- Email: [email protected]
Extra-articular features of rheumatoid arthritis
Rheumatoid arthritis
Extra-articular features of rheumatoid arthritis
What’s new? • Evidence of increased mortality from cardiovascular and respiratory involvement in RA has driven the need to identify and treat risk factors for premature death
Neil McKay Clive A Kelly
• The anti-TNF agents can benefit patients by reducing the inflammatory burden but may place others at risk by precipitating cardiac decompensation or accelerating interstitial lung disease
Abstract and is now largely the result of an excess of cardiovascular deaths. The reasons for this are complex, but there is evidence for a link with active, uncontrolled articular disease and this is discussed later in this article. The risk of malignancy is also increased in
This article summarizes the organ-specific features of rheumatoid arthritis which contribute to the high non-articular morbidity and mortality seen in this disorder. Virtually every organ can be affected by the disease and compelling evidence exists to relate active and severe rheumatoid arthritis (RA) to a marked increase in the prevalence of both cardiovascular and cerebrovascular disease. Non-specific features such as fatigue and weight loss are also seen with greater frequency in undertreated RA. Early effective management of the condition with disease modifying therapy can reduce the frequency and severity of systemic features.
Specific organ involvement in rheumatoid arthritis Haematological • Normochromic anaemia (30–50% of patients) • Microcytic anaemia (10–20%) • Large granular lymphocytosis (< 1%) • Lymphadenopathy (20%)
Keywords rheumatoid arthritis; mortality; systemic disease; vascular disease
Rheumatoid arthritis (RA) is a systemic disorder that may affect almost any organ system. Systemic features may dominate articular manifestations in some individuals and may predate joint disease. Men are more likely to suffer severe systemic disease and have greater mortality from such complications. Systemic manifestations may be divided into general and organ-specific (Table 1); the former often occur early in the disease, whereas the prevalence of the latter is greater in patients with severe articular disease of long duration. Specific extra-articular features are common, though their incidence may now be decreasing with more aggressive treatment of early disease.
Connective tissue • Tenosynovitis • Rheumatoid nodules (20%)
Non-organ-specific features
Cardiac • Mitral regurgitation (5–10%) • Pericardial effusion (5–30%) • Constrictive pericarditis (< 1%)
Cutaneous • Livedo reticularis • Palmar erythema • Pyoderma gangrenosum (< 1%) Pulmonary • Airways obstruction (35–50%) • Pleural effusion (5%) • Interstitial lung disease (2–20%)
Nonspecific features are seen in most patients with active RA and include lethargy, depression and malaise. Fever is occasionally an early feature, particularly in systemic disease. Weight loss may be a marked feature and is often associated with loss of appetite, particularly in the elderly. The resulting weakness may be exacerbated by myopathy and joint pain on active movement. Specific organ involvement may also contribute to fatigue. Mortality in RA is increased, with a slight mean reduction in life expectancy, though this effect has diminished in recent years
Vascular • Medium vessel vasculitis (< 1%) • Digital vasculitis (5–10%) • Raynaud’s phenomenon (10%) Neurological • Cervical myelopathy (2–10%) • Entrapment neuropathies (50%) • Mononeuritis multiplex • Peripheral neuropathy
Neil McKay MRCP is a Specialist Registrar in Rheumatology in the Northern Deanery, Newcastle University, Newcastle upon Tyne, UK. Conflicts of interest: none declared.
Ocular • Keratoconjunctivitis sicca (40%) • Episcleritis and scleritis (1–5%)
Clive A Kelly FRCP is Consultant Physician and Rheumatologist at the Queen Elizabeth Hospital, Gateshead, UK. Conflicts of interest: none declared.
MEDICINE 34:10
Table 1
383
© 2006 Published by Elsevier Ltd.
