Rehabilitation of the Patient with Rheumatic Diseases
Galen O. Joe
Jeanne E. Hicks
Lynn H. Gerber
Arthritic diseases are having an increasing impact on public health (1). It is estimated that musculoskeletal disorders are the most frequent cause of disability in developed countries (2). Currently, 46 million people are affected by arthritis, and this number is predicted to rise to 67 million by 2030. These individuals often sustain impairments, functional losses, and disability. The annual cost in medical care and lost wages is $128 billion (3). Twenty-first century physicians who care for these patients must be aware of current pharmacologic and rehabilitation strategies to control disease, limit impairment, preserve or enhance function, and reduce disability (1).
New trends have been developing in the management of inflammatory arthritis: (a) early use of disease-modifying antirheumatic drugs (DMARDs) in combination with reduction in disability (4), (b) a transition from passive patient involvement in treatment to self-efficacy, (c) a change from prescribing rest, to one of advocating relative rest and activity, (d) an increased use of rehabilitation early in the disease course, (e) a greater use of complementary and alternative therapies by patients and health care providers, and (f) an increased interest in which rehabilitation measures are available and are efficacious in achieving preventative and restorative goals for arthritis patients.
The specialty of rheumatology is dedicated to the understanding and control of disease activity. Physical Medicine and Rehabilitation has its roots in maintenance and restoration of function as well as prevention of dysfunction. This is achieved by having a keen knowledge of the impairments associated with the various rheumatic diseases (RDs) and the formulation of individualized treatment plans to maximize patient function by utilizing education, physical modalities and techniques, exercise, assistive and adaptive devices, energy conservation, joint protection, and vocational planning. The care of arthritis patients takes a multidisciplinary team effort. It is currently accepted that early diagnosis, medical treatment, and rehabilitation are preferable. Orthopedic interventions are often necessary and need to be appropriately timed.
This chapter addresses inflammatory diseases and their impact on the person as a whole, on specific joints, and on involved organ systems. Appropriate rehabilitation strategies are presented.
Inflammatory arthritis may involve a single joint or multiple joints, periarticular structures, and other organ systems. It may be an acute process that completely resolves (e.g., septic joint), or may be a chronic process (e.g., rheumatoid arthritis [RA]). Inflammatory arthritis may involve all the joint structures: synovium, cartilage, tendons, capsule, bone, and surrounding muscle. It is often part of a systemic RD (i.e., connective-tissue disease) such as RA, juvenile idiopathic arthritis (JIA) (formerly known as juvenile rheumatoid arthritis [JRA]), systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM-PM), progressive systemic sclerosis (PSS), or mixed connective-tissue disease (MCTD). These diseases are usually chronic, remitting, and relapsing; are variable in their course; and affect multiple organ systems in addition to joints. They most often require long-term treatments with pharmacological agents, which may have a significant impact on appearance, sleep, psychological function, and reproductive ability. The physiatrist directing the rehabilitation team must take these issues into account when evaluating and devising a treatment plan.
This chapter emphasizes the importance of a good initial evaluation, early treatment intervention, and periodic reevaluation of the arthritis patient. It describes the rational and stage-specific manner in which rehabilitative treatments are applied to the problems of patients with RDs and the current scientific evidence, or in the absence thereof, the seasoned clinical judgment for their use. Equally important is to stress the critical need of engaging the patient in his or her own treatment (5).
ARTHRITIC DISEASES
Classification
The important determinants in classifying arthritis are whether the disorder is inflammatory versus noninflammatory, symmetric versus asymmetric, or accompanied by systemic and extra-articular manifestations (Fig. 40-1). A detailed history and physical examination, and appropriate laboratory and x-ray studies will often allow a specific diagnosis to be made. Clinical features that suggest inflammatory rather than noninflammatory disease include: acute painful onset, fever, erythema
of the skin over the joint or joints involved, warmth of the joint or joints, and tenderness that usually parallel the degree of inflammation. Laboratory and x-ray findings that suggest an inflammatory process include an increased peripheral white blood cell count with left shift, an elevated erythrocyte sedimentation rate (ESR), a group II joint fluid (Table 40-1), and x-ray demonstration of soft-tissue swelling, periostitis, bony erosions, or uniform cartilage loss (Table 40-2).
of the skin over the joint or joints involved, warmth of the joint or joints, and tenderness that usually parallel the degree of inflammation. Laboratory and x-ray findings that suggest an inflammatory process include an increased peripheral white blood cell count with left shift, an elevated erythrocyte sedimentation rate (ESR), a group II joint fluid (Table 40-1), and x-ray demonstration of soft-tissue swelling, periostitis, bony erosions, or uniform cartilage loss (Table 40-2).
 FIGURE 40-1. Steps in the classification and diagnosis of RD. |
TABLE 40.1 Synovial Fluid Analysis | ||||||||||||||||||||||||||||||||||||||||||
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TABLE 40.2 Radiographic Findings in RDs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Inflammatory arthritis falls into four different groups and may be monoarticular or polyarticular (6, 7):
Inflammatory connective-tissue disease (e.g., RA, JIA, SLE, PSS, DM-PM, MCTD, psoriatic arthritis [PSA])
Inflammatory crystal-induced disease (e.g., gout, pseudogout, basic calcium phosphate)
Inflammation induced by infectious agents (e.g., bacterial, viral, spirochete, tuberculous, and fungal arthritis)
Seronegative spondyloarthropathies (e.g., ankylosing spondylitis [AS], PSA, Reiter’s syndrome [RS], inflammatory bowel disease [IBD]).
Noninflammatory arthritis may be classified as:
Degenerative, posttraumatic, or overuse (e.g., osteoarthritis [OA], posttraumatic aseptic necrosis [AN])
Inherited or metabolic (e.g., lipid storage disease, hemochromatosis, ochronosis, hypogammaglobulinemia, hemoglobinopathies).
Criteria for classification may be found in the Primer of the Rheumatic Diseases, 13th edition (8). A number of these diseases have systemic manifestations (Table 40-3), many of which should be addressed in addition to treatment of the arthritis itself. The physiatrist must be aware of the impact of a chronic, unpredictable illness on various life stages. For example, systemic disease may influence a young mother quite differently from a postmenopausal woman. In some diseases (e.g., RA, SLE, JIA, gout, AS, PSS, DM-PM), a number of set criteria delineated by the American College of Rheumatology (ACR) must be fulfilled before a definite or probable diagnosis can be made.
TABLE 40.3 Systemic Manifestations of RDs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Demographics
Many types of arthritis have a specific distribution in terms of age, gender, race, and geographic appearance. Severity of disease may vary with age and gender. Genetics and occupation may also be influencing factors. It is helpful to be familiar with those portions of the population that are more susceptible to certain diseases (Table 40-4) (9).
Etiology and Pathophysiology
Because the designation RD includes such a broad spectrum of processes and syndromes, a classification system (see Fig. 40-1) that groups arthritides to some extent by etiology may be useful.
Rheumatoid Arthritis
RA is the most common of the inflammatory arthropathies and is often difficult to diagnose in its early stages. The etiology of RA remains unknown, although much has been learned in the past two decades about the inflammatory process, its relationship to the immune system, and molecular genetic regulation (10). Of the two hypotheses in vogue, one suggests that RA is an autoimmune disorder; the other proposes that specific external agents initiate the response, which then is perpetuated or amplified by the immune host response. Data in support of the first hypothesis are derived from the fact that antibodies against autologous immunoglobulin G are present in many patients with RA, which may represent a primary abnormality in the regulation of cells that control immunoglobulin synthesis. Rheumatoid factor (RF) has been associated with more severe disease and almost exclusively with extra-articular disease. This primary defect may alter the control mechanisms, so that stimulation and control of these events are unbalanced and the response to endogenous immune products goes awry.
A more likely explanation for the etiology of RA is that specific external agents initiate an inflammatory response, and in the susceptible host, the inflammation leads to continual disease activity. Infectious agents can cause synovitis. Some replicate in the joint space (e.g., Mycobacterium, Staphylococcus), and some enter the joint space and cause synovitis initiating a local immune response (e.g., rubella, spirochete). Lyme disease is an example of a spirochete-initiated disease that can be associated with chronic arthritis. Another type of arthritis follows gastrointestinal (GI) disease (e.g., Shigella, Salmonella, Yersinia). No organism is recovered from the joint, although a reactive arthritis occurs, and the inflammatory process is initiated by a remote infection. All efforts to associate an infectious agent with RA have failed, despite sophisticated electron microscopy and molecular biology techniques. Exposure to cigarette smoke is an additional environmental factor believed to play a role in increasing the risk for development of RA (11, 12). Several components need to be acknowledged in the understanding of this process: an inciting agent, most likely exogenous and possibly a wide range of antigens; a genetic susceptibility; and an abnormality in the host immune response.
The mechanism of tissue injury in RA has been demonstrated to include the following components of the immune system and its associated mediators of inflammation. In the affected host, a stimulus initiates an inflammatory response directed against self or nonself, which sets into motion complement, leukocyte phagocytosis, lysosomal enzyme release, and several small mediators that may initiate clotting and fibrolysis. In the joint, the local reactions are helper T-cell (in particular CD4 T cells) mediators that are attracted to macrophages and dendritic cells. Antibody synthesis is initiated, thus perpetuating the immunologic activities already begun. Cytokines play a key role in the perpetuation of synovial inflammation. Many have been found in the RA synovium (11, 13). These cytokines are targets for clinical drug trial interventions. Some of the joint mononuclear cells can produce proteinases, prostaglandins (PGs), and other small mediators of inflammation.
