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RA is an autoimmune disease that affects approximately 1% of the world’s population. It is characterized by a symmetric, progressive polyarthritis. Unlike OA, RA often has systemic manifestations. Although the cause of RA is unclear, and its course in each patient can be unpredictable, the symptoms can range from mild to tremendous pain, suffering, and disability.44,45
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RA has widely varying onset, severity, and progression. It is twice as common in women as in men, and has its usual onset in the fourth and fifth decades of life. It is thought that there is a genetic predisposition to RA. Prevalence of RA increases with age. (Note: Juvenile rheumatoid arthritis [JRA] is a distinct syndrome and is discussed separately.)
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RA is characterized by an autoimmune attack on synovial tissue, leading to marked (up to 100-fold) proliferation of synovium. Adjoining tissues are affected by this synovial neoplasia, including cartilage, bone, ligaments, tendons, and bursae. This inflammation, combined with physical stress, destroys joint structure and function. In addition, extra synovial manifestations may affect almost any organ.
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A basic understanding of the pathophysiology of RA allows the emergency physician to suspect the disease in the undiagnosed patient, and to tailor treatment and detect systemic complications in all patients with RA.
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The emergency physician will encounter two main groups of patients with RA: (1) those who have not yet been diagnosed as having RA and present with polyarticular arthritis; and (2) those who have been previously diagnosed and present with an acute flare, systemic manifestations of the disease, or an unrelated medical problem.
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New-Onset Rheumatoid Arthritis
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Although etiology of RA is unclear the current thinking is that it is a combination of environmental and genetic factors. Onset is usually, but not always, articular, symmetric, and gradual. The variability of symptoms and progression in RA often makes initial diagnosis difficult: onset may be over weeks to months, duration of illness may last weeks or decades, and severity may vary from mild arthritis to crippling deformity. It should be noted that the initiation of RA probably begins years before any clinical symptoms are apparent.46 This is important to realize, because early referral to a rheumatologist and initiation of therapy can greatly improve long-term outcomes.
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RA is an autoimmune disease, and 70% to 80% of patients have rheumatoid factor (RF), an immune complex, circulating in their serum. RF is not specific for RA, and may be found in other diseases. A new test for anti-citrullinated protein antibodies (ACPA) shares the same sensitivity as rheumatoid factor, but has improved specificity. In patients with a positive RF and ACPA, the sensitivity of making a laboratory diagnosis is further improved.47
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The diagnosis of RA is still based primarily on clinical criteria. The ACR has a scoring system that includes number of joints involved, RF and ACPA, CRP and ESR, and duration of symptoms. The higher the score the more likely the patient has RA. The classification system requires observation of the patient over time (at least 6 weeks), so the initial diagnosis of RA is unlikely to be made in the acute care setting. The goal in the acute care setting is, therefore, to suspect rheumatologic disease, alleviate any acute symptoms, rule out other urgent/emergent conditions, and then refer the patient to the appropriate provider for definitive diagnosis and long-term management. The emergency physician should:
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Rule out joint infection with mono- or oligoarticular involvement (see later discussion).
Attempt to differentiate RA from other polyarthropathies, such as OA and gonococcal arthritis.
Arrange for baseline laboratory studies, including ESR, complete blood count (CBC), and creatinine level. RF and ANA tests may also be requested.
Rule out serious extra-articular disease.
Treat symptoms of pain and inflammation.
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Any patient suspected of having RA should have a primary care provider, as many of these patients will develop systemic comorbidities, such as pulmonary or renal disease. Specialty referral may be deferred to the primary care provider if the patient is not severely ill. Studies suggest that patients with RA have less morbidity when a rheumatologist is involved in their care.
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A variety of agents with varying therapeutic and side effects are used, and must often be combined for optimal results (Table 3–7). A treatment regimen should be tailored for each individual patient. Therapy with agents other than NSAIDs, and perhaps a brief course of steroids, should only be undertaken after consultation with the physician who will be following the patient.
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Nonsteroidal Anti-inflammatory Drugs
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NSAIDs are used to treat symptomatic pain and inflammation of RA, and should be used if they are not contraindicated. They can adversely affect renal function and may exacerbate or cause peptic ulcer disease. Numerous agents are available, with variable dosage and cost. Unfortunately, a given patient’s therapeutic response to each drug is not predictable, and neither are the exact side effects the patient will experience. If a patient with known RA presents with pain, the physician should ask whether the patient already knows which agent is most effective.
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These drugs may be given systemically or by local injection. Systemic corticosteroids (e.g., methylprednisolone, 100–1000 mg/d for 3 days) can improve the symptoms of an acute RA flare. However, systemic corticosteroids do not prevent joint destruction and thus have no sustained benefit for patients with RA. They also have serious side effects on many organ systems. Chronic use of systemic corticosteroids (e.g., prednisone, 5–7.5 mg/d) should be limited to severe, unremitting disease; and should be discussed with a consultant before initiation.
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Local corticosteroid injection decreases symptoms of acute inflammatory synovitis. Joint infection must be ruled out prior to administration, particularly if the flare is mono- or polyarticular.
