Cutaneous Reaction Patterns Associated with Infliximab Therapy.
Category: 17 RA—treatment
Morris Kokhab, Karina D. Torralba, Samy K. Metyas, Manjunath Vadmal, Dorothy Johnson, Daniel G. Arkfeld, Francisco P. Quismorio, Jr.. Keck School of Medicine, University of Southern California, Los Angeles, CA
Presentation Number: 767
Poster Board Number: 162
Background and Objective: Cutaneous lesions associated with infliximab therapy have been reported in 6-18% of patients. We reviewed our experience with patients on the medication focusing on the clinical features, course, and histopathology of the skin lesions.
Methods and Results: Case records of patients on infliximab seen between January 1, 2001 and April 15, 2003 were assessed retrospectively for chronic cutaneous reactions and lupus-like features. Five of 55 (9%) patients developed persistent skin lesions. Nine other patients who had urticaria as a manifestation of a hypersensitivity reaction to the medication were not included in this study.
Four rheumatoid arthritis and one juvenile chronic arthritis patient (mean age 52.4 years; range 23-72 years) developed skin lesions after a mean of 4.2 infusions (range 3-6 infusions) of infliximab. All five patients were on stable doses on infliximab and other disease modifying antirheumatic drugs.
The skin lesions were most commonly noted on the lower extremities and one patient had involvement of the face, buttocks and abdomen. Different morphological lesions were observed: erythematous macules and papules, linear hypertrophic lesions, palpable purpura, hemorrhagic bullae, and ulcerations. Two patients had pruritus.
Five skin biopsies were studied. Four biopsies showed interface dermatitis (vacuolar degeneration of the basal layer) with necrotic keratinocytes. Of these four, 2 skin biopsies showed the patterns of leukocytoclastic vasculitis and hyperkeratosis in addition to the interface dermatitis. The other two biopsies showed superficial perivascular lymphocytic infiltration. Rare eosinophils were seen in one case. The fifth biopsy showed lichenoid interface dermatitis with lymphocytes in the epidermis (epidermotropism) mimicking mycosis fungoides-like pattern.
Anti-ds DNA antibodies (C. luciliae test) were found in 3 of 4 patients tested. None developed lupus-like illness. Serum titer of anti-ds DNA decreased with discontinuation of infliximab.
The skin lesions improved over a mean of 19 weeks (range 3-45 weeks) after discontinuation of infliximab in four patients. In the patient with LCV, leflunomide was discontinued at the same time because of elevated liver enzymes. Topical corticosteroid and silver sulfadiazine were used in two patients. High-dose corticosteroids were given to the patient with LCV because of development of bullae and necrotic ulcers. One patient opted to continue infliximab therapy with informed consent and after 10 months, the rash has persisted but diminished.
Conclusion: Cutaneous lesions of varying morphology may occur in up to 9% of patients on infliximab. The histopathological findings are consisted with an immune-mediated drug reaction; however, different mechanisms including immune complex deposition and cell-mediated process may be involved in the pathogenesis of the skin lesions.