TABLE 40.4 Epidemiology of Inflammatory Arthritis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Tissue inflammation causes the synovial membrane to become hyperplastic and neoangiogenesis occur, with the production of chemokines that increase the influx of more inflammatory cells. Synovial fluid enzymes directly affect the articular cartilage. Bone erosions develop when the synovial membrane has invaded the cartilage. Production of metalloproteinases, fibroblasts, and monocytic phagocytes produced by the synovium is controlled by cytokines (IL1, TNF2, and TGF-β). These cytokines influence chondrocytes to produce less collagen and proteoglycan, and increase collagenase synthesis, which degrades type II collagen (14). As the high-intensity inflammation subsides in the joint, repair takes place, often with the proliferation of fibroblasts and scar tissue. Although it is unclear what triggers this, once the process is in place it often continues for a longer period than would be expected to successfully clear the antigen. Hence, the host immunoregulatory system, which is genetically controlled, must be abnormal. In addition, people with RA often have systemic manifestations with other organ damage mediated by immunologic processes. An example of immune abnormality in RA is the inappropriate reduction in thymic function (15).
Systemic Lupus Erythematosus
SLE is a multisystemic disease that is associated with abnormalities of immune regulation and immune complex-mediated tissue injury. It has been called a classic autoimmune disease, as a result of an abundance of autoantibodies generated against cytoplasmic and nuclear cellular components. The hallmark of these is generation of IgG antibodies to double stranded DNA. The etiology of SLE is obscure, but viral inclusion bodies have been implicated because of electron microscopic observations made in lymphocytes and vessel walls. Virus has never been isolated in patients with SLE; even those diseases with documented infectious etiologies are often multifactorial. Family members with SLE are more likely to have immunologic abnormalities than are controls. Hormonal influences are important in the expression of SLE, and women in the child-bearing years appear to be at greater risk. Women taking progestation-based oral contraceptives are at higher risk than those taking estrogen-based oral contraceptives. The pathogenesis of SLE depends on abnormalities in humoral and cellular immunity. Lymphopenia is common and is inversely related to disease activity. B-lymphocytes are normal in number but are hyperactive. T-lymphocytes are often decreased, most markedly in the T-suppressor lymphocyte subpopulation. Natural killer cell activity is diminished, but there are an increased number of lymphocytotoxic antibodies (16).
Progressive Systemic Sclerosis
PSS is a progressive disorder in which microvascular obliterative lesions in multiple organs terminate in fibrosis and atrophy. The hallmark of this disease is induration of the skin. Patients with PSS have capillary abnormalities and small artery lesions that appear late with organ involvement. The pathogenesis of organ involvement is most likely due to injury to the endothelial cell lining of vessels. Disturbing the lining activates the clotting system, with the release of vasoactive peptides. These factors stimulate smooth muscle cells to migrate in, proliferate, and deposit connective tissue, which results in the proliferative vascular lesions of PSS. The etiologic agent is obscure, and no strong hypotheses exist as to its nature (17).
Idiopathic Inflammatory Myopathies
Polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) are part of a heterogeneous group of diseases characterized by inflammation of muscle and skin, often associated with profound weakness of all striated muscle, including the heart, and elevated levels of skeletal muscle enzymes. There are six types, each of which may have a different etiology (18);
Group 1: Primary idiopathic PM
Group 2: Primary idiopathic DM
Group 3: DM-PM associated with neoplasia
Group 4: DM-PM associated with vasculitis (juvenile dermatomyositis [JDM])
Group 5: DM-PM associated with collagen vascular disease
Group 6: IBM
Two leading hypotheses may explain the etiology of DM-PM: viral infection and abnormal recognition of self. Immunoglobulins have been demonstrated in vessel walls, especially in intramuscular blood vessels, suggesting that these deposits are immune complexes to muscle. These deposits are seen in a variety of muscle-wasting conditions and may be nonspecific. Cellular immunity is abnormal with DM-PM, as demonstrated by myotoxic activity of the lymphocytes in patients with DM-PM. Skeletal muscle antigens cause lymphocytes of patients with DM-PM to proliferate, suggesting that the lymphocytes are inappropriately responding to these antigens.
Crystal-Induced Synovitis
Crystal-induced synovitis can be caused by uric acid, calcium pyrophosphate, hydroxyapatite, and cholesterol crystals. Best understood is gout, a familial disorder in which there is a deficiency of hypoxanthine-guanine phosphotransferase, resulting in an overproduction of uric acid. Hyperuricemia results, and as the concentration of urate in the blood increases, monosodium urate crystals precipitate in the tissue. It has been shown that injecting urate crystals subcutaneously will cause tophus formation, and when urate is injected into joints, gouty attacks will ensue. Other factors involved in the pathogenesis of the gouty attack include elevated temperature, which increases the joint urate concentration, lowered pH, trauma, and aging (19).
Pseudogout, or calcium pyrophosphate dihydrate deposition (CPPD), can be hereditary or sporadic. The etiologic agent is the calcium pyrophosphate crystal, which is formed secondary to a disorder of local pyrophosphate metabolism. The crystals adhere to leukocytes, and often immunoglobulin is absorbed, which stimulates phagocytosis and the perpetuation of inflammatory arthritis. These calcium-containing crystals get deposited in the pericellular matrix of cartilage and can present as chondrocalcinosis (20).
Spondyloarthropathies
Spondyloarthropathies are polyarticular disorders that primarily involve the sacroiliac joints, vertebral column and, to a lesser extent, larger, peripheral joints (shoulder and hip). There may also be an association with a variety of extraspinal lesions including the eyes, the GI track, cardiovascular system, lungs, kidneys, and skin. These arthritides share a number of additional features, including mucocutaneous lesions, sacroiliitis, heel pain, and the B27 antigen. Antecedent GI infection, caused by Salmonella, Shigella, and Yersinia, has stimulated interest that these diseases may be caused by a gram-negative organism (21). The most convincing data in support of this came from the well-documented Shigella epidemic, in which RS occurred in 344 of 150,000 infected persons in one study (22) and in nine of 602 in another study. No case occurred in anyone who was not infected. Arthritis with some additional features of RS has followed Salmonella and Yersinia infections. In PSA and AS, the data are less convincing, but evidence has linked the development of guttate psoriasis and streptococcal infection. The presence of B27 antigen appears to be the crucial link in the expression of the disease. Antecedent urethritis has also been associated with acute arthritis, and chlamydia is the organism most frequently identified.
The pathology occurs at the entheses (insertion of tendon to bone). The axial spine may fuse, but if the peripheral joints are involved, there is erosion and often bony reaction and periosteal new bone growth. Usually, there is no periarticular osteoporosis (OP). In summary, the etiology of spondyloarthropathies is most likely an infective agent, possibly Gram-negative bacteria, that interacts with a susceptible gene host: B27 in AS and RS, and perhaps B27, B38, and C6 in PSA (23).
Infectious Arthritis
A wide variety of infectious agents can cause arthritis secondary to the infection itself or as a consequence of the host’s immunologic response. The organisms can be viral (e.g., hepatitis, rubella, mumps, herpes); bacterial (e.g., Gram-positive Staphylococcus, Streptococcus, and Pneumococcus; Gram-negative Neisseria and Hemophilus influenzae; Pseudomonas, mycobacterium tuberculosis), spirochete (Lyme disease), or fungal. Recently, interest has developed in the role of hepatitis C and the development of an RA-like arthritis (24).
PATIENT EVALUATION
A detailed history, physical examination, laboratory, and x-ray findings are essential to the proper diagnosis and management of RDs. Many schemes have been developed in an attempt to construct an organized approach to the classification of RDs, including algorithms that sort signs and symptoms around the presence or absence of inflammation, symmetry, and number of involved joints. However, these categories are not very helpful in sorting out the underlying pathophysiologic processes that need therapeutic intervention. A practical approach is suggested by James Fries, in which eight specific types of musculoskeletal pathology are distinguished (25). Patients can have more than one type of pathology; for example, enthesopathy and synovitis present in patients with PSA (Table 40-5). A more recent approach to patient evaluation, incorporating the World Health Organization (WHO) biopsychosocial model for patient evaluation, may be useful (26). Patient assessment from this approach will seek out not only the primary etiology and how the disease process affects the organ or system but also the associated effects on the patient and his or her interactions with the environment.
History and Examination
A detailed description of the symptom onset, prodromal symptoms, setting, pattern, and sequence will greatly aid in establishing a differential diagnosis. Exacerbating or remitting factors, functional impairments, and therapeutic effects should also be documented (27).
TABLE 40.5 Evaluation of RDs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pain is the most likely presenting symptom. Although often difficult to define, anatomic location and symmetry, character (e.g., burning, aching), and severity or intensity (graded by a numeric ten-point scale) should be included.
Stiffness may be seen as well. This term should be well-defined and its meaning to the patient should be understood. Timing, duration, and location of stiffness should be noted. For example, in the diagnostic criteria of RA, morning stiffness lasting at least 1 hour is included. This stiffness also known as a “gelling phenomenon” can be noted after sitting or maintaining a fixed position for some period of time which in some cases may be as short as 20 to 30 minutes but typically greater than 1 hour.
