Pain in Rheumatoid Arthritis and Osteoarthritis

CHAPTER 27 PAIN IN RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS



David S. Pisetsky, MD,PhD, Gary McCleane, MD




1. What are the causes of pain in rheumatoid arthritis?


Pain in rheumatoid arthritis (RA) is multifactorial and varies in origin with duration and severity of disease. In the initial phases of RA, pain results from inflammation, as evidenced by tenderness and swelling of the joint as well as laboratory findings (e.g., increased C-reactive protein, anemia, thrombocytosis). The presence of a rheumatoid factor is also consistent with inflammation. As RA progresses, the damaging effects of erosion of cartilage and bone also cause pain. Patients with this disease may also experience pain from fibromyalgia and complications such as osteoporosis, with fracture of vertebral bodies leading to acute symptoms. When the inflammatory process settles, the joint involved may be damaged so that it is mechanically unstable and more likely to undergo degenerative changes that further contribute to pain.


When pain in RA occurs disproportionately in a single joint, it is important to exclude septic arthritis, because preexisting arthritis predisposes to joint space infection.



2. What is synovitis?


Synovitis is inflammation of the synovium, which is the lining tissue of the joint. It is the clinical hallmark of RA and produces pain, swelling, and tenderness of the joint. Other signs of inflammation (e.g., heat and redness) occur less prominently in RA than in other forms of arthritis, such as crystal-induced disease. In RA, dramatic proliferation accompanies synovitis, with a variety of cell types including lymphocytes, fibroblasts, and macrophages forming a dense cellular infiltrate that increases the synovium to many times its normal size, producing a structure called the pannus. Cells of the pannus, at the junction with cartilage and bone, cause erosion by the action of toxic products such as proteases. The end-result of this process can be deformity. Although the synovium in RA is filled with various cell types, joint space effusions have a predominance of neutrophils and are turbid and almost purulent in appearance. In advanced RA, synovium can expand so much that it is visible and easily palpable.


Synovial inflammation and proliferation can occur discordantly in RA. Thus, some patients may have exquisitely painful joints without palpable synovium, whereas others show marked tissue proliferation in the absence of tenderness and pain. In patients with longstanding disease that has “burnt out,” synovial tissue may be only minimally tender.



3. How is RA diagnosed?


RA is diagnosed on the basis of history and physical findings. The disease is usually insidious in onset and affects both large and small joints in a symmetric pattern. Characteristic sites of inflammation include the small joints of the hands and feet, wrists, elbows, shoulders, hips, knees, and ankles. The cervical spine is also a prominent location of disease and is generally the only part of the axial skeleton that is affected by RA.


The diagnosis of RA is supported by the presence of a rheumatoid factor that is an immunoglobulin M (IgM) antiimmunoglobulin G (anti-IgG) antibody. Note, however, that only about 80% of patients with RA display a rheumatoid factor, and that rheumatoid factor can also occur in other clinical settings. The presence of nodules and characteristic deformities (e.g., ulnar deviation, swan neck, and boutonniere deformities of the hands and fingers) substantiate the diagnosis, although these findings indicate more advanced disease and are not invariable.



4. What are the radiographic findings of RA?


The usual radiographic findings of RA are soft tissue swelling, juxtaarticular osteopenia, symmetric joint space narrowing, and bony erosion. Radiograph studies are performed to substantiate the diagnosis of RA, evaluate sources of pain, and stage disease to determine therapy. However, findings may be minimal in early disease. Bony erosions are indicative of tissue destruction and signify serious prognosis. Radiographs of joints in RA may also show evidence of osteoarthritis, which can occur secondary to joint destruction. With sustained disease activity, impaired mobility, and corticosteroid therapy, osteoporosis also occurs. It can be demonstrated by radiographic examination and by bone densitometry.



5. What is a flare?


RA, like other rheumatic diseases, varies in intensity over time and includes periods (“flares”) during which signs of inflammation increase dramatically. Flares can occur without cause, or may follow infection and other stresses. They are associated with increased joint pain and swelling; symptoms such as prolonged morning stiffness, weakness, malaise, and weight loss; and laboratory findings of inflammation. Because RA is a systemic disease, flares are usually polyarticular. The sudden onset of severe pain and swelling in a single joint should raise the suspicion of infection.



6. How is morning stiffness significant in RA?


Morning stiffness is a very common complaint of patients with RA and is experienced as soreness and restricted movement upon awakening. This feeling is generalized in distribution and does not simply affect the joints. Although it is a form of pain, patients may not describe it as such.


