Erythema Multiforme
The most likely diagnosis is erythema multiforme (EM), a drug-induced hypersensitivity reaction triggered by trimethoprim-sulfamethoxazole. The clinical presentation—targetoid lesions with central dark papules progressing from elbows and lower legs to involve palms and soles over 5 days—is pathognomonic for EM, and trimethoprim-sulfamethoxazole is one of the most frequently implicated medications. 1, 2, 3
Distinguishing Features That Confirm Erythema Multiforme
The key diagnostic features in this case are:
Targetoid lesions (2–3 cm) with central dark papules represent the classic "target" or "iris" lesions of EM, consisting of three concentric zones: a central dusky area, a pale edematous ring, and an outer erythematous halo. 1
Acral distribution involving palms and soles is highly characteristic of EM and helps distinguish it from other drug eruptions. 1, 3
Progressive spread from initial sites (elbows, lower legs) to extremities over several days matches the typical evolution of EM, which develops over 3–7 days. 1
Trimethoprim-sulfamethoxazole exposure is documented as one of the most common drug triggers for EM, with multiple case reports confirming this association. 2, 3, 4
Why Other Diagnoses Are Less Likely
Stevens-Johnson syndrome (SJS) can be excluded because this patient lacks the defining features: no mucosal involvement (oral, ocular, or genital erosions), no epidermal detachment or positive Nikolsky sign, and no confluent erythema with skin sloughing. SJS presents with painful mucosal erosions and widespread epidermal necrosis, not discrete targetoid papules. 1, 5
Dermatitis herpetiformis is ruled out by the absence of intensely pruritic grouped vesicles on extensor surfaces, the lack of association with celiac disease, and the wrong morphology—dermatitis herpetiformis produces small vesicles and excoriations, not 2–3 cm targetoid lesions. 1
Lyme disease does not present with targetoid lesions on palms and soles. Erythema migrans of Lyme disease is a single expanding annular patch (not multiple discrete targets), typically appears at the tick bite site (trunk, axilla, groin—not acral), and does not involve palms or soles. 1
Secondary syphilis can mimic many rashes but is excluded by the absence of systemic symptoms (fever, lymphadenopathy, condyloma lata), the wrong time course (secondary syphilis develops 4–10 weeks after primary chancre, not 5 days after drug exposure), and the presence of central dark papules rather than the copper-colored macules and papules typical of syphilis. 1
Immediate Management
Discontinue trimethoprim-sulfamethoxazole immediately as the first and most critical step, since continued exposure to the offending drug can worsen the reaction. 1, 2, 4
Symptomatic treatment for acute EM includes:
Topical corticosteroids (high-potency) applied to skin lesions to reduce inflammation and pruritus. 1
Oral antihistamines for symptomatic relief of itching. 1
Antiseptic or anesthetic solutions if mucosal involvement develops (though absent in this case). 1
Systemic corticosteroids (e.g., prednisone 0.5–1 mg/kg/day for 7–14 days with taper) are reserved for severe or extensive cutaneous involvement, though their benefit in EM is debated and they are not routinely recommended for mild-to-moderate cases. 1, 2
Monitoring and Follow-Up
Assess for mucosal involvement (oral, ocular, genital) at presentation and during follow-up, as progression to involve mucous membranes would indicate more severe disease requiring closer monitoring. 1
Educate the patient to avoid trimethoprim-sulfamethoxazole permanently and document the allergy prominently in the medical record, as re-exposure can trigger more severe reactions. 2, 3, 4
Schedule follow-up within 48–72 hours to ensure lesions are resolving and no systemic complications (fever, mucosal erosions, skin detachment) have developed. 1
Common Pitfalls to Avoid
Do not confuse EM with SJS based solely on the presence of "target" lesions—true SJS targets are atypical (two zones, not three) and accompanied by mucosal erosions and epidermal detachment, which are absent here. 1, 5
Do not prescribe systemic corticosteroids reflexively for all cases of EM; mild-to-moderate disease responds well to topical therapy and drug discontinuation alone. 1
Do not overlook the possibility of recurrent EM if the patient has a history of herpes simplex virus (HSV) infection, as HSV is the most common trigger overall (though not in this drug-induced case). 1
Do not restart trimethoprim-sulfamethoxazole or structurally related sulfonamides (e.g., sulfasalazine, furosemide) without allergy testing, as cross-reactivity can occur. 2, 3, 4