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Clinical Assessment

• Sudden onset swelling of face, arms, and hands
• Shivering (rigors) all over the body - since this morning
• Had morning meals (possible food trigger)
• No alcohol, no smoking

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Most Likely Diagnosis: Anaphylaxis / Allergic Reaction with Angioedema

Why this fits:

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Differential Diagnoses to Consider

1. Anaphylaxis (food-triggered) - Most likely. Rigors + angioedema post-meal.
2. Hereditary Angioedema (HAE) - Autosomal dominant C1 esterase inhibitor deficiency. Attacks of swelling (face, hands, arms) WITHOUT urticaria or pruritus. Triggered by minor stress. Ask: family history? recurrent attacks? abdominal pain episodes?
3. ACE inhibitor-induced angioedema - Ask about any antihypertensive medications. 0.1-0.7% incidence. NOT responsive to antihistamines/epinephrine.
4. Sepsis with early distributive phase - Rigors are a hallmark of bacteremia/septicemia. The facial swelling is less typical here - but must rule out.
5. Drug reaction - Any new medication? NSAIDs taken with morning meal?

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Immediate Assessment Priorities

CRITICAL - Airway First

Angioedema of the tongue, lips, and face carries risk of airway obstruction - which can develop rapidly and unpredictably. (Tintinalli's)

• Any throat tightness, stridor, hoarseness, difficulty swallowing?
• Tongue or lip swelling?
• Breathing difficulty?
• Blood pressure (hypotension = anaphylaxis)
• Rash, urticaria, pruritus?
• SpO2

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History to Elicit

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Emergency Management (if anaphylaxis confirmed)

1st Line - Epinephrine (MANDATORY if anaphylaxis)

• Epinephrine 0.3-0.5 mg IM (anterolateral thigh, 1:1000 concentration)
• Repeat every 5-15 min as needed
• Do NOT delay for antihistamines or steroids

Supportive

• IV access - large bore, normal saline bolus if hypotensive
• Oxygen - high flow if SpO2 decreased
• Antihistamines - H1 (diphenhydramine 25-50 mg IV/IM) + H2 (ranitidine 50 mg IV)
• Corticosteroids - Hydrocortisone 200 mg IV or Methylprednisolone 1-2 mg/kg IV (reduces biphasic reaction risk)
• Monitor for biphasic anaphylaxis (recurrence 1-72 hours later)
• Observe for minimum 4-6 hours after reaction

If HAE suspected (no urticaria, no pruritus, family history, no response to above):

• C1 esterase inhibitor concentrate (Berinert 20 U/kg IV)
• Icatibant 30 mg SC (bradykinin-2 receptor antagonist)
• Note: Antihistamines, epinephrine, and corticosteroids have minimal effect on HAE

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Red Flags - Call for Immediate Escalation

• Stridor / voice change / throat tightness - prepare for intubation
• SpO2 < 94%
• Hypotension (SBP < 90 mmHg)
• Loss of consciousness
• Rapidly worsening swelling

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Anaphylaxis Treatment Guidelines & Protocols (2024-2026)

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1. Updated Diagnostic Criteria (GA²LEN 2024 Consensus)

"Anaphylaxis is a serious allergic (hypersensitivity) reaction that can progress rapidly and may cause death."

Key update: Skin involvement is no longer required to diagnose anaphylaxis. Cardiovascular or respiratory symptoms alone after allergen exposure are sufficient.

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2. Severity Grading (WAO 2024 Updated System)

Epinephrine should be given regardless of grade - grading mainly guides monitoring intensity and adjunct therapies.

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3. Treatment Protocol - Step by Step

STEP 1: Call for Help / Activate Emergency Response

• Lay patient flat (Trendelenburg / supine with legs elevated)
• If breathing difficulties: semi-recumbent position
• Pregnant patients: left lateral tilt
• Do NOT stand a hypotensive patient upright - associated with increased mortality

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STEP 2: EPINEPHRINE (Adrenaline) - THE ONLY FIRST-LINE DRUG

• Repeat every 5-15 minutes if no response - up to 3 doses IM
• IV epinephrine only in refractory/severe cases with cardiovascular monitoring in place (higher risk of arrhythmias - use IV only in ICU/resus settings)
• New 2024-2025: Intranasal epinephrine spray (neffy®) has been approved and shows pharmacokinetics equivalent to IM injection - useful when IM access is difficult, especially in community settings

⚠️ Antihistamines and corticosteroids are adjuncts only - NOT first-line. Giving them before epinephrine causes dangerous delays and is associated with deaths.

