Systemic mastocytosis
Systemic mastocytosis is a clonal mast cell neoplasm, driven in more than 90% of adults by the somatic KIT D816V mutation, in which abnormal mast cells accumulate in bone marrow and other extracutaneous organs and release mediators that cause flushing, pruritus, diarrhea, and hypotensive anaphylaxis. Diagnosis rests on WHO criteria (one major plus one minor, or three minor) built from bone marrow mast cell aggregates, atypical morphology, KIT codon 816 mutation, CD25/CD2/CD30 expression, and baseline tryptase above 20 ng/mL; management is epinephrine readiness, trigger avoidance, and H1/H2 antihistamines, cromolyn, and leukotriene antagonists, with cytoreduction reserved for advanced forms.
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What this article covers
- Overview
Definition: systemic mastocytosis (SM) is a clonal disorder in which mast cells accumulate in bone marrow and other extracutaneous organs, unlike skin-confined cutaneous mastocytosis.
- Epidemiology
Prevalence: mastocytosis in all forms affects about 1 per 10,000 persons.
- Risk factors
Somatic KIT gain-of-function mutation: the defining lesion; the disorder is not inherited and is not passed to offspring except in rare familial cases.
- Pathophysiology
KIT drives mast cell growth: stem cell factor binds the receptor tyrosine kinase KIT (CD117), which only mast cells retain at high levels throughout life.
- Clinical features
Hypotensive anaphylaxis without hives: severe reactions to Hymenoptera stings, perioperative drugs, or no trigger, with syncope or near-syncope rather than urticaria, angioedema, or wheezing.
- Differential diagnosis
IgE-mediated anaphylaxis: tryptase rises transiently during the event but the baseline level is normal; an allergen-specific IgE explains the episode (anaphylaxis).
- Diagnosis
Establish the diagnosis by WHO criteria: SM requires one major plus at least one minor criterion, or three minor criteria; the International Consensus Classification also accepts the major criterion alone.
- Management
First, equip for anaphylaxis: prescribe at least two epinephrine autoinjectors carried at all times; for an episode give epinephrine 0.3 to 0.5 mg IM into the anterolateral thigh, repeated every 5 to…
- Complications
Fatal or near-fatal anaphylaxis: hypotensive collapse after stings, drugs, anesthesia, or contrast.
- Prognosis
Indolent SM dominates: most adults with skin lesions have indolent disease, in which routine laboratories are usually normal and the main lifelong risk is anaphylaxis.
- Prevention
Screen severe sting reactions: measure baseline tryptase after every severe systemic Hymenoptera reaction.
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