Dermatology

Hydrochlorothiazide (HCTZ) is associated with an increased risk of nonmelanoma skin cancer, and patients who take the drug should limit sun exposure and undergo regular skin cancer screening, according to updates to the medication’s label.

The skin cancer risk is small, however, and patients should continue taking HCTZ, a commonly used diuretic and antihypertensive drug, unless their doctor says otherwise, according to a U.S. Food and Drug Administration announcement about the labeling changes, which the agency approved on Aug. 20.

HCTZ, first approved in 1959, is associated with photosensitivity. Researchers identified a relationship between HCTZ and nonmelanoma skin cancer in postmarketing studies. Investigators have described dose-response patterns for basal cell carcinoma and squamous cell carcinoma (SCC).

An FDA analysis found that the risk mostly was increased for SCC. The drug was associated with approximately one additional case of SCC per 16,000 patients per year. For white patients who received a cumulative dose of 50,000 mg or more, the risk was greater. In this patient population, HCTZ was associated with about one additional case of SCC per 6,700 patients per year, according to the label.

Reliably estimating the frequency of nonmelanoma skin cancer and establishing a causal relationship to drug exposure is not possible with the available postmarketing data, the label notes

“Treatment for nonmelanoma skin cancer is typically local and successful, with very low rates of death,” the FDA said. “Meanwhile, the risks of uncontrolled blood pressure can be severe and include life-threatening heart attacks or stroke. Given this information, patients should continue to use HCTZ and take protective skin care measures to reduce their risk of nonmelanoma skin cancer, unless directed otherwise from their health care provider.”

Patients can reduce sun exposure by using broad-spectrum sunscreens with a sun protection factor value of at least 15, limiting time in the sun, and wearing protective clothing, the agency advised.

[email protected]

Hydrochlorothiazide (HCTZ) is associated with an increased risk of nonmelanoma skin cancer, and patients who take the drug should limit sun exposure and undergo regular skin cancer screening, according to updates to the medication’s label.

The skin cancer risk is small, however, and patients should continue taking HCTZ, a commonly used diuretic and antihypertensive drug, unless their doctor says otherwise, according to a U.S. Food and Drug Administration announcement about the labeling changes, which the agency approved on Aug. 20.

HCTZ, first approved in 1959, is associated with photosensitivity. Researchers identified a relationship between HCTZ and nonmelanoma skin cancer in postmarketing studies. Investigators have described dose-response patterns for basal cell carcinoma and squamous cell carcinoma (SCC).

An FDA analysis found that the risk mostly was increased for SCC. The drug was associated with approximately one additional case of SCC per 16,000 patients per year. For white patients who received a cumulative dose of 50,000 mg or more, the risk was greater. In this patient population, HCTZ was associated with about one additional case of SCC per 6,700 patients per year, according to the label.

Reliably estimating the frequency of nonmelanoma skin cancer and establishing a causal relationship to drug exposure is not possible with the available postmarketing data, the label notes

“Treatment for nonmelanoma skin cancer is typically local and successful, with very low rates of death,” the FDA said. “Meanwhile, the risks of uncontrolled blood pressure can be severe and include life-threatening heart attacks or stroke. Given this information, patients should continue to use HCTZ and take protective skin care measures to reduce their risk of nonmelanoma skin cancer, unless directed otherwise from their health care provider.”

Patients can reduce sun exposure by using broad-spectrum sunscreens with a sun protection factor value of at least 15, limiting time in the sun, and wearing protective clothing, the agency advised.

[email protected]

Hydrochlorothiazide (HCTZ) is associated with an increased risk of nonmelanoma skin cancer, and patients who take the drug should limit sun exposure and undergo regular skin cancer screening, according to updates to the medication’s label.

The skin cancer risk is small, however, and patients should continue taking HCTZ, a commonly used diuretic and antihypertensive drug, unless their doctor says otherwise, according to a U.S. Food and Drug Administration announcement about the labeling changes, which the agency approved on Aug. 20.

HCTZ, first approved in 1959, is associated with photosensitivity. Researchers identified a relationship between HCTZ and nonmelanoma skin cancer in postmarketing studies. Investigators have described dose-response patterns for basal cell carcinoma and squamous cell carcinoma (SCC).

An FDA analysis found that the risk mostly was increased for SCC. The drug was associated with approximately one additional case of SCC per 16,000 patients per year. For white patients who received a cumulative dose of 50,000 mg or more, the risk was greater. In this patient population, HCTZ was associated with about one additional case of SCC per 6,700 patients per year, according to the label.

Reliably estimating the frequency of nonmelanoma skin cancer and establishing a causal relationship to drug exposure is not possible with the available postmarketing data, the label notes

“Treatment for nonmelanoma skin cancer is typically local and successful, with very low rates of death,” the FDA said. “Meanwhile, the risks of uncontrolled blood pressure can be severe and include life-threatening heart attacks or stroke. Given this information, patients should continue to use HCTZ and take protective skin care measures to reduce their risk of nonmelanoma skin cancer, unless directed otherwise from their health care provider.”

Patients can reduce sun exposure by using broad-spectrum sunscreens with a sun protection factor value of at least 15, limiting time in the sun, and wearing protective clothing, the agency advised.

[email protected]

While the eroded scabbed area in a raised lesion with pearly borders raised the suspicion of basal cell carcinoma (BCC), a superficial shave biopsy revealed that this was sclerosing basosquamous carcinoma.

Basosquamous carcinoma is an uncommon form of BCC. It features nests/clusters of basaloid cells arising from the basal layer of the epidermis (a hallmark of BCC), as well as keratinization, which is seen in squamous cell carcinoma (SCC). Basosquamous carcinoma occurs in the same areas as more common types of nonmelanoma skin cancers (NMSCs)—that is, sun-exposed areas. Not surprisingly, then, the highest risk areas for basosquamous carcinoma are the face, hands, arms, scalp (in those without hair), and back. People with occupational or intentional sun exposure through tanning have even higher rates of NMSC than the average population; patients using tanning booths exposing their entire bodies warrant more extensive physical exams.

Basosquamous carcinoma is one of the subtypes of BCC that is associated with a higher risk of local invasion, recurrence, and metastasis. Treatment with Mohs micrographic surgery (MMS) reduces the risk of recurrence to 4% (from 12% to 51%). Even with MMS, basosquamous carcinoma can be particularly challenging. It may require additional excision stages, as well as a larger than anticipated excision size at the time of surgery.

In this case, the patient was referred for MMS due to the high-risk nature of this lesion.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

While the eroded scabbed area in a raised lesion with pearly borders raised the suspicion of basal cell carcinoma (BCC), a superficial shave biopsy revealed that this was sclerosing basosquamous carcinoma.

Basosquamous carcinoma is an uncommon form of BCC. It features nests/clusters of basaloid cells arising from the basal layer of the epidermis (a hallmark of BCC), as well as keratinization, which is seen in squamous cell carcinoma (SCC). Basosquamous carcinoma occurs in the same areas as more common types of nonmelanoma skin cancers (NMSCs)—that is, sun-exposed areas. Not surprisingly, then, the highest risk areas for basosquamous carcinoma are the face, hands, arms, scalp (in those without hair), and back. People with occupational or intentional sun exposure through tanning have even higher rates of NMSC than the average population; patients using tanning booths exposing their entire bodies warrant more extensive physical exams.

Basosquamous carcinoma is one of the subtypes of BCC that is associated with a higher risk of local invasion, recurrence, and metastasis. Treatment with Mohs micrographic surgery (MMS) reduces the risk of recurrence to 4% (from 12% to 51%). Even with MMS, basosquamous carcinoma can be particularly challenging. It may require additional excision stages, as well as a larger than anticipated excision size at the time of surgery.

In this case, the patient was referred for MMS due to the high-risk nature of this lesion.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

While the eroded scabbed area in a raised lesion with pearly borders raised the suspicion of basal cell carcinoma (BCC), a superficial shave biopsy revealed that this was sclerosing basosquamous carcinoma.

Basosquamous carcinoma is an uncommon form of BCC. It features nests/clusters of basaloid cells arising from the basal layer of the epidermis (a hallmark of BCC), as well as keratinization, which is seen in squamous cell carcinoma (SCC). Basosquamous carcinoma occurs in the same areas as more common types of nonmelanoma skin cancers (NMSCs)—that is, sun-exposed areas. Not surprisingly, then, the highest risk areas for basosquamous carcinoma are the face, hands, arms, scalp (in those without hair), and back. People with occupational or intentional sun exposure through tanning have even higher rates of NMSC than the average population; patients using tanning booths exposing their entire bodies warrant more extensive physical exams.

Basosquamous carcinoma is one of the subtypes of BCC that is associated with a higher risk of local invasion, recurrence, and metastasis. Treatment with Mohs micrographic surgery (MMS) reduces the risk of recurrence to 4% (from 12% to 51%). Even with MMS, basosquamous carcinoma can be particularly challenging. It may require additional excision stages, as well as a larger than anticipated excision size at the time of surgery.

