Inflammatory arthritides affect synovial joints and related structures. They can be monoarticular, oligoarticular, or polyarticular and acute or chronic. Four recognized groups include:
- Inflammatory connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus)
- Crystal-induced inflammatory arthritis (gout, pseudogout)
- Seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis (PsA))
- Infectious or septic arthritis (gonorrhea, tuberculosis, osteomyelitis)
The etiology is largely unknown. Inflammation and autoimmunity are considered key factors. Rheumatoid arthritis (RA) is associated with the HLA subtype DR4.1 SLE is associated with MCP-1 polymorphism.2 Bacteria, fungi, and viruses can cause infectious inflammatory arthropathies, leading to potentially serious complications including septic arthritis.3
Epidemiology including risk factors and primary prevention
Inflammatory arthritides affect all age groups although certain populations are more susceptible. The incidence of inflammatory arthritis is 115-271 per 100,000 adults, while the incidence of undifferentiated inflammatory arthritis is 41-149 per 100,000 adults. Out of the undifferentiated category, up to 54% of patients will develop rheumatoid arthritis.4 Peak incidence of RA is around 50 years old with a lifetime risk amongst women of 3.6% versus 1.7% amongst men.5 In systemic lupus erythematosus (SLE), gender differences change over time, affecting men and women equally in childhood versus women 9:1 in adulthood.6 PsA incidence is 3.6- 7.2 per 100,000.7 Gout is the most common inflammatory arthritis, with an incidence of 4 per 1000 adults in male and 1.4 in females.8 Infectious arthritis incidence is still low at 3 per 100,000, although this increases to 70 per 100,000 among patients with concurrent RA.9
Inflammatory arthritides begin with an inflammatory response, which disrupts joint structure and function. The immune response to external or self-antigen leads to an influx of inflammatory cells such as neutrophils, lymphocytes, and macrophages. T-lymphocytes induce monocytes to produce pro-inflammatory cytokines. Neutrophils release proteases and elastase which degrade joint and peri-articular components causing synovitis and cartilaginous and osseous damage.10 Monosodium urate crystals accumulate in gout, whereas calcium pyrophosphate and cholesterol crystals precipitate inflammatory responses in pseudogout.11 B-27 antigen-positive individuals are susceptible to seronegative spondyloarthropathies.12
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 wall.13 As the fusion progresses, the pain can improve. Enthesitis, or inflammation at tendon insertion points, is common among seronegative spondyloarthropathies.14 Both gout and pseudogout will typically have a sudden unilateral onset involving a toe or ankle.11 Viral-related arthritis will present with myalgias and fever, however, they 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 is associated with cardiopulmonary disease, vasculitis, renal impairment, increased lymphoma risk, and cervical spine involvement.13 Costovertebral and sternocostal involvement in AS can lead to restrictive lung disease. Seronegative arthritides affect up to 39% of patients with inflammatory bowel disease.15 Treatment-related complications like infection, demyelinating disorders, or malignancy should be screened for.14
Essentials of Assessment
Joint pain is the most common symptom. To differentiate types of inflammatory arthritides, information about symptom onset, location, symmetry, presence of stiffness, edema, or types of pain should be obtained on the initial encounter. An acute onset may suggest an infectious origin or crystalline arthropathies while a subacute or insidious onset occurs in most autoimmune inflammatory arthropathies.4 Duration and aggravating or alleviating factors can also differentiate acute inflammatory from non-inflammatory arthritis. Constitutional symptoms including fatigue, weight loss, or fever suggest the presence of systemic disease. History of previously damaged joints and lower extremities such as knees are common in bacterial infectious arthritis.4
Examine all joints, peripheral and axial, for pain, effusion, synovitis, deformities, range of motion (ROM), and strength. Note the location and number of joints affected. The first metatarsophalangeal joint is affected in approximately 50% of patients with gout on the initial encounter and is eventually involved in 90% of gout cases.4 The knees, wrists, and second and third metacarpophalangeal joints of the hands are usually associated with pseudogout.4 Small joints of the upper and lower extremities such as the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or MTP joints are commonly affected in RA, but the spine (except the C1-C2 joints) and distal interphalangeal joints in the hands are usually spared in RA.4,13 RA also has symmetrical, polyarticular involvement including extra-articular manifestations of vasculitis, nodules, or ophthalmic involvement.13 Though pauciarticular, AS commonly affects the lumbar spine and sacroiliac joints, and the cervical spine can be involved with possible fractures or kyphosis in addition to ophthalmic or gastrointestinal involvement, dactylitis, or enthesitis.12 Nail lesions or iritis suggest PsA. Acute monoarticular arthritis is likely infectious or crystal induced. Weakness and muscle pain suggest polymyositis although one cannot exclude neuromuscular disease. Dry eyes, parotid enlargement, or lymphadenopathy are observed in Sjögren syndrome; oral ulcers are seen in Behçet disease. Cognitive deficits can occur in SLE. Inflammatory arthritis secondary to viruses such as hepatitis B, hepatitis C, parvovirus B19 has a polyarticular pattern and clinical presentation similar to RA.
