Hideaki Yamakawa

Clinical investigation of nontuberculous mycobacterial lung disease in Japanese patients with rheumatoid arthritis receiving biologic therapy.

Objective. To review patients with rheumatoid arthritis (RA) receiving biologic therapy following a diagnosis of nontuberculous mycobacterial (NTM) lung disease and to evaluate disease deterioration according to clinical and radiological features and anti-NTM therapy. Methods. We retrospectively analyzed medical records of 11 human immunodeficiency virus-negative patients with RA (median age, 64 years) receiving biologic therapy following diagnosis of NTM lung disease. Results. NTM species included Mycobacterium avium complex in 9 patients (81.8%) and M. gordonae in 2 (18.2%). Underlying respiratory disease was present in 6 patients (54.5%), and most (81.8%) had radiographic features of nodular/bronchiectatic disease. Extent of NTM disease was 1–2 pulmonary lobes in 6 patients (54.5%), 3–4 lobes in 5 patients (45.5%), and 5–6 lobes in none. The results of radiological evaluations were unchanged or improved in 7 patients (63.6%) and worsened in 4 (36.4%). Radiological outcome was worse in patients with poor RA control despite their receiving biologic therapies for RA. Two of 3 patients receiving anti-NTM therapy as initial management for NTM improved, and 1 worsened. Three of 4 patients with worsened radiological outcome had high erythrocyte sedimentation rate (> 50 mm/h). Conclusion. Radiological deterioration was not observed in the majority of patients with RA receiving biologic therapy with NTM lung disease, and radiological outcome of pulmonary NTM was favorable in some patients undergoing anti-NTM therapy. Further studies focusing on disease deterioration according to biologic therapy received during NTM followup are warranted to determine appropriate treatment of RA patients with NTM lung disease.

Prognostic factors and radiographic outcomes of nontuberculous mycobacterial lung disease in rheumatoid arthritis.

Objective. The aims of our study were to retrospectively review patients with rheumatoid arthritis (RA) with nontuberculous mycobacterial (NTM) lung disease, to assess the prognostic factors, and to analyze the time to disease deterioration according to the antirheumatic drugs received during the NTM lung disease followup period. Methods. We retrospectively analyzed medical records of 98 HIV-negative RA patients with NTM lung disease treated at our institution, and investigated potential risk factors of mortality with Cox regression analysis. Time to radiologic deterioration was evaluated if antirheumatic drugs were not changed during observational periods and computed tomography was performed once each year. Results. Mean patient age was 67.6 years, and median followup period was 4.4 years. NTM species included Mycobacterium avium complex (83.7%), M. kansasii (6.1%), M. gordonae (6.1%), and others (4.1%). Radiographic features included nodular/bronchiectatic (NB) disease (57.1%), fibrocavitary (FC) disease (14.3%), FC+NB disease (16.3%), and other types (12.2%). Initial management included observation in 74 (75.5%) patients. Negative prognostic factors of mortality were C-reactive protein (CRP) ≥ 1.0 mg/dl and radiographic features of FC, FC+NB, or other disease types. Median time to radiologic deterioration was 3.6 years. Erythrocyte sedimentation rate (ESR) > 50 mm/h was a negative prognostic factor of radiologic deterioration. Conclusion. The most frequent NTM species was M. avium complex. CRP and radiographic features were prognostic factors for all-cause mortality, and ESR was a prognostic factor of radiologic deterioration. Further studies are warranted focusing on time to disease deterioration according to antirheumatic drug received during NTM followup.

Hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis: A single-center experience

In Japan, nintedanib was approved for idiopathic pulmonary fibrosis (IPF) and was clinically used from September 2015. However, we have often encountered drug-induced hepatotoxicity, which has required interruptions and/or dose reductions. Therefore, the objectives of this study were to investigate the incidence of drug-induced hepatotoxicity following the commercialization of nintedanib and to clarify the treatment status of nintedanib in our hospital.

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis.

Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD.

