Risperidone‐induced erythema multiforme minor

Abstract

Erythema multiforme (EM) is an acute, self-limiting, reactive mucocutaneous disease of the skin and mucous membranes described by Hebra in 1866 [1]. EM, as an adverse effect of antipsychotic medication, has been noted with chlorpromazine and other traditional antipsychotics. There are reports of Stevens–Johnson syndrome (SJS), also known as ‘erythema multiforme major’, with carbamazepine–neuroleptic combination [2]. However, cutaneous adverse drug eruptions are rarely noticed with atypical antipsychotics. Olanzapine has been associated with severe generalized pruritic skin eruptions as part of a hypersensitivity syndrome [3] and is also found to cause leukocytoclastic vasculitis manifesting as erythematous skin eruptions [4]. However, it has not thus far been found to be associated with EM. In fact, among atypical antipsychotics, there is only one case report of erythema multiforme associated with ziprasidone use in a 47-year-old female [5]. A thorough Pubmed search until 23 February 2006, using the names of individual atypical antipsychotics and ‘erythema multiforme’, did not reveal a single case of EM induced by any other atypical antipsychotic. We describe what we consider the first case of EM induced by risperidone. A.S., a 21-year-old male with no contributory past or family history, had had complex partial seizures for the past 6 years. He had been regularly coming for follow-up at the epilepsy clinic of the Central Institute of Psychiatry, Ranchi, and had remained seizure free for the last 3 years with oxcarbazepine 900 mg day−1. A computed tomographic scan of the brain (contrast study) and EEG had been performed twice in the past and shown no abnormality on either occasion. He was brought for psychiatric consultation in November 2005 with a 2-week history suggestive of an ICD-10 acute polymorphic psychotic disorder without symptoms of schizophrenia following failure in a university examination. Treatment was initiated with oral risperidone 2 mg day−1 which was increased to 4 mg day−1. He was brought by his uncle after 2 weeks with progressively increasing multiple rashes all over the body over the previous 9 days. There was no history suggestive of mucosal bleeding, fever, pulmonary symptoms or intake of any other medicine. On examination, there were multiple raised oedematous papules which were symmetric and acrally distributed. There was no involvement of the mucous membranes. We referred the patient to a dermatologist and stopped risperidone. When he came for follow-up after a month, all lesions had disappeared and he became completely asymptomatic. He received a clinical diagnosis of drug-induced EM minor from the dermatologist and was treated with oral prednisolone for 2 weeks, which was started 2 days after his visit to us. He did not discontinue or reduce the dose of oxcarbazepine at any time. According to the criteria given by Roujeau [6], the acrally distributed raised symmetric oedematous papules with sparing of mucosal membranes as seen in our patient are typical of erythema multiforme minor. The rapid onset upon introduction and reversibility of the skin rashes following discontinuation of risperidone suggests a causal link. Oxcarbazepine is unlikely to be the offending agent, as the drug was continued in the same dose as before. Moreover, a negative history of recurrent EM, recurrent herpes or recent clinical herpes (preceding EM within 3 weeks) reduces the likelihood of herpes infection as a possible aetiology. Similarly, the absence of symptoms suggestive of febrile pneumonia makes the possibility of mycoplasma infection being the causative event highly unlikely. The strength of association was examined using the Naranjo Adverse Drug Reaction Probability Scale [7], in which a score of + 5 was obtained suggesting a ‘probable’ link. Adverse cutaneous drug eruptions may vary from benign maculopapular rash to Lyell syndrome and depend mainly on the host response to the drug. Although the precise pathogenesis is still unknown, EM is considered to be the consequence of a cytotoxic immunological reaction against the keratinocytes expressing nonself antigens [8]. We propose that this was induced by risperidone alone or perhaps risperidone in combination with oxcarbazepine. The effect of antipsychotic medications on the immune system is currently being explored and preliminary results indicate that both typical and atypical antipsychotics (including risperidone) can alter the cytokine system in the body [9]. This is the first report to link risperidone with an adverse drug-induced skin eruption, i.e. EM. Considering the wide use of risperidone, it is important that clinicians should be aware of the possibility of EM occurring during its use.