Rheumatoid arthritis
RA; this relates principally to haematological disorders. The incidence of some solid organ tumours (e.g. adenocarcinoma of the lung) is also increased. Associations between malignancy and rheumatic diseases are discussed in MEDICINE 34:9. Reduced bone density is now recognized as a complication of RA and may lead to an increased risk of fracture. Associations with disease activity, severity and corticosteroid use have all been described. Amyloidosis is a common post-mortem finding in patients with long-standing disease but is seldom symptomatic. However, it may contribute to renal or hepatic failure in a few patients.
g angrenosum may evolve from an apparently superficial dark, tender area over the lower legs. These ulcers have the appearance of an infective lesion once established and may be difficult to heal, particularly in the presence of reduced vascularity. They may respond to corticosteroids and immunosuppressive drugs. Pulmonary involvement is more apparent on physiological and radiological assessment than might be predicted on clinical grounds. Bronchial obstruction seldom affects the major airways but is common in smaller bronchi; wheeze and exertional dyspnoea are frequent features. The severity of involvement is related to both the degree of articular disease and the number of pack-years of tobacco consumption. Bronchiolitis obliterans is very rare and is associated with penicillamine therapy in some cases. Clinically significant pleural effusions are less common than previously reported and tend to occur in early active RA, sometimes as part of generalized serositis. Empyema must be excluded in pyrexial patients by aspiration and fluid culture. Interstitial lung involvement is associated with seropositivity and bibasal lung crackles, usually without finger clubbing. Chest radiography is less sensitive than high-resolution CT, which is the investigation of choice (Figure 1). Recent data suggest that mortality related to this complication may be higher than previously appreciated and, while a response to immunosuppressive therapy has been described, there is some evidence that anti-TNF agents may exacerbate pulmonary fibrosis. The prognosis is generally better than that of cryptogenic fibrosing alveolitis, but a significant number of patients later develop lung adenocarcinoma. Cardiac – cardiac muscle involvement is less common. Myositis and coronary vasculitis are now seen only rarely, though conduction defects from rheumatoid nodules or secondary amyloid are still occasionally reported. More common features include mitral valve disease with regurgitation evident on echocardiography in 6% of patients. Pericardial disease is also common and pericarditis is often complicated by pericardial effusion in early active RA. A few patients develop breathlessness as a result of progressive pericardial constriction or tamponade, both of which may present with right heart failure from right ventricular compression. Aspiration of pericardial fluid under echocardiographic control will temporarily relieve tamponade, but a recurrence or the development of pericardial constriction usually requires formal surgical pericardial fenestration into the left pleural space. Vascular – vasculitis may affect small or medium-sized blood vessels in RA. Small vessel disease tends to produce nail-fold infarcts; these are less common than they used to be and are often asymptomatic in themselves, but may herald other systemic manifestations. Mononeuritis can result from small vessel disease in peripheral nerves and may present suddenly (e.g. peroneal nerve palsy). Involvement of larger vessels produces various clinical features including infarction of digits and necrotic ulceration, particularly over the shins and ankles. Healing may be slow and can be further delayed by incompetent venous drainage.
Organ-specific and system-specific features Sjögren’s syndrome – several syndromes may occur in conjunction with RA. The most common is Sjögren’s syndrome, which occurs in up to 40% of patients. Clinical features include dryness or discomfort in the eyes, nose and mouth as a result of generalized exocrinopathy; this process may also affect other secretory organ function. Lethargy appears more intense in these patients and there is an association with later lymphoma, though this risk is considerably less than that in patients with primary Sjögren’s syndrome. Felty’s syndrome is much less common (1%). It is characterized by severe RA, splenomegaly and neutropenia. Such individuals are at greater risk of systemic infection and often develop chronic leg ulcers. Use of disease-modifying drugs can be problematic in such patients and the articular prognosis is often poor. Haematological – anaemia occurs at some stage in more than one-half of all patients. It is most often normochromic and normocytic, and often correlates with the severity of articular disease (anaemia of chronic disease). Microcytic anaemia is also common and is usually associated with iron deficiency, sometimes as a consequence of excessive gastrointestinal bleeding caused by non-steroidal anti-inflammatory drugs. Serum ferritin can be useful in distinguishing these causes of anaemia; it may be low in iron deficiency and high when the cause is disease activity. Macrocytic anaemia is less common and may result from malabsorption, associated thyroid failure or drug-induced haemolysis. It may also occur in patients receiving sulphasalazine or methotrexate therapy. Lymphadenopathy, particularly in the neck or axillary area, is found in up to 20% of patients with early RA. Histology shows lymphoid hyperplasia and is sometimes necessary to exclude lymphoma. Connective tissue involvement is common and often includes inflammation of the tendon sheaths as an early feature in the hands and wrists. Rheumatoid nodules occur in up to 20% of patients; classically, they affect the elbow and other extensor surfaces subjected to pressure. They are associated with seropositivity and poor articular prognosis, and can affect various internal organs including the heart, lung and spinal cord. They have been reported to increase in number and size in patients taking methotrexate. Cutaneous – palmar erythema is often found in patients with early active RA but diminishes with time. Livedo reticularis is an evanescent cutaneous feature found mainly over the anterior thighs, in which the superficial venous network is visible. It is found mainly in women with vasospastic features such as Raynaud’s phenomenon. Less commonly, pyoderma
MEDICINE 34:10
Endothelial dysfunction The cardiovascular system per se is the newest extra-articular manifestation. Population data from RA and controls suggest not 384
© 2006 Published by Elsevier Ltd.