In this case, the patient was referred for MMS due to the high-risk nature of this lesion.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

For patients with chronic leg edema and recurrent cellulitis, risk for future cellulitis is reduced by 77% by wearing compression stockings or wraps, researchers report. The effect was so striking that the randomized controlled trial was stopped early and all patients in the study were given the therapy.

“In a climate of increasing antibiotic resistance, we are delighted to have discovered a nondrug management strategy that has such a dramatic impact on the risk of cellulitis,” senior author Bernie Bissett, PhD, from the Discipline of Physiotherapy, Faculty of Health, the University of Canberra, Australia, said in an interview.

“We hope this leads to a shift in preventative medical strategy for patients with chronic edema and cellulitis around the world,” she said.

Lead author Elizabeth Webb, MPH, from the Physiotherapy Department at Calvary Public Hospital Bruce, in Bruce, Australia, and colleagues report their findings in an article published online August 12 in The New England Journal of Medicine.

Dr. Bisset explained that Webb is a “leading lymphedema physiotherapist” and a PhD candidate at the University of Canberra. She added that this is the first study to show that “compression therapy dramatically reduces the risk of cellulitis for patients with chronic edema.”

Penicillin is often given preventively; some research suggests effectiveness wanes after the antibiotic is stopped.

For the current trial, Ms. Webb and colleagues enrolled 84 adults with chronic edema of the leg and recurrent cellulitis. They randomly assigned patients in a 1:1 ratio to receive leg compression therapy plus education about preventing cellulitis (compression group; n = 41) or education only (control group; n = 43).

Compression therapy consisted of wearing knee-high stockings that applied maximum compression at the ankles. The compression gradually decreased up the legs. In addition, 26 patients were treated with “therapist-applied compression bandaging” for 3 to 5 days before receiving the stockings.

Participants underwent follow-up assessments every 6 months for a maximum of 3 years or until 45 episodes of cellulitis, the primary outcome, occurred. Those in the control group crossed over to the compression group once they experienced cellulitis.

The trial was stopped early for reasons of efficacy. “The statistical analysis plan prespecified that after 23 episodes of cellulitis had occurred, an independent data monitoring committee would review the results of the interim analysis and recommend whether the trial should stop early,” the authors write.

At the time of the monitoring committee’s review, six patients (15%) who wore compression stockings and 17 (40%) in the control group had experienced a cellulitis episode (hazard ratio, 0.23; P = .002; relative risk [post hoc analysis], 0.37; P = .02). On the basis of those findings, the researchers stopped the study, and patients in the control group were started on compression therapy.

“Clinicians should definitely consider referring their patients to a skilled lymphedema therapist who can individually prescribe and fit compression garments,” Dr. Bissett said. “In our study, these were well tolerated and reduced the risk of another episode of cellulitis by a huge 77%,” she added.

Secondary outcomes included hospitalization related to cellulitis and quality-of-life assessments.

Three patients (7%) in the compression group and six (14%) in the control group were admitted to the hospital for cellulitis (hazard ratio, 0.38). There were no differences in quality of life outcomes between the treatment groups.

The authors say compression therapy has the potential to decrease cellulitis risk by reducing edema, boosting immune response and skin integrity, and protecting the skin.

“Patients with a history of leg swelling (chronic edema) and previous episodes of cellulitis are ideal candidates for this compression therapy,” Dr. Bissett said.

“Given the lack of side effects of the therapy in our study and the potential to reduce other skin problems in these patients, compression therapy is an ideal prophylactic strategy,” she said.

The authors note several study limitations, including a lack of blinding. In addition, patients in the study had to have access to lymphedema specialists, who might be unavailable to patients outside the study. This could have influenced adherence and limit generalizability. Difficulty putting on and taking off compression garments often leads patients to be less adherent to compression therapy, but 88% of patients in this study wore them at least 4 days per week.

Dr. Bissett said compression therapy would be useful for primary care physicians to consider for patients with chronic edema.

“Primary care physicians are highly likely to encounter patients with chronic edema in their day-to-day practice. We can now confidently say that referral to lymphedema therapists for compression therapy should be a first line of defense against future episodes of cellulitis in this vulnerable patient group,” she explained.

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with chronic leg edema and recurrent cellulitis, risk for future cellulitis is reduced by 77% by wearing compression stockings or wraps, researchers report. The effect was so striking that the randomized controlled trial was stopped early and all patients in the study were given the therapy.

“In a climate of increasing antibiotic resistance, we are delighted to have discovered a nondrug management strategy that has such a dramatic impact on the risk of cellulitis,” senior author Bernie Bissett, PhD, from the Discipline of Physiotherapy, Faculty of Health, the University of Canberra, Australia, said in an interview.

“We hope this leads to a shift in preventative medical strategy for patients with chronic edema and cellulitis around the world,” she said.

Lead author Elizabeth Webb, MPH, from the Physiotherapy Department at Calvary Public Hospital Bruce, in Bruce, Australia, and colleagues report their findings in an article published online August 12 in The New England Journal of Medicine.

Dr. Bisset explained that Webb is a “leading lymphedema physiotherapist” and a PhD candidate at the University of Canberra. She added that this is the first study to show that “compression therapy dramatically reduces the risk of cellulitis for patients with chronic edema.”

Penicillin is often given preventively; some research suggests effectiveness wanes after the antibiotic is stopped.

For the current trial, Ms. Webb and colleagues enrolled 84 adults with chronic edema of the leg and recurrent cellulitis. They randomly assigned patients in a 1:1 ratio to receive leg compression therapy plus education about preventing cellulitis (compression group; n = 41) or education only (control group; n = 43).

Compression therapy consisted of wearing knee-high stockings that applied maximum compression at the ankles. The compression gradually decreased up the legs. In addition, 26 patients were treated with “therapist-applied compression bandaging” for 3 to 5 days before receiving the stockings.

Participants underwent follow-up assessments every 6 months for a maximum of 3 years or until 45 episodes of cellulitis, the primary outcome, occurred. Those in the control group crossed over to the compression group once they experienced cellulitis.

The trial was stopped early for reasons of efficacy. “The statistical analysis plan prespecified that after 23 episodes of cellulitis had occurred, an independent data monitoring committee would review the results of the interim analysis and recommend whether the trial should stop early,” the authors write.

At the time of the monitoring committee’s review, six patients (15%) who wore compression stockings and 17 (40%) in the control group had experienced a cellulitis episode (hazard ratio, 0.23; P = .002; relative risk [post hoc analysis], 0.37; P = .02). On the basis of those findings, the researchers stopped the study, and patients in the control group were started on compression therapy.

“Clinicians should definitely consider referring their patients to a skilled lymphedema therapist who can individually prescribe and fit compression garments,” Dr. Bissett said. “In our study, these were well tolerated and reduced the risk of another episode of cellulitis by a huge 77%,” she added.

Secondary outcomes included hospitalization related to cellulitis and quality-of-life assessments.

Three patients (7%) in the compression group and six (14%) in the control group were admitted to the hospital for cellulitis (hazard ratio, 0.38). There were no differences in quality of life outcomes between the treatment groups.

The authors say compression therapy has the potential to decrease cellulitis risk by reducing edema, boosting immune response and skin integrity, and protecting the skin.

“Patients with a history of leg swelling (chronic edema) and previous episodes of cellulitis are ideal candidates for this compression therapy,” Dr. Bissett said.

“Given the lack of side effects of the therapy in our study and the potential to reduce other skin problems in these patients, compression therapy is an ideal prophylactic strategy,” she said.

The authors note several study limitations, including a lack of blinding. In addition, patients in the study had to have access to lymphedema specialists, who might be unavailable to patients outside the study. This could have influenced adherence and limit generalizability. Difficulty putting on and taking off compression garments often leads patients to be less adherent to compression therapy, but 88% of patients in this study wore them at least 4 days per week.

Dr. Bissett said compression therapy would be useful for primary care physicians to consider for patients with chronic edema.

“Primary care physicians are highly likely to encounter patients with chronic edema in their day-to-day practice. We can now confidently say that referral to lymphedema therapists for compression therapy should be a first line of defense against future episodes of cellulitis in this vulnerable patient group,” she explained.

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with chronic leg edema and recurrent cellulitis, risk for future cellulitis is reduced by 77% by wearing compression stockings or wraps, researchers report. The effect was so striking that the randomized controlled trial was stopped early and all patients in the study were given the therapy.

“In a climate of increasing antibiotic resistance, we are delighted to have discovered a nondrug management strategy that has such a dramatic impact on the risk of cellulitis,” senior author Bernie Bissett, PhD, from the Discipline of Physiotherapy, Faculty of Health, the University of Canberra, Australia, said in an interview.

“We hope this leads to a shift in preventative medical strategy for patients with chronic edema and cellulitis around the world,” she said.

Lead author Elizabeth Webb, MPH, from the Physiotherapy Department at Calvary Public Hospital Bruce, in Bruce, Australia, and colleagues report their findings in an article published online August 12 in The New England Journal of Medicine.

Dr. Bisset explained that Webb is a “leading lymphedema physiotherapist” and a PhD candidate at the University of Canberra. She added that this is the first study to show that “compression therapy dramatically reduces the risk of cellulitis for patients with chronic edema.”

