Continuing Education Activity

Psoriatic arthritis is a chronic, heterogeneous inflammatory arthritis associated with psoriasis that affects nearly 20% of adults with psoriasis and carries significant potential for joint destruction, functional disability, and reduced quality of life. Despite the availability of validated classification criteria, advanced imaging modalities, and an expanding arsenal of targeted therapies, many clinicians lack the competence needed to recognize the varied clinical presentations of psoriatic arthritis, apply evidence-based treatment algorithms, and effectively manage associated comorbidities. This activity provides clinicians with a comprehensive review of the pathophysiology, clinical manifestations, diagnostic evaluation, and pharmacologic and nonpharmacologic management of psoriatic arthritis, including emerging biologic and targeted synthetic therapies. Participants gain actionable skills to improve diagnostic accuracy, implement treat-to-target strategies, reduce the burden of cardiovascular and metabolic comorbidities, and strengthen interprofessional collaboration to optimize patient-centered outcomes.

Objectives:

• Identify the articular, periarticular, and extraarticular clinical manifestations of psoriatic arthritis, including peripheral arthritis, enthesitis, dactylitis, axial disease, nail disease, and uveitis, across the spectrum of disease severity.
• Apply the Classification Criteria for Psoriatic Arthritis and the American College of Rheumatology and National Psoriasis Foundation 2018 treatment guidelines to guide accurate diagnosis and evidence-based treatment selection in patients with active psoriatic arthritis.
• Interpret radiographic, musculoskeletal ultrasonography, and magnetic resonance imaging findings in psoriatic arthritis to detect early joint inflammation, structural damage, enthesitis, and axial involvement.
• Collaborate with rheumatologists, dermatologists, primary care clinicians, pharmacists, physical and occupational therapists, dietitians, mental health professionals, and nursing staff to develop and implement coordinated, interprofessional care plans that address all domains of psoriatic arthritis and support long-term patient well-being.

Access free multiple choice questions on this topic.

Introduction

Psoriatic arthritis is a chronic inflammatory arthritis associated with psoriasis, with an estimated pooled prevalence of 19.7% (95% CI, 18.5% to 20.9%) amongst adults with psoriasis.[1][2] While psoriatic arthritis is usually seronegative, some patients may be seropositive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. The clinical manifestations of psoriatic arthritis are varied and can change over time, evolving from one particular pattern to another. A considerable financial and psychological burden exists associated with this disease. However, significant progress has recently been made in understanding the disease pathogenesis, which has translated into new therapies.

Etiology

The etiology and pathogenesis of psoriatic arthritis are not fully understood; they involve a complex interaction between genetic and environmental factors, resulting in immune-mediated inflammation involving the skin, joints, and other organs. Approximately 33% to 50% of patients with psoriatic arthritis have at least 1 first-degree relative with psoriatic arthritis or psoriasis.[3] Genes related to psoriatic arthritis include those within the human leukocyte antigen (HLA) region, which are implicated in antigen presentation and immune recognition.

Additionally, non-HLA genes play a role in immune activation and inflammation, influencing intracellular signaling, cytokine expression, and T-cell effector function. The genetic associations between psoriatic arthritis and psoriasis are not identical. Some genes associated with psoriatic arthritis are not associated with psoriasis (the same is true for psoriasis).[4][5] Additionally, specific phenotypes of psoriatic arthritis are associated with certain genes.[4][6][7]

Genetic associations in psoriatic arthritis include HLA-B*08:01, HLA-B*27:05, HLA-B*38:01, HLA-B*39:01, HLA-B*44:02HLA-B*57:01, and HLA-C*06:02.[7] HLA-B*08:01 is also associated with peripheral arthritis, joint damage, asymmetric sacroiliitis, and ankylosis. HLA-B*27:05 is also associated with axial involvement with symmetric sacroiliitis, enthesitis, and dactylitis. HLA-B38 and HLA-B39 genes are associated with polyarthritis.[4][6] HLA-B*44:02/03 is protective and associated with milder disease.[7] Table 1 summarizes the genetic associations in psoriatic arthritis. The subset of patients with symmetric polyarthritis is associated with HLA-DR4 (this gene is associated with rheumatoid arthritis).

Table

Table 1. Genetic Associations in Psoriatic Arthritis .

HLA, human leukocyte antigen

Non-HLA genes associated with psoriatic arthritis include IL-23R.[5][7] These genes produce proteins involved in immune-mediated inflammation, including TNFAIP3, TNF3IP2, REL, FBX19, and PTPN22.[5][7] Table 2 summarizes the non-HLA genes associated with psoriatic arthritis.

Psoriasis is more associated with HLA-B57:01 and HLA-C06:02 (the psoriasis susceptibility region 1 [PSORS1]) than psoriatic arthritis.[4][8] The IL-12B gene is associated with psoriasis but not psoriatic arthritis.[5] Several other genes associated with psoriatic arthritis and psoriasis are not mentioned here.[9] 

However, axial disease in psoriatic arthritis is more complicated. HLA-B27 positivity is more common in patients with axial spondyloarthritis (80% to 90%) than in those with axial psoriatic arthritis (20%).[10][11] Axial psoriatic arthritis usually has an older age at onset, less prominent back pain, and more frequent cervical spine disease, with radiographic features of asymmetric sacroiliitis and nonmarginal, bulky syndesmophytes, often asymmetric.

