Interferons (IFN) are cytokines with antiviral, immunomodulatory, and anti-proliferative effects and they are widely used in viral hepatitis and malignancies such as chronic myeloid leukemia, malignant melanoma, and renal cell carcinomaCitation1. Many side effects can be observed during interferon therapy (fatigue, flu-like syndromes, thrombocytopenia, leukopenia, and neuropsychiatric abnormalities). Depression, irritability, lethargy, cognitive dysfunction, peripheral neuropathy, and mania can be observed as a neuropsychiatric syndromeCitation2; whereas movement disorders and extrapyramidal system symptoms such as Parkinson’s, chorea, akathisia, and dystonia are rarely reportedCitation3–6. Rabbit syndrome (perioral tremor) is a form of parkinsonism, which was initially thought to be a form of tardive dyskinesia. Rabbit syndrome is characterized by involuntary, rapid, and rhythmic movements in the perioral muscles, similar to the chewing of a rabbit. It is mostly reported after use of antipsychotic drugs and it has not yet been reported during interferon useCitation7. In the current report, a case in whom Rabbit syndrome has developed secondary to peginterferon alfa-2a (pegIFN-2a) due to chronic hepatitis C, is presented.
A 63 year old male patient without a known disease was diagnosed with chronic hepatitis C (genotype 1) one year ago. The only possible Hepatitis C virus infection risk factors for the patient are a previous cholecystectomy operation with a blood transfusion history during the operation 20 years ago and a previous dental treatment 10 years ago. The laboratory examination revealed the following: aspartate aminotransferase: 32 U/L, alanine aminotransferase: 52 U/L, albumin: 4.5 gr/dl, total bilirubin: 0.99 mg/dl, INR: 0.9, and HCV RNA: 8,195,000 IU/ml. PegIFN-2a 180 μg (subcutaneous, once per week; Pegasys; Roche, Cork City, Ireland) 1 × 1/week + ribavirin 1200 mg/day was initiated. After the second dose of interferon, involuntary, rhythmic movements started in the perioral muscles. The hemogram and biochemical tests were normal. In the neurological examination, rhythmic tremors and nasal flaring were observed in the perioral muscles. EEG and cranial MR were normal. The perioral movement disorder developing in the patient was thought to be Rabbit syndrome, secondary to pegIFN-2a, and therapy was terminated. The patient’s complaints regressed two weeks after stopping the drug, and the patient has been followed up without any problems for six months.
The mechanism that is responsible for extrapyramidal system symptoms developing secondary to IFN therapy is not precisely known. It has been demonstrated that neuronal dopaminergic activity is inhibited and cerebral dopamine levels are decreased in mouse brain tissue in which IFN-alfa is administeredCitation8. The pathophysiology of Rabbit syndrome has not been correlated with a specific basal ganglion; however, its induction with dopamine D2 receptor antagonists and its response to anticholinergics suggest a neuromodulatory imbalance at the level of the striatumCitation7. The current case is the first case of Rabbit syndrome developing secondary to pegIFN use. Rabbit syndrome substantially regresses after discontinuation of the drug. In some cases, anticholinergic drugs might be requiredCitation9. In the present case, complete recovery was achieved after discontinuation of the drug. It should be kept in mind that such neurological adverse effects could develop during peginterferon use.
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Declaration of funding
This letter wasn’t funded.
Declaration of financial/other relationships
O.M.S., A.P., A.C.O., B.B., and T.S. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
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