Psoriatic Arthritis

Article Author:
Vivekanand Tiwari
Article Editor:
Lawrence Brent
Updated:
8/10/2020 9:15:45 PM
PubMed Link:
Psoriatic Arthritis

Introduction

Psoriatic arthritis (PsA) is chronic inflammatory arthritis associated with psoriasis (PsO) and found in about 20 to 30% of such patients.[1]  It shares many clinical features with other spondyloarthropathies and also rheumatoid arthritis (RA). It is usually seronegative, but a small percentage of patients may be positive for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies). The clinical manifestations are varied and can change over time, evolving from one articular pattern to another.  There is a considerable financial and psychological burden associated with this disease. There has been significant progress recently in understanding the disease pathogenesis, which has translated into new therapies.

Etiology

The etiology and pathogenesis of psoriatic arthritis are not fully understood but involves a complex interaction between genetic and environmental factors resulting in immune-mediated inflammation involving the skin and joints and may involve other organs.  Approximately 33 to 50% of psoriatic arthritis patients have at least one first degree relative who also has psoriasis or psoriatic arthritis.[2]  Genes associated with psoriatic arthritis include those in the HLA region which are involved in antigen presentation and immune recognition and also non-HLA genes involved in immune activation and inflammation including intracellular signaling, cytokine expression, and signaling, and T cell effector function. The genetic associations with psoriatic arthritis and psoriasis are not identical so that some genes associated with psoriatic arthritis are not associated with psoriasis, and the same is true for psoriasis.[3][4] Also, certain genes are associated with specific phenotypes of psoriatic arthritis.[3][5] Genetic associations in psoriatic arthritis include HLA-B*08:01, HLA-B*27:05, HLA-B*38:01, HLA-B*39:01, HLA-B*57:01, and HLA-C*06:02.  The subset of patients with symmetric polyarthritis is associated with HLA-DR4HLA-B27 is associated with axial involvement, while HLA-B38 and HLA-B39 were associated with polyarthritis.[5][3] Non-HLA genes associated with psoriatic arthritis include IL-23R.[4] Psoriasis has a stronger association than psoriatic arthritis with HLA-B*57:01 and HLA-C*06:02[3](referred to as the psoriasis susceptibility region 1 or PSORS1[6]). IL-12B gene is associated with psoriasis but not psoriatic arthritis.[4]  Several other genes correlate with psoriatic arthritis and/or psoriasis not mentioned here.[7]

The role of environmental factors is suspected but has been difficult to confirm. Epidemiologic studies have shown an association between streptococcal infection and recent antibiotic exposure.[8][9][10][11] Skin trauma is known to induce flares of psoriatic skin lesions which is known as the Koebner phenomenon. There is evidence the joint trauma may induce a flare of arthritis, referred to as "internal" or "deep" Koebner phenomenon.[10][11][12] Tobacco, which is a recognized trigger for rheumatoid arthritis in patients with certain HLA-DR genes, appears to be protective for the development of psoriatic arthritis.[11]

Epidemiology

The epidemiology of psoriatic arthritis is heterogeneous and has a wide variation amongst various population groups.  It has been estimated to have a prevalence of 0.05% to 0.25% in the general population and around 6% to 41% in psoriasis patients.[13] 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%.[14] The onset of psoriatic arthritis is usually in the 30s and 40s and occurs about equally in males and females.[15] In the majority of patients, the onset of skin disease precedes that of 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 the diagnosis more difficult.[16] 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.[17][2] The cumulative incidence 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.[18][19] A severe psoriasis phenotype, scalp, intergluteal and perianal psoriasis, presence of nail pitting, low level of education, and uveitis are predictive of the development of psoriatic arthritis in patients with psoriasis.[18][2]

Pathophysiology

Various genetic risk factors predispose patients to develop psoriatic arthritis and psoriasis.[3][4][5][7][7] In these patients, an environmental trigger such as infection or mechanical stress initiates a chronic inflammatory process primarily involving the joints and skin, resulting in the production of IL-23 which is a central cytokine in the pathogenesis of psoriatic arthritis and psoriasis.[20][21]  Macrophages and dendritic cells produce IL-23.  In fact, the gastrointestinal tract may be the source of IL-23 due to disturbed barrier function or changes in the microbiota.[20][21][7] Enthesitis, which is inflammation at the site where ligaments, tendons, and joint capsules attach to the bone, is the prominent pathologic lesion in psoriatic arthritis in contrast to synovitis in rheumatoid arthritis.[22][20] Distal interphalangeal (DIP) joints are frequently involved in psoriatic arthritis but not so in rheumatoid arthritis because these joints have many entheses but very little synovial tissue. In animal models of spondyloarthropathy, IL-23 cans stimulate resident T cells which are CD3+, CD4-, CD8-, IL-23R+, ROR gamma-t+.[23] This stimulation leads to the production of IL-17, IL-22, and TNF-alpha, which promote inflammation, bone loss with erosions, and osteoproliferation.[24]

