of tinea.¹⁶ Dermoscopic findings in a cross-sectional study of 100 clinically diagnosed tinea cases included diffuse erythema with whitish scars (100.0%), follicular micropustules (36.7%), brown spots with a white-yellow halo (20.0%), wavy or broken hairs (13.0%), and Morse code– like vellus hairs (3.0%).¹⁷ In tinea incognito, features such as Morse code–like hairs, deformable translucent hairs, comma and corkscrew hairs, and perifollicular scaling may persist despite corticosteroid use.^18,19

Wood Lamp Examination—Wood lamp examination may be a helpful adjunctive tool for diagnosis of Malassezia folliculitis. In a study of 264 patients with folliculitis (49 of whom were diagnosed with Malassezia folliculitis), Wood lamp examination demonstrated yellow-green fluorescence in 66.7% of cases.²⁰ In contrast, this method has limited utility in diagnosing common dermatophyte infections, as only Microsporum and a small subset of Trichophyton species fluoresce.²¹ In a study of 50 pediatric patients with tinea capitis, Microsporum cases were identified via Wood lamp examination by bright green fluorescence. Wood lamp examination demonstrated 73% sensitivity and 100% specificity for Microsporum canis, confirmed by microscopy and culture, indicating that positive results are highly reliable for this genus, though false negatives may occur.²²

Some dermatoscopes incorporate a Wood lamp, enabling UV-induced fluorescence dermoscopy (UVFD). In a study of 208 patients with nonneoplastic dermatoses, UVFD of tinea showed light green hair shaft concretions in 27% (4/15) of patients and no fluorescence in 73% (11/15), whereas Malassezia folliculitis demonstrated blue follicular concretions in 85% (11/13) and acne showed disruption of uniform follicular red fluorescence in 81% (13/16).23 However, these dermatoscopes are not widely available.

KOH Preparation—While the aforementioned tests are useful and require minimal effort, the diagnostic test of choice for cutaneous fungal infections remains the KOH preparation, which is fast and inexpensive and offers immediate results, often while the patient is still in the office. The test should be performed by obtaining scale, ideally from an active lesion border, by gently scraping the stratum corneum, often with a #15 blade. For sampling of pustules or when there is concern for Malassezia folliculitis, optimal technique involves unroofing a pustule and transferring its contents onto a slide for KOH preparation. The specimen then is treated with KOH, a keratolytic agent that dissolves keratinocytes and facilitates visualization of fungal elements under light microscopy. Reported sensitivity and specificity of KOH preparation are approximately 73% and 78%, respectively.²⁴ Notably, sensitivity and specificity of KOH is highly dependent on expertise. A fungal culture also can be collected and sent for microbiologic analysis, although results often are delayed. In one pooled analysis of tinea pedis using clinical assessment as the reference standard, fungal culture demonstrated a sensitivity of 42% and specificity of 78%, though these estimates are highly dependent on study design and sampling technique.²⁴

Histopathology—Finally, histopathologic evaluation may be considered in diagnostically challenging cases. Histology of Malassezia folliculitis demonstrates fungal spores within the follicular lumen, while histology of acne shows irregular keratin plugging, nuclear debris within the follicular lumen, and intrafollicular inflammation. Notably, perifollicular inflammatory infiltrates are histologically similar in acne and Malassezia folliculitis.²⁵

Practical Diagnostic Approach to Differentiating Dermatophyte Infections from Acne

For physicians encountering papulopustular eruptions in acne-prone regions, distinguishing acne vulgaris from dermatophyte infection can be challenging. A stepwise approach incorporating history, morphology, and distribution can improve diagnostic accuracy and guide appropriate management.

First, obtain a thorough treatment history. Presumed acne that has failed to respond to appropriate acne therapies should prompt reconsideration of the diagnosis. Prior treatment with topical corticosteroids should be specifically assessed. Patients may not volunteer this history unless directly asked. Corticosteroid use can alter the clinical appearance of dermatophyte infections, leading to diagnostic confusion.

Second, use morphologic features and lesion distribution as diagnostic clues. The presence of comedones favors acne vulgaris, whereas their absence should raise suspicion for tinea. It is important to note, however, that certain dermatophyte infections may manifest with folliculocentric pustules, which can mimic closed comedones or inflammatory lesions seen in acne. Acne vulgaris also typically demonstrates a bilateral and relatively symmetric distribution, particularly on the face, chest, and upper back. In contrast, dermatophyte infections are more often asymmetric or localized, especially in early stages.

Patient-reported symptoms and a complete skin examination can further aid in differentiation. While acne may occasionally be pruritic, pain or tenderness is more commonly reported. In contrast, dermatophyte infections often will have prominent pruritus, which frequently is the patient’s primary complaint. The presence of tinea on the hands or feet supports a diagnosis of dermatophyte infection, whereas concurrent acneform lesions in classic seborrheic regions favor acne vulgaris. The Table outlines key clinical features that help distinguish dermatophyte infections from acne vulgaris.

When the diagnosis remains unclear after clinical assessment, physicians may utilize both bedside and laboratory tests, including dermoscopy, Wood lamp examination, in-office KOH preparation, and/or fungal culture, as discussed previously. In cases of diagnostic uncertainty, empiric antifungal therapy is preferred over topical corticosteroid therapy, as corticosteroids may exacerbate an underlying dermatophyte infection. In refractory or diagnostically challenging cases, skin biopsy with periodic acid–Schiff staining may be considered to confirm the presence of fungal organisms. Biopsy generally is reserved for cases that fail to respond to empiric therapy or when diagnostic confirmation is strongly desired. Figure 3 provides an algorithmic approach to distinguishing acne vulgaris from dermatophyte infection.

Final Thoughts

Dermatophyte infections are a common but often overlooked mimic of acne vulgaris. Clinically, acne is characterized by comedones, whereas dermatophyte infections typically demonstrate scale, though these features can be less apparent in modified presentations. In cases of diagnostic uncertainty, physicians should keep dermatophyte infections in mind and be comfortable performing bedside KOH preparations to support timely diagnosis. Early recognition is important to reduce morbidity and avoid inappropriate treatments, particularly corticosteroids, which can worsen the infection and delay improvement.

Dermatophyte infections, commonly referred to as tinea, involve the superficial epidermis and are caused by fungi belonging primarily to the genera Trichophyton, Epidermophyton, and Microsporum.¹ Malassezia are lipophilic yeasts found in the normal skin flora that can overgrow within hair follicles and trigger an inflammatory response. While both fungal infections are associated with several classic clinical features, they can demonstrate variable clinical morphology, especially when modified by previous topical treatments. In such cases, fungal infections may mimic other forms of inflammatory dermatitis and can be misdiagnosed.

Acne vulgaris is one of the most prevalent dermatologic conditions and typically is diagnosed clinically based on characteristic morphology and distribution. Despite their distinct etiologies, dermatophyte infections and acne vulgaris may manifest with overlapping features, particularly in acne-prone regions such as the face, chest, and back, which may result in diagnostic errors and inappropriate management. This review highlights dermatophyte infections as an underrecognized mimic of acne vulgaris, emphasizing key clinical distinguishing features, common diagnostic pitfalls, and a practical approach to evaluation.

Clinical Overlap of Dermatophyte Infections and Acne

Despite their fundamentally different etiologies, dermatophyte infections and acne may demonstrate overlapping clinical morphology and anatomic distribution, creating diagnostic challenges and increasing misdiagnosis risk. Clinically, acne is characterized by the presence of open and closed comedones as well as inflammatory papules, pustules, nodules, and occasionally cysts.² In contrast, dermatophyte infections classically manifest as annular erythematous plaques with peripheral scale and central clearing, primarily due to their superficial confinement to the stratum corneum; however, in certain cases the dermatophyte invades the hair follicle, which can lead to the formation of folliculocentric pustules.¹ This is known as dermatophyte folliculitis and may closely resemble the pustules observed in acne.

Follicular invasion by dermatophytes is more likely in cases in which infection has been misdiagnosed as a noninfectious inflammatory dermatosis, (eg, atopic dermatitis) and treated with topical corticosteroids. Corticosteroid-induced local immunosuppression facilitates deeper and more extensive proliferation of the invading fungus, including into the hair follicle. Topical corticosteroid use may further obscure the diagnosis of a dermatophyte infection by masking its hallmark features such as scale and annularity.³ This steroid-altered dermatophyte infection is referred to as tinea incognita and may be misdiagnosed as acne or another inflammatory dermatosis. When dermatophytes extend from the stratum corneum into the dermis due to local immunosuppression (eg, corticosteroid use), trauma, shaving, or occlusion, the resulting deep follicular infection is known as Majocchi granuloma.

Further complicating the diagnostic picture is the substantial anatomic and epidemiologic overlap between dermatophyte infections and acne vulgaris. Acne preferentially affects sebum-rich areas, including the face, chest, and back.² Dermatophytes, by contrast, thrive in keratinized tissue.¹ Because areas with a higher density of hair follicles contain abundant keratin, dermatophyte infections often involve the same sebum-rich regions affected by acne. Both acne and tinea are observed frequently in adolescents, possibly due to hormonal changes that increase sebum production and create an environment conducive to fungal growth.⁴

Pityrosporum Folliculitis Manifesting as Acne Vulgaris

Although it has been widely popularized in lay and social media, the term fungal acne is a misnomer; this entity more accurately represents a fungal folliculitis manifesting as an acneform eruption. In most cases, fungal acne refers to Malassezia folliculitis, also called pityrosporum folliculitis, which is caused by Malassezia species. Malassezia are not dermatophytes but rather lipophilic yeasts found in the normal skin flora. Whereas dermatophytes are drawn to highly keratinized tissue, Malassezia are drawn to lipid-rich environments of the skin. In these conditions, including sweating and hot or humid environments, Malassezia may proliferate to pathogenic levels within the hair follicle.⁵

Clinically, Malassezia folliculitis manifests as monomorphic, folliculocentric, dome-shaped papules and pustules with occasional progression to nodules or cysts in more severe cases.⁵ Lesions typically are intensely pruritic, a distinguishing feature that helps differentiate them from acne vulgaris.⁶ The eruption predominantly involves sebum-rich areas, including the face, hairline, chest, and upper back (Figure 1).⁵ Overall, the clinical presentation often more closely resembles steroid-induced acne than classic acne vulgaris. Antibiotic exposure is an important risk factor, potentially due to disruption of the normal skin microbiome and subsequent yeast overgrowth; for example, in a retrospective review of 110 patients (age range, 0-21 years) with Malassezia folliculitis, more than 75% had recently received antibiotics for treatment of acne.⁶ Additional predisposing factors include corticosteroid use and immunosuppression.⁵

Importantly, Malassezia folliculitis and acne vulgaris may coexist, further complicating diagnosis. In a study of 217 patients with acne vulgaris, cytologic evaluation demonstrated Malassezia overgrowth (defined as >6 spores per high-power field) in approximately 25% of patients, of whom 70% responded to antifungal therapy.⁷ Similarly, a study of 300 patients with newly diagnosed acne found a prevalence of Malassezia folliculitis of almost 30%. Patients with concurrent Malassezia folliculitis and acne were more likely to report pruritus and have involvement of the scalp, hairline, and upper back compared to those with acne alone.⁸

Tinea Faciei and Tinea Barbae Manifesting as Facial Acne

Tinea faciei describes a dermatophyte infection of the nonbearded area of the face, whereas infection of the beard-bearing region is known as tinea barbae. In North America, Trichophyton species are the leading cause of tinea faciei.¹ Clinically, tinea faciei manifests as one or more erythematous scaly plaques on the face, often associated with pruritus. Lesions often assume an annular shape with an advancing border along which pustules, vesicles, or crusting can be observed. In cases of inappropriate treatment with topical corticosteroids, lesions may lose their characteristic scale and annularity and instead become papular, mimicking the acneform eruptions of facial acne vulgaris (Figure 2).

Like tinea faciei, tinea barbae most commonly develops from infection with Trichophyton species but differs in its clinical presentation. While superficial scaly variants exist, tinea barbae more frequently manifests as a deep, papular, inflammatory folliculitis. This deeper form typically is caused by follicular infiltration by zoophilic dermatophytes such as Trichophyton verrucosum and Microsporum canis. Not surprisingly, infection by these zoophilic dermatophytes is associated with exposure to animals such as cattle, horses, dogs, and cats, and a history of agricultural work may offer a helpful clue to diagnosis.⁹ The tender, nodular, or nodulocystic lesions of severe tinea barbae infections may closely resemble nodulocystic acne.

Misdiagnosis, inappropriate treatment, and diagnostic delays are common in patients with tinea faciei and tinea barbae. In a retrospective study of 818 cases of tinea faciei, approximately 30% of patients had received prior corticosteroid treatment at the time of diagnosis.¹⁰ Similarly, a cross-sectional study of 7 adult patients with tinea barbae in a Portuguese hospital found that 3 cases initially were misdiagnosed and that in 2 cases potent topical steroids were previously applied.¹¹ Finally, in a retrospective review of 38 patients with mycologically confirmed tinea faciei, the mean duration from symptom onset to diagnosis was 3.4 months.¹⁰ Notably, nearly 60% of patients had concomitant dermatophyte infections at other body sites, most commonly involving the feet and toes, highlighting that recognition of dermatophyte infections elsewhere on physical examination may provide an important diagnostic clue.¹²

Tinea Corporis Manifesting as Truncal Acne

Tinea corporis refers to a dermatophyte infection involving the glabrous, or hairless, skin of the trunk and extremities. Trichophyton rubrum accounts for 80% to 90% of the pathogenic strains that cause tinea corporis.¹ As with other variants of superficial dermatophyte infections, tinea corporis classically manifests as annular erythematous plaques with peripheral scale and central clearing, distinguished by its involvement of the trunk. Pruritus of lesions is variable.¹

Inappropriate treatment of tinea corporis with topical corticosteroids may induce a morphologic change in the infection so that it resembles the lesions of truncal acne, which characteristically involves the chest, upper back, and shoulders, and less frequently the lower back and abdomen.² As in other forms of acne vulgaris, the lesions are characterized by a mixture of inflammatory papules, pustules, and comedones. When differentiating tinea corporis and truncal acne, consider the distribution and symmetry of the lesions. Dermatophyte infections often are localized to one area of the trunk and are asymmetric. In contrast, acne typically is generalized and manifests more symmetrically.

Additional clinical clues may aid in differentiation. An acneform eruption involving other seborrheic areas of the body (eg, the face) supports a diagnosis of truncal acne. Conversely, the presence of tinea elsewhere, particularly on the hands or feet, may suggest tinea corporis. Finally, although pustules can be seen with tinea corporis, the presence of true comedones is a key distinguishing factor favoring acne vulgaris.

Importantly, resistant dermatophyte infections have emerged as a growing concern among public health experts over the past decade. A recently described species, Trichophyton indotineae, has played a substantial role in driving these cases.¹³ While early US cases largely were limited to patients who had travelled to Bangladesh, infections now are increasingly reported in individuals without travel history.¹³ Trichophyton indotineae most commonly involves the trunk, extremities, and groin, which mirrors the distribution of truncal acne. Further complicating the clinical picture is the lack of response to standard antifungal therapies such as oral terbinafine in these patients.¹³ Failure to consider this diagnosis, particularly given its recent recognition, may lead physicians to empirically switch treatment to topical or systemic corticosteroids. This can further alter lesion morphology and increase the likelihood of misdiagnosis.

Helpful Bedside Diagnostic Tools

When clinical findings are equivocal, bedside diagnostic tools, including dermoscopy, a Wood lamp, potassium hydroxide (KOH) preparation, and histopathology, may be helpful in differentiating cutaneous fungal infections from acne.

Dermoscopy—In an observational study of 81 patients with fungal folliculitis, dermoscopy demonstrated a diagnostic accuracy of 76.5%.¹⁴ Dermoscopic findings in a cohort of 45 patients with KOH-confirmed Malassezia folliculitis included folliculocentric lesions and background erythema (100%); dotted, linear, or tortuous vessels (89%); fine white scale (78%); perifollicular hypopigmentation (64%); coiled or looped hairs (58%); and broken hairs (13%).¹⁵ Moreover, in a study comparing 36 microscopically confirmed tinea cases with 40 negative cases, peripheral scales (odds ratio [OR], 5.2; 95% CI, 2.0-13.5), moth-eaten scales (OR, 3.9; 95% CI, 1.9-8.1), broken hairs (OR, 5.8; 95% CI, 2.0-16.6), and outward-peeling scales (OR, 14.3; 95% CI, 1.3-155.2) were predictive of tinea.¹⁶ Dermoscopic findings in a cross-sectional study of 100 clinically diagnosed tinea cases included diffuse erythema with whitish scars (100.0%), follicular micropustules (36.7%), brown spots with a white-yellow halo (20.0%), wavy or broken hairs (13.0%), and Morse code– like vellus hairs (3.0%).¹⁷ In tinea incognito, features such as Morse code–like hairs, deformable translucent hairs, comma and corkscrew hairs, and perifollicular scaling may persist despite corticosteroid use.^18,19

Wood Lamp Examination—Wood lamp examination may be a helpful adjunctive tool for diagnosis of Malassezia folliculitis. In a study of 264 patients with folliculitis (49 of whom were diagnosed with Malassezia folliculitis), Wood lamp examination demonstrated yellow-green fluorescence in 66.7% of cases.²⁰ In contrast, this method has limited utility in diagnosing common dermatophyte infections, as only Microsporum and a small subset of Trichophyton species fluoresce.²¹ In a study of 50 pediatric patients with tinea capitis, Microsporum cases were identified via Wood lamp examination by bright green fluorescence. Wood lamp examination demonstrated 73% sensitivity and 100% specificity for Microsporum canis, confirmed by microscopy and culture, indicating that positive results are highly reliable for this genus, though false negatives may occur.²²

Some dermatoscopes incorporate a Wood lamp, enabling UV-induced fluorescence dermoscopy (UVFD). In a study of 208 patients with nonneoplastic dermatoses, UVFD of tinea showed light green hair shaft concretions in 27% (4/15) of patients and no fluorescence in 73% (11/15), whereas Malassezia folliculitis demonstrated blue follicular concretions in 85% (11/13) and acne showed disruption of uniform follicular red fluorescence in 81% (13/16).23 However, these dermatoscopes are not widely available.

KOH Preparation—While the aforementioned tests are useful and require minimal effort, the diagnostic test of choice for cutaneous fungal infections remains the KOH preparation, which is fast and inexpensive and offers immediate results, often while the patient is still in the office. The test should be performed by obtaining scale, ideally from an active lesion border, by gently scraping the stratum corneum, often with a #15 blade. For sampling of pustules or when there is concern for Malassezia folliculitis, optimal technique involves unroofing a pustule and transferring its contents onto a slide for KOH preparation. The specimen then is treated with KOH, a keratolytic agent that dissolves keratinocytes and facilitates visualization of fungal elements under light microscopy. Reported sensitivity and specificity of KOH preparation are approximately 73% and 78%, respectively.²⁴ Notably, sensitivity and specificity of KOH is highly dependent on expertise. A fungal culture also can be collected and sent for microbiologic analysis, although results often are delayed. In one pooled analysis of tinea pedis using clinical assessment as the reference standard, fungal culture demonstrated a sensitivity of 42% and specificity of 78%, though these estimates are highly dependent on study design and sampling technique.²⁴

Histopathology—Finally, histopathologic evaluation may be considered in diagnostically challenging cases. Histology of Malassezia folliculitis demonstrates fungal spores within the follicular lumen, while histology of acne shows irregular keratin plugging, nuclear debris within the follicular lumen, and intrafollicular inflammation. Notably, perifollicular inflammatory infiltrates are histologically similar in acne and Malassezia folliculitis.²⁵

Practical Diagnostic Approach to Differentiating Dermatophyte Infections from Acne

For physicians encountering papulopustular eruptions in acne-prone regions, distinguishing acne vulgaris from dermatophyte infection can be challenging. A stepwise approach incorporating history, morphology, and distribution can improve diagnostic accuracy and guide appropriate management.

First, obtain a thorough treatment history. Presumed acne that has failed to respond to appropriate acne therapies should prompt reconsideration of the diagnosis. Prior treatment with topical corticosteroids should be specifically assessed. Patients may not volunteer this history unless directly asked. Corticosteroid use can alter the clinical appearance of dermatophyte infections, leading to diagnostic confusion.

Second, use morphologic features and lesion distribution as diagnostic clues. The presence of comedones favors acne vulgaris, whereas their absence should raise suspicion for tinea. It is important to note, however, that certain dermatophyte infections may manifest with folliculocentric pustules, which can mimic closed comedones or inflammatory lesions seen in acne. Acne vulgaris also typically demonstrates a bilateral and relatively symmetric distribution, particularly on the face, chest, and upper back. In contrast, dermatophyte infections are more often asymmetric or localized, especially in early stages.

Patient-reported symptoms and a complete skin examination can further aid in differentiation. While acne may occasionally be pruritic, pain or tenderness is more commonly reported. In contrast, dermatophyte infections often will have prominent pruritus, which frequently is the patient’s primary complaint. The presence of tinea on the hands or feet supports a diagnosis of dermatophyte infection, whereas concurrent acneform lesions in classic seborrheic regions favor acne vulgaris. The Table outlines key clinical features that help distinguish dermatophyte infections from acne vulgaris.

When the diagnosis remains unclear after clinical assessment, physicians may utilize both bedside and laboratory tests, including dermoscopy, Wood lamp examination, in-office KOH preparation, and/or fungal culture, as discussed previously. In cases of diagnostic uncertainty, empiric antifungal therapy is preferred over topical corticosteroid therapy, as corticosteroids may exacerbate an underlying dermatophyte infection. In refractory or diagnostically challenging cases, skin biopsy with periodic acid–Schiff staining may be considered to confirm the presence of fungal organisms. Biopsy generally is reserved for cases that fail to respond to empiric therapy or when diagnostic confirmation is strongly desired. Figure 3 provides an algorithmic approach to distinguishing acne vulgaris from dermatophyte infection.

Final Thoughts

Dermatophyte infections are a common but often overlooked mimic of acne vulgaris. Clinically, acne is characterized by comedones, whereas dermatophyte infections typically demonstrate scale, though these features can be less apparent in modified presentations. In cases of diagnostic uncertainty, physicians should keep dermatophyte infections in mind and be comfortable performing bedside KOH preparations to support timely diagnosis. Early recognition is important to reduce morbidity and avoid inappropriate treatments, particularly corticosteroids, which can worsen the infection and delay improvement.

Acne vulgaris, a chronic inflammatory disease of the pilosebaceous unit, is among the most prevalent dermatologic conditions worldwide. Though symptoms range in severity, patients can experience painful irritation and scarring that can lead to substantial psychological distress and impact quality of life. Cutibacterium acnes plays a central role in acne development through biofilm formation, lipase activity, and activation of innate immune pathways, which together contribute to a cycle of inflammation and comedogenesis.¹

First-line treatments for acne vulgaris include topical benzoyl peroxide, topical retinoids, and topical antibiotics, while oral spironolactone and tetracyclines can be used alongside topical therapies for more extensive disease. Additionally, isotretinoin is generally reserved for severe or refractory cases. While these therapies are effective, each has notable limitations and adverse effects that in some cases limit adherence and efficacy. The most common adverse effects seen with topical acne therapies include irritation and dryness. Systemic therapies such as spironolactone can cause fatigue, dizziness, and birth defects, while prolonged antibiotic use can promote the risk for antimicrobial resistance.²

Hypochlorous acid (HOCl) is a naturally occurring weak acid produced by neutrophils and currently is approved by the US Food and Drug Administration for wound cleansing, burn management, and dermal lesion irrigation. Although it is not approved for the treatment of acne, stabilized HOCl formulations have been used off label in dermatology for this purpose. Interest in HOCl stems from its broad-spectrum antimicrobial activity against C acnes, anti-inflammatory properties, and favorable safety profile. This literature review examines the mechanism of action, clinical evidence, and potential role of HOCl in acne management, contextualizing its use relative to current standard therapies.

Methods

A narrative literature review was conducted to identify and synthesize peer-reviewed evidence on the use of HOCl in dermatology, with emphasis on its potential role in acne management. Searches were performed using PubMed and Scopus databases. Search terms included combinations of hypochlorous acid, acne, acne vulgaris, dermatology, antimicrobial, anti-inflammatory, biofilm, and skin barrier. Eligible publications included original research articles, randomized controlled trials, retrospective studies, preclinical in vitro and in vivo studies, and systematic reviews published in English between January 2000 and December 2024. Titles and abstracts were screened for relevance, and the final selection included 16 peer-reviewed articles that met the inclusion criteria.

Results

Hypochlorous acid exhibits rapid, broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria and fungi. In vitro time-kill assays demonstrated that stabilized HOCl was bactericidal against a variety of pathogens, including methicillin-resistant Staphylococcus aureus, methicillin-sensitive S aureus, Staphylococcus ­epidermidis, Corynebacterium species, Streptococcus ­pyogenes, Pseudomonas aeruginosa, Candida albicans, and C acnes. Specifically, HOCl achieved 99.99% or greater kill within 2 minutes.³ Moreover, HOCl’s antimicrobial efficacy against this panel of organisms was found to be comparable to or greater than that of commonly used antiseptics, including povidone-iodine, chlorhexidine gluconate, and isopropyl alcohol.³ An additional study using HOCl stabilized in 0.9% saline (pH, 3.5-4.0) confirmed its rapid activity across gram-positive, gram-negative, and fungal species, again demonstrating 99.99 % or greater reduction within 1 to 2 minutes of exposure.⁴

Hypochlorous acid also has demonstrated substantial biofilm-disruptive properties. In vitro studies demonstrated that HOCl can penetrate and disrupt early-stage biofilms by oxidizing extracellular polymeric substances and damaging bacterial membranes; however, while HOCl was effective at destroying immature biofilms and preventing biofilm formation, its efficacy against mature, fully established biofilms was more limited.⁵ Thus, topical HOCl may be most effective during the early colonization phase of acne, helping to prevent biofilm maturation and subsequent inflammatory lesion formation. Unlike traditional topical and oral antibiotics, HOCl’s nonspecific oxidative mechanism of action is less likely to contribute to microbial resistance. These findings highlight HOCl as a rapid, broad-spectrum antimicrobial with additional biofilm-disruptive activity, supporting its potential role as an early-intervention therapeutic in acne treatment.

