Prospective multicenter survey for Nursing and Healthcare-associated Pneumonia in Japan.

INTRODUCTION: Nursing and healthcare-associated pneumonia (NHCAP) was proposed by the Japanese Respiratory Society in 2011. However, the clinical characteristics of NHCAP are still unclear. Thus, this study aimed to clarify its clinical characteristics. METHODS: This multicenter prospective observational study included 596 patients with NHCAP from 73 centers in Japan between May 2014 and February 2016. RESULTS: Patient background was characterized by an older age (81.5 ± 10.1 years), most patients had complications (94.1%), and many patients had a high probability of aspiration pneumonia (68.6%). Among the isolates, Streptococcus pneumoniae was the most common (12.7%), while Pseudomonas aeruginosa was also isolated at 10.8%. The overall 30-day mortality rate for patients was 11.9%, and the factors affecting mortality were non-ambulatory status, high blood urea nitrogen level, impaired consciousness, and low albumin level. Sulbactam/ampicillin was the most commonly administered antibiotic, including in groups with high severity of illness and high risk of multidrug-resistant (MDR) pathogens. Both the A-DROP and I-ROAD scores were useful in predicting the prognosis of NHCAP. Confirmation of intention to provide do not attempt resuscitation (DNAR) instructions was given to 333 patients (55.9%), and 313 patients agreed to DNAR instructions. CONCLUSIONS: NHCAP tends to occur in elderly patients with underlying diseases. The risk of MDR pathogens and the mortality rate are intermediate for community-acquired pneumonia and hospital-acquired pneumonia. As NHCAP is considered an important concept in an aging society, such as in Japan, establishing a treatment strategy that considers not only prognosis but also quality of life would be beneficial.

Influence of pneumonia complications on the prognosis of patients with autopsy-confirmed Alzheimer's disease, dementia with Lewy bodies, and vascular dementia.

BACKGROUND: Pneumonia is a major, complicated disease in patients with dementia. However, the influence of pneumonia on the prognosis of patients with varying types of dementia has not been fully evaluated. METHODS: We retrospectively analyzed the data from medical and autopsy reports. All study patients had been hospitalized and underwent brain autopsy in a hospital in Toyohashi, Japan, between 2005 and 2014. The patients with subtypes of dementia, specifically Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or vascular dementia (VaD), were neuropathologically diagnosed and examined. Pneumonia incidence, cause of death, and the clinical time-course of dementia were compared among the dementia subtypes. The time to death from dementia onset (survival time) was compared by the Kaplan-Meier method among subtypes of dementia with or without pneumonia. Risk factors for survival time on all study patients were analyzed with the Cox proportional hazard model. RESULTS: Of the 157 eligible patients, 63 (40.1%) had AD, 42 (26.8%) had DLB, and 52 (33.1%) had VaD. Pneumonia complication was observed with high incidence in each subtype of dementia, especially in DLB (90.5%). The median total duration from dementia onset to death was 8 years in AD and DLB, and 5 years in VaD. The VaD subtype had more male patients than AD or DLB (P = 0.010), and age of death in this group was the youngest among the three groups (P = 0.018). A significant difference was observed in the survival time by the Kaplan-Meier method among the three groups (P < 0.001) and among the groups with pneumonia (P = 0.002). The factors associated with shorter survival time were male gender, pneumonia complications, diabetes mellitus, age of dementia onset ≥ 75 years, and VaD. CONCLUSIONS: Pneumonia complications shortened the survival time of patients with AD, DLB, and VaD.

[A comprehensive therapeutic strategy for osteoporosis in respiratory diseases.]

Many respiratory diseases including COPD are systemic disorders as well as pulmonary disorders. The diseases predominantly occurred in older peoples in advanced countries. Comprehensive therapeutic strategy including bronchodilators and systemic rehabilitation is necessary for maintenance of stable condition of pulmonary diseases. Importantly, physical activity is a key factor for the prognosis in the diseases, in this point, bone function and muscle function should be improved by the appropriate treatment. The regular assessment of bone density and muscle function are necessary for better prognosis of COPD patients.

[Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD.

[A case of cardiac tamponade due to malignant pericarditis with lung adenocarcinoma, effectively treated with pericardial drainage and pemetrexed plus cisplatin chemotherapy].

A 68-year-old man was diagnosed with non small cell lung cancer in May 2013. Although the patient was negative for EGFR mutation, he wished to undergo treatment with gefitinib and erlotinib as first-line therapy. However, one year later, he was admitted to our hospital because of cardiac tamponade due to malignant pericarditis. He received pericardial drainage, after which his condition was stabilized. He was diagnosed with lung adenocarcinoma by cytology of pericardial effusion and treated with pemetrexed plus cisplatin as second-line therapy. Thereafter, the malignant effusion was decreased and the primary lesion was regressed. He received six courses of chemotherapy, however, brain metastases and bone metastases appeared. The brain metastases were controlled with gamma knife radiosurgery and he received carboptatin-paclitaxel plus bevacizumab as third-line therapy. The patient is currently receiving chemotherapy without any recurrence of malignant pericarditis or cardiac tamponade.

[A case of acute respiratory failure in an elderly patient with elderly asthma-COPD overlap syndrome (ACOS) is differentiated from acute eosinophilic pneumonia].

We report a case of acute respiratory failure in a 77-year-old male with chronic obstructive pulmonary disease (COPD) who showed marked eosinophilia (61.5% of the peripheral total white blood cells [WBCs]; 13,200/mm(3)). The patient was an ex-smoker, but he had started smoking again one month previously, His forced expiratory volume in one second (FEV1) was low and dyspnea symptom was observed. Although rhonchi were detected, wheezing chest sounds were not detected. Chest X-radiography and computed tomography of the lung revealed diffuse bilateral pulmonary infiltrates and emphysematous changes. He was given intravenous methyl prednisolone (1,000 mg) for 3 consecutive days. The abnormal shadows on the chest X-ray film improved remarkably and the eosinophils in his peripheral blood were reduced. Furthermore, it was no longer necessary to administer oxygen to treat his hypoxemia. The symptomatic and clinical course mimicked to a case of acute eosinophilic pneumonia (AEP). However, transbronchial lung biopsy specimens did not reveal eosinophilic infiltration in the alveolar septa. The fraction of eosinophils in the patient's bronchoalveolar lavage was 4.4% and not greater than 25%. After hospitalization, 5-15 mg of prednisolone administered orally in combination with bronchodilators to better manage his clinical symptoms. This case was thus determined to correspond to elderly asthma-COPD overlap syndrome (ACOS).

[Two cases of pulmonary Mycobacterium avium complex disease with resistance to clarithromycin].

We encountered 2 patients with pulmonary Mycobacterium avium complex disease in whom resistance to clarithromycin (CAM) was confirmed after treatment with rifampicin, ethambutol, and CAM. We evaluated the disease course in both patients. The deterioration of radiological findings was preceded by the acquisition of resistance to CAM in both cases. When symptoms of pulmonary MAC disease exacerbate, and radiological findings deteriorate, we should reconsider the type of treatment after determination of the minimal inhibitory concentration (MIC) of CAM for culture positive MAC strains.

[Development of exudative tuberculosis during treatment for aspiration pneumonia in an elderly post-stroke patient with symptomatic epilepsy].