Some environmental factors are also suspected to play a role. Results from epidemiological studies showed an association between streptococcal infection and recent antibiotic exposure.[12][13][14][15] Skin trauma is known to induce flares of psoriatic skin lesions, known as the Koebner phenomenon. Evidence suggests that joint or enthesis trauma may trigger the development of arthritis, referred to as the internal or deep Koebner phenomenon.[14][15][16][17] Tobacco is a recognized trigger for rheumatoid arthritis in patients with certain HLA-DR genes and appears to be protective against the development of psoriatic arthritis.[15][18]

Table

Table 2. Non-HLA Genes Associated With Psoriatic Arthritis .

IL, interleukin; NF-κB, nuclear factor kappa B; TNF, tumor necrosis factor; TRAF, tumor necrosis factor receptor–associated factor 3 

Epidemiology

The epidemiology of psoriatic arthritis is heterogeneous and varies widely among various population groups. Psoriatic arthritis has an estimated prevalence of 0.05% to 0.25% in the general population and around 6% to 41% in patients with psoriasis.[19] This variability in psoriasis-related psoriatic arthritis is partially due to underdiagnosis. Results from a meta-analysis showed the prevalence of undiagnosed psoriatic arthritis may be as high as 15.5%.[20] The onset of psoriatic arthritis is usually seen in patients in their 30s and 40s and occurs about equally in men and women.[21] 

In most patients, the onset of skin disease precedes arthritis (68%); in about 15% of patients, the arthritic manifestations coincide with the skin disease, and in 17% of patients, arthritis occurs before the skin manifestations, making diagnosis more difficult.[22] This latter group is more common in childhood psoriatic arthritis. When examining the incidence of psoriatic arthritis over time in a population of patients with psoriasis, the annual incidence was 1.9% to 2.7% per 100 patients with psoriasis.[3][23] The prevalence of psoriatic arthritis in patients with psoriasis was 1.7% at 5 years, 3.1% at 10 years, 5.1% at 20 years, and 20.5% at 30 years.[24][25] A severe psoriasis phenotype, scalp, intergluteal, and perianal psoriasis, presence of nail pitting, low level of education, and uveitis predict the development of psoriatic arthritis in patients with psoriasis.[24][3]

Results from a literature review on the epidemiology of psoriatic arthritis showed that the worldwide prevalence ranges from 0.1% to 1%.[1][26] Considerable variability exists related to geographic and ethnic variation. The prevalence is higher in Europe (0.19%, with Norway at 0.67% and Sweden at 0.02%) and North America (0.13%) and lower in the Middle East (0.01%), South Asia (0.06%), Southeast Asia (0.05%), East Asia (0.17%; China 0.002%; Taiwan 0.004%; Japan 0.001%), and South America (0.07%). Evidence also suggests that the prevalence of psoriatic arthritis has been increasing over time.[1] 

The prevalence of psoriatic arthritis among patients with psoriasis is 19.7%, with 21.6% among adults and 3.3% among children.[2] The prevalence of psoriatic arthritis among patients with psoriasis was 23.8% according to the Classification Criteria for Psoriatic Arthritis (CASPAR). Psoriatic arthritis is more strongly associated with severe psoriasis than mild psoriasis (24.6% vs 15.8%). The proportion of patients with psoriasis and psoriatic arthritis varies by geography and ethnicity, with 22.7% in Europe, 19.5% in North America, 21.5% in South America, 15.5% in Africa, and 14% in Asia.[2] 

Pathophysiology

Various genetic risk factors predispose patients to psoriasis and psoriatic arthritis.[4][5][6][9] In these patients, an environmental trigger such as infection or mechanical stress initiates a chronic inflammatory process primarily involving the joints and skin, producing interleukin (IL)-23, a central cytokine in the pathogenesis of psoriatic arthritis and psoriasis.[27][28] Macrophages and dendritic cells produce IL-23. The gastrointestinal tract may be a source of IL-23 because of disturbed barrier function or changes in the microbiota.[9][27][28] Enthesitis, inflammation at the sites where ligaments, tendons, and joint capsules attach to bone, is the predominant pathologic lesion in psoriatic arthritis, compared with synovitis in rheumatoid arthritis.[27][29] 

Distal interphalangeal joints are frequently involved in psoriatic arthritis but not rheumatoid arthritis because these joints have many entheses but very little synovial tissue. In animal models of spondyloarthropathy, IL-23 stimulates resident T cells, which are CD3+, CD4-, CD8-, IL-23R+, and RORγt+.[30] This stimulation produces IL-17, IL-22, and tumor necrosis factor (TNF)-α, which promote inflammation, bone loss with erosions, and osteoproliferation.[31]

CD8+ T cells play an integral role in psoriatic arthritis, as substantiated by their association with HLA class I alleles, the oligoclonal expansion of CD8+ T cells, and their association with late-stage human immunodeficiency virus infection.[28] Other immune cells involved in the pathogenesis include CD4+ T helper 17 cells, which produce IL-17 and IL-22; type 3 innate lymphoid cells, which produce IL-17 and IL-22; and γδ T cells, which produce IL-17 and TNF-α.[27][28] These proinflammatory cytokines recruit neutrophils that enter the synovial fluid, activate synoviocytes, promote angiogenesis locally, and activate osteoclasts, resulting in bone destruction and osteoblasts that promote new bone formation.[27][28][27][32][33] Insights into basic pathophysiology have driven the development of biologic therapies.

