Psoriatic Arthritis

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 one first-degree relative with psoriatic arthritis or psoriasis.[2] Genes related to psoriatic arthritis encompass those within the HLA region, 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).[3][4] Also, certain genes are associated with specific phenotypes of psoriatic arthritis.[3][5][6]

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.[6] HLA-B*08:01 is also associated with peripheral arthritis, joint damage, asymmetric sacroiliitis, and ankylosis. HLA-B*27:05 is associated with axial involvement with symmetric sacroiliitis, enthesitis, and dactylitis. HLA-B38 and HLA-B39 genes are associated with polyarthritis.[5][3] HLA-B*44:02/03 is protective and associated with milder disease [6] (see Table 1. Genetic Associations in Psoriatic Arthritis). The subset of patients with symmetric polyarthritis is associated with HLA-DR4 (this gene is associated with RA).

Non-HLA genes associated with psoriatic arthritis include IL-23R.[4][6] These genes produce proteins involved in immune-mediated inflammation, including TNFAIP3, TNF3IP2, REL, FBX19, and PTPN22 [4][6] (see Table 2. Non-HLA Genes Associated with Psoriatic Arthritis).

Psoriasis is more associated with HLA-B*57:01 and HLA-C*06:02 (the PsO susceptibility region 1 or PSORS1) than psoriatic arthritis.[3][7] IL-12B gene is associated with psoriasis but not psoriatic arthritis.[4] (Several other genes associated with psoriatic arthritis and psoriasis are not mentioned here.)[8]

Axial disease on psoriatic arthritis is more complicated. HLA-B27 gene is present in only 20% of patients with axial psoriatic arthritis compared to 80% to 90% in patients with axial spondyloarthritis, including ankylosing spondylitis (with higher occurrences are seen in White patients.)[9][10] Axial disease in patients with psoriatic arthritis includes patients who are HLA-B27 positive and are clinically similar to ankylosing spondylitis with earlier age of onset, more back pain, and radiographically appearing more like ankylosing spondylitis. Patients with axial psoriatic arthritis who are HLA-B27 negative have different clinical features with similar frequency in women and men, with older age of onset, less back pain, more frequent cervical spine disease, with radiographic features including asymmetric sacroiliitis and non-marginal, bulky syndesmophytes—which are often asymmetric. 

Some environmental factors are also suspected but have been difficult to confirm. Epidemiological studies have shown an association between streptococcal infection and recent antibiotic exposure.[11][12][13][14] Skin trauma is known to induce flares of psoriatic skin lesions, known as the Koebner phenomenon. There is evidence that joint trauma may induce a flare of arthritis, referred to as the “internal” or “deep” Koebner phenomenon.[13][14][15] 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.[14][16][14]

Table 1. Genetic Associations in Psoriatic Arthritis 

Table 2. Non-HLA Genes Associated with Psoriatic Arthritis 

Epidemiology

The epidemiology of psoriatic arthritis is heterogeneous and varies widely among various population groups. This condition has been estimated to have a prevalence of 0.05% to 0.25% in the general population and around 6% to 41% in patients with psoriasis.[17] This variability of psoriatic arthritis in psoriasis is partially due to underdiagnosis. A meta-analysis showed the prevalence of undiagnosed psoriatic arthritis might be as high as 15.5%.[18] The onset of psoriatic arthritis is usually seen in patients in their 30s and 40s and occurs about equally in men and women.[19] 

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.[20] This latter group is more common in childhood psoriatic arthritis. When examining the occurrence of psoriatic arthritis over time in a population of patients with psoriasis, the annual incidence of psoriatic arthritis was 1.9 to 2.7% per 100 patients with psoriatic arthritis.[21][2] 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.[22][23] 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.[22][2]

A literature review of the epidemiology of psoriatic arthritis showed the worldwide prevalence of psoriatic arthritis ranges from 0.1% to 1%.[24][1] There is great variability 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%), South East Asia (0.05%), East Asia (0.17%; China 0.002%; Taiwan 0.004%; Japan 0.001%), and South America (0.07%). There is also evidence that the prevalence of psoriatic arthritis has been increasing over time.[1] 