Range-of-motion (ROM) limitations may accompany complaints of stiffness. These symptoms in the rheumatologic population are usually not transient and should not be confused with gelling or stiffness. Noting symptom onset may help to differentiate an acute from a chronic process, such as nonreducible joint subluxation. Most important is to determine if the loss of ROM is fixed or likely to be successfully ranged, as a chronic ROM limitation may indicate ankylosis or autofusion of a joint. Passive and active ROM testing should be performed to rule out weakness as an etiology for ROM limitation.
Joint swelling should be documented by onset, persistence, location, and quantity (i.e., serial circumference measurements). This helps differentiate acute inflammatory from noninflammatory involvement. The former is best not treated with heat while the latter can be treated easily with either a heat or cold modality. When pain is noted with swelling, synovitis or bursitis may be present.
It is important to differentiate weakness from fatigue. Careful documentation of patient reports on muscle groups involved and relationship to functional limitations is needed. Proximal muscle weakness may be indicative of inflammatory myopathy such as PM. Persistent rather than intermittent complaints of weakness may indicate other processes, such as neuromuscular disease (e.g., Guillain-Barré’s syndrome).
Fatigue may be one of the earliest symptoms. Some patients may have these complaints even though pain and swelling have been objectively controlled.
Biomechanics
Evaluation of mobility can be performed with visual analysis or automated measures. The former has been standardized, and the latter have been significantly advanced with videobased high-speed systems. There is an increased ability to reliably measure motion in three dimensions: in real time, ground reaction forces, and pressures on the bottoms of the feet to calculate moments of force at various joints. These procedures are now more available and being performed fairly frequently. In addition, newer instrumentation has been developed to describe foot pressure profiles and describe forces and their influences on the foot (28).
Gait abnormalities for several RDs have been noted. The RA gait has been termed apropulsive because of the absence of pushoff from the ball of the foot. Similarly, studies of differences in gait before and after surgical procedures have been reported that describe which biomechanical changes occur as a result (29).
Laboratory Tests
The laboratory evaluation of blood, urine, and synovial fluid, coupled with radiographic evaluations, history, and physical examination information, can usually help to establish a proper diagnosis. The following initial determinations are made: complete blood count, ESR, SMA 12 (sequential multiple analyzer), RF, and antinuclear antibody (ANA). An HLA B27 determination is performed if spondylitis is suspected. The acute-phase reactants (C-reactive protein [CRP], serum amyloidal [SAA], and ESR) should be monitored, as they may be part of the early defense or adaptive mechanisms that precede the immune response. Although nonspecific, moderate elevation in CRP and serum amylase can be seen in systemic diseases.
Joint fluid is easy to obtain in the presence of effusion. Analysis of fluid is essential in the diagnosis of crystal-induced arthritis and infection, and it is helpful in differentiating traumatic from inflammatory arthritis. However, rarely will the diagnosis of RA, OA, PSA, or AS be made on the basis of joint fluid alone. Rather, the fluid helps confirm a diagnosis. Joint taps must be done when a question of infection is raised and should be made before injecting steroid or other material into the joint. Classification of joint fluid into categories will help differentiate inflammatory, noninflammatory, septic, and hemorrhagic arthritis (see Table 40-1).
Radiographic Assessment
Radiography is often the most valuable technique for differentiating among arthritides. Carefully selected radiographic series with the proper projections, addition of stress, and weight-bearing views will add valuable information about the extent of soft tissue, articular surface, or bony changes. Marginal erosion of bone with juxtaarticular OP is the hallmark of RA. Nonuniform joint space losses, in association with bony sclerosis and marginal osteophytes, are the characteristic changes in OA. Spondyloarthropathies classically involve the sacroiliac joints, either symmetric, as in AS, or asymmetric, as in RS and PSA. Bony changes include periosteal new bone formation and ankylosis. Gout and pseudogout often involve only a few joints. In gout there are soft-tissue tophaceous deposits and marginal erosion with large bony overhangs, and in pseudogout there is calcinosis in fibrocartilage. Early in joint infection, the x-ray films may be negative, or there may be some joint space widening. If the process continues and osteomyelitis develops, periosteal reaction can occur, which may indicate progressive infection or bony destruction. Table 40-2 presents typical radiographic findings in patients with RDs.
Additional imaging such as computed tomography (CT), which gives good structural definition of soft tissue and bone, is often combined with arthrography to study axial structures in disorders such as sacroiliitis. Magnetic resonance imaging (MRI) allows further differentiation of soft tissue and fluid as well as use of variable imaging planes and combination. Gadolinium for contrast is of great benefit in the evaluation of joint effusions, tendonopathies, and myositis (30). Ultrasound may be useful in evaluating this patient population as well (31).
Functional Assessment
Rehabilitation assessment for patients with RDs includes both process and outcome measures. Goniometry, the measurement of joint ROM, is standardized and widely used, as is manual muscle testing (MMT). A new ten-point MMT with specific grade definitions has been devised and offers more sensitivity in the strength range that is most important to know for assessment of capability for independence (32). Quantifiable measures of spine motion are particularly useful for patients with RDs (33). They can help chart progressive loss of spinal mobility, which prompts interventions designed to preserve posture as well as chest expansion programs, as in the management of patients with spondyloarthropathies.
Patients with arthritis often have stiffness rather than pain that limits function. Both symptoms are difficult to measure. However, duration of morning stiffness may be quantified. Pain can be measured in terms of severity in a descriptive way (e.g., mild, moderate, severe) or by use of a visual analog scale (34), which is quite reliable. Measures of degree of joint tenderness, swelling, deformity, relative instability, or crepitus with active and passive movement are also useful in defining RD processes.
Fatigue is a frequent problem for patients with RD. Its cause is multifactorial: medication, chronic inflammation, abnormal posture and gait that are energy inefficient, abnormalities of the sleep cycle, and atrophy of muscle secondary to disease or chronic pain. Fatigue is difficult to quantify. A visual analog scale has been used in the subjective measurement of fatigue but it has an imprecise reference. A multidimensional assessment of fatigue (35) has been devised and validated in this population. The fatigue severity scale has also been used to assess this parameter (36). The human activity profile (HAP) is an instrument designed to measure the amount of activity and those activities that an individual is no longer able to perform. It also has a dyspnea scale. Specific activities have been correlated with metabolic equivalents required for performance (37).
Despite reliable, sensitive indices of strength, ROM, and grip strength, other measures are needed for evaluation of patients with RD. The American Rheumatism Association in 1949 devised a functional scale for patients with RA. This scale, a simple, global assessment that rated patients’ functional status as independent (i.e., class I), able to perform with pain (i.e., class II), able to do some activities (i.e., class III), and unable to perform (i.e., class IV) was revised in 1992 (38).
Two generations of functional assessments have been used in evaluating patients with RD. The first set looked primarily at performance of patients in ambulation, self-care, and other activities of daily living (ADL). Most had some testing of reliability and validity, and were relatively easy to use. The problem with them was that they defined function very narrowly and excluded psychological, social, and vocational functions. The newer functional indices are more comprehensive and offer a broader view of patients’ functioning. These global, multidimensional tools had been designed for the arthritis
population, children and adults, and have demonstrated validity and reliability (39, 40).
population, children and adults, and have demonstrated validity and reliability (39, 40).
TABLE 40.6 Functional Measures in RDs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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When rheumatologists were asked which functional measures were important to use in the evaluation of patients with RDs, the consensus was mobility, pain, self-care, and role activity (41). The evaluations needed may vary, because some RDs involve only joints (e.g., OA); others, primarily kidneys, skin, and central nervous system (e.g., SLE); and still others, different organ systems, such as cardiovascular and pulmonary systems. Table 40-6 identifies standard functional measures likely to be needed for each of the RDs. Other useful scales include The Wisconsin Brief Pain Questionnaire, The sickness impact profile (SIP) (42), Stanford health assessment questionnaire (HAQ) (43), Short form 36 (SF36) version-2 (44), arthritis impact measurement scale-2 (AIMS-2) in RA and Osteoarthritis (OA), (45) and Bath and Duogados functional indices in spondylitis (46). These functional assessment tools singly and in combination are valuable tools for measuring both physical and psychosocial health parameters (Tables 40-7 and 40-8).
Functional assessment tools are also used in combination with traditional measures of disease state, including tender and swollen joint counts (number of tender and inflamed joints), and biochemical markers of disease state such as the acute-phase reactants. The combination of these tools into core set outcome measures is used to define clinically significant improvement in diseases such as RA. The ACR has chosen the definition of 20% improvement in tender and swollen joint counts and improvement in three of the five following ACR core set measures: patient or physician global assessments of disease severity, pain, disability, and an acute-phase reactant level (47). This is commonly referred to as the ACR-20. Clinical improvement in the preceding core set measures that constitutes improvement of 50% and 70% (ACR-50 and ACR-70) are often referred to in randomized control trials. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) group has reached consensus on the required core set measures of use in OA (48) and AS (49). Core set outcome measures in other populations, such as those with DM-PM, are currently in development. Although these tools are easily administered, results are often not immediately available for use because of scoring schemes. Some of these tools (e.g., HAQ) also have limited use because of ceiling effects and often miss subtle changes in the patient’s disease process reflected in level of function; others may have significant flooring effects.
