Dermatology

The European Medicines Agency has validated the marketing authorization application for delgocitinib cream, for the treatment of adults with chronic moderate to severe hand eczema, which marks the beginning of the review process for the treatment by the EMA’s Committee for Medicinal Products for Human Use.

Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.

The development follows results reported from two phase 3 clinical trials known as DELTA 1 and DELTA 2, which evaluated the safety and efficacy of delgocitinib cream applications twice per day compared with a vehicle cream in adults with mild to severe chronic hand eczema. Results of DELTA 1 were presented at the 2023 annual meeting of the American Academy of Dermatology. A multisite, open-label extension trial known as DELTA 3 is still in progress.

According to a press release from LEO Pharma, which is developing the product, the efficacy and safety of delgocitinib cream have not been evaluated by any regulatory authority. In 2020, the drug was granted fast-track designation by the Food and Drug Administration for the potential treatment of adults with moderate to severe chronic hand eczema. There are currently no treatment options available in the United States specifically approved for treating the condition.



 

The European Medicines Agency has validated the marketing authorization application for delgocitinib cream, for the treatment of adults with chronic moderate to severe hand eczema, which marks the beginning of the review process for the treatment by the EMA’s Committee for Medicinal Products for Human Use.

Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.

The development follows results reported from two phase 3 clinical trials known as DELTA 1 and DELTA 2, which evaluated the safety and efficacy of delgocitinib cream applications twice per day compared with a vehicle cream in adults with mild to severe chronic hand eczema. Results of DELTA 1 were presented at the 2023 annual meeting of the American Academy of Dermatology. A multisite, open-label extension trial known as DELTA 3 is still in progress.

According to a press release from LEO Pharma, which is developing the product, the efficacy and safety of delgocitinib cream have not been evaluated by any regulatory authority. In 2020, the drug was granted fast-track designation by the Food and Drug Administration for the potential treatment of adults with moderate to severe chronic hand eczema. There are currently no treatment options available in the United States specifically approved for treating the condition.



 

The European Medicines Agency has validated the marketing authorization application for delgocitinib cream, for the treatment of adults with chronic moderate to severe hand eczema, which marks the beginning of the review process for the treatment by the EMA’s Committee for Medicinal Products for Human Use.

Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.

The development follows results reported from two phase 3 clinical trials known as DELTA 1 and DELTA 2, which evaluated the safety and efficacy of delgocitinib cream applications twice per day compared with a vehicle cream in adults with mild to severe chronic hand eczema. Results of DELTA 1 were presented at the 2023 annual meeting of the American Academy of Dermatology. A multisite, open-label extension trial known as DELTA 3 is still in progress.

According to a press release from LEO Pharma, which is developing the product, the efficacy and safety of delgocitinib cream have not been evaluated by any regulatory authority. In 2020, the drug was granted fast-track designation by the Food and Drug Administration for the potential treatment of adults with moderate to severe chronic hand eczema. There are currently no treatment options available in the United States specifically approved for treating the condition.



 

Among patients with female pattern hair loss taking low-dose oral minoxidil (LDOM) for at least 4 months, minimal changes from baseline were observed in systolic blood pressure, diastolic blood pressure, and heart rate, results from a small retrospective analysis showed.

“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.

At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)

To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.

The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.

Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.

The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).

The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.

At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”

He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.

The researchers reported having no relevant disclosures, and there was no funding source for the study.

Among patients with female pattern hair loss taking low-dose oral minoxidil (LDOM) for at least 4 months, minimal changes from baseline were observed in systolic blood pressure, diastolic blood pressure, and heart rate, results from a small retrospective analysis showed.

“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.

At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)

To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.

The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.

Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.

The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).

The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.

At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”

He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.

The researchers reported having no relevant disclosures, and there was no funding source for the study.

Among patients with female pattern hair loss taking low-dose oral minoxidil (LDOM) for at least 4 months, minimal changes from baseline were observed in systolic blood pressure, diastolic blood pressure, and heart rate, results from a small retrospective analysis showed.

“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.

At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)

To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.

The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.

Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.

The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).

The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.

At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”

He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.

The researchers reported having no relevant disclosures, and there was no funding source for the study.

At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.

He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.

The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
 

Diagnosis

The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.

Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.

Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.

Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.

Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
 

Multidisciplinary care

The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.

Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.

The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.

Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
 

Prognosis

Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.

Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.

Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.

Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.

At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.

He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.

The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
 

Diagnosis

The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.

Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.

Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.

Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.

Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
 

Multidisciplinary care

The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.

Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.

The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.

Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
 

Prognosis

Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.

Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.

Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.

Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.

At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.

He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.

The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
 

Diagnosis

The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.

Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.

Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.

Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.

Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
 

Multidisciplinary care

The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.

Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.

The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.

Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
 

Prognosis

Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.

Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.

Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.

Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.

While oral antibiotics remained the most prescribed systemic treatment for women with acne, spironolactone use continued to grow and became nearly as common as oral antibiotics, results from an analysis of prescribing trends from 2017 through 2020 showed.

Notably, isotretinoin prescribing among men and women decreased slightly during the study period, “which may reflect ongoing administrative burdens associated with iPLEDGE,” study author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, told this news organization.

For the cross-sectional study, which was published online as a research letter in JAMA Dermatology, Dr. Barbieri drew from the Truven Health MarketScan Commercial Claims Database from Jan. 1, 2017, to Dec. 31, 2020, to identify individuals with an encounter for acne, prescriptions for oral tetracycline antibiotics (doxycycline, minocycline), other commonly prescribed oral antibiotics (trimethoprim-sulfamethoxazole, amoxicillin, cephalexin), spironolactone, and isotretinoin. Only drug courses greater than 28 days were included in the analysis, and Dr. Barbieri stratified them according to clinician type (dermatologist, nondermatology physician, and nurse-practitioner or physician assistant). To normalize prescribing rates (to address possible changes in the number of patients treated for acne over time), the number of treatment courses prescribed each year was standardized to the number of encounters for acne with that clinician type during the same calendar year.

The study period included a mean of 1.9 million acne encounters per year.

Dr. Barbieri found that dermatologists prescribed more oral antibiotics per clinician for acne than any other major medical specialty and that oral antibiotics remained frequently prescribed for treating acne by both dermatologists and nondermatologists. “Among oral antibiotics, minocycline and trimethoprim-sulfamethoxazole remain relatively commonly prescribed, despite potential safety concerns and a lack of evidence that they are any more effective than doxycycline,” he said in an interview.

“Patient outcomes could likely be improved by reducing use of minocycline and particularly trimethoprim-sulfamethoxazole given its high risk of serious side effects such as SJS/TEN [Stevens-Johnson syndrome/toxic epidermal necrolysis] and acute respiratory failure,” he added.

Dr. Barbieri noted that there are likely opportunities to consider nonantibiotic alternatives such as hormonal therapy (spironolactone, combined oral contraceptives) and isotretinoin. “There is also a need for continued research to identify nonantibiotic treatment options for patients with acne,” he said.

The analysis revealed that for women with acne prescriptions for spironolactone increased about three- to fourfold during the study period among all clinician types. In 2017, oral antibiotics were prescribed about two- to threefold more often than spironolactone, but by 2020 they were being prescribed at about the same frequency. “Given spironolactone may have similar effectiveness to oral antibiotics in the treatment of acne, this shift in practice has the potential to improve outcomes for patients by reducing the risk of antibiotic-associated complications,” Dr. Barbieri wrote. Still, in 2020, oral antibiotics were still slightly more commonly prescribed than spironolactone by nondermatology physicians and NP or PAs.

In other findings, isotretinoin prescribing decreased slightly among male and female patients during the study period. Among antibiotic prescriptions, prescribing for doxycycline increased at a higher rate than prescribing for minocycline, especially among dermatologists and NPs or PAs.

