Whole Blood Interferon-γ Release Assay Is Insufficient for the Diagnosis of Sputum Smear Negative Pulmonary Tuberculosis

PURPOSE: We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate. MATERIALS AND METHODS: We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. RESULTS: Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. CONCLUSION: Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.ope

Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate

ABSTRACT: INTRODUCTION: We identified silent liver fibrosis in patients with rheumatoid arthritis (RA) using transient elastography, and investigated medication that correlated with abnormal liver stiffness measurement (LSM) values. METHODS: We consecutively enrolled 105 patients with RA taking methotrexate over 24 weeks with normal liver functions and no history of underlying chronic liver disease. Blood tests were performed, and body mass index and metabolic syndrome were assessed. We checked LSM values, and adopted 5.3 kPa as the cutoff for abnormal LSM values. The cumulative doses of medications including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, prednisolone, meloxicam, and celecoxib were calculated. RESULTS: The median age of patients (20 men and 85 women) was 52.4 years. The median LSM value was 4.7 kPa and 24 (22.9%) patients had abnormal LSM values. Gamma-glutamyltranspeptidase levels and the cumulative doses of leflunomide and prednisolone significantly correlated with LSM values (P<0.05). The cumulative dose of leflunomide, but not methotrexate, was significantly higher in patients with abnormal LSM values than that in patients with normal LSM values (P = 0.008). When RA patients receiving leflunomide plus methotrexate were classified into two groups according to the optimal cutoff cumulative dose of leflunomide (19,170 mg), abnormal LSM values were more frequently identified in patients with high cumulative dose of leflunomide (odds ratio, 12.750; P<0.001). CONCLUSIONS: The cumulative dose of leflunomide was the only independent predictor of abnormal LSM values in patients with RA who had received methotrexate for more than six months.ope

Two Cases of Refractory Thrombocytopenia in Systemic Lupus Erythematosus that Responded to Intravenous Low-Dose Cyclophosphamide

Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/µL. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/µL after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF.ope

Differences in Clinical Manifestations and Outcomes between Adult and Child Patients with Henoch-Schonlein Purpura

We aimed to investigate differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schönlein purpura (HSP), and to analyze the factors associated with poor prognosis for HSP nephritis. This retrospective 10-yr study enrolled 160 patients with HSP who visited Severance Hospital. Purpura was mostly detected in lower extremities, but purpura in upper extremities was more frequently observed in adults than children (41.7% vs 19.3%). Children had a greater frequency of arthralgia (55.4% vs 27.1%), while adults had a greater frequency of diarrhea (20% vs 1.6%). Anemia, elevated C-reactive protein, and level of IgA were more frequently observed in adults (25% vs 7.1%, 65.6% vs 38.4%, 26.3% vs 3.5%). Renal involvement in adults was more severe than in children (79.2% vs 30.4%). Chronic renal failure showed a significant difference in outcomes of HSP between adults (10.4%) and children (1.8%) after a follow up period of an average of 27 months. Furthermore, renal insufficiency at diagnosis was significantly related to the progression to chronic renal failure. Our results showed several differences in the clinical features of HSP between adults and children. Adults with HSP had a higher frequency of renal insufficiency and worse renal outcomes than children. Renal insufficiency at diagnosis might be of predictive value for the progression to chronic renal failure in HSP patients.ope

A Case of Atypical Giant Cell Arteritis Presenting as a Fever of Unknown Origin

Giant cell arteritis (GCA) is a systemic vasculitis predominantly found in individuals of Northern European ancestry over 50 years of age. Typically it presents with new-onset persistent headache, claudication of jaws, and existence of an abnormal temporal artery. However, the diagnosis of GCA and the assessment of its activity remain challenging, especially in patients presenting with a variety of non-specific symptoms and laboratory tests. In those cases, 18F-fluorodeoxy-glucose positron emission tomography (18F-FDG-PET) is useful for the diagnosis of GCA. Recently, the number of foreign patients who visit domestic hospitals for medical care is increasing in Korea. Here-in, we report a Russian patient who was admitted to our hospital with fever of unknown origin (FUO). FUO study was performed to search for infection or malignancy and GCA was suspected by 18F-FDG-PET. The patient was eventually diagnosed with GCA by random temporal artery biopsy.ope

Colchicine Ameliorates High Glucose-Induced ICAM-1 and Fibronectin Expression in Renal Cells via Inhibiting Locally-Produced Angiotensin II.

PURPOSE: A previous study has demonstrated that colchicine abrogated intercellular adhesion molecule (ICAM)-1 and fibronectin expression in renal cells exposed to high glucose media, but the underlying mechanism was not clarified. This study was undertaken to elucidate whether it was attributed to the inhibitory effect of colchicine on locally-produced angiotensin II (AII) under diabetic conditions. METHODS: Rat mesangial cells and NRK-52E cells were cultured in media containing 5.6 mM glucose (NG), NG+10(-7) M AII (NG+AII), or 30 mM glucose (HG) with or without 10(-8) M colchicine (Col) and/or 10(-6) M L-158,809, an AII type 1 receptor blocker (ARB). ICAM-1 and fibronectin mRNA and protein expressions were determined by real-time PCR (RT-PCR) and Western blot, respectively. AII levels in conditioned media were determined by ELISA. RESULTS: AII levels in conditioned media were significantly higher in HG-stimulated mesangial cells and NRK-52E cells compared to NG cells (p<0.05). ICAM-1 and fibronectin mRNA and protein expression were significantly increased in renal cells exposed to HG media (p<0.05 or p<0.01), and these increases were significantly ameliorated by colchicine or ARB treatment (p<0.05). Colchicine and ARB also significantly attenuated AII-induced ICAM-1 and fibronectin expression (p<0.05). However, there was no additive inhibitory effect of colchicine and ARB on the increases in ICAM-1 and fibronectin expression. CONCLUSION: Colchicine abrogated increased ICAM-1 and fibronectin expression in renal cells under diabetic conditions, which is partly mediated by inhibiting HG-induced locally-produced AII. These findings provide a new renoprotective mechanism of colchicine in diabetic nephropathy in addition to its impact on leukocyte functionsope

