Hypogeusia as an adverse reaction of phenytoin

Abstract

Taste loss (hypogeusia) may have various causes such as acute viral illness, traumatic brain injury, liver disease, and allergic rhinitis. Taste disorders can also occur during pharmacological treatment [1] and have been reported in patients who were treated with antiepileptic drugs such as carbamazepine, felbamate and lamotrigine [2–4]. Hypogeusia induced by phenytoin – one of the most widespread antiepileptic drugs – was reported only in one patient so far [5]. Since in this patient, however, liver enzymes were 10–25-fold increased, it was questioned whether a liver disease or the drug itself caused the taste impairment [6]. In this patient the ageusia developed immediately after the first infusion of phenytoin and improved quickly after the discontinuation of the drug, whereas liver enzymes remained elevated for another 2 weeks. Here, we report a patient with severe hypogeusia which is most likely to be due to treatment with phenytoin. This 64-year-old patient suffered from a monoparesis of his left leg. A magnetic resonance imaging scan revealed a right frontoparietal lesion which was surgically removed. Histology revealed a meningotheliomatous meningeoma. His preoperative medication included acetylsalicylic acid, bisoprolol, hydrochlorothiazide, amlodipine, and pravastatin, and has been taken for more than 2 years. Although the patient never had epileptic seizures, a prophylactic antiepileptic therapy with phenytoin was started postoperatively. The concomitant medication has not been changed postoperatively. Immediately after starting phenytoin therapy with a daily dose of 100 mg, the patient complained about an impaired taste, especially for sweet qualities. Ten days later, he was on a daily dose of 300 mg. The serum level of phenytoin was 51 µmol l−1 (therapeutic range 20–80 µmol l−1). Liver enzymes (AST and ALT) were four- to five-fold increased. Electrolyte levels (potassium, sodium) were normal. Within the first 5 days after the dosage elevation, the patient observed that the taste impairment became more severe. This interfered with his appetite and caused a weight loss of 12 kg over 3 months. A qualitative semiquantitative evaluation of taste with saccharose, sodium chloride, citric acid, and quinine hydrochloride, which was performed 6 weeks after the start of phenytoin treatment, revealed a severe hypogeusia for all qualities of taste. A taste disturbance was not found. A smell test was normal. Tongue morphology and sensibility were normal. As the still seizure-free patient complained about a severe impairment of quality of life due to the taste loss, the phenytoin dose was lowered 2 months later. With a daily dose of 100 mg, however, the taste impairment improved only partially, whereas liver enzymes became normal. Another 2 months later, the phenytoin therapy was discontinued, whereas the concomitant medication remained unchanged. Four days after the intake of the last phenytoin pill, the taste sensation improved markedly. Two months later, the patient still reported a partial hypogeusia, particularly for sweet qualities. A control examination with the same qualitative semiquantitative test confirmed only partial amelioration compared with the first evaluation. Six months after discontinuation of phenytoin therapy, the patient reported to have retrieved normal taste. Because of the tight temporal and dose-dependent association between taste impairment and phenytoin intake, we interprete the temporary hypogeusia as drug-induced by phenytoin. No other possible aetiology, including liver disease, could be found. Because of the unchanged long-term concomitant medication and the lack of known relevant interactions with phenytoin, we believe phenytoin was the probable cause. As the taste loss was not pronounced immediately after the removal of the right frontoparietal lesion, but exacerbated only after elevation of the phenytoin dose, we assume that the surgical procedure itself is also unlikely to have been causative for the development of hypogeusia in this patient. In summary, our case supports an uncommon causal association between reduced taste and phenytoin treatment. It has previously been suggested that altered taste can be an adverse effect of phenytoin [5], but this has been controversial [6]. Phenytoin is still used extensively world-wide and we suggest that it should be considered as a possible cause of reduced taste.