In the interview, Dr. Barbieri acknowledged certain limitations of the study, including the fact that the dataset “does not allow for evaluation of severity of acne and it is not possible to directly link prescriptions to diagnoses, so some prescriptions might not be for acne and others that are for acne might not have been included.”

Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment on the results, said that, while a course of antibiotic therapy was tied to an office visit in the analysis, the duration of each course of therapy was unclear. It would be interesting to see if antibiotic courses became shorter during the time period analyzed, such as 1-3 months versus 4 or more months, he added, “as this should reduce risks associated with long-term use of oral antibiotics.”

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

While oral antibiotics remained the most prescribed systemic treatment for women with acne, spironolactone use continued to grow and became nearly as common as oral antibiotics, results from an analysis of prescribing trends from 2017 through 2020 showed.

Notably, isotretinoin prescribing among men and women decreased slightly during the study period, “which may reflect ongoing administrative burdens associated with iPLEDGE,” study author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, told this news organization.

For the cross-sectional study, which was published online as a research letter in JAMA Dermatology, Dr. Barbieri drew from the Truven Health MarketScan Commercial Claims Database from Jan. 1, 2017, to Dec. 31, 2020, to identify individuals with an encounter for acne, prescriptions for oral tetracycline antibiotics (doxycycline, minocycline), other commonly prescribed oral antibiotics (trimethoprim-sulfamethoxazole, amoxicillin, cephalexin), spironolactone, and isotretinoin. Only drug courses greater than 28 days were included in the analysis, and Dr. Barbieri stratified them according to clinician type (dermatologist, nondermatology physician, and nurse-practitioner or physician assistant). To normalize prescribing rates (to address possible changes in the number of patients treated for acne over time), the number of treatment courses prescribed each year was standardized to the number of encounters for acne with that clinician type during the same calendar year.

The study period included a mean of 1.9 million acne encounters per year.

Dr. Barbieri found that dermatologists prescribed more oral antibiotics per clinician for acne than any other major medical specialty and that oral antibiotics remained frequently prescribed for treating acne by both dermatologists and nondermatologists. “Among oral antibiotics, minocycline and trimethoprim-sulfamethoxazole remain relatively commonly prescribed, despite potential safety concerns and a lack of evidence that they are any more effective than doxycycline,” he said in an interview.

“Patient outcomes could likely be improved by reducing use of minocycline and particularly trimethoprim-sulfamethoxazole given its high risk of serious side effects such as SJS/TEN [Stevens-Johnson syndrome/toxic epidermal necrolysis] and acute respiratory failure,” he added.

Dr. Barbieri noted that there are likely opportunities to consider nonantibiotic alternatives such as hormonal therapy (spironolactone, combined oral contraceptives) and isotretinoin. “There is also a need for continued research to identify nonantibiotic treatment options for patients with acne,” he said.

The analysis revealed that for women with acne prescriptions for spironolactone increased about three- to fourfold during the study period among all clinician types. In 2017, oral antibiotics were prescribed about two- to threefold more often than spironolactone, but by 2020 they were being prescribed at about the same frequency. “Given spironolactone may have similar effectiveness to oral antibiotics in the treatment of acne, this shift in practice has the potential to improve outcomes for patients by reducing the risk of antibiotic-associated complications,” Dr. Barbieri wrote. Still, in 2020, oral antibiotics were still slightly more commonly prescribed than spironolactone by nondermatology physicians and NP or PAs.

In other findings, isotretinoin prescribing decreased slightly among male and female patients during the study period. Among antibiotic prescriptions, prescribing for doxycycline increased at a higher rate than prescribing for minocycline, especially among dermatologists and NPs or PAs.

In the interview, Dr. Barbieri acknowledged certain limitations of the study, including the fact that the dataset “does not allow for evaluation of severity of acne and it is not possible to directly link prescriptions to diagnoses, so some prescriptions might not be for acne and others that are for acne might not have been included.”

Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment on the results, said that, while a course of antibiotic therapy was tied to an office visit in the analysis, the duration of each course of therapy was unclear. It would be interesting to see if antibiotic courses became shorter during the time period analyzed, such as 1-3 months versus 4 or more months, he added, “as this should reduce risks associated with long-term use of oral antibiotics.”

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

While oral antibiotics remained the most prescribed systemic treatment for women with acne, spironolactone use continued to grow and became nearly as common as oral antibiotics, results from an analysis of prescribing trends from 2017 through 2020 showed.

Notably, isotretinoin prescribing among men and women decreased slightly during the study period, “which may reflect ongoing administrative burdens associated with iPLEDGE,” study author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, told this news organization.

For the cross-sectional study, which was published online as a research letter in JAMA Dermatology, Dr. Barbieri drew from the Truven Health MarketScan Commercial Claims Database from Jan. 1, 2017, to Dec. 31, 2020, to identify individuals with an encounter for acne, prescriptions for oral tetracycline antibiotics (doxycycline, minocycline), other commonly prescribed oral antibiotics (trimethoprim-sulfamethoxazole, amoxicillin, cephalexin), spironolactone, and isotretinoin. Only drug courses greater than 28 days were included in the analysis, and Dr. Barbieri stratified them according to clinician type (dermatologist, nondermatology physician, and nurse-practitioner or physician assistant). To normalize prescribing rates (to address possible changes in the number of patients treated for acne over time), the number of treatment courses prescribed each year was standardized to the number of encounters for acne with that clinician type during the same calendar year.

The study period included a mean of 1.9 million acne encounters per year.

Dr. Barbieri found that dermatologists prescribed more oral antibiotics per clinician for acne than any other major medical specialty and that oral antibiotics remained frequently prescribed for treating acne by both dermatologists and nondermatologists. “Among oral antibiotics, minocycline and trimethoprim-sulfamethoxazole remain relatively commonly prescribed, despite potential safety concerns and a lack of evidence that they are any more effective than doxycycline,” he said in an interview.

“Patient outcomes could likely be improved by reducing use of minocycline and particularly trimethoprim-sulfamethoxazole given its high risk of serious side effects such as SJS/TEN [Stevens-Johnson syndrome/toxic epidermal necrolysis] and acute respiratory failure,” he added.

Dr. Barbieri noted that there are likely opportunities to consider nonantibiotic alternatives such as hormonal therapy (spironolactone, combined oral contraceptives) and isotretinoin. “There is also a need for continued research to identify nonantibiotic treatment options for patients with acne,” he said.

The analysis revealed that for women with acne prescriptions for spironolactone increased about three- to fourfold during the study period among all clinician types. In 2017, oral antibiotics were prescribed about two- to threefold more often than spironolactone, but by 2020 they were being prescribed at about the same frequency. “Given spironolactone may have similar effectiveness to oral antibiotics in the treatment of acne, this shift in practice has the potential to improve outcomes for patients by reducing the risk of antibiotic-associated complications,” Dr. Barbieri wrote. Still, in 2020, oral antibiotics were still slightly more commonly prescribed than spironolactone by nondermatology physicians and NP or PAs.

In other findings, isotretinoin prescribing decreased slightly among male and female patients during the study period. Among antibiotic prescriptions, prescribing for doxycycline increased at a higher rate than prescribing for minocycline, especially among dermatologists and NPs or PAs.

In the interview, Dr. Barbieri acknowledged certain limitations of the study, including the fact that the dataset “does not allow for evaluation of severity of acne and it is not possible to directly link prescriptions to diagnoses, so some prescriptions might not be for acne and others that are for acne might not have been included.”

Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment on the results, said that, while a course of antibiotic therapy was tied to an office visit in the analysis, the duration of each course of therapy was unclear. It would be interesting to see if antibiotic courses became shorter during the time period analyzed, such as 1-3 months versus 4 or more months, he added, “as this should reduce risks associated with long-term use of oral antibiotics.”

