Terbinafine‐induced dermatomyositis: a case report and literature review of drug‐induced dermatomyositis

Abstract

Dermatomyositis, a connective tissue disease syndrome where antibodies to the endothelium of the microvasculature of the skin, muscle and lung are implicated in lesional propagation, is characterized by photodistributed erythema, heliotrope rash, Gottron's papules, muscle weakness and interstitial pulmonary fibrosis. Endotheliotropic viruses and underlying neoplasia are among the inciting triggers. Uncommon drugs, namely the lipid-lowering agents, have been implicated in dermatomyositis. The patient, a 57-year-old man, developed a photodistributed rash and muscle weakness following treatment with the antifungal medication, terbinafine. A skin biopsy was performed, showing an atrophying interface dermatitis with pandermal mucinosis and striking vasculopathic changes including endothelial cell necrosis with denudement and basement membrane zone reduplication. Ultrastructural studies confirmed the presence of endothelial cell injury. Direct immunofluorescent testing showed prominent staining of C5b-9 along the dermal-epidermal junction and within the vasculature. Western blot studies showed strong seroreactivity of his serum to an endothelial-based protein weighing 45,000, a common target described in other microvascular injury-based syndromes. We have shown a temporal association between use of terbinafine and the development of dermatomyositis. The exact basis remains speculative. One potential hypothesis is based on the fact that terbinafine, the active agent in terbinafine, triggers apoptosis of human endothelial cells in culture. Enhanced endothelial cell apoptosis results in the displacement of various cellular antigens creating a state of neoantigenicity; its attendant sequelae is held to be one of anti-endothelial cell antibody formation, a defining pathogenetic event in the evolution of dermatomyositis. The second may be because of the effects of the drug on the promotion of an interferon-rich T-helper-1-dominant cytokine milieu.

Update on terbinafine with a focus on dermatophytoses

“…195 Recently, reports have also linked dermatomyositis and subacute cutaneous systemic lupus erythematosus to terbinafi ne. 196,197 In one patient, a skin eruption presenting 4 weeks after the onset of therapy and occurring with the triad of fever, hepatic dysfunction and lymphadenopathy led investigators to conclude the presence of hypersensitivity syndrome. Resolution was experienced within 6 weeks of discontinuing the drug.…”

A Multicenter, Randomized, Open-Label, Controlled Study Comparing the Efficacy, Safety and Cost-Effectiveness of a Sequential Therapy with RV4104A Ointment, Ciclopiroxolamine Cream and Ciclopirox Film-Forming Solution with Amorolfine Nail Lacquer Alone in Dermatophytic Onychomycosis

“…Altered taste perception is an AE associated with terbinafine [17] . Rare cases of drug-induced lupus and acute generalized exanthematous pustulosis have also been reported with terbinafine [18,19] .…”

Drug‐induced dermatomyositis after zoledronic acid

“…However other drugs implicated include d ‐penicillamine, non‐steroidal anti‐inflammatory drugs (niflumic acid, diclofenac, phenylbutazone), anti‐infective agents (penicillins, sulphonamides, isoniazid), anti‐neoplastic (tegafur, cyclophosphamide, etoposide, imatinib) and lipid lowering drugs (statins and fibrates) 2,4 . Other reports have included bacille Calmette–Guérin tuberculosis vaccine, terbinafine, omeprazole, interferon α‐2b, phenytoin, and alfuzosin 2,4,5 . It is postulated that the mechanisms by which these drugs induce autoimmunity is by promotion of apoptosis and enhancement of the innate immune response.…”