Acute Polyarthritis: A Comprehensive Guide to Differential Diagnosis

Introduction

Patients frequently present to clinicians reporting pain in “all my joints.” While the initial concern might lean towards rare or complex diagnoses, many of these cases involve transient, self-limiting, or less significant conditions. The cornerstone of effectively diagnosing polyarticular arthritis lies in meticulous history taking and a thorough physical examination. These essential steps are crucial for narrowing down the broad spectrum of potential causes to a manageable set of likely diagnoses. Subsequent confirmatory tests then serve to either substantiate or rule out the precise underlying etiology.

While advanced diagnostic tools, including blood work, various imaging modalities, tissue biopsies, and sophisticated techniques, are readily available, the most invaluable diagnostic asset remains the clinician’s ability to ask precise, detailed questions and conduct a comprehensive physical examination. This approach is not only diagnostically effective but also plays a vital role in preventing unnecessary healthcare expenditure on extensive and costly investigations.

The primary step in evaluation is to determine whether the inflammation originates within the joint itself or from adjacent structures. Non-articular and peri-articular pain are common and can be misleading, often radiating to the joint area. If the pain and inflammation are confirmed to be intra-articular, it can be further classified as either inflammatory or non-inflammatory. Non-inflammatory conditions, such as osteoarthritis (OA), are typically chronic, milder in nature, and lack the prominent inflammatory markers like redness, warmth, swelling, and systemic symptoms. In contrast, inflammatory arthritis is characterized by these features, necessitating further investigation to establish a differential diagnosis based on factors such as the number of joints involved, the pattern of joint involvement, chronicity, and symmetry.

Etiology of Polyarthritis

Understanding the broad range of potential causes is crucial in the differential diagnosis of polyarthritis. The etiologies can be broadly categorized into non-articular, peri-articular, non-inflammatory articular, and inflammatory articular conditions.

Non-articular Etiologies: These conditions mimic joint pain but do not originate from the joint itself. Common examples include:

• Hypothyroidism
• Depression
• Somatoform pain disorder

Peri-articular Etiologies: These conditions involve structures surrounding the joint, such as bursae, tendons, and nerves:

• Bursitis
• Tendinitis
• Neuropathic pain
• Metabolic bone diseases
• Soft tissue injury
• Fibromyalgia

Non-inflammatory Articular Etiologies: Osteoarthritis is the primary example in this category, characterized by degenerative joint changes rather than active inflammation.

Inflammatory Arthritis Etiologies: This category encompasses a wide array of conditions characterized by active joint inflammation. These can be further subdivided:

1. Bacterial Infections:

   • Lyme disease
   • Endocarditis
   • Septic arthritis

2. Viral Infections:

   • Hepatitis B and C
   • Epstein Barr virus
   • Parvovirus
   • Dengue fever
   • Alphaviruses
   • Rubella
   • Human immunodeficiency virus (HIV)
   • Mumps
   • Coxsackievirus

3. Collagen-Vascular Diseases (Autoimmune):

   • Rheumatoid arthritis (RA)
   • Palindromic rheumatism
   • Rheumatic fever
   • Systemic lupus erythematosus (SLE)
   • Vasculitis
   • Systemic sclerosis
   • Myositis
   • Ankylosing spondylitis
   • Psoriatic arthritis
   • Behcet’s syndrome
   • Relapsing polychondritis

4. Crystal-Induced Arthritis:

   • Gout (uric acid crystal deposition)
   • Pseudogout (calcium pyrophosphate deposition)

5. Post-Infectious or Reactive Arthritis:

   • Post-enteric infections
   • Disseminated gonococcal infection

6. Familial Mediterranean Fever: An autoinflammatory genetic disorder.

Epidemiology of Polyarthritis

Arthritis is a widespread health concern, with the Arthritis Foundation reporting over 100 types of arthritis in 2015. Approximately 91.2 million adults in the United States are estimated to have physician-diagnosed arthritis or report joint symptoms consistent with arthritis. This signifies that nearly one in three individuals aged 18-64 experience arthritis. The prevalence increases significantly with age; after 65, about half of men and two-thirds of women are affected. Incidence rates are projected to rise, with estimations suggesting that nearly half the US population will have physician-confirmed arthritis by 2040.

