Rheumatologic Rehabilitation




Introduction to Rheumatic Diseases


Rheumatic diseases manifest as painful conditions typically caused by inflammation, swelling, and pain in the joints or muscles. Because pain, swelling, and decline in functional status are the presenting symptoms, patients with rheumatic diseases can make up a large percentage of a physiatry practice ( Table 31-1 ). There have been a growing number of people with rheumatic diseases who also largely contribute to the population of the permanently disabled. This has commanded the evolution and refinement of the treatment of these diseases. Thus, it is important to keep this chapter current and informative. Physiatrists can be the primary physicians for diagnosing and coordinating treatment for most of these diseases. To diagnose and treat these disorders, one must have an understanding of the joints and their components, as well as the nomenclature involved.



Table 31-1

Main Types of Rheumatic Diseases




































Disease Group Description Examples
Degenerative and overuse syndromes Diseases where repetitive trauma and “wear and tear” cause inflammation Osteoarthritis, tendonitis, bursitis
Inflammatory arthropathies Diseases with chronic inflammation of unknown cause; classified by pattern of joint involvement and associated features Rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies
Extraarticular rheumatism Poorly understood disorders characterized by chronic pain with no evidence of inflammation Fibromyalgia, nonspecific neck pain, nonspecific back pain
Connective tissue diseases Autoimmune diseases of unknown etiology characterized by multisystem inflammation and damage Systemic lupus erythematosus, polymyositis, dermatomyositis, scleroderma, vasculitis
Crystal-associated arthropathies Diseases characterized by acute or recurrent inflammation caused by deposition of crystals in or around joints Gout, calcium pyrophosphate crystals, hydroxyapatite crystals
Infectious arthropathies Diseases caused by invasion of joint tissue by microorganisms Viral, bacterial, tuberculosis, fungi
Postinfectious arthropathies Diseases triggered by previous exposure to infectious agents Poststreptococcal, postchlamydial, postviral




Structure and Components of Joints


All joints can be affected by rheumatic diseases. Joints are classified based on structure and function. Structure classification is based on the material that binds the bones together and the presence or absence of a joint cavity. Functional classification is based on the amount of movement allowed. There are three major types of joints in the body: fibrous joints (synarthroses), cartilaginous joints (amphiarthroses), and synovial joints (diarthroses). Fibrous joints (synarthroses) are immovable and do not have a joint cavity. An example would be the sutures of the cranium. For the purposes of this chapter as it relates to physiatry, the focus will be on cartilaginous joints and synovial joints.


The cartilaginous joints are distinguished by the connection between bones being entirely made of cartilage (fibrocartilage or hyaline). They are characterized by the amount of movement allowed across the joint. It is significantly less mobile than a synovial joint. It does not have a joint cavity. As a rule, amphiarthroses usually occur in the midline of the body. There are two types, synchondroses and symphyses. The manubrium and sternum are examples of synchondroses, whereas intervertebral disks and pubic symphysis are classified as symphyses.


The synovial joint (diarthrosis) is characterized by its joint mobility. These joints are able to move freely in multiple planes. It consists of two bony surfaces that articulate with one another. It is encompassed by a fibrous capsule with a synovial lining that contains fluid. The extracellular matrix consists of water and proteoglycans (glycosaminoglycan and hyaluronic acid). The viscoelastic properties of the synovial fluid and its inherent function as a lubricant and shock absorber are largely attributed to hyaluronic acid. The fibrous capsule has a rich network of substance P (neurotransmitter for pain) with nociceptive nerve fibers that can potentially generate pain. The limb joints are typically synovial joints (hip, knee, shoulder).


While inflammation ensues, fluid and polymorphonuclear leukocytes infiltrate the joint space. Vasodilation and venous congestion all contribute to pain-provoking capsular distention and neuronal sensitization of substance P nerve fibers. It is important to understand this cascade when educating patients on why they have joint pain and why treatment is aimed at limiting the damage from this cascade. If left untreated, the inflammatory cascade can destroy the integrity of a joint and permanently impair its function. This can lead to chronic pain and disability.


