Acne

SAN DIEGO – An injectable collagen-based filler significantly outperformed saline placebo for treating acne scars, with durable effects at 12 months, according to a randomized, double-blind crossover trial of 147 adults.

The study “successfully demonstrates the effectiveness and safety of polymethylmethacrylate in atrophic acne scars,” said Dr. James Spencer, who conducted the research while at Mount Sinai School of Medicine in New York. Dr. Spencer is now in private practice in St. Petersburg, Fla.

Six months after treatment, 64% of patients who received the polymethylmethacrylate-collagen filler (or PMMA) had at least half their scars improve by at least 2 points on an acne rating scale, Dr. Spencer and his associates said at the annual meeting of the American Society for Dermatologic Surgery. Only 32% of the control group achieved that result (P = .0005). Response rates for the filler were 61% at 9 months and 70% at 12 months, and “crossover subjects subsequently treated with PMMA collagen showed similar response levels,” they said.

The PMMA-collagen filler is easy to administer; “works well on deep, severe scars; and should also work very well on shallow scars,” the researchers noted. The treatment “may enable practitioners to effectively treat acne scarring with no need for capital equipment expenditure or the risks associated with resurfacing procedures,” they said.

About 61% of patients in the study were female, participants averaged 44 years of age, and 20% were Fitzpatrick skin type V or VI. To enter the study, participants had to have at least four facial acne scars that were soft contoured, rolling, distensible, and rated moderate to severe (3-4) on a 4-point acne rating scale.

The patients were treated every 2 weeks for a month, and again at months 3 and 6. At 6 months, patients in the placebo group crossed over and received the filler, and all patients were followed for another 6 months.

Adverse effects were uncommon and included mild transient pain at the injection site, swelling, bruising, and acne, the researchers said. “There was no evidence of granulomas, changes in pigmentation, or hypertrophic scarring,” they added.

No funding source was reported for the study. Dr. Spencer and his coauthors reported financial relationships with Photomedex, Genentech, and Leo Pharma.

SAN DIEGO – An injectable collagen-based filler significantly outperformed saline placebo for treating acne scars, with durable effects at 12 months, according to a randomized, double-blind crossover trial of 147 adults.

The study “successfully demonstrates the effectiveness and safety of polymethylmethacrylate in atrophic acne scars,” said Dr. James Spencer, who conducted the research while at Mount Sinai School of Medicine in New York. Dr. Spencer is now in private practice in St. Petersburg, Fla.

Six months after treatment, 64% of patients who received the polymethylmethacrylate-collagen filler (or PMMA) had at least half their scars improve by at least 2 points on an acne rating scale, Dr. Spencer and his associates said at the annual meeting of the American Society for Dermatologic Surgery. Only 32% of the control group achieved that result (P = .0005). Response rates for the filler were 61% at 9 months and 70% at 12 months, and “crossover subjects subsequently treated with PMMA collagen showed similar response levels,” they said.

The PMMA-collagen filler is easy to administer; “works well on deep, severe scars; and should also work very well on shallow scars,” the researchers noted. The treatment “may enable practitioners to effectively treat acne scarring with no need for capital equipment expenditure or the risks associated with resurfacing procedures,” they said.

About 61% of patients in the study were female, participants averaged 44 years of age, and 20% were Fitzpatrick skin type V or VI. To enter the study, participants had to have at least four facial acne scars that were soft contoured, rolling, distensible, and rated moderate to severe (3-4) on a 4-point acne rating scale.

The patients were treated every 2 weeks for a month, and again at months 3 and 6. At 6 months, patients in the placebo group crossed over and received the filler, and all patients were followed for another 6 months.

Adverse effects were uncommon and included mild transient pain at the injection site, swelling, bruising, and acne, the researchers said. “There was no evidence of granulomas, changes in pigmentation, or hypertrophic scarring,” they added.

No funding source was reported for the study. Dr. Spencer and his coauthors reported financial relationships with Photomedex, Genentech, and Leo Pharma.

SAN DIEGO – An injectable collagen-based filler significantly outperformed saline placebo for treating acne scars, with durable effects at 12 months, according to a randomized, double-blind crossover trial of 147 adults.

The study “successfully demonstrates the effectiveness and safety of polymethylmethacrylate in atrophic acne scars,” said Dr. James Spencer, who conducted the research while at Mount Sinai School of Medicine in New York. Dr. Spencer is now in private practice in St. Petersburg, Fla.

Six months after treatment, 64% of patients who received the polymethylmethacrylate-collagen filler (or PMMA) had at least half their scars improve by at least 2 points on an acne rating scale, Dr. Spencer and his associates said at the annual meeting of the American Society for Dermatologic Surgery. Only 32% of the control group achieved that result (P = .0005). Response rates for the filler were 61% at 9 months and 70% at 12 months, and “crossover subjects subsequently treated with PMMA collagen showed similar response levels,” they said.

The PMMA-collagen filler is easy to administer; “works well on deep, severe scars; and should also work very well on shallow scars,” the researchers noted. The treatment “may enable practitioners to effectively treat acne scarring with no need for capital equipment expenditure or the risks associated with resurfacing procedures,” they said.

About 61% of patients in the study were female, participants averaged 44 years of age, and 20% were Fitzpatrick skin type V or VI. To enter the study, participants had to have at least four facial acne scars that were soft contoured, rolling, distensible, and rated moderate to severe (3-4) on a 4-point acne rating scale.

The patients were treated every 2 weeks for a month, and again at months 3 and 6. At 6 months, patients in the placebo group crossed over and received the filler, and all patients were followed for another 6 months.

Adverse effects were uncommon and included mild transient pain at the injection site, swelling, bruising, and acne, the researchers said. “There was no evidence of granulomas, changes in pigmentation, or hypertrophic scarring,” they added.

No funding source was reported for the study. Dr. Spencer and his coauthors reported financial relationships with Photomedex, Genentech, and Leo Pharma.

Fractional laser technology, often used in the removal of unwanted tattoos, can improve the appearance and texture of facial acne scars, based on data published online Nov.19 in JAMA Dermatology.

“The evolution from traditional nanosecond to picosecond lasers has been observed to produce a photomechanical effect that causes fragmentation of tattoo ink or pigment,” wrote Dr. Jeremy A. Brauer, a dermatologist in group practice in New York, and his coinvestigators. “An innovative optical attachment for the picosecond laser, a diffractive lens array, has been developed that gauges distribution of energy to the treatment area. This specialized optic affects more surface area, has a greater pattern density per pulse, and may improve the appearance of acne scars,” they reported.

© Schlegelfotos/Thinkstock

In a single-center, prospective study, Dr. Brauer and his associates enrolled 20 patients – 15 women and 5 men – based on screenings to ensure no history of skin cancer, keloidal scarring, localized or active infection, immunodeficiency disorders, and light hypersensitivity or use of medications with known phototoxic effects. Of that initial group, 17 completed all six treatments and presented for follow-up visits at 1 and 3 months. Patients were aged 27-66 (mean age, 44 years), and included Fitzpatrick skin types I (one patient), II (seven patients), III (six patients), and IV (three patients).

Subjects mostly had rolling-type scars, boxcar scars, and icepick lesions related to acne. Each subject underwent six treatments with a 755-nanometer alexandrite picosecond laser with a diffractive lens array; each treatment occurred every 4-8 weeks.

Subjects also provided a subjective score for pain experienced during each treatment on a scale of 0 (no pain) to 10 (extreme pain). The patients also used a scale of 0-4 to indicate their satisfaction with improvement of overall skin appearance and texture prior to their final treatment, at the 1-month follow-up, and at the 3-month follow-up (with 0 being total dissatisfaction and 4 total satisfaction).

At the 1-month and 3-month follow-ups, three independent dermatologists gave masked evaluations of each patient’s improvement on a 4-point scale, with 0 = 0%-25%, 1 = 26%-50%, 3 = 51%-75%, and 4 = 76%-100%.

All patients were either “satisfied” or “extremely satisfied” with the appearance and texture of their facial skin after receiving the full treatment regimen, and recorded an average pain score of 2.83 out of 10. The masked assessment scores also were favorable, averaging 1.5 of 3 and 1.4 of 3 at the 1-month and 3-month follow-ups, with a score of 0 indicating 0-25% improvement and a score of 3, greater than 75% improvement, the researchers reported.

Dr. Brauer and his associates also evaluated three-dimensional volumetric data for each subject, which showed an average of 24.0% improvement in scar volume at the 1-month follow-up and 27.2% at the 3-month follow-up. Furthermore, histologic analysis revealed elongation and increased density of elastic fibers, as well as an increase in dermal collagen and mucin.

“This is the first study, to our knowledge, that demonstrates favorable clinical outcomes in acne scar management with the 755[-nm] picosecond laser and diffractive lens array,” the researchers noted. “Observed improvement in pigmentation and texture of the surrounding skin suggests that there may be benefits for indications beyond scarring,” they wrote.

The authors disclosed that funding for this study was provided in part by Cynosure, manufacturer of the Food and Drug Administration–approved 755-nm picosecond alexandrite laser used in the study, and noted that “Cynosure had a role in the design of the study but not the conduct, collection, management, analysis, or interpretation of data. They approved the manuscript but did not prepare or decide to submit.” Dr. Brauer disclosed receiving honoraria from Cynosure/Palomar Medical Technologies and consulting for Miramar. Several other coauthors disclosed financial relationships with multiple companies, including Cynosure/Palomar Medical Technologies. 

dchitnis@frontlinemedcom.com

Fractional laser technology, often used in the removal of unwanted tattoos, can improve the appearance and texture of facial acne scars, based on data published online Nov.19 in JAMA Dermatology.

“The evolution from traditional nanosecond to picosecond lasers has been observed to produce a photomechanical effect that causes fragmentation of tattoo ink or pigment,” wrote Dr. Jeremy A. Brauer, a dermatologist in group practice in New York, and his coinvestigators. “An innovative optical attachment for the picosecond laser, a diffractive lens array, has been developed that gauges distribution of energy to the treatment area. This specialized optic affects more surface area, has a greater pattern density per pulse, and may improve the appearance of acne scars,” they reported.

© Schlegelfotos/Thinkstock

In a single-center, prospective study, Dr. Brauer and his associates enrolled 20 patients – 15 women and 5 men – based on screenings to ensure no history of skin cancer, keloidal scarring, localized or active infection, immunodeficiency disorders, and light hypersensitivity or use of medications with known phototoxic effects. Of that initial group, 17 completed all six treatments and presented for follow-up visits at 1 and 3 months. Patients were aged 27-66 (mean age, 44 years), and included Fitzpatrick skin types I (one patient), II (seven patients), III (six patients), and IV (three patients).

Subjects mostly had rolling-type scars, boxcar scars, and icepick lesions related to acne. Each subject underwent six treatments with a 755-nanometer alexandrite picosecond laser with a diffractive lens array; each treatment occurred every 4-8 weeks.

Subjects also provided a subjective score for pain experienced during each treatment on a scale of 0 (no pain) to 10 (extreme pain). The patients also used a scale of 0-4 to indicate their satisfaction with improvement of overall skin appearance and texture prior to their final treatment, at the 1-month follow-up, and at the 3-month follow-up (with 0 being total dissatisfaction and 4 total satisfaction).

At the 1-month and 3-month follow-ups, three independent dermatologists gave masked evaluations of each patient’s improvement on a 4-point scale, with 0 = 0%-25%, 1 = 26%-50%, 3 = 51%-75%, and 4 = 76%-100%.

All patients were either “satisfied” or “extremely satisfied” with the appearance and texture of their facial skin after receiving the full treatment regimen, and recorded an average pain score of 2.83 out of 10. The masked assessment scores also were favorable, averaging 1.5 of 3 and 1.4 of 3 at the 1-month and 3-month follow-ups, with a score of 0 indicating 0-25% improvement and a score of 3, greater than 75% improvement, the researchers reported.

Dr. Brauer and his associates also evaluated three-dimensional volumetric data for each subject, which showed an average of 24.0% improvement in scar volume at the 1-month follow-up and 27.2% at the 3-month follow-up. Furthermore, histologic analysis revealed elongation and increased density of elastic fibers, as well as an increase in dermal collagen and mucin.

“This is the first study, to our knowledge, that demonstrates favorable clinical outcomes in acne scar management with the 755[-nm] picosecond laser and diffractive lens array,” the researchers noted. “Observed improvement in pigmentation and texture of the surrounding skin suggests that there may be benefits for indications beyond scarring,” they wrote.

The authors disclosed that funding for this study was provided in part by Cynosure, manufacturer of the Food and Drug Administration–approved 755-nm picosecond alexandrite laser used in the study, and noted that “Cynosure had a role in the design of the study but not the conduct, collection, management, analysis, or interpretation of data. They approved the manuscript but did not prepare or decide to submit.” Dr. Brauer disclosed receiving honoraria from Cynosure/Palomar Medical Technologies and consulting for Miramar. Several other coauthors disclosed financial relationships with multiple companies, including Cynosure/Palomar Medical Technologies. 

dchitnis@frontlinemedcom.com

Fractional laser technology, often used in the removal of unwanted tattoos, can improve the appearance and texture of facial acne scars, based on data published online Nov.19 in JAMA Dermatology.

“The evolution from traditional nanosecond to picosecond lasers has been observed to produce a photomechanical effect that causes fragmentation of tattoo ink or pigment,” wrote Dr. Jeremy A. Brauer, a dermatologist in group practice in New York, and his coinvestigators. “An innovative optical attachment for the picosecond laser, a diffractive lens array, has been developed that gauges distribution of energy to the treatment area. This specialized optic affects more surface area, has a greater pattern density per pulse, and may improve the appearance of acne scars,” they reported.

© Schlegelfotos/Thinkstock

In a single-center, prospective study, Dr. Brauer and his associates enrolled 20 patients – 15 women and 5 men – based on screenings to ensure no history of skin cancer, keloidal scarring, localized or active infection, immunodeficiency disorders, and light hypersensitivity or use of medications with known phototoxic effects. Of that initial group, 17 completed all six treatments and presented for follow-up visits at 1 and 3 months. Patients were aged 27-66 (mean age, 44 years), and included Fitzpatrick skin types I (one patient), II (seven patients), III (six patients), and IV (three patients).

Subjects mostly had rolling-type scars, boxcar scars, and icepick lesions related to acne. Each subject underwent six treatments with a 755-nanometer alexandrite picosecond laser with a diffractive lens array; each treatment occurred every 4-8 weeks.

Subjects also provided a subjective score for pain experienced during each treatment on a scale of 0 (no pain) to 10 (extreme pain). The patients also used a scale of 0-4 to indicate their satisfaction with improvement of overall skin appearance and texture prior to their final treatment, at the 1-month follow-up, and at the 3-month follow-up (with 0 being total dissatisfaction and 4 total satisfaction).