Correlation between Clinical Characteristics and Chest Computed Tomography Findings of Pulmonary Cryptococcosis

Objective. The aim of this study was to review HIV-negative patients with pulmonary cryptococcosis to analyze the correlations between clinical characteristics and chest computed tomography (CT) findings. Methods. We retrospectively analyzed medical records of 16 HIV-negative patients with pulmonary cryptococcosis diagnosed at our institution, and clinical characteristics of the patients with nodules or masses without ground-glass attenuation (GGA)/consolidation type were compared with those of patients with inclusive GGA or consolidation type. Results. Host status was immunocompromised (81.2%) in most of the patients, and 6 (37.5%) were asymptomatic. The most frequent radiologic abnormalities on chest CT scans were one or more nodules (87.5%), GGA (37.5%), and consolidations (18.8%). Most lesions were located in the lower lung. Levels of hemoglobin and platelets were significantly lower in patients with inclusive GGA or consolidation type. Although the differences were not significant, patients with inclusive GGA or consolidation type tended to have a C-reactive protein level of ≥1.0 mg/dL. Conclusion. If a patient with anemia and thrombocytopenia shows GGA or consolidation in the lung, pulmonary cryptococcosis should be given careful consideration.

Pulmonary tumor thrombotic microangiopathy associated with urothelial carcinoma of the urinary bladder: antemortem diagnosis by pulmonary microvascular cytology.

PTTM (Pulmonary tumor thrombotic microangiopathy) is very difficult to diagnose before death. We report a case of urothelial carcinoma of the urinary bladder associated with PTTM in which an antemortem diagnosis by PMC (pulmonary microvascular cytology). PMC may represent the only chance for diagnosis and achievement of remission in PTTM.

Useful Strategy of Pulmonary Microvascular Cytology in the Early Diagnosis of Intravascular Large B-cell Lymphoma in a Patient with Hypoxemia: A Case Report and Literature Review

Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal lymphoma characterized by the presence of tumor cells within blood vessels, and it is considered to be a subtype of diffuse large B-cell lymphoma. We report a case of IVLBCL presenting as progressive hypoxemia. In this case, a definitive diagnosis could not be achieved by repeated transbronchial lung biopsy, a bone marrow biopsy, and a random skin biopsy, and the ultimate diagnosis was made on the basis of a pulmonary microvascular cytology (PMC) examination. Therefore, PMC is considered to be a useful strategy for the diagnosis of IVLBCL, particularly in this critically ill patient suffering from hypoxemia.

Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease

BACKGROUND Interstitial lung disease (ILD) is frequent complication of systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). The disease is heterogeneous, and its outcome is unpredictable. Some patients have severe and progressive deterioration of ILD, which is the leading cause of mortality. We aimed to determine whether serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) correlate with SSc/MCTD-associated ILD activity. METHODS We retrospectively analyzed the medical records of 40 patients with SSc/MCTD-associated ILD: 29 patients with SSc and 11 patients with MCTD. Measurement of serum KL-6 and SP-D levels, pulmonary function tests, and high-resolution computed tomography (HRCT) performed in parallel were reviewed. RESULTS Serum KL-6 correlated positively with diffusing capacity of the lung for carbon monoxide (DLCO) (% predicted) and disease extent on HRCT, and the changes in serum levels of KL-6 were significantly related to the changes in forced vital capacity (FVC) in SSc/MCTD-associated ILD. On the other hand, multivariate logistic regression analyses with calculation of the area under the curve of the receiver-operating characteristic curve suggested that a higher serum level of SP-D was a significant predictor of FVC decline in SSc/MCTD-associated ILD. CONCLUSIONS Our study suggests that serum KL-6 can be a useful monitoring tool of SSc/MCTD-associated ILD activity. In contrast, serum SP-D may be a significant predictor of potential FVC decline in the short term.

Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

Prognostic factors and disease behaviour of pathologically proven fibrotic non-specific interstitial pneumonia: Prognosis of fibrotic NSIP

Non‐specific interstitial pneumonia (NSIP) has heterogeneous characteristics in terms of background, disease behaviour and prognosis. This study of fibrotic NSIP (f‐NSIP) aimed to elucidate prognosis and disease behaviour from the viewpoint of clinical background and determine whether long‐term change of pulmonary function could provide useful prognostic information.