Emergency Medicine Hub / Dermatology, Allergy & Rheumatology • 3 min read • 2 sections

Urticaria, Severe Erythemas & Drug Exanthems

Comprehensive emergency evaluation and protocolized management of acute cutaneous hypersensitivity reactions and drug exanthems: Acute Urticaria (mast cell histamine wheals lasting < 24h per lesion, H1 and H2 antihistamine combinations), distinguishing true urticaria from Urticarial Vasculitis (lesions persisting > 24–48 hours, burning/painful rather than pruritic, leaving residual post-inflammatory purpura/ecchymosis); Erythema Multiforme (EM minor vs. EM major; HSV-1 trigger, true concentric target lesions with necrotic central centers); Serum Sickness and Serum Sickness-Like Reactions (SSLR; cefaclor, penicillins; fever, polyarthralgias, urticarial rash 1–2 weeks post-exposure); and Fixed Drug Eruptions (recurrence in the identical anatomical site).

Resuscitation Quick Actions • First 2 Minutes

High-Acuity

The 24-Hour Urticaria Rule

Individual urticarial wheals MUST resolve within 24 hours; lesions persisting > 24–48h with purpura = URTICARIAL VASCULITIS

Dual Antihistamine Cocktail

Cetirizine 10–20 mg PO (H1 blocker) + Famotidine 20 mg PO (H2 blocker); dual histamine receptor blockade is superior to H1 alone

True Target Lesions (EM)

Three concentric zones: central dark/dusky necrotic center, middle pale edematous ring, outer erythematous halo; #1 trigger is HSV

Urticarial Vasculitis Warning

Lesions burn/hurt rather than itch; leaves permanent bruising/purpura; send skin biopsy for leukocytoclastic vasculitis and check complement

Serum Sickness-Like Reaction

Occurs 1–2 weeks after antibiotic (Cefaclor, Penicillin): Triad of fever, polyarthralgias, and extensive urticarial/edematous rash

Fixed Drug Eruption

Well-demarcated dusky violaceous plaque recurring in the EXACT SAME anatomical location (genitalia, lips) upon re-exposure to drug (NSAIDs/Bactrim)

Acute Generalized Exanthematous Pustulosis (AGEP)

Rapid eruption of hundreds of small, non-follicular sterile pustules on an erythematous base, usually within 24-48 hours of drug exposure (antibiotics); associated with fever and leukocytosis; self-resolving with drug cessation.

Calciphylaxis (Calcific Uremic Arteriolopathy)

Rare, fatal condition in end-stage renal disease/dialysis patients; microvascular calcification leads to ischemic painful violaceous plaques that rapidly ulcerate into black eschars; treat with sodium thiosulfate and wound care.

Bottom-Line Clinical Pearl

Acute urticaria presents with transient, intensely pruritic, erythematous, edematous wheals with central pallor. The single most critical diagnostic rule in urticaria is: AN INDIVIDUAL WHEAL MUST RESOLVE WITHIN 24 HOURS! If individual lesions persist in the exact same location for > 24 to 48 hours, are described as burning or painful rather than itchy, and resolve with residual purpura or brown hyperpigmentation, the diagnosis is URTICARIAL VASCULITIS (leukocytoclastic vasculitis; requires systemic workup for autoimmune disease, hepatitis, or malignancy). First-line therapy for acute urticaria is a non-sedating second-generation H1 antihistamine (Cetirizine 10–20 mg PO) combined with an H2 blocker (Famotidine 20 mg PO); systemic steroids are reserved only for severe intractable symptoms. Erythema Multiforme (EM) is characterized by true target lesions (three concentric zones with central dusky necrosis); over 90% are triggered by recurrent Herpes Simplex Virus (HSV) infection.

1. Acute Urticaria vs. Urticarial Vasculitis

Acute urticaria is driven by mast cell and basophil degranulation, releasing histamine, leukotriene C4, and prostaglandin D2, causing local pre-capillary vasodilation and increased venular permeability in the superficial dermis. Distinguishing standard urticaria from true systemic vasculitis is an essential emergency skill:

Diagnostic Parameter	Acute Urticaria (True Hives)	Urticarial Vasculitis (Leukocytoclastic Vasculitis)
Duration of Single Individual Lesion	$< 24 Hours (Typically 2 to 6 hours; lesions vanish from one spot and reappear elsewhere)	$> 24 to 48 Hours in the exact same anatomical location (mark a lesion with a surgical pen to confirm!)
Primary Sensation	Intensely pruritic (itchy)	Burning, tenderness, or painful stinging; minimal itching
Resolution Sequelae	Resolves completely with normal skin; zero residual discoloration	Resolves with residual ecchymosis, purpura, or hyperpigmentation (erythrocyte extravasation)
Histopathology & Systemic Links	Dermal edema without vessel wall destruction; benign triggers (viral URIs, foods, NSAIDs)	True leukocytoclastic vasculitis: fibrinoid necrosis of post-capillary venule walls with neutrophil nuclear dust (leukocytoclasia); associated with SLE, hypocomplementemia (HUV syndrome), Hepatitis B/C.

2. High-Yield Reactive Erythemas & Exanthems

Dermatologic Condition	Etiological Triggers	Classic Morphology & Distribution	Emergency Treatment Protocols
Erythema Multiforme (EM)	Herpes Simplex Virus (HSV-1/HSV-2) accounts for $> 90\%$ of cases; Mycoplasma pneumoniae; rarely drugs	True Pathognomonic Target Lesions: three concentric zones (central dusky blister/crust, surrounding pale edematous ring, outer sharp erythematous halo). Symmetrical distribution on palms, soles, extensor forearms.	Self-limiting (resolves in 2–4 weeks). Discontinue offending drugs; supportive care; oral acyclovir/valacyclovir for recurrent HSV-associated EM.
Serum Sickness-Like Reaction (SSLR)	Occurs 7 to 14 days after exposure to Cefaclor, Amoxicillin, Ciprofloxacin, or Trimethoprim-Sulfamethoxazole	Clinical Triad: (1) Fever, (2) Polyarthralgias/arthritis (knees, wrists, ankles), and (3) Urticarial/edematous skin eruption; facial edema common	Discontinue offending antibiotic permanently; oral corticosteroids (Prednisone 1 mg/kg/day x 5–7 days) provide dramatic symptom relief within 24–48 hours.
Fixed Drug Eruption (FDE)	NSAIDs, Tetracyclines, Sulfonamides (Bactrim), Fluconazole, Barbiturates	Solitary (or few) sharply demarcated, circular, dusky violaceous erythematous plaques that recur in the PRECISE SAME ANATOMICAL SITE (glans penis, lips, hands) each time the drug is ingested; leaves residual slate-gray post-inflammatory hyperpigmentation.	Discontinue causative agent; topical high-potency corticosteroids (Clobetasol 0.05%); patient counseling.

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