Kinematics plays an important role in the development and degradation of articular cartilage. Although joints with articular surfaces need a certain amount of load to maintain its integrity, excessive loading can lead to degradation of the joint. Altered biomechanical values between two articular surfaces also influence disease formation in joints. Normal healthy cartilage responds positively to loading by increasing regional thickness. Diseased or injured cartilage degenerates in response to load and thus decreases regional thickness. Furthermore, disruption of normal gait mechanics whether from disease, acute injury, weight gain, or improper footwear shifts loading patterns during weight-bearing activity to cartilaginous regions not well adapted for that load. Loading nonadapted areas can lead to cartilage fibrillation (softening) and degeneration.


Although not a part of the synovial joint but frequently associated with them, bursae, tendon sheaths, and entheses are important to acknowledge during the physical examination and diagnostic stages of rheumatic diseases. They act to prevent friction on adjacent structures. Bursae are flattened fibrous sacs lined with a synovial membrane and contain a thin film of synovial fluid. They are common in sites where ligaments, muscles, skin, or tendons overlie and rub against bone. Tendon sheaths are elongated bursae that wrap around a tendon that is subject to friction. Entheses are the insertion sites of tendons to bones or ligaments to bones. They are functionally integrated with the synovial joint and can be involved in the rheumatic disease processes. The relationship of the surrounding soft tissue structures will be crucial for understanding the microanatomic basis for joint disease in seronegative spondyloarthropathies and other rheumatic diseases, such as osteoarthritis (OA).




Osteoarthritis


OA is one of the most common rheumatic diseases. OA has grown to affect 27 million people in the United States. It is the leading cause of musculoskeletal pain and disability. It is predicted that with the increasing rates of obesity and the increase in the aging population, there will be an epidemic of OA in the next two decades. It is more important now than ever to have a sound knowledge base for treating and preventing this disease.


OA is classified by its failure of the structure and function of synovial joints. It is characterized by its degradation of articular cartilage, subchondral bone alteration, meniscal degeneration, synovial inflammatory response, and overgrowth of bone and cartilage. The etiology of OA is multifaceted and can affect both weight-bearing and non–weight-bearing joints. OA can be initiated as a result of mechanical, structural, genetic, and environmental factors. When repeated exposure to physical activity is not offset with reciprocal time for tissue repair, bone resorption outweighs bone deposition. This cycle over time is the precursor for degenerative joint disease. Other factors that influence bone resorption include hormone levels such as estrogen and vitamin D. Estrogen influences the rate of cell turnover. Vitamin D deficiency impairs bone deposition. Now that there is an increasing population of people that are vitamin D deficient, there is a link to OA prevalence, incidence, and progression. Most studies involving this link have been site specific to the knee.


The risk of having OA is higher with age older than 45 years, women, obesity, bone deformities, joint injuries, and certain occupations with repetitive stress on particular joints. Advanced age is the strongest risk factor for the prevalence and incidence of OA. The estimates for influence of genetic factors in radiographic OA of the knee, hip, and hand are 39%, 60%, and 59%, with a similar range of estimates for cartilage volume change and progressive knee OA.


Obesity is the primary modifiable risk factor that has the greatest potential for having an impact on treating the disease. Obese and overweight people have three times the risk of knee OA. By reducing the body mass index from more than 30 to less than 25, up to 29% of knee OA could be prevented. The estimated risk of progression from symptomatic early OA to advanced OA for adults in the United States 60 to 64 years of age is 63% during a 10-year period in obese adults versus 37% in nonobese adults. In contrast to knee OA, the association between obesity and incident of hip OA has been inconsistent.


Obesity has a systemic and a local mechanical effect on joints in OA. The radiographic findings in symptomatic OA of the hand emphasize the systemic factors in the link between obesity and OA, because unlike the knees or hips the hands are not primary weight-bearing joints. It is speculated that with excessive fat accumulation and intramuscular fat, there is some low-grade systemic inflammation. This inflammation is now considered a hallmark of obesity with evidence in elevation in interleukins (IL-1beta, IL-6), tumor necrosis factor (TNF)-alpha, and the acute-phase reactant C-reactive protein (CRP).


