Urticaria

Urticaria is a common mast cell–mediated dermatologic condition characterized by pruritic, erythematous, raised wheals that individually resolve within 24 hours. It is classified as acute (<6 weeks) or chronic (≥6 weeks), with 80–90% of chronic cases being idiopathic.[1] The primary mechanism is histamine release from dermal mast cells, most commonly via IgE-mediated type 1 hypersensitivity.[1]

The following diagnostic algorithm provides a useful framework for evaluating urticarial presentations:

• Onset and timing: Acute (<6 weeks) vs. chronic (≥6 weeks); continuous vs. episodic; time of day; relationship to activities[1][3]
• Characterization of lesions: Size, shape, distribution, blanching, duration of individual wheals (<24 hours is typical; >24 hours suggests vasculitis)[1][4]
• Triggers: Foods (nuts, shellfish, eggs, dairy), medications, insect stings, infections, physical stimuli (cold, heat, pressure, exercise), stress, latex, aeroallergens[1][3]
• Temporal relationship: Food ingestion within 2 hours, new medication within days to weeks, recent infection[3][5]
• Associated symptoms: Angioedema (lip/tongue/eyelid swelling), pruritus severity, burning vs. itching quality[1]
• Important negatives: Absence of dyspnea, wheezing, stridor, lightheadedness, abdominal pain, vomiting, diarrhea, syncope (rules out anaphylaxis)[3]
• Review patient photographs of lesions if not present at time of evaluation[1][6]

• Anaphylaxis signs: Hypotension, tachycardia, bronchospasm, stridor, laryngeal edema, abdominal pain, vomiting, diarrhea, dizziness, loss of consciousness[1][3]
• Urticarial vasculitis: Wheals lasting >24 hours, burning pain (not itch), residual ecchymosis/hyperpigmentation, fever, arthralgias[1][4]
• Systemic disease clues: Fevers, night sweats, unintentional weight loss (lymphoma); joint pain, uveitis (autoimmune disease)[1]
• Angioedema without wheals: Consider bradykinin-mediated angioedema (ACE inhibitor–induced or hereditary angioedema) — antihistamines are ineffective in these cases[1][7]
• Epinephrine should be prescribed if anaphylaxis has not been excluded[3]

Common culprits/exacerbators

• NSAIDs — can induce or exacerbate urticaria via prostaglandin E2 suppression; present in up to 30% of chronic urticaria exacerbations. Recommend acetaminophen as alternative analgesic/antipyretic[1][8-9]
• ACE inhibitors — associated with bradykinin-mediated angioedema (not histamine-mediated); discontinue and observe for 6 weeks[1][3]
• β-lactam antibiotics — most common drug-induced urticaria trigger in children[5]
• Opioids, vancomycin — direct mast cell degranulation (non-IgE mediated)[1]
• Aspirin — cross-reactivity with NSAID-exacerbated urticaria

Treatments

• First-line: Second-generation H1 antihistamines (cetirizine, loratadine, fexofenadine, levocetirizine)[1]
• Refractory acute: Short course oral corticosteroids (prednisone 40–50 mg × 3–5 days), though evidence of benefit is conflicting[3][10]
• Chronic refractory: Omalizumab (Xolair) 300 mg SC q4 weeks for antihistamine-resistant chronic spontaneous urticaria[6][11]

Contraindicated/avoid

• Topical antihistamines and topical corticosteroids — not effective[1]
• Long-term systemic corticosteroids for chronic urticaria[1]

• Acute urticaria: Nuts, shellfish, eggs, cow's milk, and fish are the most common IgE-mediated food triggers[5][12]
• Histamine-rich foods may exacerbate symptoms: aged cheese, preserved/cured meats, improperly stored fish (scombroid), fermented foods, alcohol[1]
• Pseudoallergens: Food additives (tartrazine dye, benzoates, salicylates) may trigger non-IgE–mediated reactions[1][7]
• Empiric elimination diets are NOT recommended unless guided by specific history and testing[3]
• Adequate hydration is supportive but not specifically evidence-based for urticaria
• Diets rich in omega-3 fatty acids, legumes, nuts, and whole grains may have a protective association[13]

• Pulmonary: Dyspnea, wheezing, cough, stridor (anaphylaxis, angioedema)
• GI: Abdominal pain, nausea, vomiting, diarrhea (anaphylaxis, food allergy)
• Cardiovascular: Lightheadedness, syncope, palpitations (anaphylaxis)
• ENT: Lip/tongue/throat swelling, voice change, dysphagia (angioedema)
• Musculoskeletal: Joint pain, swelling (autoimmune disease, serum sickness, urticarial vasculitis)
• Constitutional: Fevers, night sweats, weight loss (lymphoma, infection, autoinflammatory syndromes)[1]
• Endocrine: Cold intolerance, weight gain, fatigue (hypothyroidism)[1]
• Dermatologic: Lesion duration, burning vs. itching, residual skin changes[1][4]

