Childhood LCH is a rare disease, affecting 4–9 per 1,000,000 children below the age of 15 years. It is driven by somatic mutations in the MAPK pathway, arising in myeloid marrow progenitors. Both genders are affected by a slight male preponderance. The clinical spectrum of LCH varies from a single lesion affecting one organ system to severe multisystem disease with dysfunction of vital organs. Likewise, variable and unpredictable is its course, spanning from self-limiting course to progression with lethal outcome. Recognized unfavorable prognostic factors are the involvement of hematopoiesis, liver, and spleen, as well as non-response to systemic treatment. Recent studies suggest that patients carrying the BRAFV600E mutation may have a more severe clinical phenotype and less favorable prognosis. The combination of prednisolone and vinblastine is the standard first-line treatment for disseminated disease. Second-line options used in clinical practice are not well evidenced. Inhibitors of the MAPK pathway are a promising alternative option.
Part of the book: Rare Diseases