Evaluation and medical management of end-stage rheumatoid arthritis

INTRODUCTION — End-stage rheumatoid arthritis (RA) is an advanced stage of disease in which there is severe joint damage and destruction in the absence of ongoing inflammation. Despite the availability of methotrexate and other nonbiologic disease-modifying antirheumatic drugs (DMARDs), as well as biologic DMARDs and kinase inhibitors, some patients with RA do not adequately respond to therapy [1,2]. The joints of such patients may eventually be destroyed by a variety of mechanisms, resulting in end-stage RA and often requiring joint arthroplasty to improve or restore function.

The evaluation and management of patients with apparent end-stage disease requires:

●Assessment of whether residual disease activity is present that may respond to adjustment of the drug therapies

●Identification of factors other than articular inflammation that may be contributing to the clinical state and may require interventions distinct from antirheumatic drug therapy

●Recognition and referral of patients who may benefit from rehabilitative or orthopaedic interventions

This topic will review the evaluation and medical management of patients with end-stage RA. The medical management of patients with active disease and the surgical management of those with end-stage RA are discussed in detail separately. (See "General principles and overview of management of rheumatoid arthritis in adults" and "Initial treatment of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial conventional synthetic (nonbiologic) DMARD therapy" and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy" and "Surgical management of end-stage rheumatoid arthritis".)

DEFINITION — End-stage rheumatoid arthritis (RA) is an advanced stage of disease in which there is severe joint damage and destruction that is accompanied by an absence of ongoing inflammation, for example, as demonstrated by a lack of evidence of synovitis or significant joint effusions, and the presence of normal laboratory markers for inflammation, such as the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). Other laboratory and imaging studies may also fail to demonstrate changes suggesting active inflammatory synovitis. However, some patients with end-stage RA do exhibit residual inflammatory activity in selected joints, while other joints exhibit only end-stage changes.

Acute phase reactants, such as the ESR and CRP, are most useful as measures of disease activity when the values associated with active disease in an individual patient are known from prior assessments, as these values can vary between patients with similar degrees of clinical activity, and one or both are sometimes not elevated with active disease as measured by joint counts and global assessments [3]. Thus, apparently normal values of these laboratory parameters may be observed not only in the context of burnt-out RA but in patients with RA at all stages of the disease. (See "Acute phase reactants", section on 'Discrepancies between acute phase reactant levels'.)

ETIOLOGIC FACTORS — The progression of disease which culminates in end-stage rheumatoid arthritis (RA) usually occurs over years to decades. The causes of joint destruction include any combination of the following:

●Prolonged delay in the initiation of traditional nonbiologic disease-modifying antirheumatic drug (DMARD) therapy or of biologic DMARDs (see "General principles and overview of management of rheumatoid arthritis in adults", section on 'General principles')

●Intolerance or development of toxicity to one or more antirheumatic therapies, thereby requiring the discontinuation of agents which may have been beneficial

●Refractory disease, which has failed to respond to multiple therapies

●Poor adherence to the therapeutic regimen

EPIDEMIOLOGY — The prevalence of end-stage disease with available therapies era is unknown but, due to effective therapy, appears to be progressively decreasing. In our experience, such patients represent only a small proportion of patients seen in clinical practice, being approximately 5 percent or less of those patients referred since the 1990s to secondary and tertiary centers who have been diagnosed with rheumatoid arthritis (RA). Such patients have usually been suboptimally treated according to guidelines developed since that time.

A 2016 systematic review of studies of the incidence, prevalence, and severity of RA described evidence for a decrease in severity of RA over the last several decades, with lower activity, fewer extraarticular manifestations, a diminished need for surgery to treat joint destruction, and less severe radiological changes. By contrast, the excess mortality associated with RA remains substantial, despite a trend toward a decrease over time [1]. (See "Disease outcome and functional capacity in rheumatoid arthritis".)