At the 1-month and 3-month follow-ups, three independent dermatologists gave masked evaluations of each patient’s improvement on a 4-point scale, with 0 = 0%-25%, 1 = 26%-50%, 3 = 51%-75%, and 4 = 76%-100%.

All patients were either “satisfied” or “extremely satisfied” with the appearance and texture of their facial skin after receiving the full treatment regimen, and recorded an average pain score of 2.83 out of 10. The masked assessment scores also were favorable, averaging 1.5 of 3 and 1.4 of 3 at the 1-month and 3-month follow-ups, with a score of 0 indicating 0-25% improvement and a score of 3, greater than 75% improvement, the researchers reported.

Dr. Brauer and his associates also evaluated three-dimensional volumetric data for each subject, which showed an average of 24.0% improvement in scar volume at the 1-month follow-up and 27.2% at the 3-month follow-up. Furthermore, histologic analysis revealed elongation and increased density of elastic fibers, as well as an increase in dermal collagen and mucin.

“This is the first study, to our knowledge, that demonstrates favorable clinical outcomes in acne scar management with the 755[-nm] picosecond laser and diffractive lens array,” the researchers noted. “Observed improvement in pigmentation and texture of the surrounding skin suggests that there may be benefits for indications beyond scarring,” they wrote.

The authors disclosed that funding for this study was provided in part by Cynosure, manufacturer of the Food and Drug Administration–approved 755-nm picosecond alexandrite laser used in the study, and noted that “Cynosure had a role in the design of the study but not the conduct, collection, management, analysis, or interpretation of data. They approved the manuscript but did not prepare or decide to submit.” Dr. Brauer disclosed receiving honoraria from Cynosure/Palomar Medical Technologies and consulting for Miramar. Several other coauthors disclosed financial relationships with multiple companies, including Cynosure/Palomar Medical Technologies. 

dchitnis@frontlinemedcom.com

The use of lasers in dermatology has had a major impact on the treatment of many dermatologic conditions. In this column practical applications of lasers in medical dermatology will be discussed to give dermatology residents a broad overview of both established indications and the reasoning behind the usage of lasers in treating these skin conditions. The applications for lasers in aesthetic dermatology are numerous and are constantly being refined and developed; they have been discussed extensively in the literature. Given the vast variety of uses of lasers in dermatology today, a comprehensive review of this topic would likely span several volumes. This article will focus on recent evidence regarding the use of lasers in medical dermatology, specifically laser treatment of selected common dermatoses and cutaneous malignancies.

Laser Treatment of Skin Diseases

Many common dermatoses seen in the dermatologist’s office (eg, discoid lupus erythematosus [DLE], morphea, alopecia) already have an established therapeutic ladder, with most patients responding to either first- or second-line therapies; however, a number of patients present with refractory disease that can be difficult to treat due to either treatment resistance or other contraindications to therapy. With the advent and development of modern lasers, we are now able to target many of these conditions and provide a viable safe treatment option for these patients. Although many physicians may be familiar with the use of the excimer laser in the treatment of psoriasis,¹ a long-standing and well-accepted treatment modality for this condition, many novel applications for different types of lasers have been developed.

First, it is important to consider what a laser is able to accomplish to modulate the skin. With ablative lasers such as the CO₂ laser, it is possible to destroy superficial layers of the skin (ie, the epidermis). It would stand to reason that this approach would be ideal for treating epidermal processes such as viral warts; in fact, this modality has been used for this indication for more than 3 decades, with the earliest references coming from the podiatric and urologic literature.^2,3 Despite conflicting reports of the risk for human papillomavirus aerosolization and subsequent contamination of the treatment area,^4,5 CO₂ laser therapy has been advocated as a nonsurgical approach to difficult-to-treat cases of viral warts.

On the other hand, the pulsed dye laser (PDL) can target blood vessels because the wavelength corresponds to the absorption spectrum of hemoglobin and penetrates to the level of the dermis, while the pulse duration can be set to be shorter than the thermal relaxation time of a small cutaneous blood vessel.⁶ In clinical practice, the PDL has been used for the treatment of vascular lesions including hemangiomas, nevus flammeus, and other vascular proliferations.^7-9 However, the PDL also can be used to target the vessels in cutaneous inflammatory diseases that feature vascular dilation and/or perivascular inflammation as a prominent feature.

Discoid lupus erythematosus is a form of chronic cutaneous lupus erythematosus that may be difficult to treat, with recalcitrant lesions displaying continued inflammation leading to chronic scarring and dyspigmentation. A small study (N=12) presented the efficacy of the PDL in the treatment of DLE lesions, suggesting that it has good efficacy in treating recalcitrant lesions with significant reduction in the cutaneous lupus erythematosus disease area and severity index after 6 weeks of treatment and 6 weeks of follow-up (P<.0001) with decreased erythema and scaling.¹⁰ It is important to note, however, that scarring, dyspigmentation, and atrophy were not affected, which suggests that early intervention may be optimal to prevent development of these sequelae. More interestingly, a more recent study expounded on this idea and attempted to examine pathophysiologic mechanisms behind this observed improvement. Evaluation of biopsy specimens before and after treatment and immunohistochemistry revealed that PDL treatment of cutaneous DLE lesions led to a decrease in vascular endothelial proteins—intercellular adhesion molecule 1 and vascular cell adhesion molecule 1—with a coincident reduction in the dermal lymphocytic infiltrate in treated lesions.¹¹ These results offer a somewhat satisfying view on the correlation between the theory and basic science of laser therapy and the subsequent clinical benefits afforded by laser treatment. A case series provided further evidence that PDL or intense pulsed light can ameliorate the cutaneous lesions of DLE in 16 patients in whom all other treatments had failed.¹²

Several other inflammatory dermatoses can be treated with PDL, though the evidence for most of these conditions is sporadic at best, consisting mostly of case reports and a few case series. Granuloma faciale is one such condition, with evidence of efficacy of the PDL dating back as far as 1999,¹³ though a more recent case series of 4 patients only showed response in 2 patients.¹⁴ Because granuloma faciale features vasculitis as a prominent feature in its pathology, targeting the blood vessels may be helpful, but it is important to remember that there is a complex interplay between multiple factors. For example, treatment with typical fluences used in dermatology can be proinflammatory, leading to tissue damage, necrosis, and posttreatment erythema. However, low-level laser therapy (LLLT) has been shown to downregulate proinflammatory mediators.¹⁵ Additionally, the presence of a large burden of inflammatory cells also may alter the effectiveness of the laser. Several case reports also the show effectiveness of both PDL and the CO₂ laser in treating lesions of cutaneous sarcoidosis, especially lupus pernio.^16-19 Of these 2 modalities, the use of the CO₂ laser for effective remodeling of lupus pernio may be more intuitive; however, it is still important to note that the mechanism of action of several of these laser modalities is unclear with regard to the clinical benefit shown. Morphea and scleroderma also have been treated with laser therapy. It is essential to understand that in many cases, laser therapy may be targeted to treat the precise cutaneous manifestations of disease in each individual patient (eg, CO₂ laser to treat disabling contractures and calcinosis cutis,^20,21 PDL to treat telangiectases related to morphea²²). Again, the most critical consideration is that the treatment modality should align with the cutaneous lesion being targeted.

A relatively recent development in the use of lasers has been LLLT, which refers to the use of lasers below levels where they would cause any thermal effects, thereby limiting tissue damage. Although the technology has existed for decades, there has been a recent flurry of reports extolling the many benefits of LLLT; however, the true physiologic effects of LLLT have yet to be determined, with many studies trying to elucidate its numerous effects on various signaling pathways, cell proliferation, and cellular respiration.^23-26 Upon reviewing the literature, the list of cutaneous conditions that are being treated with LLLT is vast, spanning acne, vitiligo, wounds, burns, psoriasis, and alopecia, among others.¹⁵ It is important to consider that the definition of LLLT in the literature is rather broad with a wide range of wavelengths, fluences, and power densities. As such, the specific laser settings and protocols may vary considerably among different practitioners and therefore the treatment results also may vary. Nevertheless, many studies have hinted at promising results in the use of LLLT in conditions that may have previously been extremely difficult to treat (eg, alopecia). Earlier trials had demonstrated a faster resolution time in patients with alopecia areata when LLLT was added to a topical regimen²⁷; however, the improvement was modest and lesions tended to improve with or without LLLT. Perhaps more compelling is the use of LLLT in treating androgenetic alopecia, a condition for which a satisfying facile treatment would truly carry great impact. Although physicians should be cautious of studies regarding LLLT and hair regrowth that are conducted by groups who may stand to benefit from producing such a device, the results are nonetheless notable, if only for the relative paucity of other therapeutic approaches toward this condition.^28,29 A randomized, double-blind, controlled, multicenter trial showed significant improvements in median hair thickness and density with LLLT (P=.01 and P=.003, respectively), though global appearance did not change significantly.³⁰

Laser Treatment of Skin Cancer

Lasers also have been used to treat cutaneous malignancies. Although they may be powerful in the treatment of these conditions, this treatment approach must be used with caution. As with any superficial treatment modality for skin cancer, it is difficult to ascertain if a lesion has been completely treated without any residual cancer cells, and therein lies the main caveat of laser treatment. With the use of a modality that causes a cutaneous response that may mask any underlying process, it is important to ensure that there is a reasonable degree of certainty that this treatment can effectively remove a cancerous lesion in its entirety while avoiding the theoretical risk that disturbing underlying vasculature and/or lymphatics may be modulating the ability of a cancer to metastasize. Thankfully, current evidence does not suggest that there are any downsides to laser treatment for malignancies. Clinically, we know that basal cell carcinomas (BCCs) often feature prominent vasculature, with telangiectases being used as a clinical marker to suggest the diagnosis of a BCC. Capitalizing on this aspect of the clinical lesion, PDL has been used to treat BCCs in 2 small studies with a response rate of approximately 75% for small BCCs in both studies.^31,32 A recent randomized controlled trial showed significant superiority of PDL as compared to the control (P<.0001) in treatment of BCC, with nearly 80% (44/56) of cases showing histologically proven complete remission at 6-month follow-up.³³ Thus, we have some promising data that suggest PDL may be a viable treatment option in BCC, especially in areas that are difficult to treat surgically.

Additionally, a newer treatment approach for BCC capitalizes on the ability of confocal microscopy to provide a feasible, bedside imaging modality to identify tumor margins. Confocal microscopy has been used as a road map to identify where and how to apply the laser treatment, thus allowing for a higher likelihood of complete destruction of the tumor, at least in theory.³⁴ Although the concept of using confocal microscopy to guide laser treatment of skin cancer has been shown in smaller proof-of-concept case series, it remains to be seen if it is not only an efficacious approach that may be widely adopted but also whether it is pragmatic to do so, as the equipment and expertise involved in using confocal microscopy is not trivial.

Finally, lasers also have been used in the treatment of mycosis fungoides (MF), or cutaneous T-cell lymphoma. It has been suggested that this modality is an excellent treatment option as a skin-directed therapy for stage IA or IB MFs limited to the acral surfaces or MF palmaris et plantaris.³⁵ The reasoning behind this approach was the effectiveness of narrowband UVB for early-stage MF, with an excimer laser operating at a similar wavelength (308 nm) and offering similar therapeutic benefits while limiting adverse effects to surrounding skin.³⁶ More recently, the excimer laser was applied to a small population of 6 patients, with 3 achieving complete response, 1 with partial response, 1 with stable disease, and 1 with progressive disease. The authors were careful to point out that the excimer laser should not be thought of as a replacement for narrowband UVB in early-stage MF but rather as an adjunctive treatment of specific targeted lesional areas.³⁶

Conclusion

Lasers are an important part of the dermatologist’s treatment arsenal. Although much attention has been focused on laser treatment for aesthetic indications, it is important not to overlook the fact that lasers also can be useful in the treatment of refractory skin diseases, as a first-line treatment in some conditions such as vascular lesions, or as an adjunctive treatment modality. There is a great deal of exciting research that may lead to new indications and a better understanding of how to best use these powerful tools, and the outlook is bright for the use of lasers in dermatology.

The use of lasers in dermatology has had a major impact on the treatment of many dermatologic conditions. In this column practical applications of lasers in medical dermatology will be discussed to give dermatology residents a broad overview of both established indications and the reasoning behind the usage of lasers in treating these skin conditions. The applications for lasers in aesthetic dermatology are numerous and are constantly being refined and developed; they have been discussed extensively in the literature. Given the vast variety of uses of lasers in dermatology today, a comprehensive review of this topic would likely span several volumes. This article will focus on recent evidence regarding the use of lasers in medical dermatology, specifically laser treatment of selected common dermatoses and cutaneous malignancies.

Laser Treatment of Skin Diseases

Many common dermatoses seen in the dermatologist’s office (eg, discoid lupus erythematosus [DLE], morphea, alopecia) already have an established therapeutic ladder, with most patients responding to either first- or second-line therapies; however, a number of patients present with refractory disease that can be difficult to treat due to either treatment resistance or other contraindications to therapy. With the advent and development of modern lasers, we are now able to target many of these conditions and provide a viable safe treatment option for these patients. Although many physicians may be familiar with the use of the excimer laser in the treatment of psoriasis,¹ a long-standing and well-accepted treatment modality for this condition, many novel applications for different types of lasers have been developed.

First, it is important to consider what a laser is able to accomplish to modulate the skin. With ablative lasers such as the CO₂ laser, it is possible to destroy superficial layers of the skin (ie, the epidermis). It would stand to reason that this approach would be ideal for treating epidermal processes such as viral warts; in fact, this modality has been used for this indication for more than 3 decades, with the earliest references coming from the podiatric and urologic literature.^2,3 Despite conflicting reports of the risk for human papillomavirus aerosolization and subsequent contamination of the treatment area,^4,5 CO₂ laser therapy has been advocated as a nonsurgical approach to difficult-to-treat cases of viral warts.

On the other hand, the pulsed dye laser (PDL) can target blood vessels because the wavelength corresponds to the absorption spectrum of hemoglobin and penetrates to the level of the dermis, while the pulse duration can be set to be shorter than the thermal relaxation time of a small cutaneous blood vessel.⁶ In clinical practice, the PDL has been used for the treatment of vascular lesions including hemangiomas, nevus flammeus, and other vascular proliferations.^7-9 However, the PDL also can be used to target the vessels in cutaneous inflammatory diseases that feature vascular dilation and/or perivascular inflammation as a prominent feature.

