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Terbinafine-Induced Lichenoid Drug Eruption: Case Report and Review of Terbinafine-Associated Cutaneous Adverse Events

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Terbinafine-Induced Lichenoid Drug Eruption: Case Report and Review of Terbinafine-Associated Cutaneous Adverse Events Volume 26 Number 7| Jul 2020| Dermatology Online Journal || Case Report 26(7):4 Terbinafine-induced lichenoid drug eruption: case report and review of terbinafine-associated cutaneous adverse events Philip R Cohen1-4 MD, Christof P Erickson5 MD, and Antoanella Calame5 MD Affiliations: 1San Diego Family Dermatology, National City, California, USA, 2Touro University California College of Osteopathic Medicine, Vallejo, California, USA, 3Scripps Family Medicine Residency, Scripps Mercy Hospital Chula Vista, Chula Vista, California, USA, 4Family Medicine Residency, Family Health Centers of San Diego, San Diego, California, USA, 5Compass Dermatopathology, San Diego, California, USA Corresponding Author: Philip R. Cohen MD, 10991 Twinleaf Court, San Diego, CA 92131-3643, Email: [email protected] Introduction Abstract Terbinafine, an allylamine, is an antifungal agent Terbinafine is an antifungal agent used in the used for the management of onychomycosis [1-13]. treatment of hair, nail, and skin dermatophyte A lichenoid drug eruption, also referred to as a lichen infections. Skin side effects to terbinafine are not common. Lichenoid drug eruption is a medication- planus-like eruption, can present with similar related adverse cutaneous event; the lesion features that are observed in patients with idiopathic morphology and pathology mimic lichen planus. A lichen planus [14-18]. A woman who developed a woman with onychomycosis developed a lichenoid lichenoid drug reaction to terbinafine is described drug eruption one week after starting terbinafine. and terbinafine-associated adverse cutaneous The features of her dermatosis and the characteristics events are reviewed. of two additional men who also experienced terbinafine-induced lichenoid drug eruption are discussed. They were receiving a daily terbinafine Case Synopsis dosage of either 125mg or 250mg to treat A 68-year-old woman presented to her primary care onychomycosis or tinea cruris. The lichenoid drug eruption presented as diffuse or symmetric lesions physician with dystrophy of her toenails. Therapy within one to two weeks after starting terbinafine was initiated with oral terbinafine at a dosage of treatment. The extremities, chest, abdomen, and/or 250mg daily. She began to develop an itchy rash on trunk were common sites. Less frequent locations her lower abdomen and groin areas after the seventh were the lips, nails, palms, soles, and suprapubic day of treatment; however, she continued to take the region; lesions did not occur on the oral or genital medication for an additional seven days. The rash mucosa. The eruption resolved after discontinuation continued to spread to her chest after she of the medication (with or without treatment using discontinued the terbinafine. One week after topical corticosteroids, systemic corticosteroids, or stopping the terbinafine she presented for both). In addition, more frequently occurring evaluation of her skin. Cutaneous examination terbinafine-associated cutaneous adverse events showed pruritic erythematous scaly plaques on her (such as urticaria, erythematous eruptions, pruritus, acute generalized exanthematous pustulosis, chest, abdomen, and suprapubic region (Figure 1). subacute cutaneous lupus erythematosus, and Skin biopsies of lesions on her right chest and right papulosquamous conditions) are reviewed. abdomen were performed. Microscopic examination of both biopsies had similar pathologic changes (Figure 2). The epidermis Keywords: adverse cutaneous, drug, effect, event, fungal, shows compact hyperkeratosis, acanthosis and lichenoid, reaction, side, skin, terbinafine hypergranulosis; there are also focal areas of - 1 - Volume 26 Number 7| Jul 2020| Dermatology Online Journal || Case Report 26(7):4 spongiosis, scattered necrotic keratinocytes, and vacuolar alteration of the basal layer. In the upper dermis, there is not only an interface dermatitis with a band-like infiltration of lymphocytes and histiocytes, but also perivascular inflammation and extravasated erythrocytes; in addition, there are numerous eosinophils. The pathologic changes are those of a lichenoid dermatitis. The presence of abundant eosinophils is consistent with the possibility of a drug-related etiology. Correlation of the clinical history, the lesion morphology, and the pathologic changes establish the diagnosis of terbinafine-induced lichenoid drug eruption. A Terbinafine had already been discontinued a week earlier. However, the patient was still developing new symptomatic lesions. Management included systemic prednisone (60mg daily for six days, B A B Figure 2. A, B). Distant (A) and closer (B) views