Penicillin is often given preventively; some research suggests effectiveness wanes after the antibiotic is stopped.

For the current trial, Ms. Webb and colleagues enrolled 84 adults with chronic edema of the leg and recurrent cellulitis. They randomly assigned patients in a 1:1 ratio to receive leg compression therapy plus education about preventing cellulitis (compression group; n = 41) or education only (control group; n = 43).

Compression therapy consisted of wearing knee-high stockings that applied maximum compression at the ankles. The compression gradually decreased up the legs. In addition, 26 patients were treated with “therapist-applied compression bandaging” for 3 to 5 days before receiving the stockings.

Participants underwent follow-up assessments every 6 months for a maximum of 3 years or until 45 episodes of cellulitis, the primary outcome, occurred. Those in the control group crossed over to the compression group once they experienced cellulitis.

The trial was stopped early for reasons of efficacy. “The statistical analysis plan prespecified that after 23 episodes of cellulitis had occurred, an independent data monitoring committee would review the results of the interim analysis and recommend whether the trial should stop early,” the authors write.

At the time of the monitoring committee’s review, six patients (15%) who wore compression stockings and 17 (40%) in the control group had experienced a cellulitis episode (hazard ratio, 0.23; P = .002; relative risk [post hoc analysis], 0.37; P = .02). On the basis of those findings, the researchers stopped the study, and patients in the control group were started on compression therapy.

“Clinicians should definitely consider referring their patients to a skilled lymphedema therapist who can individually prescribe and fit compression garments,” Dr. Bissett said. “In our study, these were well tolerated and reduced the risk of another episode of cellulitis by a huge 77%,” she added.

Secondary outcomes included hospitalization related to cellulitis and quality-of-life assessments.

Three patients (7%) in the compression group and six (14%) in the control group were admitted to the hospital for cellulitis (hazard ratio, 0.38). There were no differences in quality of life outcomes between the treatment groups.

The authors say compression therapy has the potential to decrease cellulitis risk by reducing edema, boosting immune response and skin integrity, and protecting the skin.

“Patients with a history of leg swelling (chronic edema) and previous episodes of cellulitis are ideal candidates for this compression therapy,” Dr. Bissett said.

“Given the lack of side effects of the therapy in our study and the potential to reduce other skin problems in these patients, compression therapy is an ideal prophylactic strategy,” she said.

The authors note several study limitations, including a lack of blinding. In addition, patients in the study had to have access to lymphedema specialists, who might be unavailable to patients outside the study. This could have influenced adherence and limit generalizability. Difficulty putting on and taking off compression garments often leads patients to be less adherent to compression therapy, but 88% of patients in this study wore them at least 4 days per week.

Dr. Bissett said compression therapy would be useful for primary care physicians to consider for patients with chronic edema.

“Primary care physicians are highly likely to encounter patients with chronic edema in their day-to-day practice. We can now confidently say that referral to lymphedema therapists for compression therapy should be a first line of defense against future episodes of cellulitis in this vulnerable patient group,” she explained.

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The patient was diagnosed with idiopathic facial aseptic granuloma (IFAG) based on the clinical findings, as well as the associated history of chalazia and erythematous papules seen in childhood rosacea.

She was treated with several months of azithromycin, sulfur wash, and metronidazole cream with improvement of some of the smaller lesions but no change on the larger nodules. Later she was treated with oral and topical ivermectin with no improvement. Some of the nodules slowly resolved except for the larger lesion on the right cheek. She was later treated with a 6-week course of clarithromycin with partial improvement of the nodule. The lesion resolved after 2 months of stopping clarithromycin.

IFAG is a rare condition seen in prepubescent children. The etiology of this condition is not well understood and is thought to be on the spectrum of childhood rosacea.¹ From several recent reports, IFAG usually is seen in children with associated conditions including chalazia, conjunctivitis, blepharitis, and telangiectasias, which can be seen in patients with rosacea. These associated findings suggest the possibility of IFAG being a form of granulomatous rosacea in children. Our patient presented with several lesions on the cheek and had a previous history of recurrent chalazia.

This condition presents in childhood between the ages of 8 months and 13 years. Most of the cases occur in toddlers, and girls appear to be more affected than boys. The lesions appear as pink, rubbery, nontender, nonfluctuant nodules on the cheeks, which can be single or multiple. A large prospective study in 30 children demonstrated that more 70% of the lesions cultured were negative for bacteria. Histologic analysis of some of the lesions showed a chronic dermal lymphohistiocytic granulomatous perifollicular infiltrate with numerous foreign body–type giant cells.²

The differential diagnosis of these lesions should include infectious pyodermas such as mycobacterial infections, cutaneous leishmaniasis, and botryomycosis; deep fungal infections such as sporotrichosis, coccidioidomycosis, and cryptococcosis; childhood nodulocystic acne; pilomatrixoma; epidermoid cyst; vascular tumors or malformations; and leukemia cutis.³

The diagnosis is usually clinical but in atypical cases a skin biopsy with tissue cultures should be performed. The decision to biopsy these lesions will need to be done in a one by one basis, as a biopsy may leave scaring on the area affected.

It has been postulated that a color Doppler ultrasound of the lesion may be a helpful ancillary study. Echographic findings show a well demarcated solid-cystic, hypoechoic dermal lesion, the largest axis of which lies parallel to the skin surface. The lesion lacks calcium deposits. Other findings include increased echogenicity of the underlaying hypodermis. The findings may vary depending on the stage of the lesion.⁴

The course of the condition may last on average months to years. Some lesions resolve spontaneously and others may respond to courses of oral antibiotics such as clarithromycin, azithromycin, or ivermectin. In our patient, several lesions improved with oral antibiotics, but the larger lesions were more persistent and resolved after a year.

The lesions usually resolve without scarring. In those patients with associated rosacea, maintenance topical treatments may be warranted and also may need follow-up with ophthalmology because they tend to commonly have ocular rosacea as well.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Pediatr Dermatol. 2013 Jan-Feb;30(1):109-11.

2. Br J Dermatol. 2007 Apr;156(4):705-8.

3. Pediatr Dermatol. 2018 Jul;35(4):490-3.

4. Actas Dermosifiliogr. 2019 Oct;110(8):637-41.

The patient was diagnosed with idiopathic facial aseptic granuloma (IFAG) based on the clinical findings, as well as the associated history of chalazia and erythematous papules seen in childhood rosacea.

She was treated with several months of azithromycin, sulfur wash, and metronidazole cream with improvement of some of the smaller lesions but no change on the larger nodules. Later she was treated with oral and topical ivermectin with no improvement. Some of the nodules slowly resolved except for the larger lesion on the right cheek. She was later treated with a 6-week course of clarithromycin with partial improvement of the nodule. The lesion resolved after 2 months of stopping clarithromycin.

IFAG is a rare condition seen in prepubescent children. The etiology of this condition is not well understood and is thought to be on the spectrum of childhood rosacea.¹ From several recent reports, IFAG usually is seen in children with associated conditions including chalazia, conjunctivitis, blepharitis, and telangiectasias, which can be seen in patients with rosacea. These associated findings suggest the possibility of IFAG being a form of granulomatous rosacea in children. Our patient presented with several lesions on the cheek and had a previous history of recurrent chalazia.

This condition presents in childhood between the ages of 8 months and 13 years. Most of the cases occur in toddlers, and girls appear to be more affected than boys. The lesions appear as pink, rubbery, nontender, nonfluctuant nodules on the cheeks, which can be single or multiple. A large prospective study in 30 children demonstrated that more 70% of the lesions cultured were negative for bacteria. Histologic analysis of some of the lesions showed a chronic dermal lymphohistiocytic granulomatous perifollicular infiltrate with numerous foreign body–type giant cells.²

The differential diagnosis of these lesions should include infectious pyodermas such as mycobacterial infections, cutaneous leishmaniasis, and botryomycosis; deep fungal infections such as sporotrichosis, coccidioidomycosis, and cryptococcosis; childhood nodulocystic acne; pilomatrixoma; epidermoid cyst; vascular tumors or malformations; and leukemia cutis.³

The diagnosis is usually clinical but in atypical cases a skin biopsy with tissue cultures should be performed. The decision to biopsy these lesions will need to be done in a one by one basis, as a biopsy may leave scaring on the area affected.

It has been postulated that a color Doppler ultrasound of the lesion may be a helpful ancillary study. Echographic findings show a well demarcated solid-cystic, hypoechoic dermal lesion, the largest axis of which lies parallel to the skin surface. The lesion lacks calcium deposits. Other findings include increased echogenicity of the underlaying hypodermis. The findings may vary depending on the stage of the lesion.⁴

The course of the condition may last on average months to years. Some lesions resolve spontaneously and others may respond to courses of oral antibiotics such as clarithromycin, azithromycin, or ivermectin. In our patient, several lesions improved with oral antibiotics, but the larger lesions were more persistent and resolved after a year.

