Cutaneous toxicities of mitogen-activated protein kinase inhibitors in children and young adults with neurofibromatosis-1.

PURPOSE: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein kinase inhibitors (MEKi) are generally well-tolerated treatments which target neural tumor progression in patients with NF1. However, cutaneous adverse events (CAEs) are common and may hinder patients' abilities to remain on treatment, particularly in children. We aim to characterize CAEs secondary to MEKi treatment in pediatric and young adult patients with NF1. METHODS: We reviewed institutional medical records of patients under 30 years with a diagnosis of "NF1," "NF2," or "other neurofibromatoses" on MEKi therapy between January 1, 2019 and June 1, 2022. We recorded the time-to-onset, type, and distribution of CAEs, non-cutaneous adverse events (AEs), AE management, and tumor response. RESULTS: Our cohort consisted of 40 patients with NF1 (median age, 14 years). Tumor types included low-grade gliomas (51%) and plexiform neurofibromas (38%). MEKi used included selumetinib (69%), trametinib (25%), and mirdametinib (6%). A total of 74 CAEs occurred, with 28 cases of acneiform rash (38%). Other common CAEs were paronychia, seborrheic dermatitis, eczema, xerosis, and oral mucositis. The most common treatments included oral antibiotics and topical corticosteroids. Most patients had clinical (stable or improved) tumor response (71%) while 29% had tumor progression while on a MEKi. There was no significant association between CAE presence and tumor response (p = 0.39). CONCLUSIONS: Improvement in characterization of MEKi toxicities and their management is important to develop treatment guidelines for pediatric and young adult patients with NF1 on MEKi therapy.

Annular vasculitic lesions.

Vasculitic skin findings may present with annular morphologies. This group of conditions consists of capillaritis, such as pigmented purpuric dermatoses, and vasculitis, which is often classified by the affected vessel size. Annular vasculitic lesions may be the presenting sign of systemic disease, thus requiring thorough exploration to reach an accurate diagnosis and guide proper disease management. Herein we review the clinical presentation, histopathology, and treatments for cutaneous vasculitic disease that may present with annular lesions.

Biologic Therapies for the Management of Cutaneous Findings in Genodermatoses: A Review.

Genodermatoses are genetically inherited dermatologic conditions. The management of cutaneous findings in genodermatoses is challenging, and first-line therapies, such as steroids and/or retinoids, are often inadequate. In recent years, research on the molecular basis of genodermatoses has led to the use of biologic therapies for intractable disease. Here, we review the evidence regarding the use of available biologic therapies for the management of dermatologic findings in genodermatoses. Biologic therapies appear to be promising therapeutic options for several recalcitrant genodermatoses, especially those with underlying immune dysregulation. However, not all genodermatoses are amenable to biologic therapies, and some have been shown to paradoxically worsen under treatment. Biologic therapies offer a novel avenue to target refractory genodermatoses. However, evidence supporting the use of biologic therapies in the management of genodermatoses is mostly limited to case reports and case series. Further studies are warranted to determine the safety and efficacy of biologic therapies for the management of cutaneous findings in genodermatoses.