Pediatric maculopapular cutaneous mastocytosis: Retrospective review of signs, symptoms, and associated conditions.

BACKGROUND/OBJECTIVES: Though maculopapular cutaneous mastocytosis is the most common form of pediatric mastocytosis, it remains unclear which patients will experience severe symptoms. We sought to better define the presentation and the cutaneous and systemic signs and symptoms in patients with maculopapular cutaneous mastocytosis. METHODS: We analyzed retrospective data on 227 patients diagnosed with maculopapular cutaneous mastocytosis prior to age 15 years from five US clinical sites. We collected data on signs, symptoms, age of onset, and laboratory testing. RESULTS: Median age of onset of maculopapular cutaneous mastocytosis was 3 months, with 94% of patients presenting prior to age 2 (range 0-15 years). Patients presenting before age 2 had significantly lower serum tryptase level (P = .019). Greater number of skin lesions (P = .006), number of reported skin signs and symptoms (P < .001), and higher tryptase levels (P < .001) were associated with more systemic symptoms. CONCLUSION: Children with maculopapular cutaneous mastocytosis, who have greater skin involvement, higher serum tryptase level, and more skin signs and symptoms, are more likely to have systemic symptoms.

Langerhans cell histiocytosis: A neoplastic disorder driven by Ras-ERK pathway mutations.

Langerhans cell histiocytosis (LCH) is a disorder of myeloid neoplasia of dendritic cells that affects 1 in 200,000 children <15 years of age and even fewer adults. LCH presents with a spectrum of clinical manifestations. High-risk stratification is reserved for infiltration of blood, spleen, liver, and lungs. After decades of debate on the disease pathogenesis, a neoplastic mechanism is now favored on the basis of LCH cell clonality, rare cases of familial clustering, and recent evidence of mutations involving the Ras/Raf/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway in lesional biopsy specimens. Somatic mutations are most often found in BRAF (BRAFV600E in 47.1% of reported patients) and MAP2K1 (21.7%) and uncommonly found in MAP3K1 or ARAF. Increased levels of phospho-ERK in lesional tissue, activation of Ras/Raf/MEK/ERK signaling with these mutations in vitro, and the mutual exclusivity of these mutations in a given patient suggest a central role for activation of the Ras/Raf/MEK/ERK oncogenic pathway in LCH. Immunohistochemical assessment of lesional tissue using the VE1 BRAFV600E mutation-specific antibody can serve as a screening tool for BRAFV600E-positive LCH. Case reports suggest that BRAFV600E-positive LCH unresponsive to standard therapy might respond to B-Raf-MEK pathway inhibition, but rigorous randomized clinical trials have yet to be performed.

Tattoo and vaccination sites: Possible nest for opportunistic infections, tumors, and dysimmune reactions.

Tattoos have gained worldwide popularity in recent years, and vaccinations are universal preventive measures designed to minimize morbidity associated with specific pathogens. Both dermal tattoos and vaccine injections may alter local immune responses, creating an immunocompromised district on or near the site of placement. This can lead to the development of opportunistic infections, benign and malignant tumors, and local dysimmune reactions. With regard to tattoos, a predominance of warts among a variety of opportunistic infections has been reported. These warts appear to result from a local immune dysregulation rather than from direct inoculation or coincidence. A variety of tumors including basal and squamous cell carcinomas, keratoacanthomas, and malignant melanoma also have been reported in association with tattoos. Granulomatous, lichenoid, and pseudolymphomatous reactions represent the most common dysimmune reactions. Vaccination sites similarly provide a setting for both benign and malignant tumors. Frequent reports of dermatofibrosarcoma protuberans would be unlikely to result from coincidence. Granuloma annulare and pseudolymphomatous reactions are relatively common dysimmune reactions.