The lesions usually resolve without scarring. In those patients with associated rosacea, maintenance topical treatments may be warranted and also may need follow-up with ophthalmology because they tend to commonly have ocular rosacea as well.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Pediatr Dermatol. 2013 Jan-Feb;30(1):109-11.

2. Br J Dermatol. 2007 Apr;156(4):705-8.

3. Pediatr Dermatol. 2018 Jul;35(4):490-3.

4. Actas Dermosifiliogr. 2019 Oct;110(8):637-41.

The patient was diagnosed with idiopathic facial aseptic granuloma (IFAG) based on the clinical findings, as well as the associated history of chalazia and erythematous papules seen in childhood rosacea.

She was treated with several months of azithromycin, sulfur wash, and metronidazole cream with improvement of some of the smaller lesions but no change on the larger nodules. Later she was treated with oral and topical ivermectin with no improvement. Some of the nodules slowly resolved except for the larger lesion on the right cheek. She was later treated with a 6-week course of clarithromycin with partial improvement of the nodule. The lesion resolved after 2 months of stopping clarithromycin.

IFAG is a rare condition seen in prepubescent children. The etiology of this condition is not well understood and is thought to be on the spectrum of childhood rosacea.¹ From several recent reports, IFAG usually is seen in children with associated conditions including chalazia, conjunctivitis, blepharitis, and telangiectasias, which can be seen in patients with rosacea. These associated findings suggest the possibility of IFAG being a form of granulomatous rosacea in children. Our patient presented with several lesions on the cheek and had a previous history of recurrent chalazia.

This condition presents in childhood between the ages of 8 months and 13 years. Most of the cases occur in toddlers, and girls appear to be more affected than boys. The lesions appear as pink, rubbery, nontender, nonfluctuant nodules on the cheeks, which can be single or multiple. A large prospective study in 30 children demonstrated that more 70% of the lesions cultured were negative for bacteria. Histologic analysis of some of the lesions showed a chronic dermal lymphohistiocytic granulomatous perifollicular infiltrate with numerous foreign body–type giant cells.²

The differential diagnosis of these lesions should include infectious pyodermas such as mycobacterial infections, cutaneous leishmaniasis, and botryomycosis; deep fungal infections such as sporotrichosis, coccidioidomycosis, and cryptococcosis; childhood nodulocystic acne; pilomatrixoma; epidermoid cyst; vascular tumors or malformations; and leukemia cutis.³

The diagnosis is usually clinical but in atypical cases a skin biopsy with tissue cultures should be performed. The decision to biopsy these lesions will need to be done in a one by one basis, as a biopsy may leave scaring on the area affected.

It has been postulated that a color Doppler ultrasound of the lesion may be a helpful ancillary study. Echographic findings show a well demarcated solid-cystic, hypoechoic dermal lesion, the largest axis of which lies parallel to the skin surface. The lesion lacks calcium deposits. Other findings include increased echogenicity of the underlaying hypodermis. The findings may vary depending on the stage of the lesion.⁴

The course of the condition may last on average months to years. Some lesions resolve spontaneously and others may respond to courses of oral antibiotics such as clarithromycin, azithromycin, or ivermectin. In our patient, several lesions improved with oral antibiotics, but the larger lesions were more persistent and resolved after a year.

The lesions usually resolve without scarring. In those patients with associated rosacea, maintenance topical treatments may be warranted and also may need follow-up with ophthalmology because they tend to commonly have ocular rosacea as well.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Pediatr Dermatol. 2013 Jan-Feb;30(1):109-11.

2. Br J Dermatol. 2007 Apr;156(4):705-8.

3. Pediatr Dermatol. 2018 Jul;35(4):490-3.

4. Actas Dermosifiliogr. 2019 Oct;110(8):637-41.

ANSWER

The correct answer is all the above (choice “e”).

DISCUSSION

The differential for round or annular, scaly lesions is lengthy. In addition to all 4 conditions listed above, it includes eczema, basal cell carcinoma, and irritant or contact dermatitis.

With this patient’s history, the diagnosis of fungal infection was not unreasonable. However, the total lack of response to antifungal treatment—along with a negative KOH prep—made that diagnosis questionable at best. Then there was the lack of lymphadenopathy, which would almost certainly have been present with such longstanding infection. Given her country of origin, cutaneous New World leishmaniasis (caused by a protozoan delivered to the patient by an insect vector) was a possibility.

For this patient, skin biopsy with a 4-mm punch was the only way to establish the correct diagnosis. The defect from the biopsy was closed with 5-0 nylon sutures to minimize scarring.

The pathological findings included interface dermatitis, apoptotic keratinocytes, and a brisk periadnexal lymphocytic infiltrate, which—given the morphological and historical context—were entirely consistent with discoid lupus erythematosus (DLE; otherwise known as subacute cutaneous lupus erythematosus). Subsequent bloodwork failed to show any connection with systemic lupus erythematosus (SLE), which is not surprising because only about 18% of DLE cases evolve into SLE.

DLE is more common in women, especially in those with skin of color. The associated lesions are seldom as impressive as this patient’s, manifesting as papulosquamous patches typically found on the ears, neck, face, arms, and other sun-exposed areas. Indeed, it appears that sun exposure is a major trigger for the disease—a clue that can assist with the diagnosis.

TREATMENT

In addition to proscribing excessive sun exposure, providers should encourage the use of sunscreen. DLE is often treated with topical steroids. More advanced cases, such as this patient’s, may require oral hydroxychloroquine (200 mg bid). Though these treatments are effective in most cases, DLE can leave serious scarring and/or discoloration, especially in those with darker skin.

ANSWER

The correct answer is all the above (choice “e”).

DISCUSSION

The differential for round or annular, scaly lesions is lengthy. In addition to all 4 conditions listed above, it includes eczema, basal cell carcinoma, and irritant or contact dermatitis.

With this patient’s history, the diagnosis of fungal infection was not unreasonable. However, the total lack of response to antifungal treatment—along with a negative KOH prep—made that diagnosis questionable at best. Then there was the lack of lymphadenopathy, which would almost certainly have been present with such longstanding infection. Given her country of origin, cutaneous New World leishmaniasis (caused by a protozoan delivered to the patient by an insect vector) was a possibility.

For this patient, skin biopsy with a 4-mm punch was the only way to establish the correct diagnosis. The defect from the biopsy was closed with 5-0 nylon sutures to minimize scarring.

The pathological findings included interface dermatitis, apoptotic keratinocytes, and a brisk periadnexal lymphocytic infiltrate, which—given the morphological and historical context—were entirely consistent with discoid lupus erythematosus (DLE; otherwise known as subacute cutaneous lupus erythematosus). Subsequent bloodwork failed to show any connection with systemic lupus erythematosus (SLE), which is not surprising because only about 18% of DLE cases evolve into SLE.

DLE is more common in women, especially in those with skin of color. The associated lesions are seldom as impressive as this patient’s, manifesting as papulosquamous patches typically found on the ears, neck, face, arms, and other sun-exposed areas. Indeed, it appears that sun exposure is a major trigger for the disease—a clue that can assist with the diagnosis.

TREATMENT

In addition to proscribing excessive sun exposure, providers should encourage the use of sunscreen. DLE is often treated with topical steroids. More advanced cases, such as this patient’s, may require oral hydroxychloroquine (200 mg bid). Though these treatments are effective in most cases, DLE can leave serious scarring and/or discoloration, especially in those with darker skin.

ANSWER

The correct answer is all the above (choice “e”).

DISCUSSION

The differential for round or annular, scaly lesions is lengthy. In addition to all 4 conditions listed above, it includes eczema, basal cell carcinoma, and irritant or contact dermatitis.

With this patient’s history, the diagnosis of fungal infection was not unreasonable. However, the total lack of response to antifungal treatment—along with a negative KOH prep—made that diagnosis questionable at best. Then there was the lack of lymphadenopathy, which would almost certainly have been present with such longstanding infection. Given her country of origin, cutaneous New World leishmaniasis (caused by a protozoan delivered to the patient by an insect vector) was a possibility.

For this patient, skin biopsy with a 4-mm punch was the only way to establish the correct diagnosis. The defect from the biopsy was closed with 5-0 nylon sutures to minimize scarring.

The pathological findings included interface dermatitis, apoptotic keratinocytes, and a brisk periadnexal lymphocytic infiltrate, which—given the morphological and historical context—were entirely consistent with discoid lupus erythematosus (DLE; otherwise known as subacute cutaneous lupus erythematosus). Subsequent bloodwork failed to show any connection with systemic lupus erythematosus (SLE), which is not surprising because only about 18% of DLE cases evolve into SLE.

DLE is more common in women, especially in those with skin of color. The associated lesions are seldom as impressive as this patient’s, manifesting as papulosquamous patches typically found on the ears, neck, face, arms, and other sun-exposed areas. Indeed, it appears that sun exposure is a major trigger for the disease—a clue that can assist with the diagnosis.

TREATMENT

In addition to proscribing excessive sun exposure, providers should encourage the use of sunscreen. DLE is often treated with topical steroids. More advanced cases, such as this patient’s, may require oral hydroxychloroquine (200 mg bid). Though these treatments are effective in most cases, DLE can leave serious scarring and/or discoloration, especially in those with darker skin.

