Urticaria (Hives) - Dermatology Notes

Definition: A common skin condition characterized by the sudden onset of wheals (transient, pruritic, edematous papules or plaques) and/or angioedema, resulting from mast cell degranulation and release of histamine and other vasoactive mediators.

Key Clinical Features:

• Wheal morphology: Raised, well-circumscribed, erythematous to pale-pink plaques with central pallor. Individual lesions are round, annular, or serpiginous.

• Size: Ranges from a few millimeters to several centimeters; can coalesce into giant plaques.

• Symptoms: Intense pruritus (hallmark); burning or stinging sensation.

• Duration of individual lesions: Transient – each wheal lasts less than 24 hours (typically 2–4 hours). This is a critical diagnostic criterion.

• Distribution: Anywhere on the body; often generalized. Pressure sites (waistband, bra line) may be involved in symptomatic dermographism.

• Angioedema: Deep dermal and subcutaneous swelling affecting lips, eyelids, tongue, larynx, hands, feet, or genitalia. May be painful rather than pruritic. Lasts up to 72 hours.

• Dermographism: Stroking the skin produces a linear wheal (present in 5% of normal population; more common in urticaria patients).

• Complete resolution: Lesions heal without scarring, post-inflammatory hyperpigmentation, or hypopigmentation.

Classification (board essential):

By duration:

• Acute urticaria: Duration less than 6 weeks. Most common form. Typically triggered by infection (viral upper respiratory, streptococcal), drugs (antibiotics, NSAIDs), or foods (peanuts, eggs, shellfish, milk, wheat).

• Chronic urticaria: Duration greater than 6 weeks, with daily or episodic wheals. Affects 0.5–1% of population. Female predominance (2:1). Most cases are chronic spontaneous urticaria (CSU) , formerly called chronic idiopathic urticaria.

By mechanism:

• Spontaneous (no identifiable external trigger): Acute or chronic.

• Inducible (physical urticarias): Triggered by specific physical stimuli. Includes symptomatic dermographism (mechanical shear), delayed pressure urticaria (sustained pressure), cholinergic urticaria (elevated core temperature, exercise, emotion), cold urticaria, heat urticaria, solar urticaria (UV/visible light), vibratory angioedema, and aquagenic urticaria (water contact).

Associated Conditions/Diseases:

• Autoimmune chronic urticaria: 30–50% of CSU patients have functional IgG autoantibodies against the high-affinity IgE receptor (FcεRI) or against IgE itself. Associated with autoimmune thyroid disease (Hashimoto thyroiditis – anti-TPO antibodies), vitiligo, pernicious anemia, and type 1 diabetes.

• Hereditary angioedema (C1 esterase inhibitor deficiency): Presents with angioedema without wheals; normal urticaria treatments (antihistamines, epinephrine) are ineffective. Differentiate by family history, lack of pruritus, and low C4.

• Mastocytosis (cutaneous or systemic): Urticaria pigmentosa lesions (brown macules that urticate with rubbing – Darier sign). Rule out with serum tryptase and skin biopsy.

• Schnitzler syndrome: Chronic urticarial rash + monoclonal gammopathy (IgM usually) + fever + bone pain + leukocytosis. Associated with risk of lymphoproliferative disease.

• Urticarial vasculitis: Wheals last more than 24 hours, leave residual purpura or hyperpigmentation, are painful (burning) rather than pruritic, and show leukocytoclastic vasculitis on biopsy. Associated with SLE, Sjögren syndrome, and hypocomplementemia.

• Helicobacter pylori infection: Controversial association with chronic urticaria; treatment may improve symptoms in some patients.

• Parasitic infections: Strongyloides, toxocara, giardia, anisakis (consider in travelers or endemic regions).

Prognosis:

• Acute urticaria: Excellent – self-limited over days to weeks (usually <2 weeks).

• Chronic spontaneous urticaria: 50% remit within 1 year; 80% within 5 years; 20% persist beyond 5 years. Quality of life is severely impaired (comparable to ischemic heart disease).