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions that include deep-seated nodules and abscesses, draining tracts, and fibrotic scars, and has been reported to be highly heritable. New findings now suggest that common variants associated with HS, located near the SOX9 and KLF5 genes, may raise the risk of the disease.

A genomewide association study (GWAS) that involved a meta-analysis of data from three large biobanks (UK Biobank, FinnGen, and BioVU) identified one significant locus and two suggestive loci. The researchers were able to replicate the association with HS for two loci near the SOX9 and KLF5 genes in BioVU.

In addition, they also looked at genetic correlations between HS and autoimmune and inflammatory diseases, and results suggested a positive association with inflammatory bowel disease, psoriasis, and type 2 diabetes.

However, while plausible, the variant associations near candidate genes do not prove a causal effect of these variants or genes on disease risk, and further study is needed.

“It’s possible that these genes aren’t the ones affected by the variations we describe, but both are very strong candidates,” said study author Christopher J. Sayed, MD, associate professor of dermatology, University of North Carolina at Chapel Hill. “This improves our understanding of HS as a disease that is likely related to genetic changes that result in dysregulated hair follicle maintenance, inflammation, and wound healing.”

In turn, this will allow clinicians to educate patients about the underlying genetic influences on HS, he explained, as opposed to stigmatizing misconceptions focusing only on weight, smoking, and hygiene.

“Larger studies are underway and will be needed to find variants that may predict things like disease severity and response to treatment, but this is a big first step in the right direction,” Dr. Sayed added.

The study was published online in JAMA Dermatology.
 

Loci identified

GWASs have been limited in HS, and previous research has not identified significant risk loci. In the current study, Dr. Sayed and colleagues sought to identify underlying genes and genetic mechanisms that may underlie pathogenesis in HS.

They performed a GWAS in a cohort of 720 patients who were part of the Hidradenitis Suppurativa Program for Research and Care Excellence (HS ProCARE) at the UNC department of dermatology, and controls from the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, a U.S.-based study following adolescents through adulthood.

Elsevier

The UK Biobank (UKB) is a prospective biobank with about 500,000 individuals aged 40-69 years, and FinnGen collects and analyzes genome and health data from Finnish biobank participants. To increase power to detect associations, a GWAS was performed using participants from the UKB (247 HS cases, 453,048 controls). The HS ProCARE GWAS results were meta-analyzed with UKB, along with data from FinnGen (673 HS cases, 297,544 controls). This three-way meta-analysis revealed one genomewide significant locus and two suggestive loci.

The authors found that the most strongly associated variant, rs10512572 located on chromosome 17, showed the strongest association in FinnGen; at the second locus, the most strongly associated variant was rs17090189 located on chromosome 13 and also showed the strongest association in FinnGen; and at the third locus, the most strongly associated variant, rs5792315, located on chromosome 11, showed the strongest association in HS ProCARE.

Next, they tested the 10 most strongly associated variants at the three loci in the BioVU biobank, which has 290 HS cases, including 189 individuals of European ancestry and 101 individuals of African ancestry, with 64,234 and 12,105 controls, respectively. The locus on chromosome 17 was replicated in BioVU in the same direction of effect, while one variant at the chromosome 13 locus showed nominal evidence of association in the same direction.

In a four-way meta-analysis of BioVU combined with the other three studies, the chromosome locus became more significant and the chromosome 13 locus exceeded the genomewide significance threshold. In contrast, the chromosome 11 locus was not replicated in BioVU (P = .27).

The authors pointed out that variants at these loci are located in keratinocyte regulatory elements near the genes SOX9 and KLF5, which play a role in skin and follicular inflammation, but have not previously been associated with HS pathogenesis.

Finally, they looked to see if there were shared genetic components between HS and autoimmune and inflammatory diseases. A nominally significant genetic correlation was observed between HS and inflammatory bowel disease (P = .04), psoriasis (P = .03), and type 2 diabetes (P = .04), although none reached significance.
 

Different manifestation with genetic variant

In a related study, researchers assessed the prevalence of the NCSTN:c.671_682del variant among individuals with HS in Malta, the island country in the Mediterranean, which has a high prevalence of HS and its associated risk factors, particularly obesity.

Led by Dillon Mintoff, MD, of the department of pathology at the University of Malta, Msida, they conducted a cross-sectional study of 113 adults with HS. In this group, 14 (12.39%) were found to be heterozygous for the NCSTN:c.671_682del variant. Individuals who had this variant were more likely to develop symptoms earlier and to manifest them in atypical skin sites, including the scalp, neck, torso, and antecubital fossae. Additionally, even though their symptoms weren’t more severe than those without the variant, patients with the variant were more likely to require treatment with biologic agents.

Studies move genetics in HS forward

Writing in an accompanying editorial, Atlas Khan, PhD, and Lynn Petukhova, PhD, from Columbia University, New York, noted that both of these HS genetic studies “set a solid foundation for future studies aimed at understanding the biological and clinical relevance of new HS genetic evidence.”

“Each study suggests a series of experiments that will allow us to gain new knowledge about HS,” they wrote, including coming closer to providing patients with a genetic diagnosis.

In addition, evidence from the GWAS paper suggests that with “larger HS GWASs we will be able to better prioritize drug-repurposing studies,” concluded the editorialists. “Both of these goals will help to improve health outcomes for patients with HS and their family members.”

Dr. Sayed reported grants and/or personal fees from AbbVie, Novartis, UCB, Incyte, InflaRx, Alumis, and ChemoCentryx outside the submitted work; and serving as a volunteer member of the board of the HS Foundation and member of the European HS Foundation. The study in Malta was funded by the Government of Malta’s Tertiary Education Scholarship Scheme and Institutional Funds from the University of Malta. Dr. Mintoff reported grants from the Government of Malta Ministry for Education, Sport, Youth, Research and Innovation during the conduct of the study. Dr. Khan reported receiving grants from the National Institute of Diabetes and Digestive Kidney Diseases. Dr. Petukhova reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Columbia University’s Precision Medicine Initiative, Herbert Irving Comprehensive Cancer Center, and Data Science Institute.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions that include deep-seated nodules and abscesses, draining tracts, and fibrotic scars, and has been reported to be highly heritable. New findings now suggest that common variants associated with HS, located near the SOX9 and KLF5 genes, may raise the risk of the disease.

A genomewide association study (GWAS) that involved a meta-analysis of data from three large biobanks (UK Biobank, FinnGen, and BioVU) identified one significant locus and two suggestive loci. The researchers were able to replicate the association with HS for two loci near the SOX9 and KLF5 genes in BioVU.

In addition, they also looked at genetic correlations between HS and autoimmune and inflammatory diseases, and results suggested a positive association with inflammatory bowel disease, psoriasis, and type 2 diabetes.

However, while plausible, the variant associations near candidate genes do not prove a causal effect of these variants or genes on disease risk, and further study is needed.

“It’s possible that these genes aren’t the ones affected by the variations we describe, but both are very strong candidates,” said study author Christopher J. Sayed, MD, associate professor of dermatology, University of North Carolina at Chapel Hill. “This improves our understanding of HS as a disease that is likely related to genetic changes that result in dysregulated hair follicle maintenance, inflammation, and wound healing.”

In turn, this will allow clinicians to educate patients about the underlying genetic influences on HS, he explained, as opposed to stigmatizing misconceptions focusing only on weight, smoking, and hygiene.

“Larger studies are underway and will be needed to find variants that may predict things like disease severity and response to treatment, but this is a big first step in the right direction,” Dr. Sayed added.

The study was published online in JAMA Dermatology.
 

Loci identified

GWASs have been limited in HS, and previous research has not identified significant risk loci. In the current study, Dr. Sayed and colleagues sought to identify underlying genes and genetic mechanisms that may underlie pathogenesis in HS.

