To the Editor:

Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder that can present at any age. Patients with AA have a disproportionately high comorbidity burden and low quality of life, often grappling with anxiety, depression, and psychosocial sequelae involving identity, such as reduced self-esteem.^1,2 Although conventional therapies aim to reduce hair loss, none are curative.³ Response to treatment is highly unpredictable, with current data suggesting that up to 50% of patients recover within 1 year while 14% to 25% progress to either alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss).⁴ Options for therapeutic intervention remain limited and vary in safety and effectiveness, warranting further research to identify optimal modalities and minimize side effects. Interestingly, scalp rolling has been used as an adjuvant to topical triamcinolone acetonide.^3,5 However, the extent of its effect in combination with other therapies remains unclear. We report 3 pediatric patients with confirmed AA refractory to conventional topical treatment who experienced remarkable scalp hair regrowth after adding biweekly scalp rolling as an adjuvant therapy.

A 7-year-old boy with AA presented with 95% scalp hair loss of 7 months’ duration (Figure 1A)(patient 1). Prior treatments included mometasone solution and clobetasol solution 0.05%. After 3 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 1B). No pain, bleeding, or other side effects were reported.

An 11-year-old girl with AA presented with 100% hair loss of 7 months’ duration (Figure 2A)(patient 2). Prior treatments included fluocinonide solution and intralesional Kenalog injections. After 4 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 2B). No pain, bleeding, or other side effects were reported.

A 16-year-old boy with AA presented with 30% hair loss of 4 years’ duration (Figure 3A)(patient 3). Prior treatments included squaric acid and intralesional Kenalog injections. After 2 years of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth at 17 months (Figure 3B). No pain, bleeding, or other side effects were reported.

Scalp rolling—also known as microneedling—provides a multifactorial approach to hair regrowth in patients with AA. The mechanism of action involves both the hair cycle and wound repair pathways by stimulation of the dermal papillae and stem cells.⁶ Scalp rolling has been observed to induce the expression of several hair growth pathway mediators, such as WNT3A, β-catenin, vascular endothelial growth factor, and WNT10B.⁷ Wnt/β-catenin pathway signaling is integral to multiple aspects of the hair regrowth process, including hair morphogenesis, follicle regeneration, and growth of the shaft itself.^8,9 Scalp rolling causes microinjuries to the skin, thereby diverting blood supply to the follicles and stimulating wound regeneration, a process suggested to induce follicle regeneration. This effect is due to increased expression of vascular endothelial growth factor after cutaneous injury, a mediator of both hair growth and cycling as well as wound repair.⁷ Adjuvant scalp rolling creates a synergistic effect by facilitating absorption of topical and intralesional therapies. The physical breakdown of dermal capillary barriers creates microchannels that traverse the stratum corneum, improving the permeability of small-molecule substances and allowing for relatively painless and uniform delivery of combination therapies. A secondary benefit is hypertrophy, which counteracts the atrophy caused by topical steroids via collagen induction.⁷

Additionally, scalp rolling confers minimal risk to the patient, making it safer than conventional pharmacologic therapies such as corticosteroids or Janus kinase (JAK) inhibitors. Although intralesional steroid injections are first-line treatments for limited disease, they can cause pain and skin atrophy.¹⁰ In one cohort of 54 patients, topical steroids were inferior to both oral and intralesional treatment, and oral steroids carried a systemic side-effect profile and worsening of comorbidities including hyperglycemia and hypertension as well as negative effects on bone density.¹¹ Baricitinib, a JAK inhibitor, was the first systemic treatment to gain US Food and Drug Administration approval for severe AA.¹² However, this novel therapeutic confers adverse effects including infection, acne, and hypercholesterolemia, as reported in the BRAVE-AA trials.¹³ More broadly, the US Food and Drug Administration warns of serious long-term risks such as cardiovascular events and malignancy.¹⁴ Given the tremendous potential of JAK inhibitors, further research is warranted to understand both the efficacy of topical formulations as well as the possible role of scalp rolling as its adjuvant.

Finally, scalp rolling is easily accessible and affordable to patients. Scalp rolling devices are readily available and affordable online, and they can be used autonomously at home. This pragmatic option allows patients to take control of their own treatment course and offers a financially feasible alternative to navigating insurance coverage as well as the need for extra office visits for medication refills and monitoring.

We report 3 cases of the use of scalp rolling as an adjuvant to conventional therapy for refractory AA in young patients. Although prospective research is required to establish causality and characterize age-related trends in treatment response, consideration of scalp rolling as an adjuvant to conventional therapy may help to optimize treatment regimens. Given its low risk for side effects and potential benefits, we recommend scalp rolling for patients with refractory AA.

To the Editor:

Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder that can present at any age. Patients with AA have a disproportionately high comorbidity burden and low quality of life, often grappling with anxiety, depression, and psychosocial sequelae involving identity, such as reduced self-esteem.^1,2 Although conventional therapies aim to reduce hair loss, none are curative.³ Response to treatment is highly unpredictable, with current data suggesting that up to 50% of patients recover within 1 year while 14% to 25% progress to either alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss).⁴ Options for therapeutic intervention remain limited and vary in safety and effectiveness, warranting further research to identify optimal modalities and minimize side effects. Interestingly, scalp rolling has been used as an adjuvant to topical triamcinolone acetonide.^3,5 However, the extent of its effect in combination with other therapies remains unclear. We report 3 pediatric patients with confirmed AA refractory to conventional topical treatment who experienced remarkable scalp hair regrowth after adding biweekly scalp rolling as an adjuvant therapy.

A 7-year-old boy with AA presented with 95% scalp hair loss of 7 months’ duration (Figure 1A)(patient 1). Prior treatments included mometasone solution and clobetasol solution 0.05%. After 3 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 1B). No pain, bleeding, or other side effects were reported.

An 11-year-old girl with AA presented with 100% hair loss of 7 months’ duration (Figure 2A)(patient 2). Prior treatments included fluocinonide solution and intralesional Kenalog injections. After 4 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 2B). No pain, bleeding, or other side effects were reported.

A 16-year-old boy with AA presented with 30% hair loss of 4 years’ duration (Figure 3A)(patient 3). Prior treatments included squaric acid and intralesional Kenalog injections. After 2 years of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth at 17 months (Figure 3B). No pain, bleeding, or other side effects were reported.

Scalp rolling—also known as microneedling—provides a multifactorial approach to hair regrowth in patients with AA. The mechanism of action involves both the hair cycle and wound repair pathways by stimulation of the dermal papillae and stem cells.⁶ Scalp rolling has been observed to induce the expression of several hair growth pathway mediators, such as WNT3A, β-catenin, vascular endothelial growth factor, and WNT10B.⁷ Wnt/β-catenin pathway signaling is integral to multiple aspects of the hair regrowth process, including hair morphogenesis, follicle regeneration, and growth of the shaft itself.^8,9 Scalp rolling causes microinjuries to the skin, thereby diverting blood supply to the follicles and stimulating wound regeneration, a process suggested to induce follicle regeneration. This effect is due to increased expression of vascular endothelial growth factor after cutaneous injury, a mediator of both hair growth and cycling as well as wound repair.⁷ Adjuvant scalp rolling creates a synergistic effect by facilitating absorption of topical and intralesional therapies. The physical breakdown of dermal capillary barriers creates microchannels that traverse the stratum corneum, improving the permeability of small-molecule substances and allowing for relatively painless and uniform delivery of combination therapies. A secondary benefit is hypertrophy, which counteracts the atrophy caused by topical steroids via collagen induction.⁷

Additionally, scalp rolling confers minimal risk to the patient, making it safer than conventional pharmacologic therapies such as corticosteroids or Janus kinase (JAK) inhibitors. Although intralesional steroid injections are first-line treatments for limited disease, they can cause pain and skin atrophy.¹⁰ In one cohort of 54 patients, topical steroids were inferior to both oral and intralesional treatment, and oral steroids carried a systemic side-effect profile and worsening of comorbidities including hyperglycemia and hypertension as well as negative effects on bone density.¹¹ Baricitinib, a JAK inhibitor, was the first systemic treatment to gain US Food and Drug Administration approval for severe AA.¹² However, this novel therapeutic confers adverse effects including infection, acne, and hypercholesterolemia, as reported in the BRAVE-AA trials.¹³ More broadly, the US Food and Drug Administration warns of serious long-term risks such as cardiovascular events and malignancy.¹⁴ Given the tremendous potential of JAK inhibitors, further research is warranted to understand both the efficacy of topical formulations as well as the possible role of scalp rolling as its adjuvant.