With advanced age and obesity being two of the major risk factors for having OA, it has to be mentioned that among the other joints the spine can be greatly affected. OA of the spine is a disorder of the synovial joints, the zygapophysial joints (z-joints), and the sacroiliac joint (SI joint). The z-joints function to support and stabilize the spine during loading, whereas the SI joint functions to transfer weight from the upper body to the lower extremities. OA does not account for all causes of z-joint and SI joint pain, but the relative percentage increases with age and obesity. Intervertebral disc degeneration and loss of inherent structural integrity can predispose the lumbar z-joints to degenerate. The L4 to L5 and L5 to S1 levels (both weight-bearing and mobility) are the eminent explanation for the highest incidence of OA. Degenerative arthrosis of SI joints may start at an earlier age and may predominantly affect the iliac cartilage. Blood vessels penetrate the subchondral bone plate of both the iliac and sacral facets and pass in close proximity to the articular cartilage. This may explain the high incidence of SI joint involvement in systemic inflammatory diseases.


There are various definitions of OA, both symptomatic and radiographic. Symptomatic OA usually includes pain, aching, and joint stiffness in the affected joint along with the presence of radiographic findings. Clinical criteria for diagnosis of knee and hip OA include pain, plus age older than 50 years old, stiffness for less than 30 minutes, and crepitus plus the radiographic finding of osteophytes. Knee OA may also include bony enlargement and bony tenderness.


Kellgren-Lawrence is the most common radiologic grading system ( Table 31-2 ). The Kellgren-Lawrence grading scale determines severity of knee OA on the presence and degree of osteophytosis, joint space narrowing, sclerosis, and deformity of the tibiofemoral joint. It is key to note that symptoms can appear before any changes occurring on x-ray (Grade 0). Also, the presence of an abnormal x-ray is not a reliable identifier for pain.



Table 31-2

Kellgren-Lawrence Radiographic Grading Scale for Osteoarthritis of the Tibiofemoral Joint






















Grade of Osteoarthritis Description
0 No radiographic findings of osteoarthritis
1 Doubtful narrowing of joint space and possible osteophytic lipping
2 Definite osteophytes with possible narrowed joint space
3 Definite osteophytes with moderate joint space narrowing and some sclerosis
4 Definite osteophytes with severe joint space narrowing, subchondral sclerosis, and definite deformity of bone contour


Treatment Options for Osteoarthritis


The treatment of OA has been expanding over the past few years. Treatments range from conservative and patient-driven to surgical interventions based on the severity of the disease process. Because pain and impaired function are typically the presenting symptoms, the treatment goals are directed at reducing pain and improving mobility. There is evidence that shows significant reduction in pain and improved physical performance and function in older adults after treatment that includes modest weight loss and moderate exercise. Resistance exercises to build the muscles that stabilize the involved joint have shown to reduce symptoms and improve functional mobility, even with severe OA. It has also been effective in the prehabilitation stage before a joint replacement to enhance postoperative recovery. The success of this treatment regimen, however, primarily lies in the patient’s ability to comply with caloric adjustments and exercise. The specific modalities of physical and occupational therapy will be discussed later in the chapter but need to be mentioned as an option for conservative treatment.


For acute exacerbations of OA pain, the frontline treatment is going to be pharmaceutical agents. In mild OA, acetaminophen is used as a first-line agent because of a benign safety profile. Its mechanism of action is thought to be central via its inhibition on spinal nitric oxide mechanism and substance P receptors. Despite most experts’ opinions that it does little for inflammation, it has demonstrated efficacy that is similar to that of nonsteroidal antiinflammatory drugs (NSAIDs). NSAIDs are commonly used as second-line agents in patients with moderate to severe pain. The mechanism of action is through cyclooxygenase and leukotriene inhibition, which prevents the conversion of arachidonic acid to prostaglandins. Changes in the progression of the disease have not been documented with the use of NSAIDs, despite their efficacy in reducing synovial and systemic inflammation. Long-term use of NSAIDs are associated with adverse side effects, particularly involving the gastrointestinal and renal systems. There have also been concerns regarding the cardiovascular effects of particular NSAIDs that are specific cyclooxygenase-2 inhibitors.