• Inducible urticarias: Often persist for years; may gradually improve.

Differential Diagnosis:

• Urticarial vasculitis: Lesions last >24 hours, leave residual purpura or hyperpigmentation, painful (burning), biopsy shows leukocytoclastic vasculitis.

• Erythema multiforme: Target lesions (acral), less pruritic, mucosal involvement, lesions last days to weeks, histology shows interface dermatitis.

• Bullous pemphigoid (urticarial phase): Tense bullae eventually develop, elderly patients, pruritus severe, histology shows subepidermal blister with eosinophils, DIF shows linear IgG and C3 at basement membrane.

• Mastocytosis (urticaria pigmentosa): Brown macules/papules that urticate with rubbing (Darier sign), histology shows dermal mast cell aggregates.

• Contact urticaria (immediate contact reaction): Wheal within 30 minutes of contact with allergen (latex, foods, animal saliva) – resolves within 1–2 hours.

• Erythema annulare centrifugum: Annular, expanding plaques with trailing scale (collarette), no pruritus or mild pruritus, lasts weeks to months.

• Serum sickness-like reaction: Urticaria + fever + arthralgia + lymphadenopathy, 7–14 days after drug exposure (cefaclor, amoxicillin), no true vasculitis.

• Atopic dermatitis: Chronic, dry skin, flexural distribution, lichenification, no transient wheals.

Management with Rationale (Stepped approach – board essential):

Step 1 – Identify and remove trigger (most important for acute urticaria):

• Discontinue offending drug (NSAIDs, antibiotics, opioids, ACE inhibitors – cause bradykinin-mediated angioedema).

• Avoid identified food triggers (peanuts, tree nuts, shellfish, eggs, milk, wheat, soy).

• Treat underlying infection (streptococcal pharyngitis, H. pylori, parasitic).

• Avoid physical triggers in inducible urticarias (cold, pressure, heat, exercise, vibration, water).

Step 2 – Second-generation non-sedating H1 antihistamines (first-line for all urticaria):

• Regimen: Cetirizine 10 mg daily, loratadine 10 mg daily, fexofenadine 180 mg daily, or levocetirizine 5 mg daily.

• Rationale: Block H1 receptors on endothelial cells and sensory nerves, reducing vasodilation, vascular permeability, and pruritus.

• Up-dosing (off-label but guideline-supported): Increase to up to 4 times the standard dose if standard dose fails (e.g., cetirizine 40 mg daily). Safety is excellent.

Step 3 – Add second-generation H1 antihistamine of a different class or add H2 antagonist:

• Add another H1 antihistamine (e.g., morning fexofenadine, evening cetirizine) – weak evidence.

• Add H2 antagonist (famotidine 20 mg twice daily, ranitidine – now withdrawn) – modest additive benefit.

Step 4 – First-generation sedating H1 antihistamine at bedtime:

• Example: Hydroxyzine 25–50 mg at bedtime, diphenhydramine 25–50 mg at bedtime.

• Rationale: More potent but sedating; nighttime use controls nocturnal symptoms and improves sleep. Use short-term.

Step 5 – Add leukotriene receptor antagonist (montelukast 10 mg daily):

• Rationale: Block leukotriene D4 (LTD4), which contributes to mast cell mediator release and eosinophil recruitment.

• Evidence: Modest benefit, especially in aspirin-exacerbated urticaria and chronic urticaria with autoreactivity.

Step 6 – Omalizumab (anti-IgE monoclonal antibody):

• Indication: Chronic spontaneous urticaria refractory to high-dose antihistamines (step 1–5 failure).

• Dosing: 150 mg or 300 mg subcutaneously every 4 weeks.

• Response: 70–80% respond; improvement within 1–2 weeks.

• Rationale: Binds free IgE, downregulates FcεRI on mast cells and basophils, prevents cross-linking by autoantibodies.

• Side effects: Injection site reactions; rare anaphylaxis (0.1%).

• FDA-approved specifically for chronic idiopathic urticaria.

Step 7 – Cyclosporine (off-label):

• Indication: Refractory CSU after omalizumab failure.