CLINICAL MANIFESTATIONS — The major characteristics of end-stage rheumatoid arthritis (RA) include:

●Symptoms of joint pain with activity and often at rest or at night (see 'Symptoms' below)

●Findings of destructive joint and tendon disease with fibrosis that has resulted in significant loss of joint function or the need for joint arthroplasty or fusion; poor mobility and a significant decline in functional status, resulting in disability; and periarticular muscle atrophy and weakness (see 'Physical findings' below)

●Usually a lack of laboratory evidence for ongoing systemic inflammation, although abnormalities may be observed in some patients (see 'Laboratory findings' below)

●Radiographic evidence of marked articular damage (eg, erosions and severe loss of joint space that can lead to bone-on-bone changes) (see 'Imaging abnormalities' below)

Symptoms — End-stage joint disease is characterized by pain and loss of function. Patients typically report pain in multiple joints with physical activity, although pain can be present at rest and may be bothersome during the night.

Stiffness in the joints, including morning stiffness, is sometimes described due to the presence of contractures, joint injury, and deformities, rather than being due to synovitis. Weakness may also be reported. Patients can have difficulties with activities of daily living, including use of the upper extremities and ambulation. Fine motor activities may also be impaired due to prior hand and wrist disease.

Physical findings

●The joint examination demonstrates generalized loss of motion in many joints, and deformities are often present. To minimize the level of stress on a destroyed joint, most patients decrease their activities, and immobilization can reduce the degree of synovitis [4]. However, over time, the lack of activity and the reduced ranges of motion in affected joints results in joint contractures, foreshortened tendons, muscle atrophy, and weakness. The following findings can be seen:

•In the upper extremities, multiple findings that impair range of motion and function are typically present. The hands show ulnar drift and may show subluxation at the metacarpophalangeal joints. Boutonniere and swan neck deformities can be seen. The thumb joint may show a zigzag deformity resulting in hyperextension at the thumb interphalangeal joint and little functional capacity.

The wrists may lack mobility and be partially fused. Contractures can often be observed in the joints in the upper extremities. The elbows lack full extension and elbow flexion may be significantly reduced, resulting in a very limited arc of motion. There can be reduced abduction and external rotation of the shoulders caused by chronic tearing of the rotator cuff mechanism, resulting in superior migration of the humeral head within the glenohumeral joint.

•In the lower extremities, the damage can adversely impact gait and mobility. The hips show limited mobility, especially with flexion maneuvers, resulting in hip contractures. These can be confirmed by noting a positive Thomas test (picture 1), whereby hip flexion causes the contralateral hip to rise off the exam table (see "Musculoskeletal examination of the hip and groin", section on 'Tests of hip flexors'). The knee joints may show limited range of motion with flexion and extension. There can be loss of cartilage space and bone-on-bone changes are evident on imaging studies. (See 'Imaging abnormalities' below.)

In contrast to osteoarthritis in patients without RA, there is valgus angulation at the knees which may result in ineffective transfer of forces across the knees, causing further decline in ambulatory abilities. Preexisting osteoarthritic changes may coexist, especially with onset of RA in older adult patients, or occur following remission of inflammatory features.

The ankles and feet show pes planus, and valgus angulation at the ankles is often severe and may require surgical fusion. There may be cock-up toe changes in the toes. Callus formation overlying the metatarsal phalangeal joints can be extensive, and in rare cases there may be skin ulceration over these areas.

●Rheumatoid nodules may be present, especially over the olecranon surfaces, the Achilles tendons, and sometimes the fingers. Other findings due to extraarticular disease may include pleural or parenchymal lung disease, cardiac involvement, or the development of a neuropathy. Rarely, there may be scleral inflammation affecting the eye. Involvement of the cricoarytenoid joint can result in dysphagia or respiratory stridor [5]. (See "Overview of pleuropulmonary diseases associated with rheumatoid arthritis" and "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis", section on 'Cardiac disease'.)

