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PSORIATIC ARTHRITIS
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Psoriatic Arthritis

Introduction

Background

In 1964, the American Rheumatism Association listed psoriatic arthritis as a clinical entity. However, diagnostic criteria have not been agreed on, and several proposed definitions have stressed separate features of this multifaceted disease.

The high frequency of distal joint involvement in psoriatic arthritis compared with rheumatoid arthritis (RA) and arthritis mutilans (as an unusual but characteristic manifestation) has received special attention. The great variety of clinical manifestations was framed in the definition suggested by Moll and Wright in 1973, ie, "An inflammatory arthritis associated with psoriasis, usually with a negative sheep cell agglutination (SCA) test, ie, rheumatoid factor."

Other more detailed criteria have been suggested. Psoriatic arthritis, a term used by the American Rheumatism Association, is widely accepted.

Pathophysiology

Psoriatic arthritis is an autoimmune disease with known human leukocyte antigen (HLA)–associated risk factors. Psoriatic arthritis affects the ligaments, tendons, fascia, and joints and occasionally develops in the absence of detectable psoriasis. Psoriatic arthritis may occur at higher frequencies when skin involvement is more severe, especially when pustular psoriasis is present; however, recent studies suggest that this may not be valid.

Frequency

United States

Psoriasis affects 2.5% of the white population of North America but is less prevalent in the African American and Native American populations. Psoriatic arthritis affects 5-8% of patients with psoriasis.

Recent survey results indicate approximately 1 million US adults have psoriatic arthritis. This figure is significantly higher than researchers had previously believed and suggests many people with psoriasis, a related skin disease, may not be aware that they have psoriatic arthritis. (This is according to a new study conducted by the National Psoriasis Foundation).

International

Estimated rates of the frequency of psoriatic arthritis in persons with all types of psoriasis vary widely according to the nature of the diagnostic criteria and ascertainment used, but most fall into the range of 5-8%. Considering the rate of psoriasis to be 1-3%, the rate of psoriatic arthritis in the general white population ranges from 0.05-0.24%, a value approaching half that for seropositive RA.

Mortality/Morbidity

The course of psoriatic arthritis is usually characterized by flares and remissions. Arthritis mutilans is recognized as a typical but unusual form of psoriatic arthritis. Earlier studies have reported that psoriatic arthritis results in joint destruction and severe disability in a large proportion of patients. Of patients observed in a large outpatient psoriatic arthritis clinic, 7% required musculoskeletal surgery.

Race

Psoriatic arthritis is more common in white persons than in persons of other races.

Sex

Men and women are affected equally; however, if the subsets of psoriatic arthritis are considered, male predominance occurs in the spondylitic form, whereas female predominance occurs in the rheumatoid form.

Age

Psoriatic arthritis characteristically develops in persons aged 35-55 years, but it can occur in persons of almost any age.

Clinical

History

Psoriatic arthritis may be present with or without obvious skin lesions, with minimal skin involvement (eg, scalp, umbilicus, intergluteal cleft), or with only nail malformations. Psoriasis usually precedes arthritis (occasionally by as many as 20 y); however, in as many as 15-20% of patients, arthritis appears before the psoriasis. If the latter is the case, a family history of psoriasis may reveal a hereditary pattern.

Initial symptoms may be acute. When localized to the foot or toe, symptoms may be mistaken for gout. Alternatively, patients may experience only stiffness and pain with few objective findings.

The following list details the 5 patterns of psoriatic arthritis involvement:

