Rheumatoid Arthritis beyond joints Dr. Ravi Basyal, Prof. Uma Kumar Rheumatology Division, Department of Medicine AIIMS, New Delhi If a patient has rheumatoid arthritis, focusremains on his joints. With advancing therapeutic options, remission is not a distant dream; mostof the patients with RA can be treated effectively. Nevertheless, itis important to recognize that RA is a systemic disease, and the inflammation that affects the joints can also target other parts of the body. Extra-articular manifestations (EAM) of RA are present in approximately 40% of the patients, and are associated with significant morbidity and increased mortality [Turesson C et al, 2003] Beyond musculoskeletal system, RA can affect the cardiovascular system, respiratory system, nervous system, skin, eyes, salivary glands, and bone marrow. Therefore.a patient with RA should be evaluated for systemic disease manifestations, including comorbidities, psychological aspects, and health related quality of life (HAQOL) impairments, even though joint symptoms have been controlled, Cardiovascular disease: Cardiovascular risk is doubled in RA patients compared with the general population [Peters MJ et al 2010}, and it accounts for about 50% of the total death in these patients [Avina- Zubieta JA et al, 2008].Cardiac involvements in RA include pericarditis, valvulitis, myocarditis, and an increased prevalence of atherosclerotic coronary artery disease. Studies have shown selected cardiovascular risk factors like insulin resistance, altered fat distribution, cigarette smoking, and physical inactivity are more commonly associated with RA. Epidemiological data suggest that the risk of MI in RA patients isequal to that in patients with diabetes [Lindhardsen J et al, 2011], and observational studies show similar subclinical atherosclerotic activity in the 2 disorders [Stamatelopoulos KS et al, 2011]. While acute MI risk increased by 38% in RA population compared to general population [Chung WS et al, 2013]. Importantly, Framingham Risk Score(FRS), may underestimate the non-traditional risk factors so EULAR recommends multiplying FRS scdte by 1.5 if the disease duration is>10 years, seropositive, or has EAM [M J L Peters, EULAR, 2009]. A meta-analysis on 24 studies showed there was a 50% increased risk of CVD death in patients with RA. Inflammation seems to play a key role in all stages of atherosclerosis: from endothelial dysfunction to plaque rupture and thrombosis [Libby et al, 2006]. The extent of inflammation in RA has been linked to an increased risk of cardiovascular mortality resulting from accelerated atherogenesis [Gonzalez-Gay et al, 2005]. Multiple studies have shown that patients with RA have a higher mean carotid intimal thickness (mm) compared with normal control subjects, and the presence of subclinical atherosclerosis is significantly more among RA patients ~ Hypertension (HT) contributes significantly to the development ofCVD. Pulmonary Disease: Lung disease, either as an EAM of the disease, related to the drug therapy for RA, or related to comorbid conditions, is the second commonest cause of mortality. All areas of the lung including the pleura, airways, parenchyma, and vasculature may be involved, with interstitial and pleural disease and infection being the most common problems. The most frequent patferns of interstitial lung disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumionia (NSIP)ILD is the only complication of RA reported to be increasing in prevalence and it has been shown to account for ~6% of all RA deaths. Moreover, RA patients who developed ILD had a 3-fold increase in mortality compared with RA patients without ILD. Anti-CCP antibody titers are single most strongly associated predictor of RA-ILD, while male gender, age at onset, smoking and RF were all independently associated with RA-ILD. Osteoporosis: RA is associated with systemic bone loss and increased fracture risk. The risk of hip fracture increased by 2.0-fold and vertebral fracture by 2.4-fold relative to non-RA controls, and increase risk of fracture was associated with disease duration, low body mass index, postmenopausal women and use of oral glucocorticoids [Van Staaet al, 2006]. Vitamin D deficiency has been linked to increased risk and severity of RA [Cutolo M et al, 2013]. Given the risk of osteoporosis and its potential adverse impact on outcomes, itis important for at-risk RA patients to undergo regular monitoring of bone mineral density and to receive calcium and vitamin D supplementation and preventive therapy as needed. Malignaney:In Meta-analysis by Smitten et al in 2007the risk of lymphoma was increased approximately twofold, while patients with RA were 43% more likely to develop lung cancer compared with patients without RAafteradjustments for age, gender, race, and tobacco and asbestos exposure. Eyeinvolvement in a form of keratoconjunctivitissicca, occuring in 10-20% of patients, while episcleritisd&scleritis occur in less than 5% of RA patients[Smith JR etal,2007]. Other abnormalities: Most patients with active RA have a mild anemia of chronic disease. Rheumatoid nodules are the most common cutaneous manifestation of RA. Lower extremity ulcers occurred in 1% of. patients yearly following the diagnosis of RA, and when associated with vasculitis may result in serious complications. Depression is estimated to occur in 13-20% of patientswhile Cognitive impairment was reported in 30% of RA patients compared with healthy controls [Appenzeller S. et al, 2004). There is aneed to see beyond the joint while evaluating and managing patients of RA.