They performed a GWAS in a cohort of 720 patients who were part of the Hidradenitis Suppurativa Program for Research and Care Excellence (HS ProCARE) at the UNC department of dermatology, and controls from the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, a U.S.-based study following adolescents through adulthood.

Elsevier

The UK Biobank (UKB) is a prospective biobank with about 500,000 individuals aged 40-69 years, and FinnGen collects and analyzes genome and health data from Finnish biobank participants. To increase power to detect associations, a GWAS was performed using participants from the UKB (247 HS cases, 453,048 controls). The HS ProCARE GWAS results were meta-analyzed with UKB, along with data from FinnGen (673 HS cases, 297,544 controls). This three-way meta-analysis revealed one genomewide significant locus and two suggestive loci.

The authors found that the most strongly associated variant, rs10512572 located on chromosome 17, showed the strongest association in FinnGen; at the second locus, the most strongly associated variant was rs17090189 located on chromosome 13 and also showed the strongest association in FinnGen; and at the third locus, the most strongly associated variant, rs5792315, located on chromosome 11, showed the strongest association in HS ProCARE.

Next, they tested the 10 most strongly associated variants at the three loci in the BioVU biobank, which has 290 HS cases, including 189 individuals of European ancestry and 101 individuals of African ancestry, with 64,234 and 12,105 controls, respectively. The locus on chromosome 17 was replicated in BioVU in the same direction of effect, while one variant at the chromosome 13 locus showed nominal evidence of association in the same direction.

In a four-way meta-analysis of BioVU combined with the other three studies, the chromosome locus became more significant and the chromosome 13 locus exceeded the genomewide significance threshold. In contrast, the chromosome 11 locus was not replicated in BioVU (P = .27).

The authors pointed out that variants at these loci are located in keratinocyte regulatory elements near the genes SOX9 and KLF5, which play a role in skin and follicular inflammation, but have not previously been associated with HS pathogenesis.

Finally, they looked to see if there were shared genetic components between HS and autoimmune and inflammatory diseases. A nominally significant genetic correlation was observed between HS and inflammatory bowel disease (P = .04), psoriasis (P = .03), and type 2 diabetes (P = .04), although none reached significance.
 

Different manifestation with genetic variant

In a related study, researchers assessed the prevalence of the NCSTN:c.671_682del variant among individuals with HS in Malta, the island country in the Mediterranean, which has a high prevalence of HS and its associated risk factors, particularly obesity.

Led by Dillon Mintoff, MD, of the department of pathology at the University of Malta, Msida, they conducted a cross-sectional study of 113 adults with HS. In this group, 14 (12.39%) were found to be heterozygous for the NCSTN:c.671_682del variant. Individuals who had this variant were more likely to develop symptoms earlier and to manifest them in atypical skin sites, including the scalp, neck, torso, and antecubital fossae. Additionally, even though their symptoms weren’t more severe than those without the variant, patients with the variant were more likely to require treatment with biologic agents.

Studies move genetics in HS forward

Writing in an accompanying editorial, Atlas Khan, PhD, and Lynn Petukhova, PhD, from Columbia University, New York, noted that both of these HS genetic studies “set a solid foundation for future studies aimed at understanding the biological and clinical relevance of new HS genetic evidence.”

“Each study suggests a series of experiments that will allow us to gain new knowledge about HS,” they wrote, including coming closer to providing patients with a genetic diagnosis.

In addition, evidence from the GWAS paper suggests that with “larger HS GWASs we will be able to better prioritize drug-repurposing studies,” concluded the editorialists. “Both of these goals will help to improve health outcomes for patients with HS and their family members.”

Dr. Sayed reported grants and/or personal fees from AbbVie, Novartis, UCB, Incyte, InflaRx, Alumis, and ChemoCentryx outside the submitted work; and serving as a volunteer member of the board of the HS Foundation and member of the European HS Foundation. The study in Malta was funded by the Government of Malta’s Tertiary Education Scholarship Scheme and Institutional Funds from the University of Malta. Dr. Mintoff reported grants from the Government of Malta Ministry for Education, Sport, Youth, Research and Innovation during the conduct of the study. Dr. Khan reported receiving grants from the National Institute of Diabetes and Digestive Kidney Diseases. Dr. Petukhova reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Columbia University’s Precision Medicine Initiative, Herbert Irving Comprehensive Cancer Center, and Data Science Institute.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions that include deep-seated nodules and abscesses, draining tracts, and fibrotic scars, and has been reported to be highly heritable. New findings now suggest that common variants associated with HS, located near the SOX9 and KLF5 genes, may raise the risk of the disease.

A genomewide association study (GWAS) that involved a meta-analysis of data from three large biobanks (UK Biobank, FinnGen, and BioVU) identified one significant locus and two suggestive loci. The researchers were able to replicate the association with HS for two loci near the SOX9 and KLF5 genes in BioVU.

In addition, they also looked at genetic correlations between HS and autoimmune and inflammatory diseases, and results suggested a positive association with inflammatory bowel disease, psoriasis, and type 2 diabetes.

However, while plausible, the variant associations near candidate genes do not prove a causal effect of these variants or genes on disease risk, and further study is needed.

“It’s possible that these genes aren’t the ones affected by the variations we describe, but both are very strong candidates,” said study author Christopher J. Sayed, MD, associate professor of dermatology, University of North Carolina at Chapel Hill. “This improves our understanding of HS as a disease that is likely related to genetic changes that result in dysregulated hair follicle maintenance, inflammation, and wound healing.”

In turn, this will allow clinicians to educate patients about the underlying genetic influences on HS, he explained, as opposed to stigmatizing misconceptions focusing only on weight, smoking, and hygiene.

“Larger studies are underway and will be needed to find variants that may predict things like disease severity and response to treatment, but this is a big first step in the right direction,” Dr. Sayed added.

The study was published online in JAMA Dermatology.
 

Loci identified

GWASs have been limited in HS, and previous research has not identified significant risk loci. In the current study, Dr. Sayed and colleagues sought to identify underlying genes and genetic mechanisms that may underlie pathogenesis in HS.

They performed a GWAS in a cohort of 720 patients who were part of the Hidradenitis Suppurativa Program for Research and Care Excellence (HS ProCARE) at the UNC department of dermatology, and controls from the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, a U.S.-based study following adolescents through adulthood.

Elsevier

The UK Biobank (UKB) is a prospective biobank with about 500,000 individuals aged 40-69 years, and FinnGen collects and analyzes genome and health data from Finnish biobank participants. To increase power to detect associations, a GWAS was performed using participants from the UKB (247 HS cases, 453,048 controls). The HS ProCARE GWAS results were meta-analyzed with UKB, along with data from FinnGen (673 HS cases, 297,544 controls). This three-way meta-analysis revealed one genomewide significant locus and two suggestive loci.

The authors found that the most strongly associated variant, rs10512572 located on chromosome 17, showed the strongest association in FinnGen; at the second locus, the most strongly associated variant was rs17090189 located on chromosome 13 and also showed the strongest association in FinnGen; and at the third locus, the most strongly associated variant, rs5792315, located on chromosome 11, showed the strongest association in HS ProCARE.

Next, they tested the 10 most strongly associated variants at the three loci in the BioVU biobank, which has 290 HS cases, including 189 individuals of European ancestry and 101 individuals of African ancestry, with 64,234 and 12,105 controls, respectively. The locus on chromosome 17 was replicated in BioVU in the same direction of effect, while one variant at the chromosome 13 locus showed nominal evidence of association in the same direction.

In a four-way meta-analysis of BioVU combined with the other three studies, the chromosome locus became more significant and the chromosome 13 locus exceeded the genomewide significance threshold. In contrast, the chromosome 11 locus was not replicated in BioVU (P = .27).