  • Asymmetrical oligoarticular arthritis  
    • Until recently, this was thought to be the most common type.
    • Usually, the digits of the hands and feet are affected first, with inflammation of the flexor tendon and synovium occurring simultaneously, leading to the typical "sausage" appearance (dactylitis).
    • Usually, fewer than 5 joints are affected at any one time.
  • Symmetrical polyarthritis  
    • Recently, this rheumatoidlike pattern has been recognized as one of the most common types. The hands, wrists, ankles, and feet may be involved.
    • It is differentiated from rheumatoid arthritis (RA) by the presence of distal interphalangeal (DIP) joint involvement, the relative asymmetry, the absence of subcutaneous nodules, and a negative test result for rheumatoid factor (RF). This condition generally is milder than RA, with less deformity.
  • Distal interphalangeal arthropathy  
    • Although DIP joint involvement is considered classic and unique to psoriatic arthritis, it occurs in only 5-10% of patients, primarily men.
    • Involvement of the nail with significant inflammation of the paronychia and swelling of the digital tuft may be prominent, occasionally making appreciation of the arthropathy more difficult.
  • Arthritis mutilans  
    • Resorption of bone (osteolysis) with dissolution of the joint, observed as the "pencil-in-cup" radiographic finding, leads to redundant overlying skin with a telescoping motion of the digit.

      Arthritis mutilans, a typically psoriatic pattern...

      Arthritis mutilans, a typically psoriatic pattern of arthritis, which is associated with a characteristic "pencil-in-cup" radiographic appearance of digits.

    • This "opera-glass hand" is more common in men than in women and is more frequent in early-onset disease.
  • Spondylitis with or without sacroiliitis
    • This occurs in approximately 5% of patients with psoriatic arthritis and has a male predominance.
    • Clinical evidence of spondylitis, sacroiliitis, or both can occur in conjunction with other subgroups of psoriatic arthritis.
    • Spondylitis may occur without radiologic evidence of sacroiliitis, which frequently tends to be asymmetric, or it may appear radiologically without the classic symptoms of morning stiffness in the lower back. Thus, the correlation between symptoms and radiologic signs of sacroiliitis can be poor.
    • Vertebral involvement differs from that observed in ankylosing spondylitis. Vertebrae are affected asymmetrically, and the atlantoaxial joint may be involved with erosion of the odontoid and subluxation.
    • Unusual radiologic features may be present, such as nonmarginal asymmetric syndesmophytes (characteristic), paravertebral ossification, and, less commonly, vertebral fusion with disk calcification.
  • Juvenile psoriatic arthritis  
    • Juvenile psoriatic arthritis accounts for 8-20% of childhood arthritis and is monoarticular at onset.
    • The mean age of onset is 9-10 years, with a female predominance. The disease is usually mild, although occasionally it may be severe and destructive, progressing into adulthood.
    • In 50% of children, the arthritis is monoarticular; DIP joint involvement occurs at a similar rate.
    • Tenosynovitis is present in 30% of children, and nail involvement is present in 71%, with pitting being the most common but least specific finding.
    • In 47% of children, disordered bone growth with resultant shortening may result from involvement of the unfused epiphyseal growth plate by the inflammatory process.
    • Sacroiliitis occurs in 28% of children and is usually associated with HLA-B27 positivity.
    • Although the presence of HLA-B8 may be a marker of more severe disease, HLA-B17 is usually associated with a mild form of psoriatic arthritis.
    • Children have a higher frequency of simultaneous onset of psoriasis and arthritis than adults, with arthritis preceding psoriasis in 52% of children.

Physical

Recognition of the patterns of joint involvement as described in History is essential to the diagnosis of psoriatic arthritis.