The numerous side effects of oral NSAIDs have caused a boom in the use of topical NSAIDs and analgesics. Patches and gels can be applied directly to the painful joint. There has also been an emergence of compounding pain creams that include a combination of NSAIDs and anesthetics that can be tailored to the needs of each individual patient. They can be useful also as an adjuvant with other therapies.


Most oral medications that are used for peripheral joints with OA are used for spine OA. A notable exception would be muscle relaxants, which can be beneficial in treating neck and back pain associated with OA. This class of medication decreases muscle spasms associated with spine OA. It should also be noted, however, that there is no benefit to use muscle relaxants long term. A formal spine-focused, flexion-based therapy program remains the cornerstone of treating spine OA long term. This should be used in conjunction with a home exercise program that addresses lumbar stabilization and core strengthening.


When oral medications are ineffective or if a patient has not been able to tolerate conservative treatment, intraarticular injections are considered. There are now various injectable medications including corticosteroids and viscosupplementation, such as hyaluronic acid. There are less traditional compounds that have gained a place in injectable treatment of OA, such as prolotherapy, NSAIDs, platelet-rich plasma, and botulinum toxin type A. Intraarticular injections should also be considered in patients who are surgical candidates but are trying to delay total joint replacement. Interventional spine procedures include fluoroscopy-guided corticosteroid injections and image-guided nerve blocks, particularly of the medial branches that innervate the z-joint. If this is successful in alleviating pain, the more expensive radiofrequency ablation of these branches can be considered.


Before considering surgical intervention, all nonoperative treatments should be exhausted. Total joint arthroplasty can offer some relief to those with severe refractory OA. Depending on the joint involved, there are proven long-term results. Hips and knees have the best outcome with pain relief and restoring function. Shoulders, elbows, and ankles can improve pain and function, but are associated with higher complication rates. In the spine, fusion of the z-joints and SI joints can also be considered to reduce pain and stabilize and restore function.


Note that the majority of patients will respond to conservative therapy. As the treating physiatrist, the initial plan should include education on activity modification, dietary changes, weight loss, and exercise. Pharmacologic treatment can be initiated to control symptoms but should be tailored to each individual patient based on severity, chronicity, and other organ system comorbidities. Although tramadol and opioids are potent analgesics, they should not be routinely used to treat OA long term as a result of their central nervous system side effects and risk of addiction and tolerance. Intraarticular injections should be used wisely because they have limitations in the frequency in which they are given depending on the medication being injected. Joint replacement surgery is reserved for last resort treatment.




Rheumatoid Arthritis


Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease of unknown etiology that primarily involves the joints. It also often involves soft tissues, such as tendon sheaths and bursae. In addition it may present with extraarticular manifestations. Inflammation and destruction of the joint and soft tissue may lead to joint deformity and loss of physical function. This can happen if left untreated or when the disease becomes unresponsive to treatment. The prevalence of RA varies from 0.3% to 1.5% of the population, with a female-to-male ratio of around 3 to 1.


Typically, the disease onset is insidious, with pain, stiffness, and swelling of the joints being the predominant symptoms. Morning stiffness, or stiffness after prolonged inactivity, often lasts more than an hour in the active inflammatory stage. Up to one third of patients with RA experience acute onset of polyarthritis associated with systemic symptoms including fatigue, myalgia, depression, low-grade fever, and weight loss. The most common joints involved in the early stage of the disease are the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the fingers, the interphalangeal joints of the thumb, the wrists, and the metatarsophalangeal joints of the toes. Other joints, such as the shoulders, elbows, hips, knees, and ankles are also frequently affected. Over the whole course of the disease, the facet and atlantoaxial joints of the cervical spine, and the acromioclavicular, sternoclavicular, temporomandibular, and cricoarytenoid joints may also be involved. The distal interphalangeal (DIP) joints are rarely involved in RA, perhaps resulting from less synovium than the MCPs and PIPs. In addition to involvement of the joints, tenosynovitis is also common in patients with RA, and may cause trigger finger, De Quervain disease, carpal tunnel syndrome, tendon rupture, and even compression of the cervical cord resulting from narrowing of the space available for the upper cervical cord.