Polyarticular arthritis, in particular, is more prevalent among females and individuals with obesity. Advanced age is also a significant risk factor. The economic burden of arthritis is substantial, with total costs (including medical care, lost earnings, and productivity losses) estimated at 1% of the US GDP, amounting to $304 billion in 2013.

Furthermore, arthritis is frequently associated with comorbidities. Among individuals with arthritis, approximately 33% experience depression or anxiety, 25% have cardiac issues, 20% have respiratory conditions, and 16% have diabetes. Physical inactivity, potentially stemming from arthritis-related limitations, is likely a contributing factor to these comorbidities.

Pathophysiology of Polyarthritis

The underlying mechanisms of polyarthritis differ significantly between non-inflammatory and inflammatory types.

Non-inflammatory Arthritis (Osteoarthritis): The pathophysiology is primarily mechanical, although cellular and biochemical processes are also involved. The normal cartilage remodeling process is disrupted, leading to excessive cartilage degeneration, reduced regeneration, and abnormal cartilage structure. This results in progressive cartilage loss, thickening of the subchondral bone, and cyst formation. Over time, the cartilage becomes thinner, weaker, and less resilient, causing bone-on-bone friction. This friction stimulates bone remodeling and the formation of osteophytes (bone spurs) at the joint margins. Mild inflammation may occur as a secondary consequence of this mechanical stress. These changes collectively impede smooth joint movement, causing discomfort and eventually pain.

Inflammatory Arthritis: The pathophysiology of inflammatory arthritis is diverse, encompassing infectious, crystal-induced, reactive, and autoimmune mechanisms. In collagen vascular diseases, inflammatory cytokines and autoantibodies trigger an inflammatory cascade and the formation of pannus, an abnormal layer of fibrovascular tissue. Pannus can invade and damage cartilage and bone. This inflammatory damage is typically more acute and severe than in osteoarthritis, and without prompt medical intervention, joint destruction can progress rapidly.

History and Physical Examination in Polyarthritis

A detailed history and physical examination are paramount in differentiating the causes of polyarthritis.

Chronicity and Pattern:

• Acute arthritis: Duration of symptoms less than two weeks.
• Chronic arthritis: Symptoms persisting for more than two weeks, which can be intermittent or constant.
• Pauciarticular: Involvement of two to four joints.
• Polyarticular: Involvement of five or more joints.
• Symmetry: Symmetrical involvement (e.g., both hands) is more typical of rheumatoid arthritis, while asymmetrical involvement is common in osteoarthritis and spondyloarthropathies.

Joint Distribution and Characteristics:

• Rheumatoid arthritis (RA): Typically polyarticular, affecting small joints of the hands and wrists in a symmetrical pattern. Onset is usually gradual, developing over weeks to months.
• Seronegative spondyloarthropathies: Often pauciarticular, with axial involvement (spine and sacroiliac joints) and inflammation of large joints.
• Osteoarthritis (OA): Commonly affects weight-bearing joints, is usually asymmetrical, and pain worsens with activity and improves with rest.
• Inflammatory arthritis: Generally symmetrical, with pronounced inflammatory signs in non-weight-bearing joints. Morning stiffness lasting over an hour is a hallmark of inflammatory arthritis, particularly seronegative spondyloarthropathies.

Acute Presentations:

• Migratory pattern: Joint pain that moves from one joint to another acutely may suggest viral arthritis, rheumatic fever, or disseminated gonococcal infection. Viral arthritis is the most frequent among these. Diagnosing viral arthritis can be challenging as the inflammation often resolves before definitive diagnostic tests can be performed.
• Septic arthritis: Characterized by acutely hot, swollen, red, and exquisitely painful joints with limited movement. Typically monoarticular, affecting a large joint, and accompanied by systemic symptoms. Polyarticular septic arthritis is rare, but it can occur, especially in joints already affected by a pre-existing polyarticular inflammatory condition, making diagnosis more complex.

Pain Characteristics:

• Osteoarthritis pain: Worsens with movement and is relieved by rest.
• Rheumatoid arthritis pain: Characterized by morning stiffness that improves with movement and activity.

