HSS Manual Ch. 41 - Psoriatic Arthritis

From the HSS Manual of Rheumatology and Outpatient Orthopedic Disorders

Joseph A. Markenson, MD
Joseph A. Markenson, MD
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College
Petros Efthimiou, MD
Rheumatology Fellow
Hospital for Special Surgery


  • Psoriatic Arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral joints and axial skeleton, occurring in a subset of patients with psoriasis.

  • Arthritis might precede skin psoriatic lesion in 13-17% of cases.

  • The extent of skin disease does not generally parallel arthritis activity.

  • Radiographic findings considered “classic” for PsA include asymmetric DIP joint erosion and ankylosis, “pencil-in-cup” deformity and resorption of the phalangeal tufts, and “fluffy” periostitis.

  • PsA follows a moderate course affecting few joints. However, in 20% of cases it evolves into a destructive debilitating arthritis.

  • The modern treatment paradigm is early aggressive treatment with DMARDs aiming at no evidence of disease status to avoid joint damage.


Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral joints and axial skeleton, occurring in 7–42% of patients with psoriasis, which affects 1– 3% of the general population.

  1. Psoriasis usually appears in the second to third decades but the onset of associated arthritis is usually delayed by two decades. However, 13-17% of patients with PsA will present with joint symptoms before the appearance of skin lesions, making diagnosis somewhat difficult. While skin disease is a useful diagnostic marker for PsA, its extent does not parallel the activity of arthritis.

  2. Enthesopathy or inflammation at the sites where tendons and ligaments attach to the bone is a hallmark feature of PsA. The enthesis, composed of fibrocartilage and collagen type II, is a highly vascular structure aimed to absorb and dissipate mechanical stress and appears to be the primary target in PsA.


  1. The pathogenesis of PsA remains unknown. There is evidence of distinct immunological processes causing persistent skin and synovial inflammation that are not shared with rheumatoid arthritis. A predominance of clonally expanded CD8+ T lymphocytes in both skin and synovial tissue, suggests the presence of a triggering antigen.

    1. The pattern of pro-inflammatory cytokines (TNF-a, IL-1, IL-6, and IL-8), expressed in PsA synovial fluid and surgical explants, is similar to RA, with cytokines expressed in even higher levels. Elevated levels of TNF-a are found in psoriasis in psoriatic plaques and uninvolved skin alike.
    2. Angiogenesis is believed to play a pivotal role in the pathophysiology of PsA synovitis and is controlled by growth factors such as vascular endothelial growth factor (VEGF) and angiopoietins Ang-1 and Ang-2, which in turn may be controlled by cytokines such as TNF-a.
    3. Osteoclast precursors are found in large amounts in the blood of patients with psoriatic arthritis and likely participate in the development of joint damage. Furthermore, marked upregulation of the osteoclastogenesis enhancer RANKL and low expression of its natural antagonist osteoprotegerin (OPG) were detected in psoriatic synovial tissues.

  2. Genetic factors play an important role. First degree relatives of patients with PsA have a 40-50% risk of developing the disease. Concordance between monozygotic twins is high (70%) when compared to RA (30%). HLA-B27 has clearly been associated with axial disease and HLA DR4 with peripheral polyarticular involvement in psoriatic arthritis. CARD15 is the first non-MHC gene that has been recently associated with PsA.

  3. Infectious agents have long been suspected to act as disease triggers

  4. Psoriasis and PsA tend to be more aggressive in HIV infected patients, although the incidence of psoriasis in these patients is not greater than in the general population. HLA associated genes (HLA BW38, BW39, and CW6) are found in frequency similar to that seen in HIV-uninfected patients with PsA. This is in contrast to HIV associated ReA, where frequency of HLA B27 can be higher than 75%.

  5. A history of trauma often precedes the diagnosis of psoriatic arthritis, suggesting the presence of a possible “internal” Koebner phenomenon (the appearance of psoriasis at sites of traumatic cutaneous injury).


Recent community-based epidemiological studies have suggested an incidence rate of approximately 6/100,000 per annum and a prevalence of 1/1000. The male:female ratio is 1:1, and the peak incidence occurred at 45-54 years of age.


  1. Typically, patients present with pain and stiffness of the affected joints, which tend to be less tender than affected joints in RA. Morning stiffness of more than 30 minutes is seen in higher than 50% of patients.

