Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease, 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, along with other immune cells, form granuloma-like lesions that can damage tissues and organs throughout the body. LCH is now classified as a neoplastic disorder, with somatic mutations in the MAPK/ERK signaling pathway (most commonly the BRAF V600E mutation) identified in the majority of cases. LCH can affect virtually any organ system, but the most commonly involved sites include bone (causing painful lytic lesions, particularly in the skull, ribs, pelvis, and long bones), skin (presenting as scaly, seborrheic dermatitis-like rashes, particularly on the scalp and intertriginous areas), lungs (causing cysts and pneumothorax, especially in adult smokers), the pituitary gland (leading to diabetes insipidus and other hormonal deficiencies), lymph nodes, liver, spleen, and the hematopoietic system. The disease ranges widely in severity, from a single bone lesion that may resolve spontaneously to life-threatening multisystem disease with organ dysfunction. The clinical presentation is highly variable depending on the number and type of organs involved. Single-system LCH, particularly isolated bone disease, generally carries an excellent prognosis and may be treated with curettage, local corticosteroid injection, or observation alone. Multisystem LCH, especially with involvement of risk organs (liver, spleen, or hematopoietic system), requires systemic chemotherapy, most commonly with vinblastine and prednisone as first-line treatment. Refractory or relapsed cases may be treated with cladribine, cytarabine, or targeted therapies such as BRAF inhibitors (vemurafenib) or MEK inhibitors. Long-term sequelae, including diabetes insipidus, growth hormone deficiency, neurodegeneration, hearing loss, and orthopedic complications, are common and require ongoing multidisciplinary follow-up.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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