Quincke’s Edema (Angioedema) 360°: Evidence-Based Guide to Diagnosis, Epinephrine, Icatibant, C1-INH & Airway

By HealthSpark Studio Allergy & Immunology Team | Published October 30, 2025 | Updated Ongoing | 35 min read

Quincke’s edema, lip swelling, tongue edema, stridor, epinephrine, icatibant, C1-INH, airway

Quincke’s Edema, now known as Angioedema, is a rapid, self-limited swelling of the deep dermis, subcutaneous, or submucosal tissues. First described in 1882 by Heinrich Quincke, it is a potentially life-threatening condition due to airway compromise.

Two pathways:

Histamine-mediated (allergic): urticaria, itching, responds to antihistamines
Bradykinin-mediated (HAE, ACEi): no urticaria, abdominal pain, fails antihistamines

This evidence-based guide covers:

Pathophysiology: C1-INH deficiency, ACE breakdown failure
Symptoms: Lip, tongue, laryngeal edema
Diagnosis: C4, C1-INH level/function, tryptase
Treatment: Epinephrine, icatibant, C1-INH, FFP, tranexamic acid
Management: Airway, long-term prophylaxis

95% survival with early intervention. Act in 30 min.

Epidemiology & Risk Factors

Global Burden

HAE Prevalence: 1:50,000
ACEi Angioedema: 0.3–0.7% of users
Peak Age HAE: 2nd–3rd decade
ACEi: First 30 days (50%), up to 10 years

Risk Factors

Family history (HAE)
ACE inhibitor use (OR 4.5)
African descent (ACEi)
Estrogen (HAE type III)
NSAIDs, food, stress (allergic)

J Allergy Clin Immunol 2023, Grade A

Pathophysiology

Type	Mediator	Mechanism	Urticaria	Response to Antihistamine
Allergic	Histamine	Mast cell degranulation	Yes	Yes
HAE Type I/II	Bradykinin	C1-INH deficiency → ↑ bradykinin	No	No
ACEi	Bradykinin	ACE inhibition → bradykinin accumulation	No	No

Bradykinin vs histamine pathway in angioedema

Symptoms: Ultra-Detailed Clinical Presentation

Onset: Minutes (allergic) to hours (bradykinin). Duration: 24–72h. Recurrent: HAE.

1. Lip Swelling (80%)

Appearance: Asymmetric, soft, non-pitting, pale or erythematous
Sensation: Tight, numb, burning (bradykinin); itching (histamine)
Speech: Lisping, drooling

2. Tongue Edema (60%)

Progression: Base → tip, rapid
Symptoms: Difficulty speaking, dysphagia, drooling
Airway Risk: Posterior displacement → obstruction

3. Laryngeal Edema (1–2% HAE, 50% mortality if untreated)

Voice: Hoarse, muffled
Breathing: Stridor, dyspnea, tripoding
Exam: Fiberoptic shows arytenoid edema

4. Abdominal Attacks (50% HAE)

Pain: Colicky, severe, nausea, vomiting, diarrhea
Imaging: Bowel wall edema on CT

5. Skin Involvement

Extremities, genitals: Tense, non-pruritic
Urticaria: Only in histamine-mediated

Clinical photo: asymmetric lip swelling in angioedema

Red Flag: Tongue base swelling + stridor → Intubate now. No urticaria + abdominal pain → HAE/ACEi.

Differential Diagnosis

Condition	Key Distinguisher
Anaphylaxis	Urticaria, wheezing, hypotension
Cellulitis	Fever, erythema, tenderness
Superior Vena Cava Syndrome	Chronic, facial plethora, collateral veins
Hypothyroidism	Generalized, slow onset, myxedema

Diagnostic Workup

History: Trigger, family history, ACEi use
Labs (HAE suspicion):
- C4 (low in 95% HAE)
- C1-INH level & function
- C1q (normal in HAE I/II)
Allergic: Tryptase (↑ in anaphylaxis)
Imaging: Only if abdominal pain (CT) or airway (fiberoptic)

Normal C4 during attack → rules out HAE.

Treatment & Management: Step-by-Step Protocol

Step 1: Airway Assessment (0–2 min)

Stridor, drooling → Prepare for intubation
Fiberoptic laryngoscopy
Surgical airway if failed

Step 2: Classify Type

Feature	Histamine	Bradykinin (HAE/ACEi)
Urticaria	Yes	No
Response to Antihistamine	Yes	No
Abdominal Pain	Rare	Common
Family History	No	Yes (HAE)

Step 3: Acute Treatment

Type	First-Line	Dose	Alternative
Histamine	Epinephrine IM	0.3–0.5 mg	Antihistamine, steroid
HAE	C1-INH concentrate	20 U/kg IV	Icatibant 30 mg SC
ACEi	Icatibant	30 mg SC	FFP 2 units

Do NOT use antihistamines/steroids in bradykinin-mediated.

Step 4: Supportive Care

Observe 6–24h post-resolution
Stop ACEi permanently
HAE prophylaxis: Lanadelumab, berotralstat

Ann Allergy Asthma Immunol 2023, Grade 1A

Long-Term Management

HAE: On-demand C1-INH, prophylaxis if >1 attack/month
ACEi: Switch to ARB (low risk)
Genetic counseling for HAE
Medical alert bracelet

Prevention Strategies

Avoid ACEi in HAE
Pre-procedure prophylaxis (dental, surgery)
Androgens (danazol) for HAE (not first-line)
Avoid triggers: trauma, stress, estrogen

Frequently Asked Questions

Antihistamines work in HAE?

No. Bradykinin-mediated. Use C1-INH or icatibant.

ACEi angioedema timing?

50% in first month, but can occur years later.

When to intubate?

Stridor, voice change, drooling, rapid progression.

FFP safe in HAE?

Yes, contains C1-INH. Use if targeted therapy unavailable.

Can ARB cause angioedema?

Rare (0.01%). Safer than ACEi.

Conclusion

Quincke’s edema is 100% survivable with correct pathway recognition. Urticaria? Epinephrine. No urticaria? Icatibant/C1-INH. With rapid airway control and targeted therapy, 95% resolve in 24h. One injection, one breath, one life saved.

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About the Authors

The HealthSpark Studio Allergy & Immunology Team includes board-certified allergists, immunologists, and emergency physicians. References: J Allergy Clin Immunol, WAO Guidelines, Ann Allergy. Full credentials.

Medical Disclaimer

For educational purposes only. Angioedema is a medical emergency. Seek immediate care for facial swelling, voice change, or breathing difficulty. Epinephrine, icatibant, C1-INH require specialist oversight. Call 911 or go to ER immediately.