  2. Five distinct patterns of PsA are recognized:

    1. Oligoarticular (four or fewer inflamed joints) disease that constitutes 70% of all cases of PsA, is characteristically asymmetric and affects a few scattered distal interphalangeal (DIP), proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints, knees, ankles and feet. These are often in association with dactylitis, manifested by diffuse swelling of one or more fingers and toes in a sausage digit configuration. This diffuse swelling is not seen in RA and is due to the intense and diffuse inflammatory changes both in joints and soft tissues.
    2. Asymmetric involvement of distal interphalangeal joints of the hands and feet is sometimes referred to as “classic” psoriatic arthropathy, but this pattern appears in as few as 10% of cases. Digits affected often have characteristic psoriatic nail changes.
    3. Arthritis mutilans is a particularly disabling form occurring in about 5% of all cases of PsA. The deformity, most striking in the fingers and toes, is caused by osteolysis of the affected joints.
    4. Symmetric polyarthritis (resembling rheumatoid arthritis) is usually rheumatoid factor negative, and constitutes about 15% of all cases of PsA. Constitutional symptoms such as morning stiffness and fatigue are common and tend to parallel the activity of joint disease.
    5. Psoriatic spondyloarthritis occurs in up to 5% of patients with PsA and presents with clinical and radiographic features of axial and sacroiliac inflammation. This may be indistinguishable from those of reactive arthritis and their involvement tends to be asymmetric as opposed to the symmetric spine and sacroiliac disease of ankylosing spondylitis. The histocompatibility antigen HLA B27 is found in 40% of this group.

  3. Enthesopathy, while unusual in RA, is a primary feature of PsA. Common clinical manifestations of enthesopathy in PsA include plantar fasciitis, epicondylitis, Achilles tendinitis, and enthesitis of the ligamentous insertions around the pelvic bones.

  4. Extra-articular manifestations. Conjuctivitis and uveitis occur in up to one third of patients with PsA. Aortic insufficiency may rarely complicate psoriatic arthritis.

  5. SAPHO syndrome (Synovitis, Acne, Palmoplantar pustulosis (50–60% have this or another form of psoriasis), Hyperostosis, and Osteitis) is often considered a variant of PsA Features in common with PsA include asymmetric synovitis, pustulosis, enthesopathy (e.g. anterior chest pain) and involvement of the sacroiliac joint. However the characteristic constellation of symptoms and the absence of HLA-B27 associated sacroiliitis help differentiate this syndrome. 


  1. Musculoskeletal examination shows all of the cardinal signs of inflammation in the affected peripheral, spine and sacroiliac joints. The most common form of PsA has the characteristic asymmetric pattern of digit involvement. IP joint involvement is often associated with a sausage appearance of the digits (dactylitis). The inflamed joints may have a purplish-red discoloration, a feature rarely seen in RA.

  2. Skin psoriasis may be obvious or may be represented only as an obscure patch on the scalp, umbilicus, elbows, knees or intergluteal fold, dandruff, or nail pitting (onychodystrophy). PsA usually follows well established cutaneous or nail lesions, although some patients exhibit characteristic patterns of PsA in the absence of the characteristic skin lesions (Chapter 16).

  3. Nail changes alone may not be diagnostic but greater than 20 pits is suggestive and more than 60 can be diagnostic of psoriatic arthritis. Nail involvement correlates closely with skin and arthritic changes, especially of the DIP joints. Fungal and bacterial infections can also cause hyperkeratosis and onycholysis, and should be ruled out before attributing nail changes to psoriasis.


    There are no definitive laboratory tests in psoriatic arthritis.

    1. The anemia of chronic disease can occur in PsA, as can thrombocytosis
    2. Erythrocyte sedimentation rate (ESR) and other acute phase reactants are elevated and parallel the activity of the arthritis.
    3. Polyclonal hypergammaglobulinemia and hypercomplementemia are occasionally present and reflect the inflammatory activity. .
    4. Serum uric acid may be elevated in 10-20% of patients with psoriasis as a result of high skin cell turnover.
    5. Antinuclear antibodies and rheumatoid factor tests are usually negative.
    6. HLA markers are rarely sought.


    1. Radiographic features considered classic are the erosions involving predominantly the DIP joints of fingers and the IP joints of the toes. Bony ankylosis of the DIP joints of the hand and toes, along with bony proliferation of the base of the distal phalanx, and resorption of the tufts of the distal phalanges of hands and feet are also commonly seen. These are quite distinct from the changes seen in RA.
    2. Fluffy periostitis of large joints, ‘‘pencil in cup’’ appearance of DIP joints, absence of symmetry, and gross destruction of isolated small joints. Changes in the spine and sacroiliac (SI) joints may be similar to those seen in ankylosing spondylitis, but SI joint and spine changes in PsA are often unilateral.
    3. MRI may be more sensitive than plain radiographs in detecting enthesitis and early articular and periarticular involvement. Sacroiliitis detected by MRI correlates with restricted spinal movement and longer duration of PsA. MRI evidence of increased water content in the bone marrow, known as “bone edema”, is frequently found in PsA (and other inflammatory spondyloarthropathies) and is thought to be a “forerunner” of erosions. These abnormalities do improve after therapy with anti-TNF medications.