History and Physical

The clinical presentation of psoriatic arthritis is varied. The earliest classification of psoriatic arthritis by Moll and Wright included 5 subtypes:

• Oligoarticular arthritis is asymmetric and involves less than 5 small or large joints.
• Polyarticular arthritis is usually symmetric and presents similarly to rheumatoid arthritis, but may involve the distal interphalangeal joints, and rheumatoid factor levels are within the reference range.
• Distal arthritis is signified by prominent involvement of the distal interphalangeal joints.
• Arthritis mutilans is characterized by severe, destructive joint disease with deformities, especially in the hands and feet.
• Spondyloarthritis presents with sacroiliitis and spondylitis (occurring with or without peripheral joint disease).

The asymmetric oligoarticular pattern is the most common form of psoriatic arthritis presentation, accounting for at least 60% of psoriatic arthritis cases. However, this is only true in some patient populations. Over time, most patients will develop polyarticular arthritis. Results from an analysis of 220 patients with psoriatic arthritis showed the following patterns of arthritis: oligoarticular arthritis (14%), polyarthritis (40%), distal arthritis (12%), arthritis mutilans (16%) (see Image. Arthritis Mutilans), sacroiliitis and spondylitis (30%).[22] 

The Classification of Psoriatic Arthritis (CASPAR) study identified 63% of patients with polyarticular arthritis.[34] Axial disease is often associated with one of the peripheral arthritis patterns. According to findings from one prospective cross-sectional study, the frequency of radiological axial involvement in psoriatic arthritis was about 42.9%.[35] The distal pattern is less common, occurring in less than 20% of patients, and may be present with axial disease. Arthritis mutilans prevalence can range from 2% to 21%, reflecting different definitions of this entity across studies.[36] 

The classic definition described arthritis mutilans as the most severe form; its presentation is characterized by osteolysis, leading to digital telescoping, bone resorption, and sacroiliitis. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis initiative in 2012 reached a consensus on the features related to arthritis mutilans, which involves consideration of specific features of the disease, including digital telescoping, digital shortening, pencil-in-cup deformities, osteolysis, and involvement of distal interphalangeal joints and other small joints of the hands.[37] Features of psoriasis associated with an increased risk of axial disease include active skin lesions with induration, pustular psoriasis, nail involvement, and the Koebner phenomenon.[38]

The discrepancies observed across studies are explained by heterogeneous disease patterns and by the fact that many patients transition from one arthritis pattern to another over time. This is especially true for patients presenting with asymmetric oligoarthritis, who often transition to symmetric polyarthritis. Other factors that may account for variations in psoriatic arthritis patterns include the fact that most of these studies are from referral centers for psoriatic arthritis and may overrepresent more severe patterns, such as arthritis mutilans and distal arthritis. Axial involvement has generally been thought to occur mainly in patients who have HLA-B27.

However, this may be an oversimplification. Ankylosing spondylosis with and without psoriasis has an epidemiology similar to that of typical ankylosing spondylosis, with a strong association with HLA-B27. Axial psoriatic arthritis appears to be a distinct entity; compared to ankylosing spondylosis, it has a fairly equal prevalence among women and men, an older age of onset, a much lower association with HLA-B27 (20% vs 80% to 90%), and is associated with HLA-B08 and HLA-B38. Clinically, patients with axial psoriatic arthritis have different radiographic findings, more common cervical spine involvement, and improved outcomes with TNF inhibitors (TNFi) and IL-17 inhibitors (IL-17i), and possibly IL-23 inhibitors (IL-23i).[10][11][18] The clinical features of psoriatic arthritis are described in terms of articular and extraarticular manifestations.

Articular and Periarticular Manifestations of Psoriatic Arthritis

• Peripheral arthritis presents in an oligoarticular or polyarticular pattern.
• Periarticular disease includes enthesitis (inflammation around the insertion of ligaments, tendons, or joint capsules), dactylitis (swelling of the entire digit, finger, or toe, or sausage digit), and tenosynovitis.
• Axial disease involving the sacroiliac joints is usually asymmetric.
• Spondylitis with discontinuous involvement with bulky nonmarginal syndesmophytes.

Extraarticular Manifestations of Psoriatic Arthritis

• Psoriatic skin disease usually presents before the onset of arthritis, but can occur simultaneously and even after the onset of joint disease. The severity of skin disease does not correlate well with the severity of the articular disease.[39]
• Nail disease is characterized by onycholysis, pitting, and splinter hemorrhages. The severity of nail disease correlates with the severity of skin and joint disease.[40] Nail disease is present in 80% to 90% of patients with psoriatic arthritis and is associated with distal interphalangeal joint involvement.
• Ocular disease in the form of uveitis differs from that associated with ankylosing spondylosis because it is often chronic, bilateral, and can involve the posterior elements.

