A case report of photodermatoses induced by the antifungal drug terbinafine

Abstract

Terbinafine is an antifungaldrug(inhibitor of ergosterol synthesis) known to induce skin reactions. A 58-year-old female was treated with terbinafine for onychomycosis. On the fifth day of treatment a skin rash emerged on her sun-exposed areas. Biological testing did not find any allergic signs. Other skin reactions are well known with terbinafine, but we depict here, a case of photosensitisation induced by treatment, generally unknown for this antifungal. This side effect can be prevented by medication reconciliation and pharmaceutical advice from the clinical pharmacist.

Background

Terbinafine is indicated for the treatment of fungal superficial infections of the skin and nails caused by Trichophyton, Microsporum and Epidermophyton, three genera of dermatophytes.

Terbinafine side effects are numerous, including hepatotoxicity, smell and taste disturbances, haematological effects and skin reactions. The worst cutaneous reactions are Stevens–Johnson syndrome and toxic epidermal necrolysis occurring in less than 1 per 10 000 treated patients. The most frequent cutaneous reactions are rash and urticary (estimated >1 per 10 treated patients) and the need to stop the therapy to avoid evolution towards a serious form.

Among antifungal therapy, voriconazole is also well known for the same cutaneous side effects as terbinafine, but also for cutaneous reaction after sun exposure.¹

The list of photosensitising medications is long. The most well known are anti-inflammatory drugs, such as ketoprofen, and antibiotics such as fluoroquinolones.^{2 3} Terbinafine is rarely mentioned as being photosensitising: this clinical case yields an example and highlights the importance of pharmaceutical advice about this side effect, especially in the summer season.

Case presentation

A 58-year-old female was prescribed oral terbinafine for onychomycosis of the toe. The dose used was 250 mg/day. This therapy started in July during the patient’s holiday. On the fifth day of treatment while she was outside in a swimming pool, an itching skin rash emerged on her sun-exposed areas: hand, arms, legs, back and cleavage (figure 1) and gradually aggravated. Suspecting a photoallergic reaction, the patient stopped taking her treatment and the eruptions gradually regressed.

Figure 1.

Different areas exposed to the sun.

Rashes were accompanied by a febrile syndrome: headache, slightly elevated body temperature (39.2°C) and malaise.

Investigations

Four days after the first symptoms, while the patient was still symptomatic, laboratory testing revealed complete blood count, complement levels, thyroid stimulating hormone and IgE levels (6 UI/ml) within normal limits apart from a slight eosinophilia (0.53×10⁹ L^-1, reference value <0.50×10⁹ L^-1, anteriority 0.37×10⁹ L^-1 6 months before).

No history of photosensitivity was mentioned by the patient. The patient did not take any other medications at that time and had no history of any drug or food allergies.

Treatment

In view of the probability of drug-induced photosensitivity, terbinafine treatment was stopped. Local treatment with corticosteroid was prescribed to the patient as well as an eviction sun or sun block cream.

Outcome and follow-up

The rashes completely disappeared after 2 weeks of dermal care with hydrating cream and sun protection. A biological test was done the following month. All parameters were normal.

Discussion

Faced with a rash that appeared after sun exposure, exogenous photosensitisation is most likely, especially when clinical signs appear suddenly after the introduction of a new drug, terbinafine, and where no history of solar allergy was mentioned. There are two types of photosensitisation: phototoxicity and photoallergy.⁴ Regarding our clinical case, phototoxicity is more probable since biological assessment revealed no immunological hypersensitivity reaction.

The rash completely disappeared 2 weeks after treatment interruption, with hydrating skin care and without sun exposure. This duration could be explained by a long half-life redistribution of terbinafine by sebum that is estimated at 14.5±8.5 days.⁵ In case of occurrence, this side effect requires long sun protection counselling. Moreover this oral treatment is often prescribed with the same molecule under topical formulations (cream and spray): the photosensitisation is likely to happen also with this form, as terbinafine is directly put on skin (and on sebum).

Cutaneous side effects (from urticary to toxic epidermal necrolysis) are well known with terbinafine, but these side effects are independent from sun exposure. In France, in the summary of product characteristics of terbinafine, photosensitivity reactions, photodermatosis, allergic photosensitivity reaction and polymorphic solar flare are of ‘unknown frequency’ (ie, cannot be estimated from the available data).⁶ For the Food and Drug Administration, this side effect is only a postmarketing experience not detected before commercialisation.⁷ Only two cases reported skin reaction with terbinafine after sun exposure.^{8 9} The learning point of the case report is the usefulness to report such a case of photosensitivity in order to more accurately estimate its frequency and to promote warning and prevention, especially in the case of initiation of treatment during summer periods.

In conclusion, it may be appropriate to propose or harmonise a pictogram ‘careful in the sun’ on all photosensitising drugs boxes. This pictogram would be recognisable by patients and health professionals in all countries.

Patient’s perspective.

The patient is much better, she has totally proscribed terbinafine and has not had a rash in the sun.