  1. The cutaneous lesions of reactive arthritis (ReA) often resemble pustular psoriasis. ReA usually affects large joints and infrequently involves the DIP joints or produces sausage digits. The incidence of HLA B27 is higher in ReA. In radiographs, ReA may demonstrate periostitis of the plantar surfaces of the calcaneus, metatarsal bones, or ankles. In PsA, periostitis is usually limited to the long bones.

  2. PsA should be differentiated from gout by the absence of monosodium urate crystals in the synovial fluid. Hyperuricemia may occur in up to 20% of patients with skin psoriasis but is uncommon during acute flares of PsA. In contrast to monarticular PsA, acute gouty arthritis usually resolves completely in 1– 2 weeks, even if left untreated. Occasionally the two conditions may coexist.

  3. Frequently confused with rheumatoid arthritis, PsA can be differentiated on the basis of distinct clinical (dactylitis, onycholysis, spondylitis, sacroiliitis, asymmetrical joint involvement, DIP involvement and psoriatic skin plaques), serologic (usual absence of rheumatoid factor elevation), and radiologic characteristics, including bony proliferation and osteolysis at tendon, ligament, and capsular insertions (entheses). Because both RA and psoriasis are common, they can co-exist. At times it is difficult to differentiate RA from PsA and that does not lead to therapeutic problems because their treatment is quite similar. See Table 41-1.

Table 41-1
Comparison between Psoriatic Arthritis and Rheumatoid Arthritis

Disease Characteristics PsA RA
Female preponderance - ++
DIP joint involvement ++ -
Symmetric joint involvement +/- ++
Erythema over affected joint ++ -
Sacroiliitis ++ -
Spondylitis + -
Enthesopathy ++ -
Skin lesions ++ -
Nail lesions ++ -
Dactylitis ++ -
Rheumatoid factor - ++
Osteopenia + ++
Osteopenia ++ -
Ankylosis ++ -

(-) not seen; (+/-) uncommon; (+) common; (++) very common
Adapted from Gladman D. Psoriatic Arthritis. Oxford Textbook of Rheumatology. 3rd ed.; 2004


  1. The treatment of PsA includes therapies that often work for both the skin condition and the joint disease. Rheumatologists and dermatologists need to approach the disease as a team with close collaboration for optimal results. This has been especially true after the introduction of biologic medication that have the capacity to induce remission in both psoriasis and PsA and the new paradigm of early aggressive therapy in order to arrest radiographic progression and functional limitation.

  2. The skin lesions are treated by topical medications, aimed at controlling the inflammation and skin proliferation, including tar, anthralin, vitamin D ointment and topical corticosteroids. In refractory cases, systemic medications such as methotrexate (MTX), PUVA (psoralen and ultraviolet A light), retinoic acid derivatives, cyclosporin and more recently biologic agents (TNF-inhibitors and co-stimulation blockers) are employed.

  3. NSAIDS (and selective COX-2 inhibitors) are effective in controlling mild inflammatory of PsA. However, no systematic trials exist about their use in PsA and there are no comparative studies to help the clinician select a specific compound. NSAIDs do not modify the course of the disease, nor do they prevent erosions, although they can be effective in ameliorating symptoms. They are used in conjunction with DMARDs that are begun soon after the diagnosis.

  4. DMARDs are used soon after the diagnosis is made. Combining two DMARDs (usually methotrexate with cyclosporin) can be effective even in patients unresponsive to either drug alone.

    1. Methotrexate (MTX) is the most widely used DMARD in PsA, because it is effective for skin and arthritic symptoms, fast acting and well tolerated. Concerns about severe liver disease resulting from methotrexate therapy from the early reports of its use in psoriasis seem to have been alleviated since more judicious use of folic or folinic acid has become commonplace and the weekly dose schedule is universal. Frequent monitoring of liver function tests and albumin and a liver biopsy after a cumulative dose of 1.5 grams or 4-5 years of therapy is still indicated. This is despite the American College of Rheumatology guidelines that do not recommend such a biopsy in RA patients unless there are persistent abnormalities in the above mentioned liver tests. This reflects the feeling that the presence of psoriasis changes the liver toxicity equation towards a potentially greater propensity for methotrexate-related liver damage.
    2. Cyclosporin A works well for skin and joint disease as well, but toxicity limits its usefulness. Careful observation of blood pressure and serum BUN/creatinine is essential.
    3. Sulfasalazine, leflunomide, azathioprine, mycophenolate mofetil, antimalarials, and gold have been used with modest effectiveness in PsA, Sulfasalazine may be used in HIV patients with PsA.