Associations and Comorbidities

• Inflammatory bowel disease, and particularly Crohn disease, is associated with an increased risk of psoriatic arthritis.[41]
• Psoriatic arthritis has been associated with several comorbidities, the most prevalent of which are hypertension, metabolic syndrome, obesity, hyperlipidemia, and cardiovascular disease.[42]

Evaluation

No laboratory tests exist specifically for psoriatic arthritis. As with most inflammatory diseases, acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein may be elevated. However, normal erythrocyte sedimentation rate and C-reactive protein results should not be used to rule out psoriatic arthritis, as these results are elevated in only about 40% of patients.[43]

Rheumatoid factor and anti-cyclic citrullinated peptide antibodies are classically considered absent in psoriatic arthritis. A negative rheumatoid factor result is considered a criterion for diagnosing psoriatic arthritis per the CASPAR classification criteria. Results from various studies showed positive rheumatoid factor findings in about 2% to 10% of patients diagnosed with psoriatic arthritis, and approximately 5% of anti-cyclic citrullinated peptide antibodies.[44][45] Antinuclear antibodies may also have positive results in these patients, but usually at low titers. Results from a study by Johnson et al, showed antinuclear antibodies at a titer of more than 1:80 in 14% of patients with psoriatic arthritis.[46]

Radiographic findings in psoriatic arthritis include characteristic patterns: erosive changes, gross joint destruction, joint space narrowing, and pencil-in-cup deformity.[47][48] These findings are driven by bone destruction and pathologic new bone formation, often in the same digit or even the same joint, a characteristic feature of psoriatic arthritis (eg, bone destruction with bone production). Despite treatment with disease-modifying antirheumatic drugs, psoriatic arthritis results in radiographic damage in about 47% of patients during the first 2 years of the disease.[49] The radiological features of peripheral arthritis in hands and feet include erosive changes, new bone formation, bony ankylosis, and joint osteolysis.[50] Enthesial involvement, including erosions and new bone formation, is characteristic of all spondyloarthropathies.[51] 

Axial features, including sacroiliitis and spondylitis, are characterized by the formation of syndesmophytes (ossification of the annulus fibrosis). The features that differentiate psoriatic arthritis from ankylosing spondylitis include the asymmetric, often unilateral presentation of sacroiliitis; in psoriatic arthritis, syndesmophytes are nonmarginal, bulky, asymmetric, and discontinuous, skipping vertebral levels. Plain radiography, computed tomography, ultrasonography, and MRI are all useful for assessing patients with psoriatic arthritis.[52] Imaging modalities such as musculoskeletal ultrasound (MSUS) and MRI are more sensitive than plain radiography for detecting early joint inflammation, damage, and axial changes, including sacroiliitis.[53][54] 

However, these imaging modalities are not necessary for the proper diagnosis of psoriatic arthritis. MSUS is frequently used in clinics because it is readily accessible and provides dynamic images. MSUS is especially useful in detecting subclinical synovitis, enthesitis, and dactylitis. MSUS features supportive of enthesitis include entheseal thickening, increased vascularity on power doppler, hypoechogenicity, and enthesophyte formation.[55][56] Similarly, dactylitis features on MSUS include synovial and tenosynovial inflammation.[57]

Classification Criteria

The most accepted classification criteria for psoriatic arthritis are the CASPAR criteria (see Table 3), which have been used since 2006.[34] Other classification criteria that clinicians have used include the original Moll and Wright (1973), Bennet (1979), Vassey and Espinoza (1984), and the modified European Spondyloarthropathy Study Group (1991) criteria.[58]

 Moll and Wright criteria, 1973

• Inflammatory arthritis (peripheral arthritis and sacroiliitis or spondylitis)
• The presence of psoriasis
• The absence of serologic tests for rheumatoid factor [47]

Table

Table 3. CASPAR Criteria (2006).

Per CASPAR criteria, psoriatic arthritis is present in patients with inflammatory arthritis who have at least 3 points; this has a specificity of 98.7% and a sensitivity of 91.4%.[34]

Treatment / Management

General Principles

• Guide treatment by disease severity, joint damage degree, extra-articular disease extent, patient preference, and other comorbidities.
• Nonpharmacological therapies, including physical and occupational therapy, exercise programs, and smoking cessation, should be strongly encouraged and incorporated into the treatment plan.[59]
• A treat-to-target approach is the most effective way to control disease activity and minimize joint damage.[60][61] Depending on disease extent, chronicity, and other comorbidities, low remission or low disease activity targets should be employed. 
• Due to the heterogeneous presentation of psoriatic arthritis, the type of treatment initiated depends on the domains involved, including peripheral arthritis, enthesitis, dactylitis, axial disease, and skin or nail disease.
• In treatment-naïve patients, nonsteroidal anti-inflammatory drugs (NSAIDs) are generally useful for treating mild peripheral arthritis symptoms.[62]
• Mild-to-moderate peripheral arthritis may be treated with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) such as methotrexate or occasionally sulfasalazine; the latter is ineffective for skin disease.[63]
• Severe peripheral arthritis is usually treated with biologic DMARDs, especially TNF inhibitors.
• Axial disease and enthesitis share similar treatment approaches, with a minimal role for conventional synthetic DMARDs. Patients who do not respond to NSAIDs should transition to biologic DMARDs.
• A TNF inhibitor is usually recommended rather than an IL-17 inhibitor, IL-12/23 inhibitor, abatacept, or tofacitinib.
• An IL-17 inhibitor is usually recommended over an IL-12/23 inhibitor, abatacept, or tofacitinib.
• An IL-12/23 inhibitor is usually recommended rather than abatacept or tofacitinib.
• In patients with severe psoriasis, an IL-12/23 inhibitor or an IL-17 inhibitor may be used instead of a TNF inhibitor.
• Tofacitinib may be used instead of a TNF inhibitor in patients who prefer oral medication and do not have severe psoriasis.
• The 2018 American College of Rheumatology and National Psoriasis Foundation guidelines recommend a TNF inhibitor over conventional synthetic DMARDs as a first-line treatment in treatment-naïve psoriatic arthritis.

