Author(s): Kemly Philip MD PhD MBE, Ajai Sambasivan MD and William Won
Originally published: November 10, 2011 Last updated: July 22, 2020
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DISEASE/DISORDER:

Definition

Inflammatory arthritides affect synovial joints and related structures. They can be monoarticular, oligoarticular, or polyarticular and acute or chronic. Four recognized groups include:

  1. Inflammatory connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus)
  2. Crystal-induced inflammatory arthritis (gout, pseudo-gout)
  3. Seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis (PsA))
  4. Infectious arthritis (gonorrhea, tuberculosis, osteomyelitis)

Etiology

The etiology is largely unknown. Inflammation and autoimmunity are considered key factors. The role of the immune system and genetics was unclear until recent advances in genomics1. Rheumatoid arthritis (RA) is associated with the HLA subtype DR4 2. Bacteria, fungi, and viruses can cause infectious forms, leading to potentially serious complications including septic arthritis3.

Epidemiology including risk factors and primary prevention

Inflammatory arthritides affect all age groups though certain populations are more susceptible. Peak incidence of RA is around 50 years old with a lifetime risk amongst women of 3.6% versus 1.7% amongst men4,5.  In systemic lupus erythematosus (SLE), gender differences change over time, affecting men and women equally in childhood versus women by 9:1 in adulthood6.  PsA prevalence is 1% while gout is slightly increased at 3% affecting males more than females7,8. Infectious arthritis incidence is still low at 3 per 100,000 although this increases to 70 per 100,000 among patients with concurrent RA9.

Pathophysiology

Inflammatory arthritides disrupt joint structure and function beginning with an autoimmune breach. T-lymphocytes induce monocytes to produce pro-inflammatory cytokines. Neutrophils release proteases and elastase which degrade joint and peri-articular components causing synovitis, cartilaginous and osseous damage10. Monosodium urate crystals accumulate in gout while calcium pyrophosphate and cholesterol crystals precipitate inflammatory responses in pseudogout11,12. B-27antigen-positive individuals are susceptible to seronegative spondyloarthropathies13.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Early RA presentation includes bilateral joint swelling and pain with morning stiffness that improves with activity while seronegative arthritis presents asymmetrically. Distal interphalangeal disease suggests PsA. Back pain suggests ankylosing spondylitis (AS) although sacroiliitis may not be present initially. The spine progressively stiffens with possible ankylosis, or joint fusion that can involve the chest wall14. Enthesitis, or inflammation at tendon insertion points, is common among seronegative spondyloarthropaties15. Both gout and pseudogout will typically have a sudden unilateral onset involving a toe or ankle11,12. Viral-related arthritis will present with myalgias and fever however are often self-limiting.

Specific secondary or associated conditions and complications

Skin plaques suggest PsA. SLE is associated with rashes, ulcers, and renal involvement. RA with cardiopulmonary disease, vasculitis, renal impairment, increased lymphoma risk, and cervical spine involvement13,16 Costo-vertebral and -sternal involvement in AS can cause restrictive lung disease. Seronegative arthritides affect up to 39% of patients with inflammatory bowel disease17. Treatment-related complications like infection, demyelinating disorders, or malignancy should be screened for15.

ESSENTIALS OF ASSESSMENT

History

Joint pain is most common. Note symptom onset, location, symmetry, presence of stiffness, edema, or pain. Duration and aggravating or alleviating factors can differentiate acute inflammatory from non-inflammatory arthritis. Constitutional symptoms including fatigue, weight loss, or fever suggest systemic disease.

Physical Examination

Examine all joints, peripheral and axial, for pain, effusion, synovitis, deformities, range of motion (ROM), and strength. Note location and number of joints affected. PIP, MCP, or MTP joints are commonly affected in RA with symmetrical, polyarticular involvement including extra-articular manifestations of vasculitis, nodules, or ophthalmic involvement14. Though pauciarticular, AS commonly affects the lumbar spine and sacroiliac joints, the cervical spine can be involved with possible fracture or kyphosis in addition to ophthalmic, gastrointestinal involvement, dactylitis or enthesitis13. Nail lesions or iritis suggest PsA. Acute monoarticular arthritis is likely infectious or crystal-induced. Weakness and muscle pain suggest polymyositis though cannot exclude neuromuscular disease. Dry eyes, parotid enlargement, or lymphadenopathy is observed in Sjögren syndrome; oral ulcers are seen in Behçet disease. Cognitive deficits can occur in SLE.

