42 Polyarticular Arthritis

Polyarthritis is pain of synovial or articular origin, with or without inflammation, in four or more joints.

The history and physical examination are essential elements for diagnosis.

Exclude fibromyalgia as a cause of pain, and evaluate for common causes such as osteoarthritis.

Identify patients who are likely to have persistent, destructive disease.

Initiate prompt therapy in those with poor prognostic indicators.

Articular disorders are the most common cause of disability in the United States. Recent estimates by the Centers for Disease Control and Prevention (CDC) reveal that approximately one in five (49.9 million) adults in the United States have reported doctor-diagnosed arthritis; of these, 21.1 million adults have reported arthritis-attributable activity limitation.¹ A substantial number of these patients manifest polyarticular joint involvement. The presentation of polyarticular joint pain poses a diagnostic challenge to the clinician, given the magnitude of the complaint, urgency to provide relief and preserve joint function, and the uncertainty of the outcome. Although many articular complaints (e.g., tendinitis, bursitis) are self-limiting and require only time and symptomatic management, others may present with or persist as chronic polyarthritis, with the potential for joint damage or disability. Knowledge of the most prevalent or commonly misconstrued causes of polyarthritis can facilitate an accurate diagnosis and appropriate therapy. This chapter will examine the diagnostic approach to polyarthritis, leaving its management to relevant chapters found throughout this textbook (see Chapters 71, 75 through 78, and 81).

Epidemiology and Societal Impact

The prevalence of arthritis is expected to rise as the U.S. population ages; an estimated 60% of the U.S. population older than 65 is affected by chronic joint symptoms.² In 2002, the Behavior Risk Factor Surveillance System (BRFSS), a state-based random digit–dialed telephone survey of the U.S. civilian population, found that 69.9 million Americans had chronic joint symptoms defined as pain, aching, or stiffness in or around the joints lasting longer than 3 months.³ Of these, 25.1 million had not seen a physician, and more than 2 million had activity limitations. The survey also found that those who had never seen a health care provider for their joint complaints were likely to be male, to have lower educational levels, and to have no health insurance.⁴ An estimated 25% of patients will be unable to work within 7 years of disease onset. Direct and indirect costs are estimated at 1.2% of the U.S. gross domestic product, or $128 billion.^1,⁵ These statistics encompass all forms of arthritis and extol the pervasive societal impact and cost of arthritis and the diagnostic deficit that exists. Thus a facile and accurate approach to patients with joint symptoms is sorely needed.

Defining Polyarthritis

Polyarthritis is classically defined as pain (with or without signs of inflammation) that affects four or more joints. In the pediatric literature, polyarthritis applies to those with involvement of five or more joints. The distinction between these definitions is moot in that both definitions imply a significant risk of added joint involvement over time. Hence, without an early diagnosis and appropriate management, polyarthritis begets polyarthritis. Patients with chronic involvement of one (monoarthritis) or two or three joints (oligoarthritis) are at low risk of polyarthritis, even with the passage of time.

The differential diagnoses underlying polyarticular complaints can be extensive and intimidating to the inexperienced. Narrowing these to firm a diagnosis is best accomplished in four diagnostic steps:

1. Evaluate for the most prevalent causes—trauma, osteoarthritis, and fibromyalgia.

2. Distinguish between acute and chronic polyarthritis.

3. Delineate articular from periarticular disorders.

4. Elicit clues to increase the likelihood of a diagnosis.

Although many rheumatologists advocate a chronologic (acute vs. chronic), pathophysiologic (inflammatory vs. noninflammatory), or anatomic (oligoarticular vs. polyarticular, periarticular vs. articular) approach to diagnosis, such an approach yields insight into underlying processes without focusing on the most likely conditions, thereby leaving the examiner with a wide range of possibilities. For example, the differential diagnosis of a chronic inflammatory polyarthritis may include rheumatoid arthritis (RA), undifferentiated polyarthritis, psoriatic arthritis, juvenile idiopathic arthritis (JIA), viral arthritis, serum sickness, and tophaceous gout and pseudogout, to name just a few. Regardless of the preferred approach, the diagnosis of polyarthritis relies heavily on an intelligent and accurate history and examination. Hence, key factors such as onset of acuity, course of disease progression, and evidence of inflammation are more diagnostic than a battery of poorly chosen laboratory investigations. Early diagnosis and treatment is the primary goal, particularly when inflammation is present, in which case earlier treatment can avert considerable disease-related morbidity.

