Clinical Immunology: Allergy, anaphylaxis, urticaria and angioedema

• Anaphylaxis: Allergy - Overview | Anaphylaxis - Recognition | Anaphylaxis - Emergency Treatment | After Anaphylaxis - Tryptase, Observation and Discharge
• Drug allergy: Drug Allergy | Penicillin Allergy and Delabelling | Perioperative Anaphylaxis
• Food and environment: IgE-mediated Food Allergy | Non-IgE Food Allergy and Eosinophilic Oesophagitis | Allergic Rhinitis and Allergen Immunotherapy | Insect Venom Allergy
• Skin and swelling: Urticaria | Angioedema - Histamine or Bradykinin? | Hereditary Angioedema | Mastocytosis and Mast Cell Disorders
• Revision: Allergy at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🛡️ Allergy, anaphylaxis, urticaria and angioedema - page 4 of the Clinical Immunology chapter. Allergic disease affects about a quarter of people in the UK, and anaphylaxis is one of the few true emergencies that every doctor must treat in the first minutes without waiting for help. Equally important is avoiding false labels - most people with a "penicillin allergy" are not allergic, and wrong labels lead to worse antibiotics and worse outcomes. Recognising bradykinin-mediated angioedema matters because adrenaline and antihistamines don't work.
Your four questions for every allergic reaction: Is this anaphylaxis - does it need IM adrenaline now? What was the trigger, and how strong is the evidence? Is it IgE-mediated, non-IgE, or bradykinin-mediated? What does the patient need to stay safe - avoidance, an action plan, auto-injectors, referral?

Allergy - Overview

• Allergy - a harmful immune response to a normally harmless substance (allergen) - most often IgE-mediated (type I hypersensitivity).
• Sensitisation - production of specific IgE; allergy - sensitisation plus symptoms on exposure. Many sensitised people are not allergic.
• Atopy - tendency to make IgE to environmental allergens - eczema, food allergy, asthma and allergic rhinitis often occur together and in families ("atopic march" - eczema and food allergy in infancy, then asthma and rhinitis).
• Mechanism of IgE reactions - allergen cross-links IgE on mast cells and basophils → release of histamine, tryptase, leukotrienes, prostaglandins, platelet-activating factor → vasodilatation, capillary leak, bronchospasm, itch, urticaria.
• Cofactors that lower the threshold - exercise, alcohol, NSAIDs, infection, menstruation, sleep deprivation, beta-blockers and ACE inhibitors (more severe reactions).
• Non-allergic hypersensitivity - mast cell activation without IgE (opioids, radiocontrast, vancomycin), NSAID intolerance (COX-1 inhibition - urticaria, angioedema, asthma), aspirin-exacerbated respiratory disease (asthma, nasal polyps, aspirin sensitivity - Samter's triad).
• Allergy services - adult and paediatric allergy clinics (often within immunology); demand far exceeds capacity in the UK.

Anaphylaxis - Recognition

• Anaphylaxis (Resuscitation Council UK 2021) - a serious, systemic hypersensitivity reaction that is usually rapid in onset and may cause death - with life-threatening Airway, Breathing and/or Circulation problems.
• Features:
  • A - throat and tongue swelling, hoarse voice, stridor, difficulty swallowing.
  • B - shortness of breath, wheeze, persistent cough, hypoxia, cyanosis, respiratory arrest.
  • C - hypotension, shock (pale, clammy), tachycardia (sometimes bradycardia), collapse, reduced consciousness, cardiac arrest.
  • Skin and mucosal - urticaria, flushing, angioedema - present in most, but absent in up to 1 in 5 (especially if hypotension is the main feature).
  • GI - vomiting, abdominal pain, diarrhoea (especially in food allergy).
  • A sense of impending doom.
• Skin or mucosal changes alone (urticaria, angioedema without A, B or C problems) are not anaphylaxis - but watch closely.
• Common triggers:
  • Children - foods (peanut, tree nuts, milk, egg, sesame, fish, shellfish).
  • Adults - drugs (antibiotics, NSAIDs, neuromuscular blockers, chlorhexidine, contrast), insect stings, foods.
  • Unknown (idiopathic) in a proportion - consider mastocytosis.
• Timing - IV drugs: minutes; stings: 10–15 minutes; foods: up to 30 minutes or more (delayed in alpha-gal syndrome - 3–6 hours after red meat).
• Fatal reactions - often in teenagers and young adults with food allergy and asthma, with delayed adrenaline, or when patients sit or stand up (empty ventricle).
• Mimics - vasovagal syncope (bradycardia, pale, no rash), panic attack, acute asthma, hereditary angioedema, scombroid fish poisoning (histamine in spoiled fish), carcinoid, phaeochromocytoma, sepsis.

