An 84-year-old male was admitted to our respiratory ward on November 23 last year because of intermittent fever with maximum temperature not exceeding 38.5 centigrade for more than 10 days, accompanied by cough with sputum and fatigue. He was a retired army pilot and a nonsmoker. He was treated with acetylcysteine due to PF detected by annual physical examination 5 years ago, with a coexistent anterosuperior mediastinal mass, which did not show much progression. He also had a past history of diabetes for 20 years.
On admission, his temperature was 37.6 centigrade. On physical examination, a fine moist rale over both lower lung fields was noted. Skin exam did not reveal any rash. Musculoskeletal exam revealed no joint swelling or tenderness and he had no edema of the limbs. Neurological exam was normal.
Complete blood count showed eosinophilia with an absolute value of eosinophils of 1.71 x 109/l (13%). Renal function tests were normal (urea 4.5 mmol/l, creatinine 97 mumol/l) on admission. C-reactive protein was 47.7 mg/l. Chest X-ray revealed thickened lung marking in both lower lung fields (fig. 1a). Empirical antibiotics treatment with amoxicillin potassium and doxycycline was used and was changed to piperacillin tazobactam and then tienam but the patient's symptom did not resolve. Blood culture, sputum culture, respiratory virus, sputum acid-fast bacillus smear, Streptococcus pneumoniae antigen, corps antigen, Mycoplasma pneumoniae DNA, tuberculosis DNA and tumor markers were all negative. Complement component C3 was 0.73 g/l and immunoglobulin G (IgG) was 17.94 g/l. Antinuclear antibodies and anti-double-stranded DNA antibodies were negative. Indirect immunofluorescence revealed perinuclear ANCA positive with anti-MPO ANCA specificity by ELISA (125 RU/ml, normal <20 RU/ml); immunofluorescence for cytoplasmic ANCA, and ELISA for antiproteinase 3 ANCA were negative, but anti-GBM antibodies titer (ELISA) was positive at a titer of 1:32. Tuberculosis screening for bronchoalveolar lavage fluid via bronchoscope was negative. Chest CT scan showed honeycombing, reticular and ground glass opacities in the lower lung fields (fig. 1b). Pulmonary function was roughly normal. Lung biopsy showed eosinophilia with vasculitis changes and granuloma formation (fig. 2). During his stay, the renal function was deteriorated (creatinine gradually increased to 171 mumol/l). Percutaneous renal biopsy was performed and immunofluorescence microscopy disclosed linear staining of glomerular capillary basement membrane for IgG and C3, diagnostic for anti-GBM disease (fig. 3).
Diagnosis of AAV with coexistent anti-GBM disease in the patient with acute pulmonary-renal syndrome and long-existing PF/anterosuperior mediastinal mass was made. The patient was then given a regimen consisting of i.v. methylprednisone (80 mg/day) with i.v. cyclophosphamide 0.4 g every week and plasmapheresis (PE) every other week for 6 times. Perinuclear ANCA/anti-MPO ANCA returned to normal 1 week later but anti-GBM antibodies were still positive with the same titer. The symptoms disappeared without relapse. Steroids were then tapered to 60 mg/day. Unfortunately, the patient experienced shortness of breath, palpitation and hypotension during PE, ongoing continuous bleeding from the puncture point of the femoral vein with a dramatic drop of platelet count (32 x 109/l at the lowest), which suggested the diagnosis of heparin-induced thrombocytopenia (HIT). Bilateral lower extremity compression ultrasonography was applied in this patient to rule out silent deep vein thrombosis. PE was discontinued and rivaroxaban was used until the platelet count returned to normal. Anti-GBM antibody was still positive and renal function did not ameliorate after 3 weeks of cyclophosphamide. Therefore, immunosuppressant was switched to rituximab 700 mg/week. Anti-GBM antibody turned to negative after 1 month and creatinine decreased to 149 mumol/l. Mycophenolate mofetil with the dosage of 1.5 g/day was then used for maintenance treatment and oral prednisone gradually decreased to 25 mg/day.
At the latest follow-up visit after around 4 and a half months' treatment, all the antibodies remained negative and creatinine was 123 mumol/l. Repeated chest CT revealed a novel nodule in the upper lobe of the left lung (0.9 x 1.0 cm) with concomitant mild progression of interstitial changes. A further PET/CT showed the novel lesion with a standardized uptake value of 3.0 suggesting inflammatory pseudotumor. Meanwhile, the anterosuperior mediastinal mass was remarkably diminished without thymectomy intervention (fig. 4).
CT scan. on admission. b; Chest CT scan showed honeycombing, reticular and ground glass opacities in the lower lung fields (arrows).