Rheumatoid arthritis
• inflammatory/immunological (e.g. pro-inflammatory cytokines) • traditional risk factors (e.g. obesity). The burden of inflammation in RA is undoubtedly linked and may act synergistically or independently of traditional risk factors. It is widely accepted that atherosclerosis is a chronic inflammatory process with immune activation initiating acute coronary syndromes. The circulating level of the acute phase reactant C-reactive protein (CRP) predicts outcome in this situation. Activated immune cells in the arterial plaque produce inflammatory cytokines including proteases which thin and rupture the fibrous cap inducing an acute coronary syndrome. CRP reflects the degree of cytokine activation and in RA patients correlates with joint synovial inflammation. Could the overall burden of active inflammation contribute to acute coronary syndromes? In RA, CRP levels at baseline predict CVD death independent of all other variables. The cumulative ‘area under the curve’ of CRP in RA patients not known to have CVD correlates with measures of atherosclerosis (aortic arterial stiffness and carotid intima media thickness). Vascular pathology also takes the form of angiogenesis in the synovium which is essential for perpetuating the joint inflammation. Vascular endothelial growth factor correlates with disease activity in RA and synovium vascularity. Similarly, angiogenesis inhibitors are down regulated in RA. This abnormal endothelial homeostasis is potentially reversible with treatment. Endothelial dysfunction characterizes early atherosclerosis and early RA. It can be reversed by tumour necrosis factor alpha (TNFα) blockade in RA, psoriatic arthritis, and certain systemic vasculitides. Furthermore a case comparison cohort study investigated the risk of developing a first CV event in TNFα blockade treated and control RA patients finding the risk halved with treatment. Prospective data on CV events are awaited. However, the presence of established heart failure with an ejection fraction of below 20% is a contraindication to the use of anti-TNF agents because of the risk of precipitating cardiac decompensation. The risk of CVD in RA is present early and not related to disease duration, allowing speculation on the association of acute rises of inflammatory cytokines in RA driven by synovial inflammation and the onset of CV events. However, the drugs used in arthritis (traditional and newer non-steroidal anti-inflammatory drugs, steroids, and disease modifying drugs) can also be implicated in contributing to CVD (e.g. steroids may benefit or worsen CVD mortality). Certainly, immunosuppresive treatment (e.g. methotrexate) reduces mortality in RA and anecdotally reverses endothelial dysfunction causing myocardial ischaemia.1 Consensus is emerging that RA patients require early immunosuppression, and both primary and secondary CVD prevention strategies in the manner offered to diabetics and other high risk cardiovascular groups. Neurological – cervical myelopathy is the most common rheumatological cause of death in RA. The presence of long tract signs and urinary symptoms indicates established cord compression, though early diagnosis should be sought using cervical MRI in patients with symptoms or signs of increased muscle tone. Compression may be due to atlanto-axial subluxation with or without odontoid erosion, but subaxial disease is now more common. Surgery can stabilize neurological dysfunction at either site. Careful radiological assessment of the neck prior to elective
Figure 1 a A high resolution computed tomogram of the lower chest showing bibasal pulmonary fibrosis in breathless RA patient with a normal chest X ray (b).