Anaphylaxis - Emergency Treatment

• Call for help; remove the trigger if possible (stop the infusion); ABCDE.
• Position - lie flat with legs raised if hypotensive; sit up if breathing is difficult; recovery position if unconscious; don't stand or walk the patient (sudden cardiovascular collapse).
• IM adrenaline - the most important treatment - anterolateral thigh, 1 mg/mL (1:1,000):

  Age	IM adrenaline dose
  Adult and child over 12 years	500 micrograms (0.5 mL)
  Child 6–12 years	300 micrograms (0.3 mL)
  Child 6 months – 6 years	150 micrograms (0.15 mL)
  Infant under 6 months	100–150 micrograms (0.1–0.15 mL)

• Repeat IM adrenaline after 5 minutes if A, B or C problems persist.
• High-flow oxygen; IV fluid bolus - crystalloid 500–1,000 mL in adults, 10 mL/kg in children - repeated as needed.
• Refractory anaphylaxis (no improvement after 2 doses of IM adrenaline) - expert help (critical care) for a low-dose IV adrenaline infusion; continue IM doses every 5 minutes until the infusion starts; give further fluids; consider glucagon if on beta-blockers.
• Airway - early anaesthetic input for stridor or swelling; nebulised adrenaline may help upper airway oedema; bronchodilators for persistent bronchospasm after adrenaline.
• Cardiac arrest - standard ALS; IV adrenaline 1 mg (1:10,000) - not IM.
• Antihistamines and steroids are not first-line - they don't treat airway, breathing or circulation problems; non-sedating oral antihistamines can be given for skin symptoms after stabilisation; corticosteroids are not routinely recommended (consider for refractory reactions or ongoing asthma).

⚠️ Safety Pearl: IM adrenaline is safe and its delay is what kills. Never give IV adrenaline as a bolus outside cardiac arrest (risk of arrhythmia and MI) - use IM, and leave IV infusions to those experienced in giving them. Don't let antihistamines or steroids delay adrenaline.

After Anaphylaxis - Tryptase, Observation and Discharge

• Mast cell tryptase - supports the diagnosis (doesn't delay treatment):
  • Sample 1 - as soon as possible after starting treatment.
  • Sample 2 - ideally 1–2 hours after symptom onset (no later than 4 hours).
  • Sample 3 - baseline at least 24 hours after recovery (or at the allergy clinic) - a raised baseline suggests mastocytosis or hereditary alpha-tryptasaemia.
  • A rise of 20% + 2 ng/mL over baseline supports mast cell activation; a normal tryptase doesn't exclude anaphylaxis (especially food-induced).
• Observation (RCUK 2021) - biphasic reactions occur in up to 5% (usually within 12 hours):
  • Fast-track discharge after 2 hours from resolution - good response to a single dose of adrenaline, full resolution, auto-injectors and training provided, and adequate supervision.
  • At least 6 hours - if 2 doses of adrenaline were needed or there is a previous biphasic reaction.
  • At least 12 hours - severe reactions needing more than 2 doses, severe asthma, possible ongoing absorption (e.g. slow-release drugs), late presentation, night-time presentation, or difficulty accessing emergency care.
• Before discharge:
  • Two adrenaline auto-injectors to carry at all times (MHRA), with training (patient and carers) and a written anaphylaxis action plan (e.g. BSACI plan).
  • Avoidance advice for the suspected trigger.
  • Refer to an allergy clinic - all patients with anaphylaxis (NICE CG134) to confirm the trigger and plan.
  • Optimise asthma control; review beta-blockers and ACE inhibitors.
  • Inform the GP; report suspected drug reactions via Yellow Card; record the allergy clearly.
• Using an auto-injector - outer thigh (through clothing), hold for the stated time, call 999, lie down with legs raised (or sit if breathless), use the second device after 5 minutes if no better.

