title: Accelerated nodulosis and systemic manifestations during methotrexate therapy for rheumatoid arthritis.
abstract: OBJECTIVE
  Methotrexate is successfully used in the treatment of arthritis but little is known about its effects on extra-articular manifestations of rheumatoid arthritis. We focused this work on the incidence and clinical course of extra-articular manifestations during long-term treatment with methotrexate.
  
  
  METHODS
  The effect of methotrexate on extra-articular manifestations was investigated in 176 patients with rheumatoid arthritis who had obtained, in a prospective study, a good clinical response to methotrexate (10 mg/week) taken for 33 months (range 4-68).
  
  
  RESULTS
  Before taking methotrexate, 44 patients (25.1%) had extra-articular manifestations: nodules (n = 40) and vasculitis (n = 9). With methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and worsened in 10 (23%). Among the 132 patients without extra-articular manifestations before methotrexate therapy, 15 (11%) developed accelerated nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a pericarditis during methotrexate therapy. Extra-articular manifestations occurred between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was positive in 88% of the patients with extra-articular manifestations. No relationship was noted between extra-articular manifestations and HLA type or antinuclear antibodies. In 3 out of 4 patients who developed accelerated nodulosis while taking methotrexate, the addition of hydroxychloroquine (400 mg/day) resulted in a significant reduction in the number and size of the nodules within 3 to 10 months after starting combined therapy.
  
  
  CONCLUSIONS
  These data suggest that methotrexate is not effective in the treatment of extra-articular manifestations in rheumatoid arthritis and that nodulosis may occur in about 11% of patients taking methotrexate therapy for rheumatoid arthritis. The combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis that needs to be evaluated.
authors.affiliation: Service de Rhumatologie, Hôpital Caremeau, Nîmes, France.
authors.forename: B
authors.initials: B
authors.lastname: Combe
authors.forename: C
authors.initials: C
authors.lastname: Didry
authors.forename: M
authors.initials: M
authors.lastname: Gutierrez
authors.forename: J M
authors.initials: JM
authors.lastname: Anaya
authors.forename: J
authors.initials: J
authors.lastname: Sany
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D012215:Rheumatic Nodule / Q000473:pathology*; D014657:Vasculitis / Q000473:pathology*
chemical_list: D006886:Hydroxychloroquine; D008727:Methotrexate