INFO - A Review of Methotrexate-Induced Accelerated Nodulosis

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A Review of Methotrexate-Induced Accelerated Nodulosis

from Pharmacotherapy

Posted 10/22/2002

Edna Patatanian, Pharm.D., and Dennis F. , Pharm.D., FASHP, FCCP

Abstract

Objective: To review the English-language literature on methotrexate-induced

accelerated nodulosis, compile case reports of its occurrences, and make

recommendations on the clinical management of patients.

Methods: A comprehensive search of MEDLINE, TOXLINE, and EMBASE databases

was performed, along with a bibliographic search of key articles. Case

reports were compiled separately. The Naranjo adverse drug reaction

probability scale was used to assess causality.

Results: Twenty-seven case reports of patients with methotrexate-induced

accelerated nodulosis were identified along with one series of 10 patients

and one series of 21 patients. Probability assessment for most of the case

reports was weak and left room for doubt regarding causality. Most patients

were older than 50 years, were positive for rheumatoid factor, and had

nodules on their fingers but did not have concurrent vasculitis. Some

unusual sites of nodulosis were the larynx, lungs, Achilles tendon, and

heart. Of 19 patients given hydroxychloroquine, colchicine, sulfasalazine,

azathioprine, or D-penicillamine, all except two showed regression of the

nodules; the response was unknown for one patient.

Conclusion: Controversy surrounds the management of patients who develop

accelerated nodulosis while receiving methotrexate therapy for rheumatoid

arthritis. Our review of these data does not allow definitive conclusions

because the available case reports and clinical trials are fragmented and

incomplete.

Introduction

Methotrexate is a folic acid antagonist, which in low doses has been an

important therapeutic modality in the treatment of rheumatoid arthritis.

However, a variety of adverse effects associated with methotrexate can limit

its usefulness. Gastrointestinal, hematologic, bone, lung, central nervous

system, and bone marrow effects have occurred with the drug.[1] An unusual

adverse effect associated with low-dose methotrexate in patients with

rheumatoid arthritis is the development of accelerated rheumatoid nodules.

Methotrexate-induced accelerated nodulosis usually occurs as small nodules

on the fingers, elbows, or other joints; these nodules are clinically

indistinguishable from rheumatoid nodules except for their rapid

(accelerated) onset.[2, 3] Of interest, methotrexate-induced accelerated

nodulosis can develop in patients who are negative for rheumatoid factor and

is said to arise during remission of rheumatoid symptoms. Although no

definitive evidence supports this theory, some authors have suggested that

patients with methotrexate-induced accelerated nodulosis also have a higher

frequency of concurrent vasculitis.[4-7]

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The entire article is here:

http://www.medscape.com/viewarticle/441926_1

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