GRAND ROUNDS 06 · DISEASE EDUCATION

Anaphylaxis

One mast cell, four systems — epinephrine is the answer
CRASH CARD
crashcard.co
18 × 24 IN · CLASSROOM REFERENCE
Anaphylaxis = an acute, systemic IgE-mediated (or non-IgE) hypersensitivity reaction — mast cells & basophils dump mediators, hitting skin · airway · circulation · gut at once. The diagnosis is clinical, the treatment is IM epinephrine, and delay kills. Don't wait for tests. Don't reach for antihistamines first. Give epi.
1Pathophysiologyallergen → cascade
1Sensitize — first exposure primes plasma cells → IgE coats mast cells & basophils.
2Re-expose — allergen crosslinks surface IgE → the cell is triggered.
3Degranulate — release of histamine, tryptase, leukotrienes, prostaglandins, PAF.
4Multisystem hit — vasodilation + capillary leak, bronchospasm, edema, urticaria, GI cramps.
5Distributive shock — plasma shifts into tissue → empty tank, airway swells → arrest.

Non-IgE routes (direct mast-cell activation, complement, contrast, NSAIDs, exercise) look identical & are treated identically.

2Presentationby system

Skin / mucosa (~80–90%): flushing, urticaria, pruritus, angioedema — lips, tongue, face.

Airway: throat tightness, hoarse voice, stridor, laryngeal edema, wheeze, bronchospasm.

Cardiovascular: tachycardia, hypotension, dizziness, collapse — distributive shock.

GI: cramping, vomiting, diarrhea — a clue that's easy to miss.

Biphasic: a second wave hours later (median ~8 h, up to ~72 h) with no re-exposure — why we observe.

SSeveritygrade & act early
GRADEFINDINGSACT
Mildskin / GI onlywatch, ready epi
Moderate+ resp OR GI markedgive epi
Severeairway / ↓BP / hypoxiaepi + fluids O₂
Peri-arreststridor, shock, ↓GCSepi, airway, resus

Any airway or circulatory sign = epinephrine now. Don't wait for shock to declare itself — it can be minutes.

TTriggersthe usual culprits
Foods (nuts, shellfish, egg, milk)Stings (bee · wasp) Drugs (β-lactams)NSAIDs LatexIV contrast Exercise / food-dependentIdiopathic
6Differentialthe mimics
  • Vasovagal syncope
  • Asthma (isolated)
  • Scombroid poisoning
  • Hereditary angioedema
  • Panic / anxiety attack
  • Shock of other cause
  • Carcinoid / mastocytosis
  • Vocal-cord dysfunction

Watch: Hereditary angioedema is bradykinin-driven — no urticaria, no response to epi / antihistamine / steroid. Scombroid mimics after spoiled fish and responds to antihistamines.

The Reactionmast-cell degranulation
→ four-system attack
ONE CELL, FOUR TARGETS — EPI REVERSES EACH IgE crosslink · mediators
allergen + IgE crosslink MAST CELL ① AIRWAY laryngeal / tongue edema, stridor, bronchospasm EPI β₂ → bronchodilate, α₁ → shrink mucosa ② CIRCULATION vasodilation + capillary leak → distributive shock EPI α₁ → vasoconstrict, β₁ → inotropy ③ SKIN / MUCOSA urticaria, angioedema, flush EPI stabilizes the mast cell, stops further release ④ GI cramps, vomiting, diarrhea EPINEPHRINE the antidote to all four
Airway β₂ · α₁
Edema + bronchospasm. Epi opens it & shrinks the mucosa.
Circulation α₁ · β₁
Leak + vasodilation. Epi tightens vessels, drives the heart.
Skin stabilize
Hives & angioedema. Epi halts further mediator release.
Gut ↓ mediators
Cramps & vomiting settle as the reaction is shut down.
3Diagnosisclinical — NIAID/WAO criteria
1Acute onset (min–hrs) with skin/mucosa involvement AND either respiratory compromise OR ↓BP / end-organ hypoperfusion.
2≥ 2 systems involved quickly after a likely allergen (skin, resp, CV, or persistent GI).
3↓ BP after exposure to a known allergen for that patient (isolated hypotension counts).

