Idiopathic Anaphylaxis

Idiopathic anaphylaxis is recurrent anaphylaxis for which no trigger can be found after full evaluation. It is a diagnosis of exclusion and may be frequent or infrequent.

Pathophysiology. Mast cells and basophils release mediators spontaneously or through an unidentified trigger. Some patients have underlying clonal mast cell disease, hereditary alpha tryptasaemia (extra copies of TPSAB1), or undetected food, drug or cofactor triggers.

Most patients are adults. Episodes may be single or recurrent, and the course tends to improve with time.

A search for a hidden cause is essential before the label is applied.

• Urticaria, flushing, itching and angio oedema
• Throat tightness, stridor, wheeze
• Hypotension, syncope, collapse
• Vomiting, abdominal pain, diarrhoea
• Episodes without a predictable trigger, often unrelated to meals or exercise
• Frequent episodes in a subset (6 or more in a year, or 2 or more in 2 months)
• Absent skin signs in some, which delays diagnosis

• Detailed history of foods, drugs, exercise, stings, menstrual cycle, alcohol and stress, and a symptom diary.
• Serum tryptase within 1 to 2 hours of an episode (peak 1 to 2 hours after onset) and a baseline level at least 24 hours after recovery: a rise over 20% of baseline plus 2 microgram/L supports mast cell activation.
• Baseline tryptase: over 20 microgram/L suggests systemic mastocytosis or hereditary alpha tryptasaemia (TPSAB1 copy number testing).
• Skin prick tests and specific IgE to common foods, latex, and venoms; alpha gal specific IgE.
• Drug review: non-steroidal anti-inflammatory drugs, opioids, angiotensin converting enzyme inhibitors.
• Mast cell disease workup (KIT D816V on blood, bone marrow biopsy) when tryptase is raised or there is hypotension without skin signs.
• Exclusion of other conditions: phaeochromocytoma, carcinoid, systemic mastocytosis, vocal cord dysfunction.

Differential diagnosis.

• Systemic mastocytosis and mast cell activation syndrome
• Hereditary alpha tryptasaemia
• Alpha gal syndrome and food dependent exercise induced anaphylaxis
• Hereditary and acquired angio oedema (without urticaria)
• Cardiac arrhythmia and vasovagal syncope
• Carcinoid syndrome, phaeochromocytoma and panic attacks

• Acute episode: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh, repeated after 5 minutes if no improvement, plus oxygen, intravenous fluids, and observation for at least 6 hours. Measure tryptase.
• Adrenaline auto injector: 150 microgram for 7.5 to 25 kg, 300 microgram for 25 to 50 kg, 500 microgram for over 50 kg, with a written action plan and training.
• Frequent episodes (6 or more a year, or 2 or more in 2 months): prophylaxis:
  • Prednisolone 60 mg orally daily for 1 week, then 60 mg on alternate days for 3 weeks, then reduce by 10 mg every 2 weeks to the lowest effective dose (adults), with bone, glucose and blood pressure monitoring.
  • Cetirizine 10 mg orally once daily, which may be raised to twice daily.
  • Omalizumab 300 mg subcutaneously every 4 weeks as a steroid sparing option in specialist care.
• Infrequent episodes: adrenaline auto injector, antihistamine for early symptoms, and trigger avoidance only.
• Avoid cofactors: alcohol, aspirin and other non-steroidal anti-inflammatory drugs.
• Mast cell disease: if confirmed, manage in the usual way, including lifelong adrenaline.
• Psychological support for anxiety after recurrent frightening episodes.

Special groups.

• Patients on beta blockers or angiotensin converting enzyme inhibitors: review need, since they can worsen severity and blunt adrenaline response. Glucagon 1 to 2 mg intravenously may be needed for adrenaline resistant reactions in hospital.

Monitoring. Review every 3 to 6 months at first. Episode diary. Prednisolone side effect monitoring (blood pressure, glucose, bone health). Baseline tryptase yearly.

Referral and escalation. Refer to allergy for all patients with unexplained anaphylaxis. Urgent when tryptase is raised or reactions are severe. Emergency for any anaphylaxis.