Discoid lupus erythematosus is a form of chronic cutaneous lupus erythematosus that may be difficult to treat, with recalcitrant lesions displaying continued inflammation leading to chronic scarring and dyspigmentation. A small study (N=12) presented the efficacy of the PDL in the treatment of DLE lesions, suggesting that it has good efficacy in treating recalcitrant lesions with significant reduction in the cutaneous lupus erythematosus disease area and severity index after 6 weeks of treatment and 6 weeks of follow-up (P<.0001) with decreased erythema and scaling.¹⁰ It is important to note, however, that scarring, dyspigmentation, and atrophy were not affected, which suggests that early intervention may be optimal to prevent development of these sequelae. More interestingly, a more recent study expounded on this idea and attempted to examine pathophysiologic mechanisms behind this observed improvement. Evaluation of biopsy specimens before and after treatment and immunohistochemistry revealed that PDL treatment of cutaneous DLE lesions led to a decrease in vascular endothelial proteins—intercellular adhesion molecule 1 and vascular cell adhesion molecule 1—with a coincident reduction in the dermal lymphocytic infiltrate in treated lesions.¹¹ These results offer a somewhat satisfying view on the correlation between the theory and basic science of laser therapy and the subsequent clinical benefits afforded by laser treatment. A case series provided further evidence that PDL or intense pulsed light can ameliorate the cutaneous lesions of DLE in 16 patients in whom all other treatments had failed.¹²

Several other inflammatory dermatoses can be treated with PDL, though the evidence for most of these conditions is sporadic at best, consisting mostly of case reports and a few case series. Granuloma faciale is one such condition, with evidence of efficacy of the PDL dating back as far as 1999,¹³ though a more recent case series of 4 patients only showed response in 2 patients.¹⁴ Because granuloma faciale features vasculitis as a prominent feature in its pathology, targeting the blood vessels may be helpful, but it is important to remember that there is a complex interplay between multiple factors. For example, treatment with typical fluences used in dermatology can be proinflammatory, leading to tissue damage, necrosis, and posttreatment erythema. However, low-level laser therapy (LLLT) has been shown to downregulate proinflammatory mediators.¹⁵ Additionally, the presence of a large burden of inflammatory cells also may alter the effectiveness of the laser. Several case reports also the show effectiveness of both PDL and the CO₂ laser in treating lesions of cutaneous sarcoidosis, especially lupus pernio.^16-19 Of these 2 modalities, the use of the CO₂ laser for effective remodeling of lupus pernio may be more intuitive; however, it is still important to note that the mechanism of action of several of these laser modalities is unclear with regard to the clinical benefit shown. Morphea and scleroderma also have been treated with laser therapy. It is essential to understand that in many cases, laser therapy may be targeted to treat the precise cutaneous manifestations of disease in each individual patient (eg, CO₂ laser to treat disabling contractures and calcinosis cutis,^20,21 PDL to treat telangiectases related to morphea²²). Again, the most critical consideration is that the treatment modality should align with the cutaneous lesion being targeted.

A relatively recent development in the use of lasers has been LLLT, which refers to the use of lasers below levels where they would cause any thermal effects, thereby limiting tissue damage. Although the technology has existed for decades, there has been a recent flurry of reports extolling the many benefits of LLLT; however, the true physiologic effects of LLLT have yet to be determined, with many studies trying to elucidate its numerous effects on various signaling pathways, cell proliferation, and cellular respiration.^23-26 Upon reviewing the literature, the list of cutaneous conditions that are being treated with LLLT is vast, spanning acne, vitiligo, wounds, burns, psoriasis, and alopecia, among others.¹⁵ It is important to consider that the definition of LLLT in the literature is rather broad with a wide range of wavelengths, fluences, and power densities. As such, the specific laser settings and protocols may vary considerably among different practitioners and therefore the treatment results also may vary. Nevertheless, many studies have hinted at promising results in the use of LLLT in conditions that may have previously been extremely difficult to treat (eg, alopecia). Earlier trials had demonstrated a faster resolution time in patients with alopecia areata when LLLT was added to a topical regimen²⁷; however, the improvement was modest and lesions tended to improve with or without LLLT. Perhaps more compelling is the use of LLLT in treating androgenetic alopecia, a condition for which a satisfying facile treatment would truly carry great impact. Although physicians should be cautious of studies regarding LLLT and hair regrowth that are conducted by groups who may stand to benefit from producing such a device, the results are nonetheless notable, if only for the relative paucity of other therapeutic approaches toward this condition.^28,29 A randomized, double-blind, controlled, multicenter trial showed significant improvements in median hair thickness and density with LLLT (P=.01 and P=.003, respectively), though global appearance did not change significantly.³⁰

Laser Treatment of Skin Cancer

Lasers also have been used to treat cutaneous malignancies. Although they may be powerful in the treatment of these conditions, this treatment approach must be used with caution. As with any superficial treatment modality for skin cancer, it is difficult to ascertain if a lesion has been completely treated without any residual cancer cells, and therein lies the main caveat of laser treatment. With the use of a modality that causes a cutaneous response that may mask any underlying process, it is important to ensure that there is a reasonable degree of certainty that this treatment can effectively remove a cancerous lesion in its entirety while avoiding the theoretical risk that disturbing underlying vasculature and/or lymphatics may be modulating the ability of a cancer to metastasize. Thankfully, current evidence does not suggest that there are any downsides to laser treatment for malignancies. Clinically, we know that basal cell carcinomas (BCCs) often feature prominent vasculature, with telangiectases being used as a clinical marker to suggest the diagnosis of a BCC. Capitalizing on this aspect of the clinical lesion, PDL has been used to treat BCCs in 2 small studies with a response rate of approximately 75% for small BCCs in both studies.^31,32 A recent randomized controlled trial showed significant superiority of PDL as compared to the control (P<.0001) in treatment of BCC, with nearly 80% (44/56) of cases showing histologically proven complete remission at 6-month follow-up.³³ Thus, we have some promising data that suggest PDL may be a viable treatment option in BCC, especially in areas that are difficult to treat surgically.

Additionally, a newer treatment approach for BCC capitalizes on the ability of confocal microscopy to provide a feasible, bedside imaging modality to identify tumor margins. Confocal microscopy has been used as a road map to identify where and how to apply the laser treatment, thus allowing for a higher likelihood of complete destruction of the tumor, at least in theory.³⁴ Although the concept of using confocal microscopy to guide laser treatment of skin cancer has been shown in smaller proof-of-concept case series, it remains to be seen if it is not only an efficacious approach that may be widely adopted but also whether it is pragmatic to do so, as the equipment and expertise involved in using confocal microscopy is not trivial.

Finally, lasers also have been used in the treatment of mycosis fungoides (MF), or cutaneous T-cell lymphoma. It has been suggested that this modality is an excellent treatment option as a skin-directed therapy for stage IA or IB MFs limited to the acral surfaces or MF palmaris et plantaris.³⁵ The reasoning behind this approach was the effectiveness of narrowband UVB for early-stage MF, with an excimer laser operating at a similar wavelength (308 nm) and offering similar therapeutic benefits while limiting adverse effects to surrounding skin.³⁶ More recently, the excimer laser was applied to a small population of 6 patients, with 3 achieving complete response, 1 with partial response, 1 with stable disease, and 1 with progressive disease. The authors were careful to point out that the excimer laser should not be thought of as a replacement for narrowband UVB in early-stage MF but rather as an adjunctive treatment of specific targeted lesional areas.³⁶

Conclusion

Lasers are an important part of the dermatologist’s treatment arsenal. Although much attention has been focused on laser treatment for aesthetic indications, it is important not to overlook the fact that lasers also can be useful in the treatment of refractory skin diseases, as a first-line treatment in some conditions such as vascular lesions, or as an adjunctive treatment modality. There is a great deal of exciting research that may lead to new indications and a better understanding of how to best use these powerful tools, and the outlook is bright for the use of lasers in dermatology.

The use of lasers in dermatology has had a major impact on the treatment of many dermatologic conditions. In this column practical applications of lasers in medical dermatology will be discussed to give dermatology residents a broad overview of both established indications and the reasoning behind the usage of lasers in treating these skin conditions. The applications for lasers in aesthetic dermatology are numerous and are constantly being refined and developed; they have been discussed extensively in the literature. Given the vast variety of uses of lasers in dermatology today, a comprehensive review of this topic would likely span several volumes. This article will focus on recent evidence regarding the use of lasers in medical dermatology, specifically laser treatment of selected common dermatoses and cutaneous malignancies.

Laser Treatment of Skin Diseases

Many common dermatoses seen in the dermatologist’s office (eg, discoid lupus erythematosus [DLE], morphea, alopecia) already have an established therapeutic ladder, with most patients responding to either first- or second-line therapies; however, a number of patients present with refractory disease that can be difficult to treat due to either treatment resistance or other contraindications to therapy. With the advent and development of modern lasers, we are now able to target many of these conditions and provide a viable safe treatment option for these patients. Although many physicians may be familiar with the use of the excimer laser in the treatment of psoriasis,¹ a long-standing and well-accepted treatment modality for this condition, many novel applications for different types of lasers have been developed.

First, it is important to consider what a laser is able to accomplish to modulate the skin. With ablative lasers such as the CO₂ laser, it is possible to destroy superficial layers of the skin (ie, the epidermis). It would stand to reason that this approach would be ideal for treating epidermal processes such as viral warts; in fact, this modality has been used for this indication for more than 3 decades, with the earliest references coming from the podiatric and urologic literature.^2,3 Despite conflicting reports of the risk for human papillomavirus aerosolization and subsequent contamination of the treatment area,^4,5 CO₂ laser therapy has been advocated as a nonsurgical approach to difficult-to-treat cases of viral warts.

On the other hand, the pulsed dye laser (PDL) can target blood vessels because the wavelength corresponds to the absorption spectrum of hemoglobin and penetrates to the level of the dermis, while the pulse duration can be set to be shorter than the thermal relaxation time of a small cutaneous blood vessel.⁶ In clinical practice, the PDL has been used for the treatment of vascular lesions including hemangiomas, nevus flammeus, and other vascular proliferations.^7-9 However, the PDL also can be used to target the vessels in cutaneous inflammatory diseases that feature vascular dilation and/or perivascular inflammation as a prominent feature.

Discoid lupus erythematosus is a form of chronic cutaneous lupus erythematosus that may be difficult to treat, with recalcitrant lesions displaying continued inflammation leading to chronic scarring and dyspigmentation. A small study (N=12) presented the efficacy of the PDL in the treatment of DLE lesions, suggesting that it has good efficacy in treating recalcitrant lesions with significant reduction in the cutaneous lupus erythematosus disease area and severity index after 6 weeks of treatment and 6 weeks of follow-up (P<.0001) with decreased erythema and scaling.¹⁰ It is important to note, however, that scarring, dyspigmentation, and atrophy were not affected, which suggests that early intervention may be optimal to prevent development of these sequelae. More interestingly, a more recent study expounded on this idea and attempted to examine pathophysiologic mechanisms behind this observed improvement. Evaluation of biopsy specimens before and after treatment and immunohistochemistry revealed that PDL treatment of cutaneous DLE lesions led to a decrease in vascular endothelial proteins—intercellular adhesion molecule 1 and vascular cell adhesion molecule 1—with a coincident reduction in the dermal lymphocytic infiltrate in treated lesions.¹¹ These results offer a somewhat satisfying view on the correlation between the theory and basic science of laser therapy and the subsequent clinical benefits afforded by laser treatment. A case series provided further evidence that PDL or intense pulsed light can ameliorate the cutaneous lesions of DLE in 16 patients in whom all other treatments had failed.¹²

Several other inflammatory dermatoses can be treated with PDL, though the evidence for most of these conditions is sporadic at best, consisting mostly of case reports and a few case series. Granuloma faciale is one such condition, with evidence of efficacy of the PDL dating back as far as 1999,¹³ though a more recent case series of 4 patients only showed response in 2 patients.¹⁴ Because granuloma faciale features vasculitis as a prominent feature in its pathology, targeting the blood vessels may be helpful, but it is important to remember that there is a complex interplay between multiple factors. For example, treatment with typical fluences used in dermatology can be proinflammatory, leading to tissue damage, necrosis, and posttreatment erythema. However, low-level laser therapy (LLLT) has been shown to downregulate proinflammatory mediators.¹⁵ Additionally, the presence of a large burden of inflammatory cells also may alter the effectiveness of the laser. Several case reports also the show effectiveness of both PDL and the CO₂ laser in treating lesions of cutaneous sarcoidosis, especially lupus pernio.^16-19 Of these 2 modalities, the use of the CO₂ laser for effective remodeling of lupus pernio may be more intuitive; however, it is still important to note that the mechanism of action of several of these laser modalities is unclear with regard to the clinical benefit shown. Morphea and scleroderma also have been treated with laser therapy. It is essential to understand that in many cases, laser therapy may be targeted to treat the precise cutaneous manifestations of disease in each individual patient (eg, CO₂ laser to treat disabling contractures and calcinosis cutis,^20,21 PDL to treat telangiectases related to morphea²²). Again, the most critical consideration is that the treatment modality should align with the cutaneous lesion being targeted.

A relatively recent development in the use of lasers has been LLLT, which refers to the use of lasers below levels where they would cause any thermal effects, thereby limiting tissue damage. Although the technology has existed for decades, there has been a recent flurry of reports extolling the many benefits of LLLT; however, the true physiologic effects of LLLT have yet to be determined, with many studies trying to elucidate its numerous effects on various signaling pathways, cell proliferation, and cellular respiration.^23-26 Upon reviewing the literature, the list of cutaneous conditions that are being treated with LLLT is vast, spanning acne, vitiligo, wounds, burns, psoriasis, and alopecia, among others.¹⁵ It is important to consider that the definition of LLLT in the literature is rather broad with a wide range of wavelengths, fluences, and power densities. As such, the specific laser settings and protocols may vary considerably among different practitioners and therefore the treatment results also may vary. Nevertheless, many studies have hinted at promising results in the use of LLLT in conditions that may have previously been extremely difficult to treat (eg, alopecia). Earlier trials had demonstrated a faster resolution time in patients with alopecia areata when LLLT was added to a topical regimen²⁷; however, the improvement was modest and lesions tended to improve with or without LLLT. Perhaps more compelling is the use of LLLT in treating androgenetic alopecia, a condition for which a satisfying facile treatment would truly carry great impact. Although physicians should be cautious of studies regarding LLLT and hair regrowth that are conducted by groups who may stand to benefit from producing such a device, the results are nonetheless notable, if only for the relative paucity of other therapeutic approaches toward this condition.^28,29 A randomized, double-blind, controlled, multicenter trial showed significant improvements in median hair thickness and density with LLLT (P=.01 and P=.003, respectively), though global appearance did not change significantly.³⁰

Laser Treatment of Skin Cancer

Lasers also have been used to treat cutaneous malignancies. Although they may be powerful in the treatment of these conditions, this treatment approach must be used with caution. As with any superficial treatment modality for skin cancer, it is difficult to ascertain if a lesion has been completely treated without any residual cancer cells, and therein lies the main caveat of laser treatment. With the use of a modality that causes a cutaneous response that may mask any underlying process, it is important to ensure that there is a reasonable degree of certainty that this treatment can effectively remove a cancerous lesion in its entirety while avoiding the theoretical risk that disturbing underlying vasculature and/or lymphatics may be modulating the ability of a cancer to metastasize. Thankfully, current evidence does not suggest that there are any downsides to laser treatment for malignancies. Clinically, we know that basal cell carcinomas (BCCs) often feature prominent vasculature, with telangiectases being used as a clinical marker to suggest the diagnosis of a BCC. Capitalizing on this aspect of the clinical lesion, PDL has been used to treat BCCs in 2 small studies with a response rate of approximately 75% for small BCCs in both studies.^31,32 A recent randomized controlled trial showed significant superiority of PDL as compared to the control (P<.0001) in treatment of BCC, with nearly 80% (44/56) of cases showing histologically proven complete remission at 6-month follow-up.³³ Thus, we have some promising data that suggest PDL may be a viable treatment option in BCC, especially in areas that are difficult to treat surgically.

