Psoriatic Arthritis Overview of Psoriatic Arthritis

Psoriatic arthritis is a chronic inflammatory arthritis that develops in at least 5% of patients with psoriasis. The association between psoriasis and arthritis was first made in the mid-19th century, but psoriatic arthritis was not clinically distinguished from rheumatoid arthritis (RA) until the 1960s. (An example of flexion deformity in psoriatic arthritis is shown below.)

Precisely defining psoriatic arthritis is still difficult because of a lack of specific biologic tests. Psoriatic arthritis is most commonly a seronegative oligoarthritis found in patients with psoriasis, with less common but characteristic differentiating features of distal joint involvement and arthritis mutilans. (The first image below compares sites of involvement for psoriatic arthritis with those for RA. The second and third images show distal joint pathology in psoriatic arthritis.)

Because 50% of patients with psoriatic arthritis have evidence of spondyloarthropathy, often human leukocyte antigen (HLA)-B27 associated, psoriatic arthritis has also been classified among the seronegative spondyloarthropathies.^{[1, 2, 3, 4, 5]}

Peripheral joint disease occurs in 95% of patients with psoriatic arthritis, while in the other 5%, axial spine involvement occurs exclusively.

Evidence from one study indicated that psoriatic arthritis is more frequent in patients with severe psoriasis than in those with milder cases. While this is true, no evidence indicates that the severity of the psoriasis relates to the pattern of joint involvement.

In another study, pustular psoriasis was associated with more severe psoriatic arthritis.

Elderly onset (>60 y) psoriatic arthritis has a more severe onset and more a destructive outcome than does psoriatic arthritis that affects younger subjects.

The course of psoriatic arthritis is usually characterized by flares and remissions.

The patterns of psoriatic arthritis involvement are as follows:

• Asymmetrical oligoarticular arthritis
• Symmetrical polyarthritis
• Distal interphalangeal arthropathy
• Arthritis mutilans
• Spondylitis with or without sacroiliitis

Asymmetrical oligoarticular arthritis

Until recently, this was thought to be the most common type of psoriatic arthritis.

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). A large joint, such as the knee, is also commonly involved.

Usually, fewer than 5 joints are affected at any one time.

An asymmetrical arthritis pattern is shown below.

Symmetrical polyarthritis

This rheumatoidlike pattern has been recognized as one of the most common types of psoriatic arthritis. The hands, wrists, ankles, and feet may be involved.

It is differentiated from RA by the presence of distal interphalangeal (DIP) joint involvement (as in the image below), relative asymmetry, an 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 to be a classic and unique symptom of 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

This is a rare form of psoriatic arthritis, being found in 1-5% of patients. In arthritis mutilans, resorption of bone (osteolysis), with dissolution of the joint, is observed as the "pencil-in-cup" radiographic finding and leads to redundant, overlying skin with a telescoping motion of the digit. (The effects of arthritis mutilans appear in the images below.)

This "opera-glass hand" is more common in men than in women and is more frequent in early-onset disease.

Some reports suggest that arthritis mutilans may occur in as many as 16% of patients and that it may be as severe as RA.

Spondylitis with or without sacroiliitis

This occurs in approximately 5% of patients with psoriatic arthritis and has a male predominance.

Clinical evidence of spondylitis and/or sacroiliitis can occur in conjunction with other subgroups of psoriatic arthritis.

Spondylitis may occur without radiologic evidence of sacroiliitis, which frequently tends to be asymmetrical, 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 (with attendant neurologic complications). Therapy may limit subluxation-associated disability.

Unusual radiologic features may be present, such as nonmarginal asymmetrical syndesmophytes (characteristic), paravertebral ossification, and, less commonly, vertebral fusion with disk calcification.

SAPHO syndrome

First described by Chamot et al in 1987, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by variable bone changes (hyperostosis, arthritis, aseptic osteomyelitis) of the chest wall, sacroiliac joints, and long bones. Dermatologic manifestations include palmoplantar pustulosis, hidradenitis suppurativa, pustular psoriasis, dissecting cellulitis of the scalp, Sweet syndrome, and Sneddon-Wilkinson disease. Skin and osseous involvement may occur simultaneously or be separated by as long as 20 years.^{[6, 7]}

For more information, see the following:

• Guttate Psoriasis
• Nail Psoriasis
• Plaque Psoriasis
• Pustular Psoriasis
• Psoriasis
• Imaging of Psoriatic Arthritis
• Parapsoriasis

Juvenile psoriatic arthritis accounts for 8-20% of childhood arthritis and is monoarticular at onset.

The median age of onset is 4.5 years in girls and 10 years in boys, and there is a female predominance. The disease is usually mild, although occasionally it may be severe and destructive, with the condition 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 in 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.

A large international study group developed a simple and highly specific classification system, known as CASPAR (Classification Criteria for Psoriatic Arthritis), for psoriatic arthritis.^[8] The criteria in this system 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)

The etiology of psoriatic arthritis remains unknown, but much information has been gathered. In addition to genetic influences, environmental and immunologic 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 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.

Slight differences exist in the vascular patterns of joints in psoriatic arthritis, compared with those of RA, suggesting the possibility of different etiologic mechanisms in these diseases.^[9]

Genetics

Approximately 40% of patients with psoriasis or psoriatic arthritis have a family history of these disorders in first-degree relatives.^{[10, 11]}

Twin studies indicate a concordance rate among monozygotic twins of 35-70%, compared with 12-20% for dizygotic twins.