CD8+ T cells play a central role which is supported by the association of psoriatic arthritis with HLA Class I alleles, oligoclonal expansion of CD8+ T cells, and association with late-stage HIV infection[21] Other immune cells involved in the pathogenesis include CD4+ type 17 helper (Th17) cells which produce IL-17 and IL-22, type 3 innate lymphoid (ILC3) cells which produce IL-17 and IL-22 and gamma-delta T cells which produce IL-17 and TNF-alpha.[21][20] These proinflammatory cytokines recruit neutrophils which enter the synovial fluid, activate synoviocytes, promote angiogenesis locally, active osteoclasts which result in bone destruction and osteoblasts which result in new bone formation.[20][25][21]

This information about the basic pathophysiology has been used to develop therapies such as TNF inhibitors which were initially developed for rheumatoid arthritis and inflammatory bowel disease and now routinely used for psoriatic arthritis and psoriasis. IL-17 inhibitors are FDA approved for the treatment of psoriatic arthritis and psoriasis but are not effective for rheumatoid arthritis. IL-12/23 inhibitors are FDA approved for the treatment of psoriatic arthritis and psoriasis while IL-23 inhibitors are FDA approved for psoriasis and have shown efficacy for psoriatic arthritis.

History and Physical

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

  • Oligoarticular arthritis which is asymmetric and involves less than five small or large joints
  • Polyarticular arthritis which is usually symmetric and presents similar to rheumatoid arthritis but may involve the DIP joints, rheumatoid factor negative
  • Distal arthritis signified by prominent involvement of the DIP joints
  • Arthritis mutilans characterized by a severe destructive joint disease with deformities especially in hands and feet
  • Spondyloarthritis pattern with sacroiliitis and spondylitis (this may occur with or without peripheral joint disease)

The asymmetric oligoarticular pattern is the most common form on presentation of psoriatic arthritis, accounting for at least 60% of cases of psoriatic arthritis. However, this is not true of all patient populations.  Over time the majority of patients have 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%, sacroiliitis and spondylitis - 30% (this adds up to more than 100% because axial and peripheral joint involvement may coexist.[16]  The Classification of Psoriatic Arthritis (CASPAR) study identified 63% of patients with polyarticular arthritis.[26] The spondyloarthritis is often associated with one of the patterns of peripheral arthritis. The frequency of radiological axial involvement in psoriatic arthritis has been found to be about 42.9% according to one prospective cross-sectional study.[27] The distal pattern is less common occurring in less than 20% of patients and may be present along with spondyloarthritis. Arthritis mutilans prevalence can range from 2 to 21%, reflecting different definitions of this entity adopted in various studies.[28] The classic definition referred to it as the most severe form, and its presentation was associated with osteolysis leading to digital telescoping, bone resorption, and sacroiliitis. GRAPPA initiative (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) 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 DIP joints and other small joints of the hands.[29]

The discrepancies seen in different studies can be explained by the heterogeneous patterns of the disease as well the fact that many patients experience the transition of 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. Also, the patient population may affect results particularly for axial involvement which is related to the prevalence of HLA-B27 which is higher in individuals of the White race, especially of northern European descent

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

Articular/periarticular manifestations of psoriatic arthritis.

  • Peripheral arthritis presenting in an oligoarticular vs. polyarticular pattern
  • Periarticular disease including 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 and 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.[30]
  • Nail disease characterized by onycholysis, pitting, and splinter hemorrhages.  The severity of nail disease correlates with the severity of both skin and joint disease.[31]  It is present in 80 to 90% of patients with psoriatic arthritis and is associated with DIP joint involvement.
  • Ocular disease in the form of uveitis but unlike that associated with ankylosing spondylitis, it is often chronic, bilateral, and often involves posterior elements.

Evaluation

There are no laboratory tests which are specific for psoriatic arthritis. Acute phase reactants such as ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein ) may become elevated as in most inflammatory diseases. However, a normal ESR and CRP should not be used to rule out a diagnosis of psoriatic arthritis as these levels increase in only about 40% of patients.[32] RF and anti-CCP antibodies are classically considered to be absent in psoriatic arthritis, and a negative rheumatoid factor is considered to be a criterion for the diagnosis of psoriatic arthritis as per the CASPAR classification criteria. Various studies have shown positive rheumatoid factor in about 2 to 10% of patients with a diagnosis of psoriatic arthritis, and approximately 5% are positive for anti-CCP antibodies.[33][34] ANA may also be positive in these patients but usually at low titers. One study by Johnson et al. showed an ANA at a titer >1:80 in 14% in patients with psoriatic arthritis.[35]

