Drug eruption and liver injury caused by terfenadine and oxatomide

ARTICLE

Drug eruption and drug-induced liver injury caused by antihistamines are uncommon [1-2]; the incidence of patients, who are intolerant to several drugs of this class, is very rare. We report a case of drug eruption and sustained liver injury caused by both terfenadine and oxatomide.

Case report

A 70-year-old woman was referred to our hospital on May 5, 1996. She had suffered from pruritic skin lesions, liver dysfunction, and diabetes mellitus for years. She was prescribed azelastine hydrochloride, betamethasone, d-chlorpheniramine maleate, hydroxyzine pamoate, mequitazine, oxatomide and/or terfenadine, one or two each at a time, for her skin lesions, along with trichlormethiazide, pindolol, domperidone, glyclopyramide, cilostazol, dicycloverine hydrochloride, aluminum hydroxide gel, magnesium oxide and teprenone for diabetes, hypertension and gastritis.

On admission her skin lesions consisted of psoriatic, scaly, erythematous plaques and diffuse monotonous erythema on the trunk and extremities sparing the face, palms and soles (Fig. 1). In the laboratory examination, liver dysfunction (aspartate aminotransferase (AST) 182 IU/l, alanin aminotransferase (ALT) 255 IU/l, alkaline phosphatase (ALP) 365 IU/l, lactate dehydrogenase (LDH) 705 IU/l, gamma-glutamyl transpeptidase (g-GTP) 330 IU/l, total bilirubin 8.0 mg/dl, direct bilirubin 6.5 mg/dl, NH₃78 mug/dl) was observed. Skin biopsy from the right thigh revealed psoriatic change (Fig. 2A); the left thigh biopsy disclosed acute eczematous lesion (Fig. 2B). Psoriasis, associated with drug eruption of an eczematous type and drug-induced liver injury, was suspected.

After all the prescribed drugs were discontinued, her skin lesions and liver function gradually improved in three months, although serum ammonium was sustained at a high level, and psoriatic lesions remained on the extensor aspects of elbow and knee joints. Lymphocyte stimulating test for each of the drugs resulted negative, and an oral drug challenge test was performed. Taking 60 mg of terfenadine, she developed pruritic diffuse erythema on the trunk and extremities within a day, although serum liver enzyme remained normal (AST 17, ALT 9, LDH 336, ALP 166). Receiving 30 mg of oxatomide, she developed slight erythema on the back and arms without itching, and mild liver dysfunction (AST 84, ALT 60).

Discussion

Although it is not very rare to encounter patients who developed an intolerance reaction to several drugs, the present case is the first patient for us, who has suffered from two antihistamines concurrently. Oxatomide (1-[3-[4-(difenylmethyl)-1-piperazinyl]propyl]-2-benzimidazol-2(3H)-one) and terfenadine ((±)-alpha-(p-tert-butylphenyl)-4-(hydroxydiphenylmethyl)-1-piperidinebutanol) share 'diphenylmethyl' structure; however, hydroxydine, which has not provoked an allergic reaction in oral challenge test in the present case, also possesses the structure. Moreover, not terfenadine but oxatomide alone was causative in the development of liver injury. Therefore, we now consider that in the treatment of psoriasis, the patient developed an intolerance reaction to the two drugs separately, and it is not cross-reactive.

This patient suffers from psoriasis and this cutaneous condition might have been aggravated by the two drugs, but clinically we distinguished the eczematous regions from the psoriatic ones to some extent and histopathological studies revealed the difference between these two kinds of skin regions. So we considered that psoriasis and drug eruption occurred separately in this case.

Patch testing is a suitable way to examine delayed hypersensitivity reaction: however, because of the low sensitivity of drug patch tests, and to confirm which medicine the patient could take to treat her psoriasis, we decided to perform an oral challenge test.

Along with our previous report of a Stevens-Johnson syndrome patient caused by terfenadine [3], we wish to emphasize the importance of taking full drug history and the necessity of careful challenge test of all the suspicious drugs, even if they seem unlikely to provoke an intolerance reaction.

Article accepted on 21/5/02

REFERENCES

1. Yagi H, Fukuhara F, Takigawa M. Drug eruption caused by terfenadine. Eur J Dermatol 1996; 6: 81-2.

2. Harrison PV, Stones RN. Severe exacerbation of psoriasis due to terfenadine. Clin Exp Dermatol 1988; 13: 275.

3. Sato N, Satake S, Fujiwara H, Yamada S. Stevens-Johnson syndrome caused by terfenadine. Eur J Dermatol 1996; 6: 464.