We report a 45-year-old Caucasian male diagnosed with GPA in 2001 presenting with rhinitis, sinubronchitis and a right exophthalmos, but not signs of diplopia or vision defects. The nasal mucosa showed in two different biopsies active inflammation characterized by the presence of neutrophils and active vasculitis, tissue necrosis, and granulomatous inflammation. In the lacrimal ducts, a partially scarred tissue with moderate to severe chronic signs of inflammation was observed. Lab testing revealed anti-neutrophil cytoplasmic antibodies (cANCA) and against proproteinase-3 (anti-PR3). The patient was a non-smoker and had an unapparent medical history. No signs of kidney, lung, and joint, skin or central nervous system involvement were found.

The patient met the 1990 American College of Rheumatology (ACR) classification criteria for GPA [3]. Based on the clinical practice in 2001, when rituximab was not yet available for the treatment of GPA, intermittent cycles of cyclophosphamide at 15 mg/kg every month were started and the patient later received stable doses of methotrexate (15 mg/week) and low doses of glucocorticoids (5 mg daily) as maintenance treatment. In 2010 symptoms worsened, with increasing complaints related to inflammation of the upper airways (rhinitis, sinusitis and bronchitis) requiring hospital admission and the start of high-dose steroids (1 g/day pulsed methylprednisolone for 3 days, then 1 mg/kg/day for further 10 days. Cyclophosphamide (cumulative doses of 7 g) was stopped Rituximab was initiated at doses of 1000 mg at weeks 0–2 and then 500 mg every 6 months thereafter.

GPAthen remained silent with rituximab, methotrexate (15 mg/week) and low-dose prednisolone (5 mg daily) over 1-year. Because of family planning, methotrexate was replaced by azathioprine (150 mg/day), prednisolone was stopped and rituximab was continued. Three months later, the patient presented with persistent frontal headache, protrusion of the right eyeball and increased eye watering. Conventional MRI showed a granulomatous mass in the area of the right orbita, with granulomatous changes in the left lacrimal gland, indicating progression of disease despite rituximab treatment and almost complete B-lymphocyte depletion.

In agreement with the patient and considering the substantial granuloma formation in the orbita infliximab was added to rituximab at 400 mg IV at weeks 0–2–6 and every 6 weeks thereafter. A remarkable improvement in symptoms and inflammation imaging after a 6-month follow-up was observed. This combination regimen of azathioprine, rituximab and infliximab was maintained and the patient achieved long-standing remission without infectious complications. A trimethoprim/sulfamethoxazole prophylaxis has been maintained for the last 10 years, which potentially mitigated infections. No adverse events occurred during the entire 10 years of treatment. Despite remission, ANCA remained consistently elevated during this time (Fig. 1), even considering the methods change for ANCA tests, from ELISA to chemiluninescence technique, which has been standardized and validated in our center according to international guidelines.. Currently, the patient has no complaints, the treatment has been well tolerated and MRI revealed only minimal residual lesions (3 mm in size) in the orbita in the 2019 follow-up.

cANCA/PR3 levels in the last 15 years of treatment. The dotted line indicates the upper limit of the reached cANCA/PR3, the blue line indicates the upper limit of the normal range for cANCA/PR3. RTX rituximab, IFX infliximab, AZA azathioprin