In the late stage of RA, joint deformities commonly occur. Buttonhole (or bouttonière) deformity is flexion of the PIP joints, with extension of the DIP joints ( Figure 31-1, A ). Because the central extensor tendon is destroyed by tenosynovitis, the PIP joints pop up dorsally, resulting in lateral and ventral displacement of the lateral bands of the extensor tendon. In this condition, the lateral bands of the extensor tendon act as flexors of the PIP joints and, with tendon shortening, hyperextension of the DIP joints develops. In contrast, the swan neck deformity is the opposite of the buttonhole deformity, with hyperextension of the PIP joints and flexion of the MCP and DIP joints ( Figure 31-1, B ). Shortening of the intrinsic muscle exerts tension on the dorsal tendon sheath, leading to hyperextension of the PIP joints. The lateral bands of the extensor tendon sublux dorsally as the PIP joints herniate in the ventral direction. In addition, shortening of the deep flexor tendons causes flexion of the DIP joints. Other deformities include ulnar deviation ( Figure 31-1, C ) of the MCP joints, palmar subluxation of the wrists, arthritis mutilans, hammer toe deformity, clawed toe deformity, flat feet, hallux valgus ( Figure 31-1, D ), metatarsal joint subluxation, and “Z” deformity of the thumb (hyperextension of the interphalangeal joint, flexion, and subluxation of the MCP joints).




FIGURE 31-1


Typical deformities of the hands and foot in patients with rheumatoid arthritis. A, Buttonhole (the third finger) deformity. B, Swan neck (the second finger) deformity. C, Ulnar deviation. D, Hallux valgus and toes overriding.


As a result of the extraarticular foci of the immune response, patients with RA may have different types of extraarticular manifestations during the course of the disease. Common extraarticular features include fatigue, mild normocytic normochromic anemia, rheumatoid nodule (subcutaneous nodule, occurs in 15% to 20% of patients with RA), scleritis, episcleritis, myositis, vasculitis, neuropathy, pericarditis, interstitial pneumonitis and fibrosis, nodular lung disease, myocarditis, cardiac conduction defect, Felty syndrome (RA with neutropenia and splenomegaly), Sjögren syndrome, and amyloidosis. Vasculitis is a serious condition; it can present itself in five different clinical ways: distal arteritis, cutaneous ulceration, palpable purpura, arteritis of viscera, and peripheral neuropathy (mononeuritis multiplex or distal sensory neuropathy). Extraarticular features may be associated with poor prognosis, particularly vasculitis and rheumatoid lung disease. The presence of rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPAs) is also common in patients with RA.


Until 2010, the classification criteria for RA had been based on the 1987 American Rheumatism Association (ARA) revised criteria, which included four clinical criteria (morning stiffness, arthritis of ≥ 3 joint areas, arthritis of hand joints, and symmetrical arthritis), positive RF, the presence of rheumatoid nodules, and radiographic changes ( Box 31-1 ). The four clinical criteria must have been present for 6 weeks. These criteria may be useful for clinical study and can rule out some varieties of transient polyarthritis (e.g., acute viral polyarthritis). However, a major drawback of these criteria is their ineffectiveness in identifying some patients with early disease who subsequently have typical RA because rheumatoid nodules and radiographic erosive changes are usually not present in the early stage of disease. In addition, ACPA testing (which has a similar sensitivity for RF, but is much more specific for RA) was not previously available. In contrast, the ARA criteria did not require any exclusion, thus a patient could initially fulfill the diagnostic criteria of RA, but evolve into other diagnoses later, particularly Sjögren syndrome, scleroderma, psoriatic arthritis, crystalline arthritis, and systemic lupus erythematosus (SLE). To facilitate earlier diagnosis of RA and thus early effective treatment, The Joint Working Group of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) developed new classification criteria for RA in 2010 ( Table 31-3 ). The 2010 criteria comprises four domains: (1) type and number of affected joints, (2) RF and ACPA, (3) acute phase reactants (CRP and erythrocyte sedimentation rate [ESR]), and (4) the duration of symptoms. For evaluation of a patient with suspected RA, the highest category within each domain is taken and the four respective numbers are added. The maximum possible score is 10, where any score ≥6 indicates the presence of RA. The new criteria place a greater emphasis on serology and imaging studies (ultrasound and magnetic resonance imaging [MRI]), which can also be used to evaluate synovitis.



