Urticaria
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Urticaria (Hives)
Definition
Urticaria (hives) represents one of the most common cutaneous reaction patterns. It involves dilation of vascular structures in the superficial dermis, resulting in transient, pruritic, blanching wheals. Angioedema is the deeper counterpart, originating from the deeper dermis and subcutaneous tissues. Roughly 40% of patients experience both simultaneously, and >20% of the population is affected at some point during their lifetime.
- Acute urticaria: episodes lasting <6 weeks
- Chronic urticaria: recurrence over a period of 6 weeks or more - often idiopathic
Chronic urticaria is more common in women in their 40s and 50s, while acute urticaria is seen more in children with atopic dermatitis. Chronic urticaria peaks in the third and fourth decade.
Pathophysiology
Urticaria results from local degranulation of mast cells with release of histamine and other mediators including slow-reacting substance of anaphylaxis, bradykinin, kallikrein, and acetylcholine. The triggering mechanism can be:
Immunologic:
- IgE-dependent (allergen-IgE-FcεRI activation on mast cells)
- Autoimmune - functional IgG autoantibodies against IgE or FcεRI release histamine from mast cells
- Immune complex-mediated
- Complement-kinin dependent
Nonimmunologic:
- Direct mast cell degranulation by foods, drugs (aspirin, NSAIDs, narcotics), radiocontrast agents
- Vasoactive stimuli, physical stimuli
The result is transient, localized dermal edema produced by transvascular fluid extravasation.
Classification & Causes
Acute Urticaria (< 6 weeks)
| Category | Examples |
|---|---|
| Drugs | Penicillin (most common), aspirin/NSAIDs, narcotics, ACE inhibitors |
| Foods | Seafood, tree nuts, eggs, lobster, strawberries (nonimmunologic histamine release) |
| Infections | Rhinovirus, rotavirus, hepatitis, mononucleosis, coxsackievirus, Candida, parasites |
| Insect stings/bites | Hymenoptera, arthropods |
| Contact | Foods, textiles, animal dander/saliva, topical medications, cosmetics |
| Systemic disease | SLE, lymphoma, carcinoma, hyperthyroidism, rheumatoid arthritis |
Physical (Inducible) Urticarias
- Dermatographism - most common; urticarial wheal within 30 minutes of firm skin stroking
- Pressure urticaria - onset delayed 4-8 hours after sustained pressure; distinct from dermatographism
- Cold urticaria - may be familial or acquired; associated with cryoglobulinemia, syphilis, connective tissue disease
- Cholinergic urticaria - triggered by exercise, heat, or emotional stress; tiny wheals 1-3 mm with extensive erythematous flares
- Solar urticaria - confined to sun-exposed skin; clears when light stimulus is removed
- Heat urticaria - rare
Clinical Features
- Morphology: Edematous plaques with pale centers and red borders; "wheal and flare" appearance with blanching of surrounding skin
- Individual lesions typically last <24 hours (new lesions may continuously develop)
- Pruritus is the dominant symptom
- Angioedema may accompany, particularly of the lips, eyelids, throat
Red flags requiring biopsy:
- Lesions lasting >36 hours (or painful rather than pruritic), resulting in scarring, or leaving bruising - biopsy to rule out urticarial vasculitis (fibrinoid necrosis of venules on histology)
Urticaria - characteristic raised patches (Rosen's Emergency Medicine)
Diagnosis & Workup
Acute urticaria: History alone with identification of trigger is usually sufficient. Skin testing or allergen-specific IgE assay may confirm suspected allergen.
Chronic urticaria: Extensive workup is often unrevealing; the vast majority have no laboratory abnormality. Guidelines offer two options if history and physical exam are unrevealing:
- No laboratory testing
- Limited testing: CBC with differential, ESR or CRP
Extended testing (guided by clinical suspicion):
- Thyroid function (TSH) and anti-thyroid antibodies
- Stool for H. pylori and ova/parasites
- Liver panel
- Complement levels (if isolated angioedema without urticaria - rule out C1-INH deficiency)
- Antinuclear antibodies if connective tissue disease suspected
Flushing + hyperpigmented papules that urticate with stroking (without angioedema): Suspect mastocytosis.
Evaluation & Treatment Algorithm
FIGURE - Evaluation and treatment of urticaria and angioedema (Goldman-Cecil Medicine)
Treatment
Acute Urticaria
- Remove the inciting factor when identifiable
- Second-generation H1 antihistamine (cetirizine 10 mg, levocetirizine 5 mg, fexofenadine 180 mg, loratadine 10 mg, or desloratadine 5 mg daily)
- Severe cases: Add oral corticosteroids (prednisone 20-40 mg daily x 5 days); IV corticosteroids confer no additional benefit over oral
- Anaphylaxis/airway involvement: Epinephrine (self-administered), endotracheal intubation rarely required but indicated for drooling, dyspnea, pharyngeal swelling
Chronic Urticaria - Stepwise Approach
| Step | Therapy |
|---|---|
| Step 1 | Second-generation H1 antihistamine once daily; advance dose up to 4x daily over 2-4 week intervals if needed |
| Step 2 | Add H2 antagonist (ranitidine/famotidine) + leukotriene receptor antagonist (montelukast 10 mg daily) |
| Step 3 | Omalizumab 300 mg SC every 4 weeks (monoclonal anti-IgE antibody) - initiated when high-dose antihistamines fail (~50% of patients) |
| Step 4 (refractory) | Cyclosporine, hydroxychloroquine, sulfasalazine, dapsone, tacrolimus, mycophenolate; oral corticosteroids only under expert oversight |
Avoid in chronic urticaria: NSAIDs (trigger episodes in up to 30% of patients) and opioids.
Physical urticaria: Antihistamines taken 30-60 minutes before the trigger (e.g., before cold exposure or exercise); avoid identifiable triggers.
Emerging therapies under study: Bruton tyrosine kinase inhibitors (remibrutinib), benralizumab, tezepelumab, dupilumab.
Note on first-generation antihistamines: Diphenhydramine and hydroxyzine cause sedation, psychomotor impairment, and anticholinergic effects (urinary retention, visual disturbance, constipation); non-sedating agents preferred.
Differential Diagnosis
- Drug eruption / morbilliform exanthem
- Erythema multiforme / erythema marginatum
- Urticarial vasculitis (key distinction: painful >24h lesions, leaves bruising)
- Urticarial bullous pemphigoid
- Juvenile rheumatoid arthritis
- Neutrophilic urticaria
- Mastocytosis (urticaria pigmentosa)
- Angioedema due to C1-INH deficiency (HAE) or ACE inhibitor - notably absent pruritus, no urticaria, GI involvement, duration >24h, doesn't respond to antihistamines
Prognosis
- ~50% of chronic spontaneous urticaria cases resolve within 1 year
- ~80% resolve within 3-5 years
- Patients with chronic urticaria lasting >5 years have a lower rate of spontaneous remission
- Chronic inducible urticaria tends to be more persistent
Recent Evidence
- A 2024 meta-analysis (PMID 38852861) examined leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria, providing updated evidence for step 2 therapy.
- A 2025 systematic review in JAMA Dermatology (PMID 41060663) focused on patient values and preferences in chronic urticaria treatment - relevant for shared decision-making.
- A 2025 systematic review (PMID 40745339) examined vitamin D supplementation in chronic urticaria; emerging evidence suggests a potential adjunctive role.
Sources: Harrison's Principles of Internal Medicine 22E, Goldman-Cecil Medicine, Rosen's Emergency Medicine, Fitzpatrick's Dermatology, Robbins Pathology
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