The authors pointed out that variants at these loci are located in keratinocyte regulatory elements near the genes SOX9 and KLF5, which play a role in skin and follicular inflammation, but have not previously been associated with HS pathogenesis.

Finally, they looked to see if there were shared genetic components between HS and autoimmune and inflammatory diseases. A nominally significant genetic correlation was observed between HS and inflammatory bowel disease (P = .04), psoriasis (P = .03), and type 2 diabetes (P = .04), although none reached significance.
 

Different manifestation with genetic variant

In a related study, researchers assessed the prevalence of the NCSTN:c.671_682del variant among individuals with HS in Malta, the island country in the Mediterranean, which has a high prevalence of HS and its associated risk factors, particularly obesity.

Led by Dillon Mintoff, MD, of the department of pathology at the University of Malta, Msida, they conducted a cross-sectional study of 113 adults with HS. In this group, 14 (12.39%) were found to be heterozygous for the NCSTN:c.671_682del variant. Individuals who had this variant were more likely to develop symptoms earlier and to manifest them in atypical skin sites, including the scalp, neck, torso, and antecubital fossae. Additionally, even though their symptoms weren’t more severe than those without the variant, patients with the variant were more likely to require treatment with biologic agents.

Studies move genetics in HS forward

Writing in an accompanying editorial, Atlas Khan, PhD, and Lynn Petukhova, PhD, from Columbia University, New York, noted that both of these HS genetic studies “set a solid foundation for future studies aimed at understanding the biological and clinical relevance of new HS genetic evidence.”

“Each study suggests a series of experiments that will allow us to gain new knowledge about HS,” they wrote, including coming closer to providing patients with a genetic diagnosis.

In addition, evidence from the GWAS paper suggests that with “larger HS GWASs we will be able to better prioritize drug-repurposing studies,” concluded the editorialists. “Both of these goals will help to improve health outcomes for patients with HS and their family members.”

Dr. Sayed reported grants and/or personal fees from AbbVie, Novartis, UCB, Incyte, InflaRx, Alumis, and ChemoCentryx outside the submitted work; and serving as a volunteer member of the board of the HS Foundation and member of the European HS Foundation. The study in Malta was funded by the Government of Malta’s Tertiary Education Scholarship Scheme and Institutional Funds from the University of Malta. Dr. Mintoff reported grants from the Government of Malta Ministry for Education, Sport, Youth, Research and Innovation during the conduct of the study. Dr. Khan reported receiving grants from the National Institute of Diabetes and Digestive Kidney Diseases. Dr. Petukhova reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Columbia University’s Precision Medicine Initiative, Herbert Irving Comprehensive Cancer Center, and Data Science Institute.

Dermatomyositis is a rare autoimmune condition characterized by muscle inflammation and weakness, and skin findings. The classical presentation includes symmetric proximal muscle weakness and underlying malignancy and is very common in adult patients. The etiology is unknown, however.

Courtesy Lucas Shapiro and Dr. Natalie Y. Nasser

Some studies suggest people with certain HLA subtypes are at higher risk, and various infectious and pharmacological triggers are suspected to play a role in the pathogenesis of dermatomyositis. Infectious causes include Coxsackie B, enterovirus, and parvovirus. Drugs such as antineoplastic agents, antibiotics, and NSAIDs have been found to be triggers.

The pathogenesis of dermatomyositis involves immune-mediated damage to muscle capillaries and the endothelium of arterioles. In the typical humoral immune response, complement activation occurs. One mechanism of damage in dermatomyositis occurs when the membrane attack complex formed at the end of the complement process deposits in blood vessels, causing inflammation. B cells, autoantibodies, and interferon overexpression may also play a role in damaging the vasculature and muscle fibers. Hypoxia leads to muscular atrophy, resulting in degeneration and death of the fibers. On muscle biopsy, a perivascular and perimysial inflammatory infiltrate, perifascicular atrophy, and microangiopathy may be present. Skin histology reveals vacuolar changes in the basal layer, a lymphocytic infiltrate, and increased mucin production in the dermis.

On clinical examination, patients will have proximal muscle weakness and a skin rash that may include Gottron’s papules, heliotrope erythema, V-sign, shawl sign, holster sign, scalp erythema, midfacial erythema, and photosensitivity. Scalp erythema in dermatomyositis is highly linked to pruritus, alopecia, and telogen effluvium. Patients may experience small fiber neuropathy in dermatomyositis.

Serologies for this patient, who had previously been diagnosed and treated for dermatomyositis, were significant for a positive ANA 1:2560. Anti-Jo-1 antibody was negative. Her liver function tests, aldolase, creatinine kinase, sedimentation rate, C-reactive protein, and serum protein electrophoresis were normal. Imaging revealed mild chronic interstitial lung disease. A malignancy workup was negative.

Treatment of dermatomyositis involves lifestyle changes and pharmacologic therapy. Because of the intense photosensitivity, patients should be diligent with their sun protection. Methotrexate, azathioprine, and mycophenolate mofetil are considered first-line therapies for dermatomyositis. Therapies such as cyclophosphamide, rituximab, IVIg, and plasmapheresis may also be indicated in severe or refractory cases. Additionally, patients with pulmonary involvement should be given systemic steroids. The side effects of these drugs must be considered in the context of the patient’s demographics, comorbidities and lifestyle.

This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Natalie Y. Nasser, MD, of Kaiser Permanente Riverside Medical Center, Riverside, Calif. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Qudsiya Z and Waseem M. Dermatomyositis, in “StatPearls.” Treasure Island, Fla.: StatPearls Publishing, 2023 Jan.

2. Kamperman RG et al. Int J Mol Sci. 2022 Apr 13;23(8):4301.

3. Kassamali B et al. Int J WomensDermatol. 2021 Sep 24;7(5Part A):576-82.

4. Vázquez-Herrera NE et al. Skin Appendage Disord. 2018 Aug;4(3):187-99.

Dermatomyositis is a rare autoimmune condition characterized by muscle inflammation and weakness, and skin findings. The classical presentation includes symmetric proximal muscle weakness and underlying malignancy and is very common in adult patients. The etiology is unknown, however.

Courtesy Lucas Shapiro and Dr. Natalie Y. Nasser

Some studies suggest people with certain HLA subtypes are at higher risk, and various infectious and pharmacological triggers are suspected to play a role in the pathogenesis of dermatomyositis. Infectious causes include Coxsackie B, enterovirus, and parvovirus. Drugs such as antineoplastic agents, antibiotics, and NSAIDs have been found to be triggers.

The pathogenesis of dermatomyositis involves immune-mediated damage to muscle capillaries and the endothelium of arterioles. In the typical humoral immune response, complement activation occurs. One mechanism of damage in dermatomyositis occurs when the membrane attack complex formed at the end of the complement process deposits in blood vessels, causing inflammation. B cells, autoantibodies, and interferon overexpression may also play a role in damaging the vasculature and muscle fibers. Hypoxia leads to muscular atrophy, resulting in degeneration and death of the fibers. On muscle biopsy, a perivascular and perimysial inflammatory infiltrate, perifascicular atrophy, and microangiopathy may be present. Skin histology reveals vacuolar changes in the basal layer, a lymphocytic infiltrate, and increased mucin production in the dermis.

On clinical examination, patients will have proximal muscle weakness and a skin rash that may include Gottron’s papules, heliotrope erythema, V-sign, shawl sign, holster sign, scalp erythema, midfacial erythema, and photosensitivity. Scalp erythema in dermatomyositis is highly linked to pruritus, alopecia, and telogen effluvium. Patients may experience small fiber neuropathy in dermatomyositis.