only a higher prevalence of cardiovascular disease (CVD) but also higher heart failure rates, higher case fatality, less hospitalization, and less percutaneous intervention. This is hypothesized to be a sub-clinical accelerated atherosclerosis with silent or atypical ischaemic symptoms and is not a myositis or clinically evident coronary vasculitis. Smoking increases the risk of developing RA and is more prevalent in severe RA. Yet controlling for smoking (both pre and post diagnosis), in addition to all other traditional risk factors does not abolish the CVD risk. Perhaps the prevalence of unidentified traditional risk factors is higher in RA and certainly undertreatment and underdiagnosis of hypertension is recognized. The factors contributing to CVD death in RA can be classified as: • disease severity or treatment specific factors (e.g. rheumatoid factor, steroids)
MEDICINE 34:10
385
© 2006 Published by Elsevier Ltd.
Rheumatoid arthritis
surgical or endoscopic procedures is important in all patients with established RA. Carpal tunnel syndrome is a common early feature of RA and may occur in up to 50% of patients. Typical clinical features include painful paraesthesiae and poor hand grip. Other nerves are occasionally damaged by local factors (e.g. ulnar nerve at the elbow, tarsal nerve in the ankle). Ocular – eye involvement can include keratoconjunctivitis sicca, which is common, and episcleritis, which is rare. Patients with aggressive RA can develop scleritis, but progression to scleromalacia perforans is now seldom seen. Urgent opthalmological assessment is necessary in any patient with suspected scleral involvement and treatment usually requires steroid and other immunosuppressive therapy. ◆
MEDICINE 34:10
Reference 1 Raza K, Banks M, Kitas G. Reversing myocardial microvascular disease in a patient with rheumatoid arthritis. J Rheumatol 2005; 32: 4.
Further reading Dieppe P A. Extra-articular features of rheumatoid arthritis. In: Dieppe P A, Bacon P A, Bamji A N, Watt I, eds. Atlas of clinical rheumatology. New York: Gower, 1986. (A useful review of common clinical systemic features of RA.) Kelly C A. Lung disease in rheumatic disorders. In: Kelly C A, ed. Clinical rheumatology. London: Baillière-Tindall, 1993. (A review of pulmonary aspects of lung disease in RA.)
386
© 2006 Published by Elsevier Ltd.
Extra-articular features of rheumatoid arthritis
What’s new? • Evidence of increased mortality from cardiovascular and respiratory involvement in RA has driven the need to identify and treat risk factors for premature death
Neil McKay Clive A Kelly
• The anti-TNF agents can benefit patients by reducing the inflammatory burden but may place others at risk by precipitating cardiac decompensation or accelerating interstitial lung disease
Abstract and is now largely the result of an excess of cardiovascular deaths. The reasons for this are complex, but there is evidence for a link with active, uncontrolled articular disease and this is discussed later in this article. The risk of malignancy is also increased in
This article summarizes the organ-specific features of rheumatoid arthritis which contribute to the high non-articular morbidity and mortality seen in this disorder. Virtually every organ can be affected by the disease and compelling evidence exists to relate active and severe rheumatoid arthritis (RA) to a marked increase in the prevalence of both cardiovascular and cerebrovascular disease. Non-specific features such as fatigue and weight loss are also seen with greater frequency in undertreated RA. Early effective management of the condition with disease modifying therapy can reduce the frequency and severity of systemic features.
Specific organ involvement in rheumatoid arthritis Haematological • Normochromic anaemia (30–50% of patients) • Microcytic anaemia (10–20%) • Large granular lymphocytosis (< 1%) • Lymphadenopathy (20%)
Keywords rheumatoid arthritis; mortality; systemic disease; vascular disease
Rheumatoid arthritis (RA) is a systemic disorder that may affect almost any organ system. Systemic features may dominate articular manifestations in some individuals and may predate joint disease. Men are more likely to suffer severe systemic disease and have greater mortality from such complications. Systemic manifestations may be divided into general and organ-specific (Table 1); the former often occur early in the disease, whereas the prevalence of the latter is greater in patients with severe articular disease of long duration. Specific extra-articular features are common, though their incidence may now be decreasing with more aggressive treatment of early disease.