Duration of Symptoms:

• Short episodes of synovitis (4-6 weeks) are often associated with viral infections.
• Prolonged symptoms suggest a persistent underlying condition.

Neurological Symptoms:

• Sensory disturbances like paresthesia, allodynia, or anesthesia may indicate neuropathy or radiculopathy rather than arthritis.

Extra-articular Symptoms: These are crucial clues in differential diagnosis:

• Rashes (psoriatic arthritis, lupus)
• Oral and genital lesions (Behcet’s syndrome)
• Heart murmur (endocarditis)
• Dry mouth and eyes (Sjogren’s syndrome)
• Polyserositis (lupus)

Physical Examination Techniques:

• Assess for synovitis (inflammation of the synovial membrane) and chronic arthritis changes.
• Examine muscles, joints, tendons, bursae, and soft tissues.
• Evaluate both active and passive range of motion (ROM). Non-articular conditions typically show normal passive ROM but limited active ROM (e.g., tendinitis, bursitis). Articular diseases restrict both active and passive ROM.
• Palpation can differentiate tendinitis and bursitis. Bursitis presents with localized tenderness that is not significantly affected by movement, whereas tendinitis pain worsens with tendon movement.
• Cardinal signs of inflammation: warmth, redness, swelling, and tenderness strongly suggest inflammatory arthritis. Septic arthritis exhibits these signs in a more pronounced manner.
• Crepitus (grating sound or sensation) may indicate osteoarthritis.
• Joint laxity suggests joint damage and instability.
• Extra-articular findings during physical examination are often as informative, or even more so, than joint-specific findings.

Evaluation of Polyarthritis

The evaluation of polyarthritis can be extensive and is guided by the clinical presentation and suspected underlying etiologies.

Laboratory Investigations:

A rheumatological workup is often indicated, including:

• Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (CCP): For rheumatoid arthritis.
• Antinuclear antibody (ANA): Screening test for systemic lupus erythematosus and other autoimmune conditions.
• Anti-Smith and anti-double-stranded DNA: Specific for systemic lupus erythematosus confirmation.
• Anti-Scl-70: Systemic sclerosis.
• Anti-Ro (SSA) and anti-La (SSB): Sjogren’s syndrome.
• Anti-U1-RNP: Mixed connective tissue disease.
• Anti-neutrophilic cytoplasmic antibody (ANCA): Granulomatosis with polyangiitis (C-ANCA) and microscopic polyangiitis (P-ANCA).
• Anti-Jo-1: Myositis.
• Anti-histone: Drug-induced lupus erythematosus.
• Cryoglobulin: Vasculitis associated with hepatitis C.

Inflammatory Markers:

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): Non-specific markers of inflammation, useful for detecting significant inflammation and monitoring treatment response.

Synovial Fluid Analysis:

• Polarized microscopy: Identifies crystals in crystal-induced arthritis (gout, pseudogout).
• Cell count, Gram stain, and culture: To assess for infection and inflammation.
  • Normal synovial fluid: Leukocyte count < 200/mm³.
  • Non-inflammatory arthritis: Leukocyte count 200-2,000/mm³.
  • Inflammatory arthritis: Leukocyte count > 2,000/mm³.
  • Suspect infectious arthritis: Leukocyte count > 50,000/mm³.

Infectious Disease Screening:

• Tests for hepatitis viruses, Lyme disease, and parvovirus to rule out infection-related arthritis.

Imaging Studies:

Imaging modalities play a selective role in the evaluation of polyarthritis. Routine imaging of every involved joint is generally not necessary, especially in acute polyarthritis, where findings are often non-specific early on.

• X-rays: Useful for detecting fractures, dislocations, and osteomyelitis. In advanced osteoarthritis, x-rays can show erosions, sclerosis, joint space narrowing, and osteophyte formation. However, these changes often appear late in the disease process. X-rays of the hands, wrists, and metacarpals can sometimes be helpful in rheumatoid arthritis and for monitoring disease progression. Cervical spine x-rays (C1-C2) are essential in rheumatoid arthritis follow-up to assess for potential instability and prevent pathologic fractures. X-rays can also detect calcium pyrophosphate deposition in pseudogout. Sacroiliac joint x-rays may show changes in seronegative spondyloarthropathies, although MRI is more sensitive.