Serologies for this patient, who had previously been diagnosed and treated for dermatomyositis, were significant for a positive ANA 1:2560. Anti-Jo-1 antibody was negative. Her liver function tests, aldolase, creatinine kinase, sedimentation rate, C-reactive protein, and serum protein electrophoresis were normal. Imaging revealed mild chronic interstitial lung disease. A malignancy workup was negative.

Treatment of dermatomyositis involves lifestyle changes and pharmacologic therapy. Because of the intense photosensitivity, patients should be diligent with their sun protection. Methotrexate, azathioprine, and mycophenolate mofetil are considered first-line therapies for dermatomyositis. Therapies such as cyclophosphamide, rituximab, IVIg, and plasmapheresis may also be indicated in severe or refractory cases. Additionally, patients with pulmonary involvement should be given systemic steroids. The side effects of these drugs must be considered in the context of the patient’s demographics, comorbidities and lifestyle.

This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Natalie Y. Nasser, MD, of Kaiser Permanente Riverside Medical Center, Riverside, Calif. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Qudsiya Z and Waseem M. Dermatomyositis, in “StatPearls.” Treasure Island, Fla.: StatPearls Publishing, 2023 Jan.

2. Kamperman RG et al. Int J Mol Sci. 2022 Apr 13;23(8):4301.

3. Kassamali B et al. Int J WomensDermatol. 2021 Sep 24;7(5Part A):576-82.

4. Vázquez-Herrera NE et al. Skin Appendage Disord. 2018 Aug;4(3):187-99.

Dermatomyositis is a rare autoimmune condition characterized by muscle inflammation and weakness, and skin findings. The classical presentation includes symmetric proximal muscle weakness and underlying malignancy and is very common in adult patients. The etiology is unknown, however.

Courtesy Lucas Shapiro and Dr. Natalie Y. Nasser

Some studies suggest people with certain HLA subtypes are at higher risk, and various infectious and pharmacological triggers are suspected to play a role in the pathogenesis of dermatomyositis. Infectious causes include Coxsackie B, enterovirus, and parvovirus. Drugs such as antineoplastic agents, antibiotics, and NSAIDs have been found to be triggers.

The pathogenesis of dermatomyositis involves immune-mediated damage to muscle capillaries and the endothelium of arterioles. In the typical humoral immune response, complement activation occurs. One mechanism of damage in dermatomyositis occurs when the membrane attack complex formed at the end of the complement process deposits in blood vessels, causing inflammation. B cells, autoantibodies, and interferon overexpression may also play a role in damaging the vasculature and muscle fibers. Hypoxia leads to muscular atrophy, resulting in degeneration and death of the fibers. On muscle biopsy, a perivascular and perimysial inflammatory infiltrate, perifascicular atrophy, and microangiopathy may be present. Skin histology reveals vacuolar changes in the basal layer, a lymphocytic infiltrate, and increased mucin production in the dermis.

On clinical examination, patients will have proximal muscle weakness and a skin rash that may include Gottron’s papules, heliotrope erythema, V-sign, shawl sign, holster sign, scalp erythema, midfacial erythema, and photosensitivity. Scalp erythema in dermatomyositis is highly linked to pruritus, alopecia, and telogen effluvium. Patients may experience small fiber neuropathy in dermatomyositis.

Serologies for this patient, who had previously been diagnosed and treated for dermatomyositis, were significant for a positive ANA 1:2560. Anti-Jo-1 antibody was negative. Her liver function tests, aldolase, creatinine kinase, sedimentation rate, C-reactive protein, and serum protein electrophoresis were normal. Imaging revealed mild chronic interstitial lung disease. A malignancy workup was negative.

Treatment of dermatomyositis involves lifestyle changes and pharmacologic therapy. Because of the intense photosensitivity, patients should be diligent with their sun protection. Methotrexate, azathioprine, and mycophenolate mofetil are considered first-line therapies for dermatomyositis. Therapies such as cyclophosphamide, rituximab, IVIg, and plasmapheresis may also be indicated in severe or refractory cases. Additionally, patients with pulmonary involvement should be given systemic steroids. The side effects of these drugs must be considered in the context of the patient’s demographics, comorbidities and lifestyle.

This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Natalie Y. Nasser, MD, of Kaiser Permanente Riverside Medical Center, Riverside, Calif. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Qudsiya Z and Waseem M. Dermatomyositis, in “StatPearls.” Treasure Island, Fla.: StatPearls Publishing, 2023 Jan.

2. Kamperman RG et al. Int J Mol Sci. 2022 Apr 13;23(8):4301.

3. Kassamali B et al. Int J WomensDermatol. 2021 Sep 24;7(5Part A):576-82.

4. Vázquez-Herrera NE et al. Skin Appendage Disord. 2018 Aug;4(3):187-99.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

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

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

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

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

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

This patient had more than cystic acne; he had acne conglobata. AC is a severe form of inflammatory acne leading to coalescing lesions with purulent sinus tracts under the skin. It can be seen as part of the follicular tetrad syndrome of cystic acne, hidradenitis suppurativa, dissecting cellulitis, and pilonidal disease. AC is thought to be an elevated tumor necrosis factor (TNF)-alpha response to Propionibacterium acnes (now known as Cutibacterium acnes) that leads to excessive inflammation and sterile abscesses.¹ Acne fulminans (AF) can also manifest as a purulent form of acne, but AF has associated systemic signs and symptoms that include fevers, chills, and malaise.

Due to the depth of the inflammation, AC is treated with systemic medications, most commonly isotretinoin. Isotretinoin can be started at 0.5 mg/kg (divided twice daily to enhance tolerability) and then increased to 1 mg/kg (divided twice daily) for 5 months. There is some variation in dosing regimens in practice; the target goal is 120 to 150 mg/kg over the course of treatment. In AF, the patient is pretreated with systemic steroids, and in AC, some clinicians will even prescribe systemic steroids (prednisone 0.5 mg/kg daily for the first month) along with isotretinoin.

Second-line medications include dapsone (50-150 mg/d).² Case reports describe the successful use of the TNF-alpha antagonist adalimumab, although this is not a usual practice in AC treatment.¹ Note that all of these medications have the potential for severe adverse effects and require laboratory evaluation prior to initiation.

This patient was counseled, prescribed isotretinoin (dose as above), and enrolled in the IPledge prescribing and monitoring system for isotretinoin. At 20 weeks of use, the purulent drainage ceased. The pus-filled sinus tracts and redness had resolved, although he still had thickened tissue and scarring where the tracts had been. In time, the scars will usually get flatter and softer.

If the patient’s AC were to flare, another 20-week course of isotretinoin could be prescribed after a 2-month hiatus or he could be switched to a second-line medication. Referral for any cosmetic therapy is typically delayed for another 6 months in case there is a need to treat a recurrence.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient had more than cystic acne; he had acne conglobata. AC is a severe form of inflammatory acne leading to coalescing lesions with purulent sinus tracts under the skin. It can be seen as part of the follicular tetrad syndrome of cystic acne, hidradenitis suppurativa, dissecting cellulitis, and pilonidal disease. AC is thought to be an elevated tumor necrosis factor (TNF)-alpha response to Propionibacterium acnes (now known as Cutibacterium acnes) that leads to excessive inflammation and sterile abscesses.¹ Acne fulminans (AF) can also manifest as a purulent form of acne, but AF has associated systemic signs and symptoms that include fevers, chills, and malaise.

Due to the depth of the inflammation, AC is treated with systemic medications, most commonly isotretinoin. Isotretinoin can be started at 0.5 mg/kg (divided twice daily to enhance tolerability) and then increased to 1 mg/kg (divided twice daily) for 5 months. There is some variation in dosing regimens in practice; the target goal is 120 to 150 mg/kg over the course of treatment. In AF, the patient is pretreated with systemic steroids, and in AC, some clinicians will even prescribe systemic steroids (prednisone 0.5 mg/kg daily for the first month) along with isotretinoin.