In addition to its antimicrobial effects, HOCl is a potent anti-inflammatory molecule that exerts its anti-inflammatory effects through several mechanisms. HOCl acts as a mast cell membrane stabilizer, inhibiting degranulation. Hypochlorous acid also has been demonstrated to reduce levels of leukotriene B4 and interleukin (IL) 2, which supports that HOCl has both antipruritic and anti-inflammatory properties.⁶ In keratinocytes and immune cells, HOCl has been shown to suppress the transcription of multiple proinflammatory cytokines by oxidizing IκB kinase β, which then prevents the activation of the nuclear factor kappa B (NF-κB) signaling pathway.⁷ Additionally, in a murine model of atopic dermatitis, treatment with HOCl resulted in a downregulation of key proinflammatory and Th2-associated cytokines, including IL-1β, IL-4, IL-6, IL-13, tumor necrosis factor α, thymus and activation-regulated chemokine, thymic stromal lymphopoietin, and IL-31. Parallel in vitro assays revealed that HOCl inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and inhibitor of κB, which inhibits the downstream proinflammatory pathways, thereby elucidating a mechanistic basis for its anti-inflammatory effects.⁸ C acnes has been shown to activate the toll-like receptor 2 pathway on keratinocytes and macrophages, triggering NF-κB–dependent release of IL-1β and tumor necrosis factor α.⁹

By inhibiting these same signaling pathways, HOCl may attenuate the inflammatory response associated with acne lesions while simultaneously reducing microbial load. These combined anti-inflammatory and antimicrobial effects also may contribute to improved healing outcomes. Emerging clinical evidence supports HOCl’s benefit in minimizing scarring and postinflammatory sequelae. A comparative study evaluating a silicone-based scar gel containing HOCl vs silicone gel alone found that the HOCl-containing formulation produced greater improvement in hypertrophic and keloid scar appearance and overall scar texture.¹⁰ These findings suggest that HOCl may have beneficial effects on wound healing and scar remodeling.

In murine models of acute radiation dermatitis, topical HOCl reduced NF-κB–dependent gene expression, decreased epidermal ulceration, and promoted ­re-epithelialization to near-normal histologic appearance.⁷ A double-blind, randomized controlled trial evaluating topical sodium hypochlorite 0.005%, which is a compound in equilibrium with HOCl under physiologic pH, demonstrated a statistically significant reduction in papules among patients with mild to moderate acne after 1 month of treatment (P<.0001). Female participants exhibited greater lesion improvement, suggesting possible hormonal or immunologic modulation of response.¹¹ Although limited in scale, this literature review provides preliminary clinical support for the therapeutic potential of HOCl in the treatment of acne. Collectively, these findings highlight the potential of HOCl as an emerging treatment in acne and other dermatologic conditions.

Comment

Traditional acne therapies include topical agents such as benzoyl peroxide, topical retinoids (eg, tretinoin, adapalene), and salicylic acid, as well as systemic agents such as oral antibiotics, spironolactone, and isotretinoin. While these treatments are effective, their use may be limited by irritation, antibiotic resistance, and systemic adverse effects.

Hypochlorous acid is a potential adjunctive option that acts locally with minimal irritation and without hormonal or systemic activity.¹² Its antimicrobial and anti-inflammatory mechanisms target key pathogenic pathways in acne while maintaining excellent cutaneous tolerability. In a randomized, double-blind, placebo-controlled trial of 89 patients comparing topical HOCl solution with benzoyl peroxide for mild to moderate acne, HOCl demonstrated comparable improvement in lesion counts.¹³ Importantly, no local adverse effects were reported in either group and no dose adjustments were needed during the 12-week treatment period. Although both agents were effective, the absence of irritation with HOCl contrasts with the dryness and erythema frequently associated with benzoyl peroxide.

Additionally, a clinical trial comparing HOCl 0.01% with standard antiseptics, including isopropyl alcohol, povidone-iodine, and chlorhexidine gluconate, showed that HOCl achieved comparable antibacterial reductions while remaining well tolerated and free of facial adverse effects.¹⁴ Similarly, studies evaluating HOCl’s antimicrobial efficacy have confirmed that it is nontoxic to periocular and facial tissues, further supporting its safety for use on delicate skin regions.³ Importantly, in an experimental model evaluating both healthy skin and skin with experimentally induced irritant contact dermatitis, repeated application of an HOCl-based formulation did not impair skin barrier function, underscoring its excellent cutaneous compatibility even under inflammatory conditions.¹⁵ Ultimately, these findings suggest that HOCl offers efficacy comparable to benzoyl peroxide and retinoids while eliminating the irritation and barrier disruption that can limit the use of these first-line agents.

Topical antibiotics such as clindamycin and erythromycin are used widely for their antimicrobial and anti-inflammatory properties but increasingly are undermined by antibiotic resistance. In contrast, HOCl has been shown to reduce bacterial load without altering microbial diversity, supporting its role as a resistance-neutral antimicrobial option for acne management.¹⁶ These characteristics position HOCl as a well-tolerated, resistance-neutral adjunctive treatment that warrants further investigation through larger, controlled trials.

Topical HOCl formulations, particularly those available as sprays or misting solutions, have gained attention on social media for their ease of use and versatility. Although formal studies evaluating adherence or outcomes in this context are currently limited, this emerging consumer trend underscores the perceived convenience of HOCl compared with traditional acne therapies. These formulations can be applied throughout the day, including between exercise and work, supporting adherence among patients with active lifestyles. In contrast to many conventional topical agents that require specific application timing, cleansing routines, or avoidance of cosmetic products, HOCl sprays offer flexible use without disrupting daily activities. These characteristics highlight HOCl’s potential as a user-friendly option that may support consistent application and optimize therapeutic outcomes.

Conclusion

The addition of HOCl to acne treatment regimens offers several potential benefits. Its antimicrobial and anti-inflammatory properties may help prevent new papules and pustules, while its favorable tolerability profile minimizes irritation and systemic adverse effects. Preliminary data also suggest efficacy in androgen-mediated acne, though additional studies are needed to confirm these findings.¹¹ Current evidence remains limited by small sample sizes, short follow-up durations, and a lack of comparative studies among available formulations. Accordingly, HOCl should be considered an adjunctive rather than replacement therapy pending larger studies with longer follow-up.

Acne vulgaris, a chronic inflammatory disease of the pilosebaceous unit, is among the most prevalent dermatologic conditions worldwide. Though symptoms range in severity, patients can experience painful irritation and scarring that can lead to substantial psychological distress and impact quality of life. Cutibacterium acnes plays a central role in acne development through biofilm formation, lipase activity, and activation of innate immune pathways, which together contribute to a cycle of inflammation and comedogenesis.¹

First-line treatments for acne vulgaris include topical benzoyl peroxide, topical retinoids, and topical antibiotics, while oral spironolactone and tetracyclines can be used alongside topical therapies for more extensive disease. Additionally, isotretinoin is generally reserved for severe or refractory cases. While these therapies are effective, each has notable limitations and adverse effects that in some cases limit adherence and efficacy. The most common adverse effects seen with topical acne therapies include irritation and dryness. Systemic therapies such as spironolactone can cause fatigue, dizziness, and birth defects, while prolonged antibiotic use can promote the risk for antimicrobial resistance.²

Hypochlorous acid (HOCl) is a naturally occurring weak acid produced by neutrophils and currently is approved by the US Food and Drug Administration for wound cleansing, burn management, and dermal lesion irrigation. Although it is not approved for the treatment of acne, stabilized HOCl formulations have been used off label in dermatology for this purpose. Interest in HOCl stems from its broad-spectrum antimicrobial activity against C acnes, anti-inflammatory properties, and favorable safety profile. This literature review examines the mechanism of action, clinical evidence, and potential role of HOCl in acne management, contextualizing its use relative to current standard therapies.

Methods

A narrative literature review was conducted to identify and synthesize peer-reviewed evidence on the use of HOCl in dermatology, with emphasis on its potential role in acne management. Searches were performed using PubMed and Scopus databases. Search terms included combinations of hypochlorous acid, acne, acne vulgaris, dermatology, antimicrobial, anti-inflammatory, biofilm, and skin barrier. Eligible publications included original research articles, randomized controlled trials, retrospective studies, preclinical in vitro and in vivo studies, and systematic reviews published in English between January 2000 and December 2024. Titles and abstracts were screened for relevance, and the final selection included 16 peer-reviewed articles that met the inclusion criteria.

Results

Hypochlorous acid exhibits rapid, broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria and fungi. In vitro time-kill assays demonstrated that stabilized HOCl was bactericidal against a variety of pathogens, including methicillin-resistant Staphylococcus aureus, methicillin-sensitive S aureus, Staphylococcus ­epidermidis, Corynebacterium species, Streptococcus ­pyogenes, Pseudomonas aeruginosa, Candida albicans, and C acnes. Specifically, HOCl achieved 99.99% or greater kill within 2 minutes.³ Moreover, HOCl’s antimicrobial efficacy against this panel of organisms was found to be comparable to or greater than that of commonly used antiseptics, including povidone-iodine, chlorhexidine gluconate, and isopropyl alcohol.³ An additional study using HOCl stabilized in 0.9% saline (pH, 3.5-4.0) confirmed its rapid activity across gram-positive, gram-negative, and fungal species, again demonstrating 99.99 % or greater reduction within 1 to 2 minutes of exposure.⁴

Hypochlorous acid also has demonstrated substantial biofilm-disruptive properties. In vitro studies demonstrated that HOCl can penetrate and disrupt early-stage biofilms by oxidizing extracellular polymeric substances and damaging bacterial membranes; however, while HOCl was effective at destroying immature biofilms and preventing biofilm formation, its efficacy against mature, fully established biofilms was more limited.⁵ Thus, topical HOCl may be most effective during the early colonization phase of acne, helping to prevent biofilm maturation and subsequent inflammatory lesion formation. Unlike traditional topical and oral antibiotics, HOCl’s nonspecific oxidative mechanism of action is less likely to contribute to microbial resistance. These findings highlight HOCl as a rapid, broad-spectrum antimicrobial with additional biofilm-disruptive activity, supporting its potential role as an early-intervention therapeutic in acne treatment.

In addition to its antimicrobial effects, HOCl is a potent anti-inflammatory molecule that exerts its anti-inflammatory effects through several mechanisms. HOCl acts as a mast cell membrane stabilizer, inhibiting degranulation. Hypochlorous acid also has been demonstrated to reduce levels of leukotriene B4 and interleukin (IL) 2, which supports that HOCl has both antipruritic and anti-inflammatory properties.⁶ In keratinocytes and immune cells, HOCl has been shown to suppress the transcription of multiple proinflammatory cytokines by oxidizing IκB kinase β, which then prevents the activation of the nuclear factor kappa B (NF-κB) signaling pathway.⁷ Additionally, in a murine model of atopic dermatitis, treatment with HOCl resulted in a downregulation of key proinflammatory and Th2-associated cytokines, including IL-1β, IL-4, IL-6, IL-13, tumor necrosis factor α, thymus and activation-regulated chemokine, thymic stromal lymphopoietin, and IL-31. Parallel in vitro assays revealed that HOCl inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and inhibitor of κB, which inhibits the downstream proinflammatory pathways, thereby elucidating a mechanistic basis for its anti-inflammatory effects.⁸ C acnes has been shown to activate the toll-like receptor 2 pathway on keratinocytes and macrophages, triggering NF-κB–dependent release of IL-1β and tumor necrosis factor α.⁹

By inhibiting these same signaling pathways, HOCl may attenuate the inflammatory response associated with acne lesions while simultaneously reducing microbial load. These combined anti-inflammatory and antimicrobial effects also may contribute to improved healing outcomes. Emerging clinical evidence supports HOCl’s benefit in minimizing scarring and postinflammatory sequelae. A comparative study evaluating a silicone-based scar gel containing HOCl vs silicone gel alone found that the HOCl-containing formulation produced greater improvement in hypertrophic and keloid scar appearance and overall scar texture.¹⁰ These findings suggest that HOCl may have beneficial effects on wound healing and scar remodeling.

In murine models of acute radiation dermatitis, topical HOCl reduced NF-κB–dependent gene expression, decreased epidermal ulceration, and promoted ­re-epithelialization to near-normal histologic appearance.⁷ A double-blind, randomized controlled trial evaluating topical sodium hypochlorite 0.005%, which is a compound in equilibrium with HOCl under physiologic pH, demonstrated a statistically significant reduction in papules among patients with mild to moderate acne after 1 month of treatment (P<.0001). Female participants exhibited greater lesion improvement, suggesting possible hormonal or immunologic modulation of response.¹¹ Although limited in scale, this literature review provides preliminary clinical support for the therapeutic potential of HOCl in the treatment of acne. Collectively, these findings highlight the potential of HOCl as an emerging treatment in acne and other dermatologic conditions.

Comment

Traditional acne therapies include topical agents such as benzoyl peroxide, topical retinoids (eg, tretinoin, adapalene), and salicylic acid, as well as systemic agents such as oral antibiotics, spironolactone, and isotretinoin. While these treatments are effective, their use may be limited by irritation, antibiotic resistance, and systemic adverse effects.

Hypochlorous acid is a potential adjunctive option that acts locally with minimal irritation and without hormonal or systemic activity.¹² Its antimicrobial and anti-inflammatory mechanisms target key pathogenic pathways in acne while maintaining excellent cutaneous tolerability. In a randomized, double-blind, placebo-controlled trial of 89 patients comparing topical HOCl solution with benzoyl peroxide for mild to moderate acne, HOCl demonstrated comparable improvement in lesion counts.¹³ Importantly, no local adverse effects were reported in either group and no dose adjustments were needed during the 12-week treatment period. Although both agents were effective, the absence of irritation with HOCl contrasts with the dryness and erythema frequently associated with benzoyl peroxide.

Additionally, a clinical trial comparing HOCl 0.01% with standard antiseptics, including isopropyl alcohol, povidone-iodine, and chlorhexidine gluconate, showed that HOCl achieved comparable antibacterial reductions while remaining well tolerated and free of facial adverse effects.¹⁴ Similarly, studies evaluating HOCl’s antimicrobial efficacy have confirmed that it is nontoxic to periocular and facial tissues, further supporting its safety for use on delicate skin regions.³ Importantly, in an experimental model evaluating both healthy skin and skin with experimentally induced irritant contact dermatitis, repeated application of an HOCl-based formulation did not impair skin barrier function, underscoring its excellent cutaneous compatibility even under inflammatory conditions.¹⁵ Ultimately, these findings suggest that HOCl offers efficacy comparable to benzoyl peroxide and retinoids while eliminating the irritation and barrier disruption that can limit the use of these first-line agents.

Topical antibiotics such as clindamycin and erythromycin are used widely for their antimicrobial and anti-inflammatory properties but increasingly are undermined by antibiotic resistance. In contrast, HOCl has been shown to reduce bacterial load without altering microbial diversity, supporting its role as a resistance-neutral antimicrobial option for acne management.¹⁶ These characteristics position HOCl as a well-tolerated, resistance-neutral adjunctive treatment that warrants further investigation through larger, controlled trials.

Topical HOCl formulations, particularly those available as sprays or misting solutions, have gained attention on social media for their ease of use and versatility. Although formal studies evaluating adherence or outcomes in this context are currently limited, this emerging consumer trend underscores the perceived convenience of HOCl compared with traditional acne therapies. These formulations can be applied throughout the day, including between exercise and work, supporting adherence among patients with active lifestyles. In contrast to many conventional topical agents that require specific application timing, cleansing routines, or avoidance of cosmetic products, HOCl sprays offer flexible use without disrupting daily activities. These characteristics highlight HOCl’s potential as a user-friendly option that may support consistent application and optimize therapeutic outcomes.

Conclusion

The addition of HOCl to acne treatment regimens offers several potential benefits. Its antimicrobial and anti-inflammatory properties may help prevent new papules and pustules, while its favorable tolerability profile minimizes irritation and systemic adverse effects. Preliminary data also suggest efficacy in androgen-mediated acne, though additional studies are needed to confirm these findings.¹¹ Current evidence remains limited by small sample sizes, short follow-up durations, and a lack of comparative studies among available formulations. Accordingly, HOCl should be considered an adjunctive rather than replacement therapy pending larger studies with longer follow-up.

Acne vulgaris, a chronic inflammatory disease of the pilosebaceous unit, is among the most prevalent dermatologic conditions worldwide. Though symptoms range in severity, patients can experience painful irritation and scarring that can lead to substantial psychological distress and impact quality of life. Cutibacterium acnes plays a central role in acne development through biofilm formation, lipase activity, and activation of innate immune pathways, which together contribute to a cycle of inflammation and comedogenesis.¹

First-line treatments for acne vulgaris include topical benzoyl peroxide, topical retinoids, and topical antibiotics, while oral spironolactone and tetracyclines can be used alongside topical therapies for more extensive disease. Additionally, isotretinoin is generally reserved for severe or refractory cases. While these therapies are effective, each has notable limitations and adverse effects that in some cases limit adherence and efficacy. The most common adverse effects seen with topical acne therapies include irritation and dryness. Systemic therapies such as spironolactone can cause fatigue, dizziness, and birth defects, while prolonged antibiotic use can promote the risk for antimicrobial resistance.²

Hypochlorous acid (HOCl) is a naturally occurring weak acid produced by neutrophils and currently is approved by the US Food and Drug Administration for wound cleansing, burn management, and dermal lesion irrigation. Although it is not approved for the treatment of acne, stabilized HOCl formulations have been used off label in dermatology for this purpose. Interest in HOCl stems from its broad-spectrum antimicrobial activity against C acnes, anti-inflammatory properties, and favorable safety profile. This literature review examines the mechanism of action, clinical evidence, and potential role of HOCl in acne management, contextualizing its use relative to current standard therapies.

Methods

A narrative literature review was conducted to identify and synthesize peer-reviewed evidence on the use of HOCl in dermatology, with emphasis on its potential role in acne management. Searches were performed using PubMed and Scopus databases. Search terms included combinations of hypochlorous acid, acne, acne vulgaris, dermatology, antimicrobial, anti-inflammatory, biofilm, and skin barrier. Eligible publications included original research articles, randomized controlled trials, retrospective studies, preclinical in vitro and in vivo studies, and systematic reviews published in English between January 2000 and December 2024. Titles and abstracts were screened for relevance, and the final selection included 16 peer-reviewed articles that met the inclusion criteria.

Results

Hypochlorous acid exhibits rapid, broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria and fungi. In vitro time-kill assays demonstrated that stabilized HOCl was bactericidal against a variety of pathogens, including methicillin-resistant Staphylococcus aureus, methicillin-sensitive S aureus, Staphylococcus ­epidermidis, Corynebacterium species, Streptococcus ­pyogenes, Pseudomonas aeruginosa, Candida albicans, and C acnes. Specifically, HOCl achieved 99.99% or greater kill within 2 minutes.³ Moreover, HOCl’s antimicrobial efficacy against this panel of organisms was found to be comparable to or greater than that of commonly used antiseptics, including povidone-iodine, chlorhexidine gluconate, and isopropyl alcohol.³ An additional study using HOCl stabilized in 0.9% saline (pH, 3.5-4.0) confirmed its rapid activity across gram-positive, gram-negative, and fungal species, again demonstrating 99.99 % or greater reduction within 1 to 2 minutes of exposure.⁴

Hypochlorous acid also has demonstrated substantial biofilm-disruptive properties. In vitro studies demonstrated that HOCl can penetrate and disrupt early-stage biofilms by oxidizing extracellular polymeric substances and damaging bacterial membranes; however, while HOCl was effective at destroying immature biofilms and preventing biofilm formation, its efficacy against mature, fully established biofilms was more limited.⁵ Thus, topical HOCl may be most effective during the early colonization phase of acne, helping to prevent biofilm maturation and subsequent inflammatory lesion formation. Unlike traditional topical and oral antibiotics, HOCl’s nonspecific oxidative mechanism of action is less likely to contribute to microbial resistance. These findings highlight HOCl as a rapid, broad-spectrum antimicrobial with additional biofilm-disruptive activity, supporting its potential role as an early-intervention therapeutic in acne treatment.

In addition to its antimicrobial effects, HOCl is a potent anti-inflammatory molecule that exerts its anti-inflammatory effects through several mechanisms. HOCl acts as a mast cell membrane stabilizer, inhibiting degranulation. Hypochlorous acid also has been demonstrated to reduce levels of leukotriene B4 and interleukin (IL) 2, which supports that HOCl has both antipruritic and anti-inflammatory properties.⁶ In keratinocytes and immune cells, HOCl has been shown to suppress the transcription of multiple proinflammatory cytokines by oxidizing IκB kinase β, which then prevents the activation of the nuclear factor kappa B (NF-κB) signaling pathway.⁷ Additionally, in a murine model of atopic dermatitis, treatment with HOCl resulted in a downregulation of key proinflammatory and Th2-associated cytokines, including IL-1β, IL-4, IL-6, IL-13, tumor necrosis factor α, thymus and activation-regulated chemokine, thymic stromal lymphopoietin, and IL-31. Parallel in vitro assays revealed that HOCl inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and inhibitor of κB, which inhibits the downstream proinflammatory pathways, thereby elucidating a mechanistic basis for its anti-inflammatory effects.⁸ C acnes has been shown to activate the toll-like receptor 2 pathway on keratinocytes and macrophages, triggering NF-κB–dependent release of IL-1β and tumor necrosis factor α.⁹

By inhibiting these same signaling pathways, HOCl may attenuate the inflammatory response associated with acne lesions while simultaneously reducing microbial load. These combined anti-inflammatory and antimicrobial effects also may contribute to improved healing outcomes. Emerging clinical evidence supports HOCl’s benefit in minimizing scarring and postinflammatory sequelae. A comparative study evaluating a silicone-based scar gel containing HOCl vs silicone gel alone found that the HOCl-containing formulation produced greater improvement in hypertrophic and keloid scar appearance and overall scar texture.¹⁰ These findings suggest that HOCl may have beneficial effects on wound healing and scar remodeling.

In murine models of acute radiation dermatitis, topical HOCl reduced NF-κB–dependent gene expression, decreased epidermal ulceration, and promoted ­re-epithelialization to near-normal histologic appearance.⁷ A double-blind, randomized controlled trial evaluating topical sodium hypochlorite 0.005%, which is a compound in equilibrium with HOCl under physiologic pH, demonstrated a statistically significant reduction in papules among patients with mild to moderate acne after 1 month of treatment (P<.0001). Female participants exhibited greater lesion improvement, suggesting possible hormonal or immunologic modulation of response.¹¹ Although limited in scale, this literature review provides preliminary clinical support for the therapeutic potential of HOCl in the treatment of acne. Collectively, these findings highlight the potential of HOCl as an emerging treatment in acne and other dermatologic conditions.

Comment

Traditional acne therapies include topical agents such as benzoyl peroxide, topical retinoids (eg, tretinoin, adapalene), and salicylic acid, as well as systemic agents such as oral antibiotics, spironolactone, and isotretinoin. While these treatments are effective, their use may be limited by irritation, antibiotic resistance, and systemic adverse effects.

Hypochlorous acid is a potential adjunctive option that acts locally with minimal irritation and without hormonal or systemic activity.¹² Its antimicrobial and anti-inflammatory mechanisms target key pathogenic pathways in acne while maintaining excellent cutaneous tolerability. In a randomized, double-blind, placebo-controlled trial of 89 patients comparing topical HOCl solution with benzoyl peroxide for mild to moderate acne, HOCl demonstrated comparable improvement in lesion counts.¹³ Importantly, no local adverse effects were reported in either group and no dose adjustments were needed during the 12-week treatment period. Although both agents were effective, the absence of irritation with HOCl contrasts with the dryness and erythema frequently associated with benzoyl peroxide.

Additionally, a clinical trial comparing HOCl 0.01% with standard antiseptics, including isopropyl alcohol, povidone-iodine, and chlorhexidine gluconate, showed that HOCl achieved comparable antibacterial reductions while remaining well tolerated and free of facial adverse effects.¹⁴ Similarly, studies evaluating HOCl’s antimicrobial efficacy have confirmed that it is nontoxic to periocular and facial tissues, further supporting its safety for use on delicate skin regions.³ Importantly, in an experimental model evaluating both healthy skin and skin with experimentally induced irritant contact dermatitis, repeated application of an HOCl-based formulation did not impair skin barrier function, underscoring its excellent cutaneous compatibility even under inflammatory conditions.¹⁵ Ultimately, these findings suggest that HOCl offers efficacy comparable to benzoyl peroxide and retinoids while eliminating the irritation and barrier disruption that can limit the use of these first-line agents.

Topical antibiotics such as clindamycin and erythromycin are used widely for their antimicrobial and anti-inflammatory properties but increasingly are undermined by antibiotic resistance. In contrast, HOCl has been shown to reduce bacterial load without altering microbial diversity, supporting its role as a resistance-neutral antimicrobial option for acne management.¹⁶ These characteristics position HOCl as a well-tolerated, resistance-neutral adjunctive treatment that warrants further investigation through larger, controlled trials.

Topical HOCl formulations, particularly those available as sprays or misting solutions, have gained attention on social media for their ease of use and versatility. Although formal studies evaluating adherence or outcomes in this context are currently limited, this emerging consumer trend underscores the perceived convenience of HOCl compared with traditional acne therapies. These formulations can be applied throughout the day, including between exercise and work, supporting adherence among patients with active lifestyles. In contrast to many conventional topical agents that require specific application timing, cleansing routines, or avoidance of cosmetic products, HOCl sprays offer flexible use without disrupting daily activities. These characteristics highlight HOCl’s potential as a user-friendly option that may support consistent application and optimize therapeutic outcomes.