The physiatrist’s role includes assessing function, structure, activities, participation, and quality of life (QOL). Medical Outcome Survey Short Form 26 assesses QOL.16 Functional assessment tools evaluating mobility, self-care, and pain include the 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 Scales.17,18
CBC, erythrocyte 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 as these inflammatory markers are frequently seen in all inflammatory arthropathies.4 Hyperuricemia is frequently seen in patients with gout, but during an acute attack of gout, serum uric acid levels may be falsely low.4 Patients who developed pseudogout secondary to underlying metabolic diseases such as hypercalcemia, hyperparathyroidism, hypomagnesemia, and hemochromatosis might have laboratory studies associated with the underlying causes.1 Specific auto-antibodies correlate with specific diseases, i.e. anti-cyclic citrullinated peptide antibodies are found among 66% of RA patients, and anti-double-stranded DNA/Smith antibodies are found in SLE.9,13 Synovial fluid should be sent for gram stain, culture, cell count, and crystal analysis if crystal-induced or septic arthritis is suspected.
A normal radiograph does not exclude arthritis. Early RA shows periarticular osteoporosis while marginal bony erosions appear later. Punched-out lesions adjacent to bone suggest gout while fibrocartilage calcinosis indicates pseudogout. It is advisable to pursue cervical spine imaging in RA patients with neurological symptoms, gait instability, or chronic neck pain.12
Magnetic resonance imaging (MRI) has gained attention for non-invasively detecting synovial, soft tissue, or bone changes earlier.20 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 progression.21
Ultrasound (US) offers a low-cost, portable alternative. US can detect 6.5x more erosions than radiographs in early RA patients.27 Erosions in RA suggest aggressive disease and thus, early recognition affects treatment plans and ultimate functional outcomes.28 US detects extra-articular changes including tenosynovitis, bursitis, or enthesopathies differentiating RA from other seronegative spondyloarthropathies too.
Nuclear medicine joint scans are usually not utilized in diagnosing inflammatory arthritides due to their high sensitivity but very poor specificity. Nevertheless, they can be used to evaluate the presence or absence of inflammation and to evaluate prosthetic joint infections.4
Supplemental assessment tools
Arthroscopy allows visualization of articular surfaces. Synovial biopsy to differentiate synovitis phenotypes may help diagnose ill-defined arthritis or characterize treatment-refractory arthritis.24
Early prediction of outcomes
Mortality and morbidity rates among inflammatory arthritides are inversely related to educational level.25 Positive RF and elevated acute phase markers in severe RA suggest poor outcomes. ESR, baseline joint erosions, and HLA-DR1 alleles can predict joint damage. Five-year disability correlates with HAQ scores and joint counts, and 5-year mortality rate is 17% in RA patients with cervical instability on plain radiograph.26
Assess home, workplace, and transportation to identify accommodation needs. Work disability is high so at-risk patients should be engaged in vocational rehabilitation programs.27
Social roles and social support system
Ability to function at work, in the family, and community is often disrupted. Comorbid 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
The treatment for inflammatory arthritides is largely based upon well-established treatments used in rheumatoid arthritis and spondyloarthritis. The goal of initial therapy is suppression of inflammation and prevention of further joint damage with the use of combination therapy. Conventional systemic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate, sulfasalazine, and hydroxychloroquine along with anti-inflammatory therapies, including systemic glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), effectively achieve remission and slow radiographic disease progression more than monotherapy alone in RA.28 The best outcomes are starting combination therapy started within 3 months of presentation to control disease activity, delay progression, or achieve remission.29 NSAIDs relieve symptoms; however, their use is limited due to adverse gastrointestinal, renal, and cardiovascular effects.