This pink raised nodule underlying a scaly surface was suspicious for squamous cell carcinoma (SCC). Since this was a virtual visit, and the lesion required pathology due to the likelihood of cancer, the patient was brought into the clinic for additional evaluation. A broad-based deep shave biopsy was performed to remove the visible lesion. Pathology showed SCC in situ, with borders uninvolved.

Patients who have had AKs are extremely likely to develop additional AKs. A notable percentage of AKs will, over time, develop into SCC in situ and then invasive SCC if not treated. While cryosurgery of an SK should not result in SCC, it’s most likely that in this case, an AK adjacent to the SK progressed to the SCC in situ.

There are multiple treatments available for SCC in situ. Topical imiquimod has been shown to be somewhat effective in stimulating the immune system, thus leading to resolution of SCC in situ. But there is a significant risk of recurrence. Topical 5-FU can be utilized on a daily or twice daily basis for 2 weeks (or up to several months). The risk of recurrence ranges from 7% to 33%. Electrodesiccation and curettage is often used for SCC in situ, with recurrence rates of 2% to 19%. Cryosurgery for SCC in situ requires an aggressive freeze, with freeze times of up to 30 seconds. Photodynamic therapy also is an option; however, it requires multiple sessions and is more costly than other treatment options.

This patient’s borders were uninvolved on pathology, but it was possible that there was some residual SCC in situ due to the standard “bread loaf slicing” used for routine pathology. To treat possible residual SCC in situ at the wound site and surrounding tissue, the patient was given a prescription for topical 5-FU to apply twice daily for 6 weeks. The patient was instructed to return for follow-up in 6 months, or sooner, if any problems arose.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This pink raised nodule underlying a scaly surface was suspicious for squamous cell carcinoma (SCC). Since this was a virtual visit, and the lesion required pathology due to the likelihood of cancer, the patient was brought into the clinic for additional evaluation. A broad-based deep shave biopsy was performed to remove the visible lesion. Pathology showed SCC in situ, with borders uninvolved.

Patients who have had AKs are extremely likely to develop additional AKs. A notable percentage of AKs will, over time, develop into SCC in situ and then invasive SCC if not treated. While cryosurgery of an SK should not result in SCC, it’s most likely that in this case, an AK adjacent to the SK progressed to the SCC in situ.

There are multiple treatments available for SCC in situ. Topical imiquimod has been shown to be somewhat effective in stimulating the immune system, thus leading to resolution of SCC in situ. But there is a significant risk of recurrence. Topical 5-FU can be utilized on a daily or twice daily basis for 2 weeks (or up to several months). The risk of recurrence ranges from 7% to 33%. Electrodesiccation and curettage is often used for SCC in situ, with recurrence rates of 2% to 19%. Cryosurgery for SCC in situ requires an aggressive freeze, with freeze times of up to 30 seconds. Photodynamic therapy also is an option; however, it requires multiple sessions and is more costly than other treatment options.

This patient’s borders were uninvolved on pathology, but it was possible that there was some residual SCC in situ due to the standard “bread loaf slicing” used for routine pathology. To treat possible residual SCC in situ at the wound site and surrounding tissue, the patient was given a prescription for topical 5-FU to apply twice daily for 6 weeks. The patient was instructed to return for follow-up in 6 months, or sooner, if any problems arose.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This pink raised nodule underlying a scaly surface was suspicious for squamous cell carcinoma (SCC). Since this was a virtual visit, and the lesion required pathology due to the likelihood of cancer, the patient was brought into the clinic for additional evaluation. A broad-based deep shave biopsy was performed to remove the visible lesion. Pathology showed SCC in situ, with borders uninvolved.

Patients who have had AKs are extremely likely to develop additional AKs. A notable percentage of AKs will, over time, develop into SCC in situ and then invasive SCC if not treated. While cryosurgery of an SK should not result in SCC, it’s most likely that in this case, an AK adjacent to the SK progressed to the SCC in situ.

There are multiple treatments available for SCC in situ. Topical imiquimod has been shown to be somewhat effective in stimulating the immune system, thus leading to resolution of SCC in situ. But there is a significant risk of recurrence. Topical 5-FU can be utilized on a daily or twice daily basis for 2 weeks (or up to several months). The risk of recurrence ranges from 7% to 33%. Electrodesiccation and curettage is often used for SCC in situ, with recurrence rates of 2% to 19%. Cryosurgery for SCC in situ requires an aggressive freeze, with freeze times of up to 30 seconds. Photodynamic therapy also is an option; however, it requires multiple sessions and is more costly than other treatment options.

This patient’s borders were uninvolved on pathology, but it was possible that there was some residual SCC in situ due to the standard “bread loaf slicing” used for routine pathology. To treat possible residual SCC in situ at the wound site and surrounding tissue, the patient was given a prescription for topical 5-FU to apply twice daily for 6 weeks. The patient was instructed to return for follow-up in 6 months, or sooner, if any problems arose.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

In the clinical experience of Libby Edwards, MD, the diagnosis of lichen sclerosus in a young girl often triggers worry from patients and parents alike.

“The parents are worried about the ramifications of genital diseases and they’re worried about scarring,” she said during the virtual annual meeting of the Society for Pediatric Dermatology.

Meanwhile, during the initial assessment, physicians tend to think about sexual abuse or sexually transmitted diseases as the primary culprit. “It’s really important that you consider those issues, but they’re not usually what’s going on,” said Dr. Edwards, a dermatologist who practices in Charlotte, N.C. “Also, for some reason we jump to yeast as a cause of diseases in the genital area. If the child is out of diapers and hasn’t reached puberty, it’s almost never yeast. Do a culture. Try and prove yeast. If it doesn’t respond to treatment for yeast, it’s not going to be yeast. Reassure, and don’t forget to reassure.”

The causes of lichen sclerosus in young girls are not completely understood, she continued, but a main factor is autoimmune-related, which can cause a distinctive rash that usually affects the genital skin around the vulva and anus. Lichen sclerosus presents classically as white, fragile plaques. “Textbooks say that there is cigarette paper-like crinkling of skin,” Dr. Edwards said. “I think of it being more like cellophane paper. In children, we often see it as smooth, kind of waxy and shiny, compared to adults. Children usually present with pruritus and irritation.”

Lichen sclerosus often starts in the clitoral area and on the perineum, and often with an edematous clitoral hood. “It often eventuates into clitoral phimosis, meaning that there is midline adhesion so that the clitoris is buried,” she said. “In adults, seeing this clitoral phimosis is a reliable sign of a scarring dermatosis – most often lichen sclerosus. But you can’t say that in children, because little girls will often have scarring over the clitoris. It’s just physiologic and means nothing, and it will go away at puberty. Certainly, sometimes this white discoloration can have crinkling. Purpura and tearing are common; if you look at lichen sclerosus histologically it looks like a thin epithelium that’s stretched over gelatin. Any rubbing and scratching can cause bleeding in the skin.”

Clinical appearance of well demarcated white skin with texture change drives the diagnosis. “It can be hard to tell from vitiligo at times, but there always should be texture change – whether it’s crinkling, whether it’s waxy, whether it’s smooth – and it’s symptomatic,” she said.

A biopsy is not usually required. “I think a good picture [of the affected area] or some sort of objective description in the chart is important, because most children do so well that in a few months there’s no sign of it, and the next provider [they see] may not believe that they ever had it,” she said.

The recommended initial treatment for lichen sclerosus in girls is a tiny amount of a superpotent topical corticosteroid ointment such as clobetasol or halobetasol one to two times daily until the skin is clear, which usually takes 2-4 months. “You do not treat these children until they’re comfortable, because that may be a week,” Dr. Edwards said. “You treat these children until the skin looks normal. Then you need to keep treating them, because if you don’t, the skin will relapse, even though they might not have symptoms.”

Following initial treatment, she recommends use of a superpotent corticosteroid once per day three times a week, or a midpotency steroid like triamcinolone ointment 0.1% every day. In her clinical experience, if lesions clear and remain clear with long-term treatment through puberty, the chances are good that they’ll stay clear if the medication is stopped.

“There are no studies on what to do after a patient clears,” said Dr. Edwards, chief of dermatology at Carolinas Medical Center, Charlotte, and adjunct clinical professor of dermatology at the University of North Carolina, Chapel Hill. “We have been informed by trial and error. If a child is totally clear after puberty, I will stop their medication and see them back every 3 months for about a year and a half. If they stay clear after a year and a half, I find that they stay clear. I wonder what happens at menopause. We surely don’t know.”

With consistent topical treatment, many patients will have clearing in one area of affected skin after a month or two, and it will take 3 or 4 months for the remaining area to clear. “I tend to see patients back every 6-8 weeks until they’re clear,” she said. “I do not like the idea of sending people out and saying, ‘use this medication twice a day for a month, then once a day for a month, then three times a week, then as needed.’