Functional assessment

The physiatrists role includes assessing body function, structure, activities, participation, and quality of life (QOL)18. Medical Outcome Survey Short Form 26 assesses QOL19. Functional assessment tools evaluating mobility, self-care, and pain include: Health Assessment Questionnaire (HAQ), “Timed Up and Go”, 6- minute walk test, Bath Ankylosing Spondylitis Functional Index, Psoriatic Arthritis Screening and Evaluation, and Arthritis Impact Measurement Scales14,20,21.

Laboratory studies

CBC, sedimentation rate (ESR), rheumatoid factor, and metabolic panels aid diagnosis. C-reactive protein, serum complement, and ESR are useful for disease monitoring but require clinical correlation. Specific auto-antibodies correlate with diseases i.e. anti-cyclic citrullinated peptide antibodies are found among 66% of RA patients or anti-double-stranded DNA/Smith antibodies in SLE14,22. Synovial fluid should be sent for gram stain, culture, cell count, and crystal analysis if crystal-induced or septic arthritis is suspected.

Imaging

A normal radiograph does not exclude arthritis. Early RA shows periarticular osteoporosis while marginal bony erosions appear later. Punched out lesions adjacent to bone indicates gout while fibrocartilage calcinosis indicates pseudogout. Pursue cervical spine imaging in RA patients with neurological symptoms, gait instability, or chronic neck pain13.

Magnetic resonance imaging (MRI) has gained attention for non-invasively detecting synovial, soft tissue, or bone changes earlier23. Intravenous gadolinium contrast optimizes synovitis assessment. Bone marrow edema (BME), bone erosion, or fat infiltration precede sacroiliitis visible on plain radiograph aiding in earlier AS diagnosis; BME on MRI is associated with RA disease progression24,25. Ultrasound (US) offers a low cost, portable alternative26. US can detect 6.5x more erosions than radiographs in early RA patients27. Erosions in RA suggest aggressive disease and thus, early recognition affects treatment plans and ultimate functional outcomes28.  US detects extra-articular changes including tenosynovitis, bursitis, or enthesopathies differentiating RA from other seronegative spondyloarthropathies too26.

Supplemental assessment tools

Arthroscopy allows visualization of articular surfaces. Synovial biopsy to differ synovitis phenotypes may help diagnose ill-defined arthritis or characterize treatment-refractory arthritis29.

Early prediction of outcomes

Mortality and morbidity rates among inflammatory arthritides are inversely related to educational level30. In severe RA, positive RF and elevated acute phase markers suggest poor outcome. Joint damage is predicted by ESR, baseline joint erosions, and HLA-DR1 alleles. 5-year disability correlates with HAQ scores and joint counts31. The 5-year mortality rate is 17% in RA patients with cervical instability on plain radiograph32.

Environmental

Assess home, workplace, and transportation to identify accommodation needs. Work disability is high so at-risk patients should be engaged in vocational rehabilitation programs33.  

Social role and social support system

Ability to function at work, in the family, and community is often disrupted. Co-morbid conditions including depression can increase a patient’s pain burden so patients should be periodically screened.

REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Disease modifying antirheumatic drugs (DMARDs) are started within 3 months of presentation to control disease activity, delay progression, or achieve remission34. Non-steroid anti-inflammatory drugs relieve symptoms however their use is limited due to adverse gastrointestinal, renal, and cardiovascular effects. Biologic agents include anti-cytokine therapies that block tumor necrosis factor (TNF) or agents which deplete B-cells aim14. Combination therapy effectively achieves remission and slows radiographic disease progression than monotherapy alone in RA. Immunoregulatory drugs enhance disease control. Anti-hyperuricemic agents such as allopurinol are used for crystal-induced arthritis.