Drug Allergy

• Most adverse drug reactions are not allergic (side effects, intolerance, toxicity); true drug allergy is immune-mediated.
• Types of drug allergy:
  • Immediate (IgE) - within 1 hour (or a few hours): urticaria, angioedema, bronchospasm, anaphylaxis - e.g. penicillins, cephalosporins, neuromuscular blockers, chlorhexidine.
  • Delayed (T-cell) - days to weeks: maculopapular rash (commonest - often benign, e.g. amoxicillin with EBV), fixed drug eruption, severe cutaneous adverse reactions (SCARs):
    • Stevens–Johnson syndrome / toxic epidermal necrolysis - mucosal erosions, skin detachment, fever (carbamazepine, lamotrigine, allopurinol, sulfonamides, nevirapine).
    • DRESS - rash, fever, eosinophilia, lymphadenopathy, hepatitis and other organ involvement 2–8 weeks after starting (anticonvulsants, allopurinol, vancomycin, sulfonamides).
    • AGEP - sudden sterile pustules on red skin (antibiotics).
• NICE CG183 - when a suspected drug allergy occurs:
  • Document the drug, the reaction, the date, and the route and indication.
  • Tell the patient (written information); update records across care settings.
  • Refer to specialist allergy services after anaphylaxis or severe reactions, or if the patient needs the drug class and no alternative is suitable.
  • Don't do specific IgE or skin tests in non-specialist settings.
• After a SCAR - never rechallenge with the drug; avoid structurally related drugs; consider HLA associations (see Genetics chapter).
• NSAID hypersensitivity - usually cross-reactive between NSAIDs (COX-1 mechanism) - paracetamol usually tolerated; selective COX-2 inhibitors often tolerated (specialist).
• Radiocontrast reactions - mostly non-IgE; premedication has limited evidence - use a different agent and be prepared.
• Desensitisation - temporary tolerance (e.g. chemotherapy, antibiotics in cystic fibrosis) under specialist supervision.

Penicillin Allergy and Delabelling

• About 10% of people in the UK have a penicillin allergy label - but over 90% of them are not allergic when tested.
• Harms of a wrong label - use of broader-spectrum or less effective antibiotics, more C. difficile and MRSA, more surgical site infections, longer hospital stays, antimicrobial resistance.
• Low-risk histories (suitable for delabelling) - non-allergic symptoms (nausea, diarrhoea, headache), isolated mild rash many years ago, family history only, "unknown" childhood reaction.
• Penicillin allergy delabelling - risk assessment (e.g. PEN-FAST score), then direct oral challenge with amoxicillin for low-risk patients (increasingly done by trained non-allergists, pharmacists and in pre-operative clinics); skin testing for higher-risk histories (allergy clinic).
• Cross-reactivity:
  • Cephalosporins - low risk (about 1–2%) overall; driven by similar side chains (e.g. amoxicillin–cefalexin, cefadroxil); third-generation cephalosporins with different side chains (ceftriaxone) are usually tolerated except after penicillin anaphylaxis (follow local guidance).
  • Carbapenems - under 1%.
  • Aztreonam - negligible (except ceftazidime side chain).
• Ampicillin or amoxicillin rash in glandular fever - usually not true allergy (EBV-related); delabelling is often possible.
• Record accurately - "allergy" vs "intolerance" vs "side effect" - and remove the label (in all records) when tests are negative.

Perioperative Anaphylaxis

• About 1 in 10,000 anaesthetics (NAP6 audit - Royal College of Anaesthetists, 2018) - hypotension is the commonest and often the only feature; bronchospasm, rash may be absent or hidden under drapes.
• Commonest triggers (NAP6):
  • Antibiotics - teicoplanin and co-amoxiclav (the commonest causes).
  • Neuromuscular blocking agents - suxamethonium, rocuronium, atracurium.
  • Chlorhexidine (skin preparation, coated catheters, lubricant gels - hidden exposure).
  • Patent blue dye (sentinel node biopsy - delayed, prolonged).
  • Latex - now rare.
• Treatment - standard anaphylaxis treatment; IV adrenaline titrated by anaesthetists; tryptase samples.
• Follow-up - refer to a specialist allergy or anaesthetic allergy clinic to identify the culprit (skin testing to all drugs given); give the patient a letter and alert; ensure future anaesthetics avoid the culprit.
• Sugammadex can reverse rocuronium but is itself a rare cause of anaphylaxis.