Approach to Diagnosis

Frequent Noninflammatory Polyarticular Scenarios

It is crucial that the clinician consider the most common causes of polyarticular and widespread musculoskeletal complaints—osteoarthritis (OA) and fibromyalgia (FM). Osteoarthritis affects 12 to 27 million, and fibromyalgia and related disorders (chronic fatigue syndrome, chronic widespread pain) affects 5 to 11 million in the United States alone.¹ Although these two conditions are easily distinguishable from other arthropathies on clinical grounds (without laboratory or radiographic investigation), they often are missed for several reasons. First, it is possible to have more than one condition; RA is frequently accompanied by some degree of degenerative arthritis that may be constitutive, posttraumatic, or secondary to antecedent inflammatory disease. Similarly, patients with systemic lupus erythematosus (SLE) or Sjögren’s syndrome may have secondary FM observed as uncontrolled pain and poor sleep. Second, patients who once had an arthropathy (e.g., an inflammatory arthritis such as psoriatic arthritis) may find that it evolves into another type of arthritis. For example, psoriatic arthritis may cause years of swelling, stiffness, inflammation, and joint damage, only to “burn out” years later. However, the pattern of pain and stiffness may persist owing to secondary OA or FM, even though evidence of inflammatory arthritis is limited or nonexistent. Last, a detailed and skillfully performed musculoskeletal examination is required to discern that the joint pain is articular (e.g., RA) rather than extra-articular (e.g., FM) in origin, or that the swelling is related to synovial (e.g., RA) rather than bony (e.g., OA) hypertrophy, or that widespread pain is accompanied by tender trigger points (e.g., FM) rather than enthesitis (e.g., ankylosing spondylitis).

Fibromyalgia

This condition is five times more prevalent than rheumatoid arthritis and may underlie 10% to 20% of all outpatient musculoskeletal visits.² It affects women more so than men, usually between the ages of 30 and 60 years, but people of all ages can be affected. Few patients announce widespread pain and tender points at presentation. Instead, most present because of regional joint or muscle pain, profound fatigue, and problems with mentation, memory, or headaches. Only upon further questioning will the examiner discern the wider distribution of painful tender points, joints, muscles, and tendons with an associated recent or long history of poor sleep. FM is a pain amplification disorder, with lowered pain thresholds, that often is accompanied by other “spastic conditions,” including migraine, irritable bowel syndrome, primary dysmenorrhea, atypical chest pain (often mislabeled as costochondritis), temporomandibular joint pain (without dysfunction or damage), and low back or neck pain. Diagnostic testing (laboratory tests, radiographs) is not necessary. The syndrome is established by history and examination and can be confirmed by (1) a positive response to simple analgesics, (2) improved sleep with better sleep hygiene plus sleep aids, (3) improvement attained with a stretching exercise program (e.g., swimming, Pilates, yoga, tai chi, physical therapy), and (4) uncontrolled depression or anxiety.

Age, yr	Men	Women
18-30	Spondyloarthropathies * Gout Infectious arthritis ^† Rheumatic fever	Infectious arthritis ^† RA Connective tissue disorders ^‡ Rheumatic fever Arthritis associated with oral contraceptives Sarcoidosis
30-60	Gout Spondyloarthropathy * Infectious arthritis Vasculitis ^§ Hemochromatosis	RA Infectious arthritis Arthritis of thyroid disease Vasculitis ^§ Sarcoidosis
>60	Bursitis Gout RA Pseudogout Vasculitis ^§ PMR RS3PE Arthritis of thyroid disease Amyloidosis Lymphoma Hypertrophic osteoarthropathy	Bursitis RA Gout Pseudogout Vasculitis ^§ PMR Infectious arthritis Erosive osteoarthritis Arthritis of thyroid disease Amyloidosis Lymphoma

PMR, polymyalgia rheumatica; RA, rheumatoid arthritis; RS3PE, relapsing symmetric seronegative synovitis with pitting edema.

^* Spondyloarthropathies include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis.

^† Infectious arthritis includes gonococcal arthritis, Lyme arthritis, viral arthritis, and bacterial arthritis.

^‡ Connective tissue disorders include systemic lupus erythematosus, scleroderma, Behçet’s disease, mixed connective tissue disease, and polymyositis/dermatomyositis.

^§ Vasculitis includes polyarteritis nodosa, granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), hypersensitivity vasculitis, and temporal arteritis.

Modified from Lipsky P: Algorithms for the diagnosis and management of musculoskeletal complaints, Am J Med 103:62S, 1997.

