Mast Cell Activation Syndrome

Mast cell activation syndrome is a disorder of recurrent episodes of mast cell mediator release, causing symptoms in 2 or more organ systems. It is diagnosed on strict criteria and is often over diagnosed.

Pathophysiology. Mast cells release tryptase, histamine, prostaglandin D2 and leukotrienes in response to triggers (IgE-mediated or not), causing flushing, urticaria, hypotension, gastrointestinal and respiratory symptoms. Types are primary (clonal), secondary (underlying allergy or inflammation) and idiopathic.

Genuine disease is uncommon. Many people who describe flushing, fatigue and multiple symptoms do not meet criteria.

A rise in tryptase during an episode is the central evidence.

• Recurrent episodes of flushing, itching, urticaria and angio oedema
• Abdominal cramps, nausea, diarrhoea
• Hypotension, tachycardia, presyncope or syncope
• Wheeze, throat tightness, nasal congestion
• Headache and fatigue between episodes
• Triggers: heat, exercise, alcohol, stress, drugs (opioids, NSAIDs), infection, food

• Diagnostic criteria (all 3):
  • Typical episodic symptoms in 2 or more organ systems.
  • A rise in serum tryptase of more than 20% over baseline plus 2 microgram/L, measured within 1 to 4 hours of an episode (and a baseline at least 24 hours after).
  • Response to treatment that blocks or lowers mast cell mediators.
• Other mediators: urinary N-methylhistamine, 11-beta-prostaglandin F2-alpha and leukotriene E4 (24 hour or post-episode urine).
• Baseline tryptase over 8 microgram/L: consider hereditary alpha tryptasaemia (TPSAB1 copy number testing).
• Exclusion of other conditions: allergy testing, mastocytosis (bone marrow, KIT D816V), carcinoid, phaeochromocytoma, hereditary angio oedema, anaphylaxis, panic attacks.
• Bone density scan and blood tests (full blood count, liver enzymes, calcium) if systemic mastocytosis is suspected.

Differential diagnosis.

• Systemic mastocytosis
• Anaphylaxis from an allergen
• Hereditary alpha tryptasaemia
• Carcinoid syndrome and phaeochromocytoma
• Chronic urticaria and hereditary angio oedema
• Postural tachycardia syndrome, panic attacks and menopausal flushing

• Trigger avoidance: heat, alcohol, NSAIDs and opioids where relevant, plus stress and infection control.
• H1 antihistamine daily: cetirizine 10 mg orally once daily, which may be raised to 10 mg twice daily or higher in specialist care (children 1 to 5 years 2.5 mg twice daily; 6 to 11 years 5 mg twice daily).
• H2 antihistamine: famotidine 20 mg orally twice daily (reduce at creatinine clearance under 50 mL/min).
• Mast cell stabiliser: sodium cromoglicate 200 mg orally four times daily before meals (adults), for gastrointestinal symptoms.
• Leukotriene blockade: montelukast 10 mg orally once daily at night.
• Omalizumab 150 to 300 mg subcutaneously every 4 weeks for refractory symptoms, in specialist care.
• Emergency plan: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh for anaphylaxis, with auto injector: 150 microgram for 7.5 to 25 kg, 300 microgram for 25 to 50 kg, 500 microgram for over 50 kg.
• Perioperative and procedural planning: premedication with antihistamine, careful drug choice, and monitored setting.
• Treat the underlying cause (allergy, mastocytosis, infection).
• Psychological support and avoidance of unnecessary restrictive diets.

Special groups.

• Patients on beta blockers: adrenaline response may be blunted, so review the need.
• Patients with low level symptoms and normal tryptase: look for other causes before applying the label.

Monitoring. Episode diary and symptom score every 3 months. Baseline tryptase yearly. Review treatment response at 4 to 8 weeks of each step.

Referral and escalation. Refer to allergy or immunology for suspected mast cell activation. Emergency for anaphylaxis.