  • Recently, the possibility that less joint tenderness occurs with psoriatic arthritis than with RA has been emphasized.
  • The condition termed enthesopathy or enthesitis, reflecting inflammation at tendon or ligament insertions into bone, may be seen in psoriatic arthritis as in other spondyloarthropathies. This is observed more often at the attachment of the Achilles tendon and the plantar fascia to the calcaneus with the development of insertional spurs.
  • Dactylitis with sausage digits is seen in as many as 35% of patients.
  • Skin involvement includes the following:  
    • Arthritis generally is not considered to correlate strongly to any particular type of psoriasis or to the severity of the skin disease. However, in one study, arthritis was noted more frequently in patients with severe skin disease, whereas in another, pustular psoriasis was associated with more severe psoriatic arthritis.
    • In patients presenting with an undefined seronegative polyarthritis, looking for psoriasis in hidden sites such as the scalp (where psoriasis frequently is mistaken for dandruff), perineum, intergluteal cleft, and umbilicus is extremely important.
    • A diagnosis of psoriatic arthritis may be missed because of an inadequate physical examination.
  • Nail involvement includes the following:  
    • Onycholysis, transverse ridging, and uniform nail pitting are 3 features of nail involvement that should be noted. A direct correlation exists between the number of pits and the diagnostic significance. When skin and joint disease begin simultaneously, nail involvement is frequently present at the onset.
    • Involvement of DIP joints correlates moderately well with psoriasis in adjacent nails, although this is not an invariable association.
    • Nails are involved in 80% of patients with psoriatic arthritis but in only 20% of patients with uncomplicated psoriasis.
    • Severe deforming arthritis of the hands and feet is frequently associated with extensive nail involvement.
    • Fungal infection of the nails is the main consideration in the differential diagnosis in a patient with a seronegative polyarthritis.
  • Extra-articular features include the following:  
    • Extra-articular features are observed less frequently in patients with psoriatic arthritis than in those with RA. Patients with psoriatic arthritis have a predilection for synovitis to affect flexor tendon sheaths with sparing of the extensor tendon sheath; both are commonly involved in persons with RA. Subcutaneous nodules are rare in patients with psoriatic arthritis. If nodules are present in a patient who has psoriasis and arthritis, particularly if the RF titer is positive, they suggest the coincidental occurrence of psoriasis and RA.
    • Ocular involvement may occur in 30% of patients with psoriatic arthritis, including conjunctivitis in 20% and acute anterior uveitis in 7%. In patients with uveitis, 43% have sacroiliitis and 40% are HLA-B27–positive. Scleritis and keratoconjunctivitis sicca are rare.
    • Inflammation of the aortic valve root, which may lead to insufficiency, has been described in 6 patients with psoriatic arthritis and is similar to that observed more frequently in persons with ankylosing spondylitis or Reiter syndrome. Occasionally, patients may develop secondary amyloidosis.
  • A large international study group recently developed a simple and highly specific classification known as CASPAR (classification criteria for psoriatic arthritis).1 These criteria were more specific (98.7% vs 96%) but less sensitive (91.4% vs 97.2%) than those of Vasey and Espinoza classification. The CASPAR criteria consist of established inflammatory articular disease with at least 3 points from the following features: 
    • Current psoriasis (assigned a score of 2)
    • A history of psoriasis (in the absence of current psoriasis; assigned a score of 1)
    • A family history of psoriasis (in the absence of current psoriasis and history of psoriasis; assigned a score of 1)
    • Dactylitis (assigned a score of 1)
    • Juxtaarticular new-bone formation (assigned a score of 1)
    • RF negativity (assigned a score of 1)
    • Nail dystrophy (assigned a score of 1)

Causes

The pathogenesis of psoriatic arthritis remains unknown, but much information has been gathered. In addition to the genetic influences, environmental and immunological factors are thought to be prominent in the development and perpetuation of the disease. The de novo development or exacerbation of psoriasis and psoriatic arthritis in patients with human immunodeficiency virus (HIV) infection and CD4 deficiency remains controversial.

Psoriasis may remit following allogeneic bone marrow transplantation and may exacerbate with interferon-alfa treatment for hepatitis C.

