Rheumatoid arthritis probably induced pegylated interferon in patient with hep-c

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Rheumatoid arthritis probably induced by pegylated interferon in a patient with chronic hepatitis C.

http://www.indianjgastro.com/article.asp?issn=0254-8860;year=2004;volume=23;issue=1;spage=28;epage=29;aulast=Sood

We report a 47-year-old woman who developed features of rheumatoid arthritis 20 weeks after initiation of treatment with pegylated interferon and ribavirin for chronic hepatitis C. She continued to have symptoms six months after discontinuation of the drugs which she received for 24 weeks with rival clearance.

Interferons are cytokines produced by lymphocytes and macrophages, which have antiviral, anti-tumoral and immunomodulatory properties. Recombinant interferon alpha is used in the treatment of various malignancies and chronic hepatitis B and C. Pegylated interferon has been reported to have greater therapeutic value.However, the use of interferon is associated with a number of adverse effects, ranging from influenza-like syndrome to depression, hematological abnormalities and autoimmunity.[1]A 47-year-old housewife presented with mild upper abdominal discomfort, generalized weakness and fatigue. She had no significant past history. She denied alcohol or drug abuse. She was average built, with BMI 25.5 Kg/m2, and had no abnormal general physical signs. Abdominal examination revealed the liver palpable 3 cm below the right costal margin. Rest of the systemic examination was normal. Investigations: persistently elevated AST (117-200 U/L; normal 0-40) and ALT (123-250 U/L; normal 0-35). Hematological parameters, renal function tests, blood sugar, lipid profile, serum bilirubin, alkaline phosphatase and albumin were normal. She tested positive for markers of hepatitis C virus (anti-HCV positive, HCV RNA positive, genotype 3a); and HBsAg and anti-HIV were negative. Abdominal ultrasonogram and upper gastrointestinal endoscopy were normal. Liver biopsy revealed changes consistent with chronic hepatitis (histological activity index 8, stage 3).There was no contraindication to use of antiviral drugs, and she was started on pegylated interferon (Viraferon; Fulford India, Mumbai) 80 mg subcutaneously weekly and oral ribavirin (Rabetol; Fulford India, Mumbai) 800 mg daily. She tolerated the treatment well except for mild fever, lethargy and myalgia. HCV RNA was undetectable at 12 weeks and transaminases returned to normal. However, after 20 weeks of therapy, she started experiencing pain and swelling over the metacarpo-phalangeal, wrist, metatarso-phalangeal, shoulder and ankle joints. She also had morning stiffness, lasting 2-3 hours. There was no past or family history of autoimmune disease or arthritis.Examination revealed bilateral symmetrical arthritis in these joints. Leukocyte and platelet counts and transaminases were normal. ESR was raised, rheumatoid factor was positive and antinuclear factor was negative. X-ray of the wrist and ankle were normal. She was treated with non-steroidal anti-inflammatory drugs and was able to complete 24 weeks of antiviral treatment with biochemical remission and viral clearance. However, joint pain has persisted even after stopping antiviral drugs and she needs regular dose of anti-inflammatory drugs and has limitation of movements because of pain six months later. Autoimmune disorders like hyperthyroidism, hypothyroidism, thrombocytopenic purpura, hemolytic anemia, systemic lupus erythematosus, and rheumatoid arthritis have been reported to develop with interferon therapy. Although arthralgias and myalgias are commonly reported by patients receiving interferon as part of flu-like symptoms, frank rheumatoid arthritis has not been frequently reported.[2] Our patient fulfilled five of the American Rheumatism Association criteria for rheumatoid arthritis, i.e., morning stiffness, arthritis of hand joints, several articular stations simultaneously affected, symmetric arthritis and positive rheumatoid factor.Two hypotheses to explain the occurrence of immunological disorders with interferon include de novo induction by direct toxicity or a possible exacerbation of a silent pre-existing disorder.[3],[4] These effects are attributed to the immunomodulatory effects of interferon. Hepatitis C per se also has a pathogenetic association with autoimmunity. Apart from its well-known association with essential mixed cryoglobulinemia (EMC), association with rheumatoid arthritis, Sjögren's syndrome and inflammatory myositis has also been reported.[5]As arthritis started after viral clearance in our patient, HCV was unlikely to be the cause. However, as clinical manifestations and rheumatoid factor positivity manifested after institution of therapy we believe it to be related to the drugs. We are unaware of ribavirin being associated with arthritis.

» References

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1.

Renault PF, Hoofnagle JH. Side effects of alfa interferon. Semin Liver Dis 1989;9:273-7. [PUBMED

2.

Chazerain P, Meyer O, Kahn M. Rheumatoid arthritis-like disease after alpha-interferon therapy. Ann Med 1992;116:427.

3.

Dumoulin FL, Leifeld L, Sauerbruch T, Spengler U. Autoimmunity induced by interferon alfa therapy for chronic viral hepatitis. Biomed Pharmacother 1999;53:242-54. [PUBMED

4.

Pittau E, Bogliolo A, Tinti A, Mela O, Ibba G, Salis G, et al. Development of arthritis and hypothyroidism during alfa interferon therapy for chronic hepatitis C. Clin Exptl Rheumatol 1993;15:415-9.

5.

Gordon SC. Extrahepatic manifestations of hepatitis C. Dig Dis 1996;14:157-8. It's Tax Time! Get tips, forms and advice on AOL Money Finance.