For patients concerned about the long-term use of topical steroids, the immunosuppressants tacrolimus and pimecrolimus are options. “They are often irritating on the vulva, but can work better than steroids for extragenital disease,” Dr. Edwards said. “Parents sometimes object to the use of a corticosteroid, but because these produce slower benefit and often burn with application, you can remind the parents that tacrolimus and pimecrolimus are not without side effects and are labeled as being associated with cancer. That often will prompt a parent to be willing to use a topical steroid. You can also point to studies that show the safety of topical steroids.”

Intralesional steroids are useful for thick lesions, but Dr. Edwards said that she has never had to use them in a child with lichen sclerosus. “I have found methotrexate to be useful in some people, but there is not one study on genital lichen sclerosus and methotrexate,” she said. “I find that about one in five patients with recalcitrant vulvar lichen sclerosus has had some benefit from methotrexate,” she added, noting that fractional CO₂ laser “is showing promise in these patients.”

Dr. Edwards concluded her remarks by noting that she has never cared for a child with vulvar lichen sclerosus who didn’t respond to topical super potent steroids, “except due to poor compliance.”

She reported having no relevant financial disclosures.

[email protected]

In the clinical experience of Libby Edwards, MD, the diagnosis of lichen sclerosus in a young girl often triggers worry from patients and parents alike.

“The parents are worried about the ramifications of genital diseases and they’re worried about scarring,” she said during the virtual annual meeting of the Society for Pediatric Dermatology.

Meanwhile, during the initial assessment, physicians tend to think about sexual abuse or sexually transmitted diseases as the primary culprit. “It’s really important that you consider those issues, but they’re not usually what’s going on,” said Dr. Edwards, a dermatologist who practices in Charlotte, N.C. “Also, for some reason we jump to yeast as a cause of diseases in the genital area. If the child is out of diapers and hasn’t reached puberty, it’s almost never yeast. Do a culture. Try and prove yeast. If it doesn’t respond to treatment for yeast, it’s not going to be yeast. Reassure, and don’t forget to reassure.”

The causes of lichen sclerosus in young girls are not completely understood, she continued, but a main factor is autoimmune-related, which can cause a distinctive rash that usually affects the genital skin around the vulva and anus. Lichen sclerosus presents classically as white, fragile plaques. “Textbooks say that there is cigarette paper-like crinkling of skin,” Dr. Edwards said. “I think of it being more like cellophane paper. In children, we often see it as smooth, kind of waxy and shiny, compared to adults. Children usually present with pruritus and irritation.”

Lichen sclerosus often starts in the clitoral area and on the perineum, and often with an edematous clitoral hood. “It often eventuates into clitoral phimosis, meaning that there is midline adhesion so that the clitoris is buried,” she said. “In adults, seeing this clitoral phimosis is a reliable sign of a scarring dermatosis – most often lichen sclerosus. But you can’t say that in children, because little girls will often have scarring over the clitoris. It’s just physiologic and means nothing, and it will go away at puberty. Certainly, sometimes this white discoloration can have crinkling. Purpura and tearing are common; if you look at lichen sclerosus histologically it looks like a thin epithelium that’s stretched over gelatin. Any rubbing and scratching can cause bleeding in the skin.”

Clinical appearance of well demarcated white skin with texture change drives the diagnosis. “It can be hard to tell from vitiligo at times, but there always should be texture change – whether it’s crinkling, whether it’s waxy, whether it’s smooth – and it’s symptomatic,” she said.

A biopsy is not usually required. “I think a good picture [of the affected area] or some sort of objective description in the chart is important, because most children do so well that in a few months there’s no sign of it, and the next provider [they see] may not believe that they ever had it,” she said.

The recommended initial treatment for lichen sclerosus in girls is a tiny amount of a superpotent topical corticosteroid ointment such as clobetasol or halobetasol one to two times daily until the skin is clear, which usually takes 2-4 months. “You do not treat these children until they’re comfortable, because that may be a week,” Dr. Edwards said. “You treat these children until the skin looks normal. Then you need to keep treating them, because if you don’t, the skin will relapse, even though they might not have symptoms.”

Following initial treatment, she recommends use of a superpotent corticosteroid once per day three times a week, or a midpotency steroid like triamcinolone ointment 0.1% every day. In her clinical experience, if lesions clear and remain clear with long-term treatment through puberty, the chances are good that they’ll stay clear if the medication is stopped.

“There are no studies on what to do after a patient clears,” said Dr. Edwards, chief of dermatology at Carolinas Medical Center, Charlotte, and adjunct clinical professor of dermatology at the University of North Carolina, Chapel Hill. “We have been informed by trial and error. If a child is totally clear after puberty, I will stop their medication and see them back every 3 months for about a year and a half. If they stay clear after a year and a half, I find that they stay clear. I wonder what happens at menopause. We surely don’t know.”

With consistent topical treatment, many patients will have clearing in one area of affected skin after a month or two, and it will take 3 or 4 months for the remaining area to clear. “I tend to see patients back every 6-8 weeks until they’re clear,” she said. “I do not like the idea of sending people out and saying, ‘use this medication twice a day for a month, then once a day for a month, then three times a week, then as needed.’

For patients concerned about the long-term use of topical steroids, the immunosuppressants tacrolimus and pimecrolimus are options. “They are often irritating on the vulva, but can work better than steroids for extragenital disease,” Dr. Edwards said. “Parents sometimes object to the use of a corticosteroid, but because these produce slower benefit and often burn with application, you can remind the parents that tacrolimus and pimecrolimus are not without side effects and are labeled as being associated with cancer. That often will prompt a parent to be willing to use a topical steroid. You can also point to studies that show the safety of topical steroids.”

Intralesional steroids are useful for thick lesions, but Dr. Edwards said that she has never had to use them in a child with lichen sclerosus. “I have found methotrexate to be useful in some people, but there is not one study on genital lichen sclerosus and methotrexate,” she said. “I find that about one in five patients with recalcitrant vulvar lichen sclerosus has had some benefit from methotrexate,” she added, noting that fractional CO₂ laser “is showing promise in these patients.”

Dr. Edwards concluded her remarks by noting that she has never cared for a child with vulvar lichen sclerosus who didn’t respond to topical super potent steroids, “except due to poor compliance.”

She reported having no relevant financial disclosures.

[email protected]

In the clinical experience of Libby Edwards, MD, the diagnosis of lichen sclerosus in a young girl often triggers worry from patients and parents alike.

“The parents are worried about the ramifications of genital diseases and they’re worried about scarring,” she said during the virtual annual meeting of the Society for Pediatric Dermatology.

Meanwhile, during the initial assessment, physicians tend to think about sexual abuse or sexually transmitted diseases as the primary culprit. “It’s really important that you consider those issues, but they’re not usually what’s going on,” said Dr. Edwards, a dermatologist who practices in Charlotte, N.C. “Also, for some reason we jump to yeast as a cause of diseases in the genital area. If the child is out of diapers and hasn’t reached puberty, it’s almost never yeast. Do a culture. Try and prove yeast. If it doesn’t respond to treatment for yeast, it’s not going to be yeast. Reassure, and don’t forget to reassure.”

The causes of lichen sclerosus in young girls are not completely understood, she continued, but a main factor is autoimmune-related, which can cause a distinctive rash that usually affects the genital skin around the vulva and anus. Lichen sclerosus presents classically as white, fragile plaques. “Textbooks say that there is cigarette paper-like crinkling of skin,” Dr. Edwards said. “I think of it being more like cellophane paper. In children, we often see it as smooth, kind of waxy and shiny, compared to adults. Children usually present with pruritus and irritation.”

Lichen sclerosus often starts in the clitoral area and on the perineum, and often with an edematous clitoral hood. “It often eventuates into clitoral phimosis, meaning that there is midline adhesion so that the clitoris is buried,” she said. “In adults, seeing this clitoral phimosis is a reliable sign of a scarring dermatosis – most often lichen sclerosus. But you can’t say that in children, because little girls will often have scarring over the clitoris. It’s just physiologic and means nothing, and it will go away at puberty. Certainly, sometimes this white discoloration can have crinkling. Purpura and tearing are common; if you look at lichen sclerosus histologically it looks like a thin epithelium that’s stretched over gelatin. Any rubbing and scratching can cause bleeding in the skin.”

Clinical appearance of well demarcated white skin with texture change drives the diagnosis. “It can be hard to tell from vitiligo at times, but there always should be texture change – whether it’s crinkling, whether it’s waxy, whether it’s smooth – and it’s symptomatic,” she said.

A biopsy is not usually required. “I think a good picture [of the affected area] or some sort of objective description in the chart is important, because most children do so well that in a few months there’s no sign of it, and the next provider [they see] may not believe that they ever had it,” she said.

The recommended initial treatment for lichen sclerosus in girls is a tiny amount of a superpotent topical corticosteroid ointment such as clobetasol or halobetasol one to two times daily until the skin is clear, which usually takes 2-4 months. “You do not treat these children until they’re comfortable, because that may be a week,” Dr. Edwards said. “You treat these children until the skin looks normal. Then you need to keep treating them, because if you don’t, the skin will relapse, even though they might not have symptoms.”