WAO 2020 also accepts isolated laryngo- or bronchospasm after a highly-probable allergen — skin need not be present. Tryptase (draw 15 min–3 h, peak 1–2 h; repeat baseline ≥24 h) is confirmatory, not a gatenever delay epinephrine for a level.

Biphasic Reactionwhy we observe after resolution
ONE HIT, THEN A SECOND WAVE severity vs time · no re-exposure
severity time → ( first reaction ····· asymptomatic window ~8 h (up to 72 h) ····· second wave ) EPI feels better BIPHASIC no new exposure 1st REACTION

Up to ~1 in 20 react a second time — hours after apparent resolution, with no re-exposure. That's why we observe, arm every patient with an auto-injector, and warn them to re-dose & return if it recurs.

4Treatmentepi first · adjuncts second · per protocol
Epinephrine IM 0.3–0.5 mg 1:1000 (1 mg/mL) · peds 0.01 mg/kganterolateral thigh, first-line & life-saving. Repeat q5–15 min.
Position supine, legs updo NOT sit them upright (empty-vena-cava / collapse risk). Pregnant → left lateral.
High-flow O₂; monitor; prepare a difficult airway early if the throat is swelling.
Large-bore IV × 2 + crystalloid bolus 1–2 L (peds 20 mL/kg) for shock — the tank is empty.
Adjuncts — SECOND-LINE only: antihistamines (itch/hives), steroids, inhaled β-agonist for bronchospasm. Never a substitute for epi.
Refractory: epinephrine infusion; add glucagon 1–5 mg IV if on a β-blocker; vasopressors.
5Critical Proceduresthe airway only gets harder
⚠ Secure the airway before it closes
  • Progressing angioedema → intubate early — swelling only worsens; a delayed airway becomes a surgical one.
  • Have the double setup ready (cric kit, most experienced operator); anticipate distorted anatomy.
  • Epinephrine infusion for shock not responding to repeat IM + fluids — titrate to MAP.
  • On a β-blocker & refractory? Epi is blunted — give glucagon to bypass the β-receptor.
PPitfalls & Pearls
  • EPI FIRST. Antihistamines & steroids are not the treatment — they don't reverse shock or airway edema.
  • IM, not SC or IV push for the initial dose — IV push causes arrhythmia; SC is too slow.
  • Don't sit them up. Upright posture in shock has caused fatal cardiac arrest.
  • Delayed epi = deaths. The commonest error is giving it late, or not at all.
  • Observe for biphasic reactions — a second wave can come hours later without re-exposure.
  • Angioedema without hives + no epi response? Think hereditary angioedema (bradykinin) — different drugs.
REMEMBER — One cell, four systems: airway · circulation · skin · gut. EPI IM, thigh, repeat. Lay them flat, fill the tank, oxygen. Adjuncts are second. If tests delay epi → give epi anyway.
DDisposition
OBSERVE / ADMIT
  • Observe after response per local policy (risk-stratify; longer if severe / needed >1 dose)
  • Refractory, >1 epi dose, or β-blocker → admit
  • Poor access to care / prior biphasic
DISCHARGE
  • Epi auto-injector Rx ×2 + technique taught
  • Written action plan
  • Allergist referral
  • Avoidance counseling
Sheet
Anaphylaxis
Series / No.
GRAND ROUNDS 06
Part No.
CC-GR-06
Rev
A
Status
EDUCATION REFERENCE — NOT A PROTOCOL. VERIFY LOCALLY.

SOURCES: WAO Anaphylaxis Guidance 2020 · NIAID/FAAN diagnostic criteria · AAAAI/ACAAI/JCAAI Anaphylaxis Practice Parameter (2020 update) · Resuscitation Council UK, Emergency Treatment of Anaphylactic Reactions; Tintinalli, Emergency Medicine. Doses educational — not medical advice & not a protocol; reference for trained clinicians only. Verify all drugs, doses & treatments against local protocol & current guidelines. Full disclaimer: crashcard.co/legal. © 2026 Claustrum LLC d/b/a Crash Card · crashcard.co · Printed in Minnesota.