A 90-year-old man with a previous history of brain infarction and diabetes mellitus presented with a gait disturbance. Although brain computed tomography (CT) showed no abnormalities, except for the old infarction, the patient experienced recurrent epileptic seizures. He was therefore admitted to our hospital for a further examination of the seizures. However, upon admission, he also presented with a fever and elevated C-reactive protein levels, indicating systemic inflammation. Based on the presence of bilateral infiltration visible on a chest X-radiograph, the patient was diagnosed with aspiration pneumonia. The administration of 4.5 g of sulbactam and ampicillin did not reduce the inflammation or resolve the abnormal lung findings. Therefore, he was intubated and placed on a ventilator. With the patient under ventilator management, we subsequently performed bronchoscopic alveolar lavage. Elevated neutrophil and lymphocyte counts were noted in the alveolar lavage fluid; therefore, we administered pulse steroid therapy with 500 mg of methylprednisolone. The sputum and alveolar lavage fluid samples collected 13 and 14 days, respectively, after admission were negative for Mycobacterium according to a smear test. In contrast, the cultured sputum samples collected on day 13 were positive for Mycobacterium tuberculosis; polymerase chain reaction testing confirmed the sputum culture results. A postmortem pathological examination of the lungs revealed neutrophilic exudative pneumonia as well as acute fibrinous and organizing pneumonia. Although Ziehl-Neelsen staining demonstrated a large number of positive bacteria, no epithelioid-cell granulomas were observed. M. tuberculosis lesions were also found in the liver, spleen, bones, and adrenal glands, suggesting hematogenous dissemination. Aspiration pneumonia is very common in elderly patients with a history of stroke, and these patients are also at risk of other pulmonary disorders and infections including M. tuberculosis. Prior to administering treatment for aspiration pneumonia, clinicians should consider the potential for other pulmonary infiltration disorders in the differential diagnosis, particularly in elderly post-stroke patients.

[An elderly case of post-gastrectomy aspiration pneumonia following an influenza virus A infection].

A 85-year-old female was admitted to our hospital because of a fever and unconsciousness. Three days prior to admission, she had been diagnosed to have influenza A, and oseltamivir was therefore prescribed. The symptoms due to the influenza infection, including the fever, thereafter rapidly resolved. She regularly took 10 mg zopiclone for insomnia before sleeping. On the day of admission, she was drowsy with fever. Chest radiography showed bilateral massive infiltration of the lungs. Chest CT images revealed multilobar and nodular infiltration on both lungs. She underwent the partial gastrectomy 10 years ago due to the gastrointestinal bleeding. After that, gastro-esophageal reflux syndrome was occurred in the patient. A bronchoscope was easily inserted into the trachea without anesthesia. Aspirated saliva was found in trachea. Based on her post-gastrectomy state, post-gastrectomy aspiration pneumonia was diagnosed. Sulbactam/ampicillin (SBT/ABPC) (6 g) was administered daily, which led to reduced inflammatory responses and lung infiltration. Although influenza itself is sometimes critical for the elderly, careful attention should be paid to subsequent bacterial infections in patients who are at risk for developing aspiration pneumonia.

The Clinical Significance of Anaerobic Coverage in the Antibiotic Treatment of Aspiration Pneumonia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Aspiration pneumonia is increasingly recognised as a common condition. While antibiotics covering anaerobes are thought to be necessary based on old studies reporting anaerobes as causative organisms, recent studies suggest that it may not necessarily benefit prognosis, or even be harmful. Clinical practice should be based on current data reflecting the shift in causative bacteria. The aim of this review was to investigate whether anaerobic coverage is recommended in the treatment of aspiration pneumonia. METHODS: A systematic review and meta-analysis of studies comparing antibiotics with and without anaerobic coverage in the treatment of aspiration pneumonia was performed. The main outcome studied was mortality. Additional outcomes were resolution of pneumonia, development of resistant bacteria, length of stay, recurrence, and adverse effects. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: From an initial 2523 publications, one randomised control trial and two observational studies were selected. The studies did not show a clear benefit of anaerobic coverage. Upon meta-analysis, there was no benefit of anaerobic coverage in improving mortality (Odds ratio 1.23, 95% CI 0.67-2.25). Studies reporting resolution of pneumonia, length of hospital stay, recurrence of pneumonia, and adverse effects showed no benefit of anaerobic coverage. The development of resistant bacteria was not discussed in these studies. CONCLUSION: In the current review, there are insufficient data to assess the necessity of anaerobic coverage in the antibiotic treatment of aspiration pneumonia. Further studies are needed to determine which cases require anaerobic coverage, if any.

The current definition, epidemiology, animal models and a novel therapeutic strategy for aspiration pneumonia.

