An 83-year-old Japanese man had suffered from productive cough for 6 months and visited our hospital in March 2011. He had no fever. His sputum was yellowish. He had smoked 60 pack-years until 50 years of age. He had no past history of illness. He was a tobacco farmer and had also raised silk-worms. On physical examination, there was no lymphadenopathy, no clubbing, and no edema. SpO2 was 98% and blood pressure was 150/80 mmHg. His vesicular sound was slightly decreased throughout both lung fields and no crackle was auscultated. A chest X-ray and computed tomography (CT) scan showed emphysematous changes and multiple cavities in the bilateral pulmonary fields (Figure 1). Laboratory test results were as follows: WBC, 6500/mul; RBC, 3.29 million/mul; hemoglobin, 9.9 g/dl; MCV, 94.5 fl; MCH, 30.1 pg; total protein, 6.8 g/dl; albumin, 3.0 g/dl; total cholesterol, 167 mg/ml; BUN, 29.4 mg/ml; Cr, 1.57 mg/ml; and CRP, 1.34 mg/ml. Urine examination showed a sub-nephrotic range of proteinuria (3.1 g/gCr) and many hyaline casts (>50/total fields) in the urinary sediment. Pulmonary function tests showed low%VC (70.8%) and normal range of FEV1.0% (78.1%). Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Numerous colonies of acid-fast bacilli appeared upon culture. DNA-DNA hybridization, which can detect 18 species of acid-fast bacilli using cultured colonies, failed to identify the species. The mycobacterial characteristics of a sputum sample obtained on another day were exactly the same as those of the first sample. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing, with 100% homology to the sequences.
Renal tissue samples obtained by renal biopsy mainly showed membranous glomerulonephritis (MGN), with partial hypertensive renal damage (Figure 2). In addition, the mesangial areas were slightly enlarged and mesangial cells had proliferated in part (Figure 2A). Electron-dense deposits were observed in the mesangial areas as well as the subepithelium and basement membranes (Figure 2C). Immunofluorescence analyses showed positive staining for IgG, IgA, and IgM in the basement membranes (data not shown). No granulomatous change was observed in the renal tissue samples. No acid-fast bacilli were detected by Ziehl-Neelsen staining.
Because the productive cough continued, M. tuberculosis was excluded, and a new lesion appeared on his chest X-ray, anti-mycobacterial treatment (clarithromycin, 400 mg/d; rifampicin, 300 mg/d; and ethambutol, 500 mg/d) was started before the identification of M. shimoidei. Candesartan (80 mg/d), an angiotensin II receptor blocker (ARB), was also started. After 1 month of treatment, the species was identified as M. shimoidei and the initial treatment was continued. The isolate was sensitive to ethambutol, streptomycin, kanamycin, enviomycin, ethionamide, and levofloxacin, and was resistant to isoniazid, rifampicin, cycloserine, and para-aminosalicylic acid, in in vitro drug sensitivity tests. At 2 months after starting the treatment, his sputum was clearly decreased. After 6 months of treatment, acid-fast bacilli were not detected by either Ziehl-Neelsen staining or 8-week culture, and the chest CT findings were also improved (data not shown). He continued antimycobacterial treatment for an additional 1 year (18 months in total) in accordance with the statement from the American Thoracic Society and the Infectious Diseases Society of America. The amount of urine protein decreased gradually after initiation of the antimycobacterial treatment and ARB, and reached 0.6 g/gCr. The serum albumin level recovered to 3.6 g/dl at the end of the treatment.
Chest X-ray and computed tomography. (A) Chest X-ray showing cavities (arrow), nodules, and pleural thickening (arrowhead) in the bilateral, predominantly upper, lung fields.