• Family history of urticaria or atopy (asthma, eczema, allergic rhinitis)[1]
• Hereditary angioedema (HAE types 1–3): Family history of recurrent angioedema without urticaria, autosomal dominant[7]
• Cryopyrin-associated periodic syndromes (CAPS): Familial cold autoinflammatory syndrome, Muckle-Wells syndrome[7]
• Social context: Occupational exposures (latex, chemicals), travel history (parasitic infections), sexual history and substance use (hepatitis B/C, HIV risk)[1][3]
• Transfusion history — risk for hepatitis-associated urticaria[3]

• Female sex — higher prevalence, especially for chronic spontaneous urticaria[6][13]
• Atopic history — asthma, allergic rhinitis, eczema
• Infections: Viral URIs (most common trigger in children, up to 23%), UTIs, GI infections, H. pylori[1][5]
• Autoimmune disease: Autoimmune thyroiditis, SLE, Sjögren syndrome, rheumatoid arthritis, celiac disease[1]
• Medication use: NSAIDs, ACE inhibitors, antibiotics, opioids[1][6]
• Stress — reported trigger in ~14% of chronic urticaria patients[6]
• Environmental: Air pollution (ozone, particulate matter) positively correlated with urticaria incidence[13]
• Younger age groups carry higher disease burden globally[13]

• Anaphylaxis — urticaria + systemic symptoms (hypotension, bronchospasm, GI symptoms); must be excluded in every ED presentation[3]
• Urticarial vasculitis — wheals >24 hours, burning pain, ecchymosis, residual hyperpigmentation; biopsy shows leukocytoclastic vasculitis[4][8]
• Erythema multiforme — target lesions, fixed (not migratory), often post-infectious (HSV) or drug-related
• Bullous pemphigoid — urticarial prodrome may precede blistering; older adults[8]
• Contact dermatitis — localized, distribution matches exposure
• Drug eruption — morbilliform rash, fixed drug eruption; temporal relationship to medication
• Serum sickness–like reaction — urticaria + fever + arthralgias, typically 1–3 weeks after drug exposure (cefaclor, amoxicillin)
• Hereditary angioedema — recurrent angioedema WITHOUT wheals; does not respond to antihistamines[7]
• Mastocytosis/systemic mastocytosis — urticaria pigmentosa, Darier sign[1]
• Autoinflammatory syndromes: Schnitzler syndrome (urticaria + monoclonal gammopathy), CAPS[7]
• Stevens-Johnson syndrome/TEN — painful, non-pruritic, mucosal involvement (cannot-miss)[2]

• Prior episodes of urticaria or angioedema and identified triggers
• History of atopy (asthma, allergic rhinitis, eczema)
• Autoimmune thyroid disease — most common autoimmune comorbidity[1][6]
• Prior anaphylaxis and epinephrine auto-injector use
• Chronic infections (hepatitis B/C, HIV, H. pylori)[1]
• Surgical history (implants, transfusions)
• Pregnancy — pruritic urticarial papules and plaques of pregnancy (PUPPP)[1]

• Vital signs: Tachycardia, hypotension, tachypnea → concern for anaphylaxis[3]
• Skin: Characterize wheals — raised, erythematous, blanching, well-circumscribed; note distribution, size, confluence; check for ecchymosis or residual pigmentation (vasculitis)[1][3]
• Dermatographism testing: Stroke skin with blunt end of tongue blade; positive = linear wheal at site of pressure[1]
• Angioedema: Examine lips, tongue, periorbital area, hands, feet, genitalia for deep tissue swelling[3]
• HEENT: Oropharyngeal edema, stridor, voice changes (airway compromise)[3]
• Lungs: Wheezing, decreased air entry
• Abdomen: Tenderness (visceral angioedema)
• Lymph nodes/thyroid: Lymphadenopathy (lymphoma), thyromegaly (hypothyroidism)[1][3]
• Musculoskeletal: Joint swelling/tenderness (autoimmune, vasculitis)

• Acute urticaria: Diagnostic testing is typically not required[1]

If clinically indicated (recurrent or atypical)

• CBC with differential (eosinophilia → allergic/parasitic; basopenia → autoimmune CSU)[3][6]
• ESR and/or CRP (elevated → vasculitis, infection, autoimmune)[1][6]