Biologic disease modifying antirheumatic drugs (bDMARDs) are an expensive and powerful class of medications used for the treatment of inflammatory arthritides following inadequate response to initial combination therapy for at least three months. The classes of bDMARDs available for RA are tumor necrosis factor-alpha inhibitors, CD-20 depleting antibodies, interleukin-6 inhibitors, and T cell co-stimulation inhibitors.28 These medications increase an individual’s risk for infections and are contraindicated with active infections and current malignancy.28 Trials in early RA comparing csDMARDs and glucocorticoids with the combination of csDMARDs and bDMARDs have not revealed any major differences in outcomes.30 A new class of medications called janus kinase inhibitors also known as targeted synthetic DMARDs (tsDMARDs) have been developed within the last decade and are establishing a role in the management of rheumatoid arthritis and other inflammatory arthritic conditions. Anti-hyperuricemic agents such as allopurinol are used for crystal-induced arthritis.
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 AS.31 Exercise combined with pharmacologic treatment improves spinal mobility, ADL function, and QOL in AS.32
Exercise prescriptions should target affected joints to maintain strength, ROM, bone and mineralization and increase endurance.33 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 joints. Stretching restores ROM in the absence of acute inflammation. Patients with cervical spine involvement should avoid high-impact activities due to the risk of fracture or spinal cord injury. Resistance and aerobic training decrease inflammation, disease activity, and improve function and QOL in inflammatory myositis.34 Aquatic therapy reduces joint stress and pain, while heat provides muscle relaxation with subsequent pain reduction. Cold therapy lowers synovial collagenase decreasing pain or muscle spasms.35 Transcutaneous electrical nerve stimulation for short periods reduces synovial fluid and improves analgesia and strength alongside interferential current.36 Joint protection with rest, splinting, and orthoses serves to unweigh joints, maintain alignment, mitigate deformities, and improve 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 of residual deficits thereafter.
Coordination of Care
When appropriate, an interdisciplinary approach involves communication between the rheumatologist, physiatrist, physical and occupational therapists, social workers, and mental health specialists. 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 participation.27 Stress management training improves self-efficacy, adjustment, and health status measures.
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 HAQ.37 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 level.38
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. A rheumatologic consult is indicated to:
- Confirm an unclear diagnosis, e.g., undiagnosed multi-system or systemic disease
- Assess disease severity and activity
- Manage multi-organ and extra-articular involvement
- Treat uncontrolled disease and potentially life-threatening complications
- Manage special circumstances, e.g., 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, exosomes, or microRNA-mediated targeted therapies towards immunocytes or neovascularization to decrease joint destruction.39,40 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 the immunology, genetics, and pathophysiology of inflammatory arthritides is growing. With the recent COVID-19 pandemic, the use of telemedicine to diagnose and monitor patients with inflammatory arthritides has also been on the rise.41 More well-conducted studies on the efficacy and safety of remote care for inflammatory arthritides are needed. Additionally, 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 the strength, mobility, and function of patients with inflammatory arthritides.
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- Fang WL, Zhang Q, Ma NZ, Zhang J, Ma ZQ, Sun JJ. Association between MCP-1 gene and SLE: a meta-analysis. J Eur Acad Dermatol Venereol. 2020 Apr;34(4):e198-e200.
- Hassan AS, Rao A, Manadan AM, Block JA. Peripheral bacterial septic arthritis: Review of diagnosis and management. J Clin Rheumatol. 2017;23(8):435-442.