Finally, scalp rolling is easily accessible and affordable to patients. Scalp rolling devices are readily available and affordable online, and they can be used autonomously at home. This pragmatic option allows patients to take control of their own treatment course and offers a financially feasible alternative to navigating insurance coverage as well as the need for extra office visits for medication refills and monitoring.

We report 3 cases of the use of scalp rolling as an adjuvant to conventional therapy for refractory AA in young patients. Although prospective research is required to establish causality and characterize age-related trends in treatment response, consideration of scalp rolling as an adjuvant to conventional therapy may help to optimize treatment regimens. Given its low risk for side effects and potential benefits, we recommend scalp rolling for patients with refractory AA.

To the Editor:

Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder that can present at any age. Patients with AA have a disproportionately high comorbidity burden and low quality of life, often grappling with anxiety, depression, and psychosocial sequelae involving identity, such as reduced self-esteem.^1,2 Although conventional therapies aim to reduce hair loss, none are curative.³ Response to treatment is highly unpredictable, with current data suggesting that up to 50% of patients recover within 1 year while 14% to 25% progress to either alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss).⁴ Options for therapeutic intervention remain limited and vary in safety and effectiveness, warranting further research to identify optimal modalities and minimize side effects. Interestingly, scalp rolling has been used as an adjuvant to topical triamcinolone acetonide.^3,5 However, the extent of its effect in combination with other therapies remains unclear. We report 3 pediatric patients with confirmed AA refractory to conventional topical treatment who experienced remarkable scalp hair regrowth after adding biweekly scalp rolling as an adjuvant therapy.

A 7-year-old boy with AA presented with 95% scalp hair loss of 7 months’ duration (Figure 1A)(patient 1). Prior treatments included mometasone solution and clobetasol solution 0.05%. After 3 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 1B). No pain, bleeding, or other side effects were reported.

An 11-year-old girl with AA presented with 100% hair loss of 7 months’ duration (Figure 2A)(patient 2). Prior treatments included fluocinonide solution and intralesional Kenalog injections. After 4 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 2B). No pain, bleeding, or other side effects were reported.

A 16-year-old boy with AA presented with 30% hair loss of 4 years’ duration (Figure 3A)(patient 3). Prior treatments included squaric acid and intralesional Kenalog injections. After 2 years of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth at 17 months (Figure 3B). No pain, bleeding, or other side effects were reported.

Scalp rolling—also known as microneedling—provides a multifactorial approach to hair regrowth in patients with AA. The mechanism of action involves both the hair cycle and wound repair pathways by stimulation of the dermal papillae and stem cells.⁶ Scalp rolling has been observed to induce the expression of several hair growth pathway mediators, such as WNT3A, β-catenin, vascular endothelial growth factor, and WNT10B.⁷ Wnt/β-catenin pathway signaling is integral to multiple aspects of the hair regrowth process, including hair morphogenesis, follicle regeneration, and growth of the shaft itself.^8,9 Scalp rolling causes microinjuries to the skin, thereby diverting blood supply to the follicles and stimulating wound regeneration, a process suggested to induce follicle regeneration. This effect is due to increased expression of vascular endothelial growth factor after cutaneous injury, a mediator of both hair growth and cycling as well as wound repair.⁷ Adjuvant scalp rolling creates a synergistic effect by facilitating absorption of topical and intralesional therapies. The physical breakdown of dermal capillary barriers creates microchannels that traverse the stratum corneum, improving the permeability of small-molecule substances and allowing for relatively painless and uniform delivery of combination therapies. A secondary benefit is hypertrophy, which counteracts the atrophy caused by topical steroids via collagen induction.⁷

Additionally, scalp rolling confers minimal risk to the patient, making it safer than conventional pharmacologic therapies such as corticosteroids or Janus kinase (JAK) inhibitors. Although intralesional steroid injections are first-line treatments for limited disease, they can cause pain and skin atrophy.¹⁰ In one cohort of 54 patients, topical steroids were inferior to both oral and intralesional treatment, and oral steroids carried a systemic side-effect profile and worsening of comorbidities including hyperglycemia and hypertension as well as negative effects on bone density.¹¹ Baricitinib, a JAK inhibitor, was the first systemic treatment to gain US Food and Drug Administration approval for severe AA.¹² However, this novel therapeutic confers adverse effects including infection, acne, and hypercholesterolemia, as reported in the BRAVE-AA trials.¹³ More broadly, the US Food and Drug Administration warns of serious long-term risks such as cardiovascular events and malignancy.¹⁴ Given the tremendous potential of JAK inhibitors, further research is warranted to understand both the efficacy of topical formulations as well as the possible role of scalp rolling as its adjuvant.

Finally, scalp rolling is easily accessible and affordable to patients. Scalp rolling devices are readily available and affordable online, and they can be used autonomously at home. This pragmatic option allows patients to take control of their own treatment course and offers a financially feasible alternative to navigating insurance coverage as well as the need for extra office visits for medication refills and monitoring.

We report 3 cases of the use of scalp rolling as an adjuvant to conventional therapy for refractory AA in young patients. Although prospective research is required to establish causality and characterize age-related trends in treatment response, consideration of scalp rolling as an adjuvant to conventional therapy may help to optimize treatment regimens. Given its low risk for side effects and potential benefits, we recommend scalp rolling for patients with refractory AA.

To the Editor:

Cryptococcus neoformans is an opportunistic fungus with a predilection for immunocompromised hosts, including solid organ transplant recipients (SOTRs). However, the rapid emergence of diffuse panniculitis only upon the start of therapy for extracutaneous disease is a rare phenomenon. We report the case of a liver transplant recipient who developed a paradoxical inflammatory reaction after initiating liposomal amphotericin B therapy for disseminated C neoformans, which manifested as progressive indurated plaques histologically consistent with cryptococcal panniculitis.

A 44-year-old man who received an orthotopic liver transplant 12 months prior and was on prednisone (20 mg daily) and tacrolimus (7 mg total daily) was admitted for multifocal pneumonia complicated by septic shock. Blood and respiratory cultures grew C neoformans, and lumbar puncture evaluation of cerebrospinal fluid revealed the presence of Cryptococcus antigen in 1:40 titers. Liposomal amphotericin B 5 mg/kg intravenous daily and fluconazole 400 mg intravenous daily were administered starting on the fourth day of admission; maintenance tacrolimus and steroids were stopped. Within 36 hours of treatment initiation, an erythematous papular rash was noted on the extremities, which initially was deemed an infusion reaction. Over the next 6 days, the rash became progressively confluent and hyperpigmented. A dermatologist was consulted on the fifteenth day of admission.

Physical examination by dermatology revealed diffuse, hyperpigmented to erythematous macules on the torso, back, arms, and legs that coalesced into dusky indurated plaques along the thighs, right side of the flank, and right upper arm (Figure 1). Laboratory analysis revealed thrombocytopenia but was otherwise unremarkable. Histoplasma antigen and Coccidioides IgG and IgM enzyme immunoassays were negative, as were cytomegalovirus, HIV, and rapid plasma reagin test results. Blood culture testing was repeated, and the findings were negative.