• Dosing: 3–5 mg/kg/day in divided doses.

• Rationale: Calcineurin inhibitor – inhibits T-cell activation and mast cell mediator release.

• Monitoring: Blood pressure, renal function, cyclosporine levels.

• Side effects: Nephrotoxicity, hypertension, hirsutism, gingival hyperplasia.

Step 8 – Other immunosuppressants (third-line, limited evidence):

• Mycophenolate mofetil (1–2 g/day), methotrexate (10–25 mg/week), or azathioprine (1–3 mg/kg/day).

• Rationale: Used in severe, refractory autoimmune urticaria.

Management of angioedema without wheals:

• If no response to antihistamines and no wheals – suspect hereditary angioedema or ACE inhibitor-induced angioedema. Treat with icatibant (bradykinin B2 receptor antagonist), C1 esterase inhibitor concentrate, or fresh frozen plasma. Antihistamines, corticosteroids, and epinephrine are ineffective.

Management of inducible urticarias:

• Symptomatic dermographism: Avoid friction; high-dose non-sedating antihistamines (up-dosed).

• Cholinergic urticaria: Pre-treatment with antihistamines before exercise; avoid overheating; danazol (severe cases) – reduces sweating.

• Cold urticaria: Avoid cold exposure; carry epinephrine auto-injector (risk of anaphylaxis during swimming).

• Delayed pressure urticaria: Poor response to antihistamines; montelukast, NSAIDs (if not aspirin-sensitive), or omalizumab may help.

Corticosteroids (short-term use only):

• Indication: Severe acute urticaria or angioedema (laryngeal edema) or severe exacerbation of chronic urticaria.

• Regimen: Prednisone 0.5–1 mg/kg/day for 3–7 days; no taper for short course.

• Rationale: Potent anti-inflammatory; mast cell stabilization.

• Do NOT use long-term for chronic urticaria – side effects outweigh benefits; indicates need for step-up therapy.

Epinephrine (acute anaphylaxis or laryngeal angioedema):

• Dose: 0.3 mg (adult) or 0.15 mg (child) intramuscularly into anterolateral thigh.

• Rationale: Alpha-1 mediated vasoconstriction (reduces edema), beta-2 mediated bronchodilation.

• Indication: Any sign of anaphylaxis (respiratory distress, hypotension, stridor, tongue swelling, or rapidly progressive angioedema).

Histopathology

1. FOUNDATIONS (First Principles)

• Normal dermis: Contains superficial (papillary) and deep (reticular) layers. Post-capillary venules are the primary vessels involved in urticaria.

• Normal mast cell: Resident immune cells in the dermis (perivascular location). Contain cytoplasmic granules filled with histamine, tryptase, chymase, heparin, and cytokines (TNF, IL-4, IL-13, IL-6). Mast cells are activated by cross-linking of high-affinity IgE receptors (FcεRI) or by direct stimulation (opiates, vancomycin, radiocontrast, complement anaphylatoxins C3a, C5a).

• Normal endothelial cells: Line post-capillary venules. Express adhesion molecules (E-selectin, ICAM-1, VCAM-1) when activated. Gap junctions regulate vascular permeability.

• Normal extracellular matrix: Collagen, proteoglycans, and glycosaminoglycans (hyaluronic acid) maintain tissue structure. In urticaria, edema fluid separates these components.

2. INITIATING EVENT

• Acute urticaria (IgE-mediated): Allergen (food, drug, venom, pollen) cross-links two adjacent IgE molecules bound to FcεRI on mast cells.

• Chronic spontaneous urticaria (autoimmune): Functional IgG autoantibodies against FcεRI (30–40%) or against IgE (5–10%) cross-link receptors, causing mast cell activation without exogenous allergen.

• Physical urticarias: Physical stimulus (cold, heat, pressure, friction, vibration, UV light, water, exercise) directly or indirectly activates mast cells. Mechanisms vary: cold urticaria may involve IgM anti-IgE antibodies (acquired) or unknown signals.