Additionally, a newer treatment approach for BCC capitalizes on the ability of confocal microscopy to provide a feasible, bedside imaging modality to identify tumor margins. Confocal microscopy has been used as a road map to identify where and how to apply the laser treatment, thus allowing for a higher likelihood of complete destruction of the tumor, at least in theory.³⁴ Although the concept of using confocal microscopy to guide laser treatment of skin cancer has been shown in smaller proof-of-concept case series, it remains to be seen if it is not only an efficacious approach that may be widely adopted but also whether it is pragmatic to do so, as the equipment and expertise involved in using confocal microscopy is not trivial.

Finally, lasers also have been used in the treatment of mycosis fungoides (MF), or cutaneous T-cell lymphoma. It has been suggested that this modality is an excellent treatment option as a skin-directed therapy for stage IA or IB MFs limited to the acral surfaces or MF palmaris et plantaris.³⁵ The reasoning behind this approach was the effectiveness of narrowband UVB for early-stage MF, with an excimer laser operating at a similar wavelength (308 nm) and offering similar therapeutic benefits while limiting adverse effects to surrounding skin.³⁶ More recently, the excimer laser was applied to a small population of 6 patients, with 3 achieving complete response, 1 with partial response, 1 with stable disease, and 1 with progressive disease. The authors were careful to point out that the excimer laser should not be thought of as a replacement for narrowband UVB in early-stage MF but rather as an adjunctive treatment of specific targeted lesional areas.³⁶

Conclusion

Lasers are an important part of the dermatologist’s treatment arsenal. Although much attention has been focused on laser treatment for aesthetic indications, it is important not to overlook the fact that lasers also can be useful in the treatment of refractory skin diseases, as a first-line treatment in some conditions such as vascular lesions, or as an adjunctive treatment modality. There is a great deal of exciting research that may lead to new indications and a better understanding of how to best use these powerful tools, and the outlook is bright for the use of lasers in dermatology.

Acne is a chronic inflammatory condition of the pilosebaceous unit affecting approximately 79% to 95% of adolescents in the Western world.¹ Treatment of acne depends on its severity. Topical tretinoin, adapalene, benzoyl peroxide, azelaic acid, and topical antibiotics generally are used in cases of noninflammatory or mild inflammatory disease. Isotretinoin is recommended for treatment of severe inflammatory acne (eg, nodulocystic or conglobata acne) and for cases of acne that have proven to be resistant to prior treatment with antibiotics or topical agents. Dosages of isotretinoin range from 0.5 to 2 mg/kg daily for 16 to 24 weeks.¹ Isotretinoin reduces the activity and size of the sebaceous glands, normalizes keratinization of the sebaceous follicles, and decreases the number of Propionibacterium acnes. Isotretinoin also may cause clinical side effects and laboratory changes, the most important being teratogenicity. It also may cause mucocutaneous side effects including cracked lips, dryness of the skin and nasal mucosa, skin redness, eye dryness, and eye irritation.¹ It also may cause blepharoconjuctivitis, photosensitivity, asteatotic dermatitis, pruritus, telogen effluvium, secondary bacterial colonization, nail fragility, periungual pyogenic granuloma, paronychia, myalgia, intracranial hypertension, nausea, headache, vomiting, depression, psychosis, suicide, constipation, and allergic reactions.² Isotretinoin treatment may increase serum levels of liver enzymes, triglyc-erides (TGs), and low-density lipoprotein (LDL) cholesterol, and reduce the level of high-density lipoprotein (HDL) cholesterol.¹ This retrospective study sought to evaluate the effect of isotretinoin on liver enzymes and lipids over 6 months.

Materials and Methods

Our retrospective study was conducted at the Hospital of Atatürk University in Erzurum, a city located in eastern Turkey. All patients who were treated in the department of dermatology and had received oral isotretinoin between June 2009 and June 2012 were included in the study. The study was based on an evaluation of the patients’ medical records. All patients received oral isotretinoin 0.5 to 1 mg/kg daily; the majority of patients received 30 to 40 mg daily. Patient medical records included age; gender; white blood cell (WBC) count; red blood cell (RBC) count; hemoglobin count; and aspartate aminotransferase (AST), alanine aminotransferase (ALT), TG, LDL, and HDL levels at the beginning of treatment. Aspartate aminotransferase, ALT, TG, LDL, and HDL levels also were measured at 3- and 6-month follow-up. Analysis of AST, ALT, TG, LDL, and HDL levels was based on the National Cholesterol Education Program guidelines.³ Aspartate aminotransferase and ALT levels were classified as normal (<40 U/L) and high (≥40 U/L). Triglyceride levels were classified as normal (<150 mg/dL), borderline high (150–199 mg/dL), high (200–499 mg/dL), and very high (≥500 mg/dL). Low-density lipoprotein levels were classified as optimal (<100 mg/dL), above optimal (100–129 mg/dL), borderline high (130–159 mg/dL), high (160–189 mg/dL), and very high (≥190 mg/dL). High-density lipoprotein levels were classified as low (<40 mg/dL), normal (40–59 mg/dL), and high (≥60 mg/dL). Normal WBC was defined as 3.5 to 12.5×10³/mL. Normal hemoglobin count was defined as 11.5 to 15.0×10⁶/mL for women and 13 to 17×10⁶/mL for men. Normal RBC was defined as 4.0 to 5.2×10⁶/mL for women and 4.5 to 5.9×10⁶/mL for men. Statistical analysis was performed using SPSS version 17.0. Repeated measures analysis of variance was used to compare means between 3 groups (baseline, 3-month, and 6-month values). A paired sample t test was used to compare means between any 2 groups. Results with P<.05 were considered statistically significant.

Results

Treatment with oral isotretinoin was initiated in 349 patients at our institution from June 2009 to June 2012. Twenty-seven of these patients were excluded from the study because their medical records were not available. Medical records from 322 patients were obtained. The study population consisted of 226 (70.2%) women and 96 (29.8%) men. Patients ranged in age from 17 to 64 years, with a mean age of 23.9 years. The mean (standard deviation [SD]) age of the women was 23.9 (5.4) years and the mean (SD) age of the men was 23.8 (7.02) years. Most of the patients were on a regimen of 30 or 40 mg of isotretinoin daily. Differences between dosages and laboratory values were not analyzed because we assumed there would not be a significant difference, as most patients received the same dose. The mean (SD) WBC was 8.4 (3.5)×10³/mL. The mean (SD) RBC was 4.9 (0.5)×10⁶/mL. The mean (SD) hemoglobin count was 14.3 (1.7)×10⁶/mL (women, 13.6 [1.5]×10⁶/mL; men, 15.9 [1.1]×10⁶/mL).

The study evaluated the effects of isotretinoin on liver enzymes (AST and ALT) and lipids (TGs, LDL, and HDL). Nearly all of the patients (>95%) had normal AST and ALT levels at baseline. The results are outlined in the Table. Some values were not recorded for all patients at each follow-up.

Aspartate Aminotransferase Analysis

Aspartate aminotransferase levels were classified as normal and high. At baseline, mean (SD) AST levels were 20.2 (6.6) U/L, with normal levels in 311 (96.6%) patients and high in 7 (2.2%) patients. At 3-month follow-up, mean (SD) AST levels were 20.7 (5.2) U/L, with normal levels in 270 (83.9%) patients and high levels in 3 (0.9%) patients. At 6-month follow-up, mean (SD) AST levels were 21.3 (5.7) U/L, with normal levels in 209 (64.9%) patients and high levels in 4 (1.2%) patients. Aspartate aminotransferase levels increased at 3- and 6-month follow-up compared to baseline. Differences between AST levels were statistically significant (F_2,416=4.2, P=.016). Differences between AST levels at baseline and 3-month follow-up were not statistically significant (P=.3). Differences between AST levels at 3- and 6-month follow-up were not statistically significant (P=.4). Differences between AST levels at baseline and 6-month follow-up were statistically significant (P=.07). Differences between AST classifications at the 3 time points were not statistically significant (F_2,416=0.44, P=.64). Overall, the results indicated that AST levels increased over time in patients treated with isotretinoin, but the increase was not above the normal range and was not statistically significant.

Alanine Aminotransferase Analysis

Alanine aminotransferase levels were classified as normal or high. At baseline, mean (SD) ALT levels were 16.8 (11.2) U/L, with normal levels in 303 (94.1%) patients and high in 19 (5.9%) patients. At 3-month follow-up, mean (SD) ALT levels were 16.2 (9.3) U/L, with normal levels in 263 (81.7%) patients and high in 11 (3.4%) patients. At 6-month follow-up, mean (SD) ALT levels were 17.0 (11.3) U/L, with normal levels in 201 (62.4%) patients and high in 11 (3.4%) patients. Alanine aminotransferase levels at 3-month follow-up were lower than baseline but higher at 6-month follow-up compared to baseline and 3-month follow-up. Overall, ALT levels increased with time, but the differences between baseline and 3- and 6-month follow-up were not statistically significant (F_2,416=0.32, P=.72). Differences between ALT classifications at each time point were not statistically significant (F_2,418=0.21, P=.54). Overall, the results indicated that ALT levels increased over time in patients treated with isotretinoin, but the increase was not statistically significant.

Triglycerides Analysis

Triglyceride levels were classified as normal, borderline high, high, and very high. At baseline, mean (SD) TG levels were 107 (71) mg/dL, with normal levels in 270 (83.9%) patients, borderline high in 30 (9.3%) patients, high in 20 (6.2%) patients, and very high in 2 (0.6%) patients. At 3-month follow-up, mean (SD) TG levels were 117 (60) mg/dL, with normal levels in 197 (61.2%) patients, borderline high in 38 (11.8%) patients, high in 22 (6.8%) patients, and very high in 1 (0.3%) patient. At 6-month follow-up, mean (SD) TG levels were 122 (65) mg/dL, with normal levels in 145 (45%) patients, borderline high in 36 (11.2%) patients, high in 16 (5%) patients, and very high in 0 (0%) patients. Triglyceride levels increased and differences between TG levels at baseline and 3- and 6-month follow-up were statistically significant (F_2,384=17, P<.001). Baseline TG levels compared to 3-month follow-up were statistically signif-icant (P<.001). Differences in TG levels at 6-month follow-up versus baseline were statistically significant (P<.001). However, changes in TG levels from 3- to 6-month follow-up were not statistically significant (P=.21). Differences between TG classifications at each time point were statistically significant (F_2,386=6.9, P=.001). Overall, TG levels increased from baseline during isotretinoin treatment at 3- and 6-month follow-up, and these increases were above normal range; however, there was no statistically significant increase from 3- to 6-month follow-up.

Low-Density Lipoprotein Analysis

Low-density lipoprotein levels were classified as optimal, above optimal, borderline high, high, and very high. At baseline, mean (SD) LDL levels were 102 (28) mg/dL, with optimal levels in 162 (50.3%) patients, above optimal in 95 (29.5%) patients, borderline high in 32 (9.9%) patients, high in 11 (3.4%) patients, and very high in 3 (0.9%) patients. At 3-month follow-up, mean (SD) LDL levels were 113 (30) mg/dL, with optimal levels in 89 (27.6%) patients, above optimal in 98 (30.4%) patients, borderline high in 54 (16.8%) patients, high in 12 (3.7%) patients, and very high in 5 (1.6%) patients. At 6-month follow-up, mean (SD) LDL levels were 113 (27) mg/dL, with optimal levels in 60 (18.6%) patients, above optimal in 84 (26.1%) patients, borderline high in 44 (13.7%) patients, high in 8 (2.5%) patients, and very high in 1 (0.3%) patient. Overall, there were statistically significant increases in LDL levels at 3- and 6-month follow-up (F_2,382<75, P<.001). Differences between baseline LDL levels and 3-month follow-up were statistically significant (P<.001). Differences between baseline LDL levels and 6-month follow-up were statistically significant (P<.001). However, differences in LDL levels at 3- and 6-month follow-up were not statistically significant (P=.74). Differences between LDL classifications at each time point were statistically significant (F_2,382=51.2, P<.001). Overall, statistically significant increases in LDL levels from baseline were noted during isotretinoin treatment and this increase was above normal range; however, LDL levels did not significantly increase from 3- to 6-month follow-up.

High-Density Lipoprotein Analysis

High-density lipoprotein levels were classified as low, normal, and high. At baseline, mean (SD) HDL levels were 52.4 (16) mg/dL, with low levels in 60 (18.6%) patients, normal in 173 (53.7%) patients, and high in 71 (22%) patients. At 3-month follow-up, mean (SD) HDL levels were 48 (12) mg/dL, with low levels in 63 (19.6%) patients, normal in 154 (47.8%) patients, and high in 41 (12.7%) patients. At 6-month follow-up, mean (SD) HDL levels were 47.6 (12) mg/dL, with low levels in 48 (14.9%) patients, normal in 117 (36.3%) patients, and high in 33 (10.2%) patients. Overall, statistically significant decreases were noted in HDL levels (F_2,384=19, P<.001). Differences between baseline HDL levels compared to 3-month follow-up were statistically significant (P<.001). Differences between baseline HDL levels compared to 6-month follow-up were statistically significant (P<.001). Differences in HDL levels at 3- and 6-month follow-up were statistically significant (P<.001). Differences between HDL classifications at each time point were statistically significant (F_2,384=5.2, P=.006). Overall, there were statistically significant decreases in HDL levels during isotretinoin treatment from baseline and this decrease was above normal range; however, HDL levels did not decrease at 3- and 6-month follow-up.