Box 31-1

1987 Revised American Rheumatism Association Criteria for Classification of Rheumatoid Arthritis*


Morning stiffness : Morning stiffness in and around the joints, lasting at least 1 hour, before maximal improvement.


Arthritis of three or more joint areas: Soft tissue swelling of fluid (not bony overgrowth alone) observed by a physician in at least three joint areas simultaneously. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints.


Arthritis of hand joints: At least one area swollen (as defined above) in a wrist, MCP, or PIP joint.


Symmetrical arthritis: Simultaneous involvement of the same joint areas (as defined above for criterion 2) on both sides of the body (bilateral involvement of PIP, MCP, or MTP joints is acceptable without absolute symmetry).


Rheumatoid nodules: Subcutaneous nodules, over bony prominences, on exterior surfaces, or in juxtaarticular regions, observed by a physician.


Serum rheumatoid factor: Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in less than 5% of normal controls.


Radiographic changes: Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosion or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify).


*For classification purposes, patients have rheumatoid arthritis if they have satisfied at least four of these seven criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with two clinical diagnoses are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is not to be made.


MCP, Metacarpophalangeal; MTP, metatarsophalangeal; PIP, Proximal interphalangeal.


From Arnett FC, Edworthy SM, Bloch DA, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum 31:315-324, 1988.


Table 31-3

2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis Score-Based Algorithm for Classification in an Eligible Patient (cut-off point for rheumatoid arthritis: ≥6/10)



















































Joint Involvement * (0 to 5)
1 medium to large joint 0
2 to 10 medium to large joints 1
1 to 3 small joints (with or without involvement of large joints) 2
4 to 10 small joints (with or without involvement of large joints) 3
>10 joints (at least one small joint) 5
Serology (0 to 3)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
Acute Phase Reactants 1
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
Duration of Symptoms (0 to 1)
<6 weeks 0
≥6 weeks 1

ACPA, Anticitrullinated protein/peptide antibody; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; RF, rheumatoid factor.

Adapted, with permission, from Aletaha D, Neogi T, Silman AJ, et al: 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative, Ann Rheum Dis 69:1580-1588, 2010.

* Joint involvement refers to any swollen or tender joint on examination, or evidence of synovitis on magnetic resonance imaging or ultrasonography. Distal interphalangeal joints, first carpometacarpal joint, and first metatarsophalangeal joint are excluded from assessment.


Medium to large joints refer to shoulders, elbows, hips, knees, and ankles.


Small joints refer to the metacarpophalangeal joints, proximal interphalangeal joints, metatarsophalangeal joints 2 through 5, thumb interphalangeal joints, and wrists.



The comprehensive management of RA requires a combination of nonpharmacologic measures, medical interventions, and surgery. Nonpharmacologic measures include patient education, relative rest with appropriate exercise, physical therapy with modalities, occupational therapy, proper orthoses, shoes, and durable medical equipment. Nutritional counseling, psychosocial interventions, vocational training, and measures to prevent complications of drug therapy are also an integral part of treatment. Most of these measures are covered in the domain of rehabilitation management, which will be discussed later in this chapter.