• Direct mast cell activators (pseudoallergic): Opiates, vancomycin, NSAIDs (aspirin, ibuprofen – inhibit COX-1, shunting arachidonic acid toward leukotrienes), radiocontrast media, neuromuscular blocking agents. These act directly on mast cells (not via IgE).

3. PATHOGENESIS

• Mast cell activation leads to degranulation within seconds to minutes.

• Histamine is released (stored preformed in granules) → binds to H1 receptors on endothelial cells → activates phospholipase C → increases intracellular calcium → endothelial cell contraction → widening of intercellular gaps (fenestrations) in post-capillary venules.

• Plasma leaks from vessels into the dermis → edema (wheal formation).

• Histamine also binds to H1 receptors on sensory nerves (C-fibers) → pruritus and axon reflex (flares – erythema surrounding the wheal).

• H2 receptor activation (on endothelial cells and gastric parietal cells) contributes to vasodilation but is less important than H1 in urticaria.

• Leukotrienes (LTC4, LTD4, LTE4) synthesized from arachidonic acid via 5-lipoxygenase → slow-reacting substance of anaphylaxis (SRS-A) → cause prolonged vasodilation and increased vascular permeability (hours).

• Prostaglandin D2 (PGD2) – synthesized via cyclooxygenase (COX) → vasodilation and neutrophil chemotaxis.

• Platelet-activating factor (PAF) – induces platelet aggregation, neutrophil activation, and increased vascular permeability. PAF is a key mediator in angioedema and anaphylaxis.

• TNF, IL-4, IL-13, IL-6 – recruit inflammatory cells (eosinophils, basophils, Th2 lymphocytes) to the site, contributing to late-phase reaction (4–8 hours later, less common in classic urticaria).

• Why lesions are transient (<24 hours): Histamine is rapidly degraded (half-life 1–2 minutes). Edema fluid is cleared by lymphatics. Without ongoing mast cell activation, the wheal resolves.

Why angioedema lasts longer (up to 72 hours): Bradykinin (rather than histamine) is the primary mediator in many cases of angioedema (especially ACE inhibitor-induced and hereditary angioedema). Bradykinin is degraded more slowly and causes more profound, deeper edema.

4. HISTOPATHOLOGY EXPLAINED

Low power:

• Dermal edema – pale, clear spaces separating collagen bundles in the superficial (papillary) and mid-dermis. This is the dominant finding.

• Dilated superficial dermal capillaries and venules.

• Perivascular infiltrate – sparse to moderate, primarily lymphocytes and eosinophils (not neutrophils – unless biopsy of late lesion or urticarial vasculitis).

• Epidermis – normal (no spongiosis, no acanthosis, no parakeratosis).

High power:

• Endothelial cells – swollen, plump, but intact (no necrosis).

• Perivascular infiltrate composition:

  • Lymphocytes (CD4+ > CD8+) – perivascular cuffing.

  • Eosinophils – present in 50–70% of urticaria biopsies (may be scattered, not abundant). Eosinophil granules contain major basic protein (MBP), which is toxic to endothelium and contributes to late-phase reaction.

  • Neutrophils – rare in classic urticaria; if prominent, suspect urticarial vasculitis or neutrophilic urticaria (subset of chronic urticaria).

  • Mast cells – may be increased in number (but degranulated, so difficult to identify on H&E; Giemsa or toluidine blue is required).

• No fibrinoid necrosis of vessel walls (this distinguishes urticaria from urticarial vasculitis).

• No leukocytoclasis (no nuclear dust – distinguishes from vasculitis).

Why this appearance:

• Dermal edema – Histamine-induced endothelial gap formation allows plasma to leak into the dermis, separating collagen bundles.

• Lymphocytes and eosinophils – These are recruited by chemokines (eotaxin for eosinophils) released from mast cells. Eosinophils are not always present, but their presence supports urticaria.

• No fibrinoid necrosis – Urticaria is not a vasculitis; vessel walls are edematous but not destroyed.

Late-phase reaction (4–8 hours, less common):

• More pronounced perivascular lymphocytic infiltrate (CD4+ T cells, eosinophils, basophils).

