Exacerbation of paranoid schizophrenia in a psoriatic patient after treatment with cyclosporine a, but not with etanercept

Journal of Drugs in Dermatology, Oct, 2007 by Sergio Di Nuzzo, Martina Zanni, Giuseppe De Panfilis

Abstract

Psoriasis may be frequently associated with psychiatric diseases. We present a 44-year-old man undergoing cyclosporine therapy for treatment of generalized plaque psoriasis which exacerbated his symptoms of paranoid schizophrenia, and disappeared a few days after discontinuation of cyclosporine. Replacement therapy with etanercept achieved clinical remission of psoriasis without any psychiatric side effects. Systemic medications, such as cyclosporine and etanercept, induce modifications of the cytokine network. This is pathogenetically significant in both psoriasis and psychiatric disorders. This case report suggests that dermatologists need to become more familiar with the risk-benefit of drug-induced cytokines dysregulation in psoriatic patients with comorbid psychiatric disorders.

Introduction

Psychiatric disorders among patients with established skin disease are common. Frequent psychiatric comorbidities reported in psoriasis include major depressive disorder, obsessionality, and anxiety. (1) There is little documentation of the comorbidity between schizophrenia and psoriasis. (2,3) Such a comorbidity is a source of concern because it might interfere with the psoriatic treatment chosen. We report a psoriatic patient whose schizophrenic symptoms were exacerbated during cyclosporine treatment. Replacement therapy with etanercept achieved clinical remission of psoriasis without any psychiatric side effects.

Case Report

A 44-year-old man presented with generalized plaque psoriasis involving 60% of his body surface area and concomitant schizophrenia. At the age of 23, because of auditory hallucinations, psychomotor excitement, and delusion of persecution, he was diagnosed paranoid schizophrenia, according to DMS-IV criteria. Since then, his psychiatric illness had been controlled with clozapine. He had a 13-year history of chronic plaque psoriasis, previously treated with a variety of topical agents and phototherapy. Over the last 3 years, the psoriasis had been difficult to control since his psychotic condition was associated with poor medication adherence. Therefore, we decided to start treatment with cyclosporine at the dose of 3 mg [Kg.sup.-1] per day. Within a few weeks, despite his skin condition improvement, cyclosporine was withdrawn due to exacerbation of the patient's psychomotor excitement and violent behavior, which interfered with his integration into the community. Symptoms of sickness behavior almost immediately disappeared after discontinuation of cyclosporine and this supports a causal role for the drug. Instead of cyclosporine, the patient was administered subcutaneously, about 50 days later, 25 mg of etanercept twice weekly for 12 weeks with almost complete clinical remission of psoriasis. No adverse psychiatric events were observed during the treatment.

Discussion

Psoriasis is thought to be an autoimmune disorder in which elevated levels of interleukin (IL)-2 and tumor necrosis factor (TNF)-[alpha] play a crucial pathophysiological role. Indeed, drugs that target IL-2 and TNF-[alpha], such as cyclosporine and etanercept, respectively, have been successfully employed in psoriasis. Recent advances in cytokine research have contributed to understanding the role for cytokines in the pathophysiology of specific psychiatric disorders. (4) Diminished mitogen-stimulated IL-2 production in schizophrenic patients has been reported to be associated with a younger age at onset and a preponderance of negative symptoms. (5) Although other mechanisms might be involved in the exacerbation of psychiatric symptoms, in our case cyclosporine therapy might have further diminished the levels of IL-2. This, however, never underwent any laboratory investigation. Evidence of elevated level of TNF-a in the serum of schizophrenic patients (6) and a reported clinical improvement of schizophrenia with TNF-[alpha] antagonist (7) motivated us to start treatment with the anti-TNF-[alpha] etanercept. The treatment was very active in clearing psoriasis plaques, but it didn't improve the subject's psychiatric condition. The patient's mental status, however, did not exacerbate, and remained stable for the entire duration of the therapy.

The literature includes reports of cytokine dysregulation in other psychiatric comorbidity disorders reported in psoriasis, such as major depression and obsessive-compulsive disorders. For instance, high levels of TNF-[alpha] have been found in depression (8); whereas, the plasmatic level of TNF-[alpha] was significantly lower in patients with obsessive-compulsive disorders than in controls. (9) Such cytokines pattern would suggest the use of TNF-[alpha] antagonist in the former comorbidity patients but not in the latter. Indeed, Tyring et al (10) have recently found that symptoms of depression significantly improved in psoriatic patients treated with etanercept. However, caution should be taken when treating patients with atypical major depression, since development of a manic episode has been reported in a patient with psoriatic arthritis treated with etanercept. (11)