Makindo Medical Notes

🧬 Mastocytosis is a rare mast cell disorder of children and adults caused by accumulation of abnormal mast cells and CD34+ precursors in various tissues. Most cases involve activating mutations in the KIT receptor tyrosine kinase (commonly D816V). Excessive release of mast cell mediators explains the allergic, cardiovascular, and GI symptoms seen in this condition.

📖 About

• Systemic Mastocytosis: Multisystem involvement (bone marrow, liver, spleen, GI tract, skin).
• Classification: Recognised as a myeloproliferative neoplasm (WHO).
• Cutaneous Mastocytosis: More common in children, often presents as urticaria pigmentosa.

🧬 Aetiology & Pathophysiology

• Clonal mast cell proliferation: Driven by KIT mutations (esp. D816V).
• Sites of infiltration: Skin, bone marrow, liver, spleen, GI tract.
• Mediator release: Histamine, prostaglandins, and leukotrienes cause flushing, pruritus, syncope, and GI upset.

🩺 Clinical Features

• Constitutional: Anaemia, fatigue, weight loss.
• Haematological: Cytopenias, bleeding tendencies, lymphadenopathy.
• Skin: Urticaria pigmentosa (brown macules, wheal with stroking = Darier’s sign).
• Allergic-type symptoms: Flushing, pruritus, tachycardia, syncope.
• GI: Abdominal pain, diarrhoea, peptic ulceration from gastric hypersecretion.
• Bone disease: Osteopenia, osteoporosis, pathological fractures.

🔍 Investigations

• Total Serum Tryptase: Persistent elevation (>20 ng/mL) = mast cell burden.
• Biopsy: Bone marrow aspiration/biopsy = diagnostic gold standard.
• Skin biopsy: For cutaneous forms (urticaria pigmentosa).
• Imaging: CT for hepatosplenomegaly/lymphadenopathy; bone imaging for lytic or sclerotic lesions.
• Genetic testing: Look for KIT D816V mutation.

💊 Management

• Anaphylaxis: Standard emergency management with adrenaline autoinjector prescribed.
• Symptomatic Relief:
  • H1 antihistamines (pruritus, flushing).
  • H2 blockers or PPIs (gastric hypersecretion/ulcers).
  • Leukotriene antagonists (respiratory/GI symptoms).
  • Cromolyn sodium: GI and cutaneous benefit.
• Corticosteroids: For severe symptoms, ascites, bone pain.
• Bone health: Bisphosphonates ± interferon-alpha if refractory osteopenia.
• Aspirin: Sometimes used to reduce flushing, but ⚠️ risk of provoking mediator release.

🎯 Advanced & Targeted Therapies

• Interferon-alpha, cladribine, thalidomide: Used in aggressive disease with limited success.
• Tyrosine kinase inhibitors:
  • Imatinib effective only if KIT D816V negative or if FIP1L1-PDGFRA positive.
  • Newer agents (midostaurin, avapritinib) show efficacy in advanced systemic mastocytosis.

🇬🇧 Clinical Pearls

• Any patient with recurrent unexplained anaphylaxis should be considered for mastocytosis workup.
• Children often have cutaneous forms that may resolve with age; systemic disease is more common in adults.
• NICE recommends referral to haematology centres with mastocytosis expertise.

✅ Conclusion

Mastocytosis is a rare clonal mast cell disorder ranging from indolent cutaneous forms to aggressive systemic disease. Diagnosis hinges on persistently raised tryptase and confirmatory bone marrow biopsy. Management is individualised: emergency preparedness (adrenaline), symptomatic control with antihistamines/PPIs, and targeted therapies in advanced cases.