Makindo Medical Notes

🧩 Langerhans Cell Histiocytosis (LCH) is a rare histiocytic disorder with features overlapping cancer, immune dysregulation, and inflammation. ⚖️ Experts still debate whether it should be considered a true cancer or a clonal immune disorder.

📖 About

• Rare disorder of proliferating Langerhans cells (specialised dendritic immune cells).
• Typically affects children and young adults.
• Historical term: Histiocytosis X.
• Pediatric form is often called eosinophilic granuloma.

🧬 Aetiology & Pathogenesis

• BRAF V600E mutations present in ~50% of cases → abnormal MAPK signalling.
• Leads to clonal expansion of histiocytes with cytokine release and tissue damage.
• Granuloma formation may occur in multiple organs (skin, bone, lungs, pituitary, thyroid, lymph nodes).
• Adult pulmonary LCH strongly associated with cigarette smoking.

🔎 Variants / Clinical Syndromes

• Hashimoto–Pritzker disease → congenital, self-healing skin form.
• Letterer–Siwe disease → acute, disseminated, severe, often in infants.
• Hand–Schüller–Christian disease → chronic, triad of diabetes insipidus, exophthalmos, lytic bone lesions.
• Eosinophilic granuloma → solitary or few bone lesions; most benign end of spectrum.

🩺 Clinical Features

• Bone lesions (esp. lytic skull lesions).
• Pulmonary involvement → cysts, pneumothorax, haemoptysis.
• Endocrine dysfunction → hypothalamic involvement causing diabetes insipidus (polyuria, hypernatraemia).
• CNS → cerebellar demyelination and neurodegeneration (rare).
• Cutaneous, oral, and nail lesions possible.

🧪 Investigations

• X-ray / CT: lytic bone lesions, especially skull.
• HRCT chest: apical cysts and nodules (risk of recurrent pneumothorax).
• Biopsy: Langerhans cells with coffee-bean nuclei, mixed with eosinophils. Immunohistochemistry: CD1a+, S100+, langerin+ (Birbeck granules on EM).
• Bloods: Hypernatraemia from diabetes insipidus, variable cytopenias.

⚖️ Differential Diagnosis

• Sarcoidosis.
• Lymphoma or metastatic bone disease.
• Granulomatous infections (TB, fungal).

💊 Management

• General: Multidisciplinary (haematology, oncology, respiratory, endocrinology).
• First-line: Corticosteroids for symptomatic disease.
• Systemic therapy: Vinblastine, cytarabine, methotrexate for multisystem disease.
• Targeted therapy: BRAF inhibitors (e.g., vemurafenib) in refractory BRAF-mutant cases.
• Supportive: Endocrine replacement for diabetes insipidus, stop smoking in pulmonary LCH.
• Prognosis variable: from self-resolving to progressive respiratory failure (~10% mortality in pulmonary LCH).

📚 References

• Langerhans Cell Histiocytosis (NIH Rare Diseases)
• BNF