• Endothelial cell activation persists.

• Biopsy of a late lesion may mimic a lymphocytic vasculitis.

5. NAMING LOGIC & TERMINOLOGY

• Urticaria – From Latin urtica meaning nettle (the rash resembles nettle stings).

• Wheal – From Old English hwēle meaning a raised mark (also called a hive).

• Angioedema – From Greek angeion (vessel) + oidema (swelling) – deep dermal/subcutaneous swelling.

• Dermographism – Derma (skin) + graph (writing) + -ism – writing on the skin produces a wheal.

• Chronic spontaneous urticaria – No identifiable external trigger; formerly chronic idiopathic urticaria.

• Inducible urticaria – Triggered by a specific physical stimulus.

6. STAINING & MARKERS

H&E: Diagnostic as described above – shows dermal edema, dilated vessels, perivascular lymphocytes and eosinophils, no vasculitis.

Special stains (not routinely needed):

• Giemsa or toluidine blue: Stains mast cell granules (metachromatic – purple-red). Useful if mastocytosis is suspected (shows increased mast cell aggregates). In urticaria, mast cells are present in normal numbers but may be degranulated (empty granules).

• PAS (periodic acid–Schiff): Not helpful.

Immunohistochemistry (not diagnostic for urticaria, used for research or differential):

• Tryptase (mast cell tryptase): Immunostain for mast cells. Normal perivascular mast cells are present; degranulated mast cells show weak staining.

• CD117 (c-Kit): Mast cell marker.

• Major basic protein (MBP): Stains eosinophil granules.

• CD3, CD4, CD8, CD20: Characterize lymphocytic infiltrate (CD4+ T cells predominate).

• C5b-9 (membrane attack complex): Positive in vessel walls in urticarial vasculitis (negative in urticaria).

Direct immunofluorescence (DIF) – used to rule out urticarial vasculitis:

• Urticaria: Negative (no immune deposits in vessel walls).

• Urticarial vasculitis: Granular deposition of immunoglobulins (IgG, IgM, IgA) and complement (C3, C1q) in vessel walls.

Serologic markers (clinical, not histology):

• Serum tryptase: Elevated 1–4 hours after an acute episode (mast cell degranulation). Normal baseline tryptase rules out mastocytosis (baseline tryptase >20 ng/mL suggests mastocytosis).

• Anti-FcεRI autoantibodies: Positive in 30–40% of chronic spontaneous urticaria (research assay, not widely available).

• Anti-thyroid peroxidase (TPO) antibodies: Elevated in 20–30% of chronic urticaria (associated with autoimmune thyroid disease).

• C4: Low in hereditary angioedema (C1 esterase inhibitor deficiency) – normal in urticaria.

• Cryoglobulins, ANA, anti-dsDNA, anti-Ro/SSA, anti-La/SSB: Rule out autoimmune disease (SLE, Sjögren) if urticarial vasculitis suspected.

7. TEMPORAL EVOLUTION

• Early lesion (0–2 hours, urticarial wheal): Dermal edema, dilated vessels, sparse perivascular lymphocytes and eosinophils. No endothelial necrosis. This is the most diagnostic stage.

• Established lesion (2–8 hours): Peak edema; perivascular infiltrate more prominent (lymphocytes, eosinophils, occasional neutrophils). Endothelial cells are swollen but intact.

• Late lesion (8–24 hours, resolving wheal): Edema decreases; infiltrate becomes more lymphocytic; eosinophils may persist. Biopsy at this stage may show only mild perivascular lymphocytic infiltrate and can be misinterpreted as normal.

• Beyond 24 hours: Complete resolution. If a lesion persists beyond 24 hours with purpura or hyperpigmentation, suspect urticarial vasculitis and re-biopsy.

Board critical point: If a patient has wheals lasting longer than 24 hours, biopsy is required to rule out urticarial vasculitis. Biopsy must include the earliest possible lesion (within 2–8 hours) and the oldest lesion (24+ hours) for comparison.

