Definition, Etiology, PathogenesisTop
Psoriatic arthritis (PsA) is chronic inflammatory arthritis associated with psoriasis, affecting 10% to 40% of patients with psoriasis. It appears that genetic, immunologic, and environmental factors all contribute to the development of the disease. Compared with individuals with uncomplicated psoriasis, patients with PsA have an increased frequency of HLA-B7 and HLA-B27 and lower frequency of HLA-DR7 and HLA-Cw7. However, the frequency of HLA-B27 in PsA is not as high as it is in ankylosing spondylitis or reactive arthritis and many patients are HLA-B27–negative. While skin and joint diseases appear to have similar pathogenesis, these manifestations can be highly discordant in individual patients.
Clinical Features and Natural HistoryTop
The onset of PsA is usually between the ages of 20 and 50 years but a juvenile form also occurs (usually between 9-12 years). Skin involvement generally precedes arthritis but arthritis can be the initial manifestation in ~10% of patients. There is no relationship between the severity of skin disease and degree of joint involvement. Skin involvement can be limited to minute plaques in or around the navel, intergluteal cleft, axillae, submammary folds, external genitalia, and scalp. The clinical course of PsA is highly variable, with periods of relapses and remissions. With time, the disease can lead to significant joint destruction and disability.
Periarticular involvement is common. This includes nail disease that is frequently associated with distal interphalangeal joint (DIP) involvement. Enthesitis (inflammation of the sites where tendons or ligaments attach to the bone) can occur with pain and swelling at the site. Achilles enthesitis is a common location. Dactylitis (inflammation of the joints, tendon sheaths, and other soft tissues of the toes or fingers) is usually episodic. It is commonly referred to as “sausage digits” due to the clinical appearance.
Extra-articular involvement can include psoriasis, anterior uveitis (iritis), and inflammatory bowel disease (IBD). Fatigue and depression are not uncommon.
Psoriatic arthritis can affect any joint in any pattern. Common symptoms include joint pain, swelling, warmth, and significant morning stiffness. Several common clinical patterns are recognized (the Moll and Wright classification):
1) DIP-predominant arthritis: The DIPs are primarily affected with pain, swelling, tenderness, and increasing deformity. Nails are frequently involved as the nail bed anchors in close proximity to the DIP. Other joints can be involved as well.
2) Symmetric polyarthritis: This affects large and small joints with a fairly symmetric pattern. It resembles rheumatoid arthritis, except that DIP joints can be involved in psoriatic arthritis. Deformities similar to those in rheumatoid arthritis (RA) can occur, including boutonnière and swan-neck deformities (see Fingers in Rheumatic Diseases).
3) Asymmetric oligoarticular arthritis: Asymmetric arthritis usually affecting <5 joints. Large joints (eg, knees) are commonly involved, but small joints can also be affected.
4) Axial PsA: This is similar to ankylosing spondylitis (but less symmetric on imaging) with inflammation of the joints of the spine and sacroiliac joints. It usually presents with inflammatory back pain (see Table 18.23-1). With time, limited range of motion of the cervical, thoracic, and lumbar spine can develop.
5) Arthritis mutilans: A very destructive form of psoriatic arthritis with significant osteolysis leading to bone resorption and joint destruction. Osteolysis of the phalanges leads to the formation of telescopic fingers (see Fingers in Rheumatic Diseases).
The course of PsA is highly variable. In patients with severe PsA, particularly those with coexisting axial and peripheral joint involvement, deformities and disability can develop within a few years. Adverse prognostic factors include multiple joint involvement, elevated erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) levels, clinical or radiologic features of joint damage, and treatment failure. In patients with milder PsA periods of relapses and partial remissions are observed with gradually worsening limitation of joint motion. Quality of life is frequently severely impaired and may be worse than in RA because of coexisting skin/nail disease and other extra-articular manifestations (iritis, IBD).
1. Laboratory tests: Elevated ESR/CRP can help in the assessment of clinical disease activity but these are not surrogate markers. Positive HLA-B27 is found in 60% to 70% of patients and therefore cannot be used to exclude the diagnosis of PsA.
2. Imaging studies:
1) Radiographs of peripheral joints reveal asymmetric involvement of the interphalangeal joints of the hands and feet and of large joints, erosions, new bone formation (at joint margins or along the periosteum). Osteolysis of the phalanges result in the classic “pencil-in-cup” deformity. Ankylosis of the joints of the hands and feet can be seen.