Conclusion

The addition of HOCl to acne treatment regimens offers several potential benefits. Its antimicrobial and anti-inflammatory properties may help prevent new papules and pustules, while its favorable tolerability profile minimizes irritation and systemic adverse effects. Preliminary data also suggest efficacy in androgen-mediated acne, though additional studies are needed to confirm these findings.¹¹ Current evidence remains limited by small sample sizes, short follow-up durations, and a lack of comparative studies among available formulations. Accordingly, HOCl should be considered an adjunctive rather than replacement therapy pending larger studies with longer follow-up.

To the Editor:

Isotretinoin is the most effective treatment option for acne vulgaris and is considered the first-line therapy for severe scarring acne.^1-3 Isotretinoin therapy is indicated for moderate acne when other treatments have failed or when the condition causes distress.³ While there are treatment guidelines for moderate to severe acne, there is no gold standard, and most treatment options include a combination of topical and/or oral therapies.⁴ Isotretinoin is one of the few monotherapy options available, but its use often is limited by concerns for severe internal and external birth defects if taken during pregnancy.

To manage teratogenicity risks associated with isotretinoin, the US Food and Drug Administration implemented the iPLEDGE Risk Evaluation and Mitigation Strategy in 2006.⁵ The iPLEDGE compliance requirements differ vastly depending on the reproductive potential of the patient, and the process of obtaining an isotretinoin prescription is much more cumbersome for patients who can get pregnant. Previous studies have demonstrated that males are more likely to be prescribed isotretinoin compared to females, even though females attended more acne-related office visits than males.^6,7 Additionally, the administrative burden of iPLEDGE may influence the prescribing patterns of isotretinoin. In a survey of 510 dermatologists, approximately 30% reported that they have at times chosen not to prescribe isotretinoin to patients with severe acne due to the administrative burden of iPLEDGE.⁸ In this study, we sought to further analyze the prescribing patterns of isotretinoin based on a patient’s reproductive potential.

In this single-center, retrospective cohort study, electronic medical records from 3292 patients diagnosed with acne vulgaris at the Department of Dermatology at Rush University Medical Center (Chicago, Illinois) between January 2013 and December 2019 were reviewed. A total of 188 patients who were prescribed isotretinoin for acne were identified, but only 171 met the study criteria. Eligible patients were aged 12 to 25 years and were prescribed oral isotretinoin for acne vulgaris during the study period. Patients younger than 12 or older than 25 years, those who were prescribed isotretinoin for indications other than acne vulgaris, and those who had previously received isotretinoin and either initiated an additional course or continued treatment at our institution were excluded. Eligible patients then were grouped by reproductive potential: patients who can get pregnant (positive reproductive potential [RP+]) and patients who cannot get pregnant (negative reproductive potential [RP–]). The number of months from initial acne visit, total number of office visits attended, and number of alternative medications that failed before isotretinoin therapy was discussed and initiated were compared between the 2 groups. To standardize between groups, the office visit at which patients were enrolled in iPLEDGE served as the date that isotretinoin therapy was initiated. Alternative medication type and sex of the prescriber were evaluated as secondary end points.

Eighty-nine RP+ patients and 82 RP– patients were prescribed isotretinoin for acne, including 85 females, 2 transgender males with female reproductive organs, 2 females with a history of tubal ligation, and 82 males. Of note, the iPLEDGE program considers tubal ligation as a primary form of contraception and classifies these patients as RP+. Patient demographics are summarized in eTable 1. There was a higher proportion of RP– patients aged 10 to 20 years compared to RP+ patients, for whom there was a higher number of patients aged 21 to 30 years. Most RP+ patients were White, while most RP– patients were Hispanic/Latino.

Overall isotretinoin prescribing patterns as well as prescribing patterns stratified by reproductive potential are presented in eTable 2. Overall, the average number of months before isotretinoin was discussed as a treatment option was 11.5 months and before isotretinoin therapy was initiated was 15 months. There was no significant difference between the number of months before isotretinoin was discussed (P=.83) or initiated (P=.56) between RP+ and RP– patients. On average, patients attended 2 office visits before isotretinoin was discussed as a treatment option and 3 office visits before isotretinoin therapy was initiated. The difference between the number of office visits patients attended before isotretinoin was discussed (P=.44) and before isotretinoin therapy was initiated (P=.11) was not significant between RP+ and RP– patients. The number of alternative medications that failed before initiation of isotretinoin therapy was comparable between groups. Patients in the RP– group experienced failure with an average of 5 alternative medications compared with 6 alternative medications in the RP+ group (P=.48).

As shown in eTable 3, oral antibiotic therapy commonly was prescribed prior to isotretinoin in both groups, with doxycycline being prescribed most often. Hormonal therapy, including oral contraceptives and spironolactone, was trialed in 55 of 87 (63.2%) RP+ patients. Most patients experienced failure with other oral antiacne medications before isotretinoin therapy, with only 6 (6.7%) RP+ and 5 (6.1%) RP– patients trying topical therapy only. Prior isotretinoin therapy was documented in 13 (14.6%) RP+ patients compared with only 5 (6.1%) RP– patients. Interestingly, isotretinoin was initiated at the patient’s first office visit more often in the RP+ group.

At the time isotretinoin therapy was initiated, the sex of the prescribing provider was similar within the RP+ group, with 52% (46/89) of female and 48% (43/89) of male prescribers. In the RP– group, there was a slightly higher proportion of male prescribers, with 57% (47/82) male compared to 43% (35/82) female prescribers.

iPLEDGE (https://ipledgeprogram.com) is an online system mandated by the US Food and Drug Administration to be used by patients, physicians, and pharmacists for the duration of isotretinoin therapy to prevent and track isotretinoin-associated pregnancies.⁹ At its inception, the iPLEDGE program categorized patients as females of child-bearing potential, females not of child-bearing potential, or males. The program recently moved toward transgender-inclusive categorization of patients based on reproductive potential.¹⁰ Patients who can get pregnant include cisgender females and transgender males, and patients who cannot get pregnant include cisgender males, transgender females, and females and transgender males who have undergone a hysterectomy or bilateral oophorectomy or who are postmenopausal.⁹

The iPLEDGE compliance requirements for patients who can get pregnant are extensive. Patients with reproductive potential must obtain a negative baseline pregnancy test, enroll in iPLEDGE, undergo a 30-day waiting period, and obtain a second negative pregnancy test before they can start the medication. Each month thereafter, patients must obtain a negative pregnancy test, demonstrate risk comprehension, and report their methods of contraception on iPLEDGE before they can pick up their prescription. In addition, physicians and pharmacists must confirm patient counseling and obtain authorization codes from iPLEDGE to dispense the medication. If any of these steps are not completed by the patient, physician, or pharmacist within 7 days of the patient’s negative pregnancy test, all steps must be repeated by all parties.^9,11

The efficacy and utility of iPLEDGE have been criticized and debated in the literature. Although there has been a general decrease in the number of fetal exposures to isotretinoin since the implementation of iPLEDGE in 2006, the average number of fetal exposures only decreased for 2 years until it plateaued in 2008.⁵ Some physicians have argued that the decrease in the number of fetal exposures is not attributed to the efficacy of iPLEDGE but rather because the program has made it difficult for patients who can get pregnant to obtain necessary isotretinoin prescriptions.¹² Other physicians have reported that they have chosen not to prescribe isotretinoin due to the administrative burden of iPLEDGE.⁸ Although we expected to observe similar trends in our study, we ultimately had more eligible patients with reproductive potential than patients who could not get pregnant. Additionally, there was no difference in the number of months from initial acne visit, total number of office visits, and number of alternative medications that failed before isotretinoin initiation between patients who could and could not get pregnant. These findings suggest that iPLEDGE requirements did not dissuade prescribers from treating acne with isotretinoin in patients who could get pregnant and that the prescribing patterns of isotretinoin were similar regardless of reproductive potential.

Across all primary outcomes, the standard deviation was high in the overall dataset and in the RP– and RP+ subsets, indicating substantial variability in number of months from initial acne visit, total number of visits, and number of alternative medications that failed prior to initiation of isotretinoin. This implies that the prescribing patterns of isotretinoin may be patient and prescriber dependent, and other variables may influence these outcomes aside from the reproductive potential of the patient. Although there was a marginally higher percentage of male prescribers in the RP– group, the sex of the prescriber did not seem to have a major impact on the prescribing patterns of isotretinoin. Further research is indicated to investigate the impact of other factors that may influence the prescribing patterns of isotretinoin, including insurance coverage, access to contraception, and patient concerns about adverse effects.

The types of alternative medications that patients tried prior to isotretinoin were similar among patients who could get pregnant and patients who could not get pregnant. Hormonal therapy, including oral contraception pills and spironolactone, can be very effective in treating acne in patients with reproductive potential,¹³ as evidenced by the 55 (31.1%) prescriptions written for hormonal therapy in the RP+ group. Spironolactone for acne is contraindicated in male patients due to its antiandrogenic properties and risk for gynecomastia.¹⁴ As such, males have fewer alternative medication options for acne, and this may contribute to the higher prevalence of isotretinoin therapy in males that has been demonstrated in prior studies.^6,7 Of note, patients obtained more than 100 prescriptions for oral antimicrobials in both groups. Although patients can see benefit with oral antimicrobials for acne, the volume of antimicrobial prescriptions seen in our cohort raises concerns about antibiotic stewardship.¹⁵ Whether isotretinoin is a safer therapeutic option compared to antibiotics is up for debate.^2,16

Our study included a small sample size at a single institution, which may limit the external validity of our results. Additionally, our study focused on patients who were prescribed isotretinoin prior to 2020 to control for the influence of the COVID-19 pandemic on prescribing patterns. With this, our data may not reflect postpandemic prescribing trends. Further multi-institution studies that include postpandemic patient cohorts can be conducted to validate our findings.

There were no significant differences in the number of months from initial acne visit, total number of office visits, and number of alternative medications that failed prior to discussing isotretinoin as a treatment option or initiating isotretinoin therapy between patients who can get pregnant and those who cannot get pregnant. We observed substantial variability in these outcomes across datasets, indicating that the prescribing patterns of isotretinoin may be patient and prescriber dependent regardless of the reproductive potential of the patient. Follow-up studies are warranted to further investigate the specific influence of iPLEDGE on the utilization of isotretinoin.

To the Editor:

Isotretinoin is the most effective treatment option for acne vulgaris and is considered the first-line therapy for severe scarring acne.^1-3 Isotretinoin therapy is indicated for moderate acne when other treatments have failed or when the condition causes distress.³ While there are treatment guidelines for moderate to severe acne, there is no gold standard, and most treatment options include a combination of topical and/or oral therapies.⁴ Isotretinoin is one of the few monotherapy options available, but its use often is limited by concerns for severe internal and external birth defects if taken during pregnancy.

To manage teratogenicity risks associated with isotretinoin, the US Food and Drug Administration implemented the iPLEDGE Risk Evaluation and Mitigation Strategy in 2006.⁵ The iPLEDGE compliance requirements differ vastly depending on the reproductive potential of the patient, and the process of obtaining an isotretinoin prescription is much more cumbersome for patients who can get pregnant. Previous studies have demonstrated that males are more likely to be prescribed isotretinoin compared to females, even though females attended more acne-related office visits than males.^6,7 Additionally, the administrative burden of iPLEDGE may influence the prescribing patterns of isotretinoin. In a survey of 510 dermatologists, approximately 30% reported that they have at times chosen not to prescribe isotretinoin to patients with severe acne due to the administrative burden of iPLEDGE.⁸ In this study, we sought to further analyze the prescribing patterns of isotretinoin based on a patient’s reproductive potential.

In this single-center, retrospective cohort study, electronic medical records from 3292 patients diagnosed with acne vulgaris at the Department of Dermatology at Rush University Medical Center (Chicago, Illinois) between January 2013 and December 2019 were reviewed. A total of 188 patients who were prescribed isotretinoin for acne were identified, but only 171 met the study criteria. Eligible patients were aged 12 to 25 years and were prescribed oral isotretinoin for acne vulgaris during the study period. Patients younger than 12 or older than 25 years, those who were prescribed isotretinoin for indications other than acne vulgaris, and those who had previously received isotretinoin and either initiated an additional course or continued treatment at our institution were excluded. Eligible patients then were grouped by reproductive potential: patients who can get pregnant (positive reproductive potential [RP+]) and patients who cannot get pregnant (negative reproductive potential [RP–]). The number of months from initial acne visit, total number of office visits attended, and number of alternative medications that failed before isotretinoin therapy was discussed and initiated were compared between the 2 groups. To standardize between groups, the office visit at which patients were enrolled in iPLEDGE served as the date that isotretinoin therapy was initiated. Alternative medication type and sex of the prescriber were evaluated as secondary end points.

Eighty-nine RP+ patients and 82 RP– patients were prescribed isotretinoin for acne, including 85 females, 2 transgender males with female reproductive organs, 2 females with a history of tubal ligation, and 82 males. Of note, the iPLEDGE program considers tubal ligation as a primary form of contraception and classifies these patients as RP+. Patient demographics are summarized in eTable 1. There was a higher proportion of RP– patients aged 10 to 20 years compared to RP+ patients, for whom there was a higher number of patients aged 21 to 30 years. Most RP+ patients were White, while most RP– patients were Hispanic/Latino.

Overall isotretinoin prescribing patterns as well as prescribing patterns stratified by reproductive potential are presented in eTable 2. Overall, the average number of months before isotretinoin was discussed as a treatment option was 11.5 months and before isotretinoin therapy was initiated was 15 months. There was no significant difference between the number of months before isotretinoin was discussed (P=.83) or initiated (P=.56) between RP+ and RP– patients. On average, patients attended 2 office visits before isotretinoin was discussed as a treatment option and 3 office visits before isotretinoin therapy was initiated. The difference between the number of office visits patients attended before isotretinoin was discussed (P=.44) and before isotretinoin therapy was initiated (P=.11) was not significant between RP+ and RP– patients. The number of alternative medications that failed before initiation of isotretinoin therapy was comparable between groups. Patients in the RP– group experienced failure with an average of 5 alternative medications compared with 6 alternative medications in the RP+ group (P=.48).

As shown in eTable 3, oral antibiotic therapy commonly was prescribed prior to isotretinoin in both groups, with doxycycline being prescribed most often. Hormonal therapy, including oral contraceptives and spironolactone, was trialed in 55 of 87 (63.2%) RP+ patients. Most patients experienced failure with other oral antiacne medications before isotretinoin therapy, with only 6 (6.7%) RP+ and 5 (6.1%) RP– patients trying topical therapy only. Prior isotretinoin therapy was documented in 13 (14.6%) RP+ patients compared with only 5 (6.1%) RP– patients. Interestingly, isotretinoin was initiated at the patient’s first office visit more often in the RP+ group.

At the time isotretinoin therapy was initiated, the sex of the prescribing provider was similar within the RP+ group, with 52% (46/89) of female and 48% (43/89) of male prescribers. In the RP– group, there was a slightly higher proportion of male prescribers, with 57% (47/82) male compared to 43% (35/82) female prescribers.

iPLEDGE (https://ipledgeprogram.com) is an online system mandated by the US Food and Drug Administration to be used by patients, physicians, and pharmacists for the duration of isotretinoin therapy to prevent and track isotretinoin-associated pregnancies.⁹ At its inception, the iPLEDGE program categorized patients as females of child-bearing potential, females not of child-bearing potential, or males. The program recently moved toward transgender-inclusive categorization of patients based on reproductive potential.¹⁰ Patients who can get pregnant include cisgender females and transgender males, and patients who cannot get pregnant include cisgender males, transgender females, and females and transgender males who have undergone a hysterectomy or bilateral oophorectomy or who are postmenopausal.⁹

The iPLEDGE compliance requirements for patients who can get pregnant are extensive. Patients with reproductive potential must obtain a negative baseline pregnancy test, enroll in iPLEDGE, undergo a 30-day waiting period, and obtain a second negative pregnancy test before they can start the medication. Each month thereafter, patients must obtain a negative pregnancy test, demonstrate risk comprehension, and report their methods of contraception on iPLEDGE before they can pick up their prescription. In addition, physicians and pharmacists must confirm patient counseling and obtain authorization codes from iPLEDGE to dispense the medication. If any of these steps are not completed by the patient, physician, or pharmacist within 7 days of the patient’s negative pregnancy test, all steps must be repeated by all parties.^9,11

The efficacy and utility of iPLEDGE have been criticized and debated in the literature. Although there has been a general decrease in the number of fetal exposures to isotretinoin since the implementation of iPLEDGE in 2006, the average number of fetal exposures only decreased for 2 years until it plateaued in 2008.⁵ Some physicians have argued that the decrease in the number of fetal exposures is not attributed to the efficacy of iPLEDGE but rather because the program has made it difficult for patients who can get pregnant to obtain necessary isotretinoin prescriptions.¹² Other physicians have reported that they have chosen not to prescribe isotretinoin due to the administrative burden of iPLEDGE.⁸ Although we expected to observe similar trends in our study, we ultimately had more eligible patients with reproductive potential than patients who could not get pregnant. Additionally, there was no difference in the number of months from initial acne visit, total number of office visits, and number of alternative medications that failed before isotretinoin initiation between patients who could and could not get pregnant. These findings suggest that iPLEDGE requirements did not dissuade prescribers from treating acne with isotretinoin in patients who could get pregnant and that the prescribing patterns of isotretinoin were similar regardless of reproductive potential.

Across all primary outcomes, the standard deviation was high in the overall dataset and in the RP– and RP+ subsets, indicating substantial variability in number of months from initial acne visit, total number of visits, and number of alternative medications that failed prior to initiation of isotretinoin. This implies that the prescribing patterns of isotretinoin may be patient and prescriber dependent, and other variables may influence these outcomes aside from the reproductive potential of the patient. Although there was a marginally higher percentage of male prescribers in the RP– group, the sex of the prescriber did not seem to have a major impact on the prescribing patterns of isotretinoin. Further research is indicated to investigate the impact of other factors that may influence the prescribing patterns of isotretinoin, including insurance coverage, access to contraception, and patient concerns about adverse effects.

The types of alternative medications that patients tried prior to isotretinoin were similar among patients who could get pregnant and patients who could not get pregnant. Hormonal therapy, including oral contraception pills and spironolactone, can be very effective in treating acne in patients with reproductive potential,¹³ as evidenced by the 55 (31.1%) prescriptions written for hormonal therapy in the RP+ group. Spironolactone for acne is contraindicated in male patients due to its antiandrogenic properties and risk for gynecomastia.¹⁴ As such, males have fewer alternative medication options for acne, and this may contribute to the higher prevalence of isotretinoin therapy in males that has been demonstrated in prior studies.^6,7 Of note, patients obtained more than 100 prescriptions for oral antimicrobials in both groups. Although patients can see benefit with oral antimicrobials for acne, the volume of antimicrobial prescriptions seen in our cohort raises concerns about antibiotic stewardship.¹⁵ Whether isotretinoin is a safer therapeutic option compared to antibiotics is up for debate.^2,16

Our study included a small sample size at a single institution, which may limit the external validity of our results. Additionally, our study focused on patients who were prescribed isotretinoin prior to 2020 to control for the influence of the COVID-19 pandemic on prescribing patterns. With this, our data may not reflect postpandemic prescribing trends. Further multi-institution studies that include postpandemic patient cohorts can be conducted to validate our findings.

There were no significant differences in the number of months from initial acne visit, total number of office visits, and number of alternative medications that failed prior to discussing isotretinoin as a treatment option or initiating isotretinoin therapy between patients who can get pregnant and those who cannot get pregnant. We observed substantial variability in these outcomes across datasets, indicating that the prescribing patterns of isotretinoin may be patient and prescriber dependent regardless of the reproductive potential of the patient. Follow-up studies are warranted to further investigate the specific influence of iPLEDGE on the utilization of isotretinoin.

To the Editor:

Isotretinoin is the most effective treatment option for acne vulgaris and is considered the first-line therapy for severe scarring acne.^1-3 Isotretinoin therapy is indicated for moderate acne when other treatments have failed or when the condition causes distress.³ While there are treatment guidelines for moderate to severe acne, there is no gold standard, and most treatment options include a combination of topical and/or oral therapies.⁴ Isotretinoin is one of the few monotherapy options available, but its use often is limited by concerns for severe internal and external birth defects if taken during pregnancy.

To manage teratogenicity risks associated with isotretinoin, the US Food and Drug Administration implemented the iPLEDGE Risk Evaluation and Mitigation Strategy in 2006.⁵ The iPLEDGE compliance requirements differ vastly depending on the reproductive potential of the patient, and the process of obtaining an isotretinoin prescription is much more cumbersome for patients who can get pregnant. Previous studies have demonstrated that males are more likely to be prescribed isotretinoin compared to females, even though females attended more acne-related office visits than males.^6,7 Additionally, the administrative burden of iPLEDGE may influence the prescribing patterns of isotretinoin. In a survey of 510 dermatologists, approximately 30% reported that they have at times chosen not to prescribe isotretinoin to patients with severe acne due to the administrative burden of iPLEDGE.⁸ In this study, we sought to further analyze the prescribing patterns of isotretinoin based on a patient’s reproductive potential.

In this single-center, retrospective cohort study, electronic medical records from 3292 patients diagnosed with acne vulgaris at the Department of Dermatology at Rush University Medical Center (Chicago, Illinois) between January 2013 and December 2019 were reviewed. A total of 188 patients who were prescribed isotretinoin for acne were identified, but only 171 met the study criteria. Eligible patients were aged 12 to 25 years and were prescribed oral isotretinoin for acne vulgaris during the study period. Patients younger than 12 or older than 25 years, those who were prescribed isotretinoin for indications other than acne vulgaris, and those who had previously received isotretinoin and either initiated an additional course or continued treatment at our institution were excluded. Eligible patients then were grouped by reproductive potential: patients who can get pregnant (positive reproductive potential [RP+]) and patients who cannot get pregnant (negative reproductive potential [RP–]). The number of months from initial acne visit, total number of office visits attended, and number of alternative medications that failed before isotretinoin therapy was discussed and initiated were compared between the 2 groups. To standardize between groups, the office visit at which patients were enrolled in iPLEDGE served as the date that isotretinoin therapy was initiated. Alternative medication type and sex of the prescriber were evaluated as secondary end points.

Eighty-nine RP+ patients and 82 RP– patients were prescribed isotretinoin for acne, including 85 females, 2 transgender males with female reproductive organs, 2 females with a history of tubal ligation, and 82 males. Of note, the iPLEDGE program considers tubal ligation as a primary form of contraception and classifies these patients as RP+. Patient demographics are summarized in eTable 1. There was a higher proportion of RP– patients aged 10 to 20 years compared to RP+ patients, for whom there was a higher number of patients aged 21 to 30 years. Most RP+ patients were White, while most RP– patients were Hispanic/Latino.

Overall isotretinoin prescribing patterns as well as prescribing patterns stratified by reproductive potential are presented in eTable 2. Overall, the average number of months before isotretinoin was discussed as a treatment option was 11.5 months and before isotretinoin therapy was initiated was 15 months. There was no significant difference between the number of months before isotretinoin was discussed (P=.83) or initiated (P=.56) between RP+ and RP– patients. On average, patients attended 2 office visits before isotretinoin was discussed as a treatment option and 3 office visits before isotretinoin therapy was initiated. The difference between the number of office visits patients attended before isotretinoin was discussed (P=.44) and before isotretinoin therapy was initiated (P=.11) was not significant between RP+ and RP– patients. The number of alternative medications that failed before initiation of isotretinoin therapy was comparable between groups. Patients in the RP– group experienced failure with an average of 5 alternative medications compared with 6 alternative medications in the RP+ group (P=.48).

As shown in eTable 3, oral antibiotic therapy commonly was prescribed prior to isotretinoin in both groups, with doxycycline being prescribed most often. Hormonal therapy, including oral contraceptives and spironolactone, was trialed in 55 of 87 (63.2%) RP+ patients. Most patients experienced failure with other oral antiacne medications before isotretinoin therapy, with only 6 (6.7%) RP+ and 5 (6.1%) RP– patients trying topical therapy only. Prior isotretinoin therapy was documented in 13 (14.6%) RP+ patients compared with only 5 (6.1%) RP– patients. Interestingly, isotretinoin was initiated at the patient’s first office visit more often in the RP+ group.

At the time isotretinoin therapy was initiated, the sex of the prescribing provider was similar within the RP+ group, with 52% (46/89) of female and 48% (43/89) of male prescribers. In the RP– group, there was a slightly higher proportion of male prescribers, with 57% (47/82) male compared to 43% (35/82) female prescribers.

iPLEDGE (https://ipledgeprogram.com) is an online system mandated by the US Food and Drug Administration to be used by patients, physicians, and pharmacists for the duration of isotretinoin therapy to prevent and track isotretinoin-associated pregnancies.⁹ At its inception, the iPLEDGE program categorized patients as females of child-bearing potential, females not of child-bearing potential, or males. The program recently moved toward transgender-inclusive categorization of patients based on reproductive potential.¹⁰ Patients who can get pregnant include cisgender females and transgender males, and patients who cannot get pregnant include cisgender males, transgender females, and females and transgender males who have undergone a hysterectomy or bilateral oophorectomy or who are postmenopausal.⁹

The iPLEDGE compliance requirements for patients who can get pregnant are extensive. Patients with reproductive potential must obtain a negative baseline pregnancy test, enroll in iPLEDGE, undergo a 30-day waiting period, and obtain a second negative pregnancy test before they can start the medication. Each month thereafter, patients must obtain a negative pregnancy test, demonstrate risk comprehension, and report their methods of contraception on iPLEDGE before they can pick up their prescription. In addition, physicians and pharmacists must confirm patient counseling and obtain authorization codes from iPLEDGE to dispense the medication. If any of these steps are not completed by the patient, physician, or pharmacist within 7 days of the patient’s negative pregnancy test, all steps must be repeated by all parties.^9,11

The efficacy and utility of iPLEDGE have been criticized and debated in the literature. Although there has been a general decrease in the number of fetal exposures to isotretinoin since the implementation of iPLEDGE in 2006, the average number of fetal exposures only decreased for 2 years until it plateaued in 2008.⁵ Some physicians have argued that the decrease in the number of fetal exposures is not attributed to the efficacy of iPLEDGE but rather because the program has made it difficult for patients who can get pregnant to obtain necessary isotretinoin prescriptions.¹² Other physicians have reported that they have chosen not to prescribe isotretinoin due to the administrative burden of iPLEDGE.⁸ Although we expected to observe similar trends in our study, we ultimately had more eligible patients with reproductive potential than patients who could not get pregnant. Additionally, there was no difference in the number of months from initial acne visit, total number of office visits, and number of alternative medications that failed before isotretinoin initiation between patients who could and could not get pregnant. These findings suggest that iPLEDGE requirements did not dissuade prescribers from treating acne with isotretinoin in patients who could get pregnant and that the prescribing patterns of isotretinoin were similar regardless of reproductive potential.