The duration of morning stiffness is a good indicator of disease activity, and physicians should record this value as part of the clinical assessment. Many patients take a hot shower to relieve the sensation. The “gel phenomenon”—stiffness and soreness that develops after a period of immobility (e.g., sitting in a chair)—is a related symptom.



7. Differentiate rheumatoid arthritis and osteoarthritis


RA and osteoarthritis (OA) are the two most common forms of arthritis. They are sometimes confused with each other because of their predilection for similar joints. The underlying pathophysiology of these diseases is distinct, however.


RA is inflammatory, and it initially involves the synovium and secondarily involves the cartilage. In contrast, OA primarily affects the cartilage, with this structure losing its mechanical properties from degeneration or degradation. Although cartilage in OA lacks the usual signs of inflammation such as an inflammatory cell infiltrate, chondrocytes in the cartilage may produce inflammatory mediators such as interleukin-1 (IL-1) and nitric oxide that cause breakdown of the cartilage matrix. Although OA can be polyarticular in nature, many patients have involvement of only single joints such as the knee or hip. The usual course of RA is symmetric involvement of multiple joints.


In RA, joint fluid is inflammatory and contains neutrophils in abundance (up to 50,000/ml), whereas in OA joint fluid shows few cells (≤1000/ml).


Another difference between these two diseases concerns the impact on bone. In OA, hypertrophic changes cause bony enlargements called spurs or osteophytes. Inflammation in RA lacks a bony reaction.



8. Give two alternate names for osteoarthritis


OA is also called degenerative joint disease or hypertrophic arthritis because of the pattern of cartilage and bone involvement.



9. What are Heberden’s and Bouchard’s nodes?


Heberden and Bouchard’s nodes are osteoarthritic bony enlargements in the hands.



10. Describe primary and secondary osteoarthritis


When OA occurs in the absence of a known predisposing cause, it is termed primary. If a contributing factor can be identified, e.g., congenital hip disease, fracture, or excessive motion or use, OA is termed secondary.



11. What are the demographics of RA and OA?


Both RA and OA occur more commonly in women than in men for reasons that are unknown. RA usually begins in the fourth and fifth decade of life, while OA starts later and is almost invariable among people in their 80s and 90s. Both diseases run in families, although the etiology is complex and likely multifactorial. Among genetic risk factors for RA, certain human leukocyte antigen (HLA) genes seem to predispose to disease; because disease occurs only occasionally among people genetically at risk, an environmental factor (e.g., infection) may be implicated in pathogenesis.



12. What is inflammatory OA?


Some patients with OA have especially prominent inflammation, with joint pain, tenderness, and redness. These patients are considered to have inflammatory or erosive osteoarthritis. This condition can be distinguished from RA on the basis of joint distribution, radiographs, and laboratory signs of inflammation.



13. What are the radiographic findings of OA?


The typical radiographic findings of OA are asymmetric joint space narrowing, subchondral sclerosis, cysts, and spur formation. Spurs or osteophytes represent bony outgrowths around the joint. OA and RA can be distinguished radiographically because RA causes symmetric joint space narrowing and lacks hypertrophic changes. Note that pain in arthritis can be referred; thus, a painful joint may show only limited change, necessitating radiographic study of a nearby joint to establish the cause. Knee pain, for example, may be referred from the hip.



14. Compare joint distribution in OA and RA


OA and RA involve many joints in common (e.g., proximal interphalangeal joints of the hands, hips, knees, and cervical spine), but there are important differences that have diagnostic significance.



image Affected by OA


image Distal interphalangeal joints of hands

image Lumbar spine

image Affected by RA


image Metacarpophalangeal joints of hands

image Wrists, elbows, shoulder, ankles, small joints of feet

The distribution of joints in OA suggests that this disease is not simply the result of joint use or weight bearing, but reflects particular mechanical or biochemical properties of joints.



15. What are the classes of drugs used to treat rheumatoid arthritis?


Pharmacologic therapy for RA can be divided into four main categories: (1) nonsteroidal antiinflammatory drugs (NSAIDs); (2) corticosteroids, which are antiinflammatory and immunosuppressive; (3) analgesics; and (4) disease-modifying antirheumatic drugs (DMARDs). Therapy in RA frequently involves the simultaneous administration of drugs from more than one category, and there is considerable discussion concerning the timing and duration of therapy, as well as relative toxicity and efficacy of different agents.



