[The network of methotrexate toxicity].
BACKGROUND
Methotrexate is a folic acid antagonist recognised as one of the most important DMARD's in the rheumatoid arthritis treatment. Although the indisputable efficacy and the good tolerance profile, the broad toxicity spectrum is very variable with respect both to symptoms and intensity. The side effects vary from malaise and asthenia to pneumonitis or pancytopenia, which can be fatal.


OBJECTIVE
To review the adverse effects of methotrexate in the treatment of rheumatoid arthritis.


METHODS
Literature review, using Medline as a starting point, searching with the keywords "methotrexate", "toxic effects", "adverse effects", "rheumatoid arthritis". The relevant papers and selected references found therein were used.


RESULTS
The gastrointestinal symptoms are the most frequent, but myelossupression and pneumonitis are the most feared ones. Elevation of transaminases could indicate hepatic toxicity, placing the risk of cirrhosis. Cutaneous lesions, neurologic symptoms, changes in the bone metabolism, teratogenecity and hyperhomocysteinemia are other examples of the adverse effects of methotrexate. The post-dosing reactions are still not well known. The folate supplementation is important in the prevention of folate metabolism dependent symptoms. The farmacogenomics may help to identify patients in greater risk for multiple side effects.


CONCLUSIONS
Knowing and monitoring the methotrexate side effects is extremely important and should be carefully considered in order to prevent both therapeutic withdrawals due to toxicity as well as fatal outcomes.
Neves
Clarinda
C
Interna Complementar de Medicina Interna, Unidade de Reumatologia e Serviço de Medicina 2, Hospital Infante D. Pedro EPE - Aveiro. ccn@netcabo.pt
Jorge
Rosa
R
Barcelos
Anabela
A
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001847:Bone Diseases / Q000139:chemically induced; D002493:Central Nervous System Diseases / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005492:Folic Acid / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced; D008727:Methotrexate / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D012871:Skin Diseases / Q000139:chemically induced
D018501:Antirheumatic Agents; D005492:Folic Acid; D008727:Methotrexate