●The neurologic exam may demonstrate hyperreflexia and impaired balance, which can occur in patients with cervical myelopathy, and changes due to peripheral neuropathy can be present. Periarticular muscle atrophy and resultant weakness are often present.

Laboratory findings — The complete blood count, platelet count, and acute phase reactants should be normal in patients with end-stage RA. Patients with longstanding RA often demonstrate a normochromic normocytic anemia, but in the complete absence of disease activity this anemia of chronic disease (anemia of chronic inflammation) should be absent.

The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with end-stage disease are generally in the normal range or only marginally elevated. The serum albumin may be reduced in patients with residual disease activity but is normal in patients who have no active inflammatory process.

The rheumatoid factor and anti-citrullinated peptide antibodies are often positive in patients with end-stage disease, given their prevalence in the majority of patients with RA and association with poor prognosis RA.

Joint effusions, are small if present, typically demonstrate few white blood cells with a relative lymphocytosis.

In patients who have undergone joint surgery, scant synovial tissue or advanced fibrosis is observed in those with end-stage disease, unlike the synovium in the patient with ongoing inflammation, which may show the characteristic histopathology of rheumatoid synovitis. (See "Synovial pathology in rheumatoid arthritis".)

Imaging abnormalities — Imaging in patients with end-stage RA shows joint destruction without evidence of ongoing inflammation. Plain radiographs in patients with end-stage disease show marked articular damage, including cartilage loss with severe loss of joint space that can lead to bone-on-bone changes, subluxations, and erosions, including some that have healed over time. There may be periarticular osteopenia around severely affected joints. Changes consistent with osteoarthritis may develop in joints previously damaged by an inflammatory synovitis, with bony hypertrophy and osteophyte formation.

A trace synovial effusion is sometimes evident, as in osteoarthritis, but in end-stage disease neither a power Doppler signal on ultrasound indicating joint hyperemia nor bone edema suggesting synovitis on magnetic resonance imaging (MRI) are generally observed.

Neuropathology — Several abnormalities have been described in a postmortem study of the spinal cord and brainstem in nine patients with end-stage RA [6]. Cranial nerve and brainstem pathology was rare, but in addition to craniocervical compression, there were widespread subaxial changes in the spinal cord. Pathology was localized primarily to the dorsal white matter, despite a history of ventral compression. There was no evidence of vasculitis or ischemic changes in the blood vessels.

EVALUATION OF PATIENTS WITH END-STAGE DISEASE — Recognition of patients with end-stage rheumatoid arthritis (RA) can usually be achieved without much difficulty based upon the presence of characteristic symptoms and physical findings (see 'Definition' above and 'Symptoms' above and 'Physical findings' above); however, the evaluation of patients with apparent end-stage disease also requires:

●Identification of patients who would potentially benefit from treatment with antiinflammatory and/or antirheumatic drug therapy for residual synovitis that may be present despite widespread end-stage changes.

●Detection of factors other than articular inflammation that may be contributing to the clinical state and may require interventions distinct from antirheumatic drug therapy, such as extraarticular complications, comorbid disorders, and end-stage joint destruction. The presence or absence of extraarticular disease (eg, pulmonary, cardiovascular, or neurologic involvement) may be independent of the degree of joint damage, but extraarticular disease is more often seen in patients with more aggressive forms of RA.

Attention to a number of particular features as part of the detailed evaluation of these patients facilitates the assessment. (See 'History and physical examination' below and 'Laboratory, imaging, and other studies' below.)

History and physical examination — The patient should undergo a thorough history and physical examination, with a detailed musculoskeletal examination of the upper and lower extremity joints and the spine, including the observation of the patient walking, to identify characteristic features of end-stage RA, such as multiple structural deformities, and to exclude the ongoing presence of active inflammatory synovitis, such as warm joints with soft tissue swelling and evidence of joint effusions. (See 'Clinical manifestations' above.)

