Is a single lesion on the leg of a patient with a history of urinary tract infections (UTIs) and recent use of sulfamethoxazole (Bactrim) likely an immunological reaction, specifically erythema multiforme?

Is a Single Leg Lesion Likely Erythema Multiforme from Sulfamethoxazole?

A single isolated lesion on the leg is unlikely to be erythema multiforme (EM), as EM characteristically presents with multiple symmetric targetoid lesions predominantly on the extremities' extensor surfaces, not as a solitary finding. 1, 2

Key Clinical Features That Argue Against Erythema Multiforme

Distribution Pattern

• EM classically presents with bilateral, symmetric distribution on the extremities (especially extensor surfaces) that spreads centripetally toward the trunk 1
• A single unilateral leg lesion does not fit the typical EM presentation pattern 1, 2
• EM lesions are typically multiple, not isolated 2, 3

Lesion Morphology

• EM is characterized by target or "iris" lesions with concentric zones of color change and central clearing 2, 4
• Individual EM lesions remain fixed for a minimum of 7 days, distinguishing them from urticaria which resolves within 24 hours 1
• The classic targetoid appearance with well-demarcated plaques is diagnostic 2

Sulfamethoxazole Hypersensitivity Considerations

Drug Reaction Profile

• Sulfamethoxazole can cause severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, and AGEP, but these typically present with widespread lesions, not isolated findings 5
• The FDA warns that sulfamethoxazole should be discontinued at the first appearance of skin rash, as it may progress to more severe reactions 5
• Drug-induced EM from sulfonamides typically presents with the characteristic multiple targetoid lesions, not a single lesion 2

Clinical Red Flags Requiring Immediate Action

• Discontinue sulfamethoxazole immediately if any rash appears, as it may herald a more severe reaction 5
• Monitor for systemic symptoms: fever, pharyngitis, arthralgia, cough, chest pain, dyspnea, pallor, purpura, or jaundice 5
• Mucosal involvement, blistering, or widespread erythematous macules suggest Stevens-Johnson syndrome rather than EM 1

Alternative Diagnoses to Consider for a Single Leg Lesion

Infectious Etiologies

• Cutaneous fungal infections begin as erythematous papules that may become pustular with central ulceration and elevated borders; confirm with KOH preparation 6
• Bacterial cellulitis presents as localized warmth, erythema, and induration 7
• Consider E. coli-related skin infection if there is recent UTI history, though this would typically present as cellulitis rather than a targetoid lesion 7

Inflammatory Conditions

• Erythema nodosum presents as tender, raised subcutaneous nodules (1-5 cm) on the anterior tibial area, but these are nodular rather than targetoid 6
• Fixed drug eruption can present as a solitary lesion that recurs in the same location with drug re-exposure 4

Other Considerations

• Insect bite reactions, local trauma, or contact dermatitis can present as isolated leg lesions 7, 8
• In immunocompromised patients, consider opportunistic infections like cutaneous cryptococcosis 9

Diagnostic Approach

Immediate Assessment

• Document lesion characteristics: size, morphology, presence of targetoid appearance, and any mucosal involvement 8
• Assess for systemic symptoms (fever, malaise) that would suggest serious drug reaction 5
• Examine for additional lesions on other extremities, particularly extensor surfaces 1, 2

Laboratory Evaluation

• Skin biopsy with histopathology if diagnosis remains uncertain 4
• Fungal culture and KOH preparation to exclude fungal infection 6
• Consider bacterial culture if infection suspected 8

Management Recommendations

If Sulfamethoxazole Recently Started

• Discontinue sulfamethoxazole immediately given the potential for progression to severe cutaneous reactions 5
• Switch to alternative antibiotic for UTI treatment (fluoroquinolone or first-generation cephalosporin if appropriate) 7

Symptomatic Treatment

• Topical high-potency corticosteroids for localized inflammatory lesions 3, 8
• Topical mupirocin 2% if secondary bacterial infection suspected 8
• Antihistamines for pruritus if present 1, 3

Follow-Up Monitoring

• Reassess in 48-72 hours for development of additional lesions or systemic symptoms 8
• If new targetoid lesions develop bilaterally on extremities, reconsider EM diagnosis 1, 2
• Document resolution timeline; EM lesions persist for minimum 7 days 1

Critical Clinical Pitfall

The most important pitfall is assuming a single lesion represents EM and continuing sulfamethoxazole, when the drug should be stopped immediately at any sign of rash due to risk of progression to life-threatening SCARs 5. The absence of multiple symmetric targetoid lesions makes EM unlikely, but drug hypersensitivity remains a concern requiring immediate discontinuation 5, 1.