Radiographic changes show some characteristic patterns in psoriatic arthritis, and it consists of erosive changes, gross joint destruction, joint space narrowing, and "pencil-in-cup" deformity.[1][36] 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; bone destruction with bone production.  Despite treatment with DMARDs (disease-modifying anti-rheumatic drugs), psoriatic arthritis results in radiographic damage in about 47% of patients during the first two years of the disease.[37] The radiological features of peripheral arthritis in hands and feet include erosive changes (including the MCP, PIP, DIP joints, and wrists), new bone formation, bony ankylosis, and joint osteolysis.[38] Entheseal involvement, including erosions and new bone formation, is characteristic in all spondyloarthropathies.[39] Axial features including sacroiliitis and spondylitis, including the formation of syndesmophytes (ossification of the annulus fibrosis). The features which differentiate psoriatic arthritis from ankylosing spondylitis are the asymmetric and often unilateral presentation of sacroiliitis. Syndesomophytes in psoriatic arthritis are often bulkier, asymmetric, and discontinuous skipping vertebral levels. Plain radiography, CT scan, ultrasound, and MRI are all useful in the assessment of patients with psoriatic arthritis.[40] Imaging modalities such as MRI and ultrasound are more sensitive than plain radiography for detecting early joint inflammation and damage and axial changes, including sacroiliitis.[41][42] However, they are not necessary to make a proper diagnosis of psoriatic arthritis. 

Classification Criteria

The most accepted classification criteria for psoriatic arthritis is the CASPAR criteria (Classification of Psoriatic Arthritis ) which have been in use since 2006.[26] Other classification criteria which clinicians have used include the original Moll and Wright (1973), Bennet (1979), and Vassey and Espinoza (1984), the modified ESSG (1991) criteria.[43]

 Moll and Wright criteria (1973)[1]

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

CASPAR Criteria (2006)[26]

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 to be 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%.[26]

Treatment / Management

  General Principles:

  1. Treatment should be guided by disease severity, degree of joint damage, the extent of extra-articular disease, patient preference, and other co-morbidities.
  2. Non-pharmacological therapies, including physical therapy, occupation therapy, exercise program, and smoking cessation, should be strongly encouraged and incorporated in the treatment plan.[44]
  3. Treat-to-Target approach is the most effective way to control disease activity and minimize joint damage.[45][46] A target of low remission or low disease activity should be employed depending on disease extent, chronicity, and other co-morbidities.
  4. 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/nail disease.
  5. In treatment-naïve patients, NSAIDs ( non-steroidal anti-inflammatory drugs ) are generally useful for symptoms of mild peripheral arthritis.[47]
  6. Mild to moderate peripheral arthritis may be treated with conventional synthetic DMARDs (disease-modifying antirheumatic drug ) such as methotrexate or occasionally sulfasalazine, the latter is not effective for skin disease.[48]
  7. Severe peripheral arthritis usually receives treatment with biologic DMARDs, especially TNF (tumor necrosis factor) inhibitors.
  8. Axial disease and enthesitis are usually treated the same way except for the fact that there is a minimal role of conventional synthetic DMARDs. Patients who fail NSAIDs should automatically transition to biologic DMARDs.
  9. A TNF inhibitor is usually recommended over an IL-17 inhibitor, IL-12/23 inhibitor, abatacept, or tofacitinib.
  10. An IL-17 inhibitor is usually recommended over an IL-12/23 inhibitor, abatacept, or tofacitinib.
  11. An IL-12/23 inhibitor is usually recommended over abatacept or tofacitinib.
  12. In patients with severe psoriasis, an IL-12/23 inhibitor or an IL-17 inhibitor may be used instead of a TNF inhibitor.
  13. Tofacitinib may be used instead of a TNF inhibitor in patients preferring oral medication who do not have severe psoriasis.
  14. ACR/NPF (American College of Rheumatology/National Psoriasis Foundation) 2018 guidelines recommend a TNF inhibitor over conventional synthetic DMARDs (labeled as OSM, oral small molecules) as a first-line treatment in treatment-naïve psoriatic arthritis patients.

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

Active Psoriatic Arthritis (as defined in ACR/NPF 2018 guidelines)[49]

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

ACR/NPF Guidelines for the Treatment of Psoriatic Arthritis: 2018. Initial Treatment

  • Treat with TNF inhibitor over oral small molecule (OSM): May consider OSM with mild psoriatic arthritis and psoriasis, patient preference, contraindication to TNF inhibitor
  • Treat with TNF inhibitor over IL-17 inhibitor: May consider IL-17 inhibitor with severe psoriasis or contraindication to TNF inhibitor
  • Treat with TNF inhibitor over IL-12/23 inhibitor: May consider IL-12/23 inhibitor with severe psoriasis of contraindication to TNF inhibitor
  • Treat with OSM over IL-17 inhibitor: May consider IL-17 inhibitor with severe psoriasis and/or psoriatic arthritis
  • Treat with OSM over IL-12/23 inhibitor: May consider IL-12/23 inhibitor with severe psoriasis and/or psoriatic arthritis, or concomitant IBD (inflammatory bowel disease)
  • Treat with Methotrexate over NSAIDs: May consider NSAIDs with mild psoriatic arthritis and psoriasis
  • Treat with IL-17 inhibitor over IL-12/23 inhibitor: May consider IL-12/23 inhibitor in a patient with concomitant inflammatory bowel disease