Other conditions that may be present in patients with advanced RA and cause joint pain and disability (eg, bursitis, tendinopathy, neuropathy) should be excluded as alternative causes of musculoskeletal pain. (See "Overview of soft tissue musculoskeletal disorders" and "Neurologic manifestations of rheumatoid arthritis".)

Examples of questions that may be especially useful to identify whether the patient who is suspected of having end-stage RA lacks evidence for ongoing disease activity include:

●Is there worsening or a change in the degree of morning stiffness that might suggest increased systemic inflammatory activity? It should be noted that while morning stiffness is a symptom suggesting active joint inflammation that its presence may also reflect the effects of severe joint contractures and ankylosis resulting from end-stage disease. (See "Clinical manifestations of rheumatoid arthritis".)

●Has the patient's pain changed in any way? Does the degree of pain in a particular joint correlate with the physical exam findings and the imaging studies? For example, pain around the hips or above the knee may be caused by advanced arthritis damage in the hips, but it may also be due to a lumbar radiculopathy or spinal stenosis that is not related to having RA. (See 'Laboratory, imaging, and other studies' below.)

Another cause of pain occurs in frail patients who may be predisposed to sustaining bone fractures following incidental trauma.

●Is there new nighttime pain? If so, consideration should be given to an underlying bursitis such as:

•Shoulder – Subacromial bursa

•Elbow – Medial or lateral epicondyle

•Hip – Trochanteric bursa

•Knee – Anserine bursa

●Is the pain suspicious for nerve irritation? Consider carpal tunnel syndrome, tarsal tunnel syndrome, peripheral neuropathy.

●Has there been a progressive decline in their functional status that cannot be readily explained by their structural joint disease? One should consider the diagnoses of cervical myelopathy or lumbar spinal stenosis.

●Is one particular joint most affected by pain? The combination of joint damage, poor functional status, and possibly the continued use of glucocorticoids may heighten the risk that patients with end-stage RA have for developing septic arthritis.

Additional issues of note in patients with suspected end-stage disease include the following:

●Changes consistent with osteoarthritis may develop in joints previously damaged by an inflammatory synovitis. Bony hypertrophy and osteophyte formation can, therefore, be observed. These features should not be mistaken for the synovial thickening observed in active RA. Plain radiography and/or ultrasonography may be required to identify and distinguish these possibilities. (See "Clinical manifestations and diagnosis of osteoarthritis".)

●Examination of more superficial joints, such as the elbows, wrists, knees, and metacarpophalangeal joints may provide a better assessment for the presence of synovial thickening, which is considered a hallmark feature of active, inflammatory synovitis. In patients with end-stage RA, the structural deformities and secondary bony overgrowth may contribute to a false appearance of synovitis. The development of joint contractures implies that there has been significant joint injury.

●Although pain at rest is highly suggestive of end-stage joint damage, an adjacent bursitis, tendonitis, or nerve entrapment syndrome may produce similar pain. These possibilities may be distinguished by findings on physical examination, nerve conduction studies, and radiographs of the affected joint, which should confirm the presence of joint destruction in end-stage disease. (See "Overview of soft tissue musculoskeletal disorders".)

●Neurologic examination should focus upon excluding conditions that could contribute to the functional decline of the patient. These include cervical myelopathy due to disease causing subluxation at the atlantoaxial joint and peripheral neuropathy [7]. (See "Clinical manifestations of rheumatoid arthritis" and "Cervical subluxation in rheumatoid arthritis" and "Clinical manifestations and diagnosis of rheumatoid vasculitis" and "Neurologic manifestations of rheumatoid arthritis".)

Laboratory, imaging, and other studies

●Laboratory studies – Laboratory testing should include:

•Complete blood count, differential white count, and platelet count – These findings are normal in patients with only end-stage RA, but patients with residual disease activity can exhibit anemia of chronic disease (anemia of chronic inflammation), which is normochromic and normocytic, and may have mild leukocytosis and an elevated platelet count. (See "Clinical manifestations of rheumatoid arthritis", section on 'Laboratory findings' and "Anemia of chronic disease/anemia of inflammation".)

•Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which are normal or only mildly elevated in end-stage disease, unless other conditions are present, but typically at least modestly elevated in patients with residual disease activity. (See "Biologic markers in the assessment of rheumatoid arthritis", section on 'Disease activity and prognosis: Acute phase reactants'.)

It is particularly helpful to compare the values obtained at the time of assessment with those obtained during a period of definite, ongoing inflammation. (See "General principles and overview of management of rheumatoid arthritis in adults" and "General principles and overview of management of rheumatoid arthritis in adults", section on 'Assessment and monitoring'.)

Rheumatoid factor and anti-citrullinated peptide antibody testing do not provide information regarding disease activity and are not useful to measure in patients with known RA and end-stage disease.

●Synovial fluid and tissue – In patients who do have evidence of synovial effusion, arthrocentesis should be performed to determine if inflammatory fluid and any other cause of a joint effusion are present. Testing should include a cell count, differential white count, Gram stain, microbial culture, and crystal search. Joint effusions, if present in end-stage disease, typically demonstrate few white blood cells with a relative lymphocytosis, unlike the predominant neutrophilia of inflammatory synovial fluid.

The histopathologic findings of surgically obtained synovial tissue should be reviewed in patients who have undergone joint surgery previously.

●Imaging and other studies – Previously obtained imaging studies should be reviewed to confirm the presence of joint injury, such as joint space narrowing consistent with loss of cartilage and joint erosions. If several years have elapsed since imaging studies, repeat radiographs of the severely affected joints are helpful in assessing a change in status. In patients in whom there is uncertainty regarding the possibility of active inflammation in a particular joint or a group of joints, a power Doppler ultrasound study can help to determine if active synovitis is present. (See "Musculoskeletal ultrasonography: Clinical applications", section on 'Synovitis'.)

Imaging studies may also be useful in clarifying whether bursitis, tendinopathy, or other conditions are causing pain; and whether extraarticular manifestations of RA such as pulmonary, cardiovascular, or neurologic involvement are present, as there is a high-risk of complications in patients with typically longstanding, aggressive disease, and end-stage changes, even though the presence or absence of extraarticular disease may be independent of the joint damage that has occurred. Imaging may be warranted when assessing patients for possible surgical options such as joint arthroplasty. Electrodiagnostic studies may be useful in patients suspected of cervical myelopathy or peripheral neuropathy.

MANAGEMENT — The management strategy depends upon whether the patient is on antirheumatic drug therapy at the time of the evaluation, whether there is evidence of residual disease activity, and the potential benefits and risks of surgical intervention. (See 'Disease activity present or suspected' below and 'Disease activity absent' below.)

All patients with end-stage disease should be referred for occupational therapy and/or physical therapy evaluation and management, depending upon their specific needs, if they are not already receiving such care. (See 'Rehabilitation therapies' below.)

Patients with an extraarticular manifestation or comorbid condition should be treated or referred for management of that condition by the appropriate expert depending upon the particular disorder that is present.

Disease activity present or suspected

Patients currently receiving antirheumatic drug therapy — In patients with end-stage rheumatoid arthritis (RA) and lacking evidence of disease activity (see 'Evaluation of patients with end-stage disease' above), but receiving antirheumatic drug therapy such as DMARDs (traditional DMARDs, biologic DMARDs, or a kinase inhibitor) or antiinflammatory agents (nonsteroidal antiinflammatory drugs [NSAIDs] or glucocorticoids), it should be determined whether these drugs are beneficial for the patient. Their continued use needs to be weighed carefully against the hazards associated with their long-term use, and the discontinuation of unneeded agents reduces the risk of drug-related harms.