The emergence of the rash after amphotericin initiation prompted concern that the cause was due to a drug reaction rather than cutaneous involvement of cryptococcal infection. Punch biopsies were obtained from the thigh plaque. Hematoxylin and eosin and Grocott-Gomori methenamine-silver stains revealed cryptococcal organisms in the dermis and subcutaneous fat (Figure 2). Bacterial, acid-fast bacillus, and fungal cultures showed no growth.

The patient was diagnosed with cryptococcal panniculitis. Induction therapy with liposomal amphotericin B 5 mg/kg daily and flucytosine 25 mg/kg twice daily was pursued. During the treatment, cutaneous involvement evolved into superficial desquamation. The patient ultimately died from shock secondary to persistent cryptococcal fungemia.

Cryptococcus neoformans is an opportunistic fungal infection that represents a notable hazard to SOTR, inflicting 1.5% to 2.8% of this population and carrying a 19% to 42% mortality rate.^1,2 This infection occurs at a median of 1.6 to 2.3 years after transplantation,^1,3 though liver transplant recipients and those with immune reconstitution inflammatory syndrome (IRIS)–like complications may present sooner (8.8 and 10.5 months, respectively).⁴ Cutaneous involvement comprises 17% to 21% of cases and is associated with extensive dissemination, including the central nervous system, lung, and bloodstream (61.5%, 23.1%, and 38.5%, respectively).^1-3 When Cryptococcus infects the skin, it classically manifests as multiple nodules, umbilicated papules, ulcers, or cellulitis.³ Involvement of subcutaneous adipose tissue is uncommon and primarily is observed at initial presentation alongside disseminated disease.^5-8 Our case is unique because cutaneous involvement was absent until treatment initiation.

Similar patterns of worsened or unmasked disease following treatment initiation have been observed in SOTRs with extracutaneous cryptococcus and were attributed to IRIS-like phenomena that generate a hyperactive inflammatory response to infection.^4,9 Common immunosuppressive regimens, particularly tacrolimus, depress helper T cell (T_H1) cytokine release and promote a T_H2-dominant, anti-inflammatory state.¹⁰ In cryptococcosis, the fungus itself may stimulate a comparable cytokine milieu to promote immunologic evasion and dissemination. Cryptococcal IRIS-like responses in SOTRs are precipitated by rapid reduction or withdrawal of calcineurin inhibitors and corticosteroids, in combination with the inherent mitogenicity of the C neoformans polysaccharide capsule and antifungal agents.¹⁰ In our patient, cryptococcal yeasts may have invaded subcutaneous tissues when he became fungemic but remained subclinical due to minimal inflammatory recruitment. As treatment began and immunosuppressants diminished, fungal recognition and massive cytokine release resulted in frank panniculitis via precipitous immune dysregulation.

First-line therapy of cryptococcosis entails the use of liposomal amphotericin B and flucytosine for induction, followed by fluconazole for consolidation and maintenance. Use of corticosteroids is atypical to the antifungal regimen; however, a role for them has been suggested in severe IRIS involving individuals who are HIV positive, such as those with lesions demonstrating mass effect.¹¹ Rare case reports have described their utility as adjunctive therapies against cryptococcus in SOTRs when treatment with antifungal agents alone failed.¹² Given the paucity of prospective trials to support corticosteroid use in SOTRs as well as the worse global outcomes in cases of cryptococcal meningitis,¹³ therapeutic corticosteroids were not administered in our patient.

Although our case represents a rare event, cutaneous cryptococcosis and IRIS-like phenomena are clinically relevant complications in immunocompromised patients. In particular, they should be promptly considered in SOTRs receiving maintenance immunosuppressants who demonstrate symptom aggravation despite negative microbial culture results and uninterrupted antifungal therapy.

To the Editor:

Cryptococcus neoformans is an opportunistic fungus with a predilection for immunocompromised hosts, including solid organ transplant recipients (SOTRs). However, the rapid emergence of diffuse panniculitis only upon the start of therapy for extracutaneous disease is a rare phenomenon. We report the case of a liver transplant recipient who developed a paradoxical inflammatory reaction after initiating liposomal amphotericin B therapy for disseminated C neoformans, which manifested as progressive indurated plaques histologically consistent with cryptococcal panniculitis.

A 44-year-old man who received an orthotopic liver transplant 12 months prior and was on prednisone (20 mg daily) and tacrolimus (7 mg total daily) was admitted for multifocal pneumonia complicated by septic shock. Blood and respiratory cultures grew C neoformans, and lumbar puncture evaluation of cerebrospinal fluid revealed the presence of Cryptococcus antigen in 1:40 titers. Liposomal amphotericin B 5 mg/kg intravenous daily and fluconazole 400 mg intravenous daily were administered starting on the fourth day of admission; maintenance tacrolimus and steroids were stopped. Within 36 hours of treatment initiation, an erythematous papular rash was noted on the extremities, which initially was deemed an infusion reaction. Over the next 6 days, the rash became progressively confluent and hyperpigmented. A dermatologist was consulted on the fifteenth day of admission.

Physical examination by dermatology revealed diffuse, hyperpigmented to erythematous macules on the torso, back, arms, and legs that coalesced into dusky indurated plaques along the thighs, right side of the flank, and right upper arm (Figure 1). Laboratory analysis revealed thrombocytopenia but was otherwise unremarkable. Histoplasma antigen and Coccidioides IgG and IgM enzyme immunoassays were negative, as were cytomegalovirus, HIV, and rapid plasma reagin test results. Blood culture testing was repeated, and the findings were negative.

The emergence of the rash after amphotericin initiation prompted concern that the cause was due to a drug reaction rather than cutaneous involvement of cryptococcal infection. Punch biopsies were obtained from the thigh plaque. Hematoxylin and eosin and Grocott-Gomori methenamine-silver stains revealed cryptococcal organisms in the dermis and subcutaneous fat (Figure 2). Bacterial, acid-fast bacillus, and fungal cultures showed no growth.

The patient was diagnosed with cryptococcal panniculitis. Induction therapy with liposomal amphotericin B 5 mg/kg daily and flucytosine 25 mg/kg twice daily was pursued. During the treatment, cutaneous involvement evolved into superficial desquamation. The patient ultimately died from shock secondary to persistent cryptococcal fungemia.

Cryptococcus neoformans is an opportunistic fungal infection that represents a notable hazard to SOTR, inflicting 1.5% to 2.8% of this population and carrying a 19% to 42% mortality rate.^1,2 This infection occurs at a median of 1.6 to 2.3 years after transplantation,^1,3 though liver transplant recipients and those with immune reconstitution inflammatory syndrome (IRIS)–like complications may present sooner (8.8 and 10.5 months, respectively).⁴ Cutaneous involvement comprises 17% to 21% of cases and is associated with extensive dissemination, including the central nervous system, lung, and bloodstream (61.5%, 23.1%, and 38.5%, respectively).^1-3 When Cryptococcus infects the skin, it classically manifests as multiple nodules, umbilicated papules, ulcers, or cellulitis.³ Involvement of subcutaneous adipose tissue is uncommon and primarily is observed at initial presentation alongside disseminated disease.^5-8 Our case is unique because cutaneous involvement was absent until treatment initiation.

Similar patterns of worsened or unmasked disease following treatment initiation have been observed in SOTRs with extracutaneous cryptococcus and were attributed to IRIS-like phenomena that generate a hyperactive inflammatory response to infection.^4,9 Common immunosuppressive regimens, particularly tacrolimus, depress helper T cell (T_H1) cytokine release and promote a T_H2-dominant, anti-inflammatory state.¹⁰ In cryptococcosis, the fungus itself may stimulate a comparable cytokine milieu to promote immunologic evasion and dissemination. Cryptococcal IRIS-like responses in SOTRs are precipitated by rapid reduction or withdrawal of calcineurin inhibitors and corticosteroids, in combination with the inherent mitogenicity of the C neoformans polysaccharide capsule and antifungal agents.¹⁰ In our patient, cryptococcal yeasts may have invaded subcutaneous tissues when he became fungemic but remained subclinical due to minimal inflammatory recruitment. As treatment began and immunosuppressants diminished, fungal recognition and massive cytokine release resulted in frank panniculitis via precipitous immune dysregulation.