  • Genetics
    • Approximately 40% of patients with psoriasis or psoriatic arthritis have a family history of these disorders in first-degree relatives. The exact mechanism of the association between HLA and psoriatic arthritis is not clear.
    • Twin studies indicate a concordance rate among monozygotic twins of 35-70%, compared with 12-20% for dizygotic twins.
    • HLA-B17, -Cw6, -DR4, and -DR7 are found to occur with increased frequency in persons with either psoriasis or psoriatic arthritis when compared with the general population. The HLA-Cw*0602 variant is particularly associated with an early age of onset of psoriasis.
    • Psoriatic arthritis is associated with an increased frequency of HLA-B7 and HLA-B27 and a lower frequency of HLA-DR7 and HLA-Cw7.
    • HLA-B27 in the presence of HLA-DR7, HLA-DQ3 in the absence of HLA-DR7, and HLA-B39 are predictors for disease progression, whereas HLA-B22 is protective.
    • Additional loci that demonstrate association with psoriatic arthritis include the MICA (class I MHC chain-related) gene and microsatellite polymorphisms in the tumor necrosis factor (TNF) promoter.
    • In psoriasis, linkages with loci on 17q, 4q, and 6p have been reported in whole genome scans, with the strongest evidence for linkage on 6p.
  • Immunologic factors
    • Certain immunoglobulin genes have also been suggested to be associated with psoriatic arthritis. Serum levels of immunoglobulin A and immunoglobulin G are higher in psoriatic arthritis patients, whereas immunoglobulin M levels may be normal or diminished.
    • Autoantibodies against nuclear antigens, cytokeratins, epidermal keratins, and heat-shock proteins have been reported in persons with psoriatic arthritis, indicating a humoral immune component of the disease.
    • The pathologic process of skin and joint lesions in psoriatic arthritis is an inflammatory reaction, and evidence also indicates autoimmunity, perhaps mediated by complement activation. The inflammatory nature of the skin and joint lesions in psoriatic arthritis is demonstrated by synovial-lining cell hyperplasia and mononuclear infiltration, resembling the histopathologic changes of RA. However, synovial-lining hyperplasia is less, macrophages are fewer, and vascularity is greater in psoriatic arthritis compared with RA synovium.
    • The cytokine profile for psoriatic arthritis reflects a complex interplay between T cells and monocyte macrophages. Type 1 helper T–cell cytokines (eg, TNF-alpha, interleukin [IL]–1 beta, IL-10) are more prevalent in psoriatic arthritis than in RA, suggesting that these 2 disorders may result from a different underlying mechanism.
    • Several studies have shown a significant reduction in the number and percentage of CD4+ T cells in the peripheral blood, whereas they are found throughout the skin lesions and synovium.
    • Dendritic cells have been found in the synovial fluid of patients with psoriatic arthritis and are reactive in the mixed leukocyte reaction; the inference is that the dendritic cells present an unknown antigen to CD4+ cells within the joints and skin of patients with psoriatic arthritis, leading to T-cell activation.
    • Fibroblasts from the skin and synovia of patients with psoriatic arthritis have an increased proliferative activity and the capability to secrete increased amounts of IL-1, IL-6, and platelet-derived growth factors. Several studies suggest that cytokines secreted from activated T cells and other mononuclear proinflammatory cells induce proliferation and activation of synovial and epidermal fibroblasts.
    • Psoriatic plaques in skin have increased levels of leukotriene B4. Injections of leukotriene B4 cause intraepidermal microabscesses, suggesting a role for this compound in the development of psoriasis.
  • Infections
    • The temporal relationship between certain viral or bacterial infections and the development or exacerbation of psoriasis or psoriatic arthritis suggests a possible pathogenetic role for these organisms.
    • Pustular psoriasis is a well-described sequela of streptococcal infections. However, the response to streptococcal antigens by cells from patients with psoriatic arthritis is not different from that of cells from patients with RA, making the role of Streptococcus species in psoriatic arthritis doubtful.
    • Psoriasis and psoriatic arthritis have been reported to be associated with HIV infection and to be prevalent in some HIV-endemic areas. Although the prevalence of psoriasis in patients infected with HIV is similar to that in the general population, patients with HIV infection usually have more extensive erythrodermic psoriasis and patients with psoriasis may present with exacerbation of their skin disease after being infected with HIV.
  • Trauma: A few studies have reported the occurrence of arthritis and acroosteolysis after physical trauma in patients with psoriasis.

Differential Diagnoses

Gout
Osteoarthritis
Reactive Arthritis
Rheumatoid Arthritis
Septic Arthritis

Other Problems to Be Considered

Psoriasiform skin lesions may be observed in association with Reiter disease, inflammatory bowel disease, and the syndrome of inappropriate secretion of diuretic hormone.