Differential Diagnosis

Psoriatic arthritis shares some clinical features with other inflammatory arthritides, including rheumatoid arthritis (RA), reactive arthritis (ReA), and ankylosing spondylitis (AS). In some cases, it is difficult to make a precise diagnose. Unlike psoriatic arthritis, rheumatoid arthritis tends to be symmetrical and generally spares the DIP joints. Ankylosing spondylitis has an earlier age of onset compared to psoriatic arthritis, and sacroiliac involvement is usually symmetric rather than asymmetric. Salient features of psoriatic arthritis compared to other arthritides is shown in Table 2.

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 are used to assess disease activity in clinical practice and clinical trials.

Various parameters used in assessing disease activity in psoriatic arthritis:

  1. Tender and swollen joint counts of 68 joints and 66 joints, respectively, in peripheral arthritis
  2. Axial disease activity determined by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) also used in ankylosing spondylitis
  3. Health-related QoL (Quality of Life) as measured by indices like PsAQOL
  4. Fatigue assessment by FACIT (Functional Assessment of Chronic Illness Therapy)
  5. Composite indices like DAPSA (Disease Activity Index for Psoriatic Arthritis), MDA (Minimal Disease Activity), America’s College of Rheumatology criteria viz ACR 20/50/70 (Table 3), Psoriatic Arthritis Response Criteria (PsARC)(Table 4), and CDPAI (Composite Psoriatic Disease Activity Index)(Table 5)
  6. The RAPID3 (Routine Assessment of Patient Index Data), which is useful for assessment of disease activity in rheumatoid arthritis, is simple to administer and does not require any laboratory indices.  It compares favorably to other, more complicated measures of disease activity in psoriatic arthritis and is more practical for routine clinical care.[50] The DAS28 (Disease Activity Score using 28 joints) is used frequently in the measurement of disease activity in rheumatoid arthritis, but it is inadequate as it focuses on peripheral arthritis.

 A treat-to-target approach to attain remission or minimal disease activity (MDA) is a strong recommendation.[46]  A patient is considered to have achieved MDA if they meet 5 of 7 following criteria.[51]

Minimal Disease Activity (MDA)

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

Prognosis

Psoriatic arthritis is considered to be an aggressive disease with the potential for significant morbidity and poor quality of life in patients. Some features are considered to be harbingers of a severe disease course and poor prognosis. These include a large number of actively inflamed joints or polyarticular presentation, elevated ESR, clinical or radiographic damage, loss of function, and diminished quality of life.[52]

Complications

Once considered to be a mild disease, psoriatic arthritis is now considered to be a debilitating disease requiring targeted treatment with frequent monitoring and follow-up care. Complete symptomatic relief is achievable, but a significant majority of patients continue to have persistent inflammatory disease.[53]

Deterrence and Patient Education

Patients should be extensively educated and counseled with regards to the chronic nature of psoriatic arthritis and the importance of non-pharmacological measures, including exercise, smoking cessation, weight loss, physical therapy, and occupational therapy. They should be made aware of the fluctuating nature of this disease, requiring very close monitoring by the multi-disciplinary treatment team. The side effects related to immunosuppressive medications require a detailed explanation, and an attempt should be made to educate the patient family as well.

Enhancing Healthcare Team Outcomes

Patients with psoriatic arthritis have a heterogeneous clinical presentation with the involvement of various domains and are best managed with an interprofessional approach to the treatment of articular disease, skin disease, other manifestations, and medical comorbidities. Patient education is vital to ensure that the 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 reactions, as well as monitoring agent selection, dosing, and checking for potential drug-drug interactions. Nurses should educate patients on 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. A mental health nurse and psychiatrist should be involved, as many patients do develop severe anxiety and depression. Patients should be encouraged to seek stress relief. The social worker should assess the home to ensure it can accommodate the patient's lifestyle. All of these various disciplines need to chart and share their perspectives with the rest of the team so that all members of the healthcare team are operating from the same information base.

It merits noting that psoriatic arthritis patients 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.[54] Thus, it is vital to reverse the risk factors for ischemic heart disease. Effective interprofessional coordination and communication between rheumatology, dermatology, and primary care, as well as nursing staff, pharmacy, and other ancillary healthcare team members mentioned above are required to attain the best clinical outcome in patients with psoriatic arthritis. [Level V] 



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