The prevalence of psoriatic arthritis in patients with psoriasis is 19.7%, with 21.6% in adults and 3.3% in children.[25] The prevalence of psoriatic arthritis in patients with psoriasis was 23.8% using the CASPAR Criteria. Psoriatic arthritis is more strongly associated with severe psoriasis than mild psoriasis (24.6% vs 15.8%). The proportion of patients with psoriasis with psoriatic arthritis varies depending on the geography and ethnicity of the target population, with 22.7% in Europe, 19.5% in North America, 21.5% in South America, 15.5% in Africa, and 14% in Asia.[25] 

Pathophysiology

Various genetic risk factors predispose patients to develop psoriatic arthritis and psoriasis.[3][4][5][8] In these patients, an environmental trigger such as infection or mechanical stress initiates a chronic inflammatory process primarily involving the joints and skin, producing IL-23, a central cytokine in the pathogenesis of psoriatic arthritis and psoriasis.[26][27] Macrophages and dendritic cells produce IL-23. The gastrointestinal tract may be a source of IL-23 due to disturbed barrier function or changes in the microbiota.[26][27][8] Enthesitis, inflammation at the site where ligaments, tendons, and joint capsules attach to the bone, is the prominent pathologic lesion in psoriatic arthritis compared to synovitis in rheumatoid arthritis.[28][26] 

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 ROR gamma-t+.[29] This stimulation produces IL-17, IL-22, and TNF-alpha, which promote inflammation, bone loss with erosions, and osteoproliferation.[30]

CD8+ T cells, integral to psoriatic arthritis, are substantiated by their connection with HLA Class I alleles, the oligoclonal expansion of CD8+ T cells, and their association with late-stage HIV infection.[27] Other immune cells involved in the pathogenesis include CD4+ T helper 17 cells that produce IL-17 and IL-22; type 3 innate lymphoid cells that produce IL-17 and IL-22; and gamma-delta T cells that produce IL-17 and TNF-alpha.[27][26] 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.[26][31][27][32]

Insights into basic pathophysiology have driven the development of therapies, including TNF inhibitors. Initially crafted for rheumatoid arthritis and inflammatory bowel disease, these inhibitors are now standard for managing psoriatic arthritis and psoriasis. While IL-17 inhibitors are FDA-approved for treating psoriatic arthritis and psoriasis, they lack efficacy for rheumatoid arthritis. IL-12/23 inhibitors and IL-23 inhibitors are FDA-approved for treating psoriatic arthritis and psoriasis.

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 similar to rheumatoid arthritis but may involve the distal interphalangeal joints, rheumatoid factor negative
• 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 pattern 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, the majority of patients will develop polyarticular arthritis. In an analysis of 220 patients with psoriatic arthritis, the patterns of arthritis were as follows: oligoarticular arthritis (14%), polyarthritis (40%), distal arthritis (12%), arthritis mutilans (16%) (see Image. Arthritis Mutilans), sacroiliitis and spondylitis (30%).[20] 

The Classification of Psoriatic Arthritis (CASPAR) study identified 63% of patients with polyarticular arthritis.[33] Axial disease is often associated with one of the patterns of peripheral arthritis. According to one prospective cross-sectional study, the frequency of radiological axial involvement in psoriatic arthritis was about 42.9%.[34] 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 adopted from various studies.[35] 

The classic definition described arthritis mutilans as the most severe form; its presentation is associated with osteolysis leading to digital telescoping, bone resorption, and sacroiliitis. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis initiative in 2012 was able to achieve 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.[36] 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.[37]