Comment

Studies in the literature evaluating the effects of isotretinoin on liver enzymes and lipids suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT), TGs, HDL, and LDL in various degrees.¹ Zane et al⁴ studied 13,772 patients with acne undergoing oral isotretinoin therapy between March 1995 and September 2002. The investigators found increased liver transaminase and serum lipid levels. They suggested that these abnormalities were generally transient and reversible.⁴ Bershad et al⁵ reported an increase in LDL and TG but a decrease in HDL during isotretinoin therapy. These changes in the lipid profile also appeared to be transient and returned to baseline level 2 months following the end of treatment.⁵ In another study of 130 patients who were treated with isotretinoin, Vieira et al¹ noted an increase in AST, ALT, and TG levels. Most of the studies in the literature that reported effects of isotretinoin on liver enzymes and lipids suggested that the effects were reversible.

Although many studies reported alterations in serum transaminase and lipid levels, other studies reported no effect. In one study of 150 participants, Brito et al² found no statistically significant changes in liver transaminase, TG, HDL, or LDL levels following treatment with isotretinoin. In another study of 1292 participants by Alcalay et al,⁶ serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of isotretinoin treatment. In another study of 30 participants, Baxter et al⁷ reported no significant changes in TG, LDL, or HDL levels measured at baseline or during treatment with isotretinoin.

Some studies suggest that routine laboratory tests are needed when treating patients with isotretinoin due to severe alterations in serum liver transaminase and lipid levels, while other studies conclude that the effects are minimal and laboratory tests are not needed. In the current study, we found that there were statistically significant increases in TG and LDL levels in patients who underwent treatment with isotretinoin. We also found statistically significant decreases in HDL levels. In our study, liver enzymes were less affected than lipids in patients who underwent treatment with isotretinoin. There were statistically significant increases in AST levels, but the clinical classification was not affected. There also were increases in ALT levels, but the changes were not statistically significant.

Overall, we advise dermatologists that isotretinoin can be administered with minimal concern regarding changes in serum transaminase and lipid levels; however, although severe laboratory alterations were not noted in our study, we advise physicians to use caution when administering isotretinoin in patients with a history of abnormal findings.

Acne is a chronic inflammatory condition of the pilosebaceous unit affecting approximately 79% to 95% of adolescents in the Western world.¹ Treatment of acne depends on its severity. Topical tretinoin, adapalene, benzoyl peroxide, azelaic acid, and topical antibiotics generally are used in cases of noninflammatory or mild inflammatory disease. Isotretinoin is recommended for treatment of severe inflammatory acne (eg, nodulocystic or conglobata acne) and for cases of acne that have proven to be resistant to prior treatment with antibiotics or topical agents. Dosages of isotretinoin range from 0.5 to 2 mg/kg daily for 16 to 24 weeks.¹ Isotretinoin reduces the activity and size of the sebaceous glands, normalizes keratinization of the sebaceous follicles, and decreases the number of Propionibacterium acnes. Isotretinoin also may cause clinical side effects and laboratory changes, the most important being teratogenicity. It also may cause mucocutaneous side effects including cracked lips, dryness of the skin and nasal mucosa, skin redness, eye dryness, and eye irritation.¹ It also may cause blepharoconjuctivitis, photosensitivity, asteatotic dermatitis, pruritus, telogen effluvium, secondary bacterial colonization, nail fragility, periungual pyogenic granuloma, paronychia, myalgia, intracranial hypertension, nausea, headache, vomiting, depression, psychosis, suicide, constipation, and allergic reactions.² Isotretinoin treatment may increase serum levels of liver enzymes, triglyc-erides (TGs), and low-density lipoprotein (LDL) cholesterol, and reduce the level of high-density lipoprotein (HDL) cholesterol.¹ This retrospective study sought to evaluate the effect of isotretinoin on liver enzymes and lipids over 6 months.

Materials and Methods

Our retrospective study was conducted at the Hospital of Atatürk University in Erzurum, a city located in eastern Turkey. All patients who were treated in the department of dermatology and had received oral isotretinoin between June 2009 and June 2012 were included in the study. The study was based on an evaluation of the patients’ medical records. All patients received oral isotretinoin 0.5 to 1 mg/kg daily; the majority of patients received 30 to 40 mg daily. Patient medical records included age; gender; white blood cell (WBC) count; red blood cell (RBC) count; hemoglobin count; and aspartate aminotransferase (AST), alanine aminotransferase (ALT), TG, LDL, and HDL levels at the beginning of treatment. Aspartate aminotransferase, ALT, TG, LDL, and HDL levels also were measured at 3- and 6-month follow-up. Analysis of AST, ALT, TG, LDL, and HDL levels was based on the National Cholesterol Education Program guidelines.³ Aspartate aminotransferase and ALT levels were classified as normal (<40 U/L) and high (≥40 U/L). Triglyceride levels were classified as normal (<150 mg/dL), borderline high (150–199 mg/dL), high (200–499 mg/dL), and very high (≥500 mg/dL). Low-density lipoprotein levels were classified as optimal (<100 mg/dL), above optimal (100–129 mg/dL), borderline high (130–159 mg/dL), high (160–189 mg/dL), and very high (≥190 mg/dL). High-density lipoprotein levels were classified as low (<40 mg/dL), normal (40–59 mg/dL), and high (≥60 mg/dL). Normal WBC was defined as 3.5 to 12.5×10³/mL. Normal hemoglobin count was defined as 11.5 to 15.0×10⁶/mL for women and 13 to 17×10⁶/mL for men. Normal RBC was defined as 4.0 to 5.2×10⁶/mL for women and 4.5 to 5.9×10⁶/mL for men. Statistical analysis was performed using SPSS version 17.0. Repeated measures analysis of variance was used to compare means between 3 groups (baseline, 3-month, and 6-month values). A paired sample t test was used to compare means between any 2 groups. Results with P<.05 were considered statistically significant.

Results

Treatment with oral isotretinoin was initiated in 349 patients at our institution from June 2009 to June 2012. Twenty-seven of these patients were excluded from the study because their medical records were not available. Medical records from 322 patients were obtained. The study population consisted of 226 (70.2%) women and 96 (29.8%) men. Patients ranged in age from 17 to 64 years, with a mean age of 23.9 years. The mean (standard deviation [SD]) age of the women was 23.9 (5.4) years and the mean (SD) age of the men was 23.8 (7.02) years. Most of the patients were on a regimen of 30 or 40 mg of isotretinoin daily. Differences between dosages and laboratory values were not analyzed because we assumed there would not be a significant difference, as most patients received the same dose. The mean (SD) WBC was 8.4 (3.5)×10³/mL. The mean (SD) RBC was 4.9 (0.5)×10⁶/mL. The mean (SD) hemoglobin count was 14.3 (1.7)×10⁶/mL (women, 13.6 [1.5]×10⁶/mL; men, 15.9 [1.1]×10⁶/mL).

The study evaluated the effects of isotretinoin on liver enzymes (AST and ALT) and lipids (TGs, LDL, and HDL). Nearly all of the patients (>95%) had normal AST and ALT levels at baseline. The results are outlined in the Table. Some values were not recorded for all patients at each follow-up.

Aspartate Aminotransferase Analysis

Aspartate aminotransferase levels were classified as normal and high. At baseline, mean (SD) AST levels were 20.2 (6.6) U/L, with normal levels in 311 (96.6%) patients and high in 7 (2.2%) patients. At 3-month follow-up, mean (SD) AST levels were 20.7 (5.2) U/L, with normal levels in 270 (83.9%) patients and high levels in 3 (0.9%) patients. At 6-month follow-up, mean (SD) AST levels were 21.3 (5.7) U/L, with normal levels in 209 (64.9%) patients and high levels in 4 (1.2%) patients. Aspartate aminotransferase levels increased at 3- and 6-month follow-up compared to baseline. Differences between AST levels were statistically significant (F_2,416=4.2, P=.016). Differences between AST levels at baseline and 3-month follow-up were not statistically significant (P=.3). Differences between AST levels at 3- and 6-month follow-up were not statistically significant (P=.4). Differences between AST levels at baseline and 6-month follow-up were statistically significant (P=.07). Differences between AST classifications at the 3 time points were not statistically significant (F_2,416=0.44, P=.64). Overall, the results indicated that AST levels increased over time in patients treated with isotretinoin, but the increase was not above the normal range and was not statistically significant.

Alanine Aminotransferase Analysis

Alanine aminotransferase levels were classified as normal or high. At baseline, mean (SD) ALT levels were 16.8 (11.2) U/L, with normal levels in 303 (94.1%) patients and high in 19 (5.9%) patients. At 3-month follow-up, mean (SD) ALT levels were 16.2 (9.3) U/L, with normal levels in 263 (81.7%) patients and high in 11 (3.4%) patients. At 6-month follow-up, mean (SD) ALT levels were 17.0 (11.3) U/L, with normal levels in 201 (62.4%) patients and high in 11 (3.4%) patients. Alanine aminotransferase levels at 3-month follow-up were lower than baseline but higher at 6-month follow-up compared to baseline and 3-month follow-up. Overall, ALT levels increased with time, but the differences between baseline and 3- and 6-month follow-up were not statistically significant (F_2,416=0.32, P=.72). Differences between ALT classifications at each time point were not statistically significant (F_2,418=0.21, P=.54). Overall, the results indicated that ALT levels increased over time in patients treated with isotretinoin, but the increase was not statistically significant.

Triglycerides Analysis

Triglyceride levels were classified as normal, borderline high, high, and very high. At baseline, mean (SD) TG levels were 107 (71) mg/dL, with normal levels in 270 (83.9%) patients, borderline high in 30 (9.3%) patients, high in 20 (6.2%) patients, and very high in 2 (0.6%) patients. At 3-month follow-up, mean (SD) TG levels were 117 (60) mg/dL, with normal levels in 197 (61.2%) patients, borderline high in 38 (11.8%) patients, high in 22 (6.8%) patients, and very high in 1 (0.3%) patient. At 6-month follow-up, mean (SD) TG levels were 122 (65) mg/dL, with normal levels in 145 (45%) patients, borderline high in 36 (11.2%) patients, high in 16 (5%) patients, and very high in 0 (0%) patients. Triglyceride levels increased and differences between TG levels at baseline and 3- and 6-month follow-up were statistically significant (F_2,384=17, P<.001). Baseline TG levels compared to 3-month follow-up were statistically signif-icant (P<.001). Differences in TG levels at 6-month follow-up versus baseline were statistically significant (P<.001). However, changes in TG levels from 3- to 6-month follow-up were not statistically significant (P=.21). Differences between TG classifications at each time point were statistically significant (F_2,386=6.9, P=.001). Overall, TG levels increased from baseline during isotretinoin treatment at 3- and 6-month follow-up, and these increases were above normal range; however, there was no statistically significant increase from 3- to 6-month follow-up.

Low-Density Lipoprotein Analysis

Low-density lipoprotein levels were classified as optimal, above optimal, borderline high, high, and very high. At baseline, mean (SD) LDL levels were 102 (28) mg/dL, with optimal levels in 162 (50.3%) patients, above optimal in 95 (29.5%) patients, borderline high in 32 (9.9%) patients, high in 11 (3.4%) patients, and very high in 3 (0.9%) patients. At 3-month follow-up, mean (SD) LDL levels were 113 (30) mg/dL, with optimal levels in 89 (27.6%) patients, above optimal in 98 (30.4%) patients, borderline high in 54 (16.8%) patients, high in 12 (3.7%) patients, and very high in 5 (1.6%) patients. At 6-month follow-up, mean (SD) LDL levels were 113 (27) mg/dL, with optimal levels in 60 (18.6%) patients, above optimal in 84 (26.1%) patients, borderline high in 44 (13.7%) patients, high in 8 (2.5%) patients, and very high in 1 (0.3%) patient. Overall, there were statistically significant increases in LDL levels at 3- and 6-month follow-up (F_2,382<75, P<.001). Differences between baseline LDL levels and 3-month follow-up were statistically significant (P<.001). Differences between baseline LDL levels and 6-month follow-up were statistically significant (P<.001). However, differences in LDL levels at 3- and 6-month follow-up were not statistically significant (P=.74). Differences between LDL classifications at each time point were statistically significant (F_2,382=51.2, P<.001). Overall, statistically significant increases in LDL levels from baseline were noted during isotretinoin treatment and this increase was above normal range; however, LDL levels did not significantly increase from 3- to 6-month follow-up.

High-Density Lipoprotein Analysis

High-density lipoprotein levels were classified as low, normal, and high. At baseline, mean (SD) HDL levels were 52.4 (16) mg/dL, with low levels in 60 (18.6%) patients, normal in 173 (53.7%) patients, and high in 71 (22%) patients. At 3-month follow-up, mean (SD) HDL levels were 48 (12) mg/dL, with low levels in 63 (19.6%) patients, normal in 154 (47.8%) patients, and high in 41 (12.7%) patients. At 6-month follow-up, mean (SD) HDL levels were 47.6 (12) mg/dL, with low levels in 48 (14.9%) patients, normal in 117 (36.3%) patients, and high in 33 (10.2%) patients. Overall, statistically significant decreases were noted in HDL levels (F_2,384=19, P<.001). Differences between baseline HDL levels compared to 3-month follow-up were statistically significant (P<.001). Differences between baseline HDL levels compared to 6-month follow-up were statistically significant (P<.001). Differences in HDL levels at 3- and 6-month follow-up were statistically significant (P<.001). Differences between HDL classifications at each time point were statistically significant (F_2,384=5.2, P=.006). Overall, there were statistically significant decreases in HDL levels during isotretinoin treatment from baseline and this decrease was above normal range; however, HDL levels did not decrease at 3- and 6-month follow-up.

Comment

Studies in the literature evaluating the effects of isotretinoin on liver enzymes and lipids suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT), TGs, HDL, and LDL in various degrees.¹ Zane et al⁴ studied 13,772 patients with acne undergoing oral isotretinoin therapy between March 1995 and September 2002. The investigators found increased liver transaminase and serum lipid levels. They suggested that these abnormalities were generally transient and reversible.⁴ Bershad et al⁵ reported an increase in LDL and TG but a decrease in HDL during isotretinoin therapy. These changes in the lipid profile also appeared to be transient and returned to baseline level 2 months following the end of treatment.⁵ In another study of 130 patients who were treated with isotretinoin, Vieira et al¹ noted an increase in AST, ALT, and TG levels. Most of the studies in the literature that reported effects of isotretinoin on liver enzymes and lipids suggested that the effects were reversible.