  5. Biologic agents have revolutionized the therapy of skin psoriasis and psoriatic arthritis alike. Advances in the understanding of immune mechanisms that contribute to the pathophysiology of PsA have allowed the targeting of specific components of the immune response. As a result a new class of therapeutic agents has emerged that is highly efficacious in treating symptoms (skin and joint), arresting disease progression and improving quality of life. Currently, biologic agents are divided in two broad categories (Table 41-2):

    1. TNF-inhibitors (etanercept, infliximab, adalimumab). Etanercept was the first anti-TNF agent to be approved in the US for the treatment of both psoriasis and PsA. In psoriasis it is used in higher doses (50 mg subcutaneous twice weekly) during the first three months of therapy before switching to the standard dose of 25 mg twice weekly. Infliximab and adalimumab are currently in advanced clinical trials. The effect of TNF blockade in PsA has been very dramatic, surpassing at times the therapeutic effect in RA.
    2. Co-stimulation inhibitors (alefacept, efalizumab) have both been approved for the treatment of severe skin disease and are undergoing trials for their use in PsA.

      1. Alefacept, an LFA-3/IgG1 fusion protein, blocks the interaction between CD2 on T lymphocytes and LFA-3 on antigen presenting cells (APC). It also causes apoptosis of T lymphocytes through mediation between NK and T cells. It is administered as an intramuscular injection (15mg) weekly for 12 weeks with close monitoring of the peripheral blood CD4 count (must be >250 cells/mL)
      2. Efalizumab is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1 expressed on T lymphocytes, preventing its interaction with ICAM-1 (upregulated in psoriasis), expressed on APCs, keratinocytes, endothelial cells, and fibroblasts. Block of co-stimulation causes loss of leukocyte function.

  6. Second line therapies:

    1. Systemic corticosteroids have limited application in the management of PsA but can effective for the control of acute flares.. For patients with oligoarticular disease, where disability results from involvement of one or a few joints, intraarticular steroid therapy may be preferred to systemic use.
    2. Retinoic acid derivatives (etretinate) in open trials showed some benefit but take longer to act in joint disease (3-4 months) than other therapies. Etretinate cannot be used in women of childbearing age. Side effects include mucocutaneous lesions (dryness), and proximal arthralgias. They should be avoided in axial disease, since extra-spinal calcifications can develop.
    3. Photochemotherapy with methoxypsoralen and long wave ultraviolet A light (PUVA) may benefit a group of non-spondylitic patients with synchronous joint and skin flares.

  7. Physical therapy is used as an adjunct to drug therapy to help preserve joint range of motion and minimize muscle weakness.

  8. Reconstructive surgery is of value in patients with end stage joint destruction.

Table 41-2
Treatment of Psoriatic Arthritis with Biologic Agents

TNF-a Inhibition Infliximab: chimeric (75% human, 25% mouse) mAb targeting TNFa, improves both synovitis and skin disease. It is administered as an intravenous infusion in conjunction with oral MTX, initially at weeks 0, 2, 6, and every 4-8 weeks thereafter.
Etanercept: human p75 TNF receptor/IgG1 fusion protein neutralizes both TNFa and TNFß (lymphotoxin). Improves both skin psoriasis and PsA.
Adalimumab: Humanized mAb targeting TNFa. It is administered as a sc injection every week or every other week.
Costimulation Inhibition Alefacept: is a human LFA-3/IgG1 fusion protein, which binds to the CD2 receptor on T cells, thereby selectively depleting CD45RO+ memory-effector T-cells, approved for severe skin disease, worked for PsA in a small open trial and currently undergoing RCT.
Efalizumab: humanized mAb disrupts the T cell costimulatory LFA-1-ICAM-1 interaction. It is approved for severe skin psoriasis and is currently undergoing trials for PsA indication.


The prognosis for patients with PsA generally varies according to the anatomic pattern:

  1. Most patients have mild, localized disease, affecting only a few joints. For these patients the prognosis is generally favorable.

  2. Approximately 20% of patients develop severe disabling and deforming arthritis. Adverse prognostic features during the first clinic visit include effusion in more than 5 joints and high rate of previous DMARD use, while a low ESR seemed to be protective. 

  3. The axial spondyloarthropathy of PsA is associated with many of the same extraarticular manifestations seen in idiopathic ankylosing spondylitis (uveitis, conduction defects, and aortitis). These features may significantly contribute to morbidity. Only anti-TNF medications appear to improve the spinal and sacroiliac joint inflammation.

  4. Complications of therapy, especially corticosteroids, have been a contributing factor to mortality in several large series. Patients with severe disease may have increased mortality risk.

  5. The new biologics utilized in the treatment of PsA are likely to have a profound effect on prognosis in the upcoming years, offering highly efficacious disease management with rare, albeit potentially serious, side effects. Because of the disadvantage of increased cost, criteria should be established to identify early the patients with severe disease who will benefit the most from these agents.
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