of microscopic C features of terbinafine-induced lichenoid drug eruption. There is compact hyperkeratosis and hypergranulosis. There are focal areas Figure 1. A-C). Distant (A) and closer (B, C) views of terbinafine- of spongiosis in the lower layers of the acanthotic epidermis. induced lichenoid drug eruption. Symmetrically distributed Vacuolar alteration of the epidermal basal layer is also present. A pruritic erythematous scaly plaques on the chest (A, B) and band-like infiltrate of lymphocytes, histiocytes and numerous abdomen (A, C) of a 68-year-old woman that appeared one week eosinophils fill the papillary dermis; in addition, there is after initiating terbinafine therapy (at a daily dosage of 250mg) to perivascular inflammation in the upper dermis. H&E, A) 10×; B) treat onychomycosis. 20×. - 2 - Volume 26 Number 7| Jul 2020| Dermatology Online Journal || Case Report 26(7):4 followed by 40mg daily for four days, followed by Box 1. Cutaneous adverse events associated with terbinafine. 20mg daily for two days) and topical betamethasone Acute generalized exanthematous pustulosis [23-28] dipropionate 0.05% cream three times daily to the Alopecia areata [29] lesions. The patient returned two weeks later; the Dermatitis-exacerbation [30] Dermatomyositis [31, 32] pruritus had resolved and her skin lesions had Desquamation [33] completely cleared. She decided not to treat her Erythema annulare-like psoriatic drug eruption [34] onychomycosis. There was no recurrence of the Erythema multiforme [35-39] dermatosis at follow-up examination two months Erythema nodosum [40] Erythematous eruption [29] later. Erythroderma [36]a Fixed drug eruption [41] Gray facial hyperpigmentation [42]b Hairloss [29] Case Discussion Hypersensitivity syndrome [43] Terbinafine interferes with fungal cell membrane Lichenoid drug eruption [44, 45, current report] ergosterol biosynthesis by selectively inhibiting the Pityriasis rosea-like eruption [36, 46] fungal enzyme squalene epoxidase [1-13]. Systemic Pruritus [29] Psoriasis—de novo or exacerbation [26, 28, 36, 47-49] dosing of the drug is a mainstay treatment of fungal Rash [50] nail infection and dermatophytic hair and skin Rowell syndrome [51-54]c infections [1-13]. Gastrointestinal symptoms Skin eruption-mild [55] (nausea, diarrhea, dyspepsia and abdominal pain) Skin rash-severe [56] Stevens-Johnson syndrome [57] and headaches are the main adverse events Subacute cutaneous lupus erythematosus [58-61] associated with terbinafine [1-13]. However, a Symmetric drug-related intertriginous and flexural exanthema unique terbinafine-related side effect is taste [62-64]d disturbance [19-22]. Systemic lupus erythematosus [57, 65] Toxic epidermal necrolysis [35, 66] Adverse cutaneous events to terbinafine have been Urticaria [36, 50, 67]e observed in approximately two percent of patients aA 56-year-old woman developed generalized pruritic erythroderma on (Box 1), [23-67]. The most common skin side effects day 27 after starting terbinafine; she was treated with oral prednisone and severe desquamation occurred. The erythroderma and include urticaria, erythematous dermatoses, and desquamation resolved over two weeks; however, she developed biopsy- pruritus [13, 29, 36, 50]. However, albeit uncommon, proven warts and seborrheic keratoses all over her body. life threatening conditions such as Stevens-Johnson bA 65-year-old man developed gray-brown macula on his face beginning syndrome and toxic epidermal necrolysis have been four weeks after starting terbinafine for onlychomycosis. Melanin localized within macrophages in both the upper and lower dermis was reported [35, 57, 66]. found on microscopic examination of the biopsy. Acute generalized exanthematous pustulosis is an cRowell syndrome, described in 1963, is characterized by lupus erythematosus with erythema multiforme-like lesions and specific uncommon cutaneous drug reaction characterized immunological abnormalities: a positive rheumatoid factor, a speckled by the acute onset of widespread small nonfollicular antinuclear antibody and precipitating antibodies to saline extract of intraepidermal or subcorneal sterile pustules arising human tissue (anti-SjT). Subsequently, in 2000, major (clinical features of a lupus erythematosus subtype, erythema multiforme-like lesions, and a on edematous and erythematous skin. The patients speckled pattern of antinuclear antibody) and minor [chilblains, anti- typically also have pruritus, fever, and neutrophilia. Sjogren syndrome antigen A (SS-A; also referred to as Ro) and anti- This dermatosis has been associated with several Sjogren syndrome antigen B (SS-B; also referred to as La) antibodies, and a positive rheumatoid factor]; all three major criteria and at least one of antibiotics such as ampicillin, amoxicillin, macrolides, the minor criteria are necessary to establish the diagnosis of RS. quinolones, and sulfonamides. Acute generalized d
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