Workup

Laboratory Studies

  • No specific diagnostic tests are available for psoriatic arthritis. Diagnosis of the disease is made based on clinical and radiologic criteria in a patient with psoriasis.  
    • The most characteristic laboratory abnormalities in patients with psoriatic arthritis are elevations of the erythrocyte sedimentation rate (ESR) and C-reactive protein level. The results from these laboratory tests help track the activity of the disease by measuring inflammation. An elevated ESR is usually found in approximately 40% of patients with psoriatic arthritis.
    • Patients with psoriatic arthritis are typically seronegative for RF, although RF is detected in 5-9% of patients. RF testing is usually associated with a high false-positive rate; thus, RF-positive and RF-negative patients should undergo the same treatment.
    • Antinuclear antibody titers in persons with psoriatic arthritis do not differ from those of age- and sex-matched control populations. In 10-20% of patients with generalized skin disease, the serum uric acid concentration may be increased and, on occasion, may predispose to acute gouty arthritis. Low levels of circulating immune complexes have been detected in 56% of patients with psoriatic arthritis but do not appear to parallel disease activity.
    • The associations of psoriatic arthritis with HLA-B17, -Cw6, -DR4, and -DR7 are described inGenetics. Serum immunoglobulin A levels are increased in two thirds of patients with psoriatic arthritis and in one third of patients with psoriasis.
    • Synovial fluid is inflammatory, with cell counts ranging from 5000-15,000/µL and with more than 50% of cells being polymorphonuclear leukocytes. Within the synovium, the infiltrate consists predominantly of T lymphocytes. Synovial fluid complement levels are either within reference ranges or increased, and glucose levels are within reference ranges.

Imaging Studies

  • Radiological features have helped to distinguish psoriatic arthritis from other causes of polyarthritis. In general, the common subtypes of psoriatic arthritis, such as asymmetric oligoarthritis and symmetric polyarthritis, tend to result in only mild erosive disease. Early bony erosions occur at the cartilaginous edge, and, initially, cartilage is preserved, with maintenance of a normal joint space.
  • Juxta-articular osteopenia, which is a hallmark of rheumatoid arthritis (RA), is minimal in persons with psoriatic arthritis. Asymmetric erosive changes in the small joints of the hands and feet are typical of psoriatic arthritis and have a predilection (in decreasing order) for DIP, proximal interphalangeal, metatarsophalangeal, and metacarpophalangeal joints.
  • Erosive disease frequently occurs in patients with either DIP involvement or progressive deforming arthritis and may lead to subluxation and, less commonly, bony ankylosis of the joint. Erosion of the tuft of the distal phalanx, and even the metacarpals or metatarsals, can progress to complete dissolution of the bone. Although this form of acroosteolysis is not diagnostic, it is highly suggestive of psoriatic arthritis. The pencil-in-cup deformity observed in the hands and feet of patients with severe joint disease usually affects the DIP joints but also may involve the proximal interphalangeal joints.

    Arthritis mutilans (ie, "pencil-in-cup" deformiti...

    Arthritis mutilans (ie, "pencil-in-cup" deformities).

  • CT scanning of the sacroiliac joint may be a sensitive method of visualizing involvement in patients with spondylitis or sacroiliitis.
  • Recent studies have indicated that MRI may be a sensitive method for demonstrating the typical enthesopathic pathology of psoriatic arthritis, particularly in the hands and feet.

Other Tests

  • Traditional methods of monitoring patients with rheumatic conditions include clinical assessment for joint inflammation or damage and radiographic evaluations. The radiologic scoring methods for evaluating peripheral joints in persons with psoriatic arthritis were developed for patients with RA. A study validated the original Steinbrocker method, a modified Steinbrocker method, and the Larsen method for assessment of radiographs in patients with psoriatic arthritis. The latter 2 methods can now be used to assess disease progression in patients with psoriatic arthritis.

Histologic Findings

The histopathology of psoriatic synovitis is similar to that observed in other inflammatory arthritides, with a notable lack of intrasynovial immunoglobulin and RF production and a greater propensity for fibrous ankylosis, osseous resorption, and heterotopic bone formation.

 
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