In the 21st century, aspiration pneumonia (ASP) is very common in older patients, and has a high mortality rate. ASP is diagnosed following confirmation of inflammatory findings in the lungs and overt aspiration or the existence of dysphagia. It is dominant in hospitalized community-acquired pneumonia (CAP), nursing and healthcare-associated pneumonia (NHCAP), and hospital-acquired pneumonia (HAP). The incidence of ASP is increasing every year. The human and experimental animal data revealed that micro-aspiration due to dysphagia during the night is the central mechanism of ASP. Therefore, the precise assessment of swallowing function is the key to diagnose ASP. From a therapeutic point of view, an appropriate administration of antibiotics, as well as a comprehensive approach for dysphagia plays a pivotal role in the prognosis and recovery from ASP. The non-pharmacologic approach, including swallowing rehabilitation and oral care, and a pharmacologic approach including ACE inhibitors and bronchodilators, are essential modalities for treatment and prevention of ASP. The clinical data of NHCAP provides us with a promising treatment strategy for ASP.

Diagnostic utility of C-reactive protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study.

INTRODUCTION: Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) using the plasma level of brain natriuretic peptide (BNP) alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP) in critically ill patients with pulmonary edema. METHODS: This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed. RESULTS: There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439) pg/mL and 119 (62-165) mg/L in ALI/ARDS, and 691 (416-1,194) pg/mL (p < 0.001) and 8 (2-42) mg/L (p < 0.001) in CPE. BNP or CRP alone offered good discriminatory performance (C-statistics 0.831 and 0.887), but the combination offered greater one [C-statistics 0.931 (p < 0.001 versus BNP) (p = 0.030 versus CRP)]. In multiple logistic-regression, BNP and CRP were independent predictors for the diagnosis after adjusting for other variables. CONCLUSIONS: Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.

[A case of tuberculous pleurisy developing contralateral effusion during anti-tuberculosis chemotherapy].

A 55-year-old woman was admitted to our hospital because of chest pain, fever, and right pleural effusion that was exudative and lymphocyte-dominant with a high level of adenosine deaminase (ADA). Since her blood QuantiFERON-TB 3G test (QFT) was positive, she was diagnosed with tuberculous pleurisy. After initiation of anti-tuberculosis chemotherapy with isoniazid, rifampicin, ethambutol, and pyrazinamide, her symptoms improved. Later, liquid culture of the pleural effusion turned positive for Mycobacterium tuberculosis. On the 18th day of treatment, her chest X-ray and computed tomography exhibited pleural effusion in a moderate amount in the left thorax, with subsiding pleural effusion in the right thorax. Thoracocentesis demonstrated that the left thorax effusion was also exudative and lymphocyte-dominant, with elevated QFT response and high ADA concentration, suggesting tuberculous pleurisy. Mycobacterium tuberculosis was detected in the culture of a left pleural biopsy specimen obtained by thoracoscopy. We assumed that the left pleural effusion was due to paradoxical worsening because (1) on admission no effusion or lung parenchymal lesion was detected in the left hemithorax, (2) on the 14th day of treatment she was afebrile without pleural effusion on both sides, and (3) the bacilli were sensitive to the drugs she had been taking regularly. We performed drainage of the left effusion and continued the same anti-tuberculosis drugs, which led to the elimination of all her symptoms and of the pleural effusion on both sides. In conclusion, paradoxical worsening should be included in the differential diagnosis when contralateral pleural effusion is detected during the treatment of tuberculosis.

[Chronic respiratory diseases and atherosclerosis].

Chronic respiratory diseases including chronic obstructive pulmonary disease (COPD) are recently recognized as systemic inflammatory disorders and considered to be a new risk factor for atherosclerosis. The increased serum levels of C-reactive protein, TNF, VEGF, IL-6, and ICAM-1 were known in patients with COPD. The accelerated pulse wave velocity(PWV) and the increased intima-media thickness of internal jugular artery were significantly found in the patients, when compared with the smokers without COPD. The anti-atherogenic agents including statins and ARBs are reported to be effective for the reduced mortality in the patients. The possibility of COPD as a novel atherogenic factor is discussed.

