A 50-year-old male visited our hospital in October 1996 because of abnormalities detected in a medical checkup. Urinary protein and occult hematuria had been documented in medical checkups over the previous few years, with marked proteinuria of up to 3.8 g/day being a prominent feature of his clinical presentation. Renal biopsy performed in December 1996 revealed segmental sclerosis in 1 of 7 glomeruli and deposition of immunoreactive substances into glomeruli, including IgM and complement. Therefore, a diagnosis of FSGS was made on the basis of the results of a renal biopsy. Also, chest computed tomography (CT) delineated interstitial changes accompanied by cystic lesions in the lung and pleural thickening (fig. 1a), along with chest X-ray abnormalities that had been noted in a past medical checkup. He had worked as a demolition worker and smoked approximately 30 cigarettes a day since he was 18 years old. Work- and smoking-related lung conditions were therefore the most likely causes of the pulmonary lesions. An annual chest CT showed little change over several years, in contrast to progression of the renal disorder. Pleural thickening strongly suggested concomitant TB based on epidemiological reports showing a strong association of TB with pneumoconiosis, although mycobacterium species were not detected by sputum culture tests that were repeatedly performed over a couple of years.
Cyclosporine A (CsA) was administered at doses of 50-100 mg per day under therapeutic drug monitoring (the trough level was usually around 50 ng/ml) in lieu of steroid therapy to reduce the risk of excessive immunosuppression, but the serum creatinine (Cr) level showed a rapid elevation in 2000, at approximately 3 years after biopsy (fig. 2a). He had presented with persistent microscopic hematuria, which is inconsistent with the clinical presentation of FSGS, since the first visit. By contrast, a temporary decrease in proteinuria (down to 1.3 g/day) was observed afterward, unlike with treatment-resistant FSGS. Rapidly progressive glomerulonephritis was suspected despite the biopsy findings, and circulating ANCA was measured (this test has been clinically available since 1998 in Japan). Elevation of the MPO-ANCA titer (168 EU) was found, along with an altered clinical presentation. However, potent immunosuppressive therapies such as glucocorticoids were still withheld due to the possibility of an underlying infection (TB). Apheresis was alternatively conducted in an effort to avoid decreased immune competence, but initiation of HD was required in September 2001 because of end-stage renal disease (ESRD). Thrice-weekly HD was performed uneventfully for several years, and there were also no changes in pulmonary signs. An annual CT checkup had shown little change (fig. 1b), and elevation of serum KL-6 had not been documented. In contrast, circulating MPO-ANCA had ranged from 10.5 to 32.5 U/ml, even in the dialysis period, indicating possible AAV (fig. 2b). However, steroid therapy was postponed due to the unconfirmed diagnosis, presumed TB, and lack of problematic clinical events.
Abruptly, the patient developed gross hemoptysis accompanied by severe cough at night in bed and was transported to our facility by ambulance in October 2010. Chest CT showed infiltrative shadows in the bilateral lung fields (fig. 1c). Under a presumptive diagnosis of alveolar hemorrhage associated with AAV, steroid therapy comprising 3-day intravenous infusion of 500 mg methylprednisolone followed by daily oral administration of 20 mg prednisolone (PSL) was launched. A preventive dose of 100 mg isoniazid per day was also prescribed. As expected, the hemorrhagic shadows almost disappeared as early as 2 days after hospitalization (fig. 1d), and the serum MPO-ANCA titer subsequently fell to normal (fig. 2b). The patient was discharged after 17 days and has had no recurrence of hemoptysis. At present, PSL has slowly been tapered to a daily dose of 5 mg, but there has been little change over time in the serum MPO-ANCA level and follow-up CT.
Time course of pulmonary lesions in our patient. c; Chest CT from October 2010 shows infiltrative shadows (arrows) in bilateral inferior lobes, simultaneously with hemoptysis.