Second-line medications include dapsone (50-150 mg/d).² Case reports describe the successful use of the TNF-alpha antagonist adalimumab, although this is not a usual practice in AC treatment.¹ Note that all of these medications have the potential for severe adverse effects and require laboratory evaluation prior to initiation.

This patient was counseled, prescribed isotretinoin (dose as above), and enrolled in the IPledge prescribing and monitoring system for isotretinoin. At 20 weeks of use, the purulent drainage ceased. The pus-filled sinus tracts and redness had resolved, although he still had thickened tissue and scarring where the tracts had been. In time, the scars will usually get flatter and softer.

If the patient’s AC were to flare, another 20-week course of isotretinoin could be prescribed after a 2-month hiatus or he could be switched to a second-line medication. Referral for any cosmetic therapy is typically delayed for another 6 months in case there is a need to treat a recurrence.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient had more than cystic acne; he had acne conglobata. AC is a severe form of inflammatory acne leading to coalescing lesions with purulent sinus tracts under the skin. It can be seen as part of the follicular tetrad syndrome of cystic acne, hidradenitis suppurativa, dissecting cellulitis, and pilonidal disease. AC is thought to be an elevated tumor necrosis factor (TNF)-alpha response to Propionibacterium acnes (now known as Cutibacterium acnes) that leads to excessive inflammation and sterile abscesses.¹ Acne fulminans (AF) can also manifest as a purulent form of acne, but AF has associated systemic signs and symptoms that include fevers, chills, and malaise.

Due to the depth of the inflammation, AC is treated with systemic medications, most commonly isotretinoin. Isotretinoin can be started at 0.5 mg/kg (divided twice daily to enhance tolerability) and then increased to 1 mg/kg (divided twice daily) for 5 months. There is some variation in dosing regimens in practice; the target goal is 120 to 150 mg/kg over the course of treatment. In AF, the patient is pretreated with systemic steroids, and in AC, some clinicians will even prescribe systemic steroids (prednisone 0.5 mg/kg daily for the first month) along with isotretinoin.

Second-line medications include dapsone (50-150 mg/d).² Case reports describe the successful use of the TNF-alpha antagonist adalimumab, although this is not a usual practice in AC treatment.¹ Note that all of these medications have the potential for severe adverse effects and require laboratory evaluation prior to initiation.

This patient was counseled, prescribed isotretinoin (dose as above), and enrolled in the IPledge prescribing and monitoring system for isotretinoin. At 20 weeks of use, the purulent drainage ceased. The pus-filled sinus tracts and redness had resolved, although he still had thickened tissue and scarring where the tracts had been. In time, the scars will usually get flatter and softer.

If the patient’s AC were to flare, another 20-week course of isotretinoin could be prescribed after a 2-month hiatus or he could be switched to a second-line medication. Referral for any cosmetic therapy is typically delayed for another 6 months in case there is a need to treat a recurrence.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The necrotic eschar on this patient’s thigh is calciphylaxis, also known as calcific uremic arteriolopathy (CUA). Most cases are seen in ESRD and start as painful erythematous, firm lesions that progress to necrotic eschars. Up to 4% of patients with ESRD who are on dialysis develop CUA.¹

The exact pathology of CUA is unknown. Calcification of the arterioles leads to ischemia and necrosis of tissue, which is not limited to the skin and can affect tissue elsewhere (eg, muscles, central nervous system, internal organs).²

Morbidity and mortality of CUA is often due to bacterial infections and sepsis related to the necrotic tissue. CUA can be treated with sodium thiosulfate (25 g in 100 mL of normal saline) infused intravenously during the last 30 minutes of dialysis treatment 3 times per week.³ Sodium thiosulfate (which acts as a calcium binder) and cinacalcet (a calcimimetic that leads to lower parathyroid hormone levels) have been used, but evidence of efficacy is limited. In a multicenter observational study involving 89 patients with chronic kidney disease and CUA, 17% of patients experienced complete wound healing, while 56% died over a median follow-up period of 5.8 months.¹ (No cause of death data were available; sodium thiosulfate and a calcimimetic were the most widely used treatment strategies.) This extrapolated to a mortality rate of 72 patients per 100 individuals over the course of 1 year (the 100 patient-years rate).¹

This patient continued her dialysis regimen and general care. She was seen by the wound care team and treated with topical wound care, including moist dressings for her open lesions. The eschars were not debrided because they showed no sign of active infection. Unfortunately, she was in extremely frail condition and died 1 month after evaluation.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The necrotic eschar on this patient’s thigh is calciphylaxis, also known as calcific uremic arteriolopathy (CUA). Most cases are seen in ESRD and start as painful erythematous, firm lesions that progress to necrotic eschars. Up to 4% of patients with ESRD who are on dialysis develop CUA.¹

The exact pathology of CUA is unknown. Calcification of the arterioles leads to ischemia and necrosis of tissue, which is not limited to the skin and can affect tissue elsewhere (eg, muscles, central nervous system, internal organs).²

Morbidity and mortality of CUA is often due to bacterial infections and sepsis related to the necrotic tissue. CUA can be treated with sodium thiosulfate (25 g in 100 mL of normal saline) infused intravenously during the last 30 minutes of dialysis treatment 3 times per week.³ Sodium thiosulfate (which acts as a calcium binder) and cinacalcet (a calcimimetic that leads to lower parathyroid hormone levels) have been used, but evidence of efficacy is limited. In a multicenter observational study involving 89 patients with chronic kidney disease and CUA, 17% of patients experienced complete wound healing, while 56% died over a median follow-up period of 5.8 months.¹ (No cause of death data were available; sodium thiosulfate and a calcimimetic were the most widely used treatment strategies.) This extrapolated to a mortality rate of 72 patients per 100 individuals over the course of 1 year (the 100 patient-years rate).¹

This patient continued her dialysis regimen and general care. She was seen by the wound care team and treated with topical wound care, including moist dressings for her open lesions. The eschars were not debrided because they showed no sign of active infection. Unfortunately, she was in extremely frail condition and died 1 month after evaluation.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The necrotic eschar on this patient’s thigh is calciphylaxis, also known as calcific uremic arteriolopathy (CUA). Most cases are seen in ESRD and start as painful erythematous, firm lesions that progress to necrotic eschars. Up to 4% of patients with ESRD who are on dialysis develop CUA.¹

The exact pathology of CUA is unknown. Calcification of the arterioles leads to ischemia and necrosis of tissue, which is not limited to the skin and can affect tissue elsewhere (eg, muscles, central nervous system, internal organs).²

Morbidity and mortality of CUA is often due to bacterial infections and sepsis related to the necrotic tissue. CUA can be treated with sodium thiosulfate (25 g in 100 mL of normal saline) infused intravenously during the last 30 minutes of dialysis treatment 3 times per week.³ Sodium thiosulfate (which acts as a calcium binder) and cinacalcet (a calcimimetic that leads to lower parathyroid hormone levels) have been used, but evidence of efficacy is limited. In a multicenter observational study involving 89 patients with chronic kidney disease and CUA, 17% of patients experienced complete wound healing, while 56% died over a median follow-up period of 5.8 months.¹ (No cause of death data were available; sodium thiosulfate and a calcimimetic were the most widely used treatment strategies.) This extrapolated to a mortality rate of 72 patients per 100 individuals over the course of 1 year (the 100 patient-years rate).¹

This patient continued her dialysis regimen and general care. She was seen by the wound care team and treated with topical wound care, including moist dressings for her open lesions. The eschars were not debrided because they showed no sign of active infection. Unfortunately, she was in extremely frail condition and died 1 month after evaluation.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Despite the recent uptick in leprosy cases in Central Florida, the disease is very rare, and casual contact with an infected person is likely to not result in transmission, according to Jose A. Lucar, MD.

