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10 Articles in Volume 17, Issue #5
Cross-Linked Hyaluronic Acid Injection for Neuropathic Pain
Discussing Migraine: What to Try When Nothing Is Working
IV Propofol for Treatment of Chronic Intractable Cluster Headache: A Case Series
Letters to the Editor: Rapid Opioid Metabolizer, Intractable Pain, Adrenal Suppression, Traumatic Brain Injury
Migraine Treatment: What’s Old, What’s New
Schizophrenia Spectrum and Chronic Pain: Is Pain Insensitivity a Myth?
Spinal Fluid Flow and Pain Management
Step-by-Step Technique for Targeting Superficial Radial Nerve Pain
The Primary Care Provider’s Role in Diagnosing and Treating Rheumatoid Arthritis
What is the appropriate use of phone texting between physicians and patients?

The Primary Care Provider’s Role in Diagnosing and Treating Rheumatoid Arthritis

PCPs should work closely with the rheumatologist to manage comorbid conditions with special attention to cardiovascular risk, depression, and osteoporosis.

Rheumatoid arthritis (RA) is the most common systemic, inflammatory polyarthritis. It affects between 0.5% and 1.0% of the population between age 20 and 50.1 However, RA occurs in all age groups, including children and older adults. While both men and women may develop RA, women are more susceptible to the condition.

Although the exact cause of RA is unknown, there have been major breakthroughs in understanding disease mechanisms over the past 20 years. This has resulted in significant therapeutic advances for RA. A disease that was once disabling and crippling has become very manageable and often asymptomatic.

The earlier RA therapy is initiated, the better the long-term outcome. Joint task forces of rheumatologists in the United States and United Kingdom recommend that patients should see a rheumatologist within 6 weeks of noticing RA  symptoms.2 Therefore, a timely diagnosis is central to optimal RA management. In general, primary care providers (PCPs) will be responsible for recognizing possible RA early and providing a rapid referral to a rheumatologist.

The second important role for PCPs is the ongoing management of the key comorbidities in patients with RA. These include cardiovascular risk factors, mood and sleep disturbances, and osteoporosis. Some rheumatologists elect to manage the “total patient,” but the general medical care of the RA patient is often provided by the PCP.

Role of primary care provider in identifyiing and treating rheumatoid arthritis.

Primary Care Evaluation of Possible RA

RA should be immediately considered in any patient presenting with polyarthritis of at least 6 weeks in duration. The small joints of the hands, such as the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints, and feet, such as the metatarsophalangeal (MTP) joints, are typically involved. Many patients will be systemically ill with fatigue, weight loss, and low-grade fever. Generally, RA patients are very stiff and sore for hours in the morning, or when they are inactive.

The paramount finding on examination is joint inflammation. Polyarthralgias or generalized myalgias are never sufficient for a diagnosis of probable RA. RA cannot be strongly suspected if observable joint inflammation (redness, warmth, and swelling) is not detected on examination. A major problem with this caveat is that many PCPs have received little training in performing a joint examination. They are often uncomfortable searching for subtle signs of joint inflammation.

In addition, patients with early RA often do not present with the classic, symmetrical polyarthritis involving the hands, wrists, feet, and ankles. Initially, RA often begins with just 1 or 2 inflamed joints. Other joints typically become inflamed over time. Early on, RA joint swelling may come and go, and there are few systemic symptoms. Atypical joints, such as the jaw, will be painful, mimicking temporomandibular joint disorder (TMJD). Subcutaneous nodules are rarely seen in early RA.

Laboratory testing is of limited diagnostic use in early RA, but the acute phase reactants—either an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)—should be elevated, indicating a systemic inflammatory disorder. A modest anemia and thrombocytosis also reflect the presence of an inflammatory disease.

Rheumatoid serology, either the rheumatoid factor or the anti-citrullinated peptide (anti-CCP) antibody, are present in 70% to 80% of RA patients. However, because of their relatively poor specificity, they do not need to be obtained by the PCP but could wait until rheumatology consultation. Indeed, there is evidence that a positive rheumatoid factor obtained in primary care performs badly in excluding the diagnosis of RA and delays rheumatology referral.3 In contrast, the anti-CCP antibody has greater specificity for RA and may be reasonable to test for in primary care.

Realistically, the PCP could limit initial testing in suspected RA to a complete blood count and an acute phase reactant. X-rays and imaging should not be routinely ordered during the initial evaluation of suspected RA, as radiographic changes take months to develop.

This scenario is directed to an early diagnosis of RA in the primary care setting. The longer the duration of the symmetrical polyarthritis, the more likely RA will be diagnosed and the more characteristic the presentation will be. However, a timely diagnosis and early rheumatology referral are most important. Therefore, it is incumbent on the PCP to think strongly about RA in patients who may not have yet developed the classic small-joint symmetrical polyarthritis (Table 1).