The discrepancies seen in different studies are explained by the heterogeneous patterns of the disease and the fact that many patients experience a transition from one pattern of arthritis 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 patterns of psoriatic arthritis may be related to the fact that most of these studies are from referral centers for psoriatic arthritis and may have an overrepresentation of the more severe patterns of psoriatic arthritis, such as arthritis mutilans and distal arthritis. Axial involvement has generally been thought to occur mainly in patients who are HLA-B27 positive. However, this may be an oversimplification. Ankylosing spondylosis with and without psoriasis has epidemiology similar to typical ankylosing spondylosis with a strong association with HLA-B27. Axial psoriatic arthritis appears to be a distinct entity, and compared to ankylosing spondylosis, the prevalence is fairly equal among women and men, has an older age of onset, has a much lower association with HLA-B27 (20% vs 80%-90%), and is associated with HL-B*08 and HLA-B*38. Clinically, patients with axial psoriatic arthritis have different radiographic findings, more common C-spine involvement, but improvement with TNFi and IL-17i, and possibly IL-23i.[9][10][16] 

The clinical features of psoriatic arthritis are described in terms of articular and extra-articular manifestations.

Articular/Periarticular Manifestations of Psoriatic Arthritis

• Peripheral arthritis presents in an oligoarticular vs polyarticular pattern
• The periarticular disease includes enthesitis (inflammation around the insertion of ligaments, tendons, or joint capsules), dactylitis (swelling of the entire digit, finger, or toe, “sausage digit”), and tenosynovitis
• Axial disease involving sacroiliac joints, usually asymmetric
• Spondylitis with discontinuous involvement with bulky non-marginal syndesmophytes

Extra-Articular Manifestations of Psoriatic Arthritis

• Psoriatic skin disease usually presents before the onset of arthritis but can occur simultaneously and even before the onset of joint disease. The severity of skin disease does not correlate well with the severity of the articular disease.[38]
• Nail disease is characterized by onycholysis, pitting, and splinter hemorrhages. The severity of nail disease correlates with skin and joint disease severity.[39] This condition 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 is unlike that associated with ankylosing spondylosis, as it is often chronic, bilateral, and can involve posterior elements.

Evaluation

There are no laboratory tests specifically for psoriatic arthritis. As in most inflammatory diseases, acute phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated. However, a normal ESR and CRP should not be used to rule out a diagnosis of psoriatic arthritis, as these levels are increased in only about 40% of patients.[40] Rheumatoid factor and anti-cyclic citrullinated peptide antibodies are classically considered absent in psoriatic arthritis. A negative rheumatoid factor is considered a criterion for diagnosing psoriatic arthritis per the Classification of Psoriatic Arthritis (CASPAR) classification criteria. Results from various studies have shown positive rheumatoid factor in about 2% to 10% of patients diagnosed with psoriatic arthritis, and approximately 5% are positive for anti-cyclic citrullinated peptide antibodies.[41][42] Antinuclear antibodies may also be positive in these patients but usually at low titers. Results from a study by Johnson et al, showed antinuclear antibodies at a titer >1:80 in 14% of patients with psoriatic arthritis.[43]

Radiographic changes show some characteristic patterns in psoriatic arthritis: erosive changes, gross joint destruction, joint space narrowing, and “pencil-in-cup” deformity.[44][45] These findings are driven by bone destruction and pathologic new bone formation, often in the same digit or even the same joint, which is a characteristic feature of psoriatic arthritis (eg, bone destruction with bone production). Despite treatment with disease-modifying anti-rheumatic drugs, psoriatic arthritis results in radiographic damage in about 47% of patients during the first 2 years of the disease.[46] The radiological features of peripheral arthritis in hands and feet include erosive changes, new bone formation, bony ankylosis, and joint osteolysis.[47] Entheseal involvement, including erosions and new bone formation, is characteristic in all spondyloarthropathies.[48] 

Axial features, including sacroiliitis and spondylitis, are characterized by the formation of syndesmophytes (ossification of the annulus fibrosis). The features differentiating psoriatic arthritis from ankylosing spondylitis are the asymmetric and often unilateral presentation of sacroiliitis, and syndesmophytes in psoriatic arthritis are non-marginal, bulky, asymmetric, and discontinuous skipping vertebral levels. Plain radiography, CT scan, ultrasound, and MRI are all useful in assessing patients with psoriatic arthritis.[49] 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.[50][51] However, these imaging modalities are not necessary to properly diagnose psoriatic arthritis. MSUS is used frequently in clinics as 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.[52][53] Similarly, dactylitis features on MSUS include synovial and tenosynovial inflammation.[54]