[Comprehensive management for the comorbidities and pulmonary complications in COPD].

Chronic obstructive pulmonary disease (COPD) has been recently recognized not only as inflammatory airway disorders, but also as a chronic systemic inflammatory syndrome. The systemic inflammation causes a variety of abnormalities in the patients. In the end, systemic comorbidities including cardiovascular diseases, endocrine diseases, gastrointestinal diseases and psychological disorders are highly prevalent in patients with COPD. These disorders and those related pulmonary complications have a great impact on quality of life (QOL) and mortality in the patients. For the improving the QOL and the mortality, we have to diagnose these comorbidities early and to treat the complications properly. This review discusses pathogenic mechanisms of the comorbidities and implications for the comprehensive management in patients with COPD.

A case of acute eosinophilic pneumonia following short-term passive smoking: an evidence of very high level of urinary cotinine.

Acute eosinophilic pneumonia (AEP) is characterized by febrile illness, diffuse pulmonary infiltrates with eosinophilia. The pathogenesis is not well understood. We report a case of 22-year-old men who never smoke presented with AEP 2 days after acute passive smoke exposure. He developed acute respiratory failure despite having no history of the disease. Computed tomography of the lung revealed diffuse bilateral pulmonary infiltrates. Lung biopsy specimens revealed marked eosinophil infiltration in the alveolar septa without signs of vasculitis. Two days prior to the disease, he was exposed to cigarette smoke for 2 hours in a closed area. In the absence of other causes, passive smoking may cause lung inflammatory responses. The level of urinary cotinine, which is a biomarker of smoke exposure, was considerably higher (0.198 µg/ml [201 ng/mg Creatinine]) than that in nonsmokers, but never detected following period. This case suggests that short-term passive smoking may cause AEP.

[A case of cold abscess of the chest wall due to thoracic drainage for tuberculous pleuritis].

A 56-year-old man underwent thoracic drainage for two weeks for tuberculous pleuritis. He was put on antituberculosis chemotherapy with INH (400 mg), RFP (450 mg), and EB (750 mg). Two months later, he developed an elastic hard subcutaneous mass in the area of the previous thoracic drainage. The mass was 10 cm in diameter, warm, reddish and painful. Chest computed tomography (CT) revealed localized and encapsulated empyema in the left thoracic space and a subcutaneous abscess with rim enhancement in the left lateral chest wall. Magnetic resonance imaging (MRI) demonstrated a dumbbell abscess in the subcutaneous tissue communicating with the empyema through the chest wall. A needle aspiration of the subcutaneous abscess had acid-fast bacilli smears of 2+ and tested positive by polymerase chain reaction (PCR) for Mycobacterium tuberculosis. Thus, he was diagnosed with a cold abscess of the chest, with the empyema in the thoracic space draining into the chest wall through the cut for artificial drainage. Continuation of the anti-tuberculosis treatment and the drainage of the empyema with repeated aspiration reduced the subcutaneous mass, and the clinical and radiological course was favorable. Both the smear and culture for acid-fast test became negative. After completion of chemotherapy, there has been no disease recurrence.

[Review of pulmonary Mycobacterium xenopi infection cases: 11 cases of our own and 18 other cases reported in Japan].

