From the Guidelines
Langerhans cell histiocytosis (LCH) is a rare disorder that requires individualized treatment based on the extent and severity of disease, with options ranging from topical corticosteroids for limited skin involvement to systemic chemotherapy and targeted therapies like BRAF inhibitors for multisystem disease. The treatment approach depends on the specific characteristics of the disease, including the presence of BRAF V600E mutations, which are found in approximately 50% of cases 1.
Treatment Options
- For limited skin involvement, topical corticosteroids like triamcinolone 0.1% applied twice daily for 2-4 weeks may be sufficient.
- For single bone lesions, curettage or low-dose radiation therapy (6-10 Gy) is often effective.
- Multisystem disease typically requires systemic chemotherapy, with the standard first-line regimen being vinblastine (6 mg/m² weekly for 6 weeks, then every 3 weeks) combined with prednisone (40 mg/m²/day for 4 weeks, then tapered) for 6-12 months.
- For refractory cases, cladribine (5 mg/m²/day for 5 days) or cytarabine may be used.
- BRAF inhibitors like vemurafenib are emerging as targeted therapy options for severe cases with BRAF V600E mutations.
Disease Characteristics and Complications
- LCH results from a clonal proliferation of CD1a-positive dendritic cells.
- Patients should be monitored for potential long-term complications including diabetes insipidus, growth problems, and neurodegenerative changes.
- Involvement of the lymph nodes (LNs) in LCH is rare and may be observed or require localized therapies, but when part of multisystem disease, it is thought to represent a higher risk of disease 1.
Recent Consensus Recommendations
- The diagnosis and therapy of LCH have evolved and become increasingly complex, necessitating updated guidelines 1.
- Targeted therapies like BRAF inhibitors have shown promise in treating LCH, especially in cases with BRAF V600E mutations 1.
From the Research
Definition and Classification of Langerhans Cell Histiocytosis
- Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis 2
- It can occur at any age, but is more frequent in the pediatric population 2
- LCH can be classified into different clinical syndromes, including eosinophilic granuloma, Hand-Schûller-Christian's disease, and Letterer-Siwe's disease 3
Clinical Presentation and Diagnosis
- The clinical presentation of LCH is variable and ranges from isolated skin or bone disease to a life-threatening multisystem condition 2
- Diagnosis is based on histological investigations, which show higher proliferation activity and expression of Ki-67 proliferation marker 4
- Imaging modalities, such as 18F-Fluorodeoxyglucose positron emission tomography (PET), are useful in disease diagnosis and management 5
Treatment Options
- Standard therapy for LCH includes vinblastine and prednisone with or without methotrexate and mercaptopurine 6
- Effective therapies for patients unresponsive to standard therapy include cytosine arabinoside and cladribine 6
- Targeted therapies, such as BRAF inhibitors, have been used in select patients with LCH, with encouraging results 2, 5
- Lenalidomide has been shown to induce therapeutic response in patients with aggressive multi-system LCH 4
Treatment Algorithm and Response Assessment
- The treatment algorithm for LCH in adults includes local therapies for unifocal disease, smoking cessation for single-system pulmonary LCH, and systemic treatments for multifocal and multisystem disease 5
- Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted therapies 5
- Response assessment is based on imaging modalities, such as PET, and clinical evaluation of symptoms and disease activity 5