TABLE 40.7 Assessments Measuring Physical Health Parameters | ||||||||||||||||||||||||||||||||||||||||
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In the clinical setting of RA, a combination of factors including specific clinical and laboratory values are used to produce a disease activity score (DAS28). The DAS28 is derived from the number of tender and swollen joints, patient assessment of disease activity via visual analog scale, ESR, and CRP (50).
TABLE 40.8 Assessments Measuring Psychosocial Health Parameters | ||||||||||||||||||||||||||||||||
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Compliance
It has long been recognized that a number of factors may influence compliance of patients with treatment in general:
Demographic features
Nature of the disease
Therapeutic regimens
Setting in which treatment is given
Patient-doctor relationship
Sociobehavioral features of the patient
Compliance depends on individual health beliefs, including the importance to the patient of the treatment goal, how likely the treatment is to achieve the goal and benefit the patient (51), and how likely the treatment is to lessen the disability and the physical, psychological, and functional barriers to treatment.
In our clinical experience, patients who have pain are more likely to be compliant with medication, modalities, and techniques that relieve the pain. Education significantly increases adherence to drug regimens (52). Group education enhances self-management strategies (49).
One study of adolescents with chronic diseases (including JIA) indicated that good motivation was likely to result in better treatment compliance. Support from parents, physicians, and friends also predicted good compliance with regimens (53).
Compliance with the use of splints/orthotics has been low due to cosmesis, uncomfortable fit (more likely with noncustomized items), and fear that wear at work may jeopardize job status.
Likewise, compliance with unsupervised exercise programs tends to be low. In one study, two out of three patients with some form of arthritis management information used some technical orders and rest daily, and 50% used exercise and heat (25% on a daily basis) (54). Compliance at the 1-year level in patients on a home exercise program was predicted by self-efficacy for exercise, regular ROM before study intervention, and single marital status (55). Perceived benefit of exercise was a significant predictor of participation in an aerobic exercise program. Those who reported exercising in their youth perceived more benefits. Subjects with less formal education, longer arthritis duration, and higher impact of arthritis scores perceived fewer exercise benefits (56).
Compliance with splint use has been shown to increase when patients learn the purposes of use, expectations of use, and precautions for wear and when the splint provider has a positive affective tone and gives encouragement (57). Strategies to improve compliance with exercise can be seen in Table 40-9, and Table 40-10 lists strategies for improving compliance with orthotics and gait aid.
TREATMENT
Pharmacologic Management
Pharmacologic management of RDs often requires the use of one or more of a variety of medications, the pharmacology and pharmacokinetics of which may influence physical and psychological functioning. The well-known “treatment pyramid” approach to the management of RA and other RDs was in the past based on use of initial rest, patient education, joint protection, and nonsteroidal anti-inflammatory drugs (NSAIDs) with progression to steroids and sequential monotherapy, and use of DMARDs later in the course of these diseases. This treatment approach has undergone revision with improved knowledge of the rate of disease progression, prognosis, and
severity at presentation. DMARDs are used earlier and often in combination (Fig. 40-2) (58). At the onset of disease symptoms and diagnosis, the patient would begin early rehabilitation interventions: education, orthotics, physical modalities, joint protection, energy conservation, and strengthening, along with NSAIDs and low-dose steroid therapy in some cases. As we ascend the pyramid, introduction of DMARDs used singly or in combination and earlier use of biologic agents is noted. The time interval at which new agents or dosage changes are made has also been shortened.
severity at presentation. DMARDs are used earlier and often in combination (Fig. 40-2) (58). At the onset of disease symptoms and diagnosis, the patient would begin early rehabilitation interventions: education, orthotics, physical modalities, joint protection, energy conservation, and strengthening, along with NSAIDs and low-dose steroid therapy in some cases. As we ascend the pyramid, introduction of DMARDs used singly or in combination and earlier use of biologic agents is noted. The time interval at which new agents or dosage changes are made has also been shortened.
TABLE 40.9 Strategies to Improve Compliance with Exercise | ||||||||||||||
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TABLE 40.10 Strategies to Improve Compliance with Orthotics and Gait Aids | ||||||||
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Aspirin
Aspirin, or acetylsalicylic acid (ASA), has been the foundation of management of rheumatic conditions and the symptoms of pain, fever, and inflammation. It has been shown to block the synthesis of PG in the anterior hypothalamus, which is responsible for the antipyretic effect. The analgesic effect of ASA is not entirely understood. Musculoskeletal pain may be mediated by bradykinin, a synthesizer of PG, which sensitizes nerves to painful stimuli. Aspirin blocks PG synthesis. At doses higher than those used for analgesia (e.g., 5.3 g/day), ASA reduces joint inflammation and swelling. The mechanisms for this action are multifactorial. Aspirin affects leukocyte migration and vascular permeability, both of which may be influenced by PG synthesis. The toxicities of ASA include allergy, tinnitus and hearing loss, GI blood loss, ulcer, chemical hepatitis, and reduced glomerular filtration rate. For patients who have clinically significant GI symptoms, enteric-coated preparations are usually well tolerated. Other forms of salicylate can be used that are often less GI toxic (e.g., choline salicylate).
 FIGURE 40-2. Pyramid of the medical and rehabilitation treatment approach to inflammatory arthritis. (Asterisk: Patient education, adaptive equipment and strategies, modality use, and other non-pharmacologic Rehabilitation Medicine associated therapies.) |
Nonsteroidal Anti-inflammatory Drugs
The agents that form the group of drugs called NSAIDs, which include the cyclooxygenase-2 (COX-2) inhibitors, continue to be used in part as first-line agents in the management of RDs. These drugs also suppress inflammation through the inhibition of synthesis of PG. They inhibit the COX effect on platelets and effects on leukocyte migration. Toxicities include GI bleeding, pancreatitis, hepatotoxicity, decreased renal blood flow, hypertension, peripheral edema, and allergic interstitial nephritis. Some have more GI toxicity than others and cause more sodium retention. A review of the comparative NSAIDs toxicities is available (59).
TABLE 40.11 NSAIDs in Use | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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NSAIDs were widely used as first-line drugs in the treatment of RA, JRA, OA, and the spondyloarthropathies but have more recently been replaced by the early use of DMARDs in some cases. Only tolmetin sulfate, choline magnesium trisalicylate, ibuprofen, and naproxen sodium have been approved for use in children by the U.S. Food and Drug Administration. A list of those commonly used NSAIDs in the United States is provided in Table 40-11.
Aspirin and NSAIDs are likely to provide significant clinical relief for patients with OA, RA, JIA, gout, and spondyloarthritis. These drugs are not usually effective by themselves in controlling RA and vasculitic syndromes.
The newest group of NSAIDs, the COX-2 inhibitors, has found more recent favor. They differ from traditional NSAIDs that do not inhibit COX-1 at normal therapeutic levels, thus likely avoiding some of the detrimental GI effects of other NSAIDs. Celecoxib has been shown to be effective in reducing joint pain and stiffness in RA (60). Rofecoxib has been withdrawn from the markets due to an increased risk of cardiovascular events.
Glucocorticoids
Glucocorticoids and therapeutics for RDs are inseparable and probably have been tried in every RD either systemically or locally. Exogenous glucocorticoids influence leukocyte movement, leukocyte function, and humoral factors; inhibit recruitment of neutrophils and monocytes into inflammatory sites; cause lymphocytopenia by inducing margination or redistribution of lymphocytes out of the circulation; modify the increased capillary and membrane permeability that occurs at an inflammatory site, reducing edema and antagonizing histamine-induced vasodilation; and inhibit PG synthesis.
Daily high-dose steroid use stimulates Cushing’s syndrome, in which hypertension, hirsutism, acne, striae, obesity, psychiatric symptoms, and wound-healing problems occur. With exogenous doses above 12.5 mg/day, there is an increased incidence of glaucoma, cataracts, avascular necrosis, OP, and pancreatitis. The side effects are, in part, dependent on the particular glucocorticoid used and the dose. Alternate-day steroids are associated with fewer untoward effects. Current recommendations to reduce bone loss in patients receiving a prednisone equivalent of more than 5 mg/day include (a) use of supplemental calcium and vitamin D or activated form of vitamin D, (b) use of bisphosphonates, or calcitonin as a second-line agent for those with contraindications or intolerance to bisphosphonates, (c) hormone replacement therapy in those found to be hormone deficient (61). The oral route is usually selected for ease of administration, but glucocorticoids can safely be given intramuscularly, intravenously, or intra-articularly.
Glucocorticoids are used to treat several RDs. In 2002, a consensus conference made the following recommendations for a standardized nomenclature for glucocorticoid dosing. Doses of less than 7.5 mg—low dose, 7.5 to 30 mg/day—medium dose, 30 to 100 mg—high dose, greater than 100 mg/day—very high dose, and pulse-dosed therapies given at greater than 250 mg/day (62). Higher doses are used in treating patients with SLE, vasculitis, and DM-PM (up to 100 mg prednisone every day) (63). The benefit of steroid therapy to patients with AS, PSS, and PSA has not been shown.