American College of Rheumatology/National Psoriasis Foundation (ACR/NPF) 2018 Guidelines: Definition of Active Psoriatic Arthritis

Defined as "disease-causing symptoms at an unacceptably bothersome level as reported by the patient, and judged by the examining clinician to be due to psoriatic arthritis” based on 1 or more of the following:

• Swollen joints
• Tender joints
• Dactylitis
• Enthesitis
• Axial disease
• Active skin or nail involvement
• Extraarticular inflammatory manifestations such as uveitis or inflammatory bowel disease [64]

ACR/NPF 2018 Guidelines for the Treatment of Psoriatic Arthritis

Initial treatment:

Initial treatment with oral small molecules (OSM) such as methotrexate (MTX), sulfasalazine, leflunomide, cyclosporine, apremilast:

• Treat with TNF inhibitors rather than OSM: may consider OSM, such as MTX, in patients with mild psoriatic arthritis and psoriasis, patient's preference, or contraindication to TNF inhibitors.
• Treat with a TNF inhibitor rather than an IL-17 inhibitor; consider an IL-17 inhibitor in patients with severe psoriasis or contraindications to TNF inhibitors.
• Treat with a TNF inhibitor rather than an IL-12/23 inhibitor; consider an IL-12/23 inhibitor in patients with severe psoriasis who have contraindications to TNF inhibitors.
• Treat with OSM rather than an IL-17 inhibitor; consider an IL-17 inhibitor in patients with severe psoriasis and/or psoriatic arthritis.
• Treat with OSM rather than IL-12/23 inhibitor; consider IL-12/23 inhibitor in patients with severe psoriasis or psoriatic arthritis or concomitant inflammatory bowel disease.
• Treat with MTX rather than nonsteroidal anti-inflammatory drugs; consider these drugs in patients with mild psoriatic arthritis and psoriasis.
• Treat with an IL-17 inhibitor rather than an IL-12/23 inhibitor; consider an IL-12/23 inhibitor in patients with concomitant inflammatory bowel disease.

European League Against Rheumatism Recommendations for the Management of Psoriatic Arthritis With Pharmacological Therapies: 2019 Update

Overarching principles:

• Psoriatic arthritis is a heterogeneous and potentially severe disease that may require interdisciplinary treatment.
• Treating patients with psoriatic arthritis should aim for the best care and must be based on a shared decision between the patient and rheumatologist, considering efficacy, safety, and costs.
• Rheumatologists are the specialists who should primarily care for the musculoskeletal manifestations of patients with psoriatic arthritis; if there is significant skin involvement, collaboration with a dermatologist is recommended.
• The primary goal in treating psoriatic arthritis is to maximize health-related quality of life by controlling symptoms, preventing structural damage, and normalizing physical and social function through inflammation control as a crucial component.
• When managing psoriatic arthritis, extraarticular manifestations (eg, skin, eye, and gastrointestinal tract) and comorbidities (eg, metabolic syndrome, cardiovascular disease, and depression) should be considered.[65]

Recommendations:

• Treatment should aim to achieve remission or low disease activity targets through regular assessment of disease activity and appropriate adjustments to therapy.
• NSAIDs may be used to relieve musculoskeletal signs and symptoms.
• Local corticosteroid injections should be considered adjunctive therapy in psoriatic arthritis; systemic corticosteroids may be used cautiously at the lowest effective dose.
• A conventional synthetic disease-modifying antirheumatic drug (csDMARD) should be initiated rapidly in patients with polyarthritis, with MTX preferred in those with relevant skin involvement.
• Consider a csDMARD for patients with monoarthritis or oligoarthritis, particularly those with poor prognostic factors such as structural damage, a high erythrocyte sedimentation rate or C-reactive protein level, dactylitis, or nail involvement.
• In patients with psoriatic arthritis who have an inadequate response to at least one csDMARD, therapy with a biologic disease-modifying antirheumatic drug (bDMARD) should be commenced; when relevant skin involvement is present, an IL-17 inhibitor or IL-12/23 inhibitor may be preferred.
• In patients with peripheral arthritis and an inadequate response to at least one csDMARD and at least one bDMARD, or when a bDMARD is not appropriate, a Janus kinase (JAK) inhibitor may be considered.
• In patients with mild disease and an inadequate response to at least one csDMARD, in whom neither a bDMARD nor a JAK inhibitor is appropriate, a phosphodiesterase-4 inhibitor may be considered.
• In patients with unequivocal enthesitis and insufficient response to NSAIDs or local corticosteroid injections, therapy with a bDMARD should be considered.
• In patients with predominantly axial disease that is active and has an insufficient response to NSAIDs, therapy with a bDMARD (currently a TNF inhibitor) should be considered; when there is relevant skin involvement, an IL-17 inhibitor may be preferred.
• In patients who do not respond adequately to or are intolerant of a bDMARD, switching to another bDMARD or tsDMARD should be considered, including a switch within a class.
• In patients with sustained remission, cautious tapering of DMARDs may be considered.