Medical treatment of RA aims to control synovitis and prevent joint injury. Evidence suggests that significant, irreversible joint injury may occur as early as the first 2 years. Measures aimed at identifying early active RA and reducing inflammation are essential for improving disease outcomes. Over the past 3 decades, there has been a significant increase in the number of disease-modifying antirheumatic drugs (DMARDs) available. The 2010 ACR/EULAR classification criteria for RA facilitate recognition of patients with early arthritis, who are most likely to have progressive and erosive disease. The choice of treatment depends on the level of disease activity, stage of therapy (initial versus subsequent therapy), regulatory restrictions, and patient preference. Once the diagnosis of RA is established, antiinflammatory therapy with an NSAID or a glucocorticoid is suggested, and generally nonbiologic DMARD therapy begins, including methotrexate, hydroxychloroquine, sulfasalazine, or leflunomide ( Table 31-4 ). Among the different nonbiologic DMARDs, methotrexate is most commonly used. Although NSAIDs are potent antiinflammatory drugs, they are not disease-modifying and have potential serious side effects; thus their use over time as monotherapy should be avoided. Combining NSAIDs with DMARDs is recommended. Glucocorticoids are also potent antiinflammatory drugs. They are particularly useful at the onset of disease. Glucocorticoids are used as a bridging strategy, during which they are tapered while the DMARDs take effect. They can also be used during disease flare or used as local injection agents when one or two joints or soft tissues are more inflamed.



Table 31-4

Nonbiologic Disease-Modifying Antirheumatic Drugs




















































Drug (Brand Name[s]) Response Rate; Onset of Action Magnitude of Efficacy
0 to ++++
Dosage Special Instructions Common Side Effects Comments
Hydroxychloroquine (Plaquenil) 30% to 50%
2 to 6 mo
++ 200 to 600 mg/day in 1 or 2 doses Take with milk or food, wear sunglasses in bright light Blurred vision, headache, skin pigmentation changes, rash, anorexia, abdominal cramps, nausea, vomiting Ophthalmologic examination, baseline and at 6-12 mo for retinal changes, complete blood count
Leflunomide (Arava) 50%
2 to 3 mo
++ 10 to 20 mg daily, single dose Loading dose of 100 mg/day for 3 days Alopecia, headache, hypertension, skin rash Avoid if pregnant; baseline hepatic function
Methotrexate >70%
6 to 8 wk
+++ 7.5 to 20 mg/wk in a single or divided doses Avoid alcohol, folic acid intake; adequate hydration Alopecia, headache, oral ulcers, photosensitivity, vasculitis, thrombocytopenia Baseline hepatic function; white blood cell and platelet count every 4 wk, complete blood count, creatinine, liver function test every 3-4 mo
Minocycline (Minocin, Dynacin) 200 mg/day Avoid antacid, iron, and dairy products Photosensitivity, dizziness Not FDA-approved for arthritis, check for tetracycline sensitivity
Sulfasalazine (Azulfidine) >30%
2 to 3 mo
++ 500 to 3000 mg daily; maximum 3 g in divided doses Take after meals, can permanently stain soft contact lenses yellow Headache, photosensitivity, diarrhea, vomiting, nausea, anorexia, reversible oligospermia Inadequate fluid intake can cause urine crystals

FDA, U.S. Food and Drug Administration.


If patients show an inadequate response after several months of aggressive doses of a nonbiologic DMARD, adding a second nonbiologic DMARD (step-up combination) or a biologic DMARD is suggested. Several biologic DMARDs are FDA (U.S. Food and Drug Administration)-approved for the treatment of RA. Biologic DMARDs include TNF inhibitors (etanercept, infliximab, adalimumab, and golimumab), IL-1 inhibitor (anakinra), IL-6 inhibitor (tocilizumab), T-cell costimulation inhibitor (abatacept), and B-cell depletion therapy (rituximab, an anti-CD20 chimeric monoclonal antibody) ( Table 31-5 ). Several clinical trials have shown that TNF inhibitors, IL-1 or IL-6 inhibitors are efficacious as monotherapies for the treatment of RA. The pitfalls of biologic DMARDs are the high cost, possible side effects, and some serious adverse events (infection, tuberculosis, demyelinating syndromes, increased risk of certain malignancy, and drug-induced lupus). With regular assessment of disease activity and tight control of treatment strategies, many patients with RA remain in remission or in a state of low-disease activity; thus joint destruction and physical disability are avoided. In patients with intractable pain, severe joint destruction, or poor response to long periods of medical treatment and rehabilitation, surgery may be considered. Common surgeries for patients with RA are artificial joint replacement, synovectomy (for the hand, wrist, elbow, knee, and tendon sheath), tendon repair, osteotomy, and arthrodesis (for the wrist, ankle, or cervical spine).