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STEP 3: Positioning & IV Access

• Establish large-bore IV access
• IV crystalloid bolus (normal saline): 10-20 mL/kg rapidly if hypotensive
• Continuous monitoring: SpO2, ECG, BP every 5 minutes

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STEP 4: Oxygen

• High-flow oxygen (10-15 L/min via face mask) if SpO2 <90% or respiratory distress
• Nebulized albuterol (salbutamol) for bronchospasm not resolving after epinephrine

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STEP 5: Adjunct Medications (after epinephrine)

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STEP 6: Refractory Anaphylaxis (2024 Review - Pouessel et al., Clin Exp Allergy)

1. IV epinephrine infusion: 0.1-1 mcg/kg/min (in monitored setting)
2. Aggressive IV fluid resuscitation - up to 4-5L may be needed
3. Second-line vasopressors: norepinephrine (preferred), vasopressin, dopamine
4. Methylene blue: suggested in refractory vasodilatory shock
5. Extracorporeal life support (ECLS/ECMO): rescue therapy in cardiac arrest from anaphylaxis
6. Genetic factors to investigate: platelet activating factor-acetylhydrolase deficiency, hereditary alpha-tryptasemia, mastocytosis

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4. Airway Management

• Stridor, hoarseness, or voice change = immediate preparation for advanced airway
• Nebulized racemic epinephrine for upper airway edema
• Early intubation if impending obstruction - delay is dangerous as edema progresses rapidly
• Consider surgical airway (cricothyrotomy) if intubation fails in severe laryngeal edema

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5. Observation Period

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6. Discharge & Long-Term Management

1. Epinephrine autoinjector prescription (2 devices - one for immediate use, one as backup)
2. Written anaphylaxis action plan
3. Allergen avoidance counseling (identify and label known trigger)
4. Allergy/immunology referral for trigger workup
5. Serum tryptase at follow-up (to rule out mastocytosis in severe/recurrent cases)
6. For insect venom anaphylaxis: consider venom immunotherapy (highly effective for long-term prevention)
7. Consider omalizumab for refractory/recurrent idiopathic anaphylaxis (EAACI 2025)

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7. Special Note: ACE Inhibitor-Induced Angioedema

• Epinephrine, antihistamines, and steroids are largely ineffective
• Use: Icatibant 30 mg SC (bradykinin-2 receptor antagonist) or C1 esterase inhibitor concentrate 1000 U IV

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Key Sources

• GA²LEN 2024 Consensus Report - Dribin et al., JACI 2025 [PMID: 39880313]
• Refractory Anaphylaxis Guidelines Overview - Pouessel et al., Clin Exp Allergy 2024 [PMID: 38866583]
• ERC First Aid Guidelines 2025 - Djärv et al., Resuscitation 2025 [PMID: 41117568]
• SFAR/SFA Perioperative Hypersensitivity Guidelines 2025 [PMID: 42335666]
• WAO White Book on Allergy 2026
• Recent Epidemiology & Management Review - PMC 2025

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Allergic Reaction with Redness + Angioedema

Face/Neck + Arms/Hands | Unknown Trigger

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What You Are Seeing - Urticaria with Angioedema

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Pathophysiology

Trigger (food/drug/unknown)
         ↓
IgE on mast cells/basophils cross-linked
         ↓
Degranulation → Histamine, leukotrienes, prostaglandins
         ↓
H1 receptor activation on cutaneous vessels
         ↓
Vasodilation → ERYTHEMA (redness/flushing)
Vascular leak in superficial dermis → WHEALS (urticaria)
Vascular leak in deep dermis/subcut → ANGIOEDEMA (swelling)

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Clinical Picture in This Patient

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FIRST - Assess for Anaphylaxis (MANDATORY)

If ANY of the above are present → treat as anaphylaxis (see previous protocol). Epinephrine first, everything else second.

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Management: Allergic Reaction WITHOUT Anaphylaxis Features

Step 1: H1 Antihistamines (FIRST LINE)

Up to 4x the standard dose of 2nd generation antihistamines may be used for poorly controlled reactions (Rosen's EM).

Step 2: H2 Antihistamines (ADD-ON)

• Ranitidine 50 mg IV or Famotidine 20 mg IV - 15% of dermal histamine receptors are H2; adding H2 blockade improves response
• Do NOT use as monotherapy

Step 3: Corticosteroids (for moderate-severe or widespread redness/angioedema)

• Prednisone 40-60 mg PO daily for 5-7 days
• Hydrocortisone 200 mg IV if unable to take oral
• Role: reduce prolonged/recurrent reactions; do NOT give before antihistamines
• Note: A double-blind RCT showed no additional benefit of prednisone over levocetirizine alone in acute urticaria ≤24 hrs - use clinical judgment

Step 4: Epinephrine (for severe urticaria/angioedema even without full anaphylaxis)

• 0.3-0.5 mg IM (anterolateral thigh) if symptoms are rapid/severe or worsening
• Do not withhold if there is any concern about progression

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Causes to Consider (for Unknown Trigger Workup)

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Key Differentials for Redness + Swelling

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Disposition

• Avoid suspected trigger
• Prescribe oral antihistamines (cetirizine 10 mg BD x 5-7 days)
• Consider short steroid course if angioedema present
• Allergy referral for trigger identification (skin prick test / specific IgE)
• Prescribe epinephrine autoinjector if reaction was severe or trigger unclear

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