Following initial treatment, she recommends use of a superpotent corticosteroid once per day three times a week, or a midpotency steroid like triamcinolone ointment 0.1% every day. In her clinical experience, if lesions clear and remain clear with long-term treatment through puberty, the chances are good that they’ll stay clear if the medication is stopped.

“There are no studies on what to do after a patient clears,” said Dr. Edwards, chief of dermatology at Carolinas Medical Center, Charlotte, and adjunct clinical professor of dermatology at the University of North Carolina, Chapel Hill. “We have been informed by trial and error. If a child is totally clear after puberty, I will stop their medication and see them back every 3 months for about a year and a half. If they stay clear after a year and a half, I find that they stay clear. I wonder what happens at menopause. We surely don’t know.”

With consistent topical treatment, many patients will have clearing in one area of affected skin after a month or two, and it will take 3 or 4 months for the remaining area to clear. “I tend to see patients back every 6-8 weeks until they’re clear,” she said. “I do not like the idea of sending people out and saying, ‘use this medication twice a day for a month, then once a day for a month, then three times a week, then as needed.’

For patients concerned about the long-term use of topical steroids, the immunosuppressants tacrolimus and pimecrolimus are options. “They are often irritating on the vulva, but can work better than steroids for extragenital disease,” Dr. Edwards said. “Parents sometimes object to the use of a corticosteroid, but because these produce slower benefit and often burn with application, you can remind the parents that tacrolimus and pimecrolimus are not without side effects and are labeled as being associated with cancer. That often will prompt a parent to be willing to use a topical steroid. You can also point to studies that show the safety of topical steroids.”

Intralesional steroids are useful for thick lesions, but Dr. Edwards said that she has never had to use them in a child with lichen sclerosus. “I have found methotrexate to be useful in some people, but there is not one study on genital lichen sclerosus and methotrexate,” she said. “I find that about one in five patients with recalcitrant vulvar lichen sclerosus has had some benefit from methotrexate,” she added, noting that fractional CO₂ laser “is showing promise in these patients.”

Dr. Edwards concluded her remarks by noting that she has never cared for a child with vulvar lichen sclerosus who didn’t respond to topical super potent steroids, “except due to poor compliance.”

She reported having no relevant financial disclosures.

[email protected]

All PASI 100 responses to psoriasis therapy are not the same, Andrew Blauvelt, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

He presented a first-of-its-kind study that potentially opens the door to a new, more rigorous standard for treatment success in psoriasis: Not simply cleared lesional skin as captured by a Psoriasis Area and Severity Index (PASI) 100 response, but also clearance of residual psoriasis signs and symptoms – as well as what he termed “molecular clearance.”

“We’ve found that clearing skin with drugs utilizing different mechanisms of action may lead to differential consequences for our patients,” observed Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

A PASI 100 response, traditionally considered an elusive goal for the great majority of patients with severe psoriasis, can now often be achieved using today’s top-tier, high-performance biologics. But Dr. Blauvelt and his coinvestigators are interested in pushing even beyond PASI 100 to a new frontier of therapeutic benefit.

He presented a secondary analysis of the previously reported VOYAGE 1 and 2 head-to-head randomized trials of guselkumab (Tremfya) versus adalimumab (Humira) for treatment of moderate to severe psoriasis. This new analysis, which focused exclusively on PASI 100 responders by week 24, demonstrated that patients with a PASI 100 response to guselkumab, an interleukin (IL)-23 inhibitor, had significantly fewer persistent symptoms and signs of psoriasis than those whose skin clearance was attained using adalimumab, a tumor necrosis factor (TNF) inhibitor.

Moreover, the investigators showed that the gene expression profile of PASI 100 responders who were free of signs and symptoms was more normalized than that of patients with residual symptoms despite their cleared skin.

The analysis included 16 participants in the VOYAGE trials who achieved PASI 100 at week 24 on guselkumab and 5 who did so on adalimumab. At baseline and again at week 24, these individuals completed the Psoriasis Symptoms and Signs Diary (PSSD). Also, biopsies of lesional and nonlesional skin were obtained at baseline and of cleared lesional skin at week 24 for transcriptomic microarray analysis of the expression of many thousands of genes.
 

Persistent psoriasis symptoms despite cleared skin

The PSSD involves patient ratings of various psoriasis symptoms and signs. Total scores can range from 0 (symptom- and sign-free) up to 100. At week 24, a significantly higher proportion of guselkumab-treated PASI 100 responders had a total PSSD score of zero: 55%, versus 43% in the adalimumab group. This was consistently true across the board for each of the individual signs and symptoms assessed. For example, 61% of the guselkumab group gave themselves a zero for itch, as did 50% of the adalimumab group. Sixty-four percent on guselkumab and 52% on adalimumab reported being free of redness. And 78% of the guselkumab group reported being pain-free, compared with 69% with adalimumab, Dr. Blauvelt reported.

Gene expression analysis

At baseline, more than 2,300 dysregulated genes were identified in lesional skin while functioning normally in nonlesional skin. The great majority of these initially dysregulated genes became normalized in cleared lesional skin in PASI 100 responders at week 24. However, 25 of the genes remained dysregulated in cleared lesional skin, meaning they displayed less than 75% of normal function. Ten of these 25 genes with dysregulated expression at follow-up showed abnormal function in patients with residual symptoms despite cleared skin, but they functioned normally in those without persistent symptoms. This raises the possibility that the residual symptoms of psoriasis were attributable to the abnormal gene functioning, according to Dr. Blauvelt.

Of note, 9 of the 10 dysregulated genes in cleared lesional skin of patients with residual symptoms were present in the adalimumab group; these included two genes localized to the epidermal differentiation complex as well as the psoriasis-specific proline-rich 9 gene known as PRR9, which is induced by IL-17A. In contrast, only four genes, none of which were localized to the epidermal differentiation complex, were insufficiently normalized in the cleared lesional skin of guselkumab-treated PASI-100 responders.

“Nothing like this analysis has ever been done before,” the dermatologist observed. “It’s a pilot study. Perhaps with more data like this, we’ll be using this type of information in clinical practice to go beyond clearing patients’ skin.”

Dr. Blauvelt reported serving as a scientific advisor to and paid clinical investigator for Janssen, which sponsored the study, as well as for roughly two dozen other pharmaceutical companies.

[email protected]

All PASI 100 responses to psoriasis therapy are not the same, Andrew Blauvelt, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

He presented a first-of-its-kind study that potentially opens the door to a new, more rigorous standard for treatment success in psoriasis: Not simply cleared lesional skin as captured by a Psoriasis Area and Severity Index (PASI) 100 response, but also clearance of residual psoriasis signs and symptoms – as well as what he termed “molecular clearance.”

“We’ve found that clearing skin with drugs utilizing different mechanisms of action may lead to differential consequences for our patients,” observed Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

A PASI 100 response, traditionally considered an elusive goal for the great majority of patients with severe psoriasis, can now often be achieved using today’s top-tier, high-performance biologics. But Dr. Blauvelt and his coinvestigators are interested in pushing even beyond PASI 100 to a new frontier of therapeutic benefit.

He presented a secondary analysis of the previously reported VOYAGE 1 and 2 head-to-head randomized trials of guselkumab (Tremfya) versus adalimumab (Humira) for treatment of moderate to severe psoriasis. This new analysis, which focused exclusively on PASI 100 responders by week 24, demonstrated that patients with a PASI 100 response to guselkumab, an interleukin (IL)-23 inhibitor, had significantly fewer persistent symptoms and signs of psoriasis than those whose skin clearance was attained using adalimumab, a tumor necrosis factor (TNF) inhibitor.

Moreover, the investigators showed that the gene expression profile of PASI 100 responders who were free of signs and symptoms was more normalized than that of patients with residual symptoms despite their cleared skin.

The analysis included 16 participants in the VOYAGE trials who achieved PASI 100 at week 24 on guselkumab and 5 who did so on adalimumab. At baseline and again at week 24, these individuals completed the Psoriasis Symptoms and Signs Diary (PSSD). Also, biopsies of lesional and nonlesional skin were obtained at baseline and of cleared lesional skin at week 24 for transcriptomic microarray analysis of the expression of many thousands of genes.
 

Persistent psoriasis symptoms despite cleared skin

The PSSD involves patient ratings of various psoriasis symptoms and signs. Total scores can range from 0 (symptom- and sign-free) up to 100. At week 24, a significantly higher proportion of guselkumab-treated PASI 100 responders had a total PSSD score of zero: 55%, versus 43% in the adalimumab group. This was consistently true across the board for each of the individual signs and symptoms assessed. For example, 61% of the guselkumab group gave themselves a zero for itch, as did 50% of the adalimumab group. Sixty-four percent on guselkumab and 52% on adalimumab reported being free of redness. And 78% of the guselkumab group reported being pain-free, compared with 69% with adalimumab, Dr. Blauvelt reported.

