Background: Drug-induced lupus erythematosus is a lupus variant that resolves within days to months after withdrawal of the eliciting drug, in patients without other major underlying immune system dysfunction. Case report: A 71 year old Caucasian female presented following sudden onset of an erythematous, desquamative, polycyclic, scaling and pruritic rash in sun exposed areas, 4 days after taking Lisinopril ®. Skin biopsies for hematoxylin and eosin analysis, as well as for direct immunofluorescence (DIF) were obtained. Results: The hematoxylin and eosin staining revealed basal layer vacuolar degeneration, basilar apoptotic and dyskeratotic keratinocytes, and a lymphocytic interface dermatitis with an additional superficial and deep, perivascular and periadnexal lymphohistiocytic infiltrate. A significant presence of eosinophils was noted in the inflammatory infiltrate. DIF demonstrated positive reactivity with FITC conjugated anti-human fibrinogen, especially directed against dermal neurovascular plexus components and appendageal neurovascular supply structures; this staining colocalized with glial fibrillary acidic protein staining. Overexpression of anti-plasminogen and anti-junctional adhesion molecule A was also noted in these areas. Conclusion: In this case of a lupus-like allergic drug reaction, the strong presence of dermal eosinophils, lack of basement membrane zone deposition of IgM and C3 and strong reactivity to dermal vessels with fibrinogen assisted in addressing the differential diagnosis of lupus erythematosus.