8. PATTERN RECOGNITION & DIAGNOSTIC LOGIC

• Pattern: Dermal edema + dilated superficial vessels + perivascular lymphocytic and eosinophilic infiltrate + no vessel wall destruction + no leukocytoclasis.

Diagnostic pathway (histologic, integrating clinical history):

• Dermal edema + perivascular lymphocytes/eosinophils + no fibrinoid necrosis + lesion lasts <24 hours + no purpura → Urticaria.

• Dermal edema + perivascular lymphocytes/eosinophils + lesion lasts >24 hours + residual purpura/hyperpigmentation + DIF shows immune deposits → Urticarial vasculitis (biopsy shows leukocytoclasis, fibrinoid necrosis – not just edema).

• Dermal edema + perivascular neutrophils + leukocytoclasis + fibrinoid necrosis → Leukocytoclastic vasculitis (urticarial vasculitis is a subset).

• Dermal edema + perivascular lymphocytes/eosinophils + brown macule + Darier sign positive → Urticaria pigmentosa (mastocytosis) – biopsy shows dermal mast cell aggregates.

• Dermal edema only (no infiltrate) + clinical history of short-lived wheals → Very early urticaria or suboptimal biopsy (repeat biopsy of a fresh lesion).

• Normal histology + typical clinical history of urticaria → Biopsied too late (resolving lesion) or patient on antihistamines (suppresses inflammatory infiltrate).

Key discriminator from urticarial vasculitis (board favorite):

• Urticaria: Lesions last <24 hours, no purpura, no residual hyperpigmentation, biopsy shows edema and lymphocytes/eosinophils, no fibrinoid necrosis, no leukocytoclasis, DIF negative.

• Urticarial vasculitis: Lesions last >24 hours (often 48–72 hours), leave residual purpura or hyperpigmentation, burning pain (not just pruritus), biopsy shows leukocytoclasis, fibrinoid necrosis, red blood cell extravasation, DIF shows immune deposits (IgG, IgM, C3, C1q) in vessel walls.

Key discriminator from mastocytosis:

• Urticaria: No fixed lesions, normal baseline serum tryptase, no Darier sign, no mast cell aggregates on biopsy.

• Urticaria pigmentosa (mastocytosis): Fixed brown macules/papules that urticate with rubbing (Darier sign), baseline tryptase elevated (>20 ng/mL), biopsy shows aggregates of mast cells (Giemsa or tryptase stain).

9. CLINICO-PATHOLOGICAL CORRELATION

• Wheal (raised, edematous plaque) → Dermal edema separates collagen bundles, pushing up the epidermis.

• Central pallor – Pressure from edema compresses the central capillaries, reducing blood flow, while peripheral erythema persists (due to axon reflex).

• Erythema (flare) – Histamine-induced vasodilation and axon reflex (C-fiber activation releasing substance P, calcitonin gene-related peptide).

• Pruritus – Histamine binding to H1 receptors on unmyelinated C-fibers in the dermis.

• Transient nature (<24 hours) – Histamine is rapidly degraded by histamine N-methyltransferase and diamine oxidase. Edema fluid is cleared by lymphatics.

• Angioedema (deep swelling) – Bradykinin-mediated leakage from deeper dermal and subcutaneous venules; bradykinin is degraded more slowly than histamine.

• Dermographism – Mast cells in mechanically stimulated skin degranulate (weak physical stimulus triggers histamine release in susceptible individuals).

• No scarring or pigmentation – No vessel wall destruction; no hemorrhage (unless patient scratches severely).

10. EXAM-FOCUSED INSIGHTS

• Duration of individual wheal (<24 hours) is the single most important diagnostic feature – If a patient says lesions last days, it is NOT urticaria until proven otherwise (think urticarial vasculitis, erythema multiforme, bullous pemphigoid).

• Histology is usually NOT needed for acute urticaria – Diagnosis is clinical. Biopsy is reserved for chronic urticaria (>6 weeks) to rule out urticarial vasculitis and mastocytosis.

