OBSOLETE: Langerhans cell histiocytosis in childhood and adulthood

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the abnormal proliferation and accumulation of Langerhans cells, a type of dendritic cell normally involved in immune surveillance. These abnormal cells, which express CD1a and CD207 (langerin) markers, can infiltrate virtually any organ system, leading to a wide spectrum of clinical manifestations. LCH can present in both childhood and adulthood, though it is more commonly diagnosed in children. The disease was historically known by several names including histiocytosis X, eosinophilic granuloma (single bone lesion), Hand-Schüller-Christian disease (multifocal bone lesions with diabetes insipidus and exophthalmos), and Letterer-Siwe disease (disseminated form). The body systems most commonly affected include bone (causing painful lytic lesions, particularly in the skull, ribs, pelvis, and long bones), skin (presenting as scaly, seborrheic dermatitis-like rashes or papular lesions), lungs (especially in adult smokers, causing cystic lung disease), the pituitary gland (leading to diabetes insipidus and other endocrine deficiencies), liver, spleen, lymph nodes, and the central nervous system. In children, the disease can range from a single bone lesion with an excellent prognosis to life-threatening multisystem disease involving risk organs such as the liver, spleen, and bone marrow. Adults more frequently present with isolated pulmonary LCH or single-system bone disease. Current understanding recognizes LCH as a clonal neoplastic disorder driven by activating mutations in the MAPK/ERK signaling pathway, most notably the BRAF V600E mutation found in approximately 50-60% of cases. Treatment depends on disease extent and severity. Single-system disease may require observation, curettage, or local therapy, while multisystem LCH typically requires systemic chemotherapy, with vinblastine and prednisone being the standard first-line regimen in children. Targeted therapies such as BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib) have shown promising results, particularly in refractory or relapsed cases. Prognosis varies widely, from spontaneous resolution in limited disease to significant morbidity and mortality in multisystem involvement with risk organ dysfunction.

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