Psoriatic Arthritis: The Entity

Psoriatic arthritis is an inflammatory musculoskeletal disease associated with psoriasis that is usually seronegative for rheumatoid factor. Although the occurrence of arthritis among patients with psoriasis has been known since the nineteenth century, psoriatic arthritis was initially considered a variant of rheumatoid arthritis. It was defined as an entity separate from rheumatoid arthritis primarily because of the efforts of Wright in the late 1950s and 1960s, and Moll and Wright in the 1970s. It was accepted as an entity by the American Rheumatology Association (now the American College of Rheumatology) in 1964.

Psoriatic arthritis affects men and women equally, usually during the fourth decade, although it may affect children and octogenarians. Most (70%) patients with psoriatic arthritis develop their arthritis after the onset of psoriasis. About 15% develop the skin and joint manifestations simultaneously. However, in some 15% of cases, the arthritis precedes the onset of psoriasis. Although it is possible that in many of these cases the psoriasis were missed because a careful search for hidden lesions was not performed, there are patients whose arthritis begins long before the onset of psoriasis. In these cases, the diagnosis becomes difficult, and physicians rely on the clinical features unique to psoriatic arthritis (discussed later) to make the diagnosis.

Prevalence of Psoriatic Arthritis

The prevalence of psoriatic arthritis is unknown. Estimates from population studies have ranged from 0.01% in China to 0.47% in Australian Aborigines ( Table 1 ). It is difficult to compare these prevalence data because the methodologies in studies are varied, from small population areas to large administrative databases. Some are based on patient report, others on physician observation. Moreover, the diagnosis of psoriatic arthritis may be difficult, and classification criteria have not been universally accepted until the recent Classification of Psoriatic Arthritis (CASPAR) criteria.

The prevalence of psoriatic arthritis among patients with psoriasis has also varied, from 6.25% in a study from the Mayo Clinic to 48% from a Swedish study ( Table 2 ). Because it is estimated that psoriasis occurs in 1% to 3% of the population, and the frequency of psoriatic arthritis is about 30%, it is possible that the frequency of psoriatic arthritis is between 0.3% and 1%.

Genetic Factors

There is strong evidence for familial clustering of both psoriasis and psoriatic arthritis. Twin studies show a higher concordance rate for psoriasis among monozygotic than dizygotic twins, and family studies have shown that there is a recurrence risk ratio of 4 to 10. Although a higher concordance rate was seen for psoriatic arthritis, the number of twins with this disease was low, and it was not statistically significant. Recurrence risk ratio for psoriatic arthritis is higher than for psoriasis alone, with λ ₁ of 30. Linkage studies have identified several susceptibility loci for psoriasis, including the human leukocyte antigen (HLA) locus on chromosome 6p (PSORS1), and loci on 17q (PSORS2), 4q (PSORS2), 1q (PSORS 4), 3q (PSORS5), 19p (PSORS6), 1p (PSROS7), 16q (PSORS8), 4q (PSROS9), and 18p (PSROS10). The strongest association is with a locus within the major histocompatibility complex (MHC). Only 1 genome-wide linkage scan has been reported for psoriatic arthritis identifying a locus on 16q close to the PSORS8 locus. Genome-wide association scans in psoriatic arthritis revealed associations with HLA-C, IL12B, and TNIP1, as well as with a locus on chromosome 2p. The differences between psoriasis and psoriatic arthritis have been difficult to interpret from genome-wide scans because not all patients with psoriasis were reviewed to ascertain the absence of psoriatic arthritis.

A comparison of HLA alleles between patients with psoriasis confirmed by a rheumatologist not to have psoriatic arthritis and patients with psoriatic arthritis identified that HLA-B*08, HLA-B*38, and HLA*B-27 were increased among patients with psoriatic arthritis, whereas HLA-C*0602 was higher among patients with psoriasis without arthritis.

Environmental Factors

There is also evidence that environmental factors are important in the development of psoriatic arthritis among patients with psoriasis. A recent study that compared patients with psoriatic arthritis with those with psoriasis who were confirmed not to have psoriatic arthritis by a rheumatologist revealed that infections requiring antibiotics, and trauma, were associated with the presence of psoriatic arthritis, suggesting that these factors are important in the development of psoriatic arthritis. Smoking was found to be protective, and the mechanism for that is currently under investigation.