Disease-Modifying Antirheumatic Drugs
Methotrexate
This cytotoxic agent has become one of the first line agents in the treatment of moderate to severe RA. It is a structural analog of folic acid and causes the deficiency of intracellular folate by inhibition of dihydrofolate reductase, an enzyme required for DNA synthesis. This may not be the true mechanism of action that makes methotrexate (MTX) an effective anti-inflammatory agent. MTX also may act to promote the extracellular adenosine release which promotes the down regulation of inflammatory pathways by binding surface receptors on lymphocytes, monocytes, and neutrophils and inhibit interleukin production.
MTX has been shown to be effective in RA, JRA, SLE, and PSA and is effective in combination with corticosteroids in the management of some vasculitic conditions. It can be given in an oral form once per week at doses of 7.5 to 15 mg/week. Maximum doses of 25 mg/week may be given. Weekly subcutaneous or intramuscular injections are well tolerated and are associated with less GI side effects. Side effects include increased liver transaminases,
myelosupression, pneumonitis, cirrhosis, increased risk of infection, and can be highly teratogenic.
myelosupression, pneumonitis, cirrhosis, increased risk of infection, and can be highly teratogenic.
Hydroxychloroquine
Antimalarials, such as hydroxychloroquine (HCQ), are effective in discoid lupus erythematosus and SLE. Improvements in skin involvement, arthritis, and arthralgias are noted. They can also be effective in patients with RA with improvements noted in joint count, grip strength, walk time, and sedimentation rate. The antimalarials are slow-acting, taking 4 to 6 weeks before a therapeutic effect is observed. They are as effective as some of the other DMARDs, but a lower toxicity profile makes them one of the agents of choice in combination therapy (64, 65).
The mechanism of action of these drugs is varied. They have been shown to impair enzymatic reactions, including phospholipase, cholinesterase-hyaluronidase, and proliferation of lymphocytes. They seem to block depolymerization by DNAase and interfere with DNA replication. The incidence of side effects and toxicities varies widely. GI disturbance is quite common, and retinopathy is infrequent but of greatest concern; it rarely occurs before a cumulative dose of 300 mg is reached, specifically in chloroquine, but routine ophthalmologic examinations should be performed. The antimalarial agents are most often used in the treatment of RA and SLE.
Sulfasalazine
Sulfasalazine (SSA) is an agent that combines the antibiotic sulfapyridine with the anti-inflammatory agent 5-aminosalicylic. Its proposed mechanisms of action include inhibition of folate-dependent enzymes similar to MTX, immunomodulatory functions that decrease immunoglobulin and RF production, and several anti-inflammatory properties (66). SSA has been shown to be effective in treating RA, JRA, AS, and PSA.
Leflunomide
Leflunomide is an immunosuppressive drug that inhibits de novo pyrimidine synthesis and impairs T-cell proliferation. In the treatment of RA, this drug has been shown to be as effective as MTX (67). This agent has been shown not only to be effective as monotherapy but also to be even more effective when used in combination with MTX; however, concerns remain over the toxicity profile (68). Leflunomide is shown to be effective in the treatment of RA, SLE, and PSA. Monitoring while on this medication includes (a) liver function tests for toxicity and (b) platelet count for signs of thrombocytopenia.
D-Penicillamine
D-penicillamine has been effective in the treatment of seronegative or seropositive RA but has not been used as often due to the associated high incidence of toxicity (69). The patterns of response to penicillamine are similar to those observed with gold. Toxicities include leukopenia, thrombocytopenia, proteinuria, skin rash, stomatitis, GI upset, and a variety of autoimmune syndromes, including Goodpasture disease, PM, and SLE. The mechanism of action is unknown, but it is neither cytotoxic nor anti-inflammatory.
Immunoregulatory Agents
Immunoregulatory drugs have been used in the management of RDs in an attempt to restore a balanced immune response by eliminating certain cell subsets. None of these drugs have cured patients with RDs, but they have produced some disease control and long-term remissions (70). Commonly used agents are the alkylating agents (cyclophosphamide and chlorambucil), purine analogs (azathioprine and meraptopurine), cylosporine, tacrolimus, sirolimus, mycophenolate mofetil, dapsone, and thalidomide.
Cyclophosphamide and Chlorambucil
Cyclophosphamide and Chlorambucil are alkylating agents that form active metabolites that cross-link DNA, preventing replication, and reducing DNA synthesis. Immunoregulatory effects are through the decrease of both T and B-lymphocyte proliferation, antibody production, and suppression of delayed hypersensitivity reactions to new antigens. Cyclophosphamide has been shown to be effective in treating SLE and RA, while chlorambucil is utilized for RA. These agents have toxicity profiles that include myelosupression, increased risk of infection, and risk of malignancy (70).
Azathioprine and Meraptopurine
The purine analogs, azathioprine and meraptopurine, are converted to thiopurine, metabolized, and incorporated into cellular DNA, leading to inhibition of nucleic acid synthesis. Through this mechanism, it is believed that these agents function to decrease circulating lymphocyte count, suppress lymphocyte proliferation, inhibit antibody production, and inhibit monocyte production as well as cell mediated and humoral immunity (70). These agents have been used to treat RA and SLE and are well tolerated. The most common side effects include GI symptoms, myelosuppression, and risk of infection.
Cyclosporine
Cyclosporine exerts its effects by inhibiting the production of interleukin-2 and other cytokines, leading to reduction in T-cell activation and lymphocyte proliferation. It has been used in the treatment of RA and PSA. Toxicities include GI upset, hypertension, nephrotoxicity, and increased risk of lymphoma and skin cancer. Tacrolimus, a macrolide, functions by binding to an intracellular binding protein (FK-binding protein) and in association with calcineurin suppresses the transcription of cytokines and inhibits the early steps of T-lymphocyte activation (71). Sirolimus also binds to the FK binding protein but functions through blocking the progression of the cell cycle, inhibiting cell signal transduction (72). Mycophenolate mofetil is converted to Mycophenolate acid that reversibly inhibits inosine monophosphate dehydrogenase, an enzyme required for the synthesis of purines, thus inhibiting T- and B-cell lymphocyte proliferation. It has been used in the treatment of SLE and associated nephritis.
TABLE 40.12 Therapeutic Application of Drugs in RDs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Thalidomide, a derivative of glutamic acid, is believed to exert its immunosuppressive effects through the inhibition of angiogenesis and tumor necrosis factor (TNF)-α. Its most notable toxicity is as a potent teratogen but it is also associated with peripheral neuropathy. Currently only approved for the treatment of erythema nodosum, studies are looking into its use in RA, SLE, Sjogrens’s syndrome, and AS (73). Dapsone, an antimicrobial agent, is believed to affect the neutrophil function by decreasing recruitment, chemotaxis, and inhibiting neutrophil function (74). These drugs cause marrow suppression and GI intolerance. A review of the therapeutic application of these drugs is presented in Table 40-12.
Gold
Parenteral gold, and more recently oral gold (auranofin), has been used in the treatment of synovitis in patients with RA. Gold is thought to work by inhibiting lysosomal enzymes or by inhibiting phagocytic activity in macrophages and polymorphonuclear leukocytes. It also inhibits aggregation of human γ globulin in vitro, a phenomenon that is thought to be an inflammatory antigenic stimulus in RA. These events have been observed when parenteral gold is used. The oral preparation alters all mediated immunity, inhibits DNA synthesis in vitro, and suppresses humoral immunity (75).
Adverse effects of gold compounds include rash, stomatitis, proteinuria, and hematologic disorders (e.g., leukopenia, thrombocytopenia). These side effects, combined with lack of long-term clinical efficacy, have led to decreasing use of the agent. This drug is not used in patients with SLE, partly because it may flare the skin involvement. It may be useful in treating patients with peripheral arthritis associated with psoriasis.
Antihyperuricemic Agents
Pain and inflammation of crystal-induced arthritis are frequently adequately controlled with NSAIDs. Although these drugs are effective in controlling symptoms, they do not alter the metabolism of the substances forming crystals, nor do they influence their excretion. Uricosuric agents like probenecid compete with the tubular transport mechanism for uric acid, reduce the reabsorption of uric acid, and hence increase its excretion (76). Their use is widespread, and their toxicities are well known, including nephrolithiasis, which is preventable if the urine is alkalinized and fluids are increased. Acute gout can be precipitated as the uric acid levels are lowered and GI symptoms are not infrequently seen. A second approach toward controlling serum urate levels is that of regulating production of uric acid by inhibiting xanthine oxidase. This is done by using allopurinol as an analog of hypoxanthine. It too can precipitate an acute attack of gout and can cause xanthine renal stones. Side effects include rash and, rarely, blood dyscrasia. Allopurinol should not be used with azathioprine. Allopurinol is an inhibitor of the principal pathway for the detoxification of azathioprine.
Biologic Agents-Anticytokine Therapies
Etanercept (administered subcutaneously), infliximab (administered intravenously), and adalimumab (administered subcutaneously) function to inhibit TNF and have gained increasing popularity, as studies have shown these to be as effective, if not more effective, in preventing joint damage than MTX (77). Infliximab and adalimumab are monoclonal antibodies and bind to TNF-α. Etanercept binds both to TNF-α and lymphotoxin α, neutralizing their biologic activity. It is administered in doses of 25 mg twice weekly or 50 mg once weekly. It has been shown to be effective in RA (78), AS (79), and PSA (80). The most significant side effects include injection site reactions and infections, and to a lesser extent development of autoantibodies. There is also some risk of lymphoproliferative disorders and more rarely lupus-like reactions, demyelinating disorders, as well as other malignancies (81).