IgE-mediated Food Allergy

• Affects about 6–8% of children and 2–3% of adults; the commonest cause of anaphylaxis in children.
• Main allergens - cow's milk, hen's egg, peanut, tree nuts, sesame, fish, shellfish, wheat, soya, kiwi.
• Natural history - milk and egg allergy are usually outgrown (by school age); peanut, tree nut, fish and shellfish allergy usually persist.
• Presentation - within minutes to 2 hours of eating: urticaria, angioedema, vomiting, abdominal pain, wheeze, anaphylaxis.
• Diagnosis (NICE CG116) - allergy-focused history; skin prick test or specific IgE (and component testing - Ara h 2 for peanut); oral food challenge (gold standard) if uncertain.
• Prevention - introduce allergenic foods (egg and peanut) from around 6 months, alongside other solids, and keep them in the diet regularly - including in babies with eczema (higher risk) - the LEAP study showed early peanut introduction reduces peanut allergy by about 80%; don't introduce solids before 4 months.
• Management:
  • Avoidance and label reading - 14 major allergens must be declared on food labels in the UK; Natasha's Law (2021) requires full ingredient labels on foods pre-packed for direct sale.
  • Dietitian input (nutrition, especially for milk allergy).
  • Written allergy action plan; adrenaline auto-injectors for those with previous anaphylaxis, asthma, peanut or tree nut allergy (risk factors), or limited access to care.
  • Oral immunotherapy - gradually increasing doses of allergen to raise the threshold - Palforzia (peanut) for children aged 4–17 (NICE TA769); milk and egg ladders for non-IgE and mild IgE allergy (specialist).
  • Schools - spare auto-injectors held by schools (since 2017).
• Special syndromes:
  • Pollen food syndrome (oral allergy syndrome) - itchy mouth and lips with raw fruits and vegetables (apple, cherry, carrot, hazelnut) in people with birch pollen allergy - cooked forms tolerated; usually mild.
  • Food-dependent exercise-induced anaphylaxis - e.g. wheat (omega-5 gliadin) - reaction only if food is followed by exercise.
  • Alpha-gal syndrome - delayed (3–6 hours) anaphylaxis after red meat, following tick bites; also gelatin and cetuximab reactions.
  • Lipid transfer protein allergy - peach, nuts, other plant foods - can be severe (cofactor-dependent).

Non-IgE Food Allergy and Eosinophilic Oesophagitis

• Non-IgE-mediated cow's milk allergy - the commonest in infants; delayed symptoms (hours to days):
  • Reflux, vomiting, colic, diarrhoea or constipation, blood and mucus in stools (food protein-induced proctocolitis), faltering growth, eczema.
  • Skin tests and IgE are negative - diagnosis by elimination and reintroduction (2–4 weeks).
  • Treatment - breastfeeding mothers exclude dairy (with calcium and vitamin D); formula-fed babies - extensively hydrolysed formula (or amino acid formula if severe); reintroduce via the milk ladder (iMAP) from about 9–12 months; most outgrow it.
• Food protein-induced enterocolitis syndrome (FPIES) - repetitive profuse vomiting 1–4 hours after the trigger (milk, soya, rice, oats, fish), pallor, lethargy, hypotension, sometimes diarrhoea - no skin or respiratory symptoms; adrenaline doesn't help; treat with IV fluids and ondansetron; avoid the trigger.
• Eosinophilic oesophagitis (EoE) - chronic, allergen-driven (often milk, wheat) oesophageal inflammation:
  • Adults (often young atopic men) - dysphagia and food bolus obstruction; children - feeding difficulty, vomiting, pain.
  • Endoscopy - rings ("trachealisation"), furrows, white exudates; biopsy - 15 or more eosinophils per high-power field.
  • Treatment - PPI, orodispersible budesonide, elimination diets, dupilumab (refractory - NICE criteria), endoscopic dilatation of strictures.
• Coeliac disease is an immune-mediated reaction to gluten (not an allergy) - see the Gastroenterology chapter.
• Food intolerance (non-immune) - lactose intolerance, FODMAP sensitivity, caffeine, histamine-rich foods.

