Drug-induced granulomatous interstitial nephritis in a patient with ankylosing spondylitis during therapy with adalimumab

Abstract

Tumor necrosis factor α (TNF-α) inhibitors are used in the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn disease, ankylosing spondylitis, and juvenile idiopathic arthritis. Use of TNF inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, psoriasis, and sarcoidosis/sarcoid-like granulomas). We report a case of interstitial granulomatous nephritis in a patient with ankylosing spondylitis after 18 months of treatment with adalimumab. Previously reported cases of sarcoid-like reactions secondary to the use of TNF-α inhibitors involved the liver, lung, lymph nodes, central nervous system, and skin. Granulomatous nephritis after adalimumab treatment has not been described. Close observation of patients undergoing treatment with TNF inhibitors for evolving signs and symptoms of autoimmunity is required. Organ involvement is unpredictable, which makes correct diagnosis and management extremely challenging.

Figure 1

Kidney biopsy of the patient. (A) Dense infiltration of the interstitium with mononuclear cells consisting in part of lymphocytes and epithelioid macrophages that are organized in small granulomata (arrowheads). Tubules are compressed by the interstitial inflammatory cell infiltrate. (Periodic acid–Schiff stain; original magnification, ×10.) (B) Magnification of a noncaseating granuloma with epithelioid macrophages with surrounding lymphocytes, which were T cells by immunohistochemistry (not shown). (Periodic acid–Schiff stain; original magnification, ×40.)

Figure 2

The patient’s creatinine levels, urinary protein concentration, and sequence of events during 16 months of follow-up. Prednisone treatment was begun 3 days after admission to the hospital. Kidney biopsy was performed 2 months after initial presentation. Infliximab treatment was begun 12 months after first presentation to our hospital. Follow-up shows a stable creatinine level 4 months after administration of 3 doses of infliximab (5 mg/kg body weight) with 1.67 mg/dL. There is persisting tubular proteinuria with increased levels of α₁-microglobulin (A1M; maximum, 43 mg/L) without albuminuria. Abbreviation: Alb, albumin. Factor for converting serum creatinine in mg/dL to µmol/L, ×88.4.