First-line therapy of cryptococcosis entails the use of liposomal amphotericin B and flucytosine for induction, followed by fluconazole for consolidation and maintenance. Use of corticosteroids is atypical to the antifungal regimen; however, a role for them has been suggested in severe IRIS involving individuals who are HIV positive, such as those with lesions demonstrating mass effect.¹¹ Rare case reports have described their utility as adjunctive therapies against cryptococcus in SOTRs when treatment with antifungal agents alone failed.¹² Given the paucity of prospective trials to support corticosteroid use in SOTRs as well as the worse global outcomes in cases of cryptococcal meningitis,¹³ therapeutic corticosteroids were not administered in our patient.

Although our case represents a rare event, cutaneous cryptococcosis and IRIS-like phenomena are clinically relevant complications in immunocompromised patients. In particular, they should be promptly considered in SOTRs receiving maintenance immunosuppressants who demonstrate symptom aggravation despite negative microbial culture results and uninterrupted antifungal therapy.

To the Editor:

Cryptococcus neoformans is an opportunistic fungus with a predilection for immunocompromised hosts, including solid organ transplant recipients (SOTRs). However, the rapid emergence of diffuse panniculitis only upon the start of therapy for extracutaneous disease is a rare phenomenon. We report the case of a liver transplant recipient who developed a paradoxical inflammatory reaction after initiating liposomal amphotericin B therapy for disseminated C neoformans, which manifested as progressive indurated plaques histologically consistent with cryptococcal panniculitis.

A 44-year-old man who received an orthotopic liver transplant 12 months prior and was on prednisone (20 mg daily) and tacrolimus (7 mg total daily) was admitted for multifocal pneumonia complicated by septic shock. Blood and respiratory cultures grew C neoformans, and lumbar puncture evaluation of cerebrospinal fluid revealed the presence of Cryptococcus antigen in 1:40 titers. Liposomal amphotericin B 5 mg/kg intravenous daily and fluconazole 400 mg intravenous daily were administered starting on the fourth day of admission; maintenance tacrolimus and steroids were stopped. Within 36 hours of treatment initiation, an erythematous papular rash was noted on the extremities, which initially was deemed an infusion reaction. Over the next 6 days, the rash became progressively confluent and hyperpigmented. A dermatologist was consulted on the fifteenth day of admission.

Physical examination by dermatology revealed diffuse, hyperpigmented to erythematous macules on the torso, back, arms, and legs that coalesced into dusky indurated plaques along the thighs, right side of the flank, and right upper arm (Figure 1). Laboratory analysis revealed thrombocytopenia but was otherwise unremarkable. Histoplasma antigen and Coccidioides IgG and IgM enzyme immunoassays were negative, as were cytomegalovirus, HIV, and rapid plasma reagin test results. Blood culture testing was repeated, and the findings were negative.

The emergence of the rash after amphotericin initiation prompted concern that the cause was due to a drug reaction rather than cutaneous involvement of cryptococcal infection. Punch biopsies were obtained from the thigh plaque. Hematoxylin and eosin and Grocott-Gomori methenamine-silver stains revealed cryptococcal organisms in the dermis and subcutaneous fat (Figure 2). Bacterial, acid-fast bacillus, and fungal cultures showed no growth.

The patient was diagnosed with cryptococcal panniculitis. Induction therapy with liposomal amphotericin B 5 mg/kg daily and flucytosine 25 mg/kg twice daily was pursued. During the treatment, cutaneous involvement evolved into superficial desquamation. The patient ultimately died from shock secondary to persistent cryptococcal fungemia.

Cryptococcus neoformans is an opportunistic fungal infection that represents a notable hazard to SOTR, inflicting 1.5% to 2.8% of this population and carrying a 19% to 42% mortality rate.^1,2 This infection occurs at a median of 1.6 to 2.3 years after transplantation,^1,3 though liver transplant recipients and those with immune reconstitution inflammatory syndrome (IRIS)–like complications may present sooner (8.8 and 10.5 months, respectively).⁴ Cutaneous involvement comprises 17% to 21% of cases and is associated with extensive dissemination, including the central nervous system, lung, and bloodstream (61.5%, 23.1%, and 38.5%, respectively).^1-3 When Cryptococcus infects the skin, it classically manifests as multiple nodules, umbilicated papules, ulcers, or cellulitis.³ Involvement of subcutaneous adipose tissue is uncommon and primarily is observed at initial presentation alongside disseminated disease.^5-8 Our case is unique because cutaneous involvement was absent until treatment initiation.

Similar patterns of worsened or unmasked disease following treatment initiation have been observed in SOTRs with extracutaneous cryptococcus and were attributed to IRIS-like phenomena that generate a hyperactive inflammatory response to infection.^4,9 Common immunosuppressive regimens, particularly tacrolimus, depress helper T cell (T_H1) cytokine release and promote a T_H2-dominant, anti-inflammatory state.¹⁰ In cryptococcosis, the fungus itself may stimulate a comparable cytokine milieu to promote immunologic evasion and dissemination. Cryptococcal IRIS-like responses in SOTRs are precipitated by rapid reduction or withdrawal of calcineurin inhibitors and corticosteroids, in combination with the inherent mitogenicity of the C neoformans polysaccharide capsule and antifungal agents.¹⁰ In our patient, cryptococcal yeasts may have invaded subcutaneous tissues when he became fungemic but remained subclinical due to minimal inflammatory recruitment. As treatment began and immunosuppressants diminished, fungal recognition and massive cytokine release resulted in frank panniculitis via precipitous immune dysregulation.

First-line therapy of cryptococcosis entails the use of liposomal amphotericin B and flucytosine for induction, followed by fluconazole for consolidation and maintenance. Use of corticosteroids is atypical to the antifungal regimen; however, a role for them has been suggested in severe IRIS involving individuals who are HIV positive, such as those with lesions demonstrating mass effect.¹¹ Rare case reports have described their utility as adjunctive therapies against cryptococcus in SOTRs when treatment with antifungal agents alone failed.¹² Given the paucity of prospective trials to support corticosteroid use in SOTRs as well as the worse global outcomes in cases of cryptococcal meningitis,¹³ therapeutic corticosteroids were not administered in our patient.

Although our case represents a rare event, cutaneous cryptococcosis and IRIS-like phenomena are clinically relevant complications in immunocompromised patients. In particular, they should be promptly considered in SOTRs receiving maintenance immunosuppressants who demonstrate symptom aggravation despite negative microbial culture results and uninterrupted antifungal therapy.

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

A version of this article first appeared on WebMD.com.

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

A version of this article first appeared on WebMD.com.

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

A version of this article first appeared on WebMD.com.

California’s highest court has revived a high-profile lawsuit that could have a major impact on whether insurers can punish physicians who refer patients to out-of-network providers.

The case, which has bounced around courts in the Golden State since 2012, pits the nearly 50,000-member California Medical Association (CMA) against Aetna, one of the nation’s largest health insurers. The physician group alleges that Aetna illegally retaliated against physicians who sent patients to certain out-of-network clinics.

Out-of-network providers and clinics were involved in just 4.7% of professional medical claims in 2020, according to a federal report released July 6, 2023. Such claims are more likely than others to be denied, and they result in unexpected medical bills, which have led to the passage of state and federal laws that target “surprise billing.”