Although many studies reported alterations in serum transaminase and lipid levels, other studies reported no effect. In one study of 150 participants, Brito et al² found no statistically significant changes in liver transaminase, TG, HDL, or LDL levels following treatment with isotretinoin. In another study of 1292 participants by Alcalay et al,⁶ serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of isotretinoin treatment. In another study of 30 participants, Baxter et al⁷ reported no significant changes in TG, LDL, or HDL levels measured at baseline or during treatment with isotretinoin.

Some studies suggest that routine laboratory tests are needed when treating patients with isotretinoin due to severe alterations in serum liver transaminase and lipid levels, while other studies conclude that the effects are minimal and laboratory tests are not needed. In the current study, we found that there were statistically significant increases in TG and LDL levels in patients who underwent treatment with isotretinoin. We also found statistically significant decreases in HDL levels. In our study, liver enzymes were less affected than lipids in patients who underwent treatment with isotretinoin. There were statistically significant increases in AST levels, but the clinical classification was not affected. There also were increases in ALT levels, but the changes were not statistically significant.

Overall, we advise dermatologists that isotretinoin can be administered with minimal concern regarding changes in serum transaminase and lipid levels; however, although severe laboratory alterations were not noted in our study, we advise physicians to use caution when administering isotretinoin in patients with a history of abnormal findings.

Acne is a chronic inflammatory condition of the pilosebaceous unit affecting approximately 79% to 95% of adolescents in the Western world.¹ Treatment of acne depends on its severity. Topical tretinoin, adapalene, benzoyl peroxide, azelaic acid, and topical antibiotics generally are used in cases of noninflammatory or mild inflammatory disease. Isotretinoin is recommended for treatment of severe inflammatory acne (eg, nodulocystic or conglobata acne) and for cases of acne that have proven to be resistant to prior treatment with antibiotics or topical agents. Dosages of isotretinoin range from 0.5 to 2 mg/kg daily for 16 to 24 weeks.¹ Isotretinoin reduces the activity and size of the sebaceous glands, normalizes keratinization of the sebaceous follicles, and decreases the number of Propionibacterium acnes. Isotretinoin also may cause clinical side effects and laboratory changes, the most important being teratogenicity. It also may cause mucocutaneous side effects including cracked lips, dryness of the skin and nasal mucosa, skin redness, eye dryness, and eye irritation.¹ It also may cause blepharoconjuctivitis, photosensitivity, asteatotic dermatitis, pruritus, telogen effluvium, secondary bacterial colonization, nail fragility, periungual pyogenic granuloma, paronychia, myalgia, intracranial hypertension, nausea, headache, vomiting, depression, psychosis, suicide, constipation, and allergic reactions.² Isotretinoin treatment may increase serum levels of liver enzymes, triglyc-erides (TGs), and low-density lipoprotein (LDL) cholesterol, and reduce the level of high-density lipoprotein (HDL) cholesterol.¹ This retrospective study sought to evaluate the effect of isotretinoin on liver enzymes and lipids over 6 months.

Materials and Methods

Our retrospective study was conducted at the Hospital of Atatürk University in Erzurum, a city located in eastern Turkey. All patients who were treated in the department of dermatology and had received oral isotretinoin between June 2009 and June 2012 were included in the study. The study was based on an evaluation of the patients’ medical records. All patients received oral isotretinoin 0.5 to 1 mg/kg daily; the majority of patients received 30 to 40 mg daily. Patient medical records included age; gender; white blood cell (WBC) count; red blood cell (RBC) count; hemoglobin count; and aspartate aminotransferase (AST), alanine aminotransferase (ALT), TG, LDL, and HDL levels at the beginning of treatment. Aspartate aminotransferase, ALT, TG, LDL, and HDL levels also were measured at 3- and 6-month follow-up. Analysis of AST, ALT, TG, LDL, and HDL levels was based on the National Cholesterol Education Program guidelines.³ Aspartate aminotransferase and ALT levels were classified as normal (<40 U/L) and high (≥40 U/L). Triglyceride levels were classified as normal (<150 mg/dL), borderline high (150–199 mg/dL), high (200–499 mg/dL), and very high (≥500 mg/dL). Low-density lipoprotein levels were classified as optimal (<100 mg/dL), above optimal (100–129 mg/dL), borderline high (130–159 mg/dL), high (160–189 mg/dL), and very high (≥190 mg/dL). High-density lipoprotein levels were classified as low (<40 mg/dL), normal (40–59 mg/dL), and high (≥60 mg/dL). Normal WBC was defined as 3.5 to 12.5×10³/mL. Normal hemoglobin count was defined as 11.5 to 15.0×10⁶/mL for women and 13 to 17×10⁶/mL for men. Normal RBC was defined as 4.0 to 5.2×10⁶/mL for women and 4.5 to 5.9×10⁶/mL for men. Statistical analysis was performed using SPSS version 17.0. Repeated measures analysis of variance was used to compare means between 3 groups (baseline, 3-month, and 6-month values). A paired sample t test was used to compare means between any 2 groups. Results with P<.05 were considered statistically significant.

Results

Treatment with oral isotretinoin was initiated in 349 patients at our institution from June 2009 to June 2012. Twenty-seven of these patients were excluded from the study because their medical records were not available. Medical records from 322 patients were obtained. The study population consisted of 226 (70.2%) women and 96 (29.8%) men. Patients ranged in age from 17 to 64 years, with a mean age of 23.9 years. The mean (standard deviation [SD]) age of the women was 23.9 (5.4) years and the mean (SD) age of the men was 23.8 (7.02) years. Most of the patients were on a regimen of 30 or 40 mg of isotretinoin daily. Differences between dosages and laboratory values were not analyzed because we assumed there would not be a significant difference, as most patients received the same dose. The mean (SD) WBC was 8.4 (3.5)×10³/mL. The mean (SD) RBC was 4.9 (0.5)×10⁶/mL. The mean (SD) hemoglobin count was 14.3 (1.7)×10⁶/mL (women, 13.6 [1.5]×10⁶/mL; men, 15.9 [1.1]×10⁶/mL).

The study evaluated the effects of isotretinoin on liver enzymes (AST and ALT) and lipids (TGs, LDL, and HDL). Nearly all of the patients (>95%) had normal AST and ALT levels at baseline. The results are outlined in the Table. Some values were not recorded for all patients at each follow-up.

Aspartate Aminotransferase Analysis

Aspartate aminotransferase levels were classified as normal and high. At baseline, mean (SD) AST levels were 20.2 (6.6) U/L, with normal levels in 311 (96.6%) patients and high in 7 (2.2%) patients. At 3-month follow-up, mean (SD) AST levels were 20.7 (5.2) U/L, with normal levels in 270 (83.9%) patients and high levels in 3 (0.9%) patients. At 6-month follow-up, mean (SD) AST levels were 21.3 (5.7) U/L, with normal levels in 209 (64.9%) patients and high levels in 4 (1.2%) patients. Aspartate aminotransferase levels increased at 3- and 6-month follow-up compared to baseline. Differences between AST levels were statistically significant (F_2,416=4.2, P=.016). Differences between AST levels at baseline and 3-month follow-up were not statistically significant (P=.3). Differences between AST levels at 3- and 6-month follow-up were not statistically significant (P=.4). Differences between AST levels at baseline and 6-month follow-up were statistically significant (P=.07). Differences between AST classifications at the 3 time points were not statistically significant (F_2,416=0.44, P=.64). Overall, the results indicated that AST levels increased over time in patients treated with isotretinoin, but the increase was not above the normal range and was not statistically significant.

Alanine Aminotransferase Analysis

Alanine aminotransferase levels were classified as normal or high. At baseline, mean (SD) ALT levels were 16.8 (11.2) U/L, with normal levels in 303 (94.1%) patients and high in 19 (5.9%) patients. At 3-month follow-up, mean (SD) ALT levels were 16.2 (9.3) U/L, with normal levels in 263 (81.7%) patients and high in 11 (3.4%) patients. At 6-month follow-up, mean (SD) ALT levels were 17.0 (11.3) U/L, with normal levels in 201 (62.4%) patients and high in 11 (3.4%) patients. Alanine aminotransferase levels at 3-month follow-up were lower than baseline but higher at 6-month follow-up compared to baseline and 3-month follow-up. Overall, ALT levels increased with time, but the differences between baseline and 3- and 6-month follow-up were not statistically significant (F_2,416=0.32, P=.72). Differences between ALT classifications at each time point were not statistically significant (F_2,418=0.21, P=.54). Overall, the results indicated that ALT levels increased over time in patients treated with isotretinoin, but the increase was not statistically significant.

Triglycerides Analysis

Triglyceride levels were classified as normal, borderline high, high, and very high. At baseline, mean (SD) TG levels were 107 (71) mg/dL, with normal levels in 270 (83.9%) patients, borderline high in 30 (9.3%) patients, high in 20 (6.2%) patients, and very high in 2 (0.6%) patients. At 3-month follow-up, mean (SD) TG levels were 117 (60) mg/dL, with normal levels in 197 (61.2%) patients, borderline high in 38 (11.8%) patients, high in 22 (6.8%) patients, and very high in 1 (0.3%) patient. At 6-month follow-up, mean (SD) TG levels were 122 (65) mg/dL, with normal levels in 145 (45%) patients, borderline high in 36 (11.2%) patients, high in 16 (5%) patients, and very high in 0 (0%) patients. Triglyceride levels increased and differences between TG levels at baseline and 3- and 6-month follow-up were statistically significant (F_2,384=17, P<.001). Baseline TG levels compared to 3-month follow-up were statistically signif-icant (P<.001). Differences in TG levels at 6-month follow-up versus baseline were statistically significant (P<.001). However, changes in TG levels from 3- to 6-month follow-up were not statistically significant (P=.21). Differences between TG classifications at each time point were statistically significant (F_2,386=6.9, P=.001). Overall, TG levels increased from baseline during isotretinoin treatment at 3- and 6-month follow-up, and these increases were above normal range; however, there was no statistically significant increase from 3- to 6-month follow-up.

Low-Density Lipoprotein Analysis

Low-density lipoprotein levels were classified as optimal, above optimal, borderline high, high, and very high. At baseline, mean (SD) LDL levels were 102 (28) mg/dL, with optimal levels in 162 (50.3%) patients, above optimal in 95 (29.5%) patients, borderline high in 32 (9.9%) patients, high in 11 (3.4%) patients, and very high in 3 (0.9%) patients. At 3-month follow-up, mean (SD) LDL levels were 113 (30) mg/dL, with optimal levels in 89 (27.6%) patients, above optimal in 98 (30.4%) patients, borderline high in 54 (16.8%) patients, high in 12 (3.7%) patients, and very high in 5 (1.6%) patients. At 6-month follow-up, mean (SD) LDL levels were 113 (27) mg/dL, with optimal levels in 60 (18.6%) patients, above optimal in 84 (26.1%) patients, borderline high in 44 (13.7%) patients, high in 8 (2.5%) patients, and very high in 1 (0.3%) patient. Overall, there were statistically significant increases in LDL levels at 3- and 6-month follow-up (F_2,382<75, P<.001). Differences between baseline LDL levels and 3-month follow-up were statistically significant (P<.001). Differences between baseline LDL levels and 6-month follow-up were statistically significant (P<.001). However, differences in LDL levels at 3- and 6-month follow-up were not statistically significant (P=.74). Differences between LDL classifications at each time point were statistically significant (F_2,382=51.2, P<.001). Overall, statistically significant increases in LDL levels from baseline were noted during isotretinoin treatment and this increase was above normal range; however, LDL levels did not significantly increase from 3- to 6-month follow-up.

High-Density Lipoprotein Analysis

High-density lipoprotein levels were classified as low, normal, and high. At baseline, mean (SD) HDL levels were 52.4 (16) mg/dL, with low levels in 60 (18.6%) patients, normal in 173 (53.7%) patients, and high in 71 (22%) patients. At 3-month follow-up, mean (SD) HDL levels were 48 (12) mg/dL, with low levels in 63 (19.6%) patients, normal in 154 (47.8%) patients, and high in 41 (12.7%) patients. At 6-month follow-up, mean (SD) HDL levels were 47.6 (12) mg/dL, with low levels in 48 (14.9%) patients, normal in 117 (36.3%) patients, and high in 33 (10.2%) patients. Overall, statistically significant decreases were noted in HDL levels (F_2,384=19, P<.001). Differences between baseline HDL levels compared to 3-month follow-up were statistically significant (P<.001). Differences between baseline HDL levels compared to 6-month follow-up were statistically significant (P<.001). Differences in HDL levels at 3- and 6-month follow-up were statistically significant (P<.001). Differences between HDL classifications at each time point were statistically significant (F_2,384=5.2, P=.006). Overall, there were statistically significant decreases in HDL levels during isotretinoin treatment from baseline and this decrease was above normal range; however, HDL levels did not decrease at 3- and 6-month follow-up.

Comment

Studies in the literature evaluating the effects of isotretinoin on liver enzymes and lipids suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT), TGs, HDL, and LDL in various degrees.¹ Zane et al⁴ studied 13,772 patients with acne undergoing oral isotretinoin therapy between March 1995 and September 2002. The investigators found increased liver transaminase and serum lipid levels. They suggested that these abnormalities were generally transient and reversible.⁴ Bershad et al⁵ reported an increase in LDL and TG but a decrease in HDL during isotretinoin therapy. These changes in the lipid profile also appeared to be transient and returned to baseline level 2 months following the end of treatment.⁵ In another study of 130 patients who were treated with isotretinoin, Vieira et al¹ noted an increase in AST, ALT, and TG levels. Most of the studies in the literature that reported effects of isotretinoin on liver enzymes and lipids suggested that the effects were reversible.

Although many studies reported alterations in serum transaminase and lipid levels, other studies reported no effect. In one study of 150 participants, Brito et al² found no statistically significant changes in liver transaminase, TG, HDL, or LDL levels following treatment with isotretinoin. In another study of 1292 participants by Alcalay et al,⁶ serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of isotretinoin treatment. In another study of 30 participants, Baxter et al⁷ reported no significant changes in TG, LDL, or HDL levels measured at baseline or during treatment with isotretinoin.

Some studies suggest that routine laboratory tests are needed when treating patients with isotretinoin due to severe alterations in serum liver transaminase and lipid levels, while other studies conclude that the effects are minimal and laboratory tests are not needed. In the current study, we found that there were statistically significant increases in TG and LDL levels in patients who underwent treatment with isotretinoin. We also found statistically significant decreases in HDL levels. In our study, liver enzymes were less affected than lipids in patients who underwent treatment with isotretinoin. There were statistically significant increases in AST levels, but the clinical classification was not affected. There also were increases in ALT levels, but the changes were not statistically significant.