Symptom Onset

Attention should be paid to how symptoms first began and under what circumstances. Eliciting a history of disease onset may be difficult if patients suffered from their illness for years, but identifying the acuity of symptoms may aid in diagnosis. If patients present with abrupt onset of symptoms, occurring in a matter of hours/days, the clinician may consider infection, gout, pseudogout, or trauma, whereas if symptoms were present for months/years, rheumatoid arthritis (RA), psoriatic arthritis (PsA), chronic infection (e.g., syphilis, hepatitis, human immunodeficiency virus [HIV]), FM, and OA are among the top differential diagnoses.

Pattern of Joint Involvement

Types of affected joints are often good clues to uncovering the type of arthritis. Consider patients who present with involvement of distal interphalangeal joints (DIPs); this may indicate osteoarthritis or psoriatic arthritis. Contrast these patients with those who have symptoms in their proximal interphalangeal joints (PIPs) and metacarpophalangeal joints (MCPs), where rheumatoid arthritis commonly manifests. Involvement of large joints such as hips and shoulders may suggest polymyalgia rheumatica or a spondyloarthritis.

Disease Course

Noting how the disease progresses may assist in predicting outcome. Patients who have chronic symptoms may describe varying patterns of presentation ranging from an intermittent pattern, where attacks are punctuated by periods of complete remission, to an additive pattern, where symptoms begin with a few joints and progress to involve more joints with time, or a migratory pattern, where certain joints are affected for a time, then the disease remits, only to reappear elsewhere in other joints.

Presence of Inflammation

Evaluation for inflammation may be difficult. Studies have examined features of the history that may provide diagnostic clues to inflammation, such as morning stiffness and response to activity. Clearly, patients with all or some of the cardinal signs of inflammation (redness, warmth, swelling, pain in the morning) may have an inflammatory arthropathy. Morning stiffness (an inflammatory finding) is often confused with the “gel” phenomenon (a degenerative feature). Morning stiffness, defined as the time to maximal improvement after an extended period of inactivity (an overnight rest), typically improves with movement.⁶ In patients with inflammatory arthritis, the duration of morning stiffness is typically greater than 60 minutes. The gel phenomenon refers to short-lived stiffness that is brought on by short periods of rest and is common to patients with degenerative arthritis. Patients with inflammatory arthritis may present with pain without swelling, swelling without pain, or difficulty performing their activities of daily living without pain or swelling. It is important to distinguish whether inflammation is truly present as the cause of symptoms. Both arthralgia (joint pain) and arthritis (joint swelling from synovial fluid or tissue) may be present in new-onset polyarthritis; hence the joint examination is an essential component in establishing the diagnosis.

Physical Examination

Arthralgia vs. Arthritis

Characteristics that distinguish synovitis include warmth, erythema, tenderness to palpation, and synovial effusion. Any or all of these findings may accompany arthralgia. Range of motion, muscle strength, and function may be limited around the inflamed joint. In an effort to reduce joint volume and pain, the patient often will involuntarily hold the joint in a position of partial flexion. Hence, joint contractures may indicate an underlying inflammatory process (present or past). In RA, any diarthrodial joint can be affected, but the pattern of involvement typically involves the MCPs, PIPs, wrist, metatarsophalangeal joints (MTPs), and ankle joints.⁶ This pattern of involvement should be distinguished from osteoarthritis (DIPs, PIPs, carpometacarpal [CMC]1, knee, hip, spine), psoriatic arthritis (DIPs, PIPs, wrist, toes), and pseudogout (knee, wrist, MTPs). The accuracy of identifying synovitis depends on the skills and experience of the physician. The reproducibility of the physical examination in identifying synovitis has been a subject of concern raised in several studies.⁷^–¹¹ One study looked at whether rheumatologists can agree on the diagnosis of inflammatory arthritis; 24 patients were assessed by 6 rheumatologists—complete agreement was found in only 70% of cases; disagreement in the remaining 30% of cases ranged from 1 to 4 rheumatologists recognizing synovitis when others did not.¹²

This is further illustrated by imaging studies. When the physical examination is compared with imaging, the joint examination has a reported sensitivity of 43%, specificity of 89%, and accuracy of 71% with magnetic resonance imaging (MRI) as the reference.¹¹ Given the difficulty for many practitioners of discerning synovitis, Emery and colleagues have advocated the value of the MCP or MTP “squeeze test” (Figure 42-2). Their study found that pain upon transverse compression of the MCP or MTP joints (a positive squeeze test) has better specificity in identifying persistent arthritis than in finding arthritis in three or more joints, or symmetric arthritis.¹³ Currently, the joint examination is the gold standard for detection of synovitis; however, MRI and ultrasound may provide additional diagnostic evidence of synovitis in patients with chronic synovitis that is not evident on joint examination.