In a July 17 ruling, the California Supreme Court unanimously resurrected the CMA v. Aetna case after a judge and a state appeals court killed it on the grounds that the CMA - which is affiliated with the American Medical Association (AMA) - had no standing to sue Aetna. The high state court declared that the CMA could sue on its own behalf, but the justices noted that their ruling says nothing about the merits of the case.

The ruling appears to mean that CMA’s lawsuit will head back to Superior Court in Los Angeles County. The outcome of the case won’t have a direct national effect, since the case is in state court, not federal court. However, state rulings can influence the thinking of judges elsewhere.

The case, filed in 2012, alleges that Aetna harmed patient care by harassing and sacking contract physicians who referred patients to out-of-network ambulatory surgery centers.

According to the new ruling, Aetna responded by saying that “its policy, rather than interfering in medical judgments, was designed simply to encourage participating physicians, consistent with their judgment, to use in-network care providers, such as ambulatory surgery centers, and was adopted in part in response to physicians referring patients to facilities in which they had financial interests.”

In a 2012 letter to CMA, as reported by the Los Angeles Times, an Aetna attorney went further and claimed that “physicians and their business partners secure outsized and improper windfalls at the expense of Aetna’s plan members and employer plan sponsors.”

The CMA received support for its lawsuit via friend-of-the-court legal briefs from the California attorney general, city attorneys for several major California cities, the AMA, several major labor unions, the AIDS Healthcare Foundation, and the advocacy organization Consumer Watchdog. The U.S. Chamber of Commerce, the California Association of Health Plans, and the Association of California Life and Health Insurance Companies filed briefs supporting Aetna.

Aetna, now part of CVS Health, declined to comment about the new ruling.

The CMA released a statement from its president, internist/hospitalist Donaldo M. Hernandez, MD: “The practice of threatening physicians who refer patients to out-of-network providers is unlawful, and we are pleased that the court agrees that CMA has the right to challenge these practices in court.”

In an interview, research professor emeritus Jack Hoadley, PhD, of the Health Policy Institute at Georgetown University’s McCourt School of Public Policy, noted that many health plans don’t cover out-of-network care. Those that do – including PPOs and hybrid plans – often require that patients pay a larger share of the total cost or pay a separate or higher deductible, he said.

So why would an insurer punish doctors who refer patients to health care providers who are outside the insurer’s approved network? In some cases, patients may blame insurers when they’re forced to pay higher rates for out-of-network care, Dr. Hoadley said. Insurers may also be miffed when physicians send patients out of network, he said, because insurers contract with physicians to send a certain number of patients within the insurer’s network.

The federal No Surprises Act, passed by Congress in 2020, hasn’t decreased tension between providers and insurers over out-of-network fees, Dr. Hoadley said. As the effects of the law are hammered out in court, he said, there’s still an adversarial relationship.

In California, the out-of-network landscape changed 3 years before the No Surprises Act. In 2017, the state passed its own no-surprise-billing law, which “protects consumers from surprise medical bills when they get non-emergency services, go to an in-network health facility and receive care from an out-of-network provider without their consent.” In these cases, the law says patients need to pay only in accordance with in-network cost sharing.

In 2019, a USC-Brookings Schaeffer Initiative for Health Policy report found signs that out-of-network care was fading in California other than in the emergency setting, possibly as a result of the law.

A version of this article first appeared on Medscape.com.

California’s highest court has revived a high-profile lawsuit that could have a major impact on whether insurers can punish physicians who refer patients to out-of-network providers.

The case, which has bounced around courts in the Golden State since 2012, pits the nearly 50,000-member California Medical Association (CMA) against Aetna, one of the nation’s largest health insurers. The physician group alleges that Aetna illegally retaliated against physicians who sent patients to certain out-of-network clinics.

Out-of-network providers and clinics were involved in just 4.7% of professional medical claims in 2020, according to a federal report released July 6, 2023. Such claims are more likely than others to be denied, and they result in unexpected medical bills, which have led to the passage of state and federal laws that target “surprise billing.”

In a July 17 ruling, the California Supreme Court unanimously resurrected the CMA v. Aetna case after a judge and a state appeals court killed it on the grounds that the CMA - which is affiliated with the American Medical Association (AMA) - had no standing to sue Aetna. The high state court declared that the CMA could sue on its own behalf, but the justices noted that their ruling says nothing about the merits of the case.

The ruling appears to mean that CMA’s lawsuit will head back to Superior Court in Los Angeles County. The outcome of the case won’t have a direct national effect, since the case is in state court, not federal court. However, state rulings can influence the thinking of judges elsewhere.

The case, filed in 2012, alleges that Aetna harmed patient care by harassing and sacking contract physicians who referred patients to out-of-network ambulatory surgery centers.

According to the new ruling, Aetna responded by saying that “its policy, rather than interfering in medical judgments, was designed simply to encourage participating physicians, consistent with their judgment, to use in-network care providers, such as ambulatory surgery centers, and was adopted in part in response to physicians referring patients to facilities in which they had financial interests.”

In a 2012 letter to CMA, as reported by the Los Angeles Times, an Aetna attorney went further and claimed that “physicians and their business partners secure outsized and improper windfalls at the expense of Aetna’s plan members and employer plan sponsors.”

The CMA received support for its lawsuit via friend-of-the-court legal briefs from the California attorney general, city attorneys for several major California cities, the AMA, several major labor unions, the AIDS Healthcare Foundation, and the advocacy organization Consumer Watchdog. The U.S. Chamber of Commerce, the California Association of Health Plans, and the Association of California Life and Health Insurance Companies filed briefs supporting Aetna.

Aetna, now part of CVS Health, declined to comment about the new ruling.

The CMA released a statement from its president, internist/hospitalist Donaldo M. Hernandez, MD: “The practice of threatening physicians who refer patients to out-of-network providers is unlawful, and we are pleased that the court agrees that CMA has the right to challenge these practices in court.”

In an interview, research professor emeritus Jack Hoadley, PhD, of the Health Policy Institute at Georgetown University’s McCourt School of Public Policy, noted that many health plans don’t cover out-of-network care. Those that do – including PPOs and hybrid plans – often require that patients pay a larger share of the total cost or pay a separate or higher deductible, he said.

So why would an insurer punish doctors who refer patients to health care providers who are outside the insurer’s approved network? In some cases, patients may blame insurers when they’re forced to pay higher rates for out-of-network care, Dr. Hoadley said. Insurers may also be miffed when physicians send patients out of network, he said, because insurers contract with physicians to send a certain number of patients within the insurer’s network.

The federal No Surprises Act, passed by Congress in 2020, hasn’t decreased tension between providers and insurers over out-of-network fees, Dr. Hoadley said. As the effects of the law are hammered out in court, he said, there’s still an adversarial relationship.

In California, the out-of-network landscape changed 3 years before the No Surprises Act. In 2017, the state passed its own no-surprise-billing law, which “protects consumers from surprise medical bills when they get non-emergency services, go to an in-network health facility and receive care from an out-of-network provider without their consent.” In these cases, the law says patients need to pay only in accordance with in-network cost sharing.

In 2019, a USC-Brookings Schaeffer Initiative for Health Policy report found signs that out-of-network care was fading in California other than in the emergency setting, possibly as a result of the law.

A version of this article first appeared on Medscape.com.

California’s highest court has revived a high-profile lawsuit that could have a major impact on whether insurers can punish physicians who refer patients to out-of-network providers.

The case, which has bounced around courts in the Golden State since 2012, pits the nearly 50,000-member California Medical Association (CMA) against Aetna, one of the nation’s largest health insurers. The physician group alleges that Aetna illegally retaliated against physicians who sent patients to certain out-of-network clinics.

Out-of-network providers and clinics were involved in just 4.7% of professional medical claims in 2020, according to a federal report released July 6, 2023. Such claims are more likely than others to be denied, and they result in unexpected medical bills, which have led to the passage of state and federal laws that target “surprise billing.”