Across all primary outcomes, the standard deviation was high in the overall dataset and in the RP– and RP+ subsets, indicating substantial variability in number of months from initial acne visit, total number of visits, and number of alternative medications that failed prior to initiation of isotretinoin. This implies that the prescribing patterns of isotretinoin may be patient and prescriber dependent, and other variables may influence these outcomes aside from the reproductive potential of the patient. Although there was a marginally higher percentage of male prescribers in the RP– group, the sex of the prescriber did not seem to have a major impact on the prescribing patterns of isotretinoin. Further research is indicated to investigate the impact of other factors that may influence the prescribing patterns of isotretinoin, including insurance coverage, access to contraception, and patient concerns about adverse effects.

The types of alternative medications that patients tried prior to isotretinoin were similar among patients who could get pregnant and patients who could not get pregnant. Hormonal therapy, including oral contraception pills and spironolactone, can be very effective in treating acne in patients with reproductive potential,¹³ as evidenced by the 55 (31.1%) prescriptions written for hormonal therapy in the RP+ group. Spironolactone for acne is contraindicated in male patients due to its antiandrogenic properties and risk for gynecomastia.¹⁴ As such, males have fewer alternative medication options for acne, and this may contribute to the higher prevalence of isotretinoin therapy in males that has been demonstrated in prior studies.^6,7 Of note, patients obtained more than 100 prescriptions for oral antimicrobials in both groups. Although patients can see benefit with oral antimicrobials for acne, the volume of antimicrobial prescriptions seen in our cohort raises concerns about antibiotic stewardship.¹⁵ Whether isotretinoin is a safer therapeutic option compared to antibiotics is up for debate.^2,16

Our study included a small sample size at a single institution, which may limit the external validity of our results. Additionally, our study focused on patients who were prescribed isotretinoin prior to 2020 to control for the influence of the COVID-19 pandemic on prescribing patterns. With this, our data may not reflect postpandemic prescribing trends. Further multi-institution studies that include postpandemic patient cohorts can be conducted to validate our findings.

There were no significant differences in the number of months from initial acne visit, total number of office visits, and number of alternative medications that failed prior to discussing isotretinoin as a treatment option or initiating isotretinoin therapy between patients who can get pregnant and those who cannot get pregnant. We observed substantial variability in these outcomes across datasets, indicating that the prescribing patterns of isotretinoin may be patient and prescriber dependent regardless of the reproductive potential of the patient. Follow-up studies are warranted to further investigate the specific influence of iPLEDGE on the utilization of isotretinoin.

Recent data suggest that approximately 20% to 40% of patients treated with isotretinoin have recurrence of acne. How should dermatologists interpret these findings?

DR. BARBIERI: While isotretinoin is highly effective and capable of delivering long-term remission, we should be careful to avoid describing it as a “cure” when counseling patients. Importantly, when acne does recur, it is often milder, and about half of those who have acne recurrence can be managed with topicals alone. For those who do require a subsequent course of isotretinoin, we should view this as an outcome that can be expected to happen in about 1 in 10 treated with isotretinoin rather than a treatment failure.

How important is cumulative dose in preventing relapse, and should we be rethinking traditional dosing targets?

DR. BARBIERI: Cumulative dose is one of the most important factors in preventing recurrence. Multiple studies support that higher cumulative dose is a strong predictor of long-term clearance. In contrast, daily dose does not seem to be as important a factor. However, higher cumulative dose also means longer courses and more potential for adverse effects, including long-term skin and eye dryness. For this reason, I prefer to treat to clinical endpoints of clear skin for 2 to 3 months and at least 120 to 150 mg/kg cumulative dose to balance achieving high cumulative doses with potential adverse effects and risks. For those with fewer adverse effects or who prioritize long-term clearance, we might go a little longer and for those with more adverse effects, we might use a shorter course and accept a higher risk for recurrence. By taking this approach, we can individualize our dosing approach to each patient.

What factors most strongly predict relapse after a completed isotretinoin course?

DR. BARBIERI: Some demographic factors that have been associated with higher rates of recurrence include greater baseline severity and younger age at treatment. Women with a strong hormonal component to their acne, such as those with polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome), also may be more likely to have recurrence. With respect to clinical factors, increasing cumulative dose has been associated with reduced risk for recurrence in multiple studies, and treating until a clinical endpoint of clear skin for 2 to 3 months also may be predictive of long-term clearance.

When a patient relapses, how do you decide between topical therapy, hormonal treatment, or a second isotretinoin course?

DR. BARBIERI: It depends on relapse severity and patient goals. Mild recurrence often responds well to topical therapies such as retinoids, benzoyl peroxide, antibiotics, and clascoterone. About half of those with recurrence will be able to manage it with topical therapies alone. For those with more severe acne requiring systemic therapy, about half will decide on a repeat course of isotretinoin, which I often find works faster and better than the first course. For second courses, I will typically try to use micronized isotretinoin due to the more consistent pharmacokinetics. For women—especially those with signs of hyperandrogenism such as hirsutism, irregular periods, or flaring with menstrual cycle—hormonal therapy such as combined oral contraceptives or spironolactone can be a great option. Oral antibiotics also can be a consideration for those with recurrence, though we need to be thoughtful about antimicrobial stewardship and risks of long-term antibiotic use.

Are low-dose or shorter-course regimens contributing to higher relapse rates?

DR. BARBIERI: While there is some evidence that higher daily doses may be associated with lower risk for recurrence, when you control for cumulative dose, it doesn’t seem like daily dose has much influence. In contrast, cumulative dose has a large effect on frequency of long-term clearance. While I don’t think low-dose regimens are inherently problematic, if they result in shorter cumulative dose courses, that could increase the risk for recurrence.

How does hormonal acne influence long-term outcomes after isotretinoin?

DR. BARBIERI: While all acne is “hormonal,” those with a stronger hormonal pathogenesis, such as women with polyendocrine metabolic ovarian syndrome or other signs of hyperandrogenism, may have a higher likelihood of recurrence after treatment. In these patients, I often find hormonal therapy such as combined oral contraceptives or spironolactone to be highly effective, even if they haven't worked before.

Should maintenance therapy be routine after isotretinoin, and if so, what strategies are most effective?

DR. BARBIERI: Since many patients have a goal of long-term clearance after isotretinoin, I do not routinely recommend maintenance therapy, as this seems antithetical to this goal. However, for those who are very concerned about recurrence or who would like to be on a topical retinoid for other reasons, I will sometimes start a topical retinoid after treatment with isotretinoin.

How should dermatologists counsel patients about expectations with respect to relapse before starting isotretinoin?

DR. BARBIERI: We should be careful to set appropriate expectations with isotretinoin. I counsel patients that isotretinoin is an incredibly effective therapy for severe acne, with a high likelihood of long-term remission, but not a guaranteed permanent cure. Setting this expectation upfront reduces disappointment if acne does recur and improves shared decision-making.

Recent data suggest that approximately 20% to 40% of patients treated with isotretinoin have recurrence of acne. How should dermatologists interpret these findings?

DR. BARBIERI: While isotretinoin is highly effective and capable of delivering long-term remission, we should be careful to avoid describing it as a “cure” when counseling patients. Importantly, when acne does recur, it is often milder, and about half of those who have acne recurrence can be managed with topicals alone. For those who do require a subsequent course of isotretinoin, we should view this as an outcome that can be expected to happen in about 1 in 10 treated with isotretinoin rather than a treatment failure.

How important is cumulative dose in preventing relapse, and should we be rethinking traditional dosing targets?

DR. BARBIERI: Cumulative dose is one of the most important factors in preventing recurrence. Multiple studies support that higher cumulative dose is a strong predictor of long-term clearance. In contrast, daily dose does not seem to be as important a factor. However, higher cumulative dose also means longer courses and more potential for adverse effects, including long-term skin and eye dryness. For this reason, I prefer to treat to clinical endpoints of clear skin for 2 to 3 months and at least 120 to 150 mg/kg cumulative dose to balance achieving high cumulative doses with potential adverse effects and risks. For those with fewer adverse effects or who prioritize long-term clearance, we might go a little longer and for those with more adverse effects, we might use a shorter course and accept a higher risk for recurrence. By taking this approach, we can individualize our dosing approach to each patient.

What factors most strongly predict relapse after a completed isotretinoin course?

DR. BARBIERI: Some demographic factors that have been associated with higher rates of recurrence include greater baseline severity and younger age at treatment. Women with a strong hormonal component to their acne, such as those with polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome), also may be more likely to have recurrence. With respect to clinical factors, increasing cumulative dose has been associated with reduced risk for recurrence in multiple studies, and treating until a clinical endpoint of clear skin for 2 to 3 months also may be predictive of long-term clearance.

When a patient relapses, how do you decide between topical therapy, hormonal treatment, or a second isotretinoin course?

DR. BARBIERI: It depends on relapse severity and patient goals. Mild recurrence often responds well to topical therapies such as retinoids, benzoyl peroxide, antibiotics, and clascoterone. About half of those with recurrence will be able to manage it with topical therapies alone. For those with more severe acne requiring systemic therapy, about half will decide on a repeat course of isotretinoin, which I often find works faster and better than the first course. For second courses, I will typically try to use micronized isotretinoin due to the more consistent pharmacokinetics. For women—especially those with signs of hyperandrogenism such as hirsutism, irregular periods, or flaring with menstrual cycle—hormonal therapy such as combined oral contraceptives or spironolactone can be a great option. Oral antibiotics also can be a consideration for those with recurrence, though we need to be thoughtful about antimicrobial stewardship and risks of long-term antibiotic use.

Are low-dose or shorter-course regimens contributing to higher relapse rates?

DR. BARBIERI: While there is some evidence that higher daily doses may be associated with lower risk for recurrence, when you control for cumulative dose, it doesn’t seem like daily dose has much influence. In contrast, cumulative dose has a large effect on frequency of long-term clearance. While I don’t think low-dose regimens are inherently problematic, if they result in shorter cumulative dose courses, that could increase the risk for recurrence.

How does hormonal acne influence long-term outcomes after isotretinoin?

DR. BARBIERI: While all acne is “hormonal,” those with a stronger hormonal pathogenesis, such as women with polyendocrine metabolic ovarian syndrome or other signs of hyperandrogenism, may have a higher likelihood of recurrence after treatment. In these patients, I often find hormonal therapy such as combined oral contraceptives or spironolactone to be highly effective, even if they haven't worked before.

Should maintenance therapy be routine after isotretinoin, and if so, what strategies are most effective?

DR. BARBIERI: Since many patients have a goal of long-term clearance after isotretinoin, I do not routinely recommend maintenance therapy, as this seems antithetical to this goal. However, for those who are very concerned about recurrence or who would like to be on a topical retinoid for other reasons, I will sometimes start a topical retinoid after treatment with isotretinoin.

How should dermatologists counsel patients about expectations with respect to relapse before starting isotretinoin?

DR. BARBIERI: We should be careful to set appropriate expectations with isotretinoin. I counsel patients that isotretinoin is an incredibly effective therapy for severe acne, with a high likelihood of long-term remission, but not a guaranteed permanent cure. Setting this expectation upfront reduces disappointment if acne does recur and improves shared decision-making.

Recent data suggest that approximately 20% to 40% of patients treated with isotretinoin have recurrence of acne. How should dermatologists interpret these findings?

DR. BARBIERI: While isotretinoin is highly effective and capable of delivering long-term remission, we should be careful to avoid describing it as a “cure” when counseling patients. Importantly, when acne does recur, it is often milder, and about half of those who have acne recurrence can be managed with topicals alone. For those who do require a subsequent course of isotretinoin, we should view this as an outcome that can be expected to happen in about 1 in 10 treated with isotretinoin rather than a treatment failure.

How important is cumulative dose in preventing relapse, and should we be rethinking traditional dosing targets?

DR. BARBIERI: Cumulative dose is one of the most important factors in preventing recurrence. Multiple studies support that higher cumulative dose is a strong predictor of long-term clearance. In contrast, daily dose does not seem to be as important a factor. However, higher cumulative dose also means longer courses and more potential for adverse effects, including long-term skin and eye dryness. For this reason, I prefer to treat to clinical endpoints of clear skin for 2 to 3 months and at least 120 to 150 mg/kg cumulative dose to balance achieving high cumulative doses with potential adverse effects and risks. For those with fewer adverse effects or who prioritize long-term clearance, we might go a little longer and for those with more adverse effects, we might use a shorter course and accept a higher risk for recurrence. By taking this approach, we can individualize our dosing approach to each patient.

What factors most strongly predict relapse after a completed isotretinoin course?

DR. BARBIERI: Some demographic factors that have been associated with higher rates of recurrence include greater baseline severity and younger age at treatment. Women with a strong hormonal component to their acne, such as those with polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome), also may be more likely to have recurrence. With respect to clinical factors, increasing cumulative dose has been associated with reduced risk for recurrence in multiple studies, and treating until a clinical endpoint of clear skin for 2 to 3 months also may be predictive of long-term clearance.

When a patient relapses, how do you decide between topical therapy, hormonal treatment, or a second isotretinoin course?

DR. BARBIERI: It depends on relapse severity and patient goals. Mild recurrence often responds well to topical therapies such as retinoids, benzoyl peroxide, antibiotics, and clascoterone. About half of those with recurrence will be able to manage it with topical therapies alone. For those with more severe acne requiring systemic therapy, about half will decide on a repeat course of isotretinoin, which I often find works faster and better than the first course. For second courses, I will typically try to use micronized isotretinoin due to the more consistent pharmacokinetics. For women—especially those with signs of hyperandrogenism such as hirsutism, irregular periods, or flaring with menstrual cycle—hormonal therapy such as combined oral contraceptives or spironolactone can be a great option. Oral antibiotics also can be a consideration for those with recurrence, though we need to be thoughtful about antimicrobial stewardship and risks of long-term antibiotic use.

Are low-dose or shorter-course regimens contributing to higher relapse rates?

DR. BARBIERI: While there is some evidence that higher daily doses may be associated with lower risk for recurrence, when you control for cumulative dose, it doesn’t seem like daily dose has much influence. In contrast, cumulative dose has a large effect on frequency of long-term clearance. While I don’t think low-dose regimens are inherently problematic, if they result in shorter cumulative dose courses, that could increase the risk for recurrence.

How does hormonal acne influence long-term outcomes after isotretinoin?

DR. BARBIERI: While all acne is “hormonal,” those with a stronger hormonal pathogenesis, such as women with polyendocrine metabolic ovarian syndrome or other signs of hyperandrogenism, may have a higher likelihood of recurrence after treatment. In these patients, I often find hormonal therapy such as combined oral contraceptives or spironolactone to be highly effective, even if they haven't worked before.

Should maintenance therapy be routine after isotretinoin, and if so, what strategies are most effective?

DR. BARBIERI: Since many patients have a goal of long-term clearance after isotretinoin, I do not routinely recommend maintenance therapy, as this seems antithetical to this goal. However, for those who are very concerned about recurrence or who would like to be on a topical retinoid for other reasons, I will sometimes start a topical retinoid after treatment with isotretinoin.

How should dermatologists counsel patients about expectations with respect to relapse before starting isotretinoin?

DR. BARBIERI: We should be careful to set appropriate expectations with isotretinoin. I counsel patients that isotretinoin is an incredibly effective therapy for severe acne, with a high likelihood of long-term remission, but not a guaranteed permanent cure. Setting this expectation upfront reduces disappointment if acne does recur and improves shared decision-making.

What clinical signs suggest antimicrobial resistance is affecting acne treatment response, and how can dermatologists identify them early? 

DR. ROSAMILIA: Antibiotic resistance is a difficult phenomenon to define clinically for acne due to many pathogenic contributors, namely the increase in sebum production stoked by hormonal changes, which further provokes Cutibacterium acnes biofilms, follicular plugs, and various inflammatory cascades. The sequence and primacy of these steps are enigmatic in each patient, therefore the role and extent of true antimicrobial therapy are debatable. Acne is more complex than other conditions that utilize antimicrobials, such as tinea corporis. In acne, lack of treatment response may be due to various factors, including long-term adherence challenges (such as inconsistent home dosing and trending complex over-the-counter [OTC] regimens), hormonal fluctuation, and confounders such as gram-negative or pityrosporum folliculitis. Therefore, determining if resistant bacteria are “causal” in acne recalcitrance or exacerbation is vague. In older patients (or younger patients with chronic conditions), proof of bacterial resistance from wound, pulmonary, or gastrointestinal studies might be available, but a typical acne patient would not present with these data. 

Do you routinely rotate patients off oral antibiotics after a fixed treatment period, or is it symptom based? How do you balance the risk for disease recurrence with resistance concerns? 

DR. ROSAMILIA: For my patients, the typical “triple threat” for moderate acne—oral antibiotics, topical benzoyl peroxide, and topical retinoids—still is tried and true. I typically prescribe 6 weeks of low-dose antibiotic therapy (doxycycline 50 mg daily) and arrange a telemedicine visit at 4 to 6 weeks to assess progress and adherence. Subsequently, I might substitute topical for oral antibiotics, with long-term plans to discontinue all antibiotics. In females, I might add spironolactone and/or oral contraceptive pills, and for recalcitrant or progressive acne, I would discuss isotretinoin. If the patient’s acne is under good control without antibiotics but they still experience intermittent deeper papules, I consider adding burst therapy of low-dose doxycycline for 1 week as needed, or for instance, during sports seasons. I try to maintain the lowest possible dosage of doxycycline while toeing the line between short-term antibacterial and longer-term anti-inflammatory control. In fact, I typically recommend that patients take it with their morning meal to absorb slightly less than the full 50-mg dosage, mitigate adverse effects, and increase adherence. All of these regimens include a benzoyl peroxide wash for its many anti-acne properties and in the context of this discussion to mitigate C acnes on acne-prone skin without creating antibiotic resistance. 

Do you see a future for point-of-care microbiome or resistance testing in acne management? 

DR. ROSAMILIA: I think we should be receptive to the evolution of these tests, and depending on the patient’s insurance coverage, efficient collection methods, and applicability to all patients, we someday may approach antimicrobial pharmacotherapy in a more personalized way. The microbiome is a broad topic with protean approaches to testing and prebiotic/probiotic supplementation, so openminded but cautious and well-studied utilization is key. 

What language do you find effective when setting expectations for acne treatment that avoids overreliance on antibiotics? 

DR. ROSAMILIA: I find it important to first determine the patient’s prior therapies. Many patients with acne present to dermatology after taking a full dosage of various antibiotics for broad amounts of time, and they may have experienced acne exacerbation (or at least perception of such) when the refills ran out. Also, I ask them to outline their past and current OTC regimens, which provides context for where and how the patient gets their information and advice. I like providing the patient’s next steps in written form, even telling them to tape the instructions to their bathroom mirror. It is just as vital to take time at the first office visit to explain the expected time to improvement and why acne is a multifactorial condition for which antibiotics are only part of the approach with benzoyl peroxide and retinoids. 

What are your top practical tips for incoming dermatologists to practice antibiotic stewardship in acne management? 

DR. ROSAMILIA: The American Academy of Dermatology (AAD) guidelines recommend 3 to 4 months as the maximum threshold for systemic antibiotics for moderate to severe acne, with tetracyclines having the best evidence for efficacy and safety. The AAD recommends never utilizing these as monotherapy and always including concomitant benzoyl peroxide to avoid bacterial resistance and topicals such as retinoids to provide a bridge to a maintenance phase without antibiotics. Starting there gives trainees structure within which to build their own acne management approach and style for their patient population. Some dermatologists might prescribe middle to high antibiotic dosages at first followed by a taper or initiate low antibiotic dosages with a standard 3- to 4-month follow-up, or a bit of a hybrid of these, as outlined in my approach. As mentioned, standardized testing for resistance to guide our dosing is not mainstream. There are countless ways to apply these guardrails, consider a place for hormonal or future isotretinoin therapy, and include the many varieties of OTC and prescription acne topicals to round out a personalized regimen for each patient based on their schedule, medication intolerances, skin type, fertility plans, and lifestyle. 

What’s the single most impactful change a busy dermatology clinic could make right now to reduce antibiotic overuse in acne care? 

DR. ROSAMILIA: I think telemedicine or in-person check-ins at the 1- or 2-month mark are vital to the assessment of the patient’s and/or family’s understanding of the treatment schedule, their ability to procure the prescription and OTC products successfully, and their consistency in using them. This is a good opportunity to remind them that our goal is to see true acne improvement; take fewer medications, not more; and create a reality where their acne regimen is intuitive and safe.

What clinical signs suggest antimicrobial resistance is affecting acne treatment response, and how can dermatologists identify them early? 

DR. ROSAMILIA: Antibiotic resistance is a difficult phenomenon to define clinically for acne due to many pathogenic contributors, namely the increase in sebum production stoked by hormonal changes, which further provokes Cutibacterium acnes biofilms, follicular plugs, and various inflammatory cascades. The sequence and primacy of these steps are enigmatic in each patient, therefore the role and extent of true antimicrobial therapy are debatable. Acne is more complex than other conditions that utilize antimicrobials, such as tinea corporis. In acne, lack of treatment response may be due to various factors, including long-term adherence challenges (such as inconsistent home dosing and trending complex over-the-counter [OTC] regimens), hormonal fluctuation, and confounders such as gram-negative or pityrosporum folliculitis. Therefore, determining if resistant bacteria are “causal” in acne recalcitrance or exacerbation is vague. In older patients (or younger patients with chronic conditions), proof of bacterial resistance from wound, pulmonary, or gastrointestinal studies might be available, but a typical acne patient would not present with these data. 

Do you routinely rotate patients off oral antibiotics after a fixed treatment period, or is it symptom based? How do you balance the risk for disease recurrence with resistance concerns? 

DR. ROSAMILIA: For my patients, the typical “triple threat” for moderate acne—oral antibiotics, topical benzoyl peroxide, and topical retinoids—still is tried and true. I typically prescribe 6 weeks of low-dose antibiotic therapy (doxycycline 50 mg daily) and arrange a telemedicine visit at 4 to 6 weeks to assess progress and adherence. Subsequently, I might substitute topical for oral antibiotics, with long-term plans to discontinue all antibiotics. In females, I might add spironolactone and/or oral contraceptive pills, and for recalcitrant or progressive acne, I would discuss isotretinoin. If the patient’s acne is under good control without antibiotics but they still experience intermittent deeper papules, I consider adding burst therapy of low-dose doxycycline for 1 week as needed, or for instance, during sports seasons. I try to maintain the lowest possible dosage of doxycycline while toeing the line between short-term antibacterial and longer-term anti-inflammatory control. In fact, I typically recommend that patients take it with their morning meal to absorb slightly less than the full 50-mg dosage, mitigate adverse effects, and increase adherence. All of these regimens include a benzoyl peroxide wash for its many anti-acne properties and in the context of this discussion to mitigate C acnes on acne-prone skin without creating antibiotic resistance. 

Do you see a future for point-of-care microbiome or resistance testing in acne management? 

DR. ROSAMILIA: I think we should be receptive to the evolution of these tests, and depending on the patient’s insurance coverage, efficient collection methods, and applicability to all patients, we someday may approach antimicrobial pharmacotherapy in a more personalized way. The microbiome is a broad topic with protean approaches to testing and prebiotic/probiotic supplementation, so openminded but cautious and well-studied utilization is key. 

What language do you find effective when setting expectations for acne treatment that avoids overreliance on antibiotics? 

DR. ROSAMILIA: I find it important to first determine the patient’s prior therapies. Many patients with acne present to dermatology after taking a full dosage of various antibiotics for broad amounts of time, and they may have experienced acne exacerbation (or at least perception of such) when the refills ran out. Also, I ask them to outline their past and current OTC regimens, which provides context for where and how the patient gets their information and advice. I like providing the patient’s next steps in written form, even telling them to tape the instructions to their bathroom mirror. It is just as vital to take time at the first office visit to explain the expected time to improvement and why acne is a multifactorial condition for which antibiotics are only part of the approach with benzoyl peroxide and retinoids. 

What are your top practical tips for incoming dermatologists to practice antibiotic stewardship in acne management? 

DR. ROSAMILIA: The American Academy of Dermatology (AAD) guidelines recommend 3 to 4 months as the maximum threshold for systemic antibiotics for moderate to severe acne, with tetracyclines having the best evidence for efficacy and safety. The AAD recommends never utilizing these as monotherapy and always including concomitant benzoyl peroxide to avoid bacterial resistance and topicals such as retinoids to provide a bridge to a maintenance phase without antibiotics. Starting there gives trainees structure within which to build their own acne management approach and style for their patient population. Some dermatologists might prescribe middle to high antibiotic dosages at first followed by a taper or initiate low antibiotic dosages with a standard 3- to 4-month follow-up, or a bit of a hybrid of these, as outlined in my approach. As mentioned, standardized testing for resistance to guide our dosing is not mainstream. There are countless ways to apply these guardrails, consider a place for hormonal or future isotretinoin therapy, and include the many varieties of OTC and prescription acne topicals to round out a personalized regimen for each patient based on their schedule, medication intolerances, skin type, fertility plans, and lifestyle. 

What’s the single most impactful change a busy dermatology clinic could make right now to reduce antibiotic overuse in acne care? 

DR. ROSAMILIA: I think telemedicine or in-person check-ins at the 1- or 2-month mark are vital to the assessment of the patient’s and/or family’s understanding of the treatment schedule, their ability to procure the prescription and OTC products successfully, and their consistency in using them. This is a good opportunity to remind them that our goal is to see true acne improvement; take fewer medications, not more; and create a reality where their acne regimen is intuitive and safe.

