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Psoriatic Arthritis: Established, Newer, and Emerging Therapies

A look at the mechanisms and pathophysiology that appear as contributing factors to musculoskeletal inflammation, bone irregularities, and resultant symptoms seen in this form of arthropathy.
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Psoriatic arthritis (PsA) is a type of spondyloarthritis that develops in up to 30% of patients who have psoriasis; it has an estimated prevalence between 30 and 100 cases per 10,000 people in the United States.1 The incidence of PsA is similar among men and women, and it occurs less commonly among Asian and black individuals. Although PsA generally presents about 10 years after an initial psoriasis diagnosis, the order in which symptoms of the disease manifest can vary, and multiple symptoms may occur simultaneously.

 

Clinical features of PsA may present in 6 clinical domains that direct diagnosis and treatment—peripheral disease, axial disease, enthesitis, dactylitis, skin disease, and nail disease.1 Pain and stiffness commonly occur in peripheral and/or axial joints. Enthesitis, or swelling at the insertion site of tendons or ligaments to bone, typically is seen at the Achilles tendon or plantar fascia. Dactylitis, or pain and inflammation of the toes and fingers, can be acute or chronic. Up to 50% of patients with PsA have enthesitis and dactylitis. Axial involvement of the spine and sacroiliac joint also is common.2 Nail dystrophy causing onycholysis, pitting, or hyperkeratosis is observed in a majority of patients. Patients with PsA also may be at a higher risk for cardiovascular events, type 2 diabetes, fatty liver, hypertension, and metabolic syndrome.

The spectrum of arthropathy symptoms can vary from arthritis in distal interphalangeal joints to arthritis mutilans, a highly destructive arthritis subtype that often causes shortening and malformation of the digits.

Pathophysiology and Etiology

Since not all patients with psoriasis develop PsA, several mechanisms are believed to contribute to the musculoskeletal inflammation, bone abnormalities, and resultant symptoms of PsA.1,3 In psoriasis, the effect on the skin occurs as a result of type 1 and type 17 helper T-cell (TH1 and TH17) pathways triggering release of various inflammatory substances, such as interleukin (IL)-23, IL-17, and tumor necrosis factor (TNF). These inflammatory substances induce migration of monocytes and T cells in response to local stress to a joint, resulting in synovial inflammation.

Proposed factors that put stress on joints include infection, trauma, and autoimmune reactions. The presence of interferon γ, TNFα, and various TH17 cytokines have been found during laboratory analysis of synovial fluid of patients with PsA.2 In addition to autoimmune and inflammatory markers, a high concentration of osteoclastic precursors and upregulation of receptor activator of nuclear factor κβ ligand has been detected in the synovial lining of affected patients.

The likelihood of a patient with psoriasis developing PsA increases with psoriasis severity.1,3 The risk of developing PsA also is higher in patients with a family history of PsA. Genetic alterations and the presence of certain human leukocyte antigens (HLA), such as HLA-B27, as well as major histocompatibility complex alleles, have been linked to PsA. Other factors that may increase the risk of PsA include infection, obesity, trauma, and inflammatory bowel disease.

Diagnosis

Clinicians caring for patients with psoriasis should routinely inquire about symptoms of painful joints, morning stiffness, and changes in the appearance of joints.1 The Classification Criteria for Psoriatic Arthritis (CASPAR), although not validated as diagnostic criteria, can guide clinicians in the identification of PsA in patients who present with inflammatory musculoskeletal disease of joints, the spine, or entheses.

The following criteria are used for classification:

  • Evidence of current psoriasis or a personal or family history of psoriasis
  • Nail dystrophy
  • Current or past dactylitis
  • Radiographic evidence of new bone formation
  • Negative rheumatoid factor

When present, each of these components is given a single point, except for current psoriasis (rather than personal or family history), which is assigned 2 points. A score of at least 3 points on the CASPAR classification indicates the presence of PsA. The CASPAR classification also has been used to form inclusion criteria for enrollment into clinical trials evaluating PsA treatments.

Conditions that should be ruled out before establishing a diagnosis of PsA include:

  • Gout
  • Rheumatoid arthritis (RA)
  • Ankylosing spondylitis

Laboratory measurements and imaging studies can aid in establishing a correct diagnosis. Rheumatoid factor and anti-cyclic citrullinated peptide antibodies typically are negative in patients with PsA.1,2 General markers of inflammation, such as serum C-reactive protein and erythrocyte sedimentation rate, are elevated in about 40% of patients with PsA, and 25% of patients are positive for HLA-B27. Typical findings on imaging studies include bone and cartilage destruction along with new bone formation. Patients with a poor prognosis are those with multiple affected joints and elevated inflammatory markers.4

Pharmacologic Treatment

The goals of therapy in PsA are to achieve remission and low or minimal disease activity, optimize functional status, prevent structural joint damage, and minimize complications of active disease and its treatment.

Treatment decisions should consider the presentation of disease activity in each of the 6 clinical domains of PsA. The presentation may be heterogeneous among these domains, and the domain with the most severe symptoms should direct the choice of treatment.

The most widely followed current guidelines on the treatment of PsA are those authored by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), which offer differing recommendations.4,5

Last updated on: August 16, 2017
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