The patient did not smoke and was only a social drinker. She did not use any .... Stephanos Hadziyannis MD, Hepatology Department, Henry. Dunant Hospital ...
Hashimoto Encephalopathy with Pegylated Interferon Alfa-2b and Ribavirin Melanie Deutsch, John Koskinas, Konstatinos Tzannos, Dimitrios Vassilopoulos, Antonis Mailis, George Tolis, and Stephanos Hadziyannis
OBJECTIVE: To report an instance of Hashimoto encephalopathy probably resulting from pegylated interferon alfa-2b and ribavirin. CASE SUMMARY:
A 36-year-old woman with a 10-year history of autoimmune thyroiditis presented with symptoms and signs consistent with Hashimoto encephalopathy during therapy with pegylated interferon alfa-2b and ribavirin for chronic hepatitis C.
DISCUSSION: Hashimoto encephalopathy is a rare autoimmune condition that occurs in patients with Hashimoto thyroiditis and high titers of antithyroid antibodies. It is characterized by a variety of nonspecific neuropsychiatric symptoms, increased cerebrospinal fluid protein level, and abnormal brain imaging and electroencephalogram. Prompt response to corticosteroids is observed in most cases. As of August 29, 2005, this is the first report of such an association. An objective causality assessment revealed that the Hashimoto encephalopathy was probably caused by the patient’s medications. CONCLUSIONS: Hashimoto encephalopathy may rarely be triggered by interferon alfa therapy in susceptible patients. KEY WORDS: chronic hepatitis C, Hashimoto encephalopathy, pegylated interferon alfa-2b.
Ann Pharmacother 2005;39:1745-8. Published Online, 13 Sept 2005, www.theannals.com, DOI 10.1345/aph.1G144
ashimoto encephalopathy is a rare autoimmune synH drome first described in 1966 that occurs in patients with Hashimoto thyroiditis and high levels of serum antithy-
Case Report
1
roid antibodies.2 The clinical spectrum of the disease includes a variety of neurologic and psychiatric manifestations unrelated to the well-known symptoms of thyroid hypo- or hyperfunction and usually associated with normal thyrotropin and unbound thyroxine levels. Two clinical syndromes of Hashimoto encephalopathy are recognized: vasculitic, with stroke-like episodes, epileptic seizures, and mild cognitive impairment; and diffuse progressive type, with severe cognitive defects, psychotic episodes, and altered consciousness.3 The pathogenetic mechanisms are not clear, but probably involve immune-mediated cerebral vasculitis.4 At the same time, chronic infection with hepatitis C virus (HCV) has been associated with a number of extrahepatic autoimmune manifestations,5 including autoimmune thyroid disease. It is established that treatment with interferon alfa in patients with chronic hepatitis C may trigger clinical overt autoimmune thyroid disease in susceptible patients.6 We report the case of a woman with a 10-year history of autoimmune thyroiditis who developed symptoms and signs of encephalopathy during therapy with pegylated interferon alfa-2b and ribavirin for chronic hepatitis C infection. Author information provided at the end of the text.
www.theannals.com
A 36-year-old woman presented with progressively worsening neuropsychiatric symptoms. She had a 10-year history of Hashimoto thyroiditis and was euthyroid while taking thyroid hormone (L-thyroxine 50 µg/day) replacement therapy. Three years prior to admission, chronic HCV infection was diagnosed on the basis of detectable anti-HCV antibodies and elevated serum alanine aminotransferase levels. She had positive serum HCV-RNA and genotype 1b. A liver biopsy showed features consistent with chronic hepatitis C that was scored grade 10 for necro-inflammatory changes and stage 2 for fibrosis (according to Ishak et al.’s7 scoring system, where the maximum score for grade is 18 and for stage is 6). She started treatment with subcutaneous pegylated interferon alfa-2b 100 µg/wk and oral ribavirin 800 mg/day, with a good biochemical response (sustained normal aminotransferases during treatment). At month 6 of therapy, she manifested diabetes mellitus with low serum insulin and C-peptide levels; she began insulin therapy, which normalized her blood glucose level. Two weeks before admission, she progressively became disoriented and lethargic. Pegylated interferon and ribavirin were discontinued on presentation, and she was transferred to our department. The patient did not smoke and was only a social drinker. She did not use any illicit drugs. At admission, she appeared confused, agitated, and had visual hallucinations and a panic attack (she screamed, believing that someone wanted to harm her). T was 36.6 ˚C, HR 86 beats/min, BP 130/70 mm Hg, and RR 18 breaths/min. She had no signs of hepatic failure or flapping tremor. Motor and sensory examination was negative, and signs of meningism were absent. Fundoscopy was normal. The day after admission she experienced a generalized tonic–clonic seizure and was promptly treated with intravenous administration of diazepam and phenytoin. Laboratory testing on admission showed hematocrit 36.5%, hemoglobin 12.5 g/dL, white blood cell count 6.9 × 103/mm3 (69% neutrophils, 21% lymphocytes, 10% monocytes), and platelet count 240 × 103/mm3. Erythrocyte sedimentation rate was 30 mm/h and C-reactive protein was 1.6 mg/dL. Blood glucose was 164 mg/dL, urea 14 mg/dL, serum creatinine 1.3 mg/dL, uric acid 1.9 mg/dL, sodium 133 mEq/L, and potassium
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4.9 mEq/L. Total bilirubin was 0.5 mg/dL, (direct 0.1 mg/dL), alanine aminotransferase 49 U/L (normal