What clinical signs suggest antimicrobial resistance is affecting acne treatment response, and how can dermatologists identify them early? 

DR. ROSAMILIA: Antibiotic resistance is a difficult phenomenon to define clinically for acne due to many pathogenic contributors, namely the increase in sebum production stoked by hormonal changes, which further provokes Cutibacterium acnes biofilms, follicular plugs, and various inflammatory cascades. The sequence and primacy of these steps are enigmatic in each patient, therefore the role and extent of true antimicrobial therapy are debatable. Acne is more complex than other conditions that utilize antimicrobials, such as tinea corporis. In acne, lack of treatment response may be due to various factors, including long-term adherence challenges (such as inconsistent home dosing and trending complex over-the-counter [OTC] regimens), hormonal fluctuation, and confounders such as gram-negative or pityrosporum folliculitis. Therefore, determining if resistant bacteria are “causal” in acne recalcitrance or exacerbation is vague. In older patients (or younger patients with chronic conditions), proof of bacterial resistance from wound, pulmonary, or gastrointestinal studies might be available, but a typical acne patient would not present with these data. 

Do you routinely rotate patients off oral antibiotics after a fixed treatment period, or is it symptom based? How do you balance the risk for disease recurrence with resistance concerns? 

DR. ROSAMILIA: For my patients, the typical “triple threat” for moderate acne—oral antibiotics, topical benzoyl peroxide, and topical retinoids—still is tried and true. I typically prescribe 6 weeks of low-dose antibiotic therapy (doxycycline 50 mg daily) and arrange a telemedicine visit at 4 to 6 weeks to assess progress and adherence. Subsequently, I might substitute topical for oral antibiotics, with long-term plans to discontinue all antibiotics. In females, I might add spironolactone and/or oral contraceptive pills, and for recalcitrant or progressive acne, I would discuss isotretinoin. If the patient’s acne is under good control without antibiotics but they still experience intermittent deeper papules, I consider adding burst therapy of low-dose doxycycline for 1 week as needed, or for instance, during sports seasons. I try to maintain the lowest possible dosage of doxycycline while toeing the line between short-term antibacterial and longer-term anti-inflammatory control. In fact, I typically recommend that patients take it with their morning meal to absorb slightly less than the full 50-mg dosage, mitigate adverse effects, and increase adherence. All of these regimens include a benzoyl peroxide wash for its many anti-acne properties and in the context of this discussion to mitigate C acnes on acne-prone skin without creating antibiotic resistance. 

Do you see a future for point-of-care microbiome or resistance testing in acne management? 

DR. ROSAMILIA: I think we should be receptive to the evolution of these tests, and depending on the patient’s insurance coverage, efficient collection methods, and applicability to all patients, we someday may approach antimicrobial pharmacotherapy in a more personalized way. The microbiome is a broad topic with protean approaches to testing and prebiotic/probiotic supplementation, so openminded but cautious and well-studied utilization is key. 

What language do you find effective when setting expectations for acne treatment that avoids overreliance on antibiotics? 

DR. ROSAMILIA: I find it important to first determine the patient’s prior therapies. Many patients with acne present to dermatology after taking a full dosage of various antibiotics for broad amounts of time, and they may have experienced acne exacerbation (or at least perception of such) when the refills ran out. Also, I ask them to outline their past and current OTC regimens, which provides context for where and how the patient gets their information and advice. I like providing the patient’s next steps in written form, even telling them to tape the instructions to their bathroom mirror. It is just as vital to take time at the first office visit to explain the expected time to improvement and why acne is a multifactorial condition for which antibiotics are only part of the approach with benzoyl peroxide and retinoids. 

What are your top practical tips for incoming dermatologists to practice antibiotic stewardship in acne management? 

DR. ROSAMILIA: The American Academy of Dermatology (AAD) guidelines recommend 3 to 4 months as the maximum threshold for systemic antibiotics for moderate to severe acne, with tetracyclines having the best evidence for efficacy and safety. The AAD recommends never utilizing these as monotherapy and always including concomitant benzoyl peroxide to avoid bacterial resistance and topicals such as retinoids to provide a bridge to a maintenance phase without antibiotics. Starting there gives trainees structure within which to build their own acne management approach and style for their patient population. Some dermatologists might prescribe middle to high antibiotic dosages at first followed by a taper or initiate low antibiotic dosages with a standard 3- to 4-month follow-up, or a bit of a hybrid of these, as outlined in my approach. As mentioned, standardized testing for resistance to guide our dosing is not mainstream. There are countless ways to apply these guardrails, consider a place for hormonal or future isotretinoin therapy, and include the many varieties of OTC and prescription acne topicals to round out a personalized regimen for each patient based on their schedule, medication intolerances, skin type, fertility plans, and lifestyle. 

What’s the single most impactful change a busy dermatology clinic could make right now to reduce antibiotic overuse in acne care? 

DR. ROSAMILIA: I think telemedicine or in-person check-ins at the 1- or 2-month mark are vital to the assessment of the patient’s and/or family’s understanding of the treatment schedule, their ability to procure the prescription and OTC products successfully, and their consistency in using them. This is a good opportunity to remind them that our goal is to see true acne improvement; take fewer medications, not more; and create a reality where their acne regimen is intuitive and safe.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

To the Editor:

Acne vulgaris and irritable bowel syndrome (IBS) are both associated with microbial dysbiosis and chronic inflammation.^1-3 While the prevalence of IBS among patients with acne has been examined previously,^4,5 there has been limited focus on the risk for new-onset IBS following acne diagnosis. Current evidence suggests isotretinoin may be associated with a lower risk for IBS compared to oral antibiotics⁶; however, evidence supporting this association is limited outside these cohorts, highlighting the need for further investigation. In this large-scale study, we sought to investigate the incidence of new-onset IBS among patients with acne compared with healthy controls as well as to evaluate whether oral acne treatments (ie, oral antibiotics or isotretinoin) are associated with new-onset IBS in this population.

A retrospective cohort study was conducted using data from the US Collaborative Network in TriNetX from October 2014 to October 2024. Patients were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, Current Procedural Terminology codes, Anatomical Therapeutic Chemical Classification System codes, and RxNorm codes (Table 1). These codes were selected based on prior literature review, clinical relevance, and their ability to capture diagnoses of acne and IBS as well as relevant exclusion criteria. Patients were considered eligible if they were between the ages of 18 and 90 years. Individuals with a history of IBS, inflammatory bowel disease, infectious gastroenteritis, or celiac disease were excluded from our analysis. 

To examine potential associations between acne and IBS, 2 primary cohorts were established: patients with acne who were managed without systemic medications and healthy controls (ie, patients with no history of acne) who had no exposure to systemic acne treatments (Figure). Further, to assess the relationship between oral acne treatments (macrolides, tetracyclines, isotretinoin) and IBS, additional cohorts were created for each therapy and were compared to a cohort of patients with acne who were managed without systemic medications. To control for potential concomitant treatments, patients who had received any systemic treatment other than the specific therapy for their treatment cohort were excluded from our analysis.

To account for potential confounders, all cohorts were 1:1 propensity score matched by demographics, tobacco and alcohol use, type 2 diabetes, obesity, anxiety, and depression (eTable). Each cohort was followed for 2 years after their index of event: the date of acne diagnosis for the acne cohort, the date of systemic treatment initiation for the treatment cohorts, and the date of the general adult encounter without abnormal findings for the control cohort. The primary outcome was the incidence of IBS, assessed by odds ratio (OR) and 95% CIs.

We identified 375,944 patients with acne managed without systemic treatment and 3,148,443 healthy controls who met study criteria. After the 1:1 propensity score match, each cohort included 49,690 patients (eTable). In the 2-year period after acne diagnosis, patients were more likely to develop IBS compared with controls (1421 vs 1285 [OR, 1.10; 95% CI, 1.02-1.19])(Table 2). Patients with acne who were treated with tetracyclines (n=208,971) were 30% more likely to develop IBS than those managed without systemic medications (1114 vs 856 [OR, 1.30; 95% CI, 1.19-1.42]). Within the tetracycline cohort, doxycycline-treated patients were 25% more likely to develop IBS compared with those treated with minocycline (213 vs 170 [OR, 1.25; 95% CI, 1.02-1.53]). Similarly, the use of macrolides (n=136,334) for acne treatment was significantly associated with an increased risk for IBS (1023 vs 595 [OR, 1.73; 95% CI, 1.57-1.92; P<.0001]) compared with controls. No statistically significant association was observed between isotretinoin and the incidence of IBS (Table 2).

In this large-scale cohort study, acne was associated with an increased likelihood of developing IBS within 2 years of an acne diagnosis compared with healthy controls. While a prior study also identified this association, it had a broader follow-up window ranging from 8 to 10 years.² In contrast, our analysis specifically quantified the risk within the first 2 years of diagnosis. This distinction suggested potential for earlier IBS onset in patients with acne than has previously been recognized and may serve as an early clinical indicator for IBS risk in this population. 

Our findings further suggested an association between oral tetracyclines and macrolides and an increased risk for IBS. This aligns with existing literature suggesting that oral antibiotic use can disrupt the gut microbiota and lead to potential gastrointestinal complications⁷ and reinforces the importance of careful antibiotic stewardship in dermatologic practice. 

Although isotretinoin initially was surrounded by substantial controversy regarding its potential impact on gut health—particularly in inflammatory bowel ­disease⁸—our results do not support an increased risk for IBS among patients with acne who use isotretinoin. These findings challenge previous concerns and align with research suggesting that isotretinoin could be a safer alternative to antibiotic use for eligible patients who have a history of gastrointestinal disorders.⁶

This study highlights an important but underrecognized link between acne and IBS risk, emphasizing the need for early monitoring of gastrointestinal symptoms and careful antibiotic stewardship in dermatologic practice. Gastroenterology consultation may be advisable for patients with acne who have persistent gastrointestinal symptoms to facilitate a more integrated, patient-centered approach to care.

Limitations of this study include potential misclassification of International Classification of Diseases, Tenth Revision, Clinical Modification codes, selection bias, and residual confounding from unmeasured factors such as diet, lifestyle, disease severity, and treatment adherence due to the reliance on electronic health record data.

Our findings build upon prior evidence linking acne and IBS and offer important insights into the timing of this association following acne diagnosis. Future research should explore biological mechanisms underlying the gut-skin axis and evaluate targeted interventions to mitigate IBS risk in patients with acne.

To the Editor:

Acne vulgaris and irritable bowel syndrome (IBS) are both associated with microbial dysbiosis and chronic inflammation.^1-3 While the prevalence of IBS among patients with acne has been examined previously,^4,5 there has been limited focus on the risk for new-onset IBS following acne diagnosis. Current evidence suggests isotretinoin may be associated with a lower risk for IBS compared to oral antibiotics⁶; however, evidence supporting this association is limited outside these cohorts, highlighting the need for further investigation. In this large-scale study, we sought to investigate the incidence of new-onset IBS among patients with acne compared with healthy controls as well as to evaluate whether oral acne treatments (ie, oral antibiotics or isotretinoin) are associated with new-onset IBS in this population.

A retrospective cohort study was conducted using data from the US Collaborative Network in TriNetX from October 2014 to October 2024. Patients were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, Current Procedural Terminology codes, Anatomical Therapeutic Chemical Classification System codes, and RxNorm codes (Table 1). These codes were selected based on prior literature review, clinical relevance, and their ability to capture diagnoses of acne and IBS as well as relevant exclusion criteria. Patients were considered eligible if they were between the ages of 18 and 90 years. Individuals with a history of IBS, inflammatory bowel disease, infectious gastroenteritis, or celiac disease were excluded from our analysis. 

To examine potential associations between acne and IBS, 2 primary cohorts were established: patients with acne who were managed without systemic medications and healthy controls (ie, patients with no history of acne) who had no exposure to systemic acne treatments (Figure). Further, to assess the relationship between oral acne treatments (macrolides, tetracyclines, isotretinoin) and IBS, additional cohorts were created for each therapy and were compared to a cohort of patients with acne who were managed without systemic medications. To control for potential concomitant treatments, patients who had received any systemic treatment other than the specific therapy for their treatment cohort were excluded from our analysis.

To account for potential confounders, all cohorts were 1:1 propensity score matched by demographics, tobacco and alcohol use, type 2 diabetes, obesity, anxiety, and depression (eTable). Each cohort was followed for 2 years after their index of event: the date of acne diagnosis for the acne cohort, the date of systemic treatment initiation for the treatment cohorts, and the date of the general adult encounter without abnormal findings for the control cohort. The primary outcome was the incidence of IBS, assessed by odds ratio (OR) and 95% CIs.

We identified 375,944 patients with acne managed without systemic treatment and 3,148,443 healthy controls who met study criteria. After the 1:1 propensity score match, each cohort included 49,690 patients (eTable). In the 2-year period after acne diagnosis, patients were more likely to develop IBS compared with controls (1421 vs 1285 [OR, 1.10; 95% CI, 1.02-1.19])(Table 2). Patients with acne who were treated with tetracyclines (n=208,971) were 30% more likely to develop IBS than those managed without systemic medications (1114 vs 856 [OR, 1.30; 95% CI, 1.19-1.42]). Within the tetracycline cohort, doxycycline-treated patients were 25% more likely to develop IBS compared with those treated with minocycline (213 vs 170 [OR, 1.25; 95% CI, 1.02-1.53]). Similarly, the use of macrolides (n=136,334) for acne treatment was significantly associated with an increased risk for IBS (1023 vs 595 [OR, 1.73; 95% CI, 1.57-1.92; P<.0001]) compared with controls. No statistically significant association was observed between isotretinoin and the incidence of IBS (Table 2).

In this large-scale cohort study, acne was associated with an increased likelihood of developing IBS within 2 years of an acne diagnosis compared with healthy controls. While a prior study also identified this association, it had a broader follow-up window ranging from 8 to 10 years.² In contrast, our analysis specifically quantified the risk within the first 2 years of diagnosis. This distinction suggested potential for earlier IBS onset in patients with acne than has previously been recognized and may serve as an early clinical indicator for IBS risk in this population. 

Our findings further suggested an association between oral tetracyclines and macrolides and an increased risk for IBS. This aligns with existing literature suggesting that oral antibiotic use can disrupt the gut microbiota and lead to potential gastrointestinal complications⁷ and reinforces the importance of careful antibiotic stewardship in dermatologic practice. 

Although isotretinoin initially was surrounded by substantial controversy regarding its potential impact on gut health—particularly in inflammatory bowel ­disease⁸—our results do not support an increased risk for IBS among patients with acne who use isotretinoin. These findings challenge previous concerns and align with research suggesting that isotretinoin could be a safer alternative to antibiotic use for eligible patients who have a history of gastrointestinal disorders.⁶

This study highlights an important but underrecognized link between acne and IBS risk, emphasizing the need for early monitoring of gastrointestinal symptoms and careful antibiotic stewardship in dermatologic practice. Gastroenterology consultation may be advisable for patients with acne who have persistent gastrointestinal symptoms to facilitate a more integrated, patient-centered approach to care.

Limitations of this study include potential misclassification of International Classification of Diseases, Tenth Revision, Clinical Modification codes, selection bias, and residual confounding from unmeasured factors such as diet, lifestyle, disease severity, and treatment adherence due to the reliance on electronic health record data.

Our findings build upon prior evidence linking acne and IBS and offer important insights into the timing of this association following acne diagnosis. Future research should explore biological mechanisms underlying the gut-skin axis and evaluate targeted interventions to mitigate IBS risk in patients with acne.

To the Editor:

Acne vulgaris and irritable bowel syndrome (IBS) are both associated with microbial dysbiosis and chronic inflammation.^1-3 While the prevalence of IBS among patients with acne has been examined previously,^4,5 there has been limited focus on the risk for new-onset IBS following acne diagnosis. Current evidence suggests isotretinoin may be associated with a lower risk for IBS compared to oral antibiotics⁶; however, evidence supporting this association is limited outside these cohorts, highlighting the need for further investigation. In this large-scale study, we sought to investigate the incidence of new-onset IBS among patients with acne compared with healthy controls as well as to evaluate whether oral acne treatments (ie, oral antibiotics or isotretinoin) are associated with new-onset IBS in this population.

A retrospective cohort study was conducted using data from the US Collaborative Network in TriNetX from October 2014 to October 2024. Patients were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, Current Procedural Terminology codes, Anatomical Therapeutic Chemical Classification System codes, and RxNorm codes (Table 1). These codes were selected based on prior literature review, clinical relevance, and their ability to capture diagnoses of acne and IBS as well as relevant exclusion criteria. Patients were considered eligible if they were between the ages of 18 and 90 years. Individuals with a history of IBS, inflammatory bowel disease, infectious gastroenteritis, or celiac disease were excluded from our analysis. 

To examine potential associations between acne and IBS, 2 primary cohorts were established: patients with acne who were managed without systemic medications and healthy controls (ie, patients with no history of acne) who had no exposure to systemic acne treatments (Figure). Further, to assess the relationship between oral acne treatments (macrolides, tetracyclines, isotretinoin) and IBS, additional cohorts were created for each therapy and were compared to a cohort of patients with acne who were managed without systemic medications. To control for potential concomitant treatments, patients who had received any systemic treatment other than the specific therapy for their treatment cohort were excluded from our analysis.

To account for potential confounders, all cohorts were 1:1 propensity score matched by demographics, tobacco and alcohol use, type 2 diabetes, obesity, anxiety, and depression (eTable). Each cohort was followed for 2 years after their index of event: the date of acne diagnosis for the acne cohort, the date of systemic treatment initiation for the treatment cohorts, and the date of the general adult encounter without abnormal findings for the control cohort. The primary outcome was the incidence of IBS, assessed by odds ratio (OR) and 95% CIs.

We identified 375,944 patients with acne managed without systemic treatment and 3,148,443 healthy controls who met study criteria. After the 1:1 propensity score match, each cohort included 49,690 patients (eTable). In the 2-year period after acne diagnosis, patients were more likely to develop IBS compared with controls (1421 vs 1285 [OR, 1.10; 95% CI, 1.02-1.19])(Table 2). Patients with acne who were treated with tetracyclines (n=208,971) were 30% more likely to develop IBS than those managed without systemic medications (1114 vs 856 [OR, 1.30; 95% CI, 1.19-1.42]). Within the tetracycline cohort, doxycycline-treated patients were 25% more likely to develop IBS compared with those treated with minocycline (213 vs 170 [OR, 1.25; 95% CI, 1.02-1.53]). Similarly, the use of macrolides (n=136,334) for acne treatment was significantly associated with an increased risk for IBS (1023 vs 595 [OR, 1.73; 95% CI, 1.57-1.92; P<.0001]) compared with controls. No statistically significant association was observed between isotretinoin and the incidence of IBS (Table 2).

In this large-scale cohort study, acne was associated with an increased likelihood of developing IBS within 2 years of an acne diagnosis compared with healthy controls. While a prior study also identified this association, it had a broader follow-up window ranging from 8 to 10 years.² In contrast, our analysis specifically quantified the risk within the first 2 years of diagnosis. This distinction suggested potential for earlier IBS onset in patients with acne than has previously been recognized and may serve as an early clinical indicator for IBS risk in this population. 

Our findings further suggested an association between oral tetracyclines and macrolides and an increased risk for IBS. This aligns with existing literature suggesting that oral antibiotic use can disrupt the gut microbiota and lead to potential gastrointestinal complications⁷ and reinforces the importance of careful antibiotic stewardship in dermatologic practice. 

Although isotretinoin initially was surrounded by substantial controversy regarding its potential impact on gut health—particularly in inflammatory bowel ­disease⁸—our results do not support an increased risk for IBS among patients with acne who use isotretinoin. These findings challenge previous concerns and align with research suggesting that isotretinoin could be a safer alternative to antibiotic use for eligible patients who have a history of gastrointestinal disorders.⁶

This study highlights an important but underrecognized link between acne and IBS risk, emphasizing the need for early monitoring of gastrointestinal symptoms and careful antibiotic stewardship in dermatologic practice. Gastroenterology consultation may be advisable for patients with acne who have persistent gastrointestinal symptoms to facilitate a more integrated, patient-centered approach to care.

Limitations of this study include potential misclassification of International Classification of Diseases, Tenth Revision, Clinical Modification codes, selection bias, and residual confounding from unmeasured factors such as diet, lifestyle, disease severity, and treatment adherence due to the reliance on electronic health record data.

Our findings build upon prior evidence linking acne and IBS and offer important insights into the timing of this association following acne diagnosis. Future research should explore biological mechanisms underlying the gut-skin axis and evaluate targeted interventions to mitigate IBS risk in patients with acne.

Spironolactone is increasingly used off label for acne treatment and is now being prescribed for women with acne at a frequency similar to oral antibiotics.^1,2 In this article, we provide an overview of spironolactone use for acne treatment and discuss recent clinical trials and practical strategies for patient selection, dosing, adverse effect management, and monitoring (Table).

History and Mechanism of Action

Because sebaceous gland activity is an important component of acne pathogenesis and is regulated by androgens,³ there has long been interest in identifying treatment strategies that can target the role of hormones in activating the sebaceous gland. In the 1980s, it became apparent that spironolactone, originally developed as a potassium-sparing diuretic, also might possess antiandrogenic properties that could be useful in the treatment of acne.⁴ Spironolactone has been found to decrease testosterone production, inhibit testosterone and dihydrotestosterone binding to androgen receptors,^5-8 and block 5α-reductase receptors of the sebaceous glands of skin.⁹

In 1984, Goodfellow et al¹⁰ conducted a trial in which 36 male and female patients with severe acne were randomized to placebo or spironolactone doses ranging from 50 to 200 mg/d. They found that spironolactone resulted in dose-dependent reductions of sebum production as well as improvement in patient- and clinician-reported assessments of acne. In 1986, another placebo-controlled crossover trial by Muhlemann et al¹¹ provided further support for the effectiveness of spironolactone for acne. This trial randomized 21 women to placebo or spironolactone 200 mg/d and found that spironolactone was associated with statistically significant (P<.001) improvements in acne lesion counts.

Recent Observational Studies and Trials

Following these early trials, several large case series have been published describing the successful use of spironolactone for acne, including a 2020 retrospective case series from the Mayo Clinic describing 395 patients.¹² The investigators found that almost 66% of patients had a complete response and almost 85% had a complete response or a partial response greater than 50%. They also found that the median time to initial response and maximal response were 3 and 5 months, respectively, and that efficacy was observed across acne subtypes, including for nodulocystic acne.¹² In addition, a 2021 case series describing 403 patients treated with spironolactone found that approximately 80% had reduction or complete clearance of acne, with improvements observed for both facial and truncal acne. In this cohort, doses of 100 to 150 mg/d typically were the most successful.¹³ A case series of 80 adolescent females also highlighted the efficacy of spironolactone in younger populations.¹⁴

Adding to these observational data, the multicenter, phase 3, double-blind Spironolactone for Adult Female Acne (SAFA) trial included 410 women (mean age, 29.2 years) who were randomized to receive either placebo or intervention (spironolactone 50 mg/d until week 6 and 100 mg/d until week 24).¹⁵ At 24 weeks, greater improvement in quality of life and participant self-assessed improvement were observed in the spironolactone group. In addition, at 12 weeks, rates of success were higher in the spironolactone group using the Investigator Global Assessment score (adjusted odds ratio 5.18 [95% CI, 2.18- 12.28]). Those randomized to receive spironolactone also had lower rates of oral antibiotic use at 52 weeks than the placebo group did (5.8% vs 13.5%, respectively).

In the SAFA trial, spironolactone was well tolerated; the most common adverse effects relative to placebo were lightheadedness (19% for spironolactone vs 12% for placebo) and headache (20% for spironolactone vs 12% for placebo). Notably, more than 95% of patients were able to increase from 50 mg/d to 100 mg/d at week 6, with greater than 90% tolerating 100 mg/d. As observational data suggest that spironolactone takes 3 to 5 months to reach peak efficacy, these findings provide further support that starting at a dose of at least 100 mg/d is likely optimal for most patients.¹⁶

A Potential Alternative to Oral Antibiotics

Oral antibiotics such as tetracyclines have long played a central role in the treatment of acne and remain a first-line treatment option.¹⁷ In addition, many of these antibiotic courses exceed 6 months in duration.¹ In fact, dermatologists prescribe more antibiotics per capita than any other specialty^1,18-20; however, this can be associated with the development of antibiotic resistance,^21,22 as well as other antibiotic-associated complications, including inflammatory bowel disease,²³ pharyngitis,²⁴ Clostridium difficile infections, and cancer.^25-29

In addition to these concerns, many patients may prefer nonantibiotic alternatives to oral antibiotics, with more than 75% preferring a nonantibiotic option if available. For female patients with acne, antiandrogens such as spironolactone have been suggested as a potential alternative.³⁰ A 10-year retrospective study of female patients with acne found that those who had ever received hormonal therapy (ie, spironolactone or a combined oral contraceptive) received fewer cumulative days of oral antibiotics than those who did not (226 days vs 302 days, respectively).³¹ In addition, while oral antibiotics were the most common initial therapy prescribed for patients, as they progressed through their treatment course, more patients ended up on hormonal therapy than oral antibiotics. This study suggests that hormonal therapy such as spironolactone could represent an alternative to the use of systemic antibiotics.³¹

Further supporting the role of spironolactone as an alternative to oral antibiotics, a 2018 analysis of claims data found that spironolactone may have similar effectiveness to oral antibiotics for the treatment of acne.32 After adjusting for age and topical retinoid and oral contraceptive use, this study found that there was no significant difference in the odds of being prescribed a different systemic treatment within 1 year (ie, treatment failure) among those starting spironolactone vs those starting oral tetracycline-class antibiotics as their initial therapy for acne.