Immunologic Factors

Several immunologic abnormalities have been detected among patients with psoriasis and psoriatic arthritis. The presence and activated state of both CD8+ T cells and natural killer (NK) cells in the psoriatic synovium and the response of the disease to immunomodulatory therapy indicate that the immune system, especially the lymphocytes, play an important role in the pathogenesis of psoriatic arthritis. It has been suggested that that autoimmunity directed against a common skin and joint autoantigen(s) leads to chronic autoreactive T-cell driven inflammation. Prior response to exogenous ligands encoded by pathogens, as well as prior episodes of inflammation, result in expansion of memory effector CD8+ T cells that recognize stress-related self-antigens and initiates and maintains pathways of inflammation mediated by the expression of transcription factors such as nuclear factor-κB and activator protein-1, resulting in skin and synovial inflammation. This model combines the genetic factors as well as possible environmental factors. Again, whether the same or different mechanisms operate in the development of joint versus skin disease is unclear.

Whatever the mechanism, the inflammation leads to synovial proliferation, release of cytokines, and subsequent joint destruction.

Genetic Factors

There is strong evidence for familial clustering of both psoriasis and psoriatic arthritis. Twin studies show a higher concordance rate for psoriasis among monozygotic than dizygotic twins, and family studies have shown that there is a recurrence risk ratio of 4 to 10. Although a higher concordance rate was seen for psoriatic arthritis, the number of twins with this disease was low, and it was not statistically significant. Recurrence risk ratio for psoriatic arthritis is higher than for psoriasis alone, with λ ₁ of 30. Linkage studies have identified several susceptibility loci for psoriasis, including the human leukocyte antigen (HLA) locus on chromosome 6p (PSORS1), and loci on 17q (PSORS2), 4q (PSORS2), 1q (PSORS 4), 3q (PSORS5), 19p (PSORS6), 1p (PSROS7), 16q (PSORS8), 4q (PSROS9), and 18p (PSROS10). The strongest association is with a locus within the major histocompatibility complex (MHC). Only 1 genome-wide linkage scan has been reported for psoriatic arthritis identifying a locus on 16q close to the PSORS8 locus. Genome-wide association scans in psoriatic arthritis revealed associations with HLA-C, IL12B, and TNIP1, as well as with a locus on chromosome 2p. The differences between psoriasis and psoriatic arthritis have been difficult to interpret from genome-wide scans because not all patients with psoriasis were reviewed to ascertain the absence of psoriatic arthritis.

A comparison of HLA alleles between patients with psoriasis confirmed by a rheumatologist not to have psoriatic arthritis and patients with psoriatic arthritis identified that HLA-B*08, HLA-B*38, and HLA*B-27 were increased among patients with psoriatic arthritis, whereas HLA-C*0602 was higher among patients with psoriasis without arthritis.

Environmental Factors

There is also evidence that environmental factors are important in the development of psoriatic arthritis among patients with psoriasis. A recent study that compared patients with psoriatic arthritis with those with psoriasis who were confirmed not to have psoriatic arthritis by a rheumatologist revealed that infections requiring antibiotics, and trauma, were associated with the presence of psoriatic arthritis, suggesting that these factors are important in the development of psoriatic arthritis. Smoking was found to be protective, and the mechanism for that is currently under investigation.

Immunologic Factors

Several immunologic abnormalities have been detected among patients with psoriasis and psoriatic arthritis. The presence and activated state of both CD8+ T cells and natural killer (NK) cells in the psoriatic synovium and the response of the disease to immunomodulatory therapy indicate that the immune system, especially the lymphocytes, play an important role in the pathogenesis of psoriatic arthritis. It has been suggested that that autoimmunity directed against a common skin and joint autoantigen(s) leads to chronic autoreactive T-cell driven inflammation. Prior response to exogenous ligands encoded by pathogens, as well as prior episodes of inflammation, result in expansion of memory effector CD8+ T cells that recognize stress-related self-antigens and initiates and maintains pathways of inflammation mediated by the expression of transcription factors such as nuclear factor-κB and activator protein-1, resulting in skin and synovial inflammation. This model combines the genetic factors as well as possible environmental factors. Again, whether the same or different mechanisms operate in the development of joint versus skin disease is unclear.

Whatever the mechanism, the inflammation leads to synovial proliferation, release of cytokines, and subsequent joint destruction.

