Clinical features and treatment of Langerhans cell histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) is caused by the expansion of CD1a+/CD207+ cells and is characterised by a wide spectrum of organ involvement and dysfunction, affecting all ages. While almost all organs and systems can be affected, only the involvement and dysfunction of liver, spleen, and haematopoietic system influence survival. The LCH pathogenic cells are defined by universal activation of the mitogen‐activated protein kinase (MAPK) signalling pathway. The most common alteration is a somatic BRAFV600E mutation, which is present in approximately two‐thirds of the cases, followed by MAP2K1 mutations. Treatment of LCH is risk‐adapted; patients with single lesions may respond well to local treatment, whereas patients with multi‐system disease require systemic chemotherapy. While survival for patients without organ dysfunction is excellent, mortality rates for patients with organ dysfunction may reach 20%. Despite progress made in the treatment of LCH, disease reactivation rates remain above 30%, and standard second‐line treatment has yet to be established. Long‐term effects, including neuroendocrine dysfunction and neurodegeneration, represent a major challenge for survivors. Treatment with BRAF or MEK inhibitors results in immediate responses, but reactivations are very common after discontinuation. Their role as single agents and in combination with chemotherapy is being explored.

Case Report: Disseminated Mycobacterium intracellulare Infection With More Than 1-Year Follow-Up in a Young Boy With IFNGR1 Deficiency

“…LCH pathogenic cells are defined by universal activation of the mitogen-activated protein kinase (MAPK) signaling pathway. The most common alteration in LCH is a somatic BRAF V600E mutation, which is present in approximately two-thirds of cases, followed by MAP2K1 mutations (8). The clinical presentation of LCH is widely variable, ranging from single indolent lesions to an explosive multisystem disease.…”

“…The clinical presentation of LCH is widely variable, ranging from single indolent lesions to an explosive multisystem disease. The skeleton is involved most frequently, accounting for 80% of cases (8). The most common site involving the bones is the skull (which is affected in more than two-thirds of patients with bone disease) followed by the spine, limbs, and pelvis (9).…”

“…Children with osteomyelitis caused by MAC (10,11) or Mycobacterium fortuitum (12) mimicking LCH have been reported. Therefore, in addition to clinical and radiological features, LCH diagnosis should be based on pathological findings [especially immunohistochemical examination (8)] and diagnostic approaches should be adjusted as soon as possible.…”

Rib and sternal lesions in pediatric Langerhans Cell Histiocytosis

“…In pediatric patients, treatment is usually adapted to presentation. Isolated lesions may be treated locally, while multisystemic or disseminated disease usually requires chemotherapy [12]. LCH is not always benign, with disseminated disease having increased mortality and recurrence rates [12][13][14][15].…”

Adult Langerhans Cell Histiocytosis and the Skeleton

“…Although it is more commonly diagnosed in childhood, LCH may emerge at any age and with various degrees of systemic involvement [7]. The Histiocyte Society (HS) classifies the clinical forms of LCH according to the number and type of organs involved: single system (SS) LCH if one organ/system is involved (either unifocal or multifocal) and multisystem (MS) LCH if two or more organs/systems are involved (with or without risk-organ involvement).…”