urticaria and angioedema

quick recognition

• hives — intensely pruritic erythematous plaques with surrounding flare
• angioedema — localised subcutaneous/submucosal swelling, often asymmetric and non-gravity-dependent
• ~40% of chronic spontaneous urticaria (CSU) patients have associated angioedema; ~10% have angioedema only
• hives ≠ allergic reaction; hives ≠ anaphylaxis (though must rule out clinically)

typical hives should be

• itchy but not painful
• individual lesions resolving within 24–48 h in the same spot (total episode may last days to years)
• no bruising or scarring

differential for hives

Mimic	Distinguishing features
urticarial vasculitis	painful, lasts >48 h in same spot, bruising/purpura, may scar
dermatitis (atopic, allergic, irritant)	eczematous morphology, distribution pattern
morbilliform drug rash	diffuse, non-migratory, often 7–14 d after drug start
autoimmune blistering disease	vesicles/bullae, Nikolsky sign

classification

Type	Duration	Key features
acute spontaneous	<6 weeks	most common cause of hives overall; infection, stress, idiopathic
chronic spontaneous (CSU)	≥6 weeks	lifetime prevalence ~4–5%; autoimmune spectrum; not from external allergens
inducible	variable	dermatographism, cold, cholinergic, solar, pressure, aquagenic

chronic spontaneous urticaria

• not triggered by external allergens (food, detergent, pollens, mould)
• spectrum of mild autoimmune disease — autoantibodies against IgE or FcεRI
• not life-threatening but significantly impacts quality of life
• labs and skin testing generally not needed or helpful
• targeted labs and skin biopsy only if red flags

red flags requiring further workup

• atypical hives — painful, bruising, lasting >48 h in same location
• B symptoms — fevers, night sweats, weight loss
• rheumatologic symptoms — arthralgia, oral ulcers, serositis

management of urticaria

step 1: second-generation antihistamines

Drug	Notes
cetirizine (Reactine)	safe in pregnancy and breastfeeding
loratadine (Claritin)	safe in pregnancy and breastfeeding
desloratadine (Aerius)
fexofenadine (Allegra)
bilastine (Blexten)	no renal or hepatic dose adjustment needed
rupatadine (Rupall)

• up-dose to 4× standard dose before adding other agents (e.g. cetirizine 10–40 mg daily, with renal/hepatic adjustment as needed)
• safe for long-term use
• avoid diphenhydramine (Benadryl) — anticholinergic burden, sedation, no benefit over up-dosed 2nd-generation agents (unless severe insomnia despite max-dose antihistamines)
• topical steroids are not effective for urticaria

step 2: acute flares

• short course of oral corticosteroids for symptom relief after antihistamines maxed out
• not for chronic use

step 3: refractory CSU → biologic therapy

• omalizumab (anti-IgE) — first-line biologic for antihistamine-refractory CSU
• may take several weeks to months to reach full effect
• outpatient initiation through allergist

angioedema

histaminergic vs bradykinin-mediated

Feature	Histaminergic	Bradykinin-mediated
frequency	+++common	rare
associated hives	often	never
pruritus	yes	no (burning/tingling)
responds to antihistamines	yes	no
responds to epinephrine	yes	no
responds to corticosteroids	partially	no
causes	spontaneous urticaria, allergy, anaphylaxis	hereditary angioedema, acquired AE, ACE inhibitor

angioedema vs other causes of oedema

• onset minutes to hours, spontaneously resolves in hours to days
• asymmetric distribution, not gravity-dependent
• involvement of face, lips, larynx, bowels
• if relevant, associated hives or signs of anaphylaxis

approach to angioedema

#1. Rule out anaphylaxis and airway compromise

• isolated visible angioedema alone is not anaphylaxis
• if airway compromise → call for senior staff, airway team
• consider other causes: cellulitis, lymphoedema

#2. Associated hives?

• if yes → almost always spontaneous hives with angioedema → treat with antihistamines

#3. No hives — response to antihistamines, epinephrine, corticosteroids?

• if yes → histamine-mediated angioedema (e.g. spontaneous hives)

#4. Known HAE, acquired angioedema, or ACE inhibitor angioedema?

• if yes → treat as bradykinin-mediated → see hereditary angioedema for acute treatment

#5. On ACE inhibitor?

• duration of use is irrelevant — can occur after years
• stop ACE inhibitor, treat supportively
• recurrence may persist for several months after discontinuation
• ARBs are safe to use

#6. Order serum C4 + C1 inhibitor level

• if low → consistent with hereditary or acquired angioedema
• exception: HAE with normal C1 inhibitor exists but is rare

#7. Monitor until improving

• generally uniphasic — fluctuating course within a single episode is unusual
• refer to allergy on discharge

hereditary angioedema

See hereditary angioedema for full coverage — classification, diagnostic workup, acute treatment (Berinert dosing), short-term and long-term prophylaxis, and ACE inhibitor–induced angioedema.

what NOT to do

• assume hives = allergic reaction — spontaneous urticaria is far more common
• treat angioedema as anaphylaxis when there are no other systemic features
• use first-generation antihistamines (diphenhydramine) as first-line
• prescribe long-term corticosteroids for chronic urticaria
• order extensive allergy testing for CSU — labs and skin testing are not helpful
• give epinephrine/antihistamines/steroids for suspected HAE instead of C1 inhibitor concentrate
• assume ACE inhibitor angioedema cannot occur after years of use
• dismiss factitious angioedema without first ruling out rare causes