A Case of Candida Parapsilosis Infectious Arthritis in a Patient with Enteropathic Arthritis and Ulcerative Colitis

Infectious arthritis is an important medical emergency with high morbidity. The most frequent causative organism of infectious arthritis is Staphylococcus aureus, and Candida is an uncommon pathogen. Candida arthritis has been reported to occur in seriously ill or immunocompromised patients and neonates. We report the first case of C. parapsilosis arthritis in a patient with ulcerative colitis. A 52-year-old woman was diagnosed with ulcerative colitis 1 year previously and took balsalazide. Pain and swelling in the right knee joint developed 6 months after diagnosis. She was diagnosed with enteropathic arthritis associated with ulcerative colitis and took methotrexate, sulfasalazine, and prednisolone for 3 months, but the symptoms did not improve. We finally diagnosed her with infectious C. parapsilosis arthritis by culturing the synovial fluid. The patient received amphotericin B for 6 weeks and underwent arthroscopic synovectomy. She finally experienced improvement of inflammation in the right knee jointope

Comorbidities in obstructive lung disease in Korea: data from the fourth and fifth Korean National Health and Nutrition Examination Survey

BACKGROUND: Comorbidities can occur frequently in patients with chronic obstructive pulmonary disease (COPD) and can influence mortality and morbidity independently. It is increasingly recognized that many patients with COPD have comorbidities that have a major impact on their quality of life and survival. Therefore, we investigated the prevalence of comorbidities in Korean COPD populations. METHODS: We used data obtained in the 6 years of the fourth and fifth Korean National Health and Nutrition Examination Survey (KNHANES) IV and V. Among 50,405 subjects, 16,151 subjects aged ≥40 years who performed spirometry adequately were included in this study. Airway obstruction was defined as forced expiratory volume in 1 second/forced vital capacity <0.7, and the Global Initiative For Chronic Obstructive Lung Disease stage was used to evaluate the severity of airway obstruction. Statistical analyses were performed using SAS 9.2. RESULTS: Among the 16,151 subjects (43.2% male, 56.8% female; mean age: 57.1 years for men and 57.2 years for women), 13.1% had obstructive lung function; 11.3%, restrictive lung function; and 75.6%, normal lung function. Among individuals with obstructive lung function, 45.3%, 49.4%, and 5.3% had mild, moderate, and severe and very severe airflow limitation. The prevalence of hypertension, diabetes mellitus (DM), underweight, and hypertriglyceridemia was higher in the obstructive lung function group than in the normal lung function group (49.6% vs 35.2%; 16.8% vs 10.5%; 3.3% vs 1.3%; 19.7% vs 17.0%). According to the severity of airway obstruction, hypertension and underweight were more common as severity increased, although the prevalence of DM and hypertriglyceridemia was lower in subjects with severe airway obstruction. The prevalence of hypercholesterolemia, overweight, and osteoarthritis was lower in the obstructive lung function group, especially in the severe airway obstruction groups. CONCLUSIONS: Overall, our analysis is similar to research that was conducted earlier. Our study showed that hypertension and underweight are common comorbidities in COPD patients, and are higher as the severity of airflow obstruction increased in both men and women. DM, hypertriglyceridemia, and low high-density lipoprotein cholesterol are more common in subjects with airway obstruction, although their incidence is lower in the severe group.ope

Typical 18-FDG-PET/CT Findings of Polymyalgia Rheumatica: A Case Report

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic condition characterized by generalized pain and morning stiffness in the shoulders, hip girdle, and neck. Since the pathogenesis of PMR is still uncertain, the diagnosis of PMR depends on clinical features. There have been several studies regarding radiological tools for the diagnosis of PMR. Recent studies using 18-FDG-PET showed bursitis, synovitis, uptake in the spinous process and asymptomatic large-vessel vasculitis in PMR patients. However, there was no report on the efficacy of 18-FDG-PET for diagnosis of PMR in Korea. Here, we are first reporting a case of a Korean patient with PMR, who had radiological findings including bursitis, synovitis, uptake in the spinous process and asymptomatic large-vessel vasculitis on 18-FDG-PET/CT.ope

Recurrent Acute Pericarditis Induced by 5-aminosalicylates in a Patient with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammation of the intestines. IBD treatment may require anti-inflammatory agents such as sulfasalazine or 5-aminosalicylate (5-ASA) and immunomodulators to control the symptoms. However, these agents have a variety of common adverse effects such as nausea, vomiting, skin rash, leukopenia, thrombocytopenia, and infections. Moreover, rare side effects such as nephrotic syndrome, pneumonitis, and pericarditis can occur. A 21-year-old male was admitted to the hospital due to acute chest pain, fever, and sweating. The patient had a history of Crohn's disease and had been taking mesalazine for 3 weeks. Chest x-ray, echocardiography, and clinical manifestations revealed that the patient had acute pericarditis. However, we did not recognize the relationship between these findings and 5-ASA at that time. Two years later, the patient took 5-ASA again, and similar symptoms occurred, which led us to confirm that he suffered from pericarditis induced by this drug. We report a case of acute recurrent pericarditis that developed after taking 5-ASA for IBD treatment with a review of the literature.ope