This determination can be highly subjective, although most patients are able to gauge whether they feel better when taking these drugs. Patients can often report whether their disease became more symptomatic or if joint swelling occurred when they missed one or more of their medications for some period of time. If attempted, a slow withdrawal of the medication should be initiated, and careful follow-up can determine whether the drug can be tapered to a lower dose or discontinued altogether. The frequency of follow-up for clinical assessment and frequency and nature of laboratory testing are determined by the expected duration of the clinical effect of the agent being withdrawn.

Only one drug should be withdrawn at a time. The order in which drugs are chosen to reduce doses or for discontinuation needs to be individualized and is determined by an assessment of the relative risks of the patient's therapies given their overall clinical status and comorbidities.

Patients NOT currently receiving antirheumatic drug therapy — Some patients who are characterized as having end-stage disease may nevertheless demonstrate progressive disease, and those who are not currently being treated with DMARDs or antiinflammatories may benefit from a trial of drug therapy to assess whether they note improvement in their quality of life. As examples:

●In patients with history, examination, and/or laboratory evidence of likely ongoing disease activity, despite findings also suggesting the presence of end-stage disease, we may initiate a three-month trial of a traditional nonbiologic DMARD, such as methotrexate or leflunomide; or a biologic agent such as a tumor necrosis factor (TNF) inhibitor. Before selecting an agent, the patient's past drug use should be reviewed to determine which agent may be the best choice. For example, drugs that have previously resulted in significant side effects or failed to show efficacy when prescribed in therapeutic doses should be avoided.

The approach to these patients is determined by the prior history of drug usage and the tolerance of efficacy of those agents, as in patients without end-stage disease. (See "General principles and overview of management of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial conventional synthetic (nonbiologic) DMARD therapy" and "Initial treatment of rheumatoid arthritis in adults" and "Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy".)

●In patients in whom there is uncertainty regarding whether disease activity is present, the presence of active inflammation may be confirmed by a clinical response to oral glucocorticoid therapy. A trial of low-dose prednisone, not exceeding 10 mg per day to start, might provide a fairly prompt clinical response that can be observed within weeks. If symptoms are better controlled, the drug can be slowly reduced to the lowest dose needed to control symptoms, generally between 3 to 7 mg per day. (See "Initial treatment of rheumatoid arthritis in adults", section on 'Glucocorticoids' and "Use of glucocorticoids in the treatment of rheumatoid arthritis".)

In patients in whom uncertainty remains after a trial of glucocorticoids, an ultrasound examination may be useful in identifying whether evidence of ongoing inflammatory synovitis is present. (See 'Laboratory, imaging, and other studies' above and "Musculoskeletal ultrasonography: Clinical applications", section on 'Synovitis'.)

●In patients with a small number of active joints that can be injected, intraarticular glucocorticoid injections may provide temporary pain relief and can be repeated episodically. Such injections may be of particular benefit in patients unlikely to tolerate systemic therapies. (See "Initial treatment of rheumatoid arthritis in adults", section on 'Glucocorticoids' and "Use of glucocorticoids in the treatment of rheumatoid arthritis", section on 'Intraarticular therapy' and "Intraarticular and soft tissue injections: What agent(s) to inject and how frequently?".)

Disease activity absent — Patients with end-stage joint disease no longer amenable to DMARDs and antiinflammatory therapy may benefit from surgical intervention, while others may benefit from chronic pain management interventions, including the use of opioid analgesic medications, particularly if they are not candidates for surgical intervention. (See 'Chronic pain management' below and 'Surgical management' below.)

Chronic pain management — Due to the severity of the joint damage noted in some patients, opioid analgesics may rarely be required to provide adequate pain control, particularly if the level of pain is severe and if surgical options, such as joint arthroplasty or joint fusion, are contraindicated. Thus, when necessary, a trial of an opioid drug such as tramadol might be considered ahead of more potent agents such as codeine, hydrocodone, or oxycodone. Pain-modifying drugs such as milnacipran or duloxetine, which have shown some benefit in reducing pain in patients with advanced knee osteoarthritis, might be appropriate for some patients with chronic pain related to advanced joint damage [8].