Classification Criteria

The most accepted classification criteria for psoriatic arthritis is the CASPAR criteria, which have been used since 2006.[33] 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.[55]

 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 [44]

CASPAR Criteria (2006)

Clinical Features/Characteristics/Points                                  

• Skin psoriasis: present - 2; previously present -1; family history, patient not affected - 1
• Nail lesions: onycholysis, pitting, hyperkeratosis - 1
• Dactylitis: present or past, documented by a rheumatologist - 1
• Rheumatoid factor: negative by any method except for latex - 1
• Juxta-articular bone formation: distinct from osteophytes - 1

Per CASPAR criteria, psoriatic arthritis is considered 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%.[33]

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.[56]
• A treat-to-target approach is the most effective way to control disease activity and minimize joint damage.[57][58] 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 are generally useful for treating mild peripheral arthritis symptoms.[59]
• Mild-to-moderate peripheral arthritis may be treated with conventional synthetic DMARDs (disease-modifying antirheumatic drugs) such as methotrexate or occasionally sulfasalazine; the latter is ineffective for skin disease.[60]
• Severe peripheral arthritis usually receives treatment with biologic DMARDs, especially TNF (tumor necrosis factor) inhibitors.
• Axial disease and enthesitis share similar treatment approaches, with a minimal role for conventional synthetic DMARDs. Patients who fail non-steroidal anti-inflammatory drugs should automatically transition to biologic DMARDs.
• A TNF inhibitor is usually recommended over 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 over 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 American College of Rheumatology (ACR) and National Psoriasis Foundation (NPF) 2018 guidelines recommend a TNF inhibitor over conventional synthetic DMARDs (labeled as OSM, oral small molecules) as a first-line treatment in patients with treatment-naïve psoriatic arthritis.
(A1)

A summary of various drugs used in treating psoriatic arthritis appears in a tabular form in Table 1.

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 of the following:

• Swollen joints
• Tender joints
• Dactylitis
• Enthesitis
• Axial disease
• Active skin and/or nail involvement
• Extra-articular inflammatory manifestations such as uveitis or inflammatory bowel disease [61]

ACR/NPF 2018 Guidelines for the Treatment of Psoriatic Arthritis

Initial Treatment

Oral small molecule (OSM): methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), cyclosporine (CSA), apremilast

• Treat with tumor necrosis factor (TNF) inhibitors over OSM: may consider OSM such as MTX in patients with mild psoriatic arthritis and psoriasis, patient's preference, and contraindication to TNF inhibitor.
• Treat with TNF inhibitor over IL-17 inhibitor: may consider IL-17 inhibitor in patients with severe psoriasis or contraindication to TNF inhibitor.
• Treat with TNF inhibitor over IL-12/23 inhibitor: may consider IL-12/23 inhibitor in patients with severe psoriasis of contraindication to TNF inhibitor.
• Treat with OSM over IL-17 inhibitor: may consider IL-17 inhibitor in patients with severe psoriasis and/or psoriatic arthritis.
• Treat with OSM over IL-12/23 inhibitor: may consider IL-12/23 inhibitor in patients with severe psoriasis and/or psoriatic arthritis or concomitant inflammatory bowel disease.
• Treat with MTX over non-steroidal anti-inflammatory drugs: may consider these drugs in patients with mild psoriatic arthritis and psoriasis.
• Treat with IL-17 inhibitor over IL-12/23 inhibitor: may consider 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

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Disease-modifying antirheumatic drugs (DMARD), Conventional synthetic DMARD (csDMARD), Biologic DMARD (bDMARD), Monoclonal antibody (mab) Targeted synthetic DMARD (tsDMARD), Janus kinase (JAK), Phosphodiesterase-4 (PDE4)[62]

Overarching principles

• Psoriatic arthritis is a heterogeneous and potentially severe disease that may require multidisciplinary 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, collaborate with a dermatologist.
• 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, non-musculoskeletal manifestations (eg, skin, eye, and GI tract) and comorbidities (eg, metabolic syndrome, cardiovascular disease, and depression) should be considered.

