Langerhans cell histiocytosis (ORPHA:389)
A rare systemic disease characterized by the accumulation (usually organized in granulomas) of macrophage, bearing the features of Langerhans cells in various tissues.
Epidemiology
Its prevalence is estimated at 1-2/100,000. More than 60% of the cases occur before age of 2. But the disease may be diagnosed in adults.
Clinical description
Bone is the most frequently affected organ (80% of cases), followed by the skin (35% of cases) and then the pituitary gland (25% of cases). However, involvement of these organs does not affect the vital prognosis. Involvement of the hematopoietic system (cytopenia), lungs and liver is much less common (15-20% of cases) but results in more severe disease. The aggressive nature of the hematological forms in young children, the long-term sequelae associated with lung and liver (sclerosing cholangitis) involvement, and the neurodegenerative manifestations (2-5% of cases) make LCH a severe disease. The disease may occur as one or several crises. It may result in aesthetic or functional sequelae with variable expression depending on the sites involved (deafness, respiratory or hepatic failure, diabetes insipidus, growth hormone deficiency, and cerebellar syndrome). In adults, the clinical picture is characterized by isolated lung disease, with a strong association with smoking.
Etiology
The origin of the LCH lesions, originally thought to be neoplastic proliferation of Langerhans cells, was found to instead be similar to proliferation of immature myeloid precursors, with activation of one gene of the MAPK/ERK pathway (most frequently BRAF) involving the macrophagic cells.
Diagnostic methods
Diagnosis of LCH usually relies on histological and immunohistochemical analysis of the affected tissues. A thoracic CT scan showing typical radiological findings may allow diagnosis in adults with isolated lung involvement.
Differential diagnosis
A large range of alternative diagnoses may be considered, depending on the associated clinical picture and radiological findings.
Management and treatment
The choice of therapeutic approach depends on the extent of disease, determined by routine examinations (clinical examination, hemogram, liver function tests, and bone and chest radiographs). Local treatment is usually effective for forms limited to one organ. In children, treatment of the systemic forms relies on the combination of corticosteroids and vinblastine. Smoking cessation is necessary for adults with lung involvement. Second-line treatments are available in specialized centers for patients with progressive disease. Given the polymorphic and chronic nature of the disease, management of LCH should be multidisciplinary. Treatment protocols for adult forms of the disease are less well established than those for patients with childhood onset. Long-term follow-up is needed for detection and management of later-onset sequelae.
Prognosis
The vital prognosis is not usually affected in childhood forms, except in cases with hematological involvement resistant to first-line therapies.

                            Last update: 
                            July 2023


                            - Expert reviewer(s): 
                            Dr Jean DONADIEU