EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING AS CRESCENTIC GLOMERULONEPHRITIS IN A RHEUMATOID ARYHRITIS PATIENT TREATED WITH SARILUMAB

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by bronchial asthma, sinusitis, and hypereosinophilia. Although multiple organs are commonly affected, isolated renal involvement is rare. We report a case of a patient with rheumatoid arthritis (RA) and bronchial asthma who developed myeloperoxidase (MPO)-ANCA-positive EGPA with isolated renal involvement during sarilumab treatment.

A 67-year-old woman with a 20-year history of RA, well-managed with 2 mg/day prednisolone and sarilumab (200 mg every 3 weeks), presented with general malaise, poor appetite, weight loss, hematuria, and proteinuria. She had been diagnosed with bronchial asthma 15-years earlier, which was controlled with an inhaled glucocorticoid and a long-acting β2-agonist. Four weeks before presentation, her sarilumab dose was reduced to 150 mg. Laboratory tests revealed an elevated serum CRP level (5.54 mg/dL), marked eosinophilia (9,650/μL), an elevated serum IgE level (4,443 IU/mL), and a high titer of MPO-ANCA (1,280 U/mL). Anti-nuclear antibody, peroxidase 3-ANCA, and anti-glomerular basement membrane antibody were all negative. The urinary protein-to-creatinine ratio was 1.9 g/gCr, and urinalysis showed hematuria with granular and red blood cell casts. Renal biopsy revealed 14 glomeruli, three with crescents (one with fibrinoid necrosis) (Figure B). Patchy interstitial infiltration of inflammatory cells with numerous eosinophils and periarterial granulomatous inflammation were evident (Figure A). Immunofluorescence for IgG, IgA, IgM, C3, and C1q was negative. She was diagnosed with EGPA. Despite renal lesions, no other EGPA-related features, such as mononeuritis multiplex, purpura, or pulmonary involvement, were evident. Treatment included methylprednisolone pulse therapy, oral prednisolone (30 mg/day), and rituximab (375 mg/m² weekly for 4 weeks). Eosinophilia, CRP, and symptoms improved rapidly. Proteinuria and hematuria resolved, and MPO-ANCA decreased to 102 IU/mL. Maintenance therapy with prednisolone and mepolizumab sustained disease control.

RA rarely coexists with EGPA. However, some reports suggest that EGPA can develop following the prolongation of dosing intervals for anti-IL-6 receptor antibodies, implying a possible role of elevated IL-6 levels in disease onset. Imai et al. assessed serum IL-6 levels pre- and post-EGPA development in a patient treated with tocilizumab for microscopic polyangiitis (MPA) and secondary amyloidosis. They found very high IL-6 level (1076.8 pg/mL) at the time of EGPA onset, compared to 55.3 pg/mL upon diagnosis of MPA. Increasing evidence suggests IL-6 plays a significant role in the pathogenesis of bronchial asthma and other allergic diseases. In our patient, reduction of sarilumab dose may have been associated with overproduction of IL-6, contributing to EGPA development.

We report a case of EGPA characterized by crescentic glomerulonephritis that developed during interval prolongation of anti-IL-6 receptor antibody administration. Enhanced IL-6 signaling resulting from the prolonged dosing interval of sarilumab is suggested to have contributed to the development of EGPA in our patient.