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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Urticaria = transient itchy wheals that individual lesions resolve within <24 hours without bruising
- Angioedema = deeper swelling of lips, eyelids, tongue, larynx, extremities, or GI tract
- Anaphylaxis or airway angioedema: IM epinephrine first-line, airway management, emergency care
- Chronic spontaneous urticaria lasts >6 weeks and usually needs limited testing unless history suggests systemic disease
- ACE inhibitor angioedema is bradykinin-mediated: no urticaria, may occur years after starting ACEi, and antihistamines/steroids/epinephrine may be less effective
Overview
Urticaria is caused by superficial dermal edema from mast-cell mediator release, producing transient wheals. Angioedema involves deeper dermis/subcutaneous or submucosal tissues. Acute urticaria is often triggered by infection, foods, medications, insect stings, or idiopathic causes. Chronic urticaria is usually spontaneous/autoimmune rather than allergic. Angioedema may be histamine-mediated with urticaria/anaphylaxis or bradykinin-mediated from ACE inhibitors, hereditary C1 inhibitor deficiency, or acquired C1 inhibitor deficiency.
Epidemiology
Acute urticaria is common and affects many people at some point in life. Chronic urticaria is less common, more frequent in adults, and has a female predominance. Medication triggers include NSAIDs, antibiotics, opioids, radiocontrast, and ACE inhibitors. ACE inhibitor angioedema risk is higher in Black patients, smokers, older adults, and those with prior angioedema. Hereditary angioedema often begins in childhood or adolescence and presents with recurrent swelling without hives.
Clinical Features
Symptoms
Itchy raised wheals that migrate and resolve within hours
Lip, eyelid, tongue, throat, hand, foot, or genital swelling
Wheezing, dyspnea, stridor, hypotension, syncope, vomiting, or abdominal cramps after exposure suggests anaphylaxis
Recurrent abdominal pain/swelling without urticaria suggests hereditary angioedema
Burning painful lesions lasting >24 hours with bruising suggests urticarial vasculitis
Signs
Blanching edematous wheals with central pallor and surrounding erythema
Dermatographism: linear wheal after stroking skin
Tongue/laryngeal swelling, hoarseness, drooling, stridor = airway emergency
Absence of hives with isolated angioedema points toward bradykinin-mediated disease
Purpura, fever, arthralgia, or fixed lesions suggests vasculitis or systemic disease
Investigations
First-line
Clinical diagnosisAssess morphology, lesion duration, exposures, medications, infection symptoms, airway, and anaphylaxis criteria
Medication reviewACE inhibitors, NSAIDs, antibiotics, opioids, estrogen therapy, and new medications are high-yield triggers
Second-line
Limited chronic urticaria labsCBC, ESR/CRP, TSH may be considered if chronic >6 weeks or symptoms suggest systemic disease; broad allergy panels are usually low-yield
C4 and C1 inhibitor level/functionIf recurrent angioedema without urticaria, family history, abdominal attacks, laryngeal edema, or onset in childhood
TryptaseCan support anaphylaxis/mast-cell activation when drawn shortly after severe systemic reaction
Specialist
Skin biopsyFor suspected urticarial vasculitis: lesions last >24 hours, painful/burning, bruising, systemic symptoms, low complement
Allergy/immunology referralFor recurrent anaphylaxis, suspected hereditary angioedema, refractory chronic urticaria, or unclear triggers
1
Emergency management
- Anaphylaxis: IM epinephrine into lateral thigh immediately; repeat every 5-15 min if needed
- Airway angioedema: early airway assessment, emergency support, consider intubation before complete obstruction
- Adjuncts after epinephrine: oxygen, IV fluids, H1/H2 antihistamines, bronchodilator, corticosteroid; these do not replace epinephrine
- Observe after anaphylaxis; prescribe epinephrine auto-injectors and avoidance plan on discharge
2
Acute urticaria without anaphylaxis
- Second-generation H1 antihistamines: cetirizine, loratadine, fexofenadine, levocetirizine
- Avoid triggers such as NSAIDs, alcohol, heat, pressure, or suspected foods/medications when temporally linked
- Short oral steroid course may be used for severe acute flares but is not chronic therapy
3
Chronic spontaneous urticaria
- Daily second-generation H1 antihistamine first-line
- If uncontrolled, increase dose up to 4-fold under guidance before moving to advanced therapy
- Omalizumab is preferred biologic add-on for antihistamine-refractory chronic spontaneous urticaria
- Cyclosporine is an alternative specialist option for refractory disease
4
Bradykinin-mediated angioedema
- Stop ACE inhibitor permanently; do not rechallenge
- Airway protection is the priority; standard allergy medications may have limited effect
- Hereditary angioedema attacks: C1 inhibitor concentrate, icatibant, or ecallantide depending on access and specialist protocol
Complications
- Anaphylaxis: Life-threatening systemic reaction requiring epinephrine
- Airway obstruction: Tongue/laryngeal angioedema can progress rapidly
- Chronic morbidity: Sleep disruption, anxiety, reduced quality of life in chronic urticaria
- Misdiagnosis of bradykinin angioedema: Delayed airway management if treated as simple allergy
- Urticarial vasculitis: Fixed painful lesions with bruising and systemic involvement
USMLE Step 2 CK Exam Tips
- 1Individual hive lesions disappear within <24 hours; fixed painful purpuric lesions suggest urticarial vasculitis
- 2Anaphylaxis = IM epinephrine first. Antihistamines and steroids are adjuncts only
- 3ACE inhibitor angioedema can occur years after starting; no hives; stop ACEi permanently
- 4Recurrent angioedema without urticaria + abdominal pain = hereditary angioedema; check C4/C1 inhibitor
- 5Chronic urticaria >6 weeks is usually not a food allergy; avoid broad food panels
- 6Second-generation antihistamines are preferred over diphenhydramine for routine urticaria due to less sedation
- 7Omalizumab is high-yield for antihistamine-refractory chronic spontaneous urticaria
practicetest your knowledge on urticaria & angioedemaApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — dermatology and beyond.
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