**6. References**

240 Rheumatoid Arthritis – Etiology, Consequences and Co-Morbidities

Further, as in the non-RA study cohorts, the definitions and criteria of both MetS and CVD varied. In one study, MetS, as defined by WHO criteria, was a better predictor of coronary calcification than NCEP-ATPIII criteria (Pandya et al., 2006). Though coronary calcification detection by electron beam computer tomography is a more sensitive means of detecting atherosclerosis than clinical diagnoses, the association with MetS achieved an odds ratio of 2.02, (95% CI: 1.03-3.97, p=0.04.), less than the 2.91 (95% CI: 1.95-4.34, p<0.001) in our cohort. In that study (Pandya et al, 2006), almost 50% of the patients had longstanding disease (median = 20 years), were younger than our cohort (median 59 years), and were majority female. The almost three-fold risk for CVD in our cohort was independent of anti-rheumatic treatment, smoking, age or gender. There was, however, a trend to increased risk with increasing age and DMARD therapy alone, the latter perhaps related to channeling bias or

Given the notable comorbidity in our study population, and the historically age-matched prevalence of MetS in 44% of the US NHANES III population aged 65 years, our prevalence of 28% was unexpected. The limited data from other disease cohorts involving U.S. veteran populations report higher frequencies on the order of 50% (Meyer et al., 2006; Pandya et al., 2006). However, our results are similar to another US RA cohort, 40% of whom were male. The prevalence of MetS was approximately 26% as defined by NCEP-ATPIII criteria, and was almost half that of controls (Rodriguez-Pla et al., 2007). In that study, the difference in prevalence between RA and controls could not be explained by differences in physical activity. In contrast, in 200 similarly aged but primarily female RA patients, MetS occurred in 44% of patients at a similar rate to the age- and sex- matched controls, but used ATPIII criteria (National Cholesterol Education Program, 2001). Of the 53 men in the study, approximately 30% with MetS had coronary disease (p=0.02). Not only do differences in MetS classifications make comparisons amongst cohorts difficult, but the disparate muscle loss with fat retention that occurs in RA patients, affects BMI assessments. Rheumatoid cachexia, which is present in most (two-thirds) RA patients, doesn't merely involve fat "retention"; there is exacerbated fat gain. When body composition is assessed (i.e. % body fat), up to 80% of RA patients satisfy BMI criteria for obesity i.e. ≥27% for males, and ≥38% for females (Baumgartner et al., 1999). This prevalence of obesity in RA is not reflected by BMI because of the concomitant loss of muscle. Thus, for individuals with the same BMI, an RA patient will have, on average, 4.3% higher % body fat than a healthy, age- and sexmatched subject. Therefore, in RA patients, a BMI greater than 28kg/m2 has been proposed to define obesity, and may therefore lead to higher, and more accurate, estimations of MetS

Our modified definition of MetS based on NCEP-ATPIII criteria though highly specific, may have lacked sensitivity by excluding otherwise eligible patients with discordance between waist-to-hip ratio and BMI, or those who had not received pharmacological treatment for component diseases. We recognize therefore that our prevalence estimate may have trended towards the conservative and underestimated the true impact of MetS in this population; an important concern given the strong association between MetS and CVD. However, of note is the rigor with which VA patients are screened and treated for diabetes mellitus, hypertension and hyperlipidemia based on adherence to select process indicators (Steven, 2004). Therefore it is likely that our use of medication is a reasonable surrogate for the select comorbidities of MetS. Surprisingly, our study found no significant risk of any of the individual components of MetS, and may indicate that traditional risk factors do not impart

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**14** 

*Japan* 

**Nontuberculous Mycobacterium** 

Nontuberculous mycobacteria (NTM) are a large, diverse group of ubiquitous environmental organisms found in tap water, soil, dust, plants, animals, and food. NTM infection can cause various diseases, such as pulmonary disease (PD), which are most frequently observed in immunocompromised individuals. Diseases associated with NTM are particularly severe in those receiving tumor necrosis factor (TNF)-alpha (α) blockers, which predispose individuals to NTM infection. Experts generally agree that patients with active NTM disease should receive TNF-α blockers only if they are also receiving adequate therapy for NTM disease. On the other hand, the Japanese College of Rheumatology recommends that TNF-α blockers not be used in patients with active NTM infection,

Bronchiectasis is one of the most frequent manifestations of NTM infection, not only in NTM-PD patients, but also in rheumatoid arthritis (RA) patients. It is difficult to distinguish the bronchiectasis associated with NTM-PD from that with RA on chest radiography or high-resolution computed tomography (HRCT). Due to the ease of NTM contamination from the environment, the diagnosis of NTM-PD is extremely difficult. The most recent American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) guidelines recommend diagnosing NTM-PD via a combination of clinical, radiographic, bacteriologic (two positive sputum cultures, or one positive bronchoalveolar lavage (BAL) culture or transbronchial biopsy), and histological criteria. In NTM-PD patients receiving TNF-α blockers, *Mycobacterium avium* was the most common etiologic organism, accounting for half of all NTM isolates (Winthrop et al., 2009). Recently, Kitada et al. (2008) established an enzyme immunoassay (EIA) for the serological diagnosis of *M. avium*-complex (MAC)- PD by examining the level of serum IgA antibody to the glycopeptidolipid (GPL) core, which is a MAC-specific antigen. Unlike bronchoscopy and sputum culture examinations,

In this chapter, we discuss the characteristics of NTM, relationship between NTM infections and RA patients, particularly those receiving TNF-α blockers, and diagnosis of MAC-PD

because NTM is resistant to most antimycobacterial drugs.

EIA kits are less invasive and provide more rapid diagnosis of MAC-PD.

with RA patients using the recently developed EIA kit.

**1. Introduction** 

**Infections in Rheumatoid** 

Maiko Watanabe1 and Shogo Banno2

**Arthritis Patients** 

*1Nagoya City University 2Aichi Medical University* 