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Disease-Modifying Antirheumatic Drugs (DMARDs)
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DMARDs are the mainstay of treatment in RA. Unlike corticosteroids, DMARDs may alter the destructive course of RA. For this reason, and despite the potential for toxicity, these agents are recommended early in the course of RA. The most commonly used DMARD in the initial phase of treatment is methotrexate. DMARDs are expensive, and require several weeks of use for maximal benefit. They are usually combined with NSAID therapy, and sometimes with corticosteroids. One-third of patients take more than one DMARD (Table 3–8).44
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DMARDs have the potential for severe side effects, and their use requires close follow-up and careful dose titration. Initiation of DMARD treatment without consultation is beyond the acute care scope of practice. Because patients may present with iatrogenic complications, the emergency physician should have some familiarity with the major agents used and their side effects.
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Other Therapeutic Modalities
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Other therapeutic modalities for the treatment of RA include:
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Joint immobilization or bed rest, or both; these may be useful for patients with an acute flare, but joint rest must be weighed against the effects of deconditioning.
Physical therapy.
Reconstructive surgery; this is sometimes necessary to correct deformities, particularly in the hand.
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Preexisting Rheumatoid Arthritis
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The goals in the acute care setting are to treat the patient’s pain and inflammation, limit tissue destruction, and improve daily functioning. These patients are often on immunosuppressive drugs, which predispose them to infections and may obscure signs of serious infection. Both RA and the medications used to treat it may cause systemic complications.
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Usually, symmetric and progressive joint deterioration are seen, with exacerbations and remissions over the course of the disease (Table 3–9, Figs. 3–10 and 3–11). Function is worse after immobility or sleep and improves with activity during the day. Patients report morning stiffness, usually lasting more than 30 minutes, with a median duration of 1.5 hours.
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Clinical findings include pain in the affected joints, both at rest and with motion, along with joint swelling, warmth, and tenderness. Erythema may be present with acute onset or flare; if present, the physician should consider infection. Pain, inflammation, and disuse atrophy of muscles lead to progressive functional impairment and loss of range of motion. Radiologic signs of soft-tissue swelling, symmetric joint-space narrowing, and osteopenia of adjoining bones are present.
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The “rheumatic hand” is characteristic: the (PIP), metacarpophalangeal (MCP), and wrist joints are inflamed, whereas the DIP joints are spared.
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Initial treatment is with NSAIDs and modification of activity. Rest, splinting, and preferential use of large rather than small joints (e.g., carrying a bag on the shoulder rather than in the hand) can delay joint destruction. DMARDs are added, with consultation, for progressive disease.
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Acute Rheumatoid Arthritis Flare
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In this presentation, the patient has acutely increased synovial inflammation with variable systemic and constitutional symptoms. Joint involvement is symmetric, usually with six or more painful, tender, swollen joints. Morning stiffness worsens, typically lasting over 1 hour. ESR >30 mm/h and elevated CRP levels are often present.48
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The immediate goal of treatment is alleviation of the acute pain and inflammation, followed by prompt referral to the patient’s primary care provider or rheumatologist. Joint infection must always be considered, particularly with mono- or pauciarticular flares (see later discussion).
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Bed rest may be sufficient in some patients. NSAIDs are prescribed unless contraindicated. The patient should be referred promptly to a specialist for DMARD treatment.
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A systemic steroid bolus (e.g., methylprednisolone, 100–1000 mg/d for 3 days), given after consultation, can help control a severe, generalized flare. Some patients may require up to 1 month of daily, low-dose systemic steroid therapy. Local steroid injection into the most acute joints, after infection is ruled out, can decrease local inflammation. The patient’s rheumatologist or primary care provider generally performs injection.
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Finally, the emergency physician should be alert for signs of new systemic disease, either rheumatic or iatrogenic.
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Septic Rheumatic Joint
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Patients with RA are at increased risk of joint infection as a result of inflammation and immunosuppression. Furthermore, anti-inflammatory and immunosuppressive medications may suppress clinical signs of infection and delay the diagnosis.
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There is no definitive test or finding, other than a positive synovial fluid Gram stain or culture, which can diagnose a septic joint in the setting of rheumatic inflammation. Unfortunately these two entities can present in very similar ways, and given the high morbidity of septic arthritis, the clinician should have a low threshold for performing arthrocentesis when septic arthritis is a possibility. A number of findings can guide the clinician’s diagnosis and treatment decisions.
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Joint infection is usually monoarticular. Diagnosis is much more difficult if the infection is polyarticular. Infection may be indicated by pain greater than the patient’s usual flare, fever, and systemic toxicity. Polyarticular infection is usually asymmetric, because of hematogenous spread.
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Diagnosis necessitates joint aspiration for culture, Gram stain, and cell count. The physician must ensure that a specimen of synovial fluid is obtained for culture before starting antibiotic therapy.