Connective tissue • Tenosynovitis • Rheumatoid nodules (20%)
Non-organ-specific features
Cardiac • Mitral regurgitation (5–10%) • Pericardial effusion (5–30%) • Constrictive pericarditis (< 1%)
Cutaneous • Livedo reticularis • Palmar erythema • Pyoderma gangrenosum (< 1%) Pulmonary • Airways obstruction (35–50%) • Pleural effusion (5%) • Interstitial lung disease (2–20%)
Nonspecific features are seen in most patients with active RA and include lethargy, depression and malaise. Fever is occasionally an early feature, particularly in systemic disease. Weight loss may be a marked feature and is often associated with loss of appetite, particularly in the elderly. The resulting weakness may be exacerbated by myopathy and joint pain on active movement. Specific organ involvement may also contribute to fatigue. Mortality in RA is increased, with a slight mean reduction in life expectancy, though this effect has diminished in recent years
Vascular • Medium vessel vasculitis (< 1%) • Digital vasculitis (5–10%) • Raynaud’s phenomenon (10%) Neurological • Cervical myelopathy (2–10%) • Entrapment neuropathies (50%) • Mononeuritis multiplex • Peripheral neuropathy
Neil McKay MRCP is a Specialist Registrar in Rheumatology in the Northern Deanery, Newcastle University, Newcastle upon Tyne, UK. Conflicts of interest: none declared.
Ocular • Keratoconjunctivitis sicca (40%) • Episcleritis and scleritis (1–5%)
Clive A Kelly FRCP is Consultant Physician and Rheumatologist at the Queen Elizabeth Hospital, Gateshead, UK. Conflicts of interest: none declared.
MEDICINE 34:10
Table 1
383
© 2006 Published by Elsevier Ltd.
Rheumatoid arthritis
RA; this relates principally to haematological disorders. The incidence of some solid organ tumours (e.g. adenocarcinoma of the lung) is also increased. Associations between malignancy and rheumatic diseases are discussed in MEDICINE 34:9. Reduced bone density is now recognized as a complication of RA and may lead to an increased risk of fracture. Associations with disease activity, severity and corticosteroid use have all been described. Amyloidosis is a common post-mortem finding in patients with long-standing disease but is seldom symptomatic. However, it may contribute to renal or hepatic failure in a few patients.
g angrenosum may evolve from an apparently superficial dark, tender area over the lower legs. These ulcers have the appearance of an infective lesion once established and may be difficult to heal, particularly in the presence of reduced vascularity. They may respond to corticosteroids and immunosuppressive drugs. Pulmonary involvement is more apparent on physiological and radiological assessment than might be predicted on clinical grounds. Bronchial obstruction seldom affects the major airways but is common in smaller bronchi; wheeze and exertional dyspnoea are frequent features. The severity of involvement is related to both the degree of articular disease and the number of pack-years of tobacco consumption. Bronchiolitis obliterans is very rare and is associated with penicillamine therapy in some cases. Clinically significant pleural effusions are less common than previously reported and tend to occur in early active RA, sometimes as part of generalized serositis. Empyema must be excluded in pyrexial patients by aspiration and fluid culture. Interstitial lung involvement is associated with seropositivity and bibasal lung crackles, usually without finger clubbing. Chest radiography is less sensitive than high-resolution CT, which is the investigation of choice (Figure 1). Recent data suggest that mortality related to this complication may be higher than previously appreciated and, while a response to immunosuppressive therapy has been described, there is some evidence that anti-TNF agents may exacerbate pulmonary fibrosis. The prognosis is generally better than that of cryptogenic fibrosing alveolitis, but a significant number of patients later develop lung adenocarcinoma. Cardiac – cardiac muscle involvement is less common. Myositis and coronary vasculitis are now seen only rarely, though conduction defects from rheumatoid nodules or secondary amyloid are still occasionally reported. More common features include mitral valve disease with regurgitation evident on echocardiography in 6% of patients. Pericardial disease is also common and pericarditis is often complicated by pericardial effusion in early active RA. A few patients develop breathlessness as a result of progressive pericardial constriction or tamponade, both of which may present with right heart failure from right ventricular compression. Aspiration of pericardial fluid under echocardiographic control will temporarily relieve tamponade, but a recurrence or the development of pericardial constriction usually requires formal surgical pericardial fenestration into the left pleural space. Vascular – vasculitis may affect small or medium-sized blood vessels in RA. Small vessel disease tends to produce nail-fold infarcts; these are less common than they used to be and are often asymptomatic in themselves, but may herald other systemic manifestations. Mononeuritis can result from small vessel disease in peripheral nerves and may present suddenly (e.g. peroneal nerve palsy). Involvement of larger vessels produces various clinical features including infarction of digits and necrotic ulceration, particularly over the shins and ankles. Healing may be slow and can be further delayed by incompetent venous drainage.