Overall, we advise dermatologists that isotretinoin can be administered with minimal concern regarding changes in serum transaminase and lipid levels; however, although severe laboratory alterations were not noted in our study, we advise physicians to use caution when administering isotretinoin in patients with a history of abnormal findings.

NEWPORT BEACH, CALIF.– “The group we worry about are the 1- to 7-year-olds,” when it comes to new-onset acne, Dr. Sheila Fallon Friedlander said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

In an interview at the meeting, Dr. Friedlander, a professor at the University of California, San Diego, explained the additional clinical signs that can indicate a serious problem, and what questions to ask parents.

Tune in for her tips on how to evaluate children aged 1-7 years with acne.

SDEF and this news organization are owned by Frontline Medical Communications.

hsplete@frontlinemedcom.com

NEWPORT BEACH, CALIF.– “The group we worry about are the 1- to 7-year-olds,” when it comes to new-onset acne, Dr. Sheila Fallon Friedlander said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

In an interview at the meeting, Dr. Friedlander, a professor at the University of California, San Diego, explained the additional clinical signs that can indicate a serious problem, and what questions to ask parents.

Tune in for her tips on how to evaluate children aged 1-7 years with acne.

SDEF and this news organization are owned by Frontline Medical Communications.

hsplete@frontlinemedcom.com

NEWPORT BEACH, CALIF.– “The group we worry about are the 1- to 7-year-olds,” when it comes to new-onset acne, Dr. Sheila Fallon Friedlander said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

In an interview at the meeting, Dr. Friedlander, a professor at the University of California, San Diego, explained the additional clinical signs that can indicate a serious problem, and what questions to ask parents.

Tune in for her tips on how to evaluate children aged 1-7 years with acne.

SDEF and this news organization are owned by Frontline Medical Communications.

hsplete@frontlinemedcom.com

NEWPORT BEACH, CALIF. – Do more women today really have acne? Or are they simply more likely to seek help because they learn of new and better medications?

Acne often causes more psychosocial and psychological stress in adult women than in men or adolescents, Dr. Hilary Baldwin of SUNY Downstate Medical Center, Brooklyn, N.Y., said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

In an interview at the meeting, Dr. Baldwin explained what makes the treatment of acne in adult women distinct from acne treatment for men and adolescents, and what underused medications can yield success.

SDEF and this news organization are owned by Frontline Medical Communications.

hsplete@frontlinemedcom.com

NEWPORT BEACH, CALIF. – Do more women today really have acne? Or are they simply more likely to seek help because they learn of new and better medications?

Acne often causes more psychosocial and psychological stress in adult women than in men or adolescents, Dr. Hilary Baldwin of SUNY Downstate Medical Center, Brooklyn, N.Y., said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

In an interview at the meeting, Dr. Baldwin explained what makes the treatment of acne in adult women distinct from acne treatment for men and adolescents, and what underused medications can yield success.

SDEF and this news organization are owned by Frontline Medical Communications.

hsplete@frontlinemedcom.com

NEWPORT BEACH, CALIF. – Do more women today really have acne? Or are they simply more likely to seek help because they learn of new and better medications?

Acne often causes more psychosocial and psychological stress in adult women than in men or adolescents, Dr. Hilary Baldwin of SUNY Downstate Medical Center, Brooklyn, N.Y., said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

In an interview at the meeting, Dr. Baldwin explained what makes the treatment of acne in adult women distinct from acne treatment for men and adolescents, and what underused medications can yield success.

SDEF and this news organization are owned by Frontline Medical Communications.

hsplete@frontlinemedcom.com

The skin care market includes topical product formulations (eg, foams, lotions, ointments, creams) for a number of dermatologic therapeutic targets; however, there is limited information available regarding patient preference for product vehicles by specific dermatologic disease. There are few studies in the literature examining patient adherence to topical medications.¹ In the current study, 6 focus groups comprised of patients with 3 dermatologic conditions of interest—acne, atopic dermatitis (AD), or plaque psoriasis (PP)—were surveyed to gain a better understanding of treatment preferences among patients and attributes of various formulations that are most desirable and important to this patient population.

Patient preference for a vehicle is relevant to treatment adherence in patients with conditions such as acne, AD, and PP because noncompliance is a major factor in the high rates of failure that have been associated with topical dermatologic treatments.² The aesthetic attributes of a given vehicle formulation depend on the disease state being treated, the site of application, and the length of treatment.³ A limited number of studies have linked patient preferences to the attributes of topical medications. In one study, participants preferred an aqueous gel formulation compared with previously used topical treatments for AD.³ In another study, participants ranked the following properties of a hypothetical topical medication as most important: gel formulation, room temperature storage, product life of up to 18 months once opened, application with fingers, and a once-daily regimen.² A third study found that foams were preferred among other formulations (ie, creams, gels, and ointments) for a variety of disease states, including AD, PP, and seborrheic dermatitis.⁴ The current study uses a qualitative analysis to further explore patient preferences of vehicle attributes for the topical treatment of acne, AD, and PP.

Methods

Study Participants

Six focus groups were conducted with patients who were using topical prescription medications for the treatment of acne, AD, or PP from March to April 2012. Participants were recruited from Raleigh, North Carolina, and New York, New York, with 3 focus groups (1 for each condition) from each city.

Following institutional review board approval of the study processes and recruitment materials, participants meeting the following criteria were included in the study: 18 years or older; diagnosed with acne, AD, or PP by a physician (participants who currently reported more than 1 of these conditions were not eligible); diagnosed with the respective skin condition at least 6 months prior to screening; current or prior use of topical prescription medications in at least 2 different vehicle formulations (eg, cream and foam, ointment and gel); use of at least 1 topical prescription treatment 5 or more times per month; and English speaking and able to provide written consent.

Study Design

A semistructured discussion guide was developed to ensure consistency in the topics surveyed among all 6 focus groups, and the same 2 moderators conducted the discussion for all 6 groups. At the beginning of the study, after providing written informed consent, participants were given an overview of the study and were asked general questions intended to get the participants talking about their experiences with their respective conditions. To avoid or minimize bias, participants were only asked open-ended questions designed to ascertain what symptoms they experienced in relation to their respective conditions. Finally, the discussions were focused on the topical prescription treatments that participants had tried and the properties of each treatment they liked and disliked.

The focus groups were recorded (audio) and transcribed; transcriptions were then verified through an iterative process of technical and editorial review. Analysis of the results was conducted by evaluation and review of the field notes as well as the transcripts from the focus groups.

Results

A total of 54 participants were surveyed (average age, 40.9 years). Although the average age of participants in the acne and AD groups was generally the same (35.2 and 35.4 years, respectively), the average age of participants in the PP group was higher (52.2 years). The majority of participants were white females who had at least a college degree. On average, participants had been diagnosed with their respective condition approximately 15.5 years prior to screening. Participant demographics and clinical characteristics are presented in more detail in Table 1.

At the time of screening, participants reported prior or present use of topical prescription medications in various formulations for treatment of their respective conditions. The most commonly reported vehicles across all 3 conditions were creams and ointments, followed by lotions, gels, and foams.

Symptoms Across Conditions

At the beginning of the study, participants reported symptoms they experienced in association with their respective skin conditions. Itching and redness were the only symptoms reported across all 3 conditions in all 6 focus groups. Dry skin/dryness, flaking/scaling/peeling, and pain were reported by at least 1 participant in 5 of 6 focus groups. Other common symptoms reported in at least 3 focus groups included pimples/bumps/boils, sensitivity, bleeding, discoloration of skin, cracking/cuts/skin breaking, and buildup of dead or thickened skin/chunks of skin/plaque. As shown in Table 2, there was more variability in the symptoms reported across the 2 acne groups compared with those reported by the AD and PP groups. Table 2 displays all symptoms spontaneously reported across each of the 6 focus groups. Symptoms are listed according to the terms/descriptions provided by focus group participants.

Results by Condition

Unless otherwise noted, participant responses generally were consistent across the North Carolina and New York focus groups. Results from the study, which included a total of 54 participants, suggested a high degree of similarity among preferences for topical treatment attributes across the 3 conditions. Moisturizing was the single attribute that was mentioned across all 3 conditions in all 6 focus groups as an important characteristic in a topical dermatologic treatment. Other attributes mentioned by at least 1 participant in 5 of 6 focus groups included the following: absorbs/disappears/dries quickly, available in various formulations, does not bleach or stain skin/hair/clothing, is not greasy/oily, is not sticky/tacky, is long lasting/long acting/stays on/lasts through sweating or hand washing, is fragrance or odor free, is easy to apply/simple to use, and can use all the time.

A few condition-specific attributes also were noted. An attribute was considered condition specific if it was mentioned by at least 1 participant in both groups for any condition. Preferred properties for topical medications that were specific to acne patients included the following: easy to dispense/dispenses right amount, nondrying, product goes on/spreads smoothly, container (eg, tube, pump) is not easily broken/does not leak, and creamy. Preferred properties that were specific to AD patients included the following: is not noticeable to others/conceals area, good consistency, and cooling. Preferred properties that were specific to 2 conditions included no residue among acne and AD patients and soothing among AD and PP patients. Preferred properties for topical medications across all focus groups are described in further detail in Table 3.

Regarding vehicle-type preferences, acne patients tended to prefer washes, creams, and lotions; AD patients preferred creams; and psoriasis patients preferred creams, ointments, and foams (particularly for the scalp).

Participants across all 3 conditions reported that during daytime hours (versus at night), they would be less likely to use products that are oily, shiny, thick (eg, ointments, oils); bleach or stain the skin/clothing; interfere with makeup, work, or other activities; or are visible to others. Rather, a majority of participants noted that they were more likely to use thinner, less oily products (eg, creams, lotions) during daytime hours, in social situations, or during certain activities (eg, exercise). Participants across all 3 conditions noted that they only used prescription shampoos when they had enough time to repeatedly rinse their hair to eliminate the smell. Participants across all 6 groups noted that they tended to choose creams or lotions over ointments (when available) during the summer because they considered these products to be lighter and less greasy.

Overall, participants indicated that condition-specific symptoms did not influence their preference for topical formulations; rather, they used whatever prescriptions they currently had. However, in some instances, participants noted that the location of the affected area might influence the type of product selected. For example, some participants tended not to use ointments on the scalp or in locations where their clothes might come into contact with the medicated area to avoid clothes sticking to medicated areas. Other participants used lighter, less stringent products on the face versus other locations. Participants noted that foams were preferred for more discrete localized areas.

Comment

Despite the variability in symptoms and conditions across the study population as well as participants’ varying experience with and access to topical treatments, the attributes participants valued most in topical prescription treatments were relatively consistent across the 3 conditions: moisturizing, absorbs/disappears/dries quickly, available in various formulations, does not bleach or stain skin/hair/clothing, is not greasy or oily, is not sticky or tacky, is long lasting/long acting, is fragrance or odor free, is easy to apply/simple to use, and can use all the time. Preferred vehicle attributes were generally consistent across the 3 conditions, but preferences for vehicle types tended to vary by condition. Although some vehicles were more closely associated with specific attributes (eg, the majority considered lotions to be moisturizing), no one vehicle was associated with the complete list of attributes for the ideal topical medication. Regardless of the symptoms experienced or particular situations/activities, participants noted that they tended to use the topical medications that were available to them, even if intended for different locations of the body, and nearly all reported using more than 1 type of topical treatment.

Caution should be used in interpreting these findings, as participant preferences are largely dependent on prior experience with different vehicle types. The small number of participants across the 3 conditions in this analysis also limits conclusions that can be drawn from the data sets, as each condition has different though somewhat overlapping treatment algorithms. A focused inquiry into each of these conditions through separate evaluations may provide for a more robust analysis. Future research might employ questionnaire methodology to develop items assessing the attributes of interest (eg, moisturizing ability, rate of absorption, greasiness/oiliness, stickiness/tackiness, fragrance/odor). The final set of desirable attributes may vary depending on the condition (eg, a moisturizing product may be more important to PP and AD patients than acne patients) as well as comparator products.

Acknowledgment—The authors would like to thank Jennifer Gwazdauskas, MBA, Research Triangle Park, North Carolina, of Stiefel, a GSK company, for her assistance with manuscript review.

The skin care market includes topical product formulations (eg, foams, lotions, ointments, creams) for a number of dermatologic therapeutic targets; however, there is limited information available regarding patient preference for product vehicles by specific dermatologic disease. There are few studies in the literature examining patient adherence to topical medications.¹ In the current study, 6 focus groups comprised of patients with 3 dermatologic conditions of interest—acne, atopic dermatitis (AD), or plaque psoriasis (PP)—were surveyed to gain a better understanding of treatment preferences among patients and attributes of various formulations that are most desirable and important to this patient population.

Patient preference for a vehicle is relevant to treatment adherence in patients with conditions such as acne, AD, and PP because noncompliance is a major factor in the high rates of failure that have been associated with topical dermatologic treatments.² The aesthetic attributes of a given vehicle formulation depend on the disease state being treated, the site of application, and the length of treatment.³ A limited number of studies have linked patient preferences to the attributes of topical medications. In one study, participants preferred an aqueous gel formulation compared with previously used topical treatments for AD.³ In another study, participants ranked the following properties of a hypothetical topical medication as most important: gel formulation, room temperature storage, product life of up to 18 months once opened, application with fingers, and a once-daily regimen.² A third study found that foams were preferred among other formulations (ie, creams, gels, and ointments) for a variety of disease states, including AD, PP, and seborrheic dermatitis.⁴ The current study uses a qualitative analysis to further explore patient preferences of vehicle attributes for the topical treatment of acne, AD, and PP.

Methods

Study Participants

Six focus groups were conducted with patients who were using topical prescription medications for the treatment of acne, AD, or PP from March to April 2012. Participants were recruited from Raleigh, North Carolina, and New York, New York, with 3 focus groups (1 for each condition) from each city.

Following institutional review board approval of the study processes and recruitment materials, participants meeting the following criteria were included in the study: 18 years or older; diagnosed with acne, AD, or PP by a physician (participants who currently reported more than 1 of these conditions were not eligible); diagnosed with the respective skin condition at least 6 months prior to screening; current or prior use of topical prescription medications in at least 2 different vehicle formulations (eg, cream and foam, ointment and gel); use of at least 1 topical prescription treatment 5 or more times per month; and English speaking and able to provide written consent.

Study Design

A semistructured discussion guide was developed to ensure consistency in the topics surveyed among all 6 focus groups, and the same 2 moderators conducted the discussion for all 6 groups. At the beginning of the study, after providing written informed consent, participants were given an overview of the study and were asked general questions intended to get the participants talking about their experiences with their respective conditions. To avoid or minimize bias, participants were only asked open-ended questions designed to ascertain what symptoms they experienced in relation to their respective conditions. Finally, the discussions were focused on the topical prescription treatments that participants had tried and the properties of each treatment they liked and disliked.