OBJECTIVE: To investigate clinical features of patients with pulmonary Mycobacterium xenopi infection treated at our hospital. SUBJECTS AND METHODS: We diagnosed 11 cases of M. xenopi infection at Tokyo National Hospital between 2000 and 2008 and recorded the drug susceptibility, patient characteristics, radiographic findings, treatments given and clinical courses. Eighteen other Japanese cases from the literature were discussed along with our findings. RESULTS AND METHODS: The cases of M. xenopi infection at our hospital consisted of 10 men and 1 woman with a mean age (+/- SD) of 55.1 +/- 19.4 years. Among the patients, 10 were smokers, 4 were heavy drinkers, and 6 had sequelae of pulmonary tuberculosis as an underlying disorder. Four patients had chronic obstructive pulmonary disease and 2 had diabetes mellitus, while there were 2 patients who had no underlying disease. All cases had radiographic opacities, predominantly found in the upper lung region, and cavernous lesions. These findings were demonstrated in both lungs in 5 patients, in the right lung only in 5 patients and in the left lung only in 1 patient. Concurrent aspergillosis was observed in 8 patients. The bacterial isolates from 7 cases were tested for drug sensitivity to levofloxacin (LVFX) and were found to be susceptible. M. xenopi disease was treated in 5 cases with INH+RFP+EB, in 2 cases with INH+RFP+Clarithromycin (CAM), and in 1 case with RFP+EB+CAM. Concurrent aspergillosis was treated with itraconazole in 2 cases. One patient underwent surgery for lung cancer. The duration of treatment was 16.4 +/- 12.8 months (range, 4-36 months). The radiographic findings were improved in 4 cases, deteriorated in 2 and unchanged in 5. M. xenopi was eradicated bacteriologically in 6 cases. The combination of radiographic and bacteriological findings indicated improvement in 3 cases, no change in 6 and deterioration in 2. DISCUSSION: The review of our cases disclosed that medical treatment alone was not sufficient in most cases for the control of clinical M. xenopi infection as reported overseas. Although we did not use LVFX for treatment, LVFX might be recommended for the treatment since all isolates tested proved to be susceptible to LVFX.

[Clinical investigation among elderly patients with tuberculosis].

OBJECTIVES: We discussed the factors which may confuse diagnosis and treatment of tuberculosis (TB) in elderly patients, in order to improve the situation. SUBJECTS AND METHODS: 414 patients who were hospitalized for active tuberculosis in Tokyo National Hospital were divided into three groups according to their ages (in years): less than 65, 65 to 74, and greater than 75. The three groups were compared in terms of performance status (PS), serum albumin level (whether over 3 g/dl or not), underlying diseases, symptoms at onset, sputum smear findings for acid-fast bacilli, presence or absence of cavitary lesion, regimen of treatment, adverse reaction to medications, and treatment outcome. RESULT: The older group had significantly poorer PS (3 or 4), lower albumin level, more complications, a larger proportion of non-respiratory to respiratory symptoms, less cavity formation, less likelihood of continuing to take drugs regularly and higher mortality. It is supposed that these characteristics are mostly due to the aging itself. CONCLUSION: Diagnosing and treating active tuberculosis among elderly people is difficult because of nonspecific and thus confusing findings due to other diseases or aging. Delay in diagnosis and start of treatment makes prognosis of their TB poorer. To improve this situation we should keep a high index to TB and make better use of novel diagnostic technologies. For satisfactory treatment that allows maintenance of a high level of activity of daily life, it is necessary to pay more attention to such aspects as nutrition and rehabilitation and to offer appropriate supports.

[Two cases of tuberculosis after treatment of rheumatoid arthritis with infliximab].

We report two cases of tuberculosis (TB) after treatment with infliximab (IFX) for rheumatoid arthritis (RA). The first case, a 69-year-old woman with RA, developed miliary TB with acute respiratory distress syndrome 21 months after initiation of IFX therapy. Sputum samples revealed smears and cultures positive for Mycobacterium tuberculosis and also positive polymerase chain reaction for TB (PCR-TB); in addition urine samples were smear-negative and culture-positive for TB. She was treated with corticosteroid pulse therapy and anti-tuberculosis drugs, and recovered. The second case, a 51-year-old man with RA, had had contact with a tuberculosis patient four years after initiation of IFX therapy. One year later, he developed pulmonary and pleural tuberculosis. Mycobacterium tuberculosis was detected in the bronchial lavage fluid and pleural effusion (smear-negative and culture- and PCR-TB positive). He clinically improved by treatment with anti-tuberculosis drugs. In both cases, the enzyme-linked immunosorbent spot (ELISPOT) tests revealed positive responses although the QuantiFERON TB-2G tests were not positive. We suggest that the ELISPOT test may be useful as a supportive diagnostic tool for tuberculosis in immunocompromised conditions including RA treated with a tumor necrosis factor-alpha (TNF-alpha) inhibitor.