Gene expression analysis

At baseline, more than 2,300 dysregulated genes were identified in lesional skin while functioning normally in nonlesional skin. The great majority of these initially dysregulated genes became normalized in cleared lesional skin in PASI 100 responders at week 24. However, 25 of the genes remained dysregulated in cleared lesional skin, meaning they displayed less than 75% of normal function. Ten of these 25 genes with dysregulated expression at follow-up showed abnormal function in patients with residual symptoms despite cleared skin, but they functioned normally in those without persistent symptoms. This raises the possibility that the residual symptoms of psoriasis were attributable to the abnormal gene functioning, according to Dr. Blauvelt.

Of note, 9 of the 10 dysregulated genes in cleared lesional skin of patients with residual symptoms were present in the adalimumab group; these included two genes localized to the epidermal differentiation complex as well as the psoriasis-specific proline-rich 9 gene known as PRR9, which is induced by IL-17A. In contrast, only four genes, none of which were localized to the epidermal differentiation complex, were insufficiently normalized in the cleared lesional skin of guselkumab-treated PASI-100 responders.

“Nothing like this analysis has ever been done before,” the dermatologist observed. “It’s a pilot study. Perhaps with more data like this, we’ll be using this type of information in clinical practice to go beyond clearing patients’ skin.”

Dr. Blauvelt reported serving as a scientific advisor to and paid clinical investigator for Janssen, which sponsored the study, as well as for roughly two dozen other pharmaceutical companies.

[email protected]

All PASI 100 responses to psoriasis therapy are not the same, Andrew Blauvelt, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

He presented a first-of-its-kind study that potentially opens the door to a new, more rigorous standard for treatment success in psoriasis: Not simply cleared lesional skin as captured by a Psoriasis Area and Severity Index (PASI) 100 response, but also clearance of residual psoriasis signs and symptoms – as well as what he termed “molecular clearance.”

“We’ve found that clearing skin with drugs utilizing different mechanisms of action may lead to differential consequences for our patients,” observed Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

A PASI 100 response, traditionally considered an elusive goal for the great majority of patients with severe psoriasis, can now often be achieved using today’s top-tier, high-performance biologics. But Dr. Blauvelt and his coinvestigators are interested in pushing even beyond PASI 100 to a new frontier of therapeutic benefit.

He presented a secondary analysis of the previously reported VOYAGE 1 and 2 head-to-head randomized trials of guselkumab (Tremfya) versus adalimumab (Humira) for treatment of moderate to severe psoriasis. This new analysis, which focused exclusively on PASI 100 responders by week 24, demonstrated that patients with a PASI 100 response to guselkumab, an interleukin (IL)-23 inhibitor, had significantly fewer persistent symptoms and signs of psoriasis than those whose skin clearance was attained using adalimumab, a tumor necrosis factor (TNF) inhibitor.

Moreover, the investigators showed that the gene expression profile of PASI 100 responders who were free of signs and symptoms was more normalized than that of patients with residual symptoms despite their cleared skin.

The analysis included 16 participants in the VOYAGE trials who achieved PASI 100 at week 24 on guselkumab and 5 who did so on adalimumab. At baseline and again at week 24, these individuals completed the Psoriasis Symptoms and Signs Diary (PSSD). Also, biopsies of lesional and nonlesional skin were obtained at baseline and of cleared lesional skin at week 24 for transcriptomic microarray analysis of the expression of many thousands of genes.
 

Persistent psoriasis symptoms despite cleared skin

The PSSD involves patient ratings of various psoriasis symptoms and signs. Total scores can range from 0 (symptom- and sign-free) up to 100. At week 24, a significantly higher proportion of guselkumab-treated PASI 100 responders had a total PSSD score of zero: 55%, versus 43% in the adalimumab group. This was consistently true across the board for each of the individual signs and symptoms assessed. For example, 61% of the guselkumab group gave themselves a zero for itch, as did 50% of the adalimumab group. Sixty-four percent on guselkumab and 52% on adalimumab reported being free of redness. And 78% of the guselkumab group reported being pain-free, compared with 69% with adalimumab, Dr. Blauvelt reported.

Gene expression analysis

At baseline, more than 2,300 dysregulated genes were identified in lesional skin while functioning normally in nonlesional skin. The great majority of these initially dysregulated genes became normalized in cleared lesional skin in PASI 100 responders at week 24. However, 25 of the genes remained dysregulated in cleared lesional skin, meaning they displayed less than 75% of normal function. Ten of these 25 genes with dysregulated expression at follow-up showed abnormal function in patients with residual symptoms despite cleared skin, but they functioned normally in those without persistent symptoms. This raises the possibility that the residual symptoms of psoriasis were attributable to the abnormal gene functioning, according to Dr. Blauvelt.

Of note, 9 of the 10 dysregulated genes in cleared lesional skin of patients with residual symptoms were present in the adalimumab group; these included two genes localized to the epidermal differentiation complex as well as the psoriasis-specific proline-rich 9 gene known as PRR9, which is induced by IL-17A. In contrast, only four genes, none of which were localized to the epidermal differentiation complex, were insufficiently normalized in the cleared lesional skin of guselkumab-treated PASI-100 responders.

“Nothing like this analysis has ever been done before,” the dermatologist observed. “It’s a pilot study. Perhaps with more data like this, we’ll be using this type of information in clinical practice to go beyond clearing patients’ skin.”

Dr. Blauvelt reported serving as a scientific advisor to and paid clinical investigator for Janssen, which sponsored the study, as well as for roughly two dozen other pharmaceutical companies.

[email protected]

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Lindsey Criswell, MD, MPH, DSc, has been selected as the next director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Dr. Criswell, vice chancellor of research at the University of California, San Francisco, will replace acting director Robert H. Carter, MD, who has overseen NIAMS since December 2018, following the unexpected death of longtime director Stephen I. Katz, MD, PhD, who had directed the institute since 1995. She will start her new role in early 2021, according to the NIH.

“Dr. Criswell has rich experience as a clinician, researcher, and administrator. Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well-positioned to direct NIAMS,” said NIH director Francis S. Collins, MD, PhD, said in an announcement.

Dr. Criswell, who holds the Kenneth H. Fye, M.D., endowed chair in rheumatology and the Jean S. Engleman Distinguished Professorship in Rheumatology at UCSF, spent most of her career at the university, focusing her research on the genetics and epidemiology of human autoimmune disease, particularly rheumatoid arthritis and systemic lupus erythematosus. Using genome-wide association and other genetic studies, her research team contributed to the identification of more than 30 genes linked to these disorders, according to the NIH.

NIAMS has a budget of nearly $625 million and its extramural research program supports scientific studies and research training and career development throughout the country through grants and contracts to research organizations in fields that include rheumatology, muscle biology, orthopedics, bone and mineral metabolism, and dermatology.

[email protected]

Lindsey Criswell, MD, MPH, DSc, has been selected as the next director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Dr. Criswell, vice chancellor of research at the University of California, San Francisco, will replace acting director Robert H. Carter, MD, who has overseen NIAMS since December 2018, following the unexpected death of longtime director Stephen I. Katz, MD, PhD, who had directed the institute since 1995. She will start her new role in early 2021, according to the NIH.

“Dr. Criswell has rich experience as a clinician, researcher, and administrator. Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well-positioned to direct NIAMS,” said NIH director Francis S. Collins, MD, PhD, said in an announcement.

Dr. Criswell, who holds the Kenneth H. Fye, M.D., endowed chair in rheumatology and the Jean S. Engleman Distinguished Professorship in Rheumatology at UCSF, spent most of her career at the university, focusing her research on the genetics and epidemiology of human autoimmune disease, particularly rheumatoid arthritis and systemic lupus erythematosus. Using genome-wide association and other genetic studies, her research team contributed to the identification of more than 30 genes linked to these disorders, according to the NIH.

NIAMS has a budget of nearly $625 million and its extramural research program supports scientific studies and research training and career development throughout the country through grants and contracts to research organizations in fields that include rheumatology, muscle biology, orthopedics, bone and mineral metabolism, and dermatology.

[email protected]

Lindsey Criswell, MD, MPH, DSc, has been selected as the next director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Dr. Criswell, vice chancellor of research at the University of California, San Francisco, will replace acting director Robert H. Carter, MD, who has overseen NIAMS since December 2018, following the unexpected death of longtime director Stephen I. Katz, MD, PhD, who had directed the institute since 1995. She will start her new role in early 2021, according to the NIH.

“Dr. Criswell has rich experience as a clinician, researcher, and administrator. Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well-positioned to direct NIAMS,” said NIH director Francis S. Collins, MD, PhD, said in an announcement.

Dr. Criswell, who holds the Kenneth H. Fye, M.D., endowed chair in rheumatology and the Jean S. Engleman Distinguished Professorship in Rheumatology at UCSF, spent most of her career at the university, focusing her research on the genetics and epidemiology of human autoimmune disease, particularly rheumatoid arthritis and systemic lupus erythematosus. Using genome-wide association and other genetic studies, her research team contributed to the identification of more than 30 genes linked to these disorders, according to the NIH.

NIAMS has a budget of nearly $625 million and its extramural research program supports scientific studies and research training and career development throughout the country through grants and contracts to research organizations in fields that include rheumatology, muscle biology, orthopedics, bone and mineral metabolism, and dermatology.

[email protected]