In a July 17 ruling, the California Supreme Court unanimously resurrected the CMA v. Aetna case after a judge and a state appeals court killed it on the grounds that the CMA - which is affiliated with the American Medical Association (AMA) - had no standing to sue Aetna. The high state court declared that the CMA could sue on its own behalf, but the justices noted that their ruling says nothing about the merits of the case.

The ruling appears to mean that CMA’s lawsuit will head back to Superior Court in Los Angeles County. The outcome of the case won’t have a direct national effect, since the case is in state court, not federal court. However, state rulings can influence the thinking of judges elsewhere.

The case, filed in 2012, alleges that Aetna harmed patient care by harassing and sacking contract physicians who referred patients to out-of-network ambulatory surgery centers.

According to the new ruling, Aetna responded by saying that “its policy, rather than interfering in medical judgments, was designed simply to encourage participating physicians, consistent with their judgment, to use in-network care providers, such as ambulatory surgery centers, and was adopted in part in response to physicians referring patients to facilities in which they had financial interests.”

In a 2012 letter to CMA, as reported by the Los Angeles Times, an Aetna attorney went further and claimed that “physicians and their business partners secure outsized and improper windfalls at the expense of Aetna’s plan members and employer plan sponsors.”

The CMA received support for its lawsuit via friend-of-the-court legal briefs from the California attorney general, city attorneys for several major California cities, the AMA, several major labor unions, the AIDS Healthcare Foundation, and the advocacy organization Consumer Watchdog. The U.S. Chamber of Commerce, the California Association of Health Plans, and the Association of California Life and Health Insurance Companies filed briefs supporting Aetna.

Aetna, now part of CVS Health, declined to comment about the new ruling.

The CMA released a statement from its president, internist/hospitalist Donaldo M. Hernandez, MD: “The practice of threatening physicians who refer patients to out-of-network providers is unlawful, and we are pleased that the court agrees that CMA has the right to challenge these practices in court.”

In an interview, research professor emeritus Jack Hoadley, PhD, of the Health Policy Institute at Georgetown University’s McCourt School of Public Policy, noted that many health plans don’t cover out-of-network care. Those that do – including PPOs and hybrid plans – often require that patients pay a larger share of the total cost or pay a separate or higher deductible, he said.

So why would an insurer punish doctors who refer patients to health care providers who are outside the insurer’s approved network? In some cases, patients may blame insurers when they’re forced to pay higher rates for out-of-network care, Dr. Hoadley said. Insurers may also be miffed when physicians send patients out of network, he said, because insurers contract with physicians to send a certain number of patients within the insurer’s network.

The federal No Surprises Act, passed by Congress in 2020, hasn’t decreased tension between providers and insurers over out-of-network fees, Dr. Hoadley said. As the effects of the law are hammered out in court, he said, there’s still an adversarial relationship.

In California, the out-of-network landscape changed 3 years before the No Surprises Act. In 2017, the state passed its own no-surprise-billing law, which “protects consumers from surprise medical bills when they get non-emergency services, go to an in-network health facility and receive care from an out-of-network provider without their consent.” In these cases, the law says patients need to pay only in accordance with in-network cost sharing.

In 2019, a USC-Brookings Schaeffer Initiative for Health Policy report found signs that out-of-network care was fading in California other than in the emergency setting, possibly as a result of the law.

A version of this article first appeared on Medscape.com.

Social isolation in older individuals has been linked to reduced brain volume in regions associated with memory, a new study shows.

Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.

“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.

The study was published online in Neurology.
 

A dementia prevention strategy

Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.

In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
 

Lower brain volume

Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.

White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.

Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).

The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.

Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
 

Worse physical health

The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.

“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.

Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.

“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”

He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that  isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.

“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.

The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.

A version of this article first appeared on Medscape.com.

Social isolation in older individuals has been linked to reduced brain volume in regions associated with memory, a new study shows.

Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.

“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.

The study was published online in Neurology.
 

A dementia prevention strategy

Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.

In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
 

Lower brain volume

Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.

White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.

Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).

The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.

Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
 

Worse physical health

The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.

“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.

Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.

“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”

He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that  isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.

“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.

The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.

A version of this article first appeared on Medscape.com.

Social isolation in older individuals has been linked to reduced brain volume in regions associated with memory, a new study shows.

Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.

“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.

The study was published online in Neurology.
 

A dementia prevention strategy

Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.

In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
 

Lower brain volume

Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.

White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.

Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).

The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.

Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
 

Worse physical health

The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.

“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.

Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.

“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”

He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that  isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.

“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.

The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.

A version of this article first appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Abbott is recalling the Amplatzer steerable delivery sheath, used to deliver the Amplatzer Amulet left atrial appendage occluder during cardiac catheterization, because of an increased risk of air embolism, the Food and Drug Administration has announced.

Air embolism can lead to injuries such as acute reduction in blood flow to the heart (indicated by ST elevation), tachycardia, bradycardia, hypotension, and oxygen desaturation, as well as stroke and death, the FDA said in a recall notice.

Because of the potential for serious injury or death, the agency has identified this as a class I recall, the most serious type.

To date, Abbott has reported 26 incidents, 16 injuries, and no deaths related to this issue.

According to the recall notice, the overall reported incidence rate of observed or potential cases of air embolism during procedures in which the product was used is 0.77%.

The recall includes 672 devices (model: ASDS-14F-075) that were distributed from Oct. 4, 2022, to Feb. 22, 2023.

Abbott sent a medical device recall notice to customers in June asking them to return any remaining unused Amplatzer steerable delivery sheaths to Abbott and to complete an enclosed acknowledgment form.

The company advises use of the fixed curve TorqVue 45° x 45° delivery system for future Amplatzer Amulet left atrial appendage occluder implants.

Customers with questions about this recall should contact their local Abbott representative or Abbott support at 1-800-544-1664 (option 2).

A version of this article appeared on Medscape.com.

Abbott is recalling the Amplatzer steerable delivery sheath, used to deliver the Amplatzer Amulet left atrial appendage occluder during cardiac catheterization, because of an increased risk of air embolism, the Food and Drug Administration has announced.

Air embolism can lead to injuries such as acute reduction in blood flow to the heart (indicated by ST elevation), tachycardia, bradycardia, hypotension, and oxygen desaturation, as well as stroke and death, the FDA said in a recall notice.

Because of the potential for serious injury or death, the agency has identified this as a class I recall, the most serious type.

To date, Abbott has reported 26 incidents, 16 injuries, and no deaths related to this issue.

According to the recall notice, the overall reported incidence rate of observed or potential cases of air embolism during procedures in which the product was used is 0.77%.

The recall includes 672 devices (model: ASDS-14F-075) that were distributed from Oct. 4, 2022, to Feb. 22, 2023.

Abbott sent a medical device recall notice to customers in June asking them to return any remaining unused Amplatzer steerable delivery sheaths to Abbott and to complete an enclosed acknowledgment form.

The company advises use of the fixed curve TorqVue 45° x 45° delivery system for future Amplatzer Amulet left atrial appendage occluder implants.

Customers with questions about this recall should contact their local Abbott representative or Abbott support at 1-800-544-1664 (option 2).

A version of this article appeared on Medscape.com.

Abbott is recalling the Amplatzer steerable delivery sheath, used to deliver the Amplatzer Amulet left atrial appendage occluder during cardiac catheterization, because of an increased risk of air embolism, the Food and Drug Administration has announced.

Air embolism can lead to injuries such as acute reduction in blood flow to the heart (indicated by ST elevation), tachycardia, bradycardia, hypotension, and oxygen desaturation, as well as stroke and death, the FDA said in a recall notice.

Because of the potential for serious injury or death, the agency has identified this as a class I recall, the most serious type.

To date, Abbott has reported 26 incidents, 16 injuries, and no deaths related to this issue.

According to the recall notice, the overall reported incidence rate of observed or potential cases of air embolism during procedures in which the product was used is 0.77%.