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Empiric antibiotic treatment should be started if clinical suspicion is high, or if the aspirate demonstrates positive Gram stain; leukocyte count >50,000 mm3 (unusual in RA, but possible); or PMNs >90%. Blood and other specimens, such as urine, should be cultured to increase the yield of any infecting organism, and to search for a site of initial infection.
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Antibiotic selection should be based on Gram stain results. Empirically, vancomycin and a third generation cephalosporin like ceftriaxone would be good initial choices. This will not cover special cases as in prosthetic joints or pseudomonal infections. Because of the high rate of morbidity of septic arthritis, consultation with an infectious disease specialist is highly recommended in these instances. Empiric treatment without the proper diagnostic workup may commit the patient to an unnecessary course of antibiotics and may delay initiation of appropriate anti-inflammatory therapy.
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Popliteal (Baker’s) Cyst
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Popliteal cysts are common because of the synovial proliferation that characterizes RA. A cyst may rupture spontaneously or as a result of physical activity, leading to acute calf pain and swelling. The most difficult task facing the emergency physician is ruling out an acute deep venous thrombosis (DVT). Heparinization following a misdiagnosis of DVT can lead to continuing hemorrhage into the calf, with subsequent compartment syndrome.
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Ultrasound is the least invasive test and is widely available. Venography or a contrast arthrogram is rarely necessary. Note that a crescent-shaped hemorrhage below either malleolus is characteristic of a ruptured cyst and not a DVT.
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Rest, elevation, and analgesia are usually all that is required. Intra-articular corticosteroid injection (after consultation) may help alleviate symptoms before and after rupture. Actual compartment syndrome is rare, but must be treated immediately to prevent permanent disability. Residual calf swelling usually lasts several weeks, but may persist over 3 years.
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Atlanto-Axial Subluxation
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Although spinal arthritis is common in RA, actual C1-C2 subluxation is uncommon, with an incidence of approximately 5%, overall, in RA. The incidence increases with increasing severity of the patient’s overall disease. Actual cord or vascular compromise is rare, but it does occur and can be iatrogenic, resulting from manipulation, such as intubation.
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Symptoms and signs of cord compression include severe neck pain, usually radiating to the occiput; extremity weakness, which may be upper or lower, or both (often difficult to assess because of the patient’s severe and long-standing arthritis); numbness or tingling in the fingers or feet; loss of vibration sense, with preservation of proprioception; “jumping legs,” caused by spinal reflex disinhibition; and bladder dysfunction. Patients may also have vertebral artery insufficiency, including syncope or vertigo.
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An atlanto-dens interval >2.5 mm in adults and >5 mm in children is diagnostic. Although an emergent computed tomography (CT) can help if cord compression is suspected, an MRI will give much more information and is the test of choice.
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Apply a hard cervical collar and refer the patient for traction and fusion if there are signs of neurologic or vascular compromise. Treatment is generally medical until there are signs of cord compression, at which point surgical options become the mainstay of therapy. For the emergency physician, emergent airway management is of particular importance. The clinician should avoid any aggressive airway maneuvers in patients with signs of RA, or a history of RA, if at all possible.
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RA may affect nearly any organ. Systemic disease is common, and may be life threatening. Systemic complications may be caused by the primary rheumatic disease process, a medication, or a combination of both. Signs of serious systemic disease may be missed, particularly in the patient in whom the diagnosis of RA has not yet been made. The organs that are most often affected include the lungs, heart, liver, and spleen. Blood vessel involvement is also common.
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Mild and asymptomatic pulmonary disease is common in RA. Patients may have pulmonary nodules, pleural effusion, or fibrosis. They occasionally present with restrictive, chronic obstructive pulmonary disease-like symptoms. Acute obliterative bronchiolitis is uncommon, but may be fatal; it is unclear if it is caused by the RA itself, or by the medications (DMARDs) used to treat RA.
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Pericarditis is the most common cardiac disorder. Usually, asymptomatic chronic inflammation is detected only at autopsy, but inflammation may be acute and constrictive. Rheumatic myocarditis and endocarditis occasionally occur. With endocarditis, the physician must rule out bacterial endocarditis; these patients are predisposed to bacteremia as a result of open wounds and immunosuppression.
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Hepatitis is often subclinical but may be overt. Liver abnormalities often occur as a result of drug side effects.
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Felty’s disease is defined as RA that occurs in association with an enlarged spleen and leukopenia. It usually occurs in a patient with long-standing RA, including rheumatoid nodules and marked joint deformity. Patients are subject to neutropenia and severe bacterial infections, as well as thrombocytopenia. Any patient suspected of having Felty’s disease requires emergent consultation, admission, and aggressive treatment of any suspected bacterial infections. Treatment of RA may improve the manifestations of Felty’s disease, but plasmapheresis or splenectomy may be required.
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Small vessel inflammation is integral to the pathophysiology of RA. Clinically diagnosable vasculitis may be chronic or acute. With chronic vasculitis, leg ulcers and nail fold infarcts are common. Distal sensory neuropathy may also be seen. Acute systemic vasculitis is rare and usually occurs in patients with long-standing disease.