Organ-specific and system-specific features Sjögren’s syndrome – several syndromes may occur in conjunction with RA. The most common is Sjögren’s syndrome, which occurs in up to 40% of patients. Clinical features include dryness or discomfort in the eyes, nose and mouth as a result of generalized exocrinopathy; this process may also affect other secretory organ function. Lethargy appears more intense in these patients and there is an association with later lymphoma, though this risk is considerably less than that in patients with primary Sjögren’s syndrome. Felty’s syndrome is much less common (1%). It is characterized by severe RA, splenomegaly and neutropenia. Such individuals are at greater risk of systemic infection and often develop chronic leg ulcers. Use of disease-modifying drugs can be problematic in such patients and the articular prognosis is often poor. Haematological – anaemia occurs at some stage in more than one-half of all patients. It is most often normochromic and normocytic, and often correlates with the severity of articular disease (anaemia of chronic disease). Microcytic anaemia is also common and is usually associated with iron deficiency, sometimes as a consequence of excessive gastrointestinal bleeding caused by non-steroidal anti-inflammatory drugs. Serum ferritin can be useful in distinguishing these causes of anaemia; it may be low in iron deficiency and high when the cause is disease activity. Macrocytic anaemia is less common and may result from malabsorption, associated thyroid failure or drug-induced haemolysis. It may also occur in patients receiving sulphasalazine or methotrexate therapy. Lymphadenopathy, particularly in the neck or axillary area, is found in up to 20% of patients with early RA. Histology shows lymphoid hyperplasia and is sometimes necessary to exclude lymphoma. Connective tissue involvement is common and often includes inflammation of the tendon sheaths as an early feature in the hands and wrists. Rheumatoid nodules occur in up to 20% of patients; classically, they affect the elbow and other extensor surfaces subjected to pressure. They are associated with seropositivity and poor articular prognosis, and can affect various internal organs including the heart, lung and spinal cord. They have been reported to increase in number and size in patients taking methotrexate. Cutaneous – palmar erythema is often found in patients with early active RA but diminishes with time. Livedo reticularis is an evanescent cutaneous feature found mainly over the anterior thighs, in which the superficial venous network is visible. It is found mainly in women with vasospastic features such as Raynaud’s phenomenon. Less commonly, pyoderma
MEDICINE 34:10
Endothelial dysfunction The cardiovascular system per se is the newest extra-articular manifestation. Population data from RA and controls suggest not 384
© 2006 Published by Elsevier Ltd.