16. Discuss the role of disease-modifying antirheumatic drugs in RA


DMARDs are drugs that reduce the signs and symptoms of rheumatoid arthritis and can influence the progression of tissue destruction, usually as assessed by radiographs. These drugs may also improve mobility and quality of life, as measured by various indices of patient self-report. The actions of these agents are diverse and in many instances unknown. The term DMARD is confusing, because in some patients an NSAID or corticosteroid can lead to sustained improvement. Furthermore, there is evidence that corticosteroids can also modify radiographic progression.


DMARDs include methotrexate, leflunomide, tumor necrosis factor (TNF) blockers (etanercept and infliximab), IL-1 receptor antagonist (anakinra), gold salts, penicillamine, hydroxychloroquine, and azathioprine. More potent immunosuppressants such as cyclosporine and cyclophosphamide are rarely used in RA, but are placed in this category. Sulfasalazine, which has both antiinflammatory and antibiotic potential, is also in this group.



17. What determines the selection of a DMARD over other agents?


Factors pointing to the need for DMARD therapy include the following:



image Clinical evidence of persistent disease activity (e.g., number of painful and tender joints and duration of morning stiffness)


image Inadequate response to NSAIDs


image Laboratory evidence of inflammation (e.g., sedimentation rate or C-reactive protein)


image Erosive changes on radiograph*


image Progressive deformity


image Nodules


image Titer of rheumatoid factor


*DMARDs are used widely in the setting of persistent disease activity even in the absence of radiographic evidence of joint changes, because of the potential for long-term joint damage in RA.


DMARD use is individualized for the patient depending on disease severity and activity, patient preferences, and concerns about toxicity. Methotrexate is frequently the first DMARD tried, because of its well-established efficacy.



18. What is “early aggressive” therapy of RA?


Early aggressive therapy refers to the early use of DMARDs, recognizing that erosive damage is irreversible and can begin soon after the onset of disease. In the past, DMARD therapy typically was administered only after the occurrence of erosion. This practice reflected concerns over the toxicity of the more commonly used drugs at that time (e.g., gold salts) and the risk-benefit ratio. Current DMARDs show a much more favorable profile with respect to toxicity, leading to their more widespread and earlier use. In general, DMARD therapy is indefinite, but there is evidence that the earlier they are started, the better the clinical outlook in the long term.


Recently, some clinicians have recommended an even more aggressive approach with combinations of DMARDs in association with high-dose corticosteroids as initial therapy. In this approach, sometimes called the step-down approach, steroid doses are lowered and DMARDs withdrawn gradually as disease stays quiescent. Despite evidence for the utility of the step-down approach, most clinicians start with one DMARD and gradually add others to form a combination that adequately suppresses disease activity.



19. How do NSAIDS work?


NSAIDs inhibit the enzyme cyclooxygenase and thus block the generation of prostaglandins from arachidonic acid. Because of the physiological actions of prostaglandins, NSAIDs are antiinflammatory, analgesic, and antipyretic. These activities make the NSAIDs among the most commonly used drugs in all of medicine, whether by prescription or over-the-counter purchase. As now recognized, there are two cyclooxygenase enzymes, denoted COX1 and COX2. COX1 is constitutively produced, whereas COX2 is inducible. COX1 mediates such effects as platelet aggregation and maintenance of the stomach lining. COX2 mediates inflammation and pain. Currently available NSAIDs have different side effects and also differ in their relative activity against COX1 and COX2.



20. What are coxibs?


Coxibs are NSAIDs that are highly selective for the COX2 enzyme. Because the COX2 enzyme mediates prostaglandin production responsible for inflammation and pain, coxibs are analgesic and antiinflammatory, but they lack the side effects related to inhibiting the COX1 enzyme (e.g., bleeding and gastrointestinal irritation). Like nonselective NSAIDs, which affect both COX1 and COX2 enzymes, coxibs are used in both OA and RA. The three currently approved coxibs are celecoxib, rofecoxib, and valdecoxib. Examples of nonselective NSAIDs are indomethacin, ibuprofen, and diclofenac.


Some patients respond to one NSAID or coxib but not to another; the reasons for this remain unclear. It is recommended that more than one of these drugs be tried before considering this type of therapy unsuccessful. The use of some coxibs have been restricted because of their propensity to cause increases in blood pressure and because their use is associated with a higher incidence of myocardial infarction.



21. What are the side effects of NSAIDS?

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Jun 14, 2016 | Posted by in PAIN MEDICINE | Comments Off on Pain in Rheumatoid Arthritis and Osteoarthritis

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