Concurrent terbinafine-induced acute generalised exanthematous pustulosis and hepatitis

Abstract

Terbinafine is a commonly used antifungal medication. Its side effects, while widely known, are rarely described and can be missed by the medical community. We present a 55-year-old woman who visited her primary care physician with onychomycosis. She started treatment with terbinafine, and 1 week later developed a rash in the left flank that extended to the chest, back, and upper part of lower extremities. Laboratory results showed elevated liver enzymes. A treatment with steroids did not improve the rash and she was admitted to our institution. She was started with intravenous dexamethasone, topical hydrocortisone and triamcinolone. Seven days later the liver enzymes normalised, and the rash resolved on the chest and back. Our patient had concurrent acute generalised exanthematous pustulosis and hepatitis that together has been very rarely associated with terbinafine.

Background

Terbinafine is an antifungal medication whose mechanism of action involves the inhibition of squalene epoxidase, preventing the biosynthesis of sterols in fungi, leading to eventual cell death. Its common side effects include diarrhoea, dyspepsia, nausea, flatulence, pruritus, urticaria, visual disturbances and elevation of hepatic enzymes.

Acute generalised exanthematous pustulosis (AGEP) is an extremely rare type IV hypersensitivity reaction, typically occurring in only 1–5 patients in a million. In AGEP, keratinocytes are destroyed creating a vesicle and due to immunomodulators, manifests into a pustule which rarely involves the mucosa.^{1 2}

We present a case of terbinafine-induced AGEP and hepatitis.

Case presentation

The patient, a 55-year-old woman with a medical history of osteopenia treated with alendronate, presented with an intensely pruritic rash 2-week in duration. Initially, the patient had visited her primary care physician with onychomycosis where she was treated with terbinafine and ciclopirox lacquer. One week after the initiation of treatment, the patient began to develop a rash, which began on her left flank and extendedto the chest, back and upper part of lower extremities. She was diagnosed with a drug reaction and was treated with both topical and oral steroids; however, the rash continued to worsen and she was admitted to our institution.

On physical examination, her cardiopulmonary examination was normal, and her abdomen was benign. The skin examination showed innumerable red, round to annular plaques, many coalescing with three distinct areas of colours (a classic targetoid lesion) and a few scattered pustules (figure 1).

Figure 1.

Abdomen and lower chest during admission. Innumerable red, round to annular plaques, many coalescing with three distinct areas of colours and few pustules.

Investigations

The laboratory studies revealed alanine transaminase 770 unit/L, aspartate transaminase 564 unit/L, alkaline phosphatase 169 unit/L, white cell count 15.7×10³ with normal eosinophils.

A skin biopsy was performed showing subcorneal pustule, spongiosis, papillary dermal oedema, necrotic keratinocytes, red blood cell extravasation, interstitial and perivascular inflammatory infiltrates supporting the clinical diagnosis of AGEP.²

Treatment

We further postulated terbinafine was responsible for both the induction of AGEP as well as hepatitis given the patient’s clinical presentation, elevated liver enzymes, and pharmaceutical profile. The patient started treatment with intravenous methylprednisolone, topical triamcinolone and hydrocortisone.

Outcome and follow-up

Seven days after starting the treatment the liver enzymes normalised and the rash had resolved on her chest and back. The patient was advised to limit sun exposure and to continue treatment with a titrating dose of oral steroids. The patient continued to follow-up with her primary care physician as outpatient.

Discussion

AGEP is an uncommon condition caused by drugs in more than 90% of cases.³ Non-drug causes of AGEP can be viral infections, exposure to mercury, or ingestion of food allergens. AGEP is a rare side effect of terbinafine and has a clear correlation with the treatment of our patient.^4–8 A previously reported case showed a skin rash on sun-exposed areas on the fifth day of treatment with terbinafine and was diagnosed as photosensitisation induced by the treatment.⁹ Terbinafine has also been related with drug induced hepatitis.^{10 11} A concurrent diagnosis of AGEP and hepatitis is reported in our patient secondary to terbinafine. After a perusal review of the literature, we have only found one previous case of concurrent AGEP with minimally elevated liver enzymes secondary to labetalol.³ Steroid treatment improved both side effects. Terbinafine is a commonly use antifungal medication and physicians need to be aware of AGEP in the differential diagnosis, although it is a rare side effect.

Learning points.

• Recognise the presence of acute generalised exanthematous pustulosis (AGEP) and hepatitis, two rare side effects of terbinafine, in the same patient.

• Encourage physicians to keep AGEP in the differential diagnosis of terbinafine use side effects.