Premature death in patients with RA is often due to ischaemic heart disease (IHD). There are many potential factors that may contribute towards the increased incidence of IHD in RA, such as treatment with non-steroidal anti- inflammatory drugs (NSAIDs) and corticosteroids, hypertension (Panoulas et al., 2008), dyslipidaemia (van Halm et al., 2007) and the metabolic
syndrome (da Cunha et al., 2012). Although shared risk factors for RA and IHD, such as smoking, may partially explain the association of these two conditions, persistent inflammation in RA is thought to accelerate the development of coronary artery disease. Levels of inflammatory markers have been associated with cardiovascular events in RA; however, the exact mechanisms linking inflammation and accelerated atherosclerosis are incompletely understood (reviewed by Kerola et al., 2012).
There is evidence that coronary micro-vascular dysfunction, which has been shown to precede the onset of atherosclerotic cardiovascular disease, is present in asymptomatic patients with RA. For example, coronary flow reserve (a ratio of maximal coronary blood flow to diastolic coronary blood flow where values ≥2 are considered normal) measured by transthoracic Doppler echocardiography was lower in 22 RA patients compared to 52 healthy controls (2.36 compared to 2.71, p=0.002) (Ciftci et al., 2008). In this study, the group of RA patients were similar to the control group in terms of proportion of males and means of age, body mass index (BMI), blood pressure, and blood lipids, homocysteine and insulin levels and all
participants were non smokers at the time of the study (defined as current non-smoking); however, numbers of patients with a previous history of smoking were not mentioned in the paper. Further work has shown that asymptomatic patients with RA and carotid plaques identified on ultrasound were more likely than control subjects with similar traditional cardiovascular risk factors to have coronary arterial disease identified on dopamine stress echocardiography in small study involving 18 patients with RA (Toutouzas et al., 2013). Of the 8 RA patients who then had coronary angiography,
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significant obstructive lesions that explained the ischaemic findings were identified in only 2 cases, compared to 8 of 11 control subjects. The authors of this hypothesis- generating study proposed that in patients with RA, coronary ischaemia may be due to causes other than obstructive coronary vessel disease. Although these studies are small, the evidence presented here suggests that further investigations into coronary microvascular changes in RA are warranted in order to further investigate the aetiology of cardiovascular disease in RA.
1.5.2.4 Neurological
Commonly observed neurological associations of RA result from neurological compression due to synovial inflammation. Carpal tunnel syndrome, due to compression of the median nerve at the wrist, and ulnar nerve entrapment at the elbow are two common examples. A well
recognised complication of RA is atlanto-axial subluxation, which occurs due to rheumatoid involvement of the joint between the first 2 cervical vertebrae and the surrounding structures leading to instability and subsequent
neurological impingement (Robinson, 1966). There may also be compression of the vertebral artery, leading to symptoms that include
vertigo, confusion and syncope (Jones and Kaufmann, 1976). Mononeuritis multiplex describes sensory and motor impairment of one or more peripheral nerves resulting from vasculitis of the vasa nervorum. Its onset is often rapid, affecting one distal nerve initially, but further neuropathy may develop if treatment is delayed or unsuccessful. Central nervous system vasculitis has been described in RA, but is uncommon (Gobernado et al., 1984).
1.5.2.5 Ocular
Rheumatoid disease may be associated with eye conditions, causing redness, pain, impaired vision and sometimes blindness. One of the more common ocular manifestations of RA is dryness of the eyes, or kerato- conjunctivitis sicca (KCS), which occurs due to impaired lacrimal gland function in secondary Sjogren’s syndrome. Occasionally occurring in conjunction with KCS, peripheral ulcerative keratitis (PUK) is an ocular manifestation of rheumatoid vasculitis that requires prompt immune-
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In PUK, there is vasculitis affecting the peripheral cornea (the avascular centre of this structure is unaffected) manifesting as inflammation of the episclera, conjunctiva and sclera, which can lead to perforation of the cornea (corneal melt) (reviewed by Messmer and Foster, 1999). Due to its
association with systemic vasculitis, PUK is linked to high mortality and emphasis has been placed upon prompt and aggressive treatment for patients with this condition (Foster et al., 1984).
A painful red eye in a patient with RA may be due to inflammation of the sclera (scleritis) or episclera (episcleritis). Episcleritis is uncomfortable, but usually self limiting with no long-term sequelae. Conversely, scleritis can be associated with significant morbidity. Different types of scleritis have been described, including diffuse anterior, nodular anterior, necrotising anterior and posterior (which can also be further categorised into nodular, diffuse and necrotising). Of these, the diffuse anterior type is most common and usually responds well to treatment, but can cause visual loss. Posterior types are associated with significant risk of visual impairment and require prompt treatment (McCluskey et al., 1999). Necrotising anterior scleritis can be further categorised into two types, the “inflammatory” variant presents with severe pain that improves with treatment, whereas the rarer variant,
scleromalacia perforans, is usually painless. Scleromalacia perforans may present as an area of blue discolouration where underlying choroid becomes visible through thinned sclera and perforation has been reported in some cases (Stone and Dana).