Recommendations

• Treatment should aim to reach remission or low disease activity target by regular disease activity assessment and appropriate therapy adjustment.
• NSAIDs may be used to relieve musculoskeletal signs and symptoms.
• Local glucocorticoid injections should be considered adjunctive therapy in psoriatic arthritis; systemic glucocorticoids may be used cautiously at the lowest effective dose.
• A 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 with poor prognostic factors such as structural damage, high erythrocyte sedimentation rate or c-reactive protein levels, dactylitis, or nail involvement.
• In patients with psoriatic arthritis who have an inadequate response to at least one csDMARD, therapy with a 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 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 PDE4 inhibitor may be considered.
• In patients with unequivocal enthesitis and insufficient response to NSAIDs or local glucocorticoid injections, therapy with a bDMARD should be considered.
• In patients with predominantly axial disease, which is active and has an insufficient response to NSAIDs, therapy with a bDAMRD should be considered (according to current practice, this is a TNF inhibitor); when there is relevant skin involvement, IL-17 inhibitor may be preferred.
• In patients who fail to respond adequately to or are intolerant of abDMARD, 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 arthritis, including rheumatoid arthritis, reactive arthritis, and ankylosing spondylosis. Some cases may be difficult to make a precise diagnosis. Unlike psoriatic arthritis, rheumatoid arthritis tends to be symmetrical and generally spares the distal interphalangeal joints. Ankylosing spondylosis has an earlier onset age than psoriatic arthritis, and sacroiliac involvement is usually symmetric rather than asymmetric. 

Treatment Planning

Disease Monitoring 

As with any other inflammatory arthritis, patients with psoriatic arthritis require regular disease activity monitoring and appropriate changes to therapy based on the measurement of disease activity. Evaluation of all the 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.

Various 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 determines axial disease activity and ankylosing spondylosis
• Health-related Quality of Life (QOL), as measured by indices like PsAQOL
• Functional Assessment of Chronic Illness Therapy-Fatigue Scale 
• Composite indices like 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, 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.[63] 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 as it focuses on peripheral arthritis.

 A treat-to-target approach to attain remission or minimal disease activity is strongly recommended.[58] A patient is considered to have achieved minimal disease activity if they meet 5 of the 7 following criteria.[64]

Minimal Disease Activity 

• Tender joint count of </= 1
• Swollen joint count </= 1
• Psoriasis Area and Severity Index of </= 1 or body surface area </= 3
• Patient pain visual analog scale (VAS) score </= 15 mm
• Patient global disease activity VAS score </= 20 mm
• Health Assessment Questionnaire score </= 0.5
• Tender entheseal points </= 1

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 given with 1 mg of folic acid daily
• Toxicities include oral ulcers, nausea, cytopenias, increased risk of infections, pulmonary toxicity (pneumonitis), and this drug is teratogenic 
• Advise patients to avoid drinking excessive alcohol and be cautious with patients who have chronic kidney disease 
• Check complete blood count (CBC) and comprehensive metabolic panel (CMP) every 2 to 4 months

Sulfasalazine 

• For patients with mild peripheral joint disease but is not helpful for skin disease 
• Dose: 1000 to 1500 mg twice daily 
• Toxicities: rash, nausea, diarrhea, and elevated liver enzymes on liver function tests, but rarely leukopenia/neutropenia 
• Check 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 
• Toxicities: diarrhea, hair loss, skin rash, leukopenia, elevated liver enzymes on liver function tests, and weight loss
• Check CBC and CMP every 2 to 4 months

Cyclosporine 

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

bDMARDs

TNF inhibitors (TNFi) 

• For patients with moderate-severe active psoriatic arthritis with peripheral and axial joint and skin diseases 
• All TNFIs are FFA-approved for rheumatoid arthritis and ankylosing spondylitis
• Check tuberculosis test before starting, and check CBC and CMP every 3-4 months

