Crohn’s disease, infliximab treatment and IgA nephropathy

Abstract

IgA nephropathy is one of the most common glomerular lesions worldwide, with a reported prevalence of 25–50 cases/100,000. Much like IBD, it classically affects the young. However, it has rarely been associated with Crohn's disease. Only 6 cases have been reported. We report a case of IgA nephropathy which developed in a 38 year-old Caucasian male who had a 19 year history of fistulizing Crohn's ileocolitis and perianal disease. The patient has had prior ileal resection and numerous perianal surgeries. About 2 years before the presentation of IgA nephropathy, he was placed on a regimen of infliximab infusions every 8 weeks and 6-mercaptopurine. His bowel disease was under good control when he presented with fatigue followed shortly by gross hematuria. Initially his creatinine was normal and there was no proteinuria. However, he soon developed significant proteinuria, 2.4 gm/24h, and renal insufficiency with a peak creatinine of 2.8 several months after the onset of hematuria. Renal biopsy revealed a moderately increased mesangial matrix with immunostaining against IgA showing 3–4 + mesangial deposition. There was also 4+ mesangial staining for C3. Overall the findings were felt typical for IgA nephropathy. The patient was started on a regimen of glucocorticoids, ACE inhibitors and fish oil. His creatinine and proteinuria progressively improved over the course of 6 months. During this treatment his gastrointestinal symptoms have remained quiescent. The pathogenesis of IgA nephropathy is incompletely understood but a key feature is the glomerular deposition of circulating immune complexes and activation of complement via the alternative pathway. The IgA is mainly polymeric IgA1, which is often of mucosal origin. This plus the fact that IgA nephropathy has been reported with various gastrointestinal disorders such as celiac sprue and dermatitis herpetiformis has led to speculation that IgA nephropathy is a disease of the mucosal immune system. As in Crohn's disease, antibodies to various dietary and microbial antigens have been reported in IgA nephropathy. Finally, it is possible that infliximab and the resulting generation of antibodies to infliximab (ATI) may have contributed to the development of this patient's renal disease.