title: Methotrexate-induced papular eruption in patients with rheumatic diseases: a distinctive adverse cutaneous reaction produced by methotrexate in patients with collagen vascular diseases.
abstract: BACKGROUND
  In the past few years, low doses of methotrexate have been used for treatment of patients with rheumatoid arthritis and other collagen vascular diseases, mainly as an immunosuppressive and corticosteroid-sparing drug. Several cutaneous adverse reactions have been described in association with methotrexate therapy.
  
  
  OBJECTIVE
  We describe the clinical and the histopathologic features of distinctive cutaneous lesions that appeared in 4 patients with acute bouts of collagen vascular diseases who were receiving methotrexate therapy.
  
  
  METHODS
  We clinically and histopathologically evaluated cutaneous lesions caused by methotrexate therapy in 4 patients, 2 with systemic lupus erythematosus, 1 with rheumatoid arthritis, and 1 with Sharp syndrome.
  
  
  RESULTS
  Clinically, lesions consisted of erythematous indurated papules most commonly located on proximal areas of the extremities. Histopathologic examination of these papules showed an inflammatory infiltrate mainly composed of histiocytes interstitially arranged between collagen bundles of the dermis, intermingled with few neutrophils. In some foci of deeper reticular dermis, small rosettes composed of clusters of histiocytes surrounding a thick central collagen bundle were seen. Cutaneous lesions showed a direct chronologic relationship with methotrexate therapy, and they disappeared when the drug was tapered or withdrawn and corticosteroids were increased.
  
  
  CONCLUSIONS
  Patients receiving low doses of methotrexate for acute bouts of collagen vascular diseases may experience characteristic cutaneous lesions with distinctive clinical and histopathologic findings shortly after methotrexate administration. We discuss the differential diagnosis with other dermatoses showing similar histopathologic findings that have been described in patients with collagen vascular diseases.
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003094:Collagen; D020405:Dermis / Q000473:pathology; D003937:Diagnosis, Differential; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006644:Histiocytes / Q000473:pathology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000188:drug therapy*; D009504:Neutrophils / Q000473:pathology; D012867:Skin / Q000473:pathology; D017444:Skin Diseases, Papulosquamous / Q000139:chemically induced* / Q000473:pathology; D013256:Steroids