“Contrary to historical beliefs, leprosy is not highly contagious,” Dr. Lucar, an infectious disease physician and associate professor of medicine at George Washington University, Washington, said in an interview. “For reasons that have to do with the makeup of genes that affect their immune system, most people are not susceptible to acquire leprosy. It’s really a small percentage of the population. It does require prolonged contact with someone with untreated leprosy – over several months – to acquire an infection. So, the risk from any type of casual contact is low.”

Dr. Lucar

According to a research letter published in the CDC’s Emerging Infectious Diseases, the number of reported leprosy cases has more than doubled in the past decade. Of the 159 new cases reported nationwide in 2020, Florida accounted for about one-fifth of cases, with most limited to the central part of the state. “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born," and currently, about one-third of leprosy cases are in individuals born in the United States, he noted.

The research letter described a case of leprosy in a 54-year-old man who worked in landscaping, who sought treatment at a dermatology clinic in Central Florida in 2022 for a painful and progressive erythematous rash. The lesions began on his distal extensor extremities and progressed to involve his trunk and face. According to the report, the man denied any domestic or foreign travel, exposure to armadillos (a known source of transmission), prolonged contact with immigrants from leprosy-endemic countries, or connections with someone known to have leprosy. The authors concluded that the case “adds to the growing body of literature suggesting that central Florida represents an endemic location for leprosy. Travel to this area, even in the absence of other risk factors, should prompt consideration of leprosy in the appropriate clinical context.”

Dr. Lucar said that the mechanism of leprosy transmission is not fully understood, but armadillos, which typically traverse the southern United States, are naturally infected with the bacteria that causes leprosy. “It’s possible that they can spread it to people,” he said. “People who have occupations or hobbies that put them in potential contact with wildlife should avoid any close contact with armadillos. There’s also a discussion of whether [the spike in leprosy cases] may have to do with climate change. That is not yet confirmed. It’s not entirely clear why there’s been a recent rise. It remains an area of investigation.”

Meanwhile, clinicians should keep a high level of suspicion in patients who present with skin lesions compatible with leprosy. “These are typically discolored or numb patches on the skin,” Dr. Lucar said. “This can range from a single or a few lesions to very extensive involvement of the skin. The diminished sensation or loss of sensation within those skin patches is an important sign. There’s a loss of skin color but sometimes they can be reddish.” He emphasized that leprosy “does not spread easily from person to person; casual contact will not spread leprosy. It’s important for the public to understand that.”

Dr. Lucar reported no disclosures.

Despite the recent uptick in leprosy cases in Central Florida, the disease is very rare, and casual contact with an infected person is likely to not result in transmission, according to Jose A. Lucar, MD.

“Contrary to historical beliefs, leprosy is not highly contagious,” Dr. Lucar, an infectious disease physician and associate professor of medicine at George Washington University, Washington, said in an interview. “For reasons that have to do with the makeup of genes that affect their immune system, most people are not susceptible to acquire leprosy. It’s really a small percentage of the population. It does require prolonged contact with someone with untreated leprosy – over several months – to acquire an infection. So, the risk from any type of casual contact is low.”

Dr. Lucar

According to a research letter published in the CDC’s Emerging Infectious Diseases, the number of reported leprosy cases has more than doubled in the past decade. Of the 159 new cases reported nationwide in 2020, Florida accounted for about one-fifth of cases, with most limited to the central part of the state. “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born," and currently, about one-third of leprosy cases are in individuals born in the United States, he noted.

The research letter described a case of leprosy in a 54-year-old man who worked in landscaping, who sought treatment at a dermatology clinic in Central Florida in 2022 for a painful and progressive erythematous rash. The lesions began on his distal extensor extremities and progressed to involve his trunk and face. According to the report, the man denied any domestic or foreign travel, exposure to armadillos (a known source of transmission), prolonged contact with immigrants from leprosy-endemic countries, or connections with someone known to have leprosy. The authors concluded that the case “adds to the growing body of literature suggesting that central Florida represents an endemic location for leprosy. Travel to this area, even in the absence of other risk factors, should prompt consideration of leprosy in the appropriate clinical context.”

Dr. Lucar said that the mechanism of leprosy transmission is not fully understood, but armadillos, which typically traverse the southern United States, are naturally infected with the bacteria that causes leprosy. “It’s possible that they can spread it to people,” he said. “People who have occupations or hobbies that put them in potential contact with wildlife should avoid any close contact with armadillos. There’s also a discussion of whether [the spike in leprosy cases] may have to do with climate change. That is not yet confirmed. It’s not entirely clear why there’s been a recent rise. It remains an area of investigation.”

Meanwhile, clinicians should keep a high level of suspicion in patients who present with skin lesions compatible with leprosy. “These are typically discolored or numb patches on the skin,” Dr. Lucar said. “This can range from a single or a few lesions to very extensive involvement of the skin. The diminished sensation or loss of sensation within those skin patches is an important sign. There’s a loss of skin color but sometimes they can be reddish.” He emphasized that leprosy “does not spread easily from person to person; casual contact will not spread leprosy. It’s important for the public to understand that.”

Dr. Lucar reported no disclosures.

Despite the recent uptick in leprosy cases in Central Florida, the disease is very rare, and casual contact with an infected person is likely to not result in transmission, according to Jose A. Lucar, MD.

“Contrary to historical beliefs, leprosy is not highly contagious,” Dr. Lucar, an infectious disease physician and associate professor of medicine at George Washington University, Washington, said in an interview. “For reasons that have to do with the makeup of genes that affect their immune system, most people are not susceptible to acquire leprosy. It’s really a small percentage of the population. It does require prolonged contact with someone with untreated leprosy – over several months – to acquire an infection. So, the risk from any type of casual contact is low.”

Dr. Lucar

According to a research letter published in the CDC’s Emerging Infectious Diseases, the number of reported leprosy cases has more than doubled in the past decade. Of the 159 new cases reported nationwide in 2020, Florida accounted for about one-fifth of cases, with most limited to the central part of the state. “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born," and currently, about one-third of leprosy cases are in individuals born in the United States, he noted.

The research letter described a case of leprosy in a 54-year-old man who worked in landscaping, who sought treatment at a dermatology clinic in Central Florida in 2022 for a painful and progressive erythematous rash. The lesions began on his distal extensor extremities and progressed to involve his trunk and face. According to the report, the man denied any domestic or foreign travel, exposure to armadillos (a known source of transmission), prolonged contact with immigrants from leprosy-endemic countries, or connections with someone known to have leprosy. The authors concluded that the case “adds to the growing body of literature suggesting that central Florida represents an endemic location for leprosy. Travel to this area, even in the absence of other risk factors, should prompt consideration of leprosy in the appropriate clinical context.”

Dr. Lucar said that the mechanism of leprosy transmission is not fully understood, but armadillos, which typically traverse the southern United States, are naturally infected with the bacteria that causes leprosy. “It’s possible that they can spread it to people,” he said. “People who have occupations or hobbies that put them in potential contact with wildlife should avoid any close contact with armadillos. There’s also a discussion of whether [the spike in leprosy cases] may have to do with climate change. That is not yet confirmed. It’s not entirely clear why there’s been a recent rise. It remains an area of investigation.”

Meanwhile, clinicians should keep a high level of suspicion in patients who present with skin lesions compatible with leprosy. “These are typically discolored or numb patches on the skin,” Dr. Lucar said. “This can range from a single or a few lesions to very extensive involvement of the skin. The diminished sensation or loss of sensation within those skin patches is an important sign. There’s a loss of skin color but sometimes they can be reddish.” He emphasized that leprosy “does not spread easily from person to person; casual contact will not spread leprosy. It’s important for the public to understand that.”

Dr. Lucar reported no disclosures.