Rheumatoid arthritis
• inflammatory/immunological (e.g. pro-inflammatory cytokines) • traditional risk factors (e.g. obesity). The burden of inflammation in RA is undoubtedly linked and may act synergistically or independently of traditional risk factors. It is widely accepted that atherosclerosis is a chronic inflammatory process with immune activation initiating acute coronary syndromes. The circulating level of the acute phase reactant C-reactive protein (CRP) predicts outcome in this situation. Activated immune cells in the arterial plaque produce inflammatory cytokines including proteases which thin and rupture the fibrous cap inducing an acute coronary syndrome. CRP reflects the degree of cytokine activation and in RA patients correlates with joint synovial inflammation. Could the overall burden of active inflammation contribute to acute coronary syndromes? In RA, CRP levels at baseline predict CVD death independent of all other variables. The cumulative ‘area under the curve’ of CRP in RA patients not known to have CVD correlates with measures of atherosclerosis (aortic arterial stiffness and carotid intima media thickness). Vascular pathology also takes the form of angiogenesis in the synovium which is essential for perpetuating the joint inflammation. Vascular endothelial growth factor correlates with disease activity in RA and synovium vascularity. Similarly, angiogenesis inhibitors are down regulated in RA. This abnormal endothelial homeostasis is potentially reversible with treatment. Endothelial dysfunction characterizes early atherosclerosis and early RA. It can be reversed by tumour necrosis factor alpha (TNFα) blockade in RA, psoriatic arthritis, and certain systemic vasculitides. Furthermore a case comparison cohort study investigated the risk of developing a first CV event in TNFα blockade treated and control RA patients finding the risk halved with treatment. Prospective data on CV events are awaited. However, the presence of established heart failure with an ejection fraction of below 20% is a contraindication to the use of anti-TNF agents because of the risk of precipitating cardiac decompensation. The risk of CVD in RA is present early and not related to disease duration, allowing speculation on the association of acute rises of inflammatory cytokines in RA driven by synovial inflammation and the onset of CV events. However, the drugs used in arthritis (traditional and newer non-steroidal anti-inflammatory drugs, steroids, and disease modifying drugs) can also be implicated in contributing to CVD (e.g. steroids may benefit or worsen CVD mortality). Certainly, immunosuppresive treatment (e.g. methotrexate) reduces mortality in RA and anecdotally reverses endothelial dysfunction causing myocardial ischaemia.1 Consensus is emerging that RA patients require early immunosuppression, and both primary and secondary CVD prevention strategies in the manner offered to diabetics and other high risk cardiovascular groups. Neurological – cervical myelopathy is the most common rheumatological cause of death in RA. The presence of long tract signs and urinary symptoms indicates established cord compression, though early diagnosis should be sought using cervical MRI in patients with symptoms or signs of increased muscle tone. Compression may be due to atlanto-axial subluxation with or without odontoid erosion, but subaxial disease is now more common. Surgery can stabilize neurological dysfunction at either site. Careful radiological assessment of the neck prior to elective
Figure 1 a A high resolution computed tomogram of the lower chest showing bibasal pulmonary fibrosis in breathless RA patient with a normal chest X ray (b).
only a higher prevalence of cardiovascular disease (CVD) but also higher heart failure rates, higher case fatality, less hospitalization, and less percutaneous intervention. This is hypothesized to be a sub-clinical accelerated atherosclerosis with silent or atypical ischaemic symptoms and is not a myositis or clinically evident coronary vasculitis. Smoking increases the risk of developing RA and is more prevalent in severe RA. Yet controlling for smoking (both pre and post diagnosis), in addition to all other traditional risk factors does not abolish the CVD risk. Perhaps the prevalence of unidentified traditional risk factors is higher in RA and certainly undertreatment and underdiagnosis of hypertension is recognized. The factors contributing to CVD death in RA can be classified as: • disease severity or treatment specific factors (e.g. rheumatoid factor, steroids)
MEDICINE 34:10
385
© 2006 Published by Elsevier Ltd.
Rheumatoid arthritis
surgical or endoscopic procedures is important in all patients with established RA. Carpal tunnel syndrome is a common early feature of RA and may occur in up to 50% of patients. Typical clinical features include painful paraesthesiae and poor hand grip. Other nerves are occasionally damaged by local factors (e.g. ulnar nerve at the elbow, tarsal nerve in the ankle). Ocular – eye involvement can include keratoconjunctivitis sicca, which is common, and episcleritis, which is rare. Patients with aggressive RA can develop scleritis, but progression to scleromalacia perforans is now seldom seen. Urgent opthalmological assessment is necessary in any patient with suspected scleral involvement and treatment usually requires steroid and other immunosuppressive therapy. ◆
MEDICINE 34:10
Reference 1 Raza K, Banks M, Kitas G. Reversing myocardial microvascular disease in a patient with rheumatoid arthritis. J Rheumatol 2005; 32: 4.
Further reading Dieppe P A. Extra-articular features of rheumatoid arthritis. In: Dieppe P A, Bacon P A, Bamji A N, Watt I, eds. Atlas of clinical rheumatology. New York: Gower, 1986. (A useful review of common clinical systemic features of RA.) Kelly C A. Lung disease in rheumatic disorders. In: Kelly C A, ed. Clinical rheumatology. London: Baillière-Tindall, 1993. (A review of pulmonary aspects of lung disease in RA.)
386
© 2006 Published by Elsevier Ltd.