The focus groups were recorded (audio) and transcribed; transcriptions were then verified through an iterative process of technical and editorial review. Analysis of the results was conducted by evaluation and review of the field notes as well as the transcripts from the focus groups.

Results

A total of 54 participants were surveyed (average age, 40.9 years). Although the average age of participants in the acne and AD groups was generally the same (35.2 and 35.4 years, respectively), the average age of participants in the PP group was higher (52.2 years). The majority of participants were white females who had at least a college degree. On average, participants had been diagnosed with their respective condition approximately 15.5 years prior to screening. Participant demographics and clinical characteristics are presented in more detail in Table 1.

At the time of screening, participants reported prior or present use of topical prescription medications in various formulations for treatment of their respective conditions. The most commonly reported vehicles across all 3 conditions were creams and ointments, followed by lotions, gels, and foams.

Symptoms Across Conditions

At the beginning of the study, participants reported symptoms they experienced in association with their respective skin conditions. Itching and redness were the only symptoms reported across all 3 conditions in all 6 focus groups. Dry skin/dryness, flaking/scaling/peeling, and pain were reported by at least 1 participant in 5 of 6 focus groups. Other common symptoms reported in at least 3 focus groups included pimples/bumps/boils, sensitivity, bleeding, discoloration of skin, cracking/cuts/skin breaking, and buildup of dead or thickened skin/chunks of skin/plaque. As shown in Table 2, there was more variability in the symptoms reported across the 2 acne groups compared with those reported by the AD and PP groups. Table 2 displays all symptoms spontaneously reported across each of the 6 focus groups. Symptoms are listed according to the terms/descriptions provided by focus group participants.

Results by Condition

Unless otherwise noted, participant responses generally were consistent across the North Carolina and New York focus groups. Results from the study, which included a total of 54 participants, suggested a high degree of similarity among preferences for topical treatment attributes across the 3 conditions. Moisturizing was the single attribute that was mentioned across all 3 conditions in all 6 focus groups as an important characteristic in a topical dermatologic treatment. Other attributes mentioned by at least 1 participant in 5 of 6 focus groups included the following: absorbs/disappears/dries quickly, available in various formulations, does not bleach or stain skin/hair/clothing, is not greasy/oily, is not sticky/tacky, is long lasting/long acting/stays on/lasts through sweating or hand washing, is fragrance or odor free, is easy to apply/simple to use, and can use all the time.

A few condition-specific attributes also were noted. An attribute was considered condition specific if it was mentioned by at least 1 participant in both groups for any condition. Preferred properties for topical medications that were specific to acne patients included the following: easy to dispense/dispenses right amount, nondrying, product goes on/spreads smoothly, container (eg, tube, pump) is not easily broken/does not leak, and creamy. Preferred properties that were specific to AD patients included the following: is not noticeable to others/conceals area, good consistency, and cooling. Preferred properties that were specific to 2 conditions included no residue among acne and AD patients and soothing among AD and PP patients. Preferred properties for topical medications across all focus groups are described in further detail in Table 3.

Regarding vehicle-type preferences, acne patients tended to prefer washes, creams, and lotions; AD patients preferred creams; and psoriasis patients preferred creams, ointments, and foams (particularly for the scalp).

Participants across all 3 conditions reported that during daytime hours (versus at night), they would be less likely to use products that are oily, shiny, thick (eg, ointments, oils); bleach or stain the skin/clothing; interfere with makeup, work, or other activities; or are visible to others. Rather, a majority of participants noted that they were more likely to use thinner, less oily products (eg, creams, lotions) during daytime hours, in social situations, or during certain activities (eg, exercise). Participants across all 3 conditions noted that they only used prescription shampoos when they had enough time to repeatedly rinse their hair to eliminate the smell. Participants across all 6 groups noted that they tended to choose creams or lotions over ointments (when available) during the summer because they considered these products to be lighter and less greasy.

Overall, participants indicated that condition-specific symptoms did not influence their preference for topical formulations; rather, they used whatever prescriptions they currently had. However, in some instances, participants noted that the location of the affected area might influence the type of product selected. For example, some participants tended not to use ointments on the scalp or in locations where their clothes might come into contact with the medicated area to avoid clothes sticking to medicated areas. Other participants used lighter, less stringent products on the face versus other locations. Participants noted that foams were preferred for more discrete localized areas.

Comment

Despite the variability in symptoms and conditions across the study population as well as participants’ varying experience with and access to topical treatments, the attributes participants valued most in topical prescription treatments were relatively consistent across the 3 conditions: moisturizing, absorbs/disappears/dries quickly, available in various formulations, does not bleach or stain skin/hair/clothing, is not greasy or oily, is not sticky or tacky, is long lasting/long acting, is fragrance or odor free, is easy to apply/simple to use, and can use all the time. Preferred vehicle attributes were generally consistent across the 3 conditions, but preferences for vehicle types tended to vary by condition. Although some vehicles were more closely associated with specific attributes (eg, the majority considered lotions to be moisturizing), no one vehicle was associated with the complete list of attributes for the ideal topical medication. Regardless of the symptoms experienced or particular situations/activities, participants noted that they tended to use the topical medications that were available to them, even if intended for different locations of the body, and nearly all reported using more than 1 type of topical treatment.

Caution should be used in interpreting these findings, as participant preferences are largely dependent on prior experience with different vehicle types. The small number of participants across the 3 conditions in this analysis also limits conclusions that can be drawn from the data sets, as each condition has different though somewhat overlapping treatment algorithms. A focused inquiry into each of these conditions through separate evaluations may provide for a more robust analysis. Future research might employ questionnaire methodology to develop items assessing the attributes of interest (eg, moisturizing ability, rate of absorption, greasiness/oiliness, stickiness/tackiness, fragrance/odor). The final set of desirable attributes may vary depending on the condition (eg, a moisturizing product may be more important to PP and AD patients than acne patients) as well as comparator products.

Acknowledgment—The authors would like to thank Jennifer Gwazdauskas, MBA, Research Triangle Park, North Carolina, of Stiefel, a GSK company, for her assistance with manuscript review.

The skin care market includes topical product formulations (eg, foams, lotions, ointments, creams) for a number of dermatologic therapeutic targets; however, there is limited information available regarding patient preference for product vehicles by specific dermatologic disease. There are few studies in the literature examining patient adherence to topical medications.¹ In the current study, 6 focus groups comprised of patients with 3 dermatologic conditions of interest—acne, atopic dermatitis (AD), or plaque psoriasis (PP)—were surveyed to gain a better understanding of treatment preferences among patients and attributes of various formulations that are most desirable and important to this patient population.

Patient preference for a vehicle is relevant to treatment adherence in patients with conditions such as acne, AD, and PP because noncompliance is a major factor in the high rates of failure that have been associated with topical dermatologic treatments.² The aesthetic attributes of a given vehicle formulation depend on the disease state being treated, the site of application, and the length of treatment.³ A limited number of studies have linked patient preferences to the attributes of topical medications. In one study, participants preferred an aqueous gel formulation compared with previously used topical treatments for AD.³ In another study, participants ranked the following properties of a hypothetical topical medication as most important: gel formulation, room temperature storage, product life of up to 18 months once opened, application with fingers, and a once-daily regimen.² A third study found that foams were preferred among other formulations (ie, creams, gels, and ointments) for a variety of disease states, including AD, PP, and seborrheic dermatitis.⁴ The current study uses a qualitative analysis to further explore patient preferences of vehicle attributes for the topical treatment of acne, AD, and PP.

Methods

Study Participants

Six focus groups were conducted with patients who were using topical prescription medications for the treatment of acne, AD, or PP from March to April 2012. Participants were recruited from Raleigh, North Carolina, and New York, New York, with 3 focus groups (1 for each condition) from each city.

Following institutional review board approval of the study processes and recruitment materials, participants meeting the following criteria were included in the study: 18 years or older; diagnosed with acne, AD, or PP by a physician (participants who currently reported more than 1 of these conditions were not eligible); diagnosed with the respective skin condition at least 6 months prior to screening; current or prior use of topical prescription medications in at least 2 different vehicle formulations (eg, cream and foam, ointment and gel); use of at least 1 topical prescription treatment 5 or more times per month; and English speaking and able to provide written consent.

Study Design

A semistructured discussion guide was developed to ensure consistency in the topics surveyed among all 6 focus groups, and the same 2 moderators conducted the discussion for all 6 groups. At the beginning of the study, after providing written informed consent, participants were given an overview of the study and were asked general questions intended to get the participants talking about their experiences with their respective conditions. To avoid or minimize bias, participants were only asked open-ended questions designed to ascertain what symptoms they experienced in relation to their respective conditions. Finally, the discussions were focused on the topical prescription treatments that participants had tried and the properties of each treatment they liked and disliked.

The focus groups were recorded (audio) and transcribed; transcriptions were then verified through an iterative process of technical and editorial review. Analysis of the results was conducted by evaluation and review of the field notes as well as the transcripts from the focus groups.

Results

A total of 54 participants were surveyed (average age, 40.9 years). Although the average age of participants in the acne and AD groups was generally the same (35.2 and 35.4 years, respectively), the average age of participants in the PP group was higher (52.2 years). The majority of participants were white females who had at least a college degree. On average, participants had been diagnosed with their respective condition approximately 15.5 years prior to screening. Participant demographics and clinical characteristics are presented in more detail in Table 1.

At the time of screening, participants reported prior or present use of topical prescription medications in various formulations for treatment of their respective conditions. The most commonly reported vehicles across all 3 conditions were creams and ointments, followed by lotions, gels, and foams.

Symptoms Across Conditions

At the beginning of the study, participants reported symptoms they experienced in association with their respective skin conditions. Itching and redness were the only symptoms reported across all 3 conditions in all 6 focus groups. Dry skin/dryness, flaking/scaling/peeling, and pain were reported by at least 1 participant in 5 of 6 focus groups. Other common symptoms reported in at least 3 focus groups included pimples/bumps/boils, sensitivity, bleeding, discoloration of skin, cracking/cuts/skin breaking, and buildup of dead or thickened skin/chunks of skin/plaque. As shown in Table 2, there was more variability in the symptoms reported across the 2 acne groups compared with those reported by the AD and PP groups. Table 2 displays all symptoms spontaneously reported across each of the 6 focus groups. Symptoms are listed according to the terms/descriptions provided by focus group participants.

Results by Condition

Unless otherwise noted, participant responses generally were consistent across the North Carolina and New York focus groups. Results from the study, which included a total of 54 participants, suggested a high degree of similarity among preferences for topical treatment attributes across the 3 conditions. Moisturizing was the single attribute that was mentioned across all 3 conditions in all 6 focus groups as an important characteristic in a topical dermatologic treatment. Other attributes mentioned by at least 1 participant in 5 of 6 focus groups included the following: absorbs/disappears/dries quickly, available in various formulations, does not bleach or stain skin/hair/clothing, is not greasy/oily, is not sticky/tacky, is long lasting/long acting/stays on/lasts through sweating or hand washing, is fragrance or odor free, is easy to apply/simple to use, and can use all the time.

A few condition-specific attributes also were noted. An attribute was considered condition specific if it was mentioned by at least 1 participant in both groups for any condition. Preferred properties for topical medications that were specific to acne patients included the following: easy to dispense/dispenses right amount, nondrying, product goes on/spreads smoothly, container (eg, tube, pump) is not easily broken/does not leak, and creamy. Preferred properties that were specific to AD patients included the following: is not noticeable to others/conceals area, good consistency, and cooling. Preferred properties that were specific to 2 conditions included no residue among acne and AD patients and soothing among AD and PP patients. Preferred properties for topical medications across all focus groups are described in further detail in Table 3.

Regarding vehicle-type preferences, acne patients tended to prefer washes, creams, and lotions; AD patients preferred creams; and psoriasis patients preferred creams, ointments, and foams (particularly for the scalp).

Participants across all 3 conditions reported that during daytime hours (versus at night), they would be less likely to use products that are oily, shiny, thick (eg, ointments, oils); bleach or stain the skin/clothing; interfere with makeup, work, or other activities; or are visible to others. Rather, a majority of participants noted that they were more likely to use thinner, less oily products (eg, creams, lotions) during daytime hours, in social situations, or during certain activities (eg, exercise). Participants across all 3 conditions noted that they only used prescription shampoos when they had enough time to repeatedly rinse their hair to eliminate the smell. Participants across all 6 groups noted that they tended to choose creams or lotions over ointments (when available) during the summer because they considered these products to be lighter and less greasy.

Overall, participants indicated that condition-specific symptoms did not influence their preference for topical formulations; rather, they used whatever prescriptions they currently had. However, in some instances, participants noted that the location of the affected area might influence the type of product selected. For example, some participants tended not to use ointments on the scalp or in locations where their clothes might come into contact with the medicated area to avoid clothes sticking to medicated areas. Other participants used lighter, less stringent products on the face versus other locations. Participants noted that foams were preferred for more discrete localized areas.

Comment

Despite the variability in symptoms and conditions across the study population as well as participants’ varying experience with and access to topical treatments, the attributes participants valued most in topical prescription treatments were relatively consistent across the 3 conditions: moisturizing, absorbs/disappears/dries quickly, available in various formulations, does not bleach or stain skin/hair/clothing, is not greasy or oily, is not sticky or tacky, is long lasting/long acting, is fragrance or odor free, is easy to apply/simple to use, and can use all the time. Preferred vehicle attributes were generally consistent across the 3 conditions, but preferences for vehicle types tended to vary by condition. Although some vehicles were more closely associated with specific attributes (eg, the majority considered lotions to be moisturizing), no one vehicle was associated with the complete list of attributes for the ideal topical medication. Regardless of the symptoms experienced or particular situations/activities, participants noted that they tended to use the topical medications that were available to them, even if intended for different locations of the body, and nearly all reported using more than 1 type of topical treatment.

Caution should be used in interpreting these findings, as participant preferences are largely dependent on prior experience with different vehicle types. The small number of participants across the 3 conditions in this analysis also limits conclusions that can be drawn from the data sets, as each condition has different though somewhat overlapping treatment algorithms. A focused inquiry into each of these conditions through separate evaluations may provide for a more robust analysis. Future research might employ questionnaire methodology to develop items assessing the attributes of interest (eg, moisturizing ability, rate of absorption, greasiness/oiliness, stickiness/tackiness, fragrance/odor). The final set of desirable attributes may vary depending on the condition (eg, a moisturizing product may be more important to PP and AD patients than acne patients) as well as comparator products.

Acknowledgment—The authors would like to thank Jennifer Gwazdauskas, MBA, Research Triangle Park, North Carolina, of Stiefel, a GSK company, for her assistance with manuscript review.