For the PCP, RA should be suspected in any patient with:

  • Joint swelling and inflammation in 2 or more joints
  • Symptoms present for more than 6 weeks
  • Signs of systemic inflammation, such as fever, anemia, weight loss, and fatigue
  • Morning stiffness
  • Elevated acute phase reactants

Although any joint may be involved in early RA, the joint swelling often begins in the PIP and MCP joints, which should be examined for warmth, swelling, tenderness, and limited range of motion. The swelling often feels spongy when the PIPs are palpated. Grip strength is usually reduced. Squeezing the MTPs often produces severe tenderness, even in the absence of visible swelling. Wrists and knees often demonstrate joint effusions.

The differential diagnosis may seem complex at first but can be subdivided into 3 discernible categories: inflammatory arthritis, non-inflammatory arthritis, and non-articular pain (Figure 1).

Inflammatory Arthritis

This includes joint infection and crystal-induced arthritis (gout or pseudogout). These both usually affect 1 or 2 joints, and are definitively diagnosed exclusively by a synovial fluid analysis. Therefore, the PCP (if qualified) should perform a joint aspiration with synovial fluid culture, crystal analysis, and cell count if infection or crystal-induced arthritis is suspected.

The persistence of symptoms for more than 1 month will generally exclude an infectious etiology for the polyarthritis. Most forms of non-gonococcal bacterial arthritis involve a single joint and present early with severe pain, swelling, and fever. Gonococcal arthritis may present rather insidiously and is often polyarticular. Skin lesions and tenosynovitis are seen in most cases of disseminated gonococcal infection. Viral polyarthritis may mimic early RA but usually is self-limited, spontaneously resolving within 2 to 4 weeks.

Gout and pseudogout will occasionally be polyarticular. The tophi present in chronic, poorly treated gout may mimic the subcutaneous nodules of RA. Pseudogout usually affects the knees, shoulders, or wrists.

The systemic, autoimmune connective tissue diseases rarely present solely with polyarthritis. These conditions, such as systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, or the many forms of systemic vasculitis, typically present with skin, kidney, pulmonary, or neurologic signs and symptoms. The so-called rheumatoid variants, including psoriatic arthritis, arthritis associated with inflammatory bowel disease, and the seronegative spondyloarthropathies, may mimic RA. Polymyalgia rheumatica (PMR) may mimic RA, but small joint swelling is very unusual. It is the rheumatologist’s role to properly subset these various systemic inflammatory conditions (Table 2).

Non-Inflammatory Joint Pain

Osteoarthritis (OA) tends to be very insidious, with no systemic signs of inflammation. The joints may be swollen, but the swelling is bony and generally not tender. Rather than the PIP or MCP joints, the distal interphalangeal (DIP) joints are most often hypertrophied and deformed in OA (Heberden’s nodes). The acute phase reactants should be normal. Traumatic arthritis is usually monoarticular.

Non-Articular Pain

The largest group of patients who will be seen in primary care for chronic, generalized musculoskeletal symptoms have non-articular rheumatism (Figure 1). When only a few soft tissue locations are involved, bursitis or tendonitis is usually considered, and the symptoms tend to be self-limited. When the pain is widespread and persistent, fibromyalgia (FM) is the likely diagnosis. There is no joint swelling in FM, and tenderness is most prominent at soft tissue rather than at joint sites. There are no signs or symptoms of systemic inflammation. Patients with FM do not respond well to nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids.

When there is uncertainty over the presence of systemic inflammation, it may be reasonable to consider a short course of low-dose corticosteroid therapy rather than analgesics or NSAIDs. This is especially appropriate if the patient with suspected RA is unable to see a rheumatologist for weeks. Ten to 15 mg daily of prednisone may be an effective short-term solution for early RA or another systemic inflammatory condition, as well as in treating probable PMR.

The PCP should expect a patient with suspected RA to be evaluated by a rheumatologist within 6 weeks.2 This may vary regionally but is a realistic guideline suggested by the American College of Rheumatology (ACR). The mindset for both primary care and rheumatology is that RA management, like that for cancer or coronary heart disease, requires a timely and coordinated initial evaluation.

During the past decade, PCPs have become more adept at distinguishing inflammatory from non-inflammatory joint pain, however, a timely rheumatology referral is still problematic. In a review from 2004, the diagnostic agreement regarding the diagnosis of RA between PCPs and rheumatologists was only 50% to 70% (Table 3).4 Only one-third of RA patients saw a rheumatologist within 1 year of symptom onset. PCPs tended to overdiagnose RA and rarely prescribed disease-modifying antirheumatic drugs (DMARDs).