The recall includes 672 devices (model: ASDS-14F-075) that were distributed from Oct. 4, 2022, to Feb. 22, 2023.

Abbott sent a medical device recall notice to customers in June asking them to return any remaining unused Amplatzer steerable delivery sheaths to Abbott and to complete an enclosed acknowledgment form.

The company advises use of the fixed curve TorqVue 45° x 45° delivery system for future Amplatzer Amulet left atrial appendage occluder implants.

Customers with questions about this recall should contact their local Abbott representative or Abbott support at 1-800-544-1664 (option 2).

A version of this article appeared on Medscape.com.

TOPLINE

The use of magnetic resonance–guided daily adaptive stereotactic body radiotherapy for patients with prostate cancer reduces the risk of acute urinary side effects of grade 2 or higher by 44% and the risk of acute bowel side effects of grade 2 or higher by 60%, compared with standard CT-guided SBRT (CT‐SBRT).

METHODOLOGY

• With the use of magnetic resonance–guided daily adaptive SBRT, clinicians can customize radiation dosing to accommodate changes in prostate anatomy during treatment, which may also make SBRT safer and less toxic for patients.
• To determine whether this approach does reduce patient side effects, investigators ran a meta-analysis that included 29 studies with 2547 patients comparing the incidence of short-term, physician-assessed bowel and genitourinary side effects between the MRI-guided approach and standard CT-SBRT.
• The investigators reported no statistically significant differences in age, prescribed radiation doses, planning target volumes, or International Prostatism Symptom Scores between the two groups; the use of rectal spacers and the number of patients who received pelvic lymph node radiation were low in both.
• The average window for collecting acute toxicity data was 70 days in the MRI-guided investigations and 94 days in CT-SBRT investigations.

TAKEAWAY

• The pooled estimate for acute grade 2 or higher genitourinary toxicity was 16% with MRI-guided SBRT versus 28% with CT-SBRT (odds ratio, 0.56; P = .04).
• The pooled estimate for grade 2 or higher gastrointestinal toxicity was 4% with the MRI approach versus 9% with CT-SBRT (OR, 0.40; P = .04).
• There were no differences in grade 3 or higher events, which were rare, between the groups.
• There was also no difference in toxicity among CT‐SBRT studies that used fiducial markers and those that did not.

IN PRACTICE

“These findings suggest that the technical advantages in precision of radiotherapy delivery afforded by [MRI-guided] SBRT translate to measurable clinical benefit,” the authors concluded. Potential reasons for the reduced risk of acute toxicity with the MRI-guided approach include “daily online adaptive planning, MRI‐based contouring that results in smaller treatment volumes, and MRI tracking, all of which may facilitate the precision and accuracy of treatment delivery.”

SOURCE

The study was led by Jonathan Leeman, MD, of the Dana-Farber Cancer Institute, Boston, and was published July 24 in Cancer.

LIMITATIONS

• The analysis did not account for differences in dosimetry, radiation planning, and toxicity management and assessment between the studies.
• Late toxicity and cancer control rates were not tracked and may have differed between the two approaches.

DISCLOSURES

• No external funding was reported.
• The investigators reported grants and consulting, personal, and other payments from Novartis, AstraZeneca, Janssen, and other companies.

A version of this article appeared on Medscape.com.

TOPLINE

The use of magnetic resonance–guided daily adaptive stereotactic body radiotherapy for patients with prostate cancer reduces the risk of acute urinary side effects of grade 2 or higher by 44% and the risk of acute bowel side effects of grade 2 or higher by 60%, compared with standard CT-guided SBRT (CT‐SBRT).

METHODOLOGY

• With the use of magnetic resonance–guided daily adaptive SBRT, clinicians can customize radiation dosing to accommodate changes in prostate anatomy during treatment, which may also make SBRT safer and less toxic for patients.
• To determine whether this approach does reduce patient side effects, investigators ran a meta-analysis that included 29 studies with 2547 patients comparing the incidence of short-term, physician-assessed bowel and genitourinary side effects between the MRI-guided approach and standard CT-SBRT.
• The investigators reported no statistically significant differences in age, prescribed radiation doses, planning target volumes, or International Prostatism Symptom Scores between the two groups; the use of rectal spacers and the number of patients who received pelvic lymph node radiation were low in both.
• The average window for collecting acute toxicity data was 70 days in the MRI-guided investigations and 94 days in CT-SBRT investigations.

TAKEAWAY

• The pooled estimate for acute grade 2 or higher genitourinary toxicity was 16% with MRI-guided SBRT versus 28% with CT-SBRT (odds ratio, 0.56; P = .04).
• The pooled estimate for grade 2 or higher gastrointestinal toxicity was 4% with the MRI approach versus 9% with CT-SBRT (OR, 0.40; P = .04).
• There were no differences in grade 3 or higher events, which were rare, between the groups.
• There was also no difference in toxicity among CT‐SBRT studies that used fiducial markers and those that did not.

IN PRACTICE

“These findings suggest that the technical advantages in precision of radiotherapy delivery afforded by [MRI-guided] SBRT translate to measurable clinical benefit,” the authors concluded. Potential reasons for the reduced risk of acute toxicity with the MRI-guided approach include “daily online adaptive planning, MRI‐based contouring that results in smaller treatment volumes, and MRI tracking, all of which may facilitate the precision and accuracy of treatment delivery.”

SOURCE

The study was led by Jonathan Leeman, MD, of the Dana-Farber Cancer Institute, Boston, and was published July 24 in Cancer.

LIMITATIONS

• The analysis did not account for differences in dosimetry, radiation planning, and toxicity management and assessment between the studies.
• Late toxicity and cancer control rates were not tracked and may have differed between the two approaches.

DISCLOSURES

• No external funding was reported.
• The investigators reported grants and consulting, personal, and other payments from Novartis, AstraZeneca, Janssen, and other companies.

A version of this article appeared on Medscape.com.

TOPLINE

The use of magnetic resonance–guided daily adaptive stereotactic body radiotherapy for patients with prostate cancer reduces the risk of acute urinary side effects of grade 2 or higher by 44% and the risk of acute bowel side effects of grade 2 or higher by 60%, compared with standard CT-guided SBRT (CT‐SBRT).

METHODOLOGY

• With the use of magnetic resonance–guided daily adaptive SBRT, clinicians can customize radiation dosing to accommodate changes in prostate anatomy during treatment, which may also make SBRT safer and less toxic for patients.
• To determine whether this approach does reduce patient side effects, investigators ran a meta-analysis that included 29 studies with 2547 patients comparing the incidence of short-term, physician-assessed bowel and genitourinary side effects between the MRI-guided approach and standard CT-SBRT.
• The investigators reported no statistically significant differences in age, prescribed radiation doses, planning target volumes, or International Prostatism Symptom Scores between the two groups; the use of rectal spacers and the number of patients who received pelvic lymph node radiation were low in both.
• The average window for collecting acute toxicity data was 70 days in the MRI-guided investigations and 94 days in CT-SBRT investigations.

TAKEAWAY

• The pooled estimate for acute grade 2 or higher genitourinary toxicity was 16% with MRI-guided SBRT versus 28% with CT-SBRT (odds ratio, 0.56; P = .04).
• The pooled estimate for grade 2 or higher gastrointestinal toxicity was 4% with the MRI approach versus 9% with CT-SBRT (OR, 0.40; P = .04).
• There were no differences in grade 3 or higher events, which were rare, between the groups.
• There was also no difference in toxicity among CT‐SBRT studies that used fiducial markers and those that did not.

IN PRACTICE

“These findings suggest that the technical advantages in precision of radiotherapy delivery afforded by [MRI-guided] SBRT translate to measurable clinical benefit,” the authors concluded. Potential reasons for the reduced risk of acute toxicity with the MRI-guided approach include “daily online adaptive planning, MRI‐based contouring that results in smaller treatment volumes, and MRI tracking, all of which may facilitate the precision and accuracy of treatment delivery.”