Monoclonal antibody (mab) TNFi 

• These are effective for uveitis and inflammatory bowel disease

Etanercept

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

Infliximab 

• Chimeric mab to TNF-alpha
• Dose: 5 mg/kg intravenously every 6 weeks after loading 
• FDA-approved for psoriatic arthritis and psoriasis

Adalimumab

• Human mab to TNF-alpha 
• Dose: 40 mg subcutaneously every 2 weeks 
• FDA-approved for psoriatic arthritis and psoriasis

Golimumab

• Human mab to TNF-alpha 
• Dose: 50 mg subcutaneously every month or 2 mg/kg intravenously every 2 months 
• FDA-approved for psoriatic arthritis and psoriasis

Certolizumab pegol

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

IL-17 inhibitors (IL-17i) 

• For patients with moderate-severe active psoriatic arthritis with peripheral and axial joint and skin disease
• Check TB test before starting, and check CBC and CMP every 3-4 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 for psoriatic arthritis, psoriasis, and ankylosing spondylitis
• Secukinumab at doses of 300 mg every month was effective in patients with psoriatic arthritis and axial disease in a double-blind, randomized trial [65]

Ixekizumab 

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

Brodaulmab 

• Human mab to IL-17R 
• Dose: 210 mg SC every 2 weeks after loading
• Toxicities: increased risk of infections, including mycobacterial and fungal infections and candida infections
• FDA approved for psoriasis, but not for psoriatic arthritis

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
• Check TB test before starting, and check CBC and CMP every 3-4 months.
• IL-12/23i are ineffective for the axial disease of ankylosing spondylitis or non-radiographic 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 SC every 3 months after loading (90 mg if weight >100 kg)
• FDA-approved for psoriatic arthritis, psoriasis, and Crohn’s disease

Guselkumab (IL-23i)

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

Tildrakizumab (IL-23i)

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

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 3-4 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)
• Toxicities: an increased risk of infections, including mycobacterial and fungal infections.
• FDA-approved for psoriatic arthritis and rheumatoid arthritis

In the randomized, placebo-controlled trials of bDMARs, using csDMARDs such as MTX did not improve outcomes for psoriatic arthritis or psoriasis. Analyses of large cohorts of patients with psoriatic arthritis and csDMARDs such as MTX improved clinical outcomes. Using csDMARDs improved TNFi drug survival [66] and remission rates, especially with MTX.[67] Some retrospective studies suggest that patients with psoriasis treated with bDMARDs have a lower risk of developing psoriatic arthritis.[68][69][70]

tsDMARDs

PDE-4 inhibitors

• For patients with mild psoriatic arthritis with peripheral joint and skin disease [71] 
• Also effective for enthesitis and dactylitis [72] 
• No laboratory testing is needed to monitor therapy

Apremilast

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

Janus kinase inhibitors 

• For moderate-severely active psoriatic arthritis with peripheral and axial disease 
• Check 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 for psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and ulcerative colitis

Upadicitinib

• Dose: 15 mg daily
• Toxicities: an increased risk of infections, including herpes zoster, tuberculosis, fungal infections, thromboembolism, neutropenia, elevated liver enzymes, elevated cholesterol, and gastrointestinal perforations. There is evidence of an increased risk of cardiovascular disease and cancer [73]
• FDA-approved for psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and ulcerative colitis [74]

Updates in psoriatic arthritis therapeutics

• Bimekizumab is a dual IL-17A, and IL-17F humanized monoclonal antibody. A recent double-blind placebo-controlled phase 3 published trial (BE-COMPLETE) 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 alpha inhibitors [75] 
• Selective oral TYK2 inhibitors were found to be well-tolerated and more effective compared to the placebo in psoriatic arthritis in a phase 2 trial,[76] 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 are harbingers of a severe disease course and poor prognosis. These include a large number of actively inflamed joints or polyarticular presentation, elevated erythrocyte sedimentation rate, clinical or radiographic damage, loss of function, and diminished quality of life.[77]

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.[78] 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.[79]