Anakinra (administered subcutaneously) is an anti-interleukin-1 receptor antagonist, currently approved for the treatment of RA. Doses of 1 and 2 mg/kg were shown to make improvements in joint counts, pain scores, morning stiffness, and physician assessment of disease activity (82).
Other Biologic Agents
Two of the newer biologic agents include rituximab and abatacept. Rituximab is a monoclonal antibody directed against the extracellular domain of the CD20 antigen on B-Cell and initiates compliment-mediated B-cell lysis. Abatacept binds to CD80/CD86 on the surface of antigen presenting cells and inhibits T-cell activation. These agents continue to be studied but have shown significant promise for the treatment of RA when used in combination with MTX (83, 84).
Combination Therapies
Along with a shift of the classic treatment paradigm for RDs by using DMARDs earlier in the course of disease, it has become increasingly more common to use these agents in combination. The benefits of using some of these combination therapies include additional therapeutic effects of drugs that may not have been fully effective as monotherapy and possible improvement in the toxicity profile, as lower doses of these potentially toxic agents are needed. MTX is commonly used in combination with other DMARDs. Often used combinations include the following:
Cyclosporine and MTX have shown to be very safe and useful in the treatment of severe RA (85).
MTX, HCQ, and SSA combination therapy has shown some promise with moderate efficacy and no noted increased toxicity when compared with MTX alone or SSA/HCQ in combination (86).
MTX and TNF-α blocking agent infliximab showed good overall drug tolerance and sustained efficacy over a 2-year period (87).
MTX and leflunomide as a combination has shown some associated drug toxicity but a good overall efficacy (88).
Many other combinations of these agents have been evaluated. Some have shown promise but others have been marred by intolerable side effects (89).
Complementary and Alternative Medicine
The National Institutes of Health defines complementary and alternative medicine (CAM) as encompassing those treatments and health care practices that are not widely taught in medical schools, not generally used in hospitals, and not usually reimbursed by medical insurance companies. These therapies are sometimes called unconventional therapies, since they are outside the “mainstream of Western medicine.” Often these therapies have not undergone rigorous scientific analysis in randomized controlled trials (RCTs) (89, 90, 91, 92). More medical schools have now introduced CAM into their curriculum (93).
The term alternative alone has been used to refer to practices used in place of mainstream Western medicine, such as exclusive use of herbs instead of prescription drugs. The Arthritis Foundation (AF) prefers the term complementary medicine for the use of unconventional therapies in arthritis that are used to support mainstream Western medicine.
The term alternative alone has been used to refer to practices used in place of mainstream Western medicine, such as exclusive use of herbs instead of prescription drugs. The Arthritis Foundation (AF) prefers the term complementary medicine for the use of unconventional therapies in arthritis that are used to support mainstream Western medicine.
There has been an increasing use of CAM in the general population to treat disease. One recent study (94) indicated that 42% of patients use at least one of 16 CAM therapies, and 50% of these patients had musculoskeletal disease. The study indicated that CAM is used as an adjunct to conventional therapies. Visits to CAM practitioners exceeded those to primary care physicians, and patient expenditure was $27 billion/year, similar to expenditures for all U.S. physician services.
Because of the chronic painful nature of RDs and the fact that they often are not cured by Western medicine, arthritis patients often seek CAM treatments (95). A 1998 review of surveys indicates use by 30% to 100% of arthritis patients. A 2004 study showed 90% of primary care clinic patients with arthritis use CAM, and RA patients used an average of 4.4 CAM therapies (96). A 2004 study revealed 33% of JIA patients use CAM as parents sought it for pain relief for their children (97). However, only 38% to 55% of patients reveal their use of CAM to their physicians (95). A more recent study cited 70% of RA patients revealed their CAM use to physicians (96). Physicians should ask patients about their use of CAM, as some treatments are contraindicated when used with conventional therapies (98). Arthritis patients and physicians have different perceptions about the usefulness of CAM. Arthritis patients generally perceive its usefulness (99). In a group of mixed arthritis patients in a 2005 review, homeopathy and acupuncture were the most used type of CAM (44% and 41%, respectively). Significantly higher self-perceived efficacy scores were seen for CAM use in patients with spondyloarthropathies and OA. The lowest scores were among RA and connective tissue diseases (100). Some rheumatologists do not recommend them (101) and others do (102). The general trend is toward more approval by health care providers.
A number of practitioners and treatments are included under CAM (Table 40-13). The main categories are alternative healing systems; mind, body, and spirit treatments; prayer and spirituality; moving medicine; massage and touch; herbs and supplements; and miscellaneous treatments. In one study, RA patients most commonly used relaxation, glucosamine, and vitamin C. There was less common use of fish oil and gamma-linolenic acid (GLA) containing supplements. Patients used therapies to relieve pain, prevent disease progression, and to feel better (96).
The benefit of some CAM therapies has been researched, while others have been minimally studied. Much of the older research consists of nonrandomized, noncontrolled trials. The issue of efficacy of popular CAM therapies (acupuncture, herbs, or homeopathy) used by the general population has been explored in recent meta-analysis reviews of controlled trials (103, 104, 105). The publications listed in references (72) and (87, 88, 89, 90, 91, 92, 93, 94) are available for review of CAM benefits. Most of the literature refers to neck and back pain, fibromyalgia (FM), and OA. The literature is sparse on the benefits of CAM in inflammatory arthritis.
TABLE 40.13 Alternative and Complementary Medicine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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There continues to be a growing interest in the use of herbal therapies in RA. A systematic review of RCTs in this area resulted in 14 such trials. There was moderate support for GLA for reducing pain, joint count, and stiffness. Further research is needed to examine the safety and efficacy of herbal remedies (106).
A 2005 review summarizes the efficacy and toxicities of herbal remedies used in CAM therapies for RDs. It elucidated the immune pathways through which they have antiinflammatory and/or immunomodulatory activity that may provide a scientific basis for efficacy. For instance, GLA acts
as a competitive inhibitor of PG E2 and leukotrienes (LTs). It appears to be efficacious in RA (107).
as a competitive inhibitor of PG E2 and leukotrienes (LTs). It appears to be efficacious in RA (107).
Proven benefits in noninflammatory arthritis include the following: (a) glucosamine/chondroitin decreases knee pain and slows disease progression in OA (108) and (b) acupuncture significantly decreases knee pain in OA (109).
Analysis of 17 acupuncture trials in 1997 (110) failed to show benefits of acupuncture in RA, SLE, AS, and PSS. AF reviews confirm this (91). In a 2005 systematic review of studies on acupuncture and electroacupuncture for RA, the reviews concluded that although electroacupuncture showed significant knee pain reduction 24 hours and 4 months posttreatment, the poor quality of the trial, including small sample size, precluded its recommendation. They further conclude from the studies reviewed that acupuncture has no significant effect on ESR, CRP, pain, patient global assessment, number of tender joints, general health, disease activity, and reduction of pain medications (111). A recent pilot study of two treatment groups of SLE patients (acupuncture or minimal needling) versus usual care revealed a more than 30% improvement in pain measures in the acupuncture and minimal needling groups with no improvement in the control-usual care group (112).
Other CAM modalities/treatments have also been studied. Low-level laser treatment decreased pain in RA in a Dutch study (113). A cognitive behavioral intervention (biofeedback) resulted in a decreased number of clinic visits and hospital days, and medical costs in RA (114).
A yoga program based on upper-body posture flexibility; correct hand, wrist, arm, and shoulder alignment; and stretching provided significant reduction in pain and increased grip strength in Carpal Tunnel syndrome (a common problem in RA) (115). An NIH consensus conference in 1998 concluded that acupuncture was useful for Raynaud’s syndrome (a common problem in SLE, MCTD, PSS) (116). A study by Yocum indicated that biofeedback increased the fingertip temperature in Raynaud’s syndrome in SLE and PSS (117). Intercessory prayer in one uncontrolled study significantly decreased the number of swollen joints, pain, and disability in RA patients (118). Tai chi is safe in RA but benefits are not proven. A 2007 systematic review of 45 studies of tai chi for RA, found only two RCTs and three non-randomized controlled clinical trials (CCTs) meeting the Jadad score for methodological quality. The RCTs demonstrated some positive findings for tai chi on disability index quality of life, depression, and mood but not on pain reduction. It was concluded by the author that collectively, at the current time, evidence is not convincing enough to suggest tai chi is an effective treatment for RA (119). A 1997 study indicated massage decreased pain and joint stiffness in JIA (120).
In general, diet can influence gout, but other than that, there is no definite evidence that diet can cure arthritis (72). There is some suggestive evidence that a decrease of omega fatty acids and substituting omega-3 oils may decrease pain and inflammation. Sources of omega-3 oils include cold-water oily fish, sardines, green soybeans, tofu, canola, and olive oils (89).