A multicenter, randomized, double-blind trial (Female Acne Spironolactone vs doxyCycline Efficacy [FASCE]) also evaluated the comparative effectiveness of doxycycline 100 mg/d for 3 months followed by an oral placebo for 3 months vs spironolactone 150 mg/d for 6 months among 133 adult women with acne. This study found that spironolactone had statistically significantly greater rates of Investigator Global Assessment treatment success after 6 months (odds ratio 2.87 [95% CI, 1.38-5.99; P=.007]).³³ Since spironolactone historically has been prescribed less often than oral antibiotics for women with acne, these findings support spironolactone as an underutilized treatment alternative. The ongoing Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial—a 16-week, blinded trial comparing 100 mg/d doses of both drugs—should provide additional evidence regarding the relative role of spironolactone and oral antibiotics in the management of acne.³⁴

Ultimately, the decision to use spironolactone or other treatments such as oral antibiotics should be based on shared decision making between clinician and patient. Spironolactone has a relatively slow onset of efficacy, and other options such as oral antibiotics might be preferred by those looking for more immediate results; however, as women with acne often have activity that persists into adulthood, spironolactone might be preferable as a long-term maintenance therapy to avoid complications of prolonged antibiotic use.³⁵ Comorbidities also will influence the optimal choice of therapy (eg, spironolactone might be preferred in someone with inflammatory bowel disease, and oral antibiotics might be preferred in someone with orthostatic hypotension).

Patient Selection

Acne occurring along the lower face or jawline in adult women sometimes is referred to as hormonal acne, but this dogma is not particularly evidence based. An observational study of 374 patients found that almost 90% of adult women had acne involving multiple facial zones with a spectrum of facial acne severity similar to that in adolescents.³⁶ Only a small subset of these patients (11.2%) had acne localized solely to the mandibular area. In addition, acne along the lower face is not predictive of hyperandrogenism (eg, polycystic ovary syndrome).³⁷ Antiandrogen therapies such as spironolactone and clascoterone are effective in both men and women with acne^10,38 and in adolescents and adults, suggesting that hormones play a fundamental role in all acne and that addressing this mechanism can be useful broadly. Therefore, hormonal therapies such as spironolactone should not be restricted to only adult women with acne along the lower face.

While spironolactone can be effective for acne treatment in any age group, it may be most effective for adult women with acne. In the SAFA trial, prespecified subgroup analyses showed a statistically significant (P=.005) interaction term for age (categorized as <25 years and ≥25 years), which suggested that spironolactone might be a more effective treatment for women 25 years and older.¹⁵ In addition, subgroup analyses in the aforementioned 2018 analysis of claims data found that spironolactone was more effective relative to oral antibiotics in adults vs adolescents.³² Despite these limitations, several case series have highlighted that spironolactone is effective among adolescent populations with acne. A case series of spironolactone use in 73 patients aged 19 years or younger found that 68% of patients demonstrated resolution or improvement in their acne after spironolactone treatment.³⁹ Another case series among 80 adolescent females reported 80% of patients experiencing improvement of their acne.¹⁴

For those with more severe acne, spironolactone can be combined with other complementary treatment approaches such as topicals, oral antibiotics, or procedural modalities.⁴⁰

Dosing

We recommend starting spironolactone at a dose of 100 mg/d (the patient can take 50 mg/d for 1 week, then increase to 100 mg/d if there are no adverse effects at the lower dose). In the 1984 trial by Goodfellow et al,¹⁰ participants were randomized to doses of 50 mg/d, 100 mg/d, 150 mg/d, and 200 mg/d. In this trial, efficacy assessed by objective and subjective outcomes did not plateau until doses of 100 mg/d to 150 mg/d. In addition, a case series of 403 patients found that the most successful dosage of spironolactone generally was 100 mg/d or higher.¹³ Most of the patients who were started at this dosage either stayed at this level or escalated, whereas patients who started at lower dosages (25-75 mg/d) frequently increased their dosage over time. The SAFA trial also highlighted that most patients can tolerate a spironolactone dose of 100 mg/d.¹⁵ For specific populations, such as patients with polycystic ovary syndrome, a higher dose (mean dosage of 143 mg/d) may be required for efficacy.⁴¹ Given the slow onset of efficacy, typically taking 3 to 5 months, and the low rate of adverse effects, we believe the optimal starting dose is 100 mg/s to 150 mg/d. If adverse effects occur or lesions clear, then the dosage may be reduced.

Adverse Effects

Spironolactone generally is well tolerated; in the SAFA and FASCE trials, fewer than 1% of participants discontinued due to adverse effects.^15,33 Rates of discontinuation due to adverse effects typically have been less than 5% in case series of patients treated in routine clinical practice.^12-14

Because spironolactone is a diuretic and antihypertensive, the most common adverse effects are related to these characteristics. In the SAFA trial, dizziness, lightheadedness, and vertigo were reported more commonly in the spironolactone group than in the placebo group (19% vs 12%, respectively). Similarly, headaches also were reported more frequently in the spironolactone group than in the placebo group (20% vs 12%, respectively).¹⁵ One case series found that, among the 267 patients on spironolactone whose blood pressure was monitored, the mean reduction in systolic blood pressure was 3.5 mm Hg and the mean reduction in diastolic blood pressure was 0.9 mm Hg.¹³ For those with baseline orthostasis or in those who experience adverse effects related to hypotension, reducing the dose often can be helpful. Of note, while doses of 100 mg/d to 150 mg/d often are the most effective, randomized trials have found that spironolactone still can be effective for acne at doses as low as 25 mg/d to 50 mg/d.^10,38

Menstrual irregularities are another commonly cited adverse effect of spironolactone. While a systematic review found that 15% to 30% of patients treated with spironolactone experience menstrual irregularities, it has been difficult to evaluate whether this is due to the medication or other comorbidities, such as polycystic ovary syndrome.⁴² Notably, in the SAFA trial, rates of menstrual irregularities were equivalent between the spironolactone and placebo groups at a dose of 100 mg/d (32% vs 35%, respectively).¹⁵ In contrast, in the FASCE trial, menstrual irregularities were more commonly reported at a dose of 150 mg/d.³³ These findings are consistent with observational data suggesting that menstrual irregularities are much more common at spironolactone doses greater than 100 mg/d.⁴² Additionally, some evidence supports that for some patients these menstrual irregularities may resolve within 2 to 3 months of continued treatment.⁴³ It has been noted in several studies that menstrual irregularities are less likely to occur in patients who are using combined oral contraceptives; therefore, for patients who are amenable and have no contraindications, combined oral contraceptives can be considered to prevent or address menstrual irregularities.^13,42,44

More generally, combined oral contraceptives can be an excellent combination with spironolactone, as they have complementary characteristics. Spironolactone primarily blocks the effects of androgens, while combined oral contraceptives predominantly block the production of androgens. Whereas spironolactone typically causes hypotension and menstrual irregularities, combined oral contraceptives cause hypertension and help to regulate the menstrual cycle.

Spironolactone carries an official US Food and Drug Administration warning regarding possible tumorigenicity that is based on animal studies that used up to 150 times the normal dose of spironolactone used in humans⁴⁵; however, observational studies in humans have not identified such an association when spironolactone is used in normal clinical settings. A systematic review and metanalysis in 2022 reviewed data from a total population of more than 4 million individuals and found that there was no statistically significant association between spironolactone use and the risk for breast, ovarian, bladder, kidney, gastric, or esophageal cancers.⁴⁶ Additional studies also found no association between spironolactone use and cancers.⁴⁸ A more recent cohort study specifically among patients treated with spironolactone for acne also found no significant increased risk for breast cancer.⁴⁹

Combined oral contraceptives are associated with an increased risk for venous thromboembolisms, and there have been concerns that this risk may be greater in combined oral contraceptives that contain drospirenone.⁵⁰ Drospirenone is molecularly related to spironolactone, which has prompted the consideration of whether spironolactone use also conveys a risk for venous thromboembolism. Reassuringly, a retrospective study of claims data found that individuals on spironolactone were not more likely to develop a pulmonary embolism or a deep venous thrombosis than matched controls treated with tetracycline antibiotics, with a point estimate favoring decreased risk.⁵¹

Monitoring

Given that one of spironolactone’s mechanisms of action is aldosterone antagonism and thus the inhibition of potassium excretion, there have been concerns regarding risk for hyperkalemia. A retrospective study analyzing data from 2000 to 2014 found that, among 974 young women receiving spironolactone therapy, the rate of hyperkalemia was 0.72%, which is equivalent to the 0.76% baseline rate of hyperkalemia in the same population.⁵² Subsequent studies also have found that spironolactone does not appear to be associated with a meaningful risk for hyperkalemia among young healthy patients treated for acne.^38,53 These studies suggest that routine potassium monitoring is of low usefulness for healthy young women taking spironolactone for acne. The 2024 American Academy of Dermatology guidelines on the management of acne also state that potassium monitoring is not needed in healthy patients but that potassium testing should be considered for those with risk factors for hyperkalemia (eg, older age, medical comorbidities, medications).⁴⁰ Clinicians should still engage in shared decision making with patients to determine whether to check potassium. If potassium is to be monitored, it should be checked 1 to 2 weeks after spironolactone is started.^45,54

Since drospirenone also has aldosterone antagonistic properties,⁵⁵ there have been concerns about whether concomitant use of spironolactone and drospirenone-containing combined oral contraceptives might increase the risk for hyperkalemia.⁵⁶ However, a retrospective cohort study analyzing data from more than 1 million women found that drospirenone is not any more likely than levonorgestrel to cause hyperkalemia and that there is no interaction between drospirenone and spironolactone for hyperkalemia.⁵⁷ A subsequent prospective study of 27 women treated with combined oral contraceptives containing ethinyl estradiol/drospirenone and spironolactone also did not find any significant elevations in potassium.⁵⁸ Data from these studies suggest that spironolactone can safely be co-administered with drospirenone-containing combined oral contraceptives.

Reproductive Risks

Despite its utility in treating acne, spironolactone should not be used during pregnancy, and appropriate pregnancy prevention is recommended. Spironolactone crosses the placenta, and some animal studies have shown feminization of male fetuses.⁵⁹ While human data are limited to a few case reports that did not demonstrate an association of major malformations,⁶⁰ it generally is recommended to avoid spironolactone during pregnancy. Small studies have found that spironolactone has minimal transfer to breastmilk and is not associated with adverse effects in breastfed infants.^61-63 Accordingly, the World Health Organization considers spironolactone to be compatible with breastfeeding.⁶⁴ Notably, spironolactone may be associated with lactation suppression^65,66; therefore, it may be best if lactating patients ensure that their milk production is established prior to starting spironolactone and to increase their water intake to offset the diuretic effects.

Spironolactone also can result in gynecomastia in men and therefore typically is not prescribed for the treatment of acne in this population in oral form¹⁰; however, topical antiandrogens such as clascoterone can be used in both women and men with acne.⁶⁷

Conclusion

Spironolactone is a well-tolerated and effective treatment for women with acne, both in adult and adolescent populations. It is a potentially underutilized alternative to oral antibiotics. Spironolactone also is affordable, fully covered without any requirements in almost 90% of states under Medicaid and with a monthly cost of only $4.00 when obtained through major retailers in the United States, making it an optimal long-term treatment option for many patients.^52,68 We recommend a starting dose of 100 mg/d, which can be increased to 150 mg/d to 200 mg/d if needed for better acne control or decreased if adverse effects occur or acne clears. Potassium monitoring is of low usefulness in young healthy women, and studies have not identified an association between spironolactone use and increased risk for cancer.

Spironolactone is increasingly used off label for acne treatment and is now being prescribed for women with acne at a frequency similar to oral antibiotics.^1,2 In this article, we provide an overview of spironolactone use for acne treatment and discuss recent clinical trials and practical strategies for patient selection, dosing, adverse effect management, and monitoring (Table).

History and Mechanism of Action

Because sebaceous gland activity is an important component of acne pathogenesis and is regulated by androgens,³ there has long been interest in identifying treatment strategies that can target the role of hormones in activating the sebaceous gland. In the 1980s, it became apparent that spironolactone, originally developed as a potassium-sparing diuretic, also might possess antiandrogenic properties that could be useful in the treatment of acne.⁴ Spironolactone has been found to decrease testosterone production, inhibit testosterone and dihydrotestosterone binding to androgen receptors,^5-8 and block 5α-reductase receptors of the sebaceous glands of skin.⁹

In 1984, Goodfellow et al¹⁰ conducted a trial in which 36 male and female patients with severe acne were randomized to placebo or spironolactone doses ranging from 50 to 200 mg/d. They found that spironolactone resulted in dose-dependent reductions of sebum production as well as improvement in patient- and clinician-reported assessments of acne. In 1986, another placebo-controlled crossover trial by Muhlemann et al¹¹ provided further support for the effectiveness of spironolactone for acne. This trial randomized 21 women to placebo or spironolactone 200 mg/d and found that spironolactone was associated with statistically significant (P<.001) improvements in acne lesion counts.

Recent Observational Studies and Trials

Following these early trials, several large case series have been published describing the successful use of spironolactone for acne, including a 2020 retrospective case series from the Mayo Clinic describing 395 patients.¹² The investigators found that almost 66% of patients had a complete response and almost 85% had a complete response or a partial response greater than 50%. They also found that the median time to initial response and maximal response were 3 and 5 months, respectively, and that efficacy was observed across acne subtypes, including for nodulocystic acne.¹² In addition, a 2021 case series describing 403 patients treated with spironolactone found that approximately 80% had reduction or complete clearance of acne, with improvements observed for both facial and truncal acne. In this cohort, doses of 100 to 150 mg/d typically were the most successful.¹³ A case series of 80 adolescent females also highlighted the efficacy of spironolactone in younger populations.¹⁴

Adding to these observational data, the multicenter, phase 3, double-blind Spironolactone for Adult Female Acne (SAFA) trial included 410 women (mean age, 29.2 years) who were randomized to receive either placebo or intervention (spironolactone 50 mg/d until week 6 and 100 mg/d until week 24).¹⁵ At 24 weeks, greater improvement in quality of life and participant self-assessed improvement were observed in the spironolactone group. In addition, at 12 weeks, rates of success were higher in the spironolactone group using the Investigator Global Assessment score (adjusted odds ratio 5.18 [95% CI, 2.18- 12.28]). Those randomized to receive spironolactone also had lower rates of oral antibiotic use at 52 weeks than the placebo group did (5.8% vs 13.5%, respectively).

In the SAFA trial, spironolactone was well tolerated; the most common adverse effects relative to placebo were lightheadedness (19% for spironolactone vs 12% for placebo) and headache (20% for spironolactone vs 12% for placebo). Notably, more than 95% of patients were able to increase from 50 mg/d to 100 mg/d at week 6, with greater than 90% tolerating 100 mg/d. As observational data suggest that spironolactone takes 3 to 5 months to reach peak efficacy, these findings provide further support that starting at a dose of at least 100 mg/d is likely optimal for most patients.¹⁶

A Potential Alternative to Oral Antibiotics

Oral antibiotics such as tetracyclines have long played a central role in the treatment of acne and remain a first-line treatment option.¹⁷ In addition, many of these antibiotic courses exceed 6 months in duration.¹ In fact, dermatologists prescribe more antibiotics per capita than any other specialty^1,18-20; however, this can be associated with the development of antibiotic resistance,^21,22 as well as other antibiotic-associated complications, including inflammatory bowel disease,²³ pharyngitis,²⁴ Clostridium difficile infections, and cancer.^25-29

In addition to these concerns, many patients may prefer nonantibiotic alternatives to oral antibiotics, with more than 75% preferring a nonantibiotic option if available. For female patients with acne, antiandrogens such as spironolactone have been suggested as a potential alternative.³⁰ A 10-year retrospective study of female patients with acne found that those who had ever received hormonal therapy (ie, spironolactone or a combined oral contraceptive) received fewer cumulative days of oral antibiotics than those who did not (226 days vs 302 days, respectively).³¹ In addition, while oral antibiotics were the most common initial therapy prescribed for patients, as they progressed through their treatment course, more patients ended up on hormonal therapy than oral antibiotics. This study suggests that hormonal therapy such as spironolactone could represent an alternative to the use of systemic antibiotics.³¹

Further supporting the role of spironolactone as an alternative to oral antibiotics, a 2018 analysis of claims data found that spironolactone may have similar effectiveness to oral antibiotics for the treatment of acne.32 After adjusting for age and topical retinoid and oral contraceptive use, this study found that there was no significant difference in the odds of being prescribed a different systemic treatment within 1 year (ie, treatment failure) among those starting spironolactone vs those starting oral tetracycline-class antibiotics as their initial therapy for acne.

A multicenter, randomized, double-blind trial (Female Acne Spironolactone vs doxyCycline Efficacy [FASCE]) also evaluated the comparative effectiveness of doxycycline 100 mg/d for 3 months followed by an oral placebo for 3 months vs spironolactone 150 mg/d for 6 months among 133 adult women with acne. This study found that spironolactone had statistically significantly greater rates of Investigator Global Assessment treatment success after 6 months (odds ratio 2.87 [95% CI, 1.38-5.99; P=.007]).³³ Since spironolactone historically has been prescribed less often than oral antibiotics for women with acne, these findings support spironolactone as an underutilized treatment alternative. The ongoing Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial—a 16-week, blinded trial comparing 100 mg/d doses of both drugs—should provide additional evidence regarding the relative role of spironolactone and oral antibiotics in the management of acne.³⁴

Ultimately, the decision to use spironolactone or other treatments such as oral antibiotics should be based on shared decision making between clinician and patient. Spironolactone has a relatively slow onset of efficacy, and other options such as oral antibiotics might be preferred by those looking for more immediate results; however, as women with acne often have activity that persists into adulthood, spironolactone might be preferable as a long-term maintenance therapy to avoid complications of prolonged antibiotic use.³⁵ Comorbidities also will influence the optimal choice of therapy (eg, spironolactone might be preferred in someone with inflammatory bowel disease, and oral antibiotics might be preferred in someone with orthostatic hypotension).

Patient Selection

Acne occurring along the lower face or jawline in adult women sometimes is referred to as hormonal acne, but this dogma is not particularly evidence based. An observational study of 374 patients found that almost 90% of adult women had acne involving multiple facial zones with a spectrum of facial acne severity similar to that in adolescents.³⁶ Only a small subset of these patients (11.2%) had acne localized solely to the mandibular area. In addition, acne along the lower face is not predictive of hyperandrogenism (eg, polycystic ovary syndrome).³⁷ Antiandrogen therapies such as spironolactone and clascoterone are effective in both men and women with acne^10,38 and in adolescents and adults, suggesting that hormones play a fundamental role in all acne and that addressing this mechanism can be useful broadly. Therefore, hormonal therapies such as spironolactone should not be restricted to only adult women with acne along the lower face.

While spironolactone can be effective for acne treatment in any age group, it may be most effective for adult women with acne. In the SAFA trial, prespecified subgroup analyses showed a statistically significant (P=.005) interaction term for age (categorized as <25 years and ≥25 years), which suggested that spironolactone might be a more effective treatment for women 25 years and older.¹⁵ In addition, subgroup analyses in the aforementioned 2018 analysis of claims data found that spironolactone was more effective relative to oral antibiotics in adults vs adolescents.³² Despite these limitations, several case series have highlighted that spironolactone is effective among adolescent populations with acne. A case series of spironolactone use in 73 patients aged 19 years or younger found that 68% of patients demonstrated resolution or improvement in their acne after spironolactone treatment.³⁹ Another case series among 80 adolescent females reported 80% of patients experiencing improvement of their acne.¹⁴

For those with more severe acne, spironolactone can be combined with other complementary treatment approaches such as topicals, oral antibiotics, or procedural modalities.⁴⁰

Dosing

We recommend starting spironolactone at a dose of 100 mg/d (the patient can take 50 mg/d for 1 week, then increase to 100 mg/d if there are no adverse effects at the lower dose). In the 1984 trial by Goodfellow et al,¹⁰ participants were randomized to doses of 50 mg/d, 100 mg/d, 150 mg/d, and 200 mg/d. In this trial, efficacy assessed by objective and subjective outcomes did not plateau until doses of 100 mg/d to 150 mg/d. In addition, a case series of 403 patients found that the most successful dosage of spironolactone generally was 100 mg/d or higher.¹³ Most of the patients who were started at this dosage either stayed at this level or escalated, whereas patients who started at lower dosages (25-75 mg/d) frequently increased their dosage over time. The SAFA trial also highlighted that most patients can tolerate a spironolactone dose of 100 mg/d.¹⁵ For specific populations, such as patients with polycystic ovary syndrome, a higher dose (mean dosage of 143 mg/d) may be required for efficacy.⁴¹ Given the slow onset of efficacy, typically taking 3 to 5 months, and the low rate of adverse effects, we believe the optimal starting dose is 100 mg/s to 150 mg/d. If adverse effects occur or lesions clear, then the dosage may be reduced.

Adverse Effects

Spironolactone generally is well tolerated; in the SAFA and FASCE trials, fewer than 1% of participants discontinued due to adverse effects.^15,33 Rates of discontinuation due to adverse effects typically have been less than 5% in case series of patients treated in routine clinical practice.^12-14

Because spironolactone is a diuretic and antihypertensive, the most common adverse effects are related to these characteristics. In the SAFA trial, dizziness, lightheadedness, and vertigo were reported more commonly in the spironolactone group than in the placebo group (19% vs 12%, respectively). Similarly, headaches also were reported more frequently in the spironolactone group than in the placebo group (20% vs 12%, respectively).¹⁵ One case series found that, among the 267 patients on spironolactone whose blood pressure was monitored, the mean reduction in systolic blood pressure was 3.5 mm Hg and the mean reduction in diastolic blood pressure was 0.9 mm Hg.¹³ For those with baseline orthostasis or in those who experience adverse effects related to hypotension, reducing the dose often can be helpful. Of note, while doses of 100 mg/d to 150 mg/d often are the most effective, randomized trials have found that spironolactone still can be effective for acne at doses as low as 25 mg/d to 50 mg/d.^10,38

Menstrual irregularities are another commonly cited adverse effect of spironolactone. While a systematic review found that 15% to 30% of patients treated with spironolactone experience menstrual irregularities, it has been difficult to evaluate whether this is due to the medication or other comorbidities, such as polycystic ovary syndrome.⁴² Notably, in the SAFA trial, rates of menstrual irregularities were equivalent between the spironolactone and placebo groups at a dose of 100 mg/d (32% vs 35%, respectively).¹⁵ In contrast, in the FASCE trial, menstrual irregularities were more commonly reported at a dose of 150 mg/d.³³ These findings are consistent with observational data suggesting that menstrual irregularities are much more common at spironolactone doses greater than 100 mg/d.⁴² Additionally, some evidence supports that for some patients these menstrual irregularities may resolve within 2 to 3 months of continued treatment.⁴³ It has been noted in several studies that menstrual irregularities are less likely to occur in patients who are using combined oral contraceptives; therefore, for patients who are amenable and have no contraindications, combined oral contraceptives can be considered to prevent or address menstrual irregularities.^13,42,44

More generally, combined oral contraceptives can be an excellent combination with spironolactone, as they have complementary characteristics. Spironolactone primarily blocks the effects of androgens, while combined oral contraceptives predominantly block the production of androgens. Whereas spironolactone typically causes hypotension and menstrual irregularities, combined oral contraceptives cause hypertension and help to regulate the menstrual cycle.

Spironolactone carries an official US Food and Drug Administration warning regarding possible tumorigenicity that is based on animal studies that used up to 150 times the normal dose of spironolactone used in humans⁴⁵; however, observational studies in humans have not identified such an association when spironolactone is used in normal clinical settings. A systematic review and metanalysis in 2022 reviewed data from a total population of more than 4 million individuals and found that there was no statistically significant association between spironolactone use and the risk for breast, ovarian, bladder, kidney, gastric, or esophageal cancers.⁴⁶ Additional studies also found no association between spironolactone use and cancers.⁴⁸ A more recent cohort study specifically among patients treated with spironolactone for acne also found no significant increased risk for breast cancer.⁴⁹

Combined oral contraceptives are associated with an increased risk for venous thromboembolisms, and there have been concerns that this risk may be greater in combined oral contraceptives that contain drospirenone.⁵⁰ Drospirenone is molecularly related to spironolactone, which has prompted the consideration of whether spironolactone use also conveys a risk for venous thromboembolism. Reassuringly, a retrospective study of claims data found that individuals on spironolactone were not more likely to develop a pulmonary embolism or a deep venous thrombosis than matched controls treated with tetracycline antibiotics, with a point estimate favoring decreased risk.⁵¹

Monitoring

Given that one of spironolactone’s mechanisms of action is aldosterone antagonism and thus the inhibition of potassium excretion, there have been concerns regarding risk for hyperkalemia. A retrospective study analyzing data from 2000 to 2014 found that, among 974 young women receiving spironolactone therapy, the rate of hyperkalemia was 0.72%, which is equivalent to the 0.76% baseline rate of hyperkalemia in the same population.⁵² Subsequent studies also have found that spironolactone does not appear to be associated with a meaningful risk for hyperkalemia among young healthy patients treated for acne.^38,53 These studies suggest that routine potassium monitoring is of low usefulness for healthy young women taking spironolactone for acne. The 2024 American Academy of Dermatology guidelines on the management of acne also state that potassium monitoring is not needed in healthy patients but that potassium testing should be considered for those with risk factors for hyperkalemia (eg, older age, medical comorbidities, medications).⁴⁰ Clinicians should still engage in shared decision making with patients to determine whether to check potassium. If potassium is to be monitored, it should be checked 1 to 2 weeks after spironolactone is started.^45,54

Since drospirenone also has aldosterone antagonistic properties,⁵⁵ there have been concerns about whether concomitant use of spironolactone and drospirenone-containing combined oral contraceptives might increase the risk for hyperkalemia.⁵⁶ However, a retrospective cohort study analyzing data from more than 1 million women found that drospirenone is not any more likely than levonorgestrel to cause hyperkalemia and that there is no interaction between drospirenone and spironolactone for hyperkalemia.⁵⁷ A subsequent prospective study of 27 women treated with combined oral contraceptives containing ethinyl estradiol/drospirenone and spironolactone also did not find any significant elevations in potassium.⁵⁸ Data from these studies suggest that spironolactone can safely be co-administered with drospirenone-containing combined oral contraceptives.