SOURCE

The study was led by Jonathan Leeman, MD, of the Dana-Farber Cancer Institute, Boston, and was published July 24 in Cancer.

LIMITATIONS

• The analysis did not account for differences in dosimetry, radiation planning, and toxicity management and assessment between the studies.
• Late toxicity and cancer control rates were not tracked and may have differed between the two approaches.

DISCLOSURES

• No external funding was reported.
• The investigators reported grants and consulting, personal, and other payments from Novartis, AstraZeneca, Janssen, and other companies.

A version of this article appeared on Medscape.com.

Family members with pulmonary fibrosis showed correlations for predicted forced vital capacity trajectories and computed tomography patterns, based on data from 101 individuals in 45 families.

Patients with familial pulmonary fibrosis (FPF), defined as fibrotic interstitial lung disease among two or more first-degree or second-degree relatives, have worse survival than that of patients with sporadic pulmonary fibrosis, wrote Tinne Goos, MD, of KU Leuven, Belgium, and colleagues. Diagnosis of FPF diagnosis is mainly based on family history, and data on intrafamilial correlations are lacking, they said.

In a study published in the journal Chest, the researchers identified FPF patients treated at a single center. The study population included 101 patients from 45 families; most of these (34) were siblings. Overall, 61.4% of the participants were men, 69.3% were ever-smokers, and 84.2% had idiopathic pulmonary fibrosis.

The analysis included data on computed tomography (CT) scanning and predicted forced vital capacity (FVC%), as well as age at diagnosis, treatment type, gender, smoking history, and date of diagnosis.

Overall, FVC%predicted was significantly correlated within families, with a correlation of 0.75. The annual change in FVC was –158.2 mL, and the annual change in FVC%predicted was –6.3%.

Sixty-five patients received antifibrotic treatment, and 18 received immunosuppressive treatment. Immunosuppressive treatment remained significantly correlated among families in a multivariate analysis, with a correlation of 0.77.

“Age at diagnosis correlated within a generation, while patients from a second generation were diagnosed younger,” the researchers noted. The current study findings and results from other studies suggest a genetic basis for FPF age of onset, and determining an age range for screening unaffected relatives based on the age at diagnosis of affected relatives might be useful, they said.

In addition, 42.2% of families showed concordance of CT scan patterns. Typical usual interstitial pneumonia (UIP) appeared in 35 patients, atypical UIP in 36 patients, UIP with emphysema in 9 patients, and findings incompatible with UIP in 21 patients.

The study findings were limited by several factors including the retrospective design and use of data from a single center, as well as by the changes in clinical practice guidelines between 2004 and 2019, with increases in genetic testing, the researchers noted.

However, the current study is the first known to report on FVC evolution within families in FPF, they said. Future studies of both intra- and interfamilial correlation and variability are needed to identify the genetic and environmental factors that may affect disease manifestation and progression, they concluded.

The study was supported by Research Foundation-Flanders. Dr. Goos had no financial conflicts to disclose.

Family members with pulmonary fibrosis showed correlations for predicted forced vital capacity trajectories and computed tomography patterns, based on data from 101 individuals in 45 families.

Patients with familial pulmonary fibrosis (FPF), defined as fibrotic interstitial lung disease among two or more first-degree or second-degree relatives, have worse survival than that of patients with sporadic pulmonary fibrosis, wrote Tinne Goos, MD, of KU Leuven, Belgium, and colleagues. Diagnosis of FPF diagnosis is mainly based on family history, and data on intrafamilial correlations are lacking, they said.

In a study published in the journal Chest, the researchers identified FPF patients treated at a single center. The study population included 101 patients from 45 families; most of these (34) were siblings. Overall, 61.4% of the participants were men, 69.3% were ever-smokers, and 84.2% had idiopathic pulmonary fibrosis.

The analysis included data on computed tomography (CT) scanning and predicted forced vital capacity (FVC%), as well as age at diagnosis, treatment type, gender, smoking history, and date of diagnosis.

Overall, FVC%predicted was significantly correlated within families, with a correlation of 0.75. The annual change in FVC was –158.2 mL, and the annual change in FVC%predicted was –6.3%.

Sixty-five patients received antifibrotic treatment, and 18 received immunosuppressive treatment. Immunosuppressive treatment remained significantly correlated among families in a multivariate analysis, with a correlation of 0.77.

“Age at diagnosis correlated within a generation, while patients from a second generation were diagnosed younger,” the researchers noted. The current study findings and results from other studies suggest a genetic basis for FPF age of onset, and determining an age range for screening unaffected relatives based on the age at diagnosis of affected relatives might be useful, they said.

In addition, 42.2% of families showed concordance of CT scan patterns. Typical usual interstitial pneumonia (UIP) appeared in 35 patients, atypical UIP in 36 patients, UIP with emphysema in 9 patients, and findings incompatible with UIP in 21 patients.

The study findings were limited by several factors including the retrospective design and use of data from a single center, as well as by the changes in clinical practice guidelines between 2004 and 2019, with increases in genetic testing, the researchers noted.

However, the current study is the first known to report on FVC evolution within families in FPF, they said. Future studies of both intra- and interfamilial correlation and variability are needed to identify the genetic and environmental factors that may affect disease manifestation and progression, they concluded.

The study was supported by Research Foundation-Flanders. Dr. Goos had no financial conflicts to disclose.

Family members with pulmonary fibrosis showed correlations for predicted forced vital capacity trajectories and computed tomography patterns, based on data from 101 individuals in 45 families.

Patients with familial pulmonary fibrosis (FPF), defined as fibrotic interstitial lung disease among two or more first-degree or second-degree relatives, have worse survival than that of patients with sporadic pulmonary fibrosis, wrote Tinne Goos, MD, of KU Leuven, Belgium, and colleagues. Diagnosis of FPF diagnosis is mainly based on family history, and data on intrafamilial correlations are lacking, they said.

In a study published in the journal Chest, the researchers identified FPF patients treated at a single center. The study population included 101 patients from 45 families; most of these (34) were siblings. Overall, 61.4% of the participants were men, 69.3% were ever-smokers, and 84.2% had idiopathic pulmonary fibrosis.

The analysis included data on computed tomography (CT) scanning and predicted forced vital capacity (FVC%), as well as age at diagnosis, treatment type, gender, smoking history, and date of diagnosis.

Overall, FVC%predicted was significantly correlated within families, with a correlation of 0.75. The annual change in FVC was –158.2 mL, and the annual change in FVC%predicted was –6.3%.

Sixty-five patients received antifibrotic treatment, and 18 received immunosuppressive treatment. Immunosuppressive treatment remained significantly correlated among families in a multivariate analysis, with a correlation of 0.77.

“Age at diagnosis correlated within a generation, while patients from a second generation were diagnosed younger,” the researchers noted. The current study findings and results from other studies suggest a genetic basis for FPF age of onset, and determining an age range for screening unaffected relatives based on the age at diagnosis of affected relatives might be useful, they said.

In addition, 42.2% of families showed concordance of CT scan patterns. Typical usual interstitial pneumonia (UIP) appeared in 35 patients, atypical UIP in 36 patients, UIP with emphysema in 9 patients, and findings incompatible with UIP in 21 patients.

The study findings were limited by several factors including the retrospective design and use of data from a single center, as well as by the changes in clinical practice guidelines between 2004 and 2019, with increases in genetic testing, the researchers noted.

However, the current study is the first known to report on FVC evolution within families in FPF, they said. Future studies of both intra- and interfamilial correlation and variability are needed to identify the genetic and environmental factors that may affect disease manifestation and progression, they concluded.

The study was supported by Research Foundation-Flanders. Dr. Goos had no financial conflicts to disclose.

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³