Chronic urticaria workup

• CBC with differential, ESR, CRP[1]
• Total IgE[1]
• TSH and anti-thyroid peroxidase (anti-TPO) IgG[1][6]
• Consider: hepatitis B/C serologies, HIV, H. pylori testing if history suggests[1][6]
• Complement levels (C3, C4, CH50) if urticarial vasculitis or hereditary angioedema suspected[1][4]
• Tryptase — if mastocytosis or anaphylaxis suspected
• Intensive and costly general screening programs are strongly advised against[6-7]

• Imaging is generally NOT indicated for uncomplicated urticaria
• Consider chest X-ray if respiratory symptoms present to evaluate for alternative diagnoses
• CT neck/soft tissue if concern for airway-compromising angioedema not responding to treatment
• Imaging for underlying malignancy only if constitutional symptoms (weight loss, night sweats, fevers) are present[1]

• Urticaria Activity Score (UAS7): Patient-reported daily wheal count and itch severity over 7 days; useful for monitoring chronic urticaria[1][6]
• Urticaria Control Test (UCT): 4-item questionnaire to assess disease control; guides step-up therapy decisions[6]
• Skin-prick testing: For suspected IgE-mediated food or venom allergy; perform after acute episode resolves and antihistamines are held[3]
• Serum-specific IgE: Alternative to skin-prick testing, especially with dermatographism[3]
• Autologous serum skin test (ASST): Screens for autoimmune urticaria (functional autoantibodies)[1]
• Basophil activation test / basophil histamine release assay: Identifies autoimmune CSU[6]
• Skin biopsy: Indicated if wheals last >24 hours, are painful/burning, leave ecchymosis, or vasculitis is suspected[1][4]
• Physical provocation testing: Ice cube test (cold urticaria), exercise challenge (cholinergic), pressure test (delayed pressure urticaria)[7]

• Not routinely indicated for uncomplicated urticaria

Obtain ECG if

• Anaphylaxis is suspected (Kounis syndrome — allergic coronary vasospasm)
• Hemodynamic instability or chest pain
• Pre-existing cardiac disease with epinephrine administration
• Patterns to recognize: Sinus tachycardia (anaphylaxis), ST changes (Kounis syndrome), arrhythmias in setting of epinephrine use

• Acute urticaria is self-limited in most cases; the most common cause in children is viral infection[3][5]
• Chronic spontaneous urticaria is idiopathic in 80–90% of cases; remission occurs in ~50% within 1–5 years[1][9]
• Severity stratification: Isolated wheals (mild) → widespread wheals with angioedema (moderate) → systemic symptoms/anaphylaxis (severe)[3]
• Atypical features warranting further workup: wheals >24 hours, burning pain, residual hyperpigmentation, systemic symptoms, isolated angioedema without wheals[1][4][8]
• Complications: Anaphylaxis, airway compromise from angioedema, significant quality-of-life impairment, sleep disruption, psychological distress[1][9]

Acute Urticaria — ED/Urgent Care

• First-line: Second-generation H1 antihistamine (e.g., cetirizine 10 mg PO, fexofenadine 180 mg PO)[1][14]
• If IV needed in ED: IV second-generation antihistamine preferred over first-generation (lower return-to-ED rate, fewer adverse events)[14]
• Refractory to antihistamines: Consider short course oral prednisone 40–50 mg/day × 3–5 days, though evidence of benefit is conflicting and one RCT found no benefit of adding IV dexamethasone. Continue antihistamines during and after steroid course[1][3][10]
• If anaphylaxis suspected: IM epinephrine 0.3–0.5 mg (1:1000) into anterolateral thigh; repeat q5–15 min as needed[3]
• Prescribe epinephrine auto-injector if anaphylaxis cannot be excluded[3]

Chronic Urticaria — Stepped Approach

• Step 1: Second-generation H1 antihistamine at standard dose (daily, not PRN)[3][9]
• Step 2: Increase dose up to 4× standard dose (e.g., cetirizine 10 mg QID) — FDA-approved, minimal additional adverse effects[1][6][9]
• Step 3: Add leukotriene receptor antagonist (montelukast) or H2 blocker (evidence is conflicting); consider hydroxyzine or doxepin at bedtime[1][3]
• Step 4: Omalizumab 300 mg SC q4 weeks for antihistamine-refractory CSU[6][11]
• Step 5: Cyclosporine 3 mg/kg/day (off-label) for omalizumab-refractory cases; requires BP and renal monitoring[6]
• Avoid long-term systemic corticosteroids for chronic urticaria[1]
• Non-pharmacologic: Avoid known triggers, NSAIDs, tight clothing, excessive heat, alcohol, stress[3][9]