Radiographs of the spine can reveal changes similar to ankylosing spondylitis, but changes can be asymmetric. Sacroiliitis (unilateral or bilateral) can be evidenced by joint space loss, sclerosis, erosions, and ankylosis. Syndesmophytes tend to be larger and more asymmetric than in ankylosing spondylitis (termed “chunky syndesmophytes”).
2) Power Doppler ultrasonography is useful in detecting peripheral arthritis (synovitis) and enthesitis.
3) Magnetic resonance imaging (MRI) of the spine is useful for early sacroiliitis and spondylitis, showing bone marrow edema, erosions, and enthesitis.
3. Synovial fluid examination can be performed if there is diagnostic uncertainty. It typically reveals features of inflammation.
There are no diagnostic criteria. However, the Classification of Psoriatic Arthritis (CASPAR) criteria are often adapted in clinical practice: Table 18.23-5.
Differential diagnosis mainly includes RA, osteoarthritis, and other spondyloarthritides (see Table 18.23-4).
The main goals of treatment are to prevent disease progression, achieve remission, and optimize long-term health-related quality of life. Assessment of disease activity must consider the many domains of psoriatic arthritis: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease. The level of disease activity is also crucial for determining therapy.
Treatment may involve the following:
1) Education of the patient and family or caregivers.
2) Rehabilitation, including physiotherapy and kinesiotherapy.
3) Pharmacologic treatment.
4) Orthopedic treatment (when indicated because of disability).
Pharmacologic therapy of PsA is based on the main domains involved and the level of disease activity.
1. Nonsteroidal anti-inflammatory drug (NSAIDs) are used as first-line drugs in mild peripheral arthritis, axial disease, enthesitis, and dactylitis. Agents and dosage: see Table 18.13-2.
2. Local glucocorticoid injections can be used for symptomatic treatment of peripheral arthritis, sacroiliitis, enthesitis, and dactylitis. Their role in sacroiliitis is mainly if there are contraindications to biologic therapy. Intra-articular injections are generally limited to 3 per joint per year. In patients with dactylitis injections can be delivered to tendon sheaths. Enthesitis can be treated with injections around the entheses. In general, injections around the Achilles tendon are avoided because of the risk of tendon rupture. In very symptomatic peripheral arthritis, systemic glucocorticoids (oral or IM) can be considered. There is a small risk of worsening skin disease on withdrawal, particularly in those who are not receiving concomitant disease-modifying antirheumatic drug (DMARD) therapy or in whom the dose of glucocorticoids is reduced too rapidly.
3. Oral small molecules (OSMs) include conventional synthetic DMARDs (methotrexate, sulfasalazine, leflunomide) and apremilast (a phosphodiesterase-4 [PDE-4] inhibitor). These agents are used in peripheral arthritis of varying severity (including patients with mild disease when NSAIDs or glucocorticoid injections are inadequate, not tolerated or contraindicated). They can also be helpful for skin and nail disease but have limited efficacy.
OSMs can be used as monotherapy or combination therapy in peripheral PsA. Methotrexate is the most frequent first-line agent.Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness of doses, duration, and outcome measures. Note: Low doses (15 mg or less per week) of oral methotrexate might be slightly more effective than placebo when taken for 6 months; however, the balance of risks and benefits and the role of higher doses over a longer period of time is uncertain or unknown. Wilsdon TD, Whittle SL, Thynne TR, Mangoni AA. Methotrexate for psoriatic arthritis. Cochrane Database Syst Rev. 2019 Jan 18;1:CD012722. doi: 10.1002/14651858.CD012722.pub2. PubMed PMID: 30656673; PubMed Central PMCID: PMC6353064. Sulfasalazine or leflunomide can be used in combination with methotrexate in case of inadequate response or instead of methotrexate if it is contraindicated or not tolerated. In patients with inadequate response or intolerance of or contraindications to methotrexate, use sulfasalazine and/or leflunomide. Due to the cost, apremilast is often used as a second-line agent but can also be used as a first-line option.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Strength of Recommendation lowered due to clinical experience of limited efficacy in moderate to severe disease. High Quality of Evidence (high confidence that we know true effects of the intervention). Kavanaugh A, Gladman DD, Edwards CJ, et al. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res Ther. 2019 May 10;21(1):118. doi: 10.1186/s13075-019-1901-3. PubMed PMID: 31077258; PubMed Central PMCID: PMC6509758. Dosage, contraindications, and adverse effects of DMARDs: see Table 18.21-3.