Differential Diagnosis

Psoriatic arthritis shares some clinical features with other inflammatory arthritides, including rheumatoid arthritis, reactive arthritis, and axial spondyloarthritis. Unlike psoriatic arthritis, rheumatoid arthritis tends to be symmetrical and generally spares the distal interphalangeal joints. Axial spondyloarthritis usually has an earlier age of onset than psoriatic arthritis, and sacroiliac involvement is usually symmetric rather than asymmetric.

Treatment Planning

Disease Monitoring 

As with other inflammatory arthritides, patients with psoriatic arthritis require regular monitoring of disease activity and appropriate changes to therapy based on these measurements. Evaluation of all domains, including peripheral joints, entheses, digits, axial involvement, and skin and nails, is crucial. The following methods assess disease activity in clinical practice and clinical trials.

Parameters used to assess disease activity in psoriatic arthritis

• Tender and swollen joint counts of 68 joints and 66 joints, respectively, in peripheral arthritis
• The Bath Ankylosing Spondylitis Disease Activity Index:

  • This determines axial disease activity and ankylosing spondylosis.
• Health-related quality of life, as measured by indices such as the Psoriatic Arthritis Quality of Life  scale
• Functional Assessment of Chronic Illness Therapy-Fatigue Scale 
• Composite indices like the Disease Activity Index for Psoriatic Arthritis, Minimal Disease Activity, America’s College of Rheumatology criteria (ACR) 20/50/70, Psoriatic Arthritis Response Criteria, and Composite Psoriatic Disease Activity Index
• The Routine Assessment of Patient Index Data, or RAPID3

  • This is useful for assessing disease activity in rheumatoid arthritis, is simple to administer, and does not require any laboratory indices. This assessment compares favorably to other, more complicated measures of disease activity in psoriatic arthritis and is more practical for routine clinical care.[66] The Disease Activity Score using 28 joints is frequently used to measure disease activity in rheumatoid arthritis. However, this assessment is inadequate for psoriatic arthritis because it focuses on peripheral arthritis.

A treat-to-target approach to attain remission or minimal disease activity is strongly recommended.[61] A patient is considered to have achieved minimal disease activity if the patient meets 5 of the following 7 criteria:

Minimal disease activity: 

• Tender joint count of 1 or fewer
• Swollen joint count of 1 or fewer
• Psoriasis Area and Severity Index of 1 or fewer, or body surface area of 3% or less
• Patient pain visual analog scale score of 15 mm or less
• Patient global disease activity visual analog scale score of 20 mm or less
• Health Assessment Questionnaire score of 0.5 or less
• Tender entheseal points of 1 or fewer [67]

Specific Agents

csDMARDs

Methotrexate:

• For patients with mild peripheral joint and skin disease 
• Dose: 7.5 to 25 mg weekly by mouth or subcutaneously, usually administered with 1 mg of folic acid daily
• Adverse effects: oral ulcers, nausea, cytopenias, increased risk of infections, and pulmonary toxicity (pneumonitis)
• Methotrexate is teratogenic; obtain pregnancy test prior to starting methotrexate in women of childbearing age
• Alcohol, kidney disease

  • Advise patients to avoid drinking excessive alcohol and be cautious with patients who have chronic kidney disease 
• Monitoring: Complete blood count (CBC) and comprehensive metabolic panel (CMP) every 2 to 4 months

Sulfasalazine:

• For patients with mild peripheral joint disease, it is not helpful for skin disease
• Dose: 1000 to 1500 mg twice daily 
• Adverse effects: rash, nausea, diarrhea, and elevated liver enzyme results on liver function tests, but rarely leukopenia/neutropenia
• Monitoring: CBC and CMP every 2 to 4 months

Leflunomide:

• For patients with mild peripheral joint and skin disease
• Dose: 10 to 20 mg every day 
• Adverse effects: diarrhea, hair loss, skin rash, leukopenia, elevated liver enzyme results on liver function tests, and weight loss
• Leflunomide is teratogenic and requires washout with cholestyramine
• Monitoring: CBC and CMP every 3 to 4 months

Cyclosporine:

• For patients with active skin disease but not peripheral joint disease 
• Dose: 2.5 to 5 mg/kg/d twice a day (usually 3 mg/kg/d)
• Adverse effects: decreased kidney function, hypertension, headache, elevated cholesterol, excessive hair growth, and gum hypertrophy

  • Cyclosporine has several drug-drug interactions and should be prescribed with caution.

bDMARDs

TNF inhibitors, TNFi:

• For patients with moderate-severe active psoriatic arthritis with peripheral and axial joint and skin diseases 
• All TNFIs are approved for rheumatoid arthritis and ankylosing spondylitis
• Prebiologic labs, including tuberculosis testing and hepatitis B and C panels, should be obtained
• Monitoring: CBC and CMP every 3 to 4 months

Etanercept:

• A p75 TNF-α receptor; IgG Fc fusion protein 
• Dose: 50 mg subcutaneously every week 
• Food and Drug Administration (FDA)-approved for psoriatic arthritis and psoriasis; not recommended for patients with uveitis or inflammatory bowel disease

Infliximab:

• Chimeric monoclonal antibody (mAb) to TNF-α
• Dose: 5 mg/kg intravenously every 6 weeks after loading 
• FDA-approved for psoriatic arthritis and psoriasis
• Effective for uveitis and inflammatory bowel disease

Adalimumab:

• Human mAb to TNF-α
• Dose: 40 mg subcutaneously every 2 weeks 
• FDA-approved for psoriatic arthritis and psoriasis
• Effective for uveitis and inflammatory bowel disease

Golimumab:

• Human mAb to TNF-α
• Dose: 50 mg subcutaneously every month or 2 mg/kg intravenously every 2 months 
• FDA-approved: psoriatic arthritis and psoriasis
• Effective for uveitis and inflammatory bowel disease

Certolizumab pegol:

• Humanized Fab fragment specific for TNF-α conjugated to 40-kDa polyethylene glycol
• Dose: 200 mg subcutaneously every 2 weeks after loading 
• Adverse effects: administration reactions, increased risk of infections, including mycobacterial and fungal infections, demyelination, congestive heart failure, drug-induced lupus, and paradoxically, psoriasis
• FDA-approved: psoriatic arthritis and effective for treating psoriasis

IL-17 inhibitors (IL-17i):

• For moderate-severe active psoriatic arthritis with peripheral and axial joint and skin disease.
• Obtain tuberculosis test before starting, and obtain CBC and CMP every 3 to 4 months.
• IL-17i is ineffective for uveitis or inflammatory bowel syndrome.

Secukinumab:

• Human mAb to IL-17A
• Dose: 150 to 300 mg subcutaneously every month after loading
• FDA-approved: psoriatic arthritis, psoriasis, and ankylosing spondylitis
• Trial:

  • Results from a double-blind, randomized trial showed that secukinumab at doses of 300 mg every month was effective in patients with psoriatic arthritis and axial disease.[68]

Ixekizumab:

• Humanized mAb to IL-17A
• Dose: 80 mg subcutaneously every month after loading 
• FDA-approved: psoriatic arthritis, psoriasis, and ankylosing spondylitis

Brodaulmab:

• Human mAb to IL-17R 
• Dose: 210 mg subcutaneously every 2 weeks after loading
• Adverse effects: increased risk of infections, including mycobacterial and fungal infections, and candidal infections
• FDA-approved: psoriasis but not for psoriatic arthritis

Bimekizumab:

• A dual IL-17A and IL-17F humanized monoclonal antibody
• Dose: 160 mg subcutaneously every 4 weeks for 5 doses, followed by 320 mg every 8 weeks thereafter
• Trial:

  • Results from a recent double-blind, placebo-controlled phase 3 trial, the Bimekizumab Efficacy and Safety in Patients With Active Psoriatic Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Alpha Inhibitors (BE-COMPLETE) trial, showed superior improvements in joint and skin disease outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNF-α inhibitors.[69] 

IL-12/23 and IL-23 inhibitors (IL12/23i, IL-23i):

• For patients with moderate-severe active psoriatic arthritis with peripheral joint and skin disease.
• Obtain tuberculosis test before starting, and check CBC and CMP every 3 to 4 months.
• IL-12/23i are ineffective for the axial disease of ankylosing spondylitis or nonradiographic axial psoriatic arthritis, but may be effective for axial psoriatic arthritis.

Ustekinumab (IL12/23i):

• Human mAb to IL-12/23 p40 subunit 
• Dose: 45 mg subcutaneously every 3 months after loading (90 mg if weight > 100 kg)
• FDA-approved: psoriatic arthritis, psoriasis, and Crohn disease

Guselkumab (IL-23i):

• Human mAb to IL-23 p19 subunit
• Dose: 100 mg subcutaneously every 2 months after loading 
• FDA-approved: psoriatic arthritis and psoriasis

Tildrakizumab (IL-23i):

• Human mAb to p19 subunit of IL-23 
• Dose: 100 mg SC every three months after loading 
• Adverse effects: increased risk of infections, including mycobacterial and fungal infections
• FDA-approved: psoriatic arthritis and psoriasis

Icotrokinra (IL-23i):

• A targeted oral peptide that selectively binds the IL-23 receptor showed promising results for plaque psoriasis compared to placebo; a phase 3 clinical trial is underway to evaluate its efficacy in psoriatic arthritis.[70][ClinicalTrials.gov ID NCT06878404]

T-cell costimulatory inhibitors:

• For patients with mild-moderate psoriatic arthritis with peripheral joint disease.
• Check tuberculosis test before starting, and check CBC and CMP every 3 to 4 months.
• Minimally effective for psoriasis.