Admission criteria

• Anaphylaxis requiring epinephrine or hemodynamic support
• Airway-compromising angioedema (laryngeal, oropharyngeal)
• Refractory symptoms despite ED treatment with ongoing systemic symptoms
• Concern for serious underlying etiology (vasculitis with systemic involvement, serum sickness)

Observation

• Post-anaphylaxis observation for 4–6 hours minimum (biphasic reaction risk)
• Angioedema involving face/neck with good response to treatment — observe for rebound

Discharge criteria

• Isolated urticaria without systemic symptoms
• Symptoms improving with antihistamines
• Able to tolerate oral medications
• No airway involvement

Specialist consultation triggers

• Wheals lasting >24 hours with residual hyperpigmentation → dermatology/allergy (biopsy for vasculitis)[6]
• Antihistamine-refractory chronic urticaria → allergy/immunology[6]
• Isolated angioedema without wheals → allergy (rule out HAE)[7]
• Extracutaneous symptoms (fever, arthralgias, abdominal pain) → allergy/rheumatology[6]

Follow-up timing

• Acute urticaria: PCP follow-up within 1–2 weeks if symptoms persist; most cases resolve spontaneously[1][3]
• If approaching 6 weeks of symptoms → initiate chronic urticaria workup[3]
• Chronic urticaria: Regular follow-up q4–8 weeks to titrate therapy and assess disease control (UCT score)[6]

Return precautions — seek immediate care for

• Difficulty breathing, throat tightness, voice changes, tongue/lip swelling
• Lightheadedness, dizziness, fainting
• Abdominal pain, vomiting, diarrhea with hives
• Rapid spread of hives with worsening symptoms despite antihistamines

Patient counseling

• Urticaria is common and usually self-limited; most acute cases resolve within days to weeks[1]
• Take antihistamines daily (not PRN) for best control[9]
• Avoid NSAIDs (use acetaminophen instead), alcohol, and known triggers[6][9]
• Photograph lesions when they appear — transient nature makes clinic evaluation challenging[1][6]
• Chronic urticaria may wax and wane; ~50% achieve remission within 1–5 years[9]

1. Acute and Chronic Urticaria: Evaluation and Treatment. — Semenya AM, Pienkowski S, Bhatnagar P. American Family Physician. 2026.

2. Urticaria. — Gary Foley Clinical Guide to Paediatrics. 2022.

3. The Diagnosis and Management of Acute and Chronic Urticaria: 2014 Update. — Bernstein JA, Lang DM, Khan DA, et al. The Journal of Allergy and Clinical Immunology. 2014.

4. Urticarial Vasculitis: Clinical and Laboratory Findings With a Particular Emphasis on Differential Diagnosis. — Marzano AV, Maronese CA, Genovese G, et al. The Journal of Allergy and Clinical Immunology. 2022.

5. The common triggers of urticaria in children admitted to the pediatric emergency room. — Bezirganoglu H, Arik Yilmaz E, Sahiner UM, et al. Pediatric Dermatology. 2022.

6. Chronic Spontaneous Urticaria: A Review. — Kolkhir P, Bonnekoh H, Metz M, Maurer M. The Journal of the American Medical Association. 2024.

7. The EAACI/­GA²LEN/­EDF/­WAO Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. — Zuberbier T, Aberer W, Asero R, et al. Allergy. 2018.

8. Chronic Spontaneous Urticaria. — Yosipovitch G, Maderal AD, Elman SA. JAMA Dermatology. 2025.

9. Chronic Urticaria. — Lang DM. The New England Journal of Medicine. 2022.

10. A Randomized Controlled Trial of Adding Intravenous Corticosteroids to H1 Antihistamines in Patients With Acute Urticaria. — Palungwachira P, Vilaisri K, Musikatavorn K, Wongpiyabovorn J. The American Journal of Emergency Medicine. 2021.

11. FDA Orange Book. — FDA Orange Book. 2026.

12. Nutrition and Urticaria. — Shao K, Feng H. Clinics in Dermatology. 2021.

13. Global, Regional, and National Burden of Urticaria (1990-2021), Its Potential Risk Factors, and Projections to 2046. — Tan S, Chen Z, Lin T. BMC Public Health. 2025.

14. Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis. — Jamjanya S, Danpanichkul P, Ongsupankul S, et al. The Journal of Allergy and Clinical Immunology. In Practice. 2024.