Exercise considerations

Rehabilitation includes orthoses, joint protection, energy conservation, strengthening, stretching, and modalities. Activity pacing reduces joint inflammation. Muscle-strengthening with moderate-impact aerobic activity decreases disease activity, depression, and femoral bone loss while improving sleep and QOL in RA; similar evidence supports an anti-inflammatory role of physical activity in juvenile idiopathic arthritis, inflammatory myositis, SLE, and AS35,36. Exercise combined with pharmacologic treatment improves spinal mobility, ADL function, and QOL in AS37.

Exercise prescriptions should target affected joints with the goals of maintaining strength, ROM, bone mineralization, and increasing endurance38. Isotonic exercise is suitable for joints without deformity or acute inflammation. Isometric exercise limits joint stress, maintains and restores strength and is preferred for mechanically disrupted joints39. Stretching restores ROM in the absence of acute inflammation. Patients with cervical spine involvement should modify avoid high-impact activities due to fracture or spinal cord injury risk. Resistance and aerobic training decreases inflammation, disease activity, and improve function and QOL in inflammatory myositis40. Aquatic therapy decreases joint stress and pain while heat provides muscle relaxation with subsequent pain reduction41. Cold therapy lowers synovial collagenase decreasing pain or muscle spasm42. Transcutaneous electrical nerve stimulation for short periods reduces synovial fluid, improves analgesia and strength alongside interferential current43. Joint protection with rest, splinting, or orthoses unweighs joints, maintains alignment, mitigates deformities, and improves stability. Assistive devices or adaptive equipment decrease functional deficits.

Joint replacement surgery is indicated in refractory pain or severe joint damage or disability, warranting inpatient rehabilitation thereafter of residual deficits.

Coordination of Care

An interdisciplinary approach involves communication between the rheumatologist, physiatrist, physical and occupational therapists, social work, and mental health specialist when appropriate. Group or supervised individual sessions with educational and consistent support are most effective.

Patient & family education

Patient education targeted towards coping with pain, anticipated disease course, diet, joint protection, and disability are cost-effective and improve work and social participation33. Stress management training improves self-efficacy, adjustment, and health status measures as well.

Measurement of Patient Outcomes

ACR endorses functional assessment with the Patient-reported Outcomes Measurement Information System physical function 10-item short form, HAQ-II, and multidimensional HAQ44. The Disease Activity Scale-28, Clinical Disease Activity Index, Simplified Disease Activity Index, Routine Assessment of Patient Index Data 3, and the Patient Activity Scale-II count involved joints and reflect patient’s pain and functional level45.

Translation into practice

The ACR provides clinical documentation and patient encounter forms. Multidisciplinary teamwork and structured patient management lead to better outcomes. Education improves compliance and patient-provider communication. Rheumatologic consult is indicated to:

  1. Confirm an unclear diagnosis, e.g., undiagnosed multi-system or systemic disease
  2. Assess disease severity and activity
  3. Manage multi-organ and extra-articular involvement
  4. Treat uncontrolled disease and potentially life-threatening complications
  5. Manage special circumstances i.e. pregnancy

CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

New medications markedly improve outcomes; however, in long-standing disease, achieving low disease activity is a practical goal. Current research focuses on novel treatments with fewer adverse effects including stem cells or microRNA-mediated targeted therapies towards immunocytes or neovascularization to decrease joint destruction46. Biomarker identification aids with diagnosis, prognosis, and monitoring disease progression – all pivotal to stratifying treatments with the goal of improving long-term outcomes.

GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Knowledge regarding immunology, genetics, and pathophysiology of inflammatory arthritides is growing. Moreover, despite advances in pharmacologic treatments, physiatrists still play a crucial role in comprehensively assessing impairments, activity limitations, participation restrictions, and coordinating effective education and rehabilitation programs to preserve strength, mobility, and function of patients with inflammatory arthritides.

References

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Original Version of the Topic

Mary Catherine Spires, MD. Inflammatory Arthritides. 11/10/2011.

Author Disclosure

Kemly Philip MD PhD MBE
Nothing to Disclose

Ajai Sambasivan MD
Nothing to Disclose

William Won
Nothing to Disclose