Referral to a chronic pain specialist may also be of benefit in such patients. (See "Approach to the management of chronic non-cancer pain in adults".)

Surgical management — A careful review of the patient's history and their joint exam can help determine whether a patient may benefit from an orthopedic intervention such as joint arthroplasty or fusion for relief of pain and sometimes for improvement in function. Plain radiographs may confirm the presence of end-stage changes in a particular joint. This finding may help confirm the need for joint arthroplasty in a shoulder, elbow, hip, or knee. Similar changes in the hands or ankles may suggest the need for fusion of these joints. (See "Surgical management of end-stage rheumatoid arthritis".)

The need for intervention for cervical spine involvement should be assessed. (See "Cervical subluxation in rheumatoid arthritis", section on 'Surgery'.)

Pain emanating from a nerve impingement syndrome such as carpal or tarsal tunnel syndrome may be alleviated by surgical decompression. Pain due to lumbar radiculopathy either at the cervical or lumbar level may benefit from a surgical evaluation.

Rehabilitation therapies — Patients with end-stage disease should undergo a careful evaluation by an experienced physical and/or occupational therapist. (See "Nonpharmacologic therapies for patients with rheumatoid arthritis", section on 'Occupational therapy' and "Nonpharmacologic therapies for patients with rheumatoid arthritis", section on 'Physical therapy'.)

The goals of such an assessment should include:

●Development of a home exercise program to maintain joint range of motion and to prevent further functional decline

●The use of splints to prevent or correct joint contractures

●An assessment of activities of daily living to evaluate whether assistive devices would benefit the patient

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Rheumatoid arthritis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Rheumatoid arthritis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Rheumatoid arthritis treatment (Beyond the Basics)" and "Patient education: Disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Events that may culminate in end-stage rheumatoid arthritis (RA) usually occur over years to decades and include any combination of the following: refractory disease, which has failed to respond to multiple therapies; intolerance or development of toxicity to one or more antirheumatic therapies, thereby requiring the discontinuation of agents which may have been beneficial; prolonged delay in the initiation of traditional disease-modifying antirheumatic drug (DMARD) therapy or of a biologic agent; and poor compliance with the therapeutic regimen. (See 'Etiologic factors' above.)

●End-stage RA is characterized clinically by pain occurring with minimal activity and at rest, periarticular muscle atrophy and weakness, a significant decline in functional status resulting in disability, and radiographic evidence of articular damage (eg, severe loss of joint space and/or erosions). There is usually an absence of evidence for inflammation on the complete blood count and on measurement of acute phase reactants and serum albumin. Synovial histopathology in patients requiring surgery demonstrates advanced fibrosis, without evidence of active synovitis. (See 'Clinical manifestations' above and 'Laboratory findings' above.)

●Patients presumed to have end-stage RA should be carefully evaluated to exclude the possibility of untreated active synovitis and to determine if factors other than articular inflammation may be contributing the symptoms and findings; they should also be assessed for the presence of extraarticular disease manifestations. (See 'Evaluation of patients with end-stage disease' above.)

●The management strategy depends upon whether the patient is on antirheumatic drug therapy at the time of the evaluation, whether there is evidence of residual disease activity, and the potential benefits and risks of surgical intervention. Low-dose oral glucocorticoids, intraarticular glucocorticoids, and various analgesic medications may be of benefit; a trial of low-dose oral glucocorticoids may be of use particularly in patients in whom the presence of active joint disease remains uncertain. (See 'Disease activity present or suspected' above and 'Disease activity absent' above.)

●Surgery, including interventions for severe cervical spine involvement, may play an important role in the management of patients with end-stage RA. (See 'Surgical management' above.)

●All patients with end-stage disease should be referred for occupational therapy and/or physical therapy evaluation and management, depending upon their specific needs, if they are not already receiving such care. (See 'Rehabilitation therapies' above.)