• Ultrasound: Readily accessible and useful for detecting erosions and synovitis, and for guiding joint injections.

• Computed tomography (CT): Limited role, primarily to exclude other conditions.

• Magnetic resonance imaging (MRI): Highly sensitive for detecting early joint inflammation and early bone or soft tissue infections, especially sacroiliac joints in spondyloarthropathies.

• Radionuclide scans: Rarely used, but can be helpful in specific situations such as suspected metastases, Paget’s disease of bone, or osteomyelitis.

Biopsy:

Biopsy is rarely needed in polyarthritis diagnosis due to the availability of other diagnostic modalities. However, it may be necessary to diagnose or confirm vasculitis, arteritis, infectious etiologies, or granulomatous diseases in certain cases.

Treatment and Management of Polyarthritis

Treatment strategies for polyarthritis are dictated by the underlying diagnosis.

Osteoarthritis Management:

• Correction of biomechanical abnormalities
• Weight loss (if applicable)
• Reduction of joint stress
• Heat and warmth application
• Strengthening exercises
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroid injections
• Joint replacement therapy (in advanced cases)

Collagen Vascular Diseases Management:

• Disease-modifying antirheumatic drugs (DMARDs), including biologics and conventional DMARDs (e.g., methotrexate). Early, aggressive treatment with DMARDs has revolutionized management, preventing joint damage and improving outcomes.
• NSAIDs for palliative pain relief, particularly in advanced disease or before surgical interventions.
• Newer biologic agents are available in oral and injectable forms for various approved indications.

Infectious Arthritis Management:

• Antibiotic therapy targeted at the identified pathogen.

Crystal-Induced Arthritis Management:

• Medications to lower serum uric acid levels in gout (e.g., allopurinol, febuxostat).
• Pain management during acute flares (e.g., NSAIDs, colchicine, corticosteroids).

Differential Diagnosis of Acute Polyarthritis

The differential diagnosis of acute polyarthritis is broad and requires careful consideration of various conditions. Key conditions to rule out include:

• Psoriatic arthritis
• Tophaceous gout
• Undifferentiated seronegative polyarthritis
• Erosive inflammatory arthritis
• Enteropathic arthritis (arthritis associated with inflammatory bowel disease)
• Systemic lupus erythematosus (SLE)
• Scleroderma
• Polymyalgia rheumatica

Prognosis of Polyarthritis

The prognosis of polyarthritis is variable and depends on several factors:

• Duration of symptoms before diagnosis and treatment
• Age at disease onset
• Male gender (often associated with poorer prognosis in some conditions)
• Obesity
• Number of joints involved
• Lower limb joint involvement
• Severity of inflammation
• Elevated inflammatory markers in laboratory tests

Complications of Polyarthritis

Polyarthritis can lead to a range of complications, varying with the specific underlying disease, severity, location of inflammation, individual patient factors, and treatment approaches. Complications may include joint damage, disability, pain, and systemic manifestations depending on the etiology.

Deterrence and Patient Education

Patient education is crucial in managing arthritis effectively. Numerous resources are available, including the Arthritis Foundation, Mayo Clinic, and Johns Hopkins Medicine, offering comprehensive information on various aspects of arthritis. These resources provide guidance on disease understanding, pain and disability management, nutrition, rehabilitation, exercise, yoga, medical treatments, and medication side effects.

Enhancing Healthcare Team Outcomes in Polyarthritis Management

Effective management of polyarticular arthritis necessitates a collaborative, interprofessional healthcare team. This team often includes primary care physicians, nurses, pharmacists, rheumatologists, orthopedic surgeons, neurologists, physical and occupational therapists, radiologists, pathologists, and rehabilitation specialists. Each member contributes their expertise to the diagnostic and management process. Coordinated care and communication among team members are essential for accurate diagnosis and optimized patient outcomes, especially given the diverse etiologies of polyarthritis.

Review Questions

(The original article includes review questions and references here)

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