Reproductive Risks

Despite its utility in treating acne, spironolactone should not be used during pregnancy, and appropriate pregnancy prevention is recommended. Spironolactone crosses the placenta, and some animal studies have shown feminization of male fetuses.⁵⁹ While human data are limited to a few case reports that did not demonstrate an association of major malformations,⁶⁰ it generally is recommended to avoid spironolactone during pregnancy. Small studies have found that spironolactone has minimal transfer to breastmilk and is not associated with adverse effects in breastfed infants.^61-63 Accordingly, the World Health Organization considers spironolactone to be compatible with breastfeeding.⁶⁴ Notably, spironolactone may be associated with lactation suppression^65,66; therefore, it may be best if lactating patients ensure that their milk production is established prior to starting spironolactone and to increase their water intake to offset the diuretic effects.

Spironolactone also can result in gynecomastia in men and therefore typically is not prescribed for the treatment of acne in this population in oral form¹⁰; however, topical antiandrogens such as clascoterone can be used in both women and men with acne.⁶⁷

Conclusion

Spironolactone is a well-tolerated and effective treatment for women with acne, both in adult and adolescent populations. It is a potentially underutilized alternative to oral antibiotics. Spironolactone also is affordable, fully covered without any requirements in almost 90% of states under Medicaid and with a monthly cost of only $4.00 when obtained through major retailers in the United States, making it an optimal long-term treatment option for many patients.^52,68 We recommend a starting dose of 100 mg/d, which can be increased to 150 mg/d to 200 mg/d if needed for better acne control or decreased if adverse effects occur or acne clears. Potassium monitoring is of low usefulness in young healthy women, and studies have not identified an association between spironolactone use and increased risk for cancer.

Spironolactone is increasingly used off label for acne treatment and is now being prescribed for women with acne at a frequency similar to oral antibiotics.^1,2 In this article, we provide an overview of spironolactone use for acne treatment and discuss recent clinical trials and practical strategies for patient selection, dosing, adverse effect management, and monitoring (Table).

History and Mechanism of Action

Because sebaceous gland activity is an important component of acne pathogenesis and is regulated by androgens,³ there has long been interest in identifying treatment strategies that can target the role of hormones in activating the sebaceous gland. In the 1980s, it became apparent that spironolactone, originally developed as a potassium-sparing diuretic, also might possess antiandrogenic properties that could be useful in the treatment of acne.⁴ Spironolactone has been found to decrease testosterone production, inhibit testosterone and dihydrotestosterone binding to androgen receptors,^5-8 and block 5α-reductase receptors of the sebaceous glands of skin.⁹

In 1984, Goodfellow et al¹⁰ conducted a trial in which 36 male and female patients with severe acne were randomized to placebo or spironolactone doses ranging from 50 to 200 mg/d. They found that spironolactone resulted in dose-dependent reductions of sebum production as well as improvement in patient- and clinician-reported assessments of acne. In 1986, another placebo-controlled crossover trial by Muhlemann et al¹¹ provided further support for the effectiveness of spironolactone for acne. This trial randomized 21 women to placebo or spironolactone 200 mg/d and found that spironolactone was associated with statistically significant (P<.001) improvements in acne lesion counts.

Recent Observational Studies and Trials

Following these early trials, several large case series have been published describing the successful use of spironolactone for acne, including a 2020 retrospective case series from the Mayo Clinic describing 395 patients.¹² The investigators found that almost 66% of patients had a complete response and almost 85% had a complete response or a partial response greater than 50%. They also found that the median time to initial response and maximal response were 3 and 5 months, respectively, and that efficacy was observed across acne subtypes, including for nodulocystic acne.¹² In addition, a 2021 case series describing 403 patients treated with spironolactone found that approximately 80% had reduction or complete clearance of acne, with improvements observed for both facial and truncal acne. In this cohort, doses of 100 to 150 mg/d typically were the most successful.¹³ A case series of 80 adolescent females also highlighted the efficacy of spironolactone in younger populations.¹⁴

Adding to these observational data, the multicenter, phase 3, double-blind Spironolactone for Adult Female Acne (SAFA) trial included 410 women (mean age, 29.2 years) who were randomized to receive either placebo or intervention (spironolactone 50 mg/d until week 6 and 100 mg/d until week 24).¹⁵ At 24 weeks, greater improvement in quality of life and participant self-assessed improvement were observed in the spironolactone group. In addition, at 12 weeks, rates of success were higher in the spironolactone group using the Investigator Global Assessment score (adjusted odds ratio 5.18 [95% CI, 2.18- 12.28]). Those randomized to receive spironolactone also had lower rates of oral antibiotic use at 52 weeks than the placebo group did (5.8% vs 13.5%, respectively).

In the SAFA trial, spironolactone was well tolerated; the most common adverse effects relative to placebo were lightheadedness (19% for spironolactone vs 12% for placebo) and headache (20% for spironolactone vs 12% for placebo). Notably, more than 95% of patients were able to increase from 50 mg/d to 100 mg/d at week 6, with greater than 90% tolerating 100 mg/d. As observational data suggest that spironolactone takes 3 to 5 months to reach peak efficacy, these findings provide further support that starting at a dose of at least 100 mg/d is likely optimal for most patients.¹⁶

A Potential Alternative to Oral Antibiotics

Oral antibiotics such as tetracyclines have long played a central role in the treatment of acne and remain a first-line treatment option.¹⁷ In addition, many of these antibiotic courses exceed 6 months in duration.¹ In fact, dermatologists prescribe more antibiotics per capita than any other specialty^1,18-20; however, this can be associated with the development of antibiotic resistance,^21,22 as well as other antibiotic-associated complications, including inflammatory bowel disease,²³ pharyngitis,²⁴ Clostridium difficile infections, and cancer.^25-29

In addition to these concerns, many patients may prefer nonantibiotic alternatives to oral antibiotics, with more than 75% preferring a nonantibiotic option if available. For female patients with acne, antiandrogens such as spironolactone have been suggested as a potential alternative.³⁰ A 10-year retrospective study of female patients with acne found that those who had ever received hormonal therapy (ie, spironolactone or a combined oral contraceptive) received fewer cumulative days of oral antibiotics than those who did not (226 days vs 302 days, respectively).³¹ In addition, while oral antibiotics were the most common initial therapy prescribed for patients, as they progressed through their treatment course, more patients ended up on hormonal therapy than oral antibiotics. This study suggests that hormonal therapy such as spironolactone could represent an alternative to the use of systemic antibiotics.³¹

Further supporting the role of spironolactone as an alternative to oral antibiotics, a 2018 analysis of claims data found that spironolactone may have similar effectiveness to oral antibiotics for the treatment of acne.32 After adjusting for age and topical retinoid and oral contraceptive use, this study found that there was no significant difference in the odds of being prescribed a different systemic treatment within 1 year (ie, treatment failure) among those starting spironolactone vs those starting oral tetracycline-class antibiotics as their initial therapy for acne.

A multicenter, randomized, double-blind trial (Female Acne Spironolactone vs doxyCycline Efficacy [FASCE]) also evaluated the comparative effectiveness of doxycycline 100 mg/d for 3 months followed by an oral placebo for 3 months vs spironolactone 150 mg/d for 6 months among 133 adult women with acne. This study found that spironolactone had statistically significantly greater rates of Investigator Global Assessment treatment success after 6 months (odds ratio 2.87 [95% CI, 1.38-5.99; P=.007]).³³ Since spironolactone historically has been prescribed less often than oral antibiotics for women with acne, these findings support spironolactone as an underutilized treatment alternative. The ongoing Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial—a 16-week, blinded trial comparing 100 mg/d doses of both drugs—should provide additional evidence regarding the relative role of spironolactone and oral antibiotics in the management of acne.³⁴

Ultimately, the decision to use spironolactone or other treatments such as oral antibiotics should be based on shared decision making between clinician and patient. Spironolactone has a relatively slow onset of efficacy, and other options such as oral antibiotics might be preferred by those looking for more immediate results; however, as women with acne often have activity that persists into adulthood, spironolactone might be preferable as a long-term maintenance therapy to avoid complications of prolonged antibiotic use.³⁵ Comorbidities also will influence the optimal choice of therapy (eg, spironolactone might be preferred in someone with inflammatory bowel disease, and oral antibiotics might be preferred in someone with orthostatic hypotension).

Patient Selection

Acne occurring along the lower face or jawline in adult women sometimes is referred to as hormonal acne, but this dogma is not particularly evidence based. An observational study of 374 patients found that almost 90% of adult women had acne involving multiple facial zones with a spectrum of facial acne severity similar to that in adolescents.³⁶ Only a small subset of these patients (11.2%) had acne localized solely to the mandibular area. In addition, acne along the lower face is not predictive of hyperandrogenism (eg, polycystic ovary syndrome).³⁷ Antiandrogen therapies such as spironolactone and clascoterone are effective in both men and women with acne^10,38 and in adolescents and adults, suggesting that hormones play a fundamental role in all acne and that addressing this mechanism can be useful broadly. Therefore, hormonal therapies such as spironolactone should not be restricted to only adult women with acne along the lower face.

While spironolactone can be effective for acne treatment in any age group, it may be most effective for adult women with acne. In the SAFA trial, prespecified subgroup analyses showed a statistically significant (P=.005) interaction term for age (categorized as <25 years and ≥25 years), which suggested that spironolactone might be a more effective treatment for women 25 years and older.¹⁵ In addition, subgroup analyses in the aforementioned 2018 analysis of claims data found that spironolactone was more effective relative to oral antibiotics in adults vs adolescents.³² Despite these limitations, several case series have highlighted that spironolactone is effective among adolescent populations with acne. A case series of spironolactone use in 73 patients aged 19 years or younger found that 68% of patients demonstrated resolution or improvement in their acne after spironolactone treatment.³⁹ Another case series among 80 adolescent females reported 80% of patients experiencing improvement of their acne.¹⁴

For those with more severe acne, spironolactone can be combined with other complementary treatment approaches such as topicals, oral antibiotics, or procedural modalities.⁴⁰

Dosing

We recommend starting spironolactone at a dose of 100 mg/d (the patient can take 50 mg/d for 1 week, then increase to 100 mg/d if there are no adverse effects at the lower dose). In the 1984 trial by Goodfellow et al,¹⁰ participants were randomized to doses of 50 mg/d, 100 mg/d, 150 mg/d, and 200 mg/d. In this trial, efficacy assessed by objective and subjective outcomes did not plateau until doses of 100 mg/d to 150 mg/d. In addition, a case series of 403 patients found that the most successful dosage of spironolactone generally was 100 mg/d or higher.¹³ Most of the patients who were started at this dosage either stayed at this level or escalated, whereas patients who started at lower dosages (25-75 mg/d) frequently increased their dosage over time. The SAFA trial also highlighted that most patients can tolerate a spironolactone dose of 100 mg/d.¹⁵ For specific populations, such as patients with polycystic ovary syndrome, a higher dose (mean dosage of 143 mg/d) may be required for efficacy.⁴¹ Given the slow onset of efficacy, typically taking 3 to 5 months, and the low rate of adverse effects, we believe the optimal starting dose is 100 mg/s to 150 mg/d. If adverse effects occur or lesions clear, then the dosage may be reduced.

Adverse Effects

Spironolactone generally is well tolerated; in the SAFA and FASCE trials, fewer than 1% of participants discontinued due to adverse effects.^15,33 Rates of discontinuation due to adverse effects typically have been less than 5% in case series of patients treated in routine clinical practice.^12-14

Because spironolactone is a diuretic and antihypertensive, the most common adverse effects are related to these characteristics. In the SAFA trial, dizziness, lightheadedness, and vertigo were reported more commonly in the spironolactone group than in the placebo group (19% vs 12%, respectively). Similarly, headaches also were reported more frequently in the spironolactone group than in the placebo group (20% vs 12%, respectively).¹⁵ One case series found that, among the 267 patients on spironolactone whose blood pressure was monitored, the mean reduction in systolic blood pressure was 3.5 mm Hg and the mean reduction in diastolic blood pressure was 0.9 mm Hg.¹³ For those with baseline orthostasis or in those who experience adverse effects related to hypotension, reducing the dose often can be helpful. Of note, while doses of 100 mg/d to 150 mg/d often are the most effective, randomized trials have found that spironolactone still can be effective for acne at doses as low as 25 mg/d to 50 mg/d.^10,38

Menstrual irregularities are another commonly cited adverse effect of spironolactone. While a systematic review found that 15% to 30% of patients treated with spironolactone experience menstrual irregularities, it has been difficult to evaluate whether this is due to the medication or other comorbidities, such as polycystic ovary syndrome.⁴² Notably, in the SAFA trial, rates of menstrual irregularities were equivalent between the spironolactone and placebo groups at a dose of 100 mg/d (32% vs 35%, respectively).¹⁵ In contrast, in the FASCE trial, menstrual irregularities were more commonly reported at a dose of 150 mg/d.³³ These findings are consistent with observational data suggesting that menstrual irregularities are much more common at spironolactone doses greater than 100 mg/d.⁴² Additionally, some evidence supports that for some patients these menstrual irregularities may resolve within 2 to 3 months of continued treatment.⁴³ It has been noted in several studies that menstrual irregularities are less likely to occur in patients who are using combined oral contraceptives; therefore, for patients who are amenable and have no contraindications, combined oral contraceptives can be considered to prevent or address menstrual irregularities.^13,42,44

More generally, combined oral contraceptives can be an excellent combination with spironolactone, as they have complementary characteristics. Spironolactone primarily blocks the effects of androgens, while combined oral contraceptives predominantly block the production of androgens. Whereas spironolactone typically causes hypotension and menstrual irregularities, combined oral contraceptives cause hypertension and help to regulate the menstrual cycle.

Spironolactone carries an official US Food and Drug Administration warning regarding possible tumorigenicity that is based on animal studies that used up to 150 times the normal dose of spironolactone used in humans⁴⁵; however, observational studies in humans have not identified such an association when spironolactone is used in normal clinical settings. A systematic review and metanalysis in 2022 reviewed data from a total population of more than 4 million individuals and found that there was no statistically significant association between spironolactone use and the risk for breast, ovarian, bladder, kidney, gastric, or esophageal cancers.⁴⁶ Additional studies also found no association between spironolactone use and cancers.⁴⁸ A more recent cohort study specifically among patients treated with spironolactone for acne also found no significant increased risk for breast cancer.⁴⁹

Combined oral contraceptives are associated with an increased risk for venous thromboembolisms, and there have been concerns that this risk may be greater in combined oral contraceptives that contain drospirenone.⁵⁰ Drospirenone is molecularly related to spironolactone, which has prompted the consideration of whether spironolactone use also conveys a risk for venous thromboembolism. Reassuringly, a retrospective study of claims data found that individuals on spironolactone were not more likely to develop a pulmonary embolism or a deep venous thrombosis than matched controls treated with tetracycline antibiotics, with a point estimate favoring decreased risk.⁵¹

Monitoring

Given that one of spironolactone’s mechanisms of action is aldosterone antagonism and thus the inhibition of potassium excretion, there have been concerns regarding risk for hyperkalemia. A retrospective study analyzing data from 2000 to 2014 found that, among 974 young women receiving spironolactone therapy, the rate of hyperkalemia was 0.72%, which is equivalent to the 0.76% baseline rate of hyperkalemia in the same population.⁵² Subsequent studies also have found that spironolactone does not appear to be associated with a meaningful risk for hyperkalemia among young healthy patients treated for acne.^38,53 These studies suggest that routine potassium monitoring is of low usefulness for healthy young women taking spironolactone for acne. The 2024 American Academy of Dermatology guidelines on the management of acne also state that potassium monitoring is not needed in healthy patients but that potassium testing should be considered for those with risk factors for hyperkalemia (eg, older age, medical comorbidities, medications).⁴⁰ Clinicians should still engage in shared decision making with patients to determine whether to check potassium. If potassium is to be monitored, it should be checked 1 to 2 weeks after spironolactone is started.^45,54

Since drospirenone also has aldosterone antagonistic properties,⁵⁵ there have been concerns about whether concomitant use of spironolactone and drospirenone-containing combined oral contraceptives might increase the risk for hyperkalemia.⁵⁶ However, a retrospective cohort study analyzing data from more than 1 million women found that drospirenone is not any more likely than levonorgestrel to cause hyperkalemia and that there is no interaction between drospirenone and spironolactone for hyperkalemia.⁵⁷ A subsequent prospective study of 27 women treated with combined oral contraceptives containing ethinyl estradiol/drospirenone and spironolactone also did not find any significant elevations in potassium.⁵⁸ Data from these studies suggest that spironolactone can safely be co-administered with drospirenone-containing combined oral contraceptives.

Reproductive Risks

Despite its utility in treating acne, spironolactone should not be used during pregnancy, and appropriate pregnancy prevention is recommended. Spironolactone crosses the placenta, and some animal studies have shown feminization of male fetuses.⁵⁹ While human data are limited to a few case reports that did not demonstrate an association of major malformations,⁶⁰ it generally is recommended to avoid spironolactone during pregnancy. Small studies have found that spironolactone has minimal transfer to breastmilk and is not associated with adverse effects in breastfed infants.^61-63 Accordingly, the World Health Organization considers spironolactone to be compatible with breastfeeding.⁶⁴ Notably, spironolactone may be associated with lactation suppression^65,66; therefore, it may be best if lactating patients ensure that their milk production is established prior to starting spironolactone and to increase their water intake to offset the diuretic effects.

Spironolactone also can result in gynecomastia in men and therefore typically is not prescribed for the treatment of acne in this population in oral form¹⁰; however, topical antiandrogens such as clascoterone can be used in both women and men with acne.⁶⁷

Conclusion

Spironolactone is a well-tolerated and effective treatment for women with acne, both in adult and adolescent populations. It is a potentially underutilized alternative to oral antibiotics. Spironolactone also is affordable, fully covered without any requirements in almost 90% of states under Medicaid and with a monthly cost of only $4.00 when obtained through major retailers in the United States, making it an optimal long-term treatment option for many patients.^52,68 We recommend a starting dose of 100 mg/d, which can be increased to 150 mg/d to 200 mg/d if needed for better acne control or decreased if adverse effects occur or acne clears. Potassium monitoring is of low usefulness in young healthy women, and studies have not identified an association between spironolactone use and increased risk for cancer.

How did I develop a strong interest in acne and rosacea? Interest on a personal level was with me throughout my adolescence and post-teen years as I suffered with very severe facial acne from ages 13 through 23 (1967-1977). I was sometimes called “pizza face” in high school, and biweekly trips to a dermatology office that always had a packed waiting room were of little help that I could appreciate visibly. Six straight years of extractions, intralesional injections, draining of fluctuant cysts, UVC light treatments, oral tetracycline, irritating topical formulations of benzoyl peroxide and tretinoin, and topical sulfacetamide-sulfur products resulted in minimal improvement. However, maybe all of this did something to what was happening underneath the skin surface, as I have no residual acne scars. I do recall vividly that I walked the halls in high school and college consistently affected by a very red face from the topical agents and smelling like rotten eggs from the topical sulfur application. I fortunately handled it well emotionally and socially, for which I am very thankful. Many people affected with acne do not.

In dermatology, I have always had a strong interest in pathophysiology and therapeutics, rooted I am sure in my background as a pharmacist. Although I was always interested in acne therapy, I was fully captivated by a presentation given by Dr. Jim Leyden many years ago at a small meeting in Myrtle Beach, South Carolina. He brought the subject of acne to life in a way that more than grabbed my complete attention and ignited an interest in learning everything I could about it. Over time, I was fortunate enough to work alongside Dr. Leyden and many other household names in acne at meetings and publications to further education on one of the most common disease states seen in ambulatory dermatology practices worldwide. The rest is history, leading to almost 4 decades of work in acne on many levels in dermatology, all being efforts that I am grateful for.

What I have observed to date is that we have had few revolutionary advances in acne therapy, the major one being oral isotretinoin, which was first brought to market in 1982. We are still utilizing many of the same therapeutic agents that I used back when I was treated for acne. A few new topical compounds have emerged, such as dapsone and clascoterone, and a narrow-spectrum tetracycline agent, sarecycline, also was developed. These agents do represent important advances with some specific benefits. There have been many major improvements in drug delivery formulations, including several vehicle technologies that allow augmented skin tolerability, increased efficacy, and improved stability, allowing for combination therapy products containing 2 or 3 active ingredients. A recent example is the first triple-combination topical acne therapy with excellent supporting data on speed of onset, efficacy, and safety.¹

Technological advances also have aided in the development of modified- or extended-release formulations of oral antibiotics, such as doxycycline and minocycline, which allow for reduced adverse effects and lower daily dosages. Lidose formulations of isotretinoin have circumvented the need for concurrent ingestion of a high-fat meal to facilitate its absorption in the gastrointestinal tract (as required with conventional formulations). Many hours also have been spent on delivery devices and vehicles such as pumps, foams, and aqueous-based gels. Let us not forget the efforts and myriad products directed at skin care, cosmeceuticals, and physical devices (lasers and lights) for acne. Regardless of the above, we have not seen the monumental therapeutic and research revolution for acne that we have experienced more recently with biologic agents, Janus kinase inhibitors, and other modes of action for many common disease states such as atopic dermatitis, psoriasis, alopecia areata, vitiligo, hidradenitis suppurativa, prurigo nodularis, and chronic spontaneous urticaria.

Unfortunately, the slow development of advances in treatments for acne has been compounded further by the widespread availability of generic equivalents of most topical and oral therapies along with several over-the- counter topical medications. The expanded skin care and cosmeceutical product world has further diluted the perceived value of topical prescription therapies for acne. The marked difficulty in achieving and sustaining total clearance of acne, with the exception of many individuals treated with oral isotretinoin, results in many patients searching for other options, often through sources beyond dermatology practices (eg, the internet). While some of these sources may provide valid suggestions, they often are not truly substantiated by valid clinical research and are not formally regulated by the US Food and Drug Administration.

All of the above, in addition to the barriers to medication coverage put in place by third-party organizations such as pharmacy benefit managers, have contributed to the extreme slowdown in the development of new prescription therapies for acne. What this leads me to believe is that until there is a true meeting of the minds of all stakeholders on policies that facilitate access to both established and newly available acne therapies, there will be an enduring diminished incentive to support the development of newer acne treatments that will continue to spiral progressively downward. Some research on acne will always continue, such as the search for an acne vaccine and cutaneous microbiome alterations that are in progress.^2,3 However, I do not see much happening in the foreseeable future. I am not inherently a pessimist or a “prophet of doom,” so I sincerely hope I am wrong.

How did I develop a strong interest in acne and rosacea? Interest on a personal level was with me throughout my adolescence and post-teen years as I suffered with very severe facial acne from ages 13 through 23 (1967-1977). I was sometimes called “pizza face” in high school, and biweekly trips to a dermatology office that always had a packed waiting room were of little help that I could appreciate visibly. Six straight years of extractions, intralesional injections, draining of fluctuant cysts, UVC light treatments, oral tetracycline, irritating topical formulations of benzoyl peroxide and tretinoin, and topical sulfacetamide-sulfur products resulted in minimal improvement. However, maybe all of this did something to what was happening underneath the skin surface, as I have no residual acne scars. I do recall vividly that I walked the halls in high school and college consistently affected by a very red face from the topical agents and smelling like rotten eggs from the topical sulfur application. I fortunately handled it well emotionally and socially, for which I am very thankful. Many people affected with acne do not.

In dermatology, I have always had a strong interest in pathophysiology and therapeutics, rooted I am sure in my background as a pharmacist. Although I was always interested in acne therapy, I was fully captivated by a presentation given by Dr. Jim Leyden many years ago at a small meeting in Myrtle Beach, South Carolina. He brought the subject of acne to life in a way that more than grabbed my complete attention and ignited an interest in learning everything I could about it. Over time, I was fortunate enough to work alongside Dr. Leyden and many other household names in acne at meetings and publications to further education on one of the most common disease states seen in ambulatory dermatology practices worldwide. The rest is history, leading to almost 4 decades of work in acne on many levels in dermatology, all being efforts that I am grateful for.

What I have observed to date is that we have had few revolutionary advances in acne therapy, the major one being oral isotretinoin, which was first brought to market in 1982. We are still utilizing many of the same therapeutic agents that I used back when I was treated for acne. A few new topical compounds have emerged, such as dapsone and clascoterone, and a narrow-spectrum tetracycline agent, sarecycline, also was developed. These agents do represent important advances with some specific benefits. There have been many major improvements in drug delivery formulations, including several vehicle technologies that allow augmented skin tolerability, increased efficacy, and improved stability, allowing for combination therapy products containing 2 or 3 active ingredients. A recent example is the first triple-combination topical acne therapy with excellent supporting data on speed of onset, efficacy, and safety.¹

Technological advances also have aided in the development of modified- or extended-release formulations of oral antibiotics, such as doxycycline and minocycline, which allow for reduced adverse effects and lower daily dosages. Lidose formulations of isotretinoin have circumvented the need for concurrent ingestion of a high-fat meal to facilitate its absorption in the gastrointestinal tract (as required with conventional formulations). Many hours also have been spent on delivery devices and vehicles such as pumps, foams, and aqueous-based gels. Let us not forget the efforts and myriad products directed at skin care, cosmeceuticals, and physical devices (lasers and lights) for acne. Regardless of the above, we have not seen the monumental therapeutic and research revolution for acne that we have experienced more recently with biologic agents, Janus kinase inhibitors, and other modes of action for many common disease states such as atopic dermatitis, psoriasis, alopecia areata, vitiligo, hidradenitis suppurativa, prurigo nodularis, and chronic spontaneous urticaria.

Unfortunately, the slow development of advances in treatments for acne has been compounded further by the widespread availability of generic equivalents of most topical and oral therapies along with several over-the- counter topical medications. The expanded skin care and cosmeceutical product world has further diluted the perceived value of topical prescription therapies for acne. The marked difficulty in achieving and sustaining total clearance of acne, with the exception of many individuals treated with oral isotretinoin, results in many patients searching for other options, often through sources beyond dermatology practices (eg, the internet). While some of these sources may provide valid suggestions, they often are not truly substantiated by valid clinical research and are not formally regulated by the US Food and Drug Administration.