OSMs have no role in the treatment of axial PsA. Treatment is similar to AS (see Ankylosing Spondylitis).
4. Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib, baricitinib) are effective for the treatment of peripheral PsA and can be used as first-line or second-line agents.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). So A, Inman RD. An overview of biologic disease-modifying antirheumatic drugs in axial spondyloarthritis and psoriatic arthritis. Best Pract Res Clin Rheumatol. 2018 Jun;32(3):453-471. doi: 10.1016/j.berh.2018.12.002. Epub 2019 Mar 21. Review. PubMed PMID: 31171315.
5. Biologic agents are used in both peripheral arthritis and axial PsA. They can also be used for refractory enthesitis and dactylitis.
For peripheral PsA, biologics are initiated in patients with persistent moderate to high peripheral disease activity despite treatment with ≥1 OSM administered at an optimal dose for 3 to 6 months. Tumor necrosis factor (TNF) inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab) were the first class of biologics in PsA.Evidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Saad AA, Symmons DP, Noyce PR, Ashcroft DM. Risks and benefits of tumor necrosis factor-alpha inhibitors in the management of psoriatic arthritis: systematic review and metaanalysis of randomized controlled trials. J Rheumatol. 2008 May;35(5):883-90. Epub 2008 Mar 15. Review. PubMed PMID: 18381787. Ustekinumab (anti-interleukin-12/23 [anti-IL-12/23]) is also an option. Anti-IL-17 (secukinumab, ixekizumab) agents are also highly effective.Evidence 5Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). McInnes IB, Mease PJ, Kirkham B, et al; FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 Sep 19;386(9999):1137-46. doi: 10.1016/S0140-6736(15)61134-5. Epub 2015 Jun 28. PubMed PMID: 26135703. Anti-IL-23 (guselkumab) is the most recently approved biologic for PsA.Evidence 6Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Deodhar A, Gottlieb AB, Boehncke WH, et al; CNTO1959PSA2001 Study Group. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2018 Jun 2;391(10136):2213-2224. doi: 10.1016/S0140-6736(18)30952-8. Epub 2018 Jun 1. PMID: 29893222. In patients with very high disease activity, treatment with a JAK inhibitor or biologic agent may be considered as first-line treatment, without a prior trial of an OSM. In case of primary failure, it is best to switch classes (mechanisms) of biologics. In case of secondary failure after an initial response, one can switch within the same class or out of class.
For axial PsA, treatment is similar to AS (see Ankylosing Spondylitis), with biologics initiated if NSAIDs are contraindicated or after ≥1 NSAID in case of inefficacy or intolerance.
Assess the effects of treatment using a clinical evaluation tool, such as the swollen joint count, tender joint count, enthesitis scores, or number of dactylitic digits. Skin involvement is measured through body surface area (BSA) and Psoriasis Area Severity Index (PASI) (available at pasi.corti.li). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (available at qxmd.com) is a patient-reported questionnaire for gauging spine involvement. The Health Assessment Questionnaire (HAQ) provides a measure of overall function.
To meet the CASPAR criteria, the patient must have inflammatory articular disease (joint, spine, or enthesitis) plus ≥3 points from any of the following 5 categories:
1. Evidence of psoriasis:
1) Evidence of current psoriasis (psoriatic lesions diagnosed by a rheumatologist or dermatologist): 2 points
2) Personal history of psoriasis or family history of psoriasis (in a first-degree or second-degree relative): 1 point
2. Typical psoriatic nail dystrophy (onycholysis, pitting, and hyperkeratosis) observed on current physical examination: 1 point
3. Negative test result for rheumatoid factor (any assay except for the latex test), preferably using ELISA or nephelometry: 1 point
4. Current dactylitis (defined as swelling of an entire digit [so-called sausage digit]) or history of dactylitis recorded by a rheumatologist: 1 point
5. Radiographic evidence of juxta-articular new bone formation seen as ill-defined ossification near joint margins (excluding osteophyte formation) in the hand or foot: 1 point
Adapted from Arthritis Rheum. 2006;54(8):2665-73.
CASPAR, ClASsification criteria for Psoriatic ARthritis; ELISA, enzyme-linked immunosorbent assay.