Abatacept CTLA4

• IgG Fc fusion protein 
• Dose: 125 mg subcutaneously every week or 500 to 1000 mg every month after loading (depending on weight)
• Adverse effects: increased risk of infections, including mycobacterial and fungal infections
• FDA-approved: psoriatic arthritis and rheumatoid arthritis

IL-17A inhibitors have demonstrated robust efficacy across multiple psoriatic arthritis domains. For skin disease, IL-17 and IL-23 inhibitors show superiority over TNF inhibitors.[71] Current evidence suggests that IL-17 inhibitors and TNF-α inhibitors are more effective for the management of psoriatic arthritis with axial involvement than IL-23i.[71] Regarding enthesitis, IL23i have been shown to be superior to TNF-α inhibitors.[72][73] Results from several trials have shown that IL-17A inhibitors are noninferior to TNF-α inhibitors for peripheral arthritis, though some data suggest a numerical superiority of secukinumab compared with adalimumab.[74]

Results from randomized, placebo-controlled trials of bDMARDs showed that csDMARDs, such as MTX, did not improve outcomes in psoriatic arthritis or psoriasis. However, results from analyses of large cohorts of patients with psoriatic arthritis showed that csDMARDs such as MTX improved clinical outcomes. Using csDMARDs improved TNFi drug survival,[75] and remission rates, especially with MTX.[76] Results from some retrospective studies suggest that patients with psoriasis treated with bDMARDs have a lower risk of developing psoriatic arthritis.[77][78][79]

tsDMARDs:

Phosphodiesterase-4 inhibitors:

• This is for patients with mild psoriatic arthritis with peripheral joint and skin disease.[80] This is also effective for enthesitis and dactylitis.[81] 
• No laboratory testing is needed to monitor therapy.

Apremilast:

• Dose: 30 mg twice daily after titration
• Adverse effects: gastrointestinal intolerance, nausea, diarrhea, weight loss, and depression

Janus kinase inhibitors:

• This is for moderate-severe active psoriatic arthritis with peripheral and axial disease.
• Obtain a tuberculosis test before starting. Check CBC, neutrophil count, and CMP every 3 months. Perform a lipid panel.

Tofacitinib:

• Dose: 5 mg by mouth 2 times a day or extended release, 11 mg by mouth every day 
• FDA-approved: psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and ulcerative colitis

Upadicitinib:

• Dose: 15 mg daily
• Adverse effects: increased risk of infections, including herpes zoster, tuberculosis, fungal infections, thromboembolism, neutropenia, elevated liver enzyme results, elevated cholesterol, and gastrointestinal perforations. Evidence suggests an increased risk of cardiovascular disease and cancer [82]
• FDA-approved: psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and ulcerative colitis [83]

Tyrosine kinase (TYK2) inhibitors:

• Deucravacitinib, a selective oral TYK2 inhibitor, was well-tolerated and more effective than placebo in psoriatic arthritis in a phase 2 trial,[84] and a phase 3 clinical trial is currently underway.

Prognosis

Psoriatic arthritis is considered an aggressive disease with the potential for significant morbidity and poor quality of life in patients. Some features predict a severe disease course and poor prognosis. These include a large number of actively inflamed joints or polyarticular presentation, elevated erythrocyte sedimentation rate results, clinical or radiographic damage, loss of function, and diminished quality of life.[84]

Complications

Once considered a mild disease, psoriatic arthritis is now considered a debilitating disease requiring targeted treatment with frequent monitoring and follow-up care. Complete symptomatic relief is achievable, but most patients continue to have persistent inflammatory disease.[85] Patients with uveitis will require evaluation and treatment by an ophthalmologist. Patients with psoriatic arthritis have an increased prevalence of comorbidities, including metabolic syndrome, obesity, diabetes mellitus, hyperlipidemia, hypertension, and cardiovascular disease.[42] 

Consultations

Psoriatic arthritis is best treated by rheumatologists but in collaboration with dermatologists for patients with significant psoriasis.

Deterrence and Patient Education

Patients should be educated and counseled about the chronic nature of psoriatic arthritis and the importance of nonpharmacological measures, including exercise, smoking cessation, weight loss, and physical and occupational therapy. Patients should be aware of the disease's fluctuating nature, which requires close monitoring by the interdisciplinary treatment team. The adverse effects of immunosuppressive medications require a detailed explanation, and efforts should be made to educate the patient's family as well.

Enhancing Healthcare Team Outcomes

Patients with psoriatic arthritis have a heterogeneous clinical presentation involving various domains. The condition is best managed through an interprofessional team approach to treating articular disease, skin disease, other manifestations, and medical comorbidities. Patient education is vital to ensure symptoms are under control. The physical therapist should encourage exercises to restore joint function. The pharmacist should educate the patient on different medications, their benefits, and adverse effects, monitor the selection and dosing of agents, and check for potential drug-drug interactions.

Nurses should inform patients of the importance of abstaining from alcohol and discontinuing tobacco, answer questions, and help monitor treatment progress. The dietitian should encourage a healthy diet and weight management. A mental health nurse and psychiatrist should be involved, because many patients develop severe anxiety and depression. Patients should be encouraged to seek stress relief. The social worker should assess the home to ensure the environment can accommodate the patient's lifestyle. These disciplines need to chart and share their perspectives with the rest of the team so all healthcare team members operate from the same information base, and corrective actions can be taken when necessary.

Patients with psoriatic arthritis are also at increased risk of death compared to the general population from cardiovascular diseases such as coronary artery disease, leading to angina and myocardial infarction.[86] Consequently, reversing the risk factors for ischemic heart disease is vital. Effective interprofessional coordination and communication among rheumatology, dermatology, primary care, nursing staff, pharmacy, and other ancillary healthcare team members are required to attain the best clinical outcome in patients with psoriatic arthritis. 

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Disclosure: Mery Deeb declares no relevant financial relationships with ineligible companies.

Disclosure: Lewena Maher declares no relevant financial relationships with ineligible companies.