• Biopsy of urticaria must be performed on a very fresh lesion (2–8 hours old) – Older lesions show only mild lymphocytic infiltrate and may be indistinguishable from normal skin.

• Eosinophils in the perivascular infiltrate support urticaria – But absence does not exclude it.

• Neutrophils in urticaria are abnormal – Prominent neutrophils suggest urticarial vasculitis, neutrophilic urticaria (a rare subset), or autoinflammatory syndrome (cryopyrin-associated periodic syndrome – CAPS).

• Chronic spontaneous urticaria is an autoimmune disease in 30–50% – Associated with anti-FcεRI autoantibodies and anti-thyroid antibodies. This is a board favorite.

• Omalizumab is first-line biologic for refractory CSU – More effective than cyclosporine and better tolerated.

• Corticosteroids have no role in long-term management of chronic urticaria – Use only for acute severe flares (3–7 days). Long-term use indicates failure of step therapy.

• ACE inhibitor angioedema is NOT histamine-mediated – Treat with icatibant or fresh frozen plasma; antihistamines and epinephrine are ineffective.

• Hereditary angioedema presents with angioedema without wheals – C1 esterase inhibitor deficiency (type I low levels; type II dysfunctional protein). Low C4 is the screening test.

• Physical urticarias are diagnosed by provocation testing – Ice cube test (cold urticaria), exercise challenge (cholinergic), pressure test (delayed pressure), UV challenge (solar), vibration test (vibratory).

Must-Know Board Exam Questions & Answers

Q1: A 30-year-old woman presents with recurrent, intensely pruritic, raised red plaques that appear on her trunk and extremities. Each individual lesion resolves completely within 4 hours. What is the most likely diagnosis?

A: Urticaria.

Q2: What is the critical clinical feature that distinguishes urticaria from urticarial vasculitis?

A: Duration of individual lesions. Urticaria wheals last less than 24 hours; urticarial vasculitis lesions last more than 24 hours and leave residual purpura or hyperpigmentation.

Q3: A patient with chronic urticaria fails standard-dose cetirizine. What is the next step in management according to treatment guidelines?

A: Up-dosing of second-generation non-sedating H1 antihistamine (e.g., cetirizine 20–40 mg daily, off-label but guideline-supported).

Q4: What is the mechanism of action of omalizumab in chronic spontaneous urticaria?

A: Omalizumab binds free IgE, downregulates the high-affinity IgE receptor (FcεRI) on mast cells and basophils, and prevents cross-linking by autoantibodies (anti-FcεRI or anti-IgE).

Q5: A skin biopsy of a patient with suspected urticaria shows dermal edema, dilated vessels, and a perivascular infiltrate of lymphocytes and eosinophils. There is no fibrinoid necrosis and no leukocytoclasis. What is the diagnosis?

A: Urticaria.

Q6: A 40-year-old man presents with recurrent angioedema (swelling of lips and eyelids) without wheals. He has no response to antihistamines. His family history is positive for similar episodes. What lab test should be ordered first?

A: Serum C4 (low in hereditary angioedema due to C1 esterase inhibitor deficiency). Confirm with C1 esterase inhibitor level and function.

Q7: Name two autoimmune conditions associated with chronic spontaneous urticaria.

A: Autoimmune thyroid disease (Hashimoto thyroiditis) and vitiligo. Also pernicious anemia and type 1 diabetes.

Q8: A 25-year-old develops generalized urticaria and difficulty breathing 10 minutes after eating shrimp. What is the immediate treatment?

A: Intramuscular epinephrine (0.3 mg adult, 0.15 mg child) into the anterolateral thigh.

Q9: What histologic finding on biopsy of a chronic urticaria patient should prompt immediate reconsideration of the diagnosis?

A: Neutrophils, leukocytoclasis, or fibrinoid necrosis – these suggest urticarial vasculitis, not simple urticaria.

Q10: A patient develops wheals after cold exposure. What is the name of this condition, and what is a life-threatening risk?

A: Cold urticaria. Life-threatening risk is anaphylaxis during swimming in cold water (massive mast cell degranulation from whole-body cold exposure).