A total of 60 patients (35 males and 25 females) were diagnosed with GPA over a period of 10 years (2002–2012). Forty-eight (80%) patients fulfilled the ACR criteria, and the rest were treated as GPA in view of ANCA positivity and/or histopathological evidence in appropriate clinical setting. The mean age at diagnosis was 44 years (range 16–85). There was a male preponderance in this cohort (1.4:1). Fifty-one (82%) patients were followed up for mean duration of 56 months (4 months to 11 years), and 9 (18%) were lost to follow-up. ANCA were positive in 56 cases of which 52 (93%) were cANCA positive and 4 (7%) were pANCA positive, and two patients exhibited dual positivity.
The spectrum of clinical manifestations at presentation and during the course of disease is illustrated in Table 1. Fever and fatigue as a nonspecific complaint was noted in 80% of the patients. The predominant system involved was renal followed by respiratory system.
Out of 60 patients, initial BVAS assessment showed that 57 (95%) patients had severe disease, while only three (5%) patients had limited disease where median BVAS was 21.5 (range 17–44). In follow-up BVAS evaluation for severe disease, 13 (22.8%) patients continued with severe disease of which nine patients did not survive, 24 (42.3%) had remission, 11 (19.2%) had persistent disease, and 9 (15.7%) were lost to follow-up. The mean VDI Score was 2.5 ± 2.
Multi-organ involvement is frequently observed in GPA patients. We noted single-organ involvement in only 20 out of over 60 patients (8 renal alone, 4 respiratory tracts alone). All others had multiple organs involved by the disease process, the most common being renal and respiratory dual involvement. Seven patients had three or more organ system involvement.
Renal involvement was established in 42 (70%) patients. Twenty-eight (66.6%) patients had rapidly progressive glomerulonephritis (RPGN). Nephrotic syndrome was present in 8 (19%), and 7 (16%) had asymptomatic urinary sediments.
All patients with renal involvement had hematuria. Macroscopic hematuria was seen in 5 (11%), and 37 (89%) had microscopic hematuria. Hypertension was present in all 42 (100%) patients with renal disease. Mean creatinine of this subgroup at presentation was 4.5 mg/dl (range from 2 to 10 mg/dl).
Thirty-four (80%) patients underwent renal biopsy. Histopathological findings included crescents, glomerulonephritis, and fibrinoid necrosis in 24 (70.5%), mesangio-proliferative glomerulonephritis in 7 (20.5%), and 3 (9%) showed granuloma formation.
Follow-up of the 28 (66%) of subjects with RPGN showed that 19 (67.8%) progressed to end-stage renal disease (ESRD), 6 (21.4%) required interim hemodialysis (HD), and only 3 (10.8%) recovered with treatment. Among the 19 patients who progressed to ESRD, 17 (89.4%) requiring long-term dialysis and 2 (10.6%) patients underwent renal transplant. Nine (53%) patients with ESRD expired due to either progressive disease or complications of treatment.
Respiratory tract involvement
Upper and lower respiratory involvement was noted in 38 (63%) subjects. Cough in 14 (36%) patients was the most common symptom followed by hemoptysis in 6 (16%) patients. The other symptoms included dyspnea in 8 (21%), nasal discharge in 5 (13%), chronic sinusitis in 4 (11%), ear discharge in 2 (5%) patients. Nasal palate syndrome was seen in 2 (5%) patients. Saddle nose and subglottic stenosis were not noted in any. Diffuse alveolar hemorrhage was seen in 2 (5%), and both required plasmapheresis.
Of the 38 patients with respiratory involvement, 28 patients had abnormal chest radiology at presentation. Radiological findings included infiltrates 14 (50%), cavities 8 (29%), and nodules in 6 (21%). Six (16%) patients were treated for pulmonary tuberculosis before a diagnosis of GPA was made.
Lung biopsies were performed in 7 (18%) patients, and granuloma was seen in 2 (5%) biopsies. Five (13%) biopsies from the upper respiratory tract and one from the mastoid antrum also showed granuloma formation.
Nervous system disease
Nervous system involvement was noted in the 15 (25%) patients. Neurological manifestation in the form of peripheral neuropathy was seen in 7 (46%), 4 (27%) had mononeuritis multiplex, 3 (20%) had foot drop, and 1 (7%) had stroke as an initial presentation. Nerve conduction studies showed sensory motor involvement as the most common abnormality.
Four (26%) patients underwent nerve biopsies with evidence of vasculitis in two.
Other system involvement
Articular manifestations were seen in 16 (27%) patients. Skin rashes, oral ulcer, and gangrene were observed in 29 (32%) patients. Of the 9 (31%) dermal biopsies, 2 (7%) showed leukocytoclastic vasculitis, and others were nonspecific.
In our cohort, we had a patient with intracardiac mass which was resected, and biopsy showed granuloma suggestive of GPA.
A large number of biopsies were performed in this cohort. Based on clinical grounds, 65 biopsies from various sites were performed. However, only 12 biopsies showed granuloma, and majority of yield was from upper respiratory tract followed by those from the kidney (Table 2).
All the patients were induced with intravenous methyl prednisone 1 g/day for 3 days followed by 1–2 mg/kg/day of oral steroids. Majority of patients (n = 50) received 750 mg/m2 cyclophosphamide as monthly pulse. Methotrexate, azathioprine, and mycophenolate mofetil were used for remission maintenance, and IVIG and plasmapheresis were used in two patients each. Cotrimoxazole prophylaxis was used in all patients. All the treatments administered are represented in Table 3.
Complications and mortality
Forty-four (73%) patients had one or more complications. The most common complication noted during the study period was infections in 30 (68%) patients followed by blood dyscrasias in 22 (50%) patients. In all patients with infection, one or more bacterial infections were confirmed. Mucocutaneous candidiasis was noted in 18 (41%) patients, and dermatomal herpes zoster was documented in 6 (14%) patients. In addition, cytomegalovirus (CMV) colitis was noted in one and BK virus infection in a renal transplant recipient. Among the blood dyscrasias, anemia was noted in two-third of patients and 7 (32%) had pancytopenia. Rarer complications included seizures in 2 (5%), congestive cardiac failure in 2 (5%), and carcinoma breast in 1 (2%) patient.
At the time of this data analysis in September 2013, out of the 60 patients, 51 (85%) patients were followed up for a mean duration of 56 months ranging from 4 to 11 months. Nine (15%) were lost to follow-up, and hence their outcome was unknown. Twenty-four patients achieved remission of which eight patients suffered relapse. Out of 42 patients with renal GPA, 25 (42%) patients required initial dialysis, and 17 (28%) patients were dialysis dependent.
Mortality related to GPA or its treatment occurred in 11 (18%) patients (Table 4). ESRD was the most common cause of death seen in 9 (82%) patients. Two (18%) patients died of diffuse alveolar hemorrhage.