In 2 more recent Canadian surveys, the vast majority of RA patients had not seen a rheumatologist in a timely fashion. In 2007, only 27% of new- onset RA patients had seen a rheumatologist within 3 years.5 Of those who had seen a rheumatologist, the median time to consultation was 79 days. In a 2017 survey, the median time for consultation in RA patients was 327 days.6 Only one-third of the RA patients had started a DMARD within 6 months of symptom onset. Strategies to promote early rheumatology referral have included primary care education programs and dedicated websites that prioritize use of RA diagnostic classification criteria to primary care referrals.7,8

Earlier RA diagnostic criteria were designed primarily to differentiate RA from other forms of inflammatory arthritis. However, the 2010 ACR and the European League Against Rheumatism (EULAR) classification criteria focused on an earlier diagnosis of RA and can be useful in primary care.9 These criteria include the number and sites of involved joints, symptom duration of at least 6 weeks, elevated acute phase reactants, and serological abnormality. The comfort level of PCPs in evaluating a patient with suspected RA varies with training as well as the adequacy of rheumatology referral patterns.

Primary Care Management: General Medical Care in RA

Cardiovascular Risk

There is a significant increased cardiovascular disease (CVD) risk in RA patients compared to that in the age-matched general population. This increased risk is related to traditional CVD risk factors, such as hyperlipidemia, smoking, and obesity, but it’s also connected to the inflammatory process itself. Inflammation may increase atherosclerosis via immune and cytokine mechanisms, as well as by inducing a hypercoagulable state and enhancing insulin resistance. Joint damage and disability often lead to inactivity and exercise intolerance, increasing the risk of weight gain, obesity, diabetes, and dyslipidemia. Chronic glucocorticoid therapy further increases traditional CVD risk. There is also evidence that selective cyclooxygenase (COX)-2 inhibitors may increase the risk of coronary artery disease (CAD).

In the largest prospective studies, traditional CVD risk factors did not differ much between RA patients and matched controls, but biomarkers of inflammation, such as the CRP, did vary greatly.10 However, these traditional CVD risk factors may be more difficult to treat in RA patients, especially in relationship to the importance of regular exercise.

It is important to screen for CAD in RA, including an annual comprehensive cardiovascular examination in any RA patient over age 50 years. Clinically silent CAD is more common in RA patients than the general population.

Optimal management of CVD in RA requires coordination between primary care and rheumatology, often with cardiology consultation. Traditional CVD risk factors should be identified and aggressively treated, including statin therapy for hyperlipidemia and management of comorbid hypertension and hyperglycemia, if present. In RA patients whose joint disease prevents adequate exercise and weight reduction, tailored approaches, such as a supervised water exercise program, are recommended. Long-term glucocorticoid or COX-2 medication regimens should be discouraged. Nearly 50% of RA patients and 50% of their PCPs reported that they were unaware of the increased risk of CVD in RA patients.11

In keeping with the notion that RA inflammation drives the excess CVD risk, there is now evidence that effective treatment of RA, especially with the newer biologic agents, reduces the CVD burden. For example, the rates of subsequent myocardial infarction in 8,760 RA patients were lower in those who responded well to tumor necrosis factor (TNF) inhibitor therapy compared to those who did not respond.12

Depression and Other Mood Disturbances

There is a 3- to 4-fold increased lifetime history of depression in RA patients compared to the general population.13 In various reports, 15% to 40% of RA patients were depressed.13,14 RA patients with depression have greater levels of pain, poorer quality of life, and poorer general outcomes than RA patients without depression.14 Central pain and generalized allodynia correlate with depression and sleep disturbances in RA patients.15 Depression in RA patients increased fatigue and cognitive disturbances, and was an independent risk factor for mortality with a 2.2 odds ratio (Table 4).16,17

Therefore, PCPs should be alert to the co-occurrence of depression and other mood disorders in RA patients. Antidepressant medications and cognitive behavioral therapy should be used in a timely fashion, when appropriate.

Osteoporosis

RA patients also have an increased risk of osteoporosis, particularly in men and premenopausal women. Immobility, lack of weight-bearing exercise, and use of glucocorticoid medications each contribute to this increased risk. Therefore, dual-energy x-ray absorptiometry (DXA) should be considered at an earlier age in men and women with RA than in the general population. Optimal control of RA reduces the risk of osteoporosis, but bisphosphonate therapy significantly increased the spine bone mineral density (BMD) during a 5-year study—even in RA subjects with good disease control.18 BMD interval testing should be adjusted based on the RA patient’s baseline BMD T-scores.

Conclusion

PCPs should work closely with the rheumatologist, and manage comorbid conditions with special attention to excess cardiovascular risk, depression, and osteoporosis (Table 5). Patients with RA are twice as likely to develop a myocardial infarction, and 70% more likely to develop a stroke or serious infection compared to the general population. The life expectancy in RA is reduced by as much as 18 years compared to age- and sex-matched controls without RA. It is well established that a timely diagnosis and rapid referral to rheumatology are key variables in long-term RA patient outcomes.19

PCPs are generally the first to evaluate RA patients, and potentially impact the early diagnosis and referral. Early referral should be considered in any patient with inflammation in 2 or more joints lasting at least 6 weeks. This is especially important when signs of systemic inflammation are present. Acute phase reactants should be obtained and are usually elevated. Other testing can await subspecialty referral, although some would recommend testing for anti-CCP antibody.

Last updated on: September 26, 2017
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Cross-Linked Hyaluronic Acid Injection for Neuropathic Pain

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