Diagnosis: Disseminated fixed-drug eruption
The diagnosis was based on the morphologic characteristics of the eruption and the patient’s history of similar lesions that appeared in the exact same initial locations (chin and glans penis) following previous treatment with TMP-SMX.
A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with our patient).
The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.1
The diagnosis is usually made based on a history of similar lesions recurring at the same location in response to a specific drug2 and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. To confirm a fixed-drug eruption in the case of clinical equipoise, a skin biopsy may be performed.
Classic histologic findings of a fixed-drug eruption include:
- band-like lichenoid lymphocytic infiltrates with vacuolar changes at the dermoepidermal junction,
- mixed cellular infiltrates, including eosinophils, throughout the dermis and occasional superficial and deep mixed cellular perivascular infiltrates, and
- abundant melanophages suggesting pigment incontinence.
There are several reports of similar TMP-SMX–induced generalized fixed-drug eruptions in the literature.3 One study of 64 cases of fixed-drug eruption found that TMP-SMX was the most common offender, causing 75% of fixed-drug eruption cases; naproxen sodium came in second with 12.5%.3 Other common culprits include the antipyretic metamizole and other pyrazolone derivatives such as tetracycline, metronidazole, ciprofloxacin, and phenytoin sodium.4 There is evidence supporting a correlation between the offending drug and the subsequent site of reaction; TMP-SMX is associated with mucosal junction and genital involvement.4,5 This finding may aid physicians in the investigation of provoking agents.
Distinguish fixed-drug eruptions from serious bullous diseases
Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches. Fixed-drug eruptions can be distinguished by the lack of simultaneous involvement of 2 mucosal surfaces, lack of generalized desquamation, and normal vital signs and lab values, including white blood cell count and erythrocyte sedimentation rate/C-reactive protein.