Allergic Rhinitis and Allergen Immunotherapy

• Allergic rhinitis - sneezing, rhinorrhoea, nasal blockage and itch, often with allergic conjunctivitis; affects about 1 in 5 people.
  • Seasonal (hay fever) - tree pollen (spring), grass pollen (early summer - commonest in the UK), weed pollen (late summer).
  • Perennial - house dust mite, pets, moulds, occupational allergens.
• Link with asthma - "united airway" - poorly controlled rhinitis worsens asthma; thunderstorm asthma in grass pollen allergy.
• Treatment (step up):
  • Allergen avoidance; saline nasal douching.
  • Non-sedating oral antihistamines (cetirizine, loratadine, fexofenadine) or intranasal antihistamine (azelastine).
  • Intranasal corticosteroids (mometasone, fluticasone) - the most effective single treatment - regular use, correct technique, start before the pollen season.
  • Combined intranasal steroid and antihistamine (fluticasone–azelastine).
  • Short courses of oral steroids rarely (e.g. exams); avoid depot IM steroid injections.
  • Leukotriene antagonists (montelukast) - limited role (neuropsychiatric side effects).
• Allergen immunotherapy - for persistent moderate to severe symptoms despite treatment, with a single dominant allergen (grass, tree pollen, house dust mite, venom):
  • Sublingual (SLIT) - daily tablets (e.g. grass pollen, house dust mite) at home after the first dose in clinic.
  • Subcutaneous (SCIT) - injections in specialist clinics (anaphylaxis risk - observe for 1 hour).
  • Course of 3 years - benefit persists for years after stopping; may reduce the development of asthma in children.
  • Avoid in uncontrolled asthma.

Insect Venom Allergy

• Hymenoptera stings - wasps (commonest in the UK - late summer) and honeybees (beekeepers and their families; stinger left in the skin).
• Reaction types:
  • Large local reaction - swelling over 10 cm lasting over 24 hours - common; low risk of future systemic reaction; treat with antihistamines, cold compresses, short oral steroid if severe; not cellulitis (usually no antibiotics).
  • Systemic reaction - urticaria beyond the sting site, angioedema, anaphylaxis - refer to allergy clinic.
• Investigations - specific IgE to bee and wasp venom (and components), baseline tryptase (systemic mastocytosis is common in severe venom anaphylaxis - especially with hypotension and no urticaria).
• Venom immunotherapy - for systemic reactions beyond the skin (and in some with skin-only systemic reactions and high exposure) - subcutaneous injections for 3–5 years - reduces the risk of a future systemic reaction from about 30–60% to under 5–10%; longer or lifelong if mastocytosis.
• Practical - two adrenaline auto-injectors, avoidance (shoes outdoors, care with food and drink outside, beekeeping), sting action plan.
• Beta-blockers and ACE inhibitors - may worsen reactions; review case by case (specialist advice).

Urticaria

• Urticaria - itchy, raised wheals (hives) with surrounding redness, each lasting under 24 hours, with or without angioedema.
• Acute urticaria (under 6 weeks) - common; causes - viral infection (especially in children), foods, drugs (NSAIDs, antibiotics, opioids), insect stings; often no cause found - non-sedating antihistamine; short oral steroid course if severe.
• Chronic urticaria (6 weeks or more):
  • Chronic spontaneous urticaria - no external trigger; autoimmune in many (IgG against IgE or its receptor; associated thyroid autoimmunity); worse with stress, infection, NSAIDs, alcohol; usually resolves within 2–5 years; allergy tests aren't helpful (it's rarely due to food).
  • Chronic inducible urticaria - physical triggers - dermographism (commonest - scratching), cold (risk of anaphylaxis when swimming in cold water), cholinergic (small wheals with heat, exercise, sweating), delayed pressure, solar, aquagenic, vibratory.
• Investigations in chronic spontaneous urticaria - limited: FBC, CRP or ESR; TFTs and thyroid antibodies if suggested; more if atypical.
• Treatment (BSACI and international guidelines):
  1. Regular second-generation antihistamine (cetirizine, loratadine, fexofenadine) at the standard dose.
  2. Increase up to 4 times the licensed dose (off-label) if needed.
  3. Omalizumab (anti-IgE - NICE TA339) for severe chronic spontaneous urticaria not controlled by antihistamines.
  4. Ciclosporin if omalizumab fails (specialist); remibrutinib and dupilumab are newer options.
• Avoid NSAIDs, codeine and excess alcohol; avoid long-term oral steroids.
• Urticarial vasculitis - wheals lasting over 24 hours, burning rather than itch, leaving bruising or pigmentation; may have low complement (hypocomplementaemic urticarial vasculitis - associated with SLE) - skin biopsy.

Angioedema - Histamine or Bradykinin?

