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Methotrexate (MTX), which has been used for years in cancer treatment, is now being proposed as a first-line treatment for rheumatoid arthritis (RA), despite its potential side effects. The aim of this study was to investigate the short-term efficacy, safety and relative cost of low-dose MTX for the treatment of RA. We carried out an open, nonrandomized trial in which patients received a 7 mg injection of MTX once per week, with clinical and biological follow up. A single physician performed the weekly assessments, which involved evaluation of the duration of morning stiffness, the number of night awakenings, the number of painful and swollen joints and Ritchie's index. Blood cell count and erythrocyte sedimentation rate were determined monthly. Twelve RA patients were enrolled in the trial, over a mean treatment period of 356 +/- 175 days. A significant improvement was observed in all variables except the number of swollen joints. Ritchie's index decreased from a mean of 31.8 +/- 11.85 to 6.5 +/- 8.98 (p<1.6 x 10- 4). Minor adverse reactions were observed but none indicated treatment withdrawal: 6 cases of nausea, 2 of a moderate increase in transaminase activity, 1 of bronchitis, in which the responsibility of MTX was not definitely established and 3 cases in which hemoglobin levels decreased. The monthly cost of the treatment, including the drug itself and laboratory tests, is lower than that of gold salt injection. Three issues of key importance in our region were investigated in this study: 1) the possible desire to become pregnant of female patients undergoing MTX treatment. In addition, some of the young and unmarried patients did not understand or appreciate the contraceptive effects of the treatment; 2) poor compliance with the treatment due to limited financial resources. Many patients did not regularly attend for their follow-up appointments and many stopped taking the medication. One third of the patients were lost to follow-up during this study; 3) the prevalence of chronic hepatitis, which may limit the use of MTX in our region. Serological tests should be performed before the treatment is started and a liver biopsy is recommended for patients with chronic hepatitis B or C.

Adult↗

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[Methotrexate, liver and rheumatoid arthritis in tropical areas].

Rheumatoid arthritis (RA) is a common disease in tropical areas. Methotrexate which has become the main first-line treatment in western countries is increasingly used in tropics. Well documented liver toxicity of methotrexate led the American College of Rheumatology to provide guidelines about monitoring patients. In endemic areas of hepatitis B and C methotrexate may interfere with the natural history of these infections and exarcerbate liver damage, on the other hand, RA causes extra-articular manifestations which are rare and exceptionnally serious in the liver. The most important hepatic disorders associated with RA are: intrahepatic portal hypertension without cirrhosis, amyloidosis, drug hepato-toxicity and viral interferences. - Intrahepatic portal hypertension Several cases of portal hypertension without cirrhosis have been reported. Most cases were related to Nodural Regenerative Hyperplasia (NRH) which is made of diffuse nodules of hepatocytes without fibrosis. The pathogenesis of this entity is unknown. Distal vascular changes and abnormal perfusion of liver are mentioned. Presentation is cholestasis in one third of cases. Portal hypertension has no particularity and may cause esophageal variceal bleeding. NRH is closely associateed with Felty's syndrome. - Amyloidosis Hepatic amyloidosis is a classical complication of RA even rare. It is a secondary amyloidosis of AA type. Hepatic injury is generally silent and renal symptoms are dominant. - Drug hepatotoxicity Several medications used in the management of RA are potentially hepatotoxic : salicylates, nonsteroidal antiinflammatory drugs (NSAID), corticosteroids, gold, sulfasalazine and methotrexate above all. Methotrexate hepatotoxicity is well documented in carcinology with high doses but also in psoriasis patients treated with low doses. Hepatic damage related to methotrexate includes elevation of aminotransferases, portal fibrosis and cirrhosis. But data on methotrexate toxicity show small risk of serious liver disease in RA patients. Long duration of therapy and age (> 60 years) have been found to be independent risk factors for the development of hepatic disease. Other identified risk factors are alcohol intake, diabetes, obesity and prior history of hepatitis B or C. The American College of Rheumatology has published guidelines about monitoring patients for liver toxicity. Hepatic tests and Hepatitis B and C serologic studies are recommended before starting treatment with methotrexate. Liver biopsy is only recommended in case of alcoholism, prolonged abnormalities of aminotransferases and chronic hepatitis B or C infection. - Methotrexate and hepatitis B or C infection These infections are endemic in tropical areas. Chronic hepatitis B or C is a contra indication for methotrexate therapy, due to the immuno-suppressive effect of the drug. Positive ELISA tests to C virus must be confirmed with RIBA tests to avoïd false positive tests which have been reported in Africa. The "healthy" HBs Ag carrier state is not in theory a contra indication for methotrexate therapy but the risk of hepatitis B reactivation needs a close monitoring. The biological tests required for are sophisticated and quite impossible in routine practice in tropical areas. So HBs Ag carrier state is usually incompatible with methotrexate treatment. Studies would be useful to prove that in endemic areas of viral hepatitis B and C as in western countries, methotrexate is enough safe to become the main first-line treatment of rheumatoid arthritis.

Amyloidosis↗