All of the above, in addition to the barriers to medication coverage put in place by third-party organizations such as pharmacy benefit managers, have contributed to the extreme slowdown in the development of new prescription therapies for acne. What this leads me to believe is that until there is a true meeting of the minds of all stakeholders on policies that facilitate access to both established and newly available acne therapies, there will be an enduring diminished incentive to support the development of newer acne treatments that will continue to spiral progressively downward. Some research on acne will always continue, such as the search for an acne vaccine and cutaneous microbiome alterations that are in progress.^2,3 However, I do not see much happening in the foreseeable future. I am not inherently a pessimist or a “prophet of doom,” so I sincerely hope I am wrong.

How did I develop a strong interest in acne and rosacea? Interest on a personal level was with me throughout my adolescence and post-teen years as I suffered with very severe facial acne from ages 13 through 23 (1967-1977). I was sometimes called “pizza face” in high school, and biweekly trips to a dermatology office that always had a packed waiting room were of little help that I could appreciate visibly. Six straight years of extractions, intralesional injections, draining of fluctuant cysts, UVC light treatments, oral tetracycline, irritating topical formulations of benzoyl peroxide and tretinoin, and topical sulfacetamide-sulfur products resulted in minimal improvement. However, maybe all of this did something to what was happening underneath the skin surface, as I have no residual acne scars. I do recall vividly that I walked the halls in high school and college consistently affected by a very red face from the topical agents and smelling like rotten eggs from the topical sulfur application. I fortunately handled it well emotionally and socially, for which I am very thankful. Many people affected with acne do not.

In dermatology, I have always had a strong interest in pathophysiology and therapeutics, rooted I am sure in my background as a pharmacist. Although I was always interested in acne therapy, I was fully captivated by a presentation given by Dr. Jim Leyden many years ago at a small meeting in Myrtle Beach, South Carolina. He brought the subject of acne to life in a way that more than grabbed my complete attention and ignited an interest in learning everything I could about it. Over time, I was fortunate enough to work alongside Dr. Leyden and many other household names in acne at meetings and publications to further education on one of the most common disease states seen in ambulatory dermatology practices worldwide. The rest is history, leading to almost 4 decades of work in acne on many levels in dermatology, all being efforts that I am grateful for.

What I have observed to date is that we have had few revolutionary advances in acne therapy, the major one being oral isotretinoin, which was first brought to market in 1982. We are still utilizing many of the same therapeutic agents that I used back when I was treated for acne. A few new topical compounds have emerged, such as dapsone and clascoterone, and a narrow-spectrum tetracycline agent, sarecycline, also was developed. These agents do represent important advances with some specific benefits. There have been many major improvements in drug delivery formulations, including several vehicle technologies that allow augmented skin tolerability, increased efficacy, and improved stability, allowing for combination therapy products containing 2 or 3 active ingredients. A recent example is the first triple-combination topical acne therapy with excellent supporting data on speed of onset, efficacy, and safety.¹

Technological advances also have aided in the development of modified- or extended-release formulations of oral antibiotics, such as doxycycline and minocycline, which allow for reduced adverse effects and lower daily dosages. Lidose formulations of isotretinoin have circumvented the need for concurrent ingestion of a high-fat meal to facilitate its absorption in the gastrointestinal tract (as required with conventional formulations). Many hours also have been spent on delivery devices and vehicles such as pumps, foams, and aqueous-based gels. Let us not forget the efforts and myriad products directed at skin care, cosmeceuticals, and physical devices (lasers and lights) for acne. Regardless of the above, we have not seen the monumental therapeutic and research revolution for acne that we have experienced more recently with biologic agents, Janus kinase inhibitors, and other modes of action for many common disease states such as atopic dermatitis, psoriasis, alopecia areata, vitiligo, hidradenitis suppurativa, prurigo nodularis, and chronic spontaneous urticaria.

Unfortunately, the slow development of advances in treatments for acne has been compounded further by the widespread availability of generic equivalents of most topical and oral therapies along with several over-the- counter topical medications. The expanded skin care and cosmeceutical product world has further diluted the perceived value of topical prescription therapies for acne. The marked difficulty in achieving and sustaining total clearance of acne, with the exception of many individuals treated with oral isotretinoin, results in many patients searching for other options, often through sources beyond dermatology practices (eg, the internet). While some of these sources may provide valid suggestions, they often are not truly substantiated by valid clinical research and are not formally regulated by the US Food and Drug Administration.

All of the above, in addition to the barriers to medication coverage put in place by third-party organizations such as pharmacy benefit managers, have contributed to the extreme slowdown in the development of new prescription therapies for acne. What this leads me to believe is that until there is a true meeting of the minds of all stakeholders on policies that facilitate access to both established and newly available acne therapies, there will be an enduring diminished incentive to support the development of newer acne treatments that will continue to spiral progressively downward. Some research on acne will always continue, such as the search for an acne vaccine and cutaneous microbiome alterations that are in progress.^2,3 However, I do not see much happening in the foreseeable future. I am not inherently a pessimist or a “prophet of doom,” so I sincerely hope I am wrong.

Spironolactone is an aldosterone antagonist that first was used as a potassium-sparing diuretic to treat heart failure and hypertension. It also possesses antiandrogenic mechanisms including competitively inhibiting androgen receptors, increasing steroid hormone–binding globulin production, and decreasing 5α-reductase activity.¹ These properties have been leveraged in off-label use for dermatologic conditions including acne, hidradenitis suppurativa, androgenic alopecia, and hirsutism.^1,2 Despite being used off-label to treat acne for more than 40 years, spironolactone has not received US Food and Drug Administration approval for this indication.³ Herein, we review the current evidence for use of spironolactone in acne management.

Spironolactone Efficacy

Spironolactone is efficacious for facial and truncal acne in adult females; it cannot be used in males given its anti-androgenic effects.^4,5 In 2 large studies, spironolactone completely or partially cleared facial acne in 75.5% to 85.1% of patients.^4,5 In the first study, which included 395 patients on a median dose of 100 mg/d (range, 25-200 mg/d), clearance of comedonal, papulopustular, and nodulocystic acne was observed.⁴ The second study included 403 patients, most of whom started on spironolactone at 100 mg/d (range, 25-200 mg/d). In addition to facial clearance, patients in this study demonstrated similar rates of partial or complete clearance of acne on the chest (84.0%) and back (80.2%) assessed via a comprehensive acne severity scale.⁵ In both studies, doses of 100 mg/d or higher were most effective, and the median time to initial acne improvement was 3 months, with peak effects occurring after 4 to 6 months of treatment.^4,5 Most patients were using spironolactone monotherapy or spironolactone in combination with topical therapies; however, a minority used it concurrently with oral antibiotics and/or combined oral contraceptives.

Spironolactone has demonstrated comparable efficacy to tetracycline antibiotics. A study comparing the rate of switching to another systemic therapy within 1 year of treatment initiation identified similar rates in patients started on spironolactone (n=962) and those started on tetracyclines (n=4236)(14.4% vs 13.4%, respectively). As switching may indicate treatment failure due to insufficient efficacy, adverse effects, or other causes, these findings may suggest similar effectiveness for spironolactone and tetracyclines.⁶ These treatments also were compared in a randomized controlled trial of 133 patients receiving topical benzoyl peroxide 5% for 6 months and either spironolactone 150 mg/d for 6 months or doxycycline 100 mg/d for 3 months followed by oral placebo for 3 months. At 4 months, spironolactone performed better than doxycycline as assessed using the Adult Female Acne Scoring Tool.³ Although doxycycline was stopped after 3 months and only topical therapy was continued, this finding is notable because guidelines from the American Academy of Dermatology recommend limiting tetracycline use to 3 to 4 months, whereas spironolactone may be continued for prolonged durations.^1,4

While most studies have evaluated the efficacy of spironolactone in adult females, it is increasingly being prescribed in adolescents.⁷ In a study that included 80 females aged 14 to 20 years, 80% (64/80) experienced acne improvement on a median dose of 100 mg/d.⁸ Additionally, in the study evaluating treatment switching rates, more than 80% of 1139 adolescents who were started on spironolactone were not switched to a different systemic therapy within the first year of treatment, demonstrating the efficacy of spironolactone in this demographic.⁶ However, treatment switching was more common among adolescents started on spironolactone compared with those who started on tetracyclines. As noted for adults, the treatment switching rates were the same for spironolactone and tetracycline users; the difference in adolescents may be due to lower influence of hormonal factors or higher therapeutic expectations in this population.⁶

Spironolactone Safety

Spironolactone is well tolerated at doses of 25 to 200 mg/d for acne management. Common adverse effects include diuresis (29% [26/90]), menstrual irregularities (22% [20/90]), fatigue (17% [15/90]), headache (14% [13/90]), and dizziness (12% [11/90]), but they infrequently lead to treatment discontinuation.^4,9 Rates of adverse effects are lower in adolescents compared to adults, although the effects of spironolactone on early endocrine development in adolescents are unknown.⁷ Spironolactone should not be used during pregnancy, and concurrent contraception use is advised because spironolactone has caused feminization of male fetuses in animal studies.^1,10-11

While concerns about potentially severe adverse effects including hypotension, hyperkalemia, and tumorigenicity have been raised, their occurrence in the literature is rare.^5,12-18 In a study evaluating hypotension in 2084 patients taking spironolactone 50 to 200 mg/day for acne, hair loss, and/or hirsutism, 3.1% experienced absolute hypotension, and only 0.26% required dose reduction or discontinuation.¹² Another study of 403 patients taking spironolactone for acne reported a statistically significant but clinically insignificant mean reduction in systolic blood pressure of 3.5 mm Hg.⁵ While clinically relevant hypotension is unlikely to occur, some authors still recommend measuring baseline blood pressure before spironolactone initiation.¹²

Many large studies have demonstrated that hyperkalemia with spironolactone use is rare in young healthy women.^13-15 In one study of patients aged 18 to 45 years treated with spironolactone for acne, only 0.72% of 1802 serum potassium measurements fell within the range of mild hyperkalemia.¹³ Another study found a significantly greater incidence of hyperkalemia in healthy women aged 46 to 65 years compared with women younger than 45 years (16.7% vs <1%; P=.0245).¹⁴ Additionally, among 27 patients taking spironolactone and oral contraceptives containing drospirenone (a spironolactone analog), none had elevated potassium levels.¹⁵ Given these findings, American Academy of Dermatology guidelines suggest that monitoring potassium in young healthy women has low utility but should be considered in those with risk factors including older age; renal and cardiovascular disease; and concurrent medications that interfere with renal, adrenal, and hepatic function.¹ If performed, monitoring should be done within the first few weeks of initiating spironolactone for early detection of hyperkalemia.¹⁶

Spironolactone has a US Food and Drug Administration warning for tumorigenicity based on studies in rats that were given up to 150 times the amount for human therapeutic doses and subsequently developed thyroid, hepatic, testicular, and breast adenomas.¹ However, several large studies in humans have not found an association between spironolactone and breast cancer (BC) development.^1,17,18 Furthermore, a large retrospective study found no increased risk for recurrence in BC survivors treated with spironolactone.² Most carcinogenicity studies include older women, which may limit generalizability of the findings to younger women, who comprise the majority of patients being treated for acne. Recently, however, a retrospective study evaluating healthy females aged 9 to 40 years with acne identified no significant increased risk for BC in patients treated with spironolactone.¹⁷ When compared to tetracyclines, there was a slightly decreased BC risk with spironolactone, providing further support for the latter’s safety. Finally, a large systematic review identified no association between spironolactone and ovarian, bladder, kidney, gastric, or esophageal cancers.¹⁸

Final Thoughts

Over the past several years, an ever-expanding body of literature supporting the efficacy and safety of spironolactone has emerged. While spironolactone has been used off label for decades to treat acne in healthy adult females, there are now strong data to support its efficacy in adolescent females. Notably, spironolactone consistently demonstrates similar effectiveness to first-line tetracycline antibiotics. Additionally, data suggest that spironolactone is safe in patients with a history of BC. Overall, spironolactone is a safe, comparable, and promising alternative to antibiotics for acne management in adult and adolescent females.

Spironolactone is an aldosterone antagonist that first was used as a potassium-sparing diuretic to treat heart failure and hypertension. It also possesses antiandrogenic mechanisms including competitively inhibiting androgen receptors, increasing steroid hormone–binding globulin production, and decreasing 5α-reductase activity.¹ These properties have been leveraged in off-label use for dermatologic conditions including acne, hidradenitis suppurativa, androgenic alopecia, and hirsutism.^1,2 Despite being used off-label to treat acne for more than 40 years, spironolactone has not received US Food and Drug Administration approval for this indication.³ Herein, we review the current evidence for use of spironolactone in acne management.

Spironolactone Efficacy

Spironolactone is efficacious for facial and truncal acne in adult females; it cannot be used in males given its anti-androgenic effects.^4,5 In 2 large studies, spironolactone completely or partially cleared facial acne in 75.5% to 85.1% of patients.^4,5 In the first study, which included 395 patients on a median dose of 100 mg/d (range, 25-200 mg/d), clearance of comedonal, papulopustular, and nodulocystic acne was observed.⁴ The second study included 403 patients, most of whom started on spironolactone at 100 mg/d (range, 25-200 mg/d). In addition to facial clearance, patients in this study demonstrated similar rates of partial or complete clearance of acne on the chest (84.0%) and back (80.2%) assessed via a comprehensive acne severity scale.⁵ In both studies, doses of 100 mg/d or higher were most effective, and the median time to initial acne improvement was 3 months, with peak effects occurring after 4 to 6 months of treatment.^4,5 Most patients were using spironolactone monotherapy or spironolactone in combination with topical therapies; however, a minority used it concurrently with oral antibiotics and/or combined oral contraceptives.

Spironolactone has demonstrated comparable efficacy to tetracycline antibiotics. A study comparing the rate of switching to another systemic therapy within 1 year of treatment initiation identified similar rates in patients started on spironolactone (n=962) and those started on tetracyclines (n=4236)(14.4% vs 13.4%, respectively). As switching may indicate treatment failure due to insufficient efficacy, adverse effects, or other causes, these findings may suggest similar effectiveness for spironolactone and tetracyclines.⁶ These treatments also were compared in a randomized controlled trial of 133 patients receiving topical benzoyl peroxide 5% for 6 months and either spironolactone 150 mg/d for 6 months or doxycycline 100 mg/d for 3 months followed by oral placebo for 3 months. At 4 months, spironolactone performed better than doxycycline as assessed using the Adult Female Acne Scoring Tool.³ Although doxycycline was stopped after 3 months and only topical therapy was continued, this finding is notable because guidelines from the American Academy of Dermatology recommend limiting tetracycline use to 3 to 4 months, whereas spironolactone may be continued for prolonged durations.^1,4

While most studies have evaluated the efficacy of spironolactone in adult females, it is increasingly being prescribed in adolescents.⁷ In a study that included 80 females aged 14 to 20 years, 80% (64/80) experienced acne improvement on a median dose of 100 mg/d.⁸ Additionally, in the study evaluating treatment switching rates, more than 80% of 1139 adolescents who were started on spironolactone were not switched to a different systemic therapy within the first year of treatment, demonstrating the efficacy of spironolactone in this demographic.⁶ However, treatment switching was more common among adolescents started on spironolactone compared with those who started on tetracyclines. As noted for adults, the treatment switching rates were the same for spironolactone and tetracycline users; the difference in adolescents may be due to lower influence of hormonal factors or higher therapeutic expectations in this population.⁶

Spironolactone Safety

Spironolactone is well tolerated at doses of 25 to 200 mg/d for acne management. Common adverse effects include diuresis (29% [26/90]), menstrual irregularities (22% [20/90]), fatigue (17% [15/90]), headache (14% [13/90]), and dizziness (12% [11/90]), but they infrequently lead to treatment discontinuation.^4,9 Rates of adverse effects are lower in adolescents compared to adults, although the effects of spironolactone on early endocrine development in adolescents are unknown.⁷ Spironolactone should not be used during pregnancy, and concurrent contraception use is advised because spironolactone has caused feminization of male fetuses in animal studies.^1,10-11

While concerns about potentially severe adverse effects including hypotension, hyperkalemia, and tumorigenicity have been raised, their occurrence in the literature is rare.^5,12-18 In a study evaluating hypotension in 2084 patients taking spironolactone 50 to 200 mg/day for acne, hair loss, and/or hirsutism, 3.1% experienced absolute hypotension, and only 0.26% required dose reduction or discontinuation.¹² Another study of 403 patients taking spironolactone for acne reported a statistically significant but clinically insignificant mean reduction in systolic blood pressure of 3.5 mm Hg.⁵ While clinically relevant hypotension is unlikely to occur, some authors still recommend measuring baseline blood pressure before spironolactone initiation.¹²

Many large studies have demonstrated that hyperkalemia with spironolactone use is rare in young healthy women.^13-15 In one study of patients aged 18 to 45 years treated with spironolactone for acne, only 0.72% of 1802 serum potassium measurements fell within the range of mild hyperkalemia.¹³ Another study found a significantly greater incidence of hyperkalemia in healthy women aged 46 to 65 years compared with women younger than 45 years (16.7% vs <1%; P=.0245).¹⁴ Additionally, among 27 patients taking spironolactone and oral contraceptives containing drospirenone (a spironolactone analog), none had elevated potassium levels.¹⁵ Given these findings, American Academy of Dermatology guidelines suggest that monitoring potassium in young healthy women has low utility but should be considered in those with risk factors including older age; renal and cardiovascular disease; and concurrent medications that interfere with renal, adrenal, and hepatic function.¹ If performed, monitoring should be done within the first few weeks of initiating spironolactone for early detection of hyperkalemia.¹⁶

Spironolactone has a US Food and Drug Administration warning for tumorigenicity based on studies in rats that were given up to 150 times the amount for human therapeutic doses and subsequently developed thyroid, hepatic, testicular, and breast adenomas.¹ However, several large studies in humans have not found an association between spironolactone and breast cancer (BC) development.^1,17,18 Furthermore, a large retrospective study found no increased risk for recurrence in BC survivors treated with spironolactone.² Most carcinogenicity studies include older women, which may limit generalizability of the findings to younger women, who comprise the majority of patients being treated for acne. Recently, however, a retrospective study evaluating healthy females aged 9 to 40 years with acne identified no significant increased risk for BC in patients treated with spironolactone.¹⁷ When compared to tetracyclines, there was a slightly decreased BC risk with spironolactone, providing further support for the latter’s safety. Finally, a large systematic review identified no association between spironolactone and ovarian, bladder, kidney, gastric, or esophageal cancers.¹⁸

Final Thoughts

Over the past several years, an ever-expanding body of literature supporting the efficacy and safety of spironolactone has emerged. While spironolactone has been used off label for decades to treat acne in healthy adult females, there are now strong data to support its efficacy in adolescent females. Notably, spironolactone consistently demonstrates similar effectiveness to first-line tetracycline antibiotics. Additionally, data suggest that spironolactone is safe in patients with a history of BC. Overall, spironolactone is a safe, comparable, and promising alternative to antibiotics for acne management in adult and adolescent females.

Spironolactone is an aldosterone antagonist that first was used as a potassium-sparing diuretic to treat heart failure and hypertension. It also possesses antiandrogenic mechanisms including competitively inhibiting androgen receptors, increasing steroid hormone–binding globulin production, and decreasing 5α-reductase activity.¹ These properties have been leveraged in off-label use for dermatologic conditions including acne, hidradenitis suppurativa, androgenic alopecia, and hirsutism.^1,2 Despite being used off-label to treat acne for more than 40 years, spironolactone has not received US Food and Drug Administration approval for this indication.³ Herein, we review the current evidence for use of spironolactone in acne management.

Spironolactone Efficacy

Spironolactone is efficacious for facial and truncal acne in adult females; it cannot be used in males given its anti-androgenic effects.^4,5 In 2 large studies, spironolactone completely or partially cleared facial acne in 75.5% to 85.1% of patients.^4,5 In the first study, which included 395 patients on a median dose of 100 mg/d (range, 25-200 mg/d), clearance of comedonal, papulopustular, and nodulocystic acne was observed.⁴ The second study included 403 patients, most of whom started on spironolactone at 100 mg/d (range, 25-200 mg/d). In addition to facial clearance, patients in this study demonstrated similar rates of partial or complete clearance of acne on the chest (84.0%) and back (80.2%) assessed via a comprehensive acne severity scale.⁵ In both studies, doses of 100 mg/d or higher were most effective, and the median time to initial acne improvement was 3 months, with peak effects occurring after 4 to 6 months of treatment.^4,5 Most patients were using spironolactone monotherapy or spironolactone in combination with topical therapies; however, a minority used it concurrently with oral antibiotics and/or combined oral contraceptives.

Spironolactone has demonstrated comparable efficacy to tetracycline antibiotics. A study comparing the rate of switching to another systemic therapy within 1 year of treatment initiation identified similar rates in patients started on spironolactone (n=962) and those started on tetracyclines (n=4236)(14.4% vs 13.4%, respectively). As switching may indicate treatment failure due to insufficient efficacy, adverse effects, or other causes, these findings may suggest similar effectiveness for spironolactone and tetracyclines.⁶ These treatments also were compared in a randomized controlled trial of 133 patients receiving topical benzoyl peroxide 5% for 6 months and either spironolactone 150 mg/d for 6 months or doxycycline 100 mg/d for 3 months followed by oral placebo for 3 months. At 4 months, spironolactone performed better than doxycycline as assessed using the Adult Female Acne Scoring Tool.³ Although doxycycline was stopped after 3 months and only topical therapy was continued, this finding is notable because guidelines from the American Academy of Dermatology recommend limiting tetracycline use to 3 to 4 months, whereas spironolactone may be continued for prolonged durations.^1,4

While most studies have evaluated the efficacy of spironolactone in adult females, it is increasingly being prescribed in adolescents.⁷ In a study that included 80 females aged 14 to 20 years, 80% (64/80) experienced acne improvement on a median dose of 100 mg/d.⁸ Additionally, in the study evaluating treatment switching rates, more than 80% of 1139 adolescents who were started on spironolactone were not switched to a different systemic therapy within the first year of treatment, demonstrating the efficacy of spironolactone in this demographic.⁶ However, treatment switching was more common among adolescents started on spironolactone compared with those who started on tetracyclines. As noted for adults, the treatment switching rates were the same for spironolactone and tetracycline users; the difference in adolescents may be due to lower influence of hormonal factors or higher therapeutic expectations in this population.⁶

Spironolactone Safety

Spironolactone is well tolerated at doses of 25 to 200 mg/d for acne management. Common adverse effects include diuresis (29% [26/90]), menstrual irregularities (22% [20/90]), fatigue (17% [15/90]), headache (14% [13/90]), and dizziness (12% [11/90]), but they infrequently lead to treatment discontinuation.^4,9 Rates of adverse effects are lower in adolescents compared to adults, although the effects of spironolactone on early endocrine development in adolescents are unknown.⁷ Spironolactone should not be used during pregnancy, and concurrent contraception use is advised because spironolactone has caused feminization of male fetuses in animal studies.^1,10-11

While concerns about potentially severe adverse effects including hypotension, hyperkalemia, and tumorigenicity have been raised, their occurrence in the literature is rare.^5,12-18 In a study evaluating hypotension in 2084 patients taking spironolactone 50 to 200 mg/day for acne, hair loss, and/or hirsutism, 3.1% experienced absolute hypotension, and only 0.26% required dose reduction or discontinuation.¹² Another study of 403 patients taking spironolactone for acne reported a statistically significant but clinically insignificant mean reduction in systolic blood pressure of 3.5 mm Hg.⁵ While clinically relevant hypotension is unlikely to occur, some authors still recommend measuring baseline blood pressure before spironolactone initiation.¹²

Many large studies have demonstrated that hyperkalemia with spironolactone use is rare in young healthy women.^13-15 In one study of patients aged 18 to 45 years treated with spironolactone for acne, only 0.72% of 1802 serum potassium measurements fell within the range of mild hyperkalemia.¹³ Another study found a significantly greater incidence of hyperkalemia in healthy women aged 46 to 65 years compared with women younger than 45 years (16.7% vs <1%; P=.0245).¹⁴ Additionally, among 27 patients taking spironolactone and oral contraceptives containing drospirenone (a spironolactone analog), none had elevated potassium levels.¹⁵ Given these findings, American Academy of Dermatology guidelines suggest that monitoring potassium in young healthy women has low utility but should be considered in those with risk factors including older age; renal and cardiovascular disease; and concurrent medications that interfere with renal, adrenal, and hepatic function.¹ If performed, monitoring should be done within the first few weeks of initiating spironolactone for early detection of hyperkalemia.¹⁶

Spironolactone has a US Food and Drug Administration warning for tumorigenicity based on studies in rats that were given up to 150 times the amount for human therapeutic doses and subsequently developed thyroid, hepatic, testicular, and breast adenomas.¹ However, several large studies in humans have not found an association between spironolactone and breast cancer (BC) development.^1,17,18 Furthermore, a large retrospective study found no increased risk for recurrence in BC survivors treated with spironolactone.² Most carcinogenicity studies include older women, which may limit generalizability of the findings to younger women, who comprise the majority of patients being treated for acne. Recently, however, a retrospective study evaluating healthy females aged 9 to 40 years with acne identified no significant increased risk for BC in patients treated with spironolactone.¹⁷ When compared to tetracyclines, there was a slightly decreased BC risk with spironolactone, providing further support for the latter’s safety. Finally, a large systematic review identified no association between spironolactone and ovarian, bladder, kidney, gastric, or esophageal cancers.¹⁸

Final Thoughts

Over the past several years, an ever-expanding body of literature supporting the efficacy and safety of spironolactone has emerged. While spironolactone has been used off label for decades to treat acne in healthy adult females, there are now strong data to support its efficacy in adolescent females. Notably, spironolactone consistently demonstrates similar effectiveness to first-line tetracycline antibiotics. Additionally, data suggest that spironolactone is safe in patients with a history of BC. Overall, spironolactone is a safe, comparable, and promising alternative to antibiotics for acne management in adult and adolescent females.