Table 31-5

Biologic Agents for Rheumatoid Arthritis
















































































Drug (Brand Name) Molecular Structures Response Rate; Onset of Action Dosage Administration Instructions Common Side Effects Other Comments
Non-TNF
Abatacept (Orencia) Recombinant receptor-IgG
Fc fusion protein; T-cell costimulation inhibition
50% to 70%; 4 wk IV infusion, 500 to 1000 mg, repeat at 2 and 4 wk, and every 4 wk thereafter; or 125 mg SC once weekly IV: Infuse over 30 min; administer through a 0.2 to 1.2 micron low-protein–binding filter
SC: Allow prefilled syringe to warm to room temperature (for 30 to 60 min) before administration
Headache, dizziness, nausea, dyspepsia, abdominal pain, diarrhea, nasopharyngitis, upper respiratory tract infection, urinary tract infection, other infections, hypertension, skin rash Higher incidences of infection and malignancy were observed in the older adult population; use caution with chronic obstructive pulmonary disease
Rituximab (Rituxan) Chimeric monoclonal antibody specific to CD20 (B-cell depletion) 65% to 85%; 4 to 12 wk IV infusion: 1000 mg on days 1 and 15 in combination with methotrexate; subsequent courses may be administered every 24 wk Dilute to a concentration of 1 to 4 mg/mL in either 0.9% sodium chloride or 5% dextrose
IV infusion: Start rate of 50 mg/hr; if there is no reaction, increase the rate by 50 mg/hr increments every 30 min, to a maximum rate of 400 mg/hr
Peripheral edema, hypertension, fever, fatigue, chills, headache, insomnia, pain, rash, nausea, neuropathy, abnormal liver function, hematologic abnormality Risk of reactivation of hepatitis B virus infection; do not administer IV push or bolus; severe infusion-related reaction may happen
Tocilizumab (Actemra) Anti–interleukin-6 receptor monoclonal antibody IV: Initial: 4 mg/kg every 4 wk; may be increased to 8 mg/kg (maximum dose: 800 mg)
SC: <100 kg: 162 mg every other week; increase to every week based on clinical response; ≥100 kg: 162 mg every wk
IV: Allow diluted solution for infusion to reach room temperature before administration; infuse over 60 min with a dedicated IV line
SC: Administer the full amount in the prefilled syringe; rotate injection sites
Anaphylaxis/hypersensitivity reactions, elevated liver enzymes, fatal infection, gastrointestinal perforation, neutropenia, thrombocytopenia Tuberculosis and malignancy have been reported; use is not recommended in patients with active hepatic disease or hepatic impairment; use with caution in patients with central nervous system demyelinating disease
Anti-TNF
Adalimumab (Humira) Human monoclonal antibody 46% to 73% 40 mg SC every 2 wk Prefilled pens, syringes, and vials are available for use; inject into thigh or lower abdomen Headache, skin rash, positive ANA titer, serious infection, local injection site reaction, increased creatinine phosphokinase, upper respiratory tract infection, sinusitis Live vaccines should not be given concurrently; anaphylaxis, tuberculosis, malignancy, demyelinating disease, heart failure are rarely reported
Etanercept Human recombinant receptor/Fc fusion protein 59% to 86%; 2 to 4 wk 25 mg SC on 2 different days, or 50 mg once weekly
Infliximab Chimeric monoclonal antibody
Certolizumab pegol (Cimzia) Humanized Fab fragment
Golimumab (Simponi) Humanized monoclonal antibody

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Feb 14, 2019 | Posted by in PHYSICAL MEDICINE & REHABILITATION | Comments Off on Rheumatologic Rehabilitation

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