Most CAM therapies are low risk, but some do involve risks (89). Herbs can interfere with prescription medication. The following increased sensitivity to anticoagulants: bromelain, chondroitin, fish oil, GLA, garlic, ginkgo, ginger, ginseng, evening primrose oil. Folic acid interferes with MTX. Ginger can increase NSAID effects. Ginseng may increase the effects of glucocorticoids and estrogens, and should not be used in diabetes mellitus or with monoamine oxidase (MAO) inhibitors. Kava Kava increases the effects of alcohol, sedatives, and tranquilizers. Magnesium may interfere with blood pressure medication. St. John’s Wort enhances the effects of narcotics, alcohol, and antidepressants, and increases the risk of sunburn and can interfere with iron absorption. Valerian increases sedative effects. Zinc interferes with glucocorticoid and immunosuppressive drugs (89).
Caution should be noted in patients with inflammatory arthritis receiving manipulation therapy. These patients often have damaged joints that can sublux (RA, JIA) (121) and ligamentous laxity (122). Patients with significant AS have rigid spines and can fracture. Those with moderate to severe OP from disease and steroids can also fracture. Spinal fractures can result in neurologic compromise. Patients with RA have C1-2 laxity or instability, and can sublux with neurologic compromise.
Precautionary advice in CAM administration includes use of only sterile disposable needles, and prohibiting the use of pulse electromagnetic field therapy in pregnant or cancer patients, and magnets in those with implanted electronic devices or electric blankets.
Surgery: Soft-Tissue and Reconstructive Procedures
Indications for surgeries in the RDs include the restoration or preservation of joint mechanics and function, and relief of pain. In general, pain relief is a more predictable outcome in arthritis surgery than is functional restoration. Contributors to functional outcome include motor strength, motivation, postoperative complications, and participation in rehabilitation, all of which are highly variable.
The decision to operate on a patient with RD requires a thorough preoperative evaluation. This must include the overall health status of the individual and identification of the medications that might increase the risk of surgical complications. This population is likely to be more than 55 years of age, have an altered immune system, and be receiving medication that could influence healing. Examples of these medications include steroids, NSAIDs, MTX, and the newer cytokine inhibitors. Information about disease status and medication will help illuminate any additional risks for surgery.
Equally important is to perform a comprehensive physical examination and review of x-rays. The decision about which procedure to perform depends on properly identifying the cause of symptoms and the ability to determine whether they are likely to be correctable by the proposed procedure. Efforts to realign joints or soft tissue, although important, should be considered within the context of functional needs
and symptom control. For example, pain is usually the result of joint deformity and its sequelae, but nerve entrapment, referred pain, and myopathy might need to be ruled out before surgery.
and symptom control. For example, pain is usually the result of joint deformity and its sequelae, but nerve entrapment, referred pain, and myopathy might need to be ruled out before surgery.
Proper identification of potential risk factors for anesthesia, surgery, or postoperative course is also important. For example, C1-2 subluxation poses a significant risk for intubation. Carious teeth may increase the likelihood of developing postoperative infection. Obesity may make rehabilitation difficult and compromise the long-term outcome of surgery. These problems would need to be treated or accommodated before surgery.
Timing of surgery may be critical to outcome. For example, shoulder replacement in a patient who has had long-standing ROM deficits, in whom rotator cuff function is limited or absent, will have a poorer functional outcome than someone whose rotator cuff is still working. When possible, surgery should be considered before the development of significant joint contracture, muscle atrophy, and instability.
The surgical procedures relevant for joint and soft-tissue management include synovectomy and joint debridement, tendon repair and realignment, osteotomy, arthrodesis, and arthroplasty. Each procedure has specific indications. Much has been written about the success of these procedures, their life expectancy, and long- and short-term complications. Rehabilitation professionals can assist in preparing patients for optimal outcomes by assisting patients to achieve a higher preoperative level of fitness, helping set realistic expectations, and educating them about health and function-promoting behaviors. These might include developing a strengthening program for the hip girdle muscles for those undergoing hip surgeries, encouraging the use of a cane until the hip abductor is adequately strengthened and Trendelenburg gait is eliminated, and eliminating leg length discrepancies (123).
Synovectomies
Synovectomies were first performed by Volkmann in 1877 for tuberculosis of the knee. Today they are sometimes performed on RA patients, most commonly to relieve pain and inflammation associated with chronic swelling uncontrolled by medication; to retard the progression of joint destruction, which is a controversial issue; and to prevent and retard tendon rupture. Other indications include the alleviation of decreased ROM caused by hypertrophied synovial tissue and denervation effect with reduced pain and inflammatory response.
Synovectomies are usually performed on the knee and wrist, and may be performed by arthrotomy or arthroscopically. They are most frequently done in hemophilic arthropathy, for pigmented villonodular synovitis or early RA.
Tenosynovectomy is most frequently performed for the extensor tendons of the hand. Regrowth of synovium commonly occurs postoperatively, so the procedure is not a curative one. Often local management using intra-articular injections of long-acting corticosteroids is tried, along with splinting of the joint when feasible and education to help develop alternative strategies that prevent overuse (124, 125).
Tendon Surgery
Tendon surgery is common in inflammatory disease. Frequent indications for surgery include repair of ruptured extensor tendons, realignment of tendons of the hand, synovectomies for tendons with severe tenosynovitis, and reanastomosis following tendon ruptures (Achilles and patellar tendons) and tendon releases for intrinsic tightness (126).
Arthrodesis
Arthrodesis is performed less often today than in the past because of the popularity and success of joint replacement. It may still be the best procedure to eradicate resistant infection that has destroyed significant bone. The stability provided by an arthrodesis should be permanent. Adolescents and young adults with many more years of activity might well be considered for an arthrodesis in selected instances rather than a joint replacement, which often does not stand the stress placed on it by a young, vigorous patient. Arthrodesis for patients with arthritis is usually limited to the wrist, interphalangeal (IP) joints of the hand, first metacarpal phalangeal (MCP) joint, subtalar joints, and vertebral bodies. The triple arthrodesis remains one of the best procedures for reconstructing the hind-foot and restoring a pain-free, functional foot. Postoperative rehabilitation for this procedure requires 4 to 6 weeks of non-weight bearing, for which a rollabout can be prescribed for mobility. The rollabout is an ambulation aid, similar to a scooter, mounted 22 in. above the floor on four small wheels. It has a handle, a hand brake, and a padded shelf on which the leg is placed at 90 degrees of knee flexion. It is propelled by the nonoperative lower extremity and permits a reasonably rapid ambulation speed. The next level of independence is the cast boot and then a shoe with a custom insert and a rocker sole that assists in push off. Somewhat more controversial is knee arthrodesis, a procedure that is rarely done but is occasionally suggested for the very young and highly mobile patient.
Common indications for arthrodesis of a joint are to relieve persistent pain, to provide stability where there is mechanical destruction of a joint, and to halt progress of the disease (e.g., infection, RA). Joints should be fused in optimal functional position (127). Contraindications for arthrodesis include significant bilateral joint disease. Joint replacement is indicated more in this instance and arthrodesis of the same joint on the contralateral side.
Joint Replacements
Upper Extremity
Upper extremity joint replacements have become more common today (128). Patients with RA, JIA, OA, and AN in SLE may require joint replacement. Common indications for replacement are persistent pain despite adequate medical and rehabilitative management, loss of critical motion in the involved joint, and loss of functional status.
The main contraindications for joint replacement are inadequate bone stock and periarticular support, serious
medical risk factors, and presence of significant infection. Other contraindications include lack of patient motivation to cooperate in a postoperative rehabilitation program and inability of the procedure to increase the patient’s total functional level.
medical risk factors, and presence of significant infection. Other contraindications include lack of patient motivation to cooperate in a postoperative rehabilitation program and inability of the procedure to increase the patient’s total functional level.
Wrist arthroplasty is recommended for those with adequate bone stock, who have relatively low use requirements. Loosening over time is common (129). MCP arthroplasty is performed for the preservation of function due to the relative frequency of subluxation and progression to dislocation in RA. Surgery performed before MCP dislocation usually has a better outcome (130).
Elbow surgery is usually restricted to radial head excision and arthroscopic synovectomy. Results from these procedures deteriorate over time (131). Elbow replacements have been shown to be effective in reducing pain and in improving ROM in pronation/supination, though improvement in flexion/extension is modest (132). Total elbow replacement has been recently used for patients with inflammatory arthritis with good success. Patients have noted substantial reduction in pain and improved functional ROM (133). Excision of the radial head, however, remains one of the best procedures for pain reduction and improvement in elbow ROM.
Shoulder arthroplasty has been shown to be beneficial in relieving pain. Older patients have better function and longerlasting results than younger patients. Those with rotator cuff tears have 33% to 50% return of ROM following surgery, which is approximately half of those without significant tears that undergo arthroplasty (134). Long-term reports suggest that it is also associated with good functional outcome when rotator cuff function is intact (135). The shoulder is stiff, but flexion and abduction can be performed (<50 degrees) using scapulothoracic movement.
Indication for fusion of the cervical spine in patients with RA remains somewhat controversial. There is agreement that pain, unresponsive to nonsurgical treatment, cord compression, or peripheral sensory and/or motor loss are indications for cervical spine stabilization and/or cord decompression. Some studies suggest that early intervention is associated with better neurologic outcome. Instability of more than 10 mm at the atlantoaxial joint, or greater than 4 mm of basilar invagination suggests the need for spinal stabilization.