- Poudel P, Goyal A, Lappin SL. Inflammatory Arthritis. [Updated 2022 Apr 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.
- Van der Woude, D, van der Helm-van Mil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best Pract Res Clin Rheumatol 2018; 32 (2): 174-187.
- Margery-Muir AA, Bundell C, Nelson D, Groth DM, Wetherall JD. Gender balance in patients with systemic lupus erythematosus. Autoimmun Rev. 2017; 16 (3): 258-268.
- Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheum Dis Clin North Am. 2015 Nov;41(4):545-68. doi: 10.1016/j.rdc.2015.07.001. Epub 2015 Sep 11. PMID: 26476218; PMCID: PMC4610151.
- Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. Contemporary prevalence of gout and hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007-2016. Arthritis Rheumatol 2019; 71 (6): 991-999.
- Garcia-de la Torre I, Nava-Zavala A. Gonococcal and Nongonococcal Arthritis. Rheum Dis Clin North AM. 2009; 35 (1): 63-73. Doi: 10.1016/j.rdc.2009.03.001.
- Muley MM, Reid AR, Botz B, Bolcskei K, Helyes Z, and McDougall JJ. Neutrophil elastase induces inflammation and pain in mouse knee joints via activation of proteinase-activated receptor-2. British Journal of Pharmacology (2016) 173: 766-777.
- Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet. 2016;388(10055):2039-2052.
- Duba AS, Mathew SD. The Seronegative Spondyloarthropathies. Prim Care – Clin Off Pract. 2018;45(2):271-287.
- Cha TD and An HS. Cervical spine manifestations in patients with inflammatory arthritides. Nat. Rev. Rheumatol 2013; 9: 423-432.
- Brent LH. Inflammatory Arthritis: An Overview for Primary Care Physicians. Postgraduate Medicine 2015; 121 (2): 148-162.
- Arvikar SL and Fisher MC. Inflammatory bowel disease associated arthropathy. Curr Rev Musculoskeletal Med (2011) 4: 123-131.
- Gladman DD. Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases? Ann Rheum Dis 2006; 65: iii22-iii24.
- Kojima et al. Validation and Reliability of the Timed Up and GO Test for Measuring Objective Functional Impairment in Patients with Long-standing Rheumatoid Arthritis: A Cross-Sectional Study. Int J Rheum Dis. 2018; 21(10): 1793-1800.
- Sanges et al. Factors associated with the 6-minute walk distance in patients with systemic sclerosis. Arthritis Research & Therapy. 2017; 19(279).
- Pujalte G GA and Albano-Aluquin SA. Differenial Diagnosis of Polyarticular Arthritis. American Family Physician (2015) 92(1): 35-41.
- Weber U, Ostergaard M, Lambert RGW, Maksymowych WP. The impact of MRI on the clinical management of inflammatory arthritides. Skeletal Radiol (2011) 40:1153–1173.
- Hetland ML, Stengaard-Pedersen K, Junker P, Østergaard M, Ejbjerg BJ, Jacobsen S, et al. Radiographic progression and remission rates in early rheumatoid arthritis—MRI bone oedema and anti-CCP predicted radiographic progression in the 5-year extension of the double-blind randomised CIMESTRA trial. Ann Rheum Dis. 2010;69:1789–95.
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- Spencer SP, Ganeshalingam S, Kelly S, Ahmad M. The role of ultrasound in the diagnosis and follow-up of early inflammatory arthritis. Clin Radiol 2012; 67: 15-23.
- Manzo A, Bugattti S, Caporali R, and Montecucco C. Histopathology of the synovial tissue: perspectives for biomarker development in chronic inflammatory arthritis. Rheumatismo 2018; 70(3): 121-132.
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Original Version of the Topic
Mary Catherine Spires, MD. Inflammatory Arthritides. 11/10/2011.
Previous Revision(s) of the Topic
Kemly Philip MD PhD MBE, Ajai Sambasivan MD and William Won. Inflammatory Arthritides. 7/22/2020
Loc Lam, DO
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Royce Copeland, DO
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Gaibo Yan, MD
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Emanuel Narcis Husu, MD
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