IgA nephropathy in adult-onset Still’s disease after tocilizumab treatment: a case report

Abstract

Tocilizumab, an interleukin (IL)-6 inhibitor, is a treatment option in refractory adult-onset Still’s disease (AOSD). A 28-year-old man presented to the emergency department with a high fever lasting for more than 2 weeks, a non-pruritic salmon-coloured skin rash, multiple arthritis involving the shoulders and knees, lymphadenopathy in the right lower neck and both axillary areas, sore throat, and splenomegaly. His white blood cell count was 26,500 with 92.1% neutrophils. His ferritin level was 36,344 ng/mL, and his C-reactive protein level was 25.29 mg/dL. A biopsy of the lymph node in the right axillary area showed reactive lymphadenopathy, and the culture findings were negative. His serologic results, including rheumatoid factor, anti-cyclic citrullinated peptide antibody, and anti-nuclear antibody, were negative. He was diagnosed with AOSD according to the criteria by Yamaguchi [1]. The patient was treated with methylprednisolone 1 mg/kg for 2 weeks. Subsequently, despite the administration of 2 weeks’ high-dose intravenous methylprednisolone therapy, continued along with oral methotrexate (10 mg weekly) and folate, his symptoms, such as fever, rash, and arthralgia, were not controlled. Therefore, we added cyclosporin (50 mg daily) on day 24 during hospitalisation. After shifting to and tapering down oral administration of prednisolone on day 35, the patient received increased dosages of oral methotrexate (12.5 mg weekly) and oral cyclosporin (100 mg daily). Although the patient was treated with high dosages of prednisolone, methotrexate, and calcineurin inhibitor for 6 months after diagnosis, his symptoms, including fever, skin rash, and arthritis, were intermittent and uncontrolled. Thus, the patient received tocilizumab, an IL-6 inhibitor intravenously monthly. His symptoms improved after tocilizumab therapy, and this improved symptom was maintained for 4 weeks. At the seventh month of the monthly tocilizumab therapy, sudden gross haematuria was detected. The urinalysis revealed protein > 341 mg/day and red blood cell (RBC) > 100/high power field with 50% of dysmorphic RBC. The urine albumin to creatinine ratio was 760.1 mg/g Cr, and the estimated glomerular filtration rate was 110.8 mL/min/1.73 m2 (Table 1). Therefore, the patient underwent renal biopsy, which showed immunoglobulin (Ig) A nephropathy with variable glomerular basement membrane thickening and foot process effacement, focal and microvillous transformation, and electron-dense deposit in the mesangium. In addition, immunofluorescence staining showed positivity for IgA, C3, fibrinogen, kappa, and lambda in the mesangium. He was diagnosed with IgA nephropathy, and tocilizumab therapy was tapered by increasing the interval of the injections from monthly to bimonthly. Eventually, the treatment regimen was discontinued. Currently, his IgA nephropathy and AOSD symptoms have been well-controlled 1 year after tocilizumab therapy discontinuation. The pathophysiology behind immunoglobulin (Ig) A nephropathy is still unclear. The most commonly known mechanism is IgA deposition, which causes inflammation and damages renal tissues [2]. The cause of this disease is associated with factors such as genes, other auto-immune diseases, kidney diseases, chronic liver diseases, infections, and drugs [2]. Several cases of IgA nephropathy were reported after tumour necrosis factor (TNF)-alpha inhibitor treatment. Previous reports on IgA nephropathy following administration of TNF inhibitors mention that possible mechanisms are co-existence of autoantibodies along with transient deposition of immune complexes, and worsening of the renal function owing to infectious complications [3, 4]. To the best of our knowledge, this was the first report to demonstrate IgA nephropathy as a complication of tocilizumab therapy in a patient with * Ji-Hyoun Kang [email protected]