A 39-year old man was presented with painful sensation, redness and blurred vision of both eyes for 3 weeks. He also had multiple violaceous skin lesions on both arms and legs. His medical history was unremarkable. He was a non-smoker, but he was social alcohol drinker. He did not have a history of tuberculosis contact. He recalled no family history of cancer, tuberculosis, nor autoimmune diseases.
Physical examination revealed a temperature 38.1  C, blood pressure 126/85 mmHg, pulse rate 90/minute, respiratory rate 16/minute, and O2 saturation 98% on ambient air. Ophthalmic examination revealed bilateral swollen lids, chemosis, ciliary injection, compatible with bilateral diffuse scleritis. He did not have an oral ulcer, saddle-nose deformity, sinus tenderness, or hair loss. Multiple pulpable painless violaceous papules were found along his legs and arms. The neurological, heart, lungs, abdomen, lymph nodes and musculoskeletal examinations were unremarkable.
The laboratory examination showed a hemoglobin of 10.3 g/dL, white blood cell count 11.9 x 103/muL (77% neutrophils, 11% lymphocytes), a platelet count 366 x 103/muL, CRP-QT 204.48, ESR 91 mm/hr, serum creatinine (Cr) 0.58 mg/dL, globulin 4.5 g/dL, albumin 3.6 g/dL, ALP 227 U/L (30-120), AST 39 U/L (0-32), ALT 25 U/L (0-25). Urinalysis revealed 2+ protein, dysmorphic RBC of 10-20 cells/HPF. A 24-h urine total protein was 1333 mg/volume. Hepatitis B, hepatitis C, and anti-HIV antibodies were negative. Serum VDRL, TPHA, RT-PCR for herpes virus, and QuantiFERON-TB gold tests were also negative. The c-ANCA (indirect immunofluorescent assay, IFA) and anti-PR3 antibodies (western blotting) were positive. Anti-RF antibody was positive 26.4 IU/L (0-20.0). Anti-MPO, ANA, anti-Ro and anti-La antibodies were negative.
Initially, infectious scleritis was suspected. An orbits CT showed left eye proptosis with bilateral scleritis, enlargement of bilateral lacrimal glands with mildly retrobulbar fat stranding and sinusitis at bilateral sphenoid and ethmoid sinuses. Nasal endoscopy revealed suppurative discharge in sphenoid and ethmoid recesses and nasal crust without mass. A pus culture was negative.
Chest radiography showed multiple pulmonary nodules in both lungs. A chest CT showed multiple lung masses with peripheral enhancements and perilesional ground glass opacities, the largest mass was 10.1 x 5.6 x 6.0 cm. Sub-centimeter mediastinal lymphadenopathy was noted (Fig. 1a). An abdominal CT showed 10.5-cm heterogenous enhancements of the spleen without space-occupying lesion. Liver and portal veins were unremarkable. Neither adenopathy nor ascites were seen.
Bilateral conjunctival debridement and administration of topical and systemic ceftazidime and vancomycin were done. The scleritis, however, did not improve, and no organisms were found, conjunctival recess resection was performed. Conjunctival tissues revealed focal multinucleated giant cells with necrotizing vasculitis. AFB stains were negative. The IgG4 to IgG ratio was 0.29:1. Tissues from violaceous skin lesions were compatible with leukocytoclastic vasculitis.
The CT-guided lung mass biopsies for cultures, PCR for Xpert MTB/RIF assay, PCR for 18s rRNA were negative. The lung tissues showed geographic necrosis with few multinucleated giant cells, special staining for AFB, GMS, PAS, and cultures were negative.
The overall findings were compatible with GPA by ACR/EULAR 2017 provisional classification criteria. Prednisolone 1 mg/kg/day and intravenous cyclophosphamide 800 mg were started. The scleritis and lung mass were improved. Bronchoscopy was done 6 days later, hypervascularization and inflammation were seen along the bronchus (Fig. 2a). A transbronchial biopsy was done at the lateral segment of right middle lobe, and showed organizing pneumonia foci, a few necrotic tissues, no chronic granulomatous inflammation, no neoplasm, no vasculitis lesions, special staining for AFB, GMS, PAS, and cultures were negative. The final diagnosis was GPA with diffuse scleral, sinopulmonary, splenic, and mild renal involvements.
After the 3rd dose of cyclophosphamide, the bilateral scleritis deteriorated, the right lung mass was enlarged, and the patient also had a new onset of bilateral sensorineural hearing loss. ESR was raised from 29 to 58 mm/hr. Bronchoscopy revealed progression of bronchial inflammation, and a transbronchial biopsy showed necrotic tissue with neutrophil infiltration. The bronchoalveolar lavage for mycobacterial, fungal cultures, and PCR for herpes were negative. Intravenous rituximab 375 mg/m2 was given due to clinical deterioration. During treatment, he developed severe secondary infection, clinical deterioration, and then expired.