Lower Extremity
Total hip replacement surgery has been performed in the United States for more than 30 years. More than 120,000 hip replacements are done annually, and function remains good 25 years after surgery (136). Hip surgeries are no longer limited to patients more than 60 years of age. Infection rates have been dramatically reduced to less than 1% (137). Loosening of the prosthesis is the reason for long-term failure. The acetabular component is more likely to loosen than the femoral component, even in younger patients (138). Uncommented acetabular and femoral components may offer greater prosthetic durability.
Hip replacement surgery offers patients with RA, SLE (avascular necrosis), and AS pain relief and improved function. The decision about whether to offer a cemented or noncemented prosthesis is usually based on the age and the functional requirements of the population to be treated. The older (>70 years of age) patients most frequently receive a cemented prosthesis, which provides good, immediate stability. The noncemented prosthesis is associated with better preservation of bone but may be associated with persistent thigh pain.
Patients are given prophylactic antibiotics before surgery and low-molecular-weight heparin the night of surgery and for the duration of the hospital stay. Antibiotic prophylaxis is recommended for dental work. A good discussion by Sledge of the operative and postoperative course is recommended to the reader (139).
Total knee replacement surgery is commonly used for patients with bi- and unicompartmental joint space destruction, persistent pain from poor joint mechanics, and functional loss. Long-term complications tend to result from uneven patellar surface wear and loosening. Total knee arthroplasty has provided excellent pain relief and good functional outcomes for arthritics. Studies report prosthetic longevity with sustained, excellent function for more than 12 years (140). Problems with the patellar components are the most significant cause of knee joint replacement failure.
Ankle replacement arthroplasties have not been demonstrated to be effective over time. Loosening remains the most serious complication (141). Those patients with very limited mobility who require ambulatory function may be reasonable candidates for this procedure. Forefoot arthroplasty with total resection of the metatarsal heads is an excellent pain-relieving procedure. This enables patients to walk on a pain-free foot, although the toes become floppy, the foot size is smaller, and the mechanics of pushoff, which are usually improved from the painful state, are not returned to normal. Use of a roller sole helps correct the dynamic abnormality (142).
Preoperative Rehabilitation Management
To maximize postoperative gains, preoperative rehabilitation interventions are desirable. These interventions include teaching the patient crutch walking with the appropriate type of crutch; weight reduction for the obese patient; and strengthening of the quadriceps before knee replacement and the hip abductors before hip surgery. Orienting patients to the types of pain they may experience postoperatively—such as acute, incisional; muscle strain or fatigue; and nerve root irritation—may help allay fears about the stability of the hip. Descriptions of the usual course of recovery may also prepare them for what to expect.
Postoperative Rehabilitation Management
The rehabilitation management goals of a total joint replacement program are to relieve pain, to redevelop comfortable musculoskeletal function, and to use joint protection techniques to avoid overstressing the prosthetic joint. The postoperative management of a hip replacement is individualized
based on the preferences of the orthopedic surgeon and the needs of the patient. However, the program usually includes bed mobility. ROM is started immediately with ankle pumps, and isometric exercise to the quadriceps. The patients are usually made to stand by the bedside with full weight bearing crutches if the hip is cemented, or partial weight bearing if it is uncemented. Patients are placed in an abduction sling and told to restrict hip flexion to less than 90 degrees and to limit adduction and internal rotation (IR). While in bed, they are to sleep in a supine position with a pillow between their knees for a month. They need to be carefully monitored for signs of deep venous thrombosis, fever, excessive wound drainage, and/or infection. Patients should be instructed to use an elevated toilet seat and an elevated chair seat to minimize hip flexion. Discharge from the hospital is usually on the fifth day, provided they can get in and out of bed independently, walk independently with crutches or walker, and manage stairs. Key exercises include quadriceps, hip abductor, and hip flexor strengthening. Patients should expect to use a cane until hip abductor strength is in the four (based on the medical research council [MRC] scale) range and there is no Trendelenburg sign. Many orthopedists permit return to full activity, including recreational tennis, cycling, and gardening (143).
based on the preferences of the orthopedic surgeon and the needs of the patient. However, the program usually includes bed mobility. ROM is started immediately with ankle pumps, and isometric exercise to the quadriceps. The patients are usually made to stand by the bedside with full weight bearing crutches if the hip is cemented, or partial weight bearing if it is uncemented. Patients are placed in an abduction sling and told to restrict hip flexion to less than 90 degrees and to limit adduction and internal rotation (IR). While in bed, they are to sleep in a supine position with a pillow between their knees for a month. They need to be carefully monitored for signs of deep venous thrombosis, fever, excessive wound drainage, and/or infection. Patients should be instructed to use an elevated toilet seat and an elevated chair seat to minimize hip flexion. Discharge from the hospital is usually on the fifth day, provided they can get in and out of bed independently, walk independently with crutches or walker, and manage stairs. Key exercises include quadriceps, hip abductor, and hip flexor strengthening. Patients should expect to use a cane until hip abductor strength is in the four (based on the medical research council [MRC] scale) range and there is no Trendelenburg sign. Many orthopedists permit return to full activity, including recreational tennis, cycling, and gardening (143).
The postoperative management of knee replacement includes the following procedures: Begin knee ROM immediately postoperatively, often with the aid of a continuous passive motion machine. Total weight bearing (to tolerance) with crutches and ad lib ambulation is started on the first postoperative day using crutches or a walker. Active assistive flexion is the cornerstone of management and usually needs to be done under supervision of the physical therapist. Knee replacement patients, unlike those undergoing hip replacement, frequently need some additional rehabilitation requiring admission to a rehabilitation center (skilled nursing level or if accompanied by significant comorbidities, an inpatient rehabilitation facility [IRF]).
The extent of rotator cuff repair and function in part dictates the nature of the post-shoulder arthroplasty rehabilitation program, but the postoperative management of total shoulder replacement usually includes the following: Immobilization of the shoulder for 2 to 8 weeks in an airplane splint with the shoulder in 80 degrees of flexion, 70 degrees of abduction, and 5 degrees of IR. Passive motion through range, in excess of where the limb is in the splint, is performed in the supine position. At the eighth to tenth postoperative day, active, assistive shoulder exercise is begun in the sitting position to 110 degrees of flexion and 20 degrees of external rotation (ER). At 6 weeks after surgery, active, unrestricted ROM is permitted, sometimes using an overhead pulley to assist in end range. Lifting up to 10 lb is permitted (144).
REHABILITATION INTERVENTIONS
Rehabilitation treatment plans must be individualized for the patient’s needs; they should be practical, economical, and valued by the patient to enhance compliance. Treatment should begin early in the disease process to help prevent impairment and functional decline so that the patient identifies this as part of the overall management plan. There is scientific and clinical rationale for the use of some specific rehabilitation treatments; others are based on clinical judgment. Rehabilitative rheumatology treatments and techniques must be monitored carefully, and periodic reevaluation of the patient with adjustments in treatment should be made.
Rest
Three forms of rest have been used by persons with arthritis: complete bed rest, local rest of a joint or joints with splints or casts, and short rest periods of 15 to 30 minutes dispersed throughout the day.
Systemic Rest
In the 1960s and 1970s, the literature revealed studies supporting bed rest for up to 4 weeks for persons with RA to decrease the number of inflamed joints, joint stiffness, and disease activity. However, systemic rest has many adverse effects, including muscle weakness and bone loss. Currently, the approach to the management of RA has changed. Much more adequate pharmacologic management of disease activity exists, such as early treatment with DMARDs. In addition, the literature clearly supports mobilizing and exercising patients with inactive and subacute inflammatory arthritis and encouraging them to be proactive in maintaining fitness and healthy lifestyle behaviors through exercise and symptom control throughout the disease course.
Depending on the disease severity, shorter periods of complete bed rest than formerly used may be needed. Several days of bed rest may be indicated for severe new-onset RA, SLE, and PM and for severe acute flares during the course of these diseases when intravenous medication may be needed.
Local Rest
Local rest of acutely or subacutely inflamed joints at night with nonfunctional resting splints and during the day with functional splints reduces inflammation and pain, and may help prevent contracture. Immobilization of the wrist for painful periarticular syndromes (e.g., de Quervain’s syndrome and carpal tunnel syndrome) is useful to relieve pain. One ROM exercise daily for joints during rest of 2 weeks’ duration is not noted to cause an adverse effect. In terms of muscle effect, 4 weeks of knee immobilization in nonarthritic population causes a 21% decrease in muscle mass determined by computerized tomography and biopsy (145).
Short Rest Periods
Provision of short rest periods during the day of 20 to 30 minutes along with appropriate local splinting is considered the appropriate way to manage patients with inflammatory arthritis to help control joint inflammation and fatigue. Some workplace sites now provide rest areas for persons, complete with cots. Negotiation with employers may also result in a person with an office being allowed to keep a small cot or sofa for napping.
Exercise
Arthritis commonly produces decreased biomechanical integrity of joints and their surrounding structures, which results in decreased joint motion, muscle atrophy, weakness, joint effusion, pain, instability, energy inefficient gait patterns, and altered joint loading responses (146, 147).
Arthritis patients may lose muscle strength and bulk because of inactivity. A muscle can lose 30% of its bulk in a week and up to 5% of its strength a day when maintained at strict bed rest (148). Other factors contributing to loss of strength are myositis, myopathy secondary to steroids (149
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