– Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.

“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.

Skin-limited Langerhans cell histiocytosis

Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.

Dr. Jennifer Huang, a pediatric dermatologist at Boston Children's Hospital and Harvard Medical School Bruce Jancin/MDedge News

Dr. Jennifer Huang

A pair of studies published several years ago provide guidance on how to best manage such patients. In one study of 26 patients with LCH with skin involvement, 16 had skin-limited LCH which was present at birth and 10 had multisystem disease. During a mean 19.5 months of follow-up only 1 of the 16 with skin-limited LCH went on to multisystem involvement; the other 15 experienced complete resolution of their skin disease by age 7 months (J Pediatr Hematol Oncol. 2014 Nov;36(8):613-6). The other study included 71 patients with skin-involved LCH; none of the 21 patients with the skin-limited variety progressed to multisystem LCH during 3 years of follow-up (J Pediatr. 2014 Nov;165[5]:990-6).

“It’s very rare for patients who present with skin-limited LCH alone to develop multisystem disease and to require chemotherapy or other more aggressive treatment,” Dr. Huang said. “I think that skin-limited LCH is probably a separate entity with its own natural history distinct from multisystem disease. We can see that with current genomic testing: in multisystem LCH, BRAF mutations are identified in at least half of patients, but very few with skin-limited disease express those mutations.

“The clinical pearl here is if you have a patient with skin-limited LCH it very rarely progresses to multisystem involvement. It’s associated with a good prognosis. That doesn’t mean you shouldn’t monitor them, but I think it can be reassuring information for the family,” she said.

Basal cell nevus syndrome and medulloblastoma

“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.

BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.

“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.

Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.

BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.

Dr. Lawrence F. Eichenfield is the vice chair of the department of dermatology and a professor of dermatology and pediatrics at the University of California, San Diego

Dr. Lawrence F. Eichenfield

Children with BCNS can develop hundreds of initially tiny skin tumors. Session chair Lawrence F. Eichenfield, MD, observed that treatment can be tricky. Hedgehog pathway inhibitors such as vismodegib (Erivedge) are contraindicated in children. He shared a tip he learned from a colleague: treat these numerous microbasal cells using a stacked pulse dye laser without cooling.

“I’ve treated a hundred at a time. It’s incredibly successful. It’s locally destructive. It leaves a little bit of hypopigmentation but no scar, which the CO2 laser will do in this instance. It’s actually a pretty cool modality,” said Dr. Eichenfield, professor of dermatology and pediatrics at Rady Children’s Hospital and the University of California, San Diego.

Follicular eruptions in cancer patients on MAPK inhibitors

Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.

The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.

Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.

“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.

She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.

D. folliculitis in immunocompromised patients

“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.

Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.

In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.

Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.

Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.

Dr. Huang reported having no financial conflicts of interest regarding her presentation.

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