• ACE inhibitor angioedema:
  • About 1 in 200 people on ACE inhibitors; more common in people of Black African or Caribbean ancestry, smokers and women.
  • Can occur at any time - even after years of uneventful use; typically lips, tongue, face, larynx; sometimes bowel (abdominal pain).
  • Management - airway first (early senior anaesthetic and ENT involvement - fibreoptic intubation or surgical airway may be needed); stop the ACE inhibitor permanently; adrenaline may be tried if the cause is unclear but often doesn't work; icatibant or C1 inhibitor concentrate (or FFP) are sometimes used (limited evidence).
  • ARBs - small risk of recurrence - use with caution if needed.
• Isolated angioedema without urticaria - always think of drugs and check C4 (low in HAE and acquired C1-INH deficiency).

Hereditary Angioedema

• Autosomal dominant - SERPING1 gene - about 1 in 50,000; about a quarter are de novo (no family history).
• Types:
  • Type 1 (about 85%) - low C1 inhibitor level and function.
  • Type 2 - normal or high level but low function.
  • HAE with normal C1 inhibitor - factor XII, plasminogen and other genes - often oestrogen-dependent (women).
• Features - usually start in childhood or adolescence, worse at puberty:
  • Recurrent non-itchy swelling of limbs, face, genitals - lasting 2–5 days.
  • Abdominal attacks - severe pain, vomiting, ascites - mistaken for an acute abdomen (unnecessary laparotomies).
  • Laryngeal oedema - can be fatal.
  • No urticaria; a prodromal non-itchy serpiginous rash (erythema marginatum).
  • Triggers - trauma (dental work, surgery), stress, infection, oestrogen (combined pill, HRT, pregnancy), ACE inhibitors.
• Tests - C4 (low - best screening test, even between attacks), C1 inhibitor level and function; C1q (normal in HAE, low in acquired angioedema).
• Acute attacks - C1 inhibitor concentrate (IV) or icatibant (bradykinin B2 receptor antagonist - SC; self-administered); fresh frozen plasma if nothing else is available; airway support; analgesia and fluids for abdominal attacks. Adrenaline, antihistamines and steroids don't work.
• Short-term prophylaxis - C1 inhibitor concentrate before dental work, surgery or endoscopy.
• Long-term prophylaxis - lanadelumab (plasma kallikrein inhibitor antibody - SC every 2–4 weeks), berotralstat (oral daily), SC or IV C1 inhibitor; older options - danazol, tranexamic acid.
• Avoid ACE inhibitors and oestrogen-containing contraception or HRT (progestogen-only is preferred); emergency plan, home therapy, alert card; test relatives.
• Acquired angioedema - C1 inhibitor consumption or antibodies - older adults, lymphoproliferative disease or MGUS - low C1q; look for lymphoma.

Mastocytosis and Mast Cell Disorders

• Mastocytosis - clonal expansion of mast cells (usually KIT D816V variant).
  • Cutaneous mastocytosis - mainly children - urticaria pigmentosa (brown macules that urticate when rubbed - Darier's sign), mastocytoma; often improves by adolescence.
  • Systemic mastocytosis - adults - bone marrow involvement; raised baseline tryptase (over 20 ng/mL); features - flushing, itch, diarrhoea, abdominal pain, recurrent anaphylaxis (especially to venom - often hypotension without urticaria), osteoporosis and fractures, hepatosplenomegaly; advanced forms with organ damage (aggressive SM, mast cell leukaemia).
  • Diagnosis - tryptase, KIT D816V in blood or marrow, bone marrow biopsy (WHO criteria).
  • Treatment - avoid triggers (heat, friction, alcohol, some drugs - opioids, NSAIDs, contrast), antihistamines (H1 and H2), sodium cromoglicate (GI), montelukast, adrenaline auto-injectors, bone protection, venom immunotherapy (lifelong); midostaurin or avapritinib for advanced disease.
• Hereditary alpha-tryptasaemia - extra copies of TPSAB1 - common (about 5%) - baseline tryptase above 8 ng/mL; associated with flushing, IBS-type symptoms, joint hypermobility and more severe venom reactions in some.
• Mast cell activation syndrome - episodic multi-system symptoms with documented rise in tryptase and response to mast cell treatments - a strict diagnosis (over-diagnosed).
• Scombroid poisoning - histamine from spoiled fish (tuna, mackerel) - flushing, headache, peppery taste - not allergy; antihistamines.

Allergy at a Glance

Spot the Diagnosis