Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors

Arch Dermatol. 2006 Feb;142(2):198-202. doi: 10.1001/archderm.142.2.198.


Background: Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Accordingly, TNF-alpha inhibitors, such as thalidomide, infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel), have been used with success in the treatment of autoimmune disorders, including psoriasis, rheumatoid arthritis, inflammatory bowel diseases, and lymphoproliferative disorders. Although anti-TNF-alpha therapy is safe and well tolerated, various adverse cutaneous reactions have been reported.

Observations: We encountered 5 patients who developed erythematous annular plaques on the trunk and extremities while receiving 4 different medications with inhibitory activity against TNF-alpha. One patient was treated with lenalidomide (Revlimid) for multiple myeloma, 2 received infliximab, and 1 received etanercept for severe rheumatoid arthritis; the last patient was in a clinical trial of adalimumab for psoriatic arthritis. Skin biopsy specimens revealed diffuse interstitial granulomatous infiltrates of lymphocytes, histiocytes, and eosinophils, palisading degenerated collagen. Withdrawal of the medications led to complete resolution of the skin lesions.

Conclusion: Interstitial granulomatous dermatitis should be considered in the differential diagnosis of skin lesions occurring in the setting of anti-TNF-alpha therapy.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Psoriatic / drug therapy
  • Arthritis, Rheumatoid / drug therapy
  • Biopsy
  • Diagnosis, Differential
  • Drug Eruptions / etiology*
  • Drug Eruptions / pathology
  • Etanercept
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Lenalidomide
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use
  • Skin / pathology
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • Infliximab
  • Lenalidomide
  • Adalimumab
  • Etanercept