Peripheral Arthritis

Psoriatic arthritis affects the peripheral joints of the hands and feet in most patients. The arthritis is inflammatory in nature, and there is prolonged morning stiffness in about half the patients ( Fig. 1 ). There is improvement of the pain and stiffness with activity and worsening with rest. Unlike rheumatoid arthritis, the inflamed joints in psoriatic arthritis have a purplish discoloration. At onset, the arthritis tends to be oligoarticular, involving 4 or fewer joints, and asymmetric. Although all joints may be affected by psoriatic arthritis, at least 53% of patients have distal joint involvement. As the disease progresses it may become more polyarticular. As more joints are accrued it becomes more symmetric. Therefore patients with long-standing disease are more likely to have polyarticular and symmetric disease. Patients with psoriatic arthritis do not complain of as much pain as patients with rheumatoid arthritis, the prototype inflammatory form of arthritis. Thus, the diagnosis of psoriatic arthritis is often missed among patients with psoriasis.

Inflammatory arthritis, oligoarticular.

Axial Disease

Half of the patients with psoriatic arthritis have inflammatory spinal disease as well. As in ankylosing spondylitis, the apophyseal joints of the spine and the sacroiliac joints are affected ( Fig. 2 ). In a small minority, the axial disease occurs without any peripheral arthritis. In these cases, it is difficult to determine whether the patient has ankylosing spondylitis with psoriasis, or axial psoriatic arthritis. As noted for the peripheral joints, patients with axial psoriatic arthritis do not have as much pain as patients with ankylosing spondylitis, and the condition is often missed, especially if radiographs are not performed.

Sacroiliitis.

Enthesitis

Inflammation at insertion of tendons into bones (enthesitis) is a feature common to the seronegative spondyloarthropathies ( Fig. 3 ). It is more common in patients with psoriatic arthritis than in patients with ankylosing spondylitis. It most commonly affects the plantar fascia and Achilles tendon, but several enthesitis sites have been recognized and grouped in different indices. Enthesitis may be the only musculoskeletal manifestation among patients with psoriasis.

Enthesitis.

Dactylitis

Dactylitis, or sausage digit, results from inflammation of a whole digit, including the joints and tendons ( Fig. 4 ). It is another typical manifestation of psoriatic arthritis occurring in close to 50% of patients. Dactylitis is an important feature of psoriatic arthritis because it is associated with greater joint damage.

Dactylitis.

What is Early Psoriatic Arthritis?

Most drug trials and observational cohort studies included patients with long disease duration, on average between 7 and 9 years. The concept of early psoriatic arthritis is recent, and has become more relevant since the advent of new therapies that seem to prevent disease progression and may even lead to healing of erosions and restoration of cartilage. Nonetheless, there is still no widely accepted definition of early disease. Should only patients with recent onset of joint symptoms be included? Should it be a short duration from the time of diagnosis? Because patients with psoriatic arthritis often do not complain of pain, it is difficult to rely only on onset of symptoms. It is more appropriate to consider the duration from the time of diagnosis. Most investigators consider early disease within 1 or 2 years of the diagnosis of psoriatic arthritis.

Why Should Psoriatic Arthritis be Identified Early?

Wright described psoriatic arthritis as milder than rheumatoid arthritis, an observation supported by another study from the United Kingdom. However, in the past few decades, it has become clear that the disease is more common and more severe than was previously appreciated. Psoriatic arthritis causes deformities and joint damage leading to impaired quality of life and function, and is associated with an increased mortality risk. Moreover, psoriatic arthritis is associated with important comorbidities that add to the disease burden.

Psoriatic arthritis is now recognized as a major health issue with important consequences. Most studies reporting on outcome in patients with psoriatic arthritis include patients with long-standing disease. One study included patients with psoriatic arthritis within 2 years of onset of symptoms, with a mean duration of disease from onset of symptoms of 5 months. Of the 129 patients identified as having psoriatic arthritis among the more than 1000 patients seen in the early arthritis clinic, 27% had at least 1 joint erosion at presentation to the early arthritis clinic, suggesting that the disease may be aggressive at an early stage. At their 2-year follow-up, 47% of these patients were found to have erosive disease despite most having been treated with disease-modifying antirheumatic drugs (DMARDs). A recent study showed that disease progression is more marked in those patients presenting with established disease of more than 2 years’ duration.

Until 2000, there were no treatments that led to reduction in progression of joint damage. However, with the advent of anti–tumor necrosis factor (TNF) agents, it is now possible to arrest progression of damage in these patients. Because it has been shown that the degree of inflammation predicts progression of both clinical and radiological damage, both as a global feature and in the individual joint, clinicians and patients should obtain appropriate therapy in a timely fashion to prevent joint damage progression.