The following important genetic susceptibility loci have been elucidated^{[12, 13, 14, 15, 16, 17, 18, 19]} :

• Early-onset psoriasis - HLA-Cw6, HLA-B57, HLA-DR7, and HLA-B17 with HLA-Cw*0602 variant found to be highly associated
• Psoriasis - HLA-Cw6 (or psoriasis susceptibility 1 [PSOR1] on chromosome 6) and 6 other psoriasis susceptibility loci (PSOR2, PSOR3, PSOR4, PSOR5, PSOR6, PSOR7), transcription factor RUNX1
• Psoriatic arthritis - HLA-B7, HLA-B27, HLA-DR4, HLA-38, and HLA-DR7
• Psoriasis and psoriatic arthritis - HLA-Cw6, HLA-B13, HLA-B17, HLA-B57, and HLA-B39
• Predictors for gene progression - HLA-B39; HLA-B27 in the presence of HLA-DR7; HLA-DQ3 in the absence of HLA-DR7
• Protective - HLA-B22

The exact mechanism of the association between HLA and psoriatic arthritis is not clear.

The following associated gene polymorphisms are also thought to be associated with psoriasis and psoriatic arthritis^{[12, 14, 16, 20]} :

• Tumor necrosis factor (TNF)-alpha promoter
• MHC class I-chained related gene A (MICA)
• Caspase-activating recruitment domain (CARD) 15
• Interleukin (IL)-12/IL-23p40 and IL-23 receptor

Additional loci that demonstrate an association with psoriatic arthritis include microsatellite polymorphisms in the 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.

It has also been suggested that certain immunoglobulin genes are 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.

Immunologic factors

Autoantibodies against nuclear antigens, cytokeratins, epidermal keratins, and heat-shock proteins have been reported in persons with psoriatic arthritis, indicating that the disease has a humoral immune component.

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 than in 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, 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.^[17]

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 and bacterial infections and the development or exacerbation of psoriasis and psoriatic arthritis suggests a possible pathogenetic role for viruses and bacteria.

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 acro-osteolysis after physical trauma in patients with psoriasis.

Environmental factors

The theory of environmental factors playing a role in the etiology of psoriatic arthritis involves a process of superantigens reacting with autoantigens.

Incidence in the 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 is thought to occur in up to 1% of the general population. However, prevalence rates vary widely between studies. A random telephone survey of 27,220 US residents found a 0.25% prevalence rate for psoriatic arthritis in the general population and an 11% prevalence rate in patients with psoriasis. However, the exact frequency of the condition in patients with psoriasis remains uncertain, with the estimated rate ranging from 5-30%.^{[17, 21]}

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

Since the late 20^th century, the incidence of psoriatic arthritis appears to have been rising in men and women. Reasons for the increase are unknown; it may be related to a true change in incidence or to a greater overall awareness of the diagnosis by physicians.^[22]

International incidence

Depending on the population studied, the prevalence of psoriatic arthritis ranges from less than 1% to 40%. One Italian study reported a prevalence of 0.4 %.

There is a high prevalence of previously undiagnosed active psoriatic arthritis among patients with psoriasis who are seen by dermatologists. In a 2009 prospective German study, of 1511 patients with plaque-type psoriasis, 20.6% were found to have psoriatic arthritis, with 85% of the cases having been previously undiagnosed.^[1]

The number of diagnosed cases of psoriasis and psoriatic arthritis has risen dramatically in sub-Saharan Africa in association with the area’s escalating epidemic of human immunodeficiency virus (HIV) infection. Although HIV infection is not known to affect the incidence of psoriasis, it may significantly exacerbate otherwise limited disease. The evolution of mild psoriasis to erythroderma in the setting of a flare-up of psoriatic arthritis may be a sign of HIV infection.

Mortality and morbidity in psoriatic arthritis

Although psoriatic arthritis was originally thought to be relatively mild, as many as 40% of patients may develop erosive and deforming arthritis. Of patients observed in a large outpatient psoriatic arthritis clinic, 7% required musculoskeletal surgery.

A cohort study from the United Kingdom showed no increase in mortality among 453 patients with psoriatic arthritis compared with the general population.^[23]

The results from another study suggest that psoriatic arthritis is associated with a significantly greater risk of hypertension, obesity, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular events compared with psoriasis without arthritis. Psoriatic arthritis was also associated with infections not treated with antibiotics, neurologic conditions, gastrointestinal disorders, and liver disease.^[24]

Race predilection

Race predilection in psoriatic arthritis has not been well studied. However, whites are known to be affected more commonly than are persons of other racial groups.

Sex predilection

The male-to-female ratio for psoriatic arthritis is 1:1, with the exception of some subsets of patients.

Females are more commonly affected with the symmetrical polyarthritis that resembles RA and the juvenile form.

A preponderance of males has been noted in the spondylitic form of psoriatic arthritis, which affects the axial spine, with the male-to-female ratio being 3:1.

Age predilection

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

In the juvenile form, the age of onset is 9-11 years.

Psoriasis appears to precede the onset of psoriatic arthritis in 60-80% of patients. (occasionally by as many as 20 y, but usually by less than 10 y). However, in as many as 15-20% of patients, arthritis appears before the psoriasis, in which case, a family history of psoriasis may reveal a hereditary pattern. Occasionally, arthritis and psoriasis appear simultaneously.

In some cases, patients may experience only stiffness and pain, with few objective findings.

In a patient who presents with musculoskeletal symptoms without a history of psoriasis, the diagnosis can be suspected based on a family history of psoriasis and the pattern of arthritis. (See Overview of Psoriatic Arthritis, above.)

In most patients, the musculoskeletal symptoms are insidious in onset, but an acute onset has been reported in one third of all patients.

Factors that increase the risk of a patient with psoriasis developing arthritis in their lifetime include the presence of nail lesions, as well as more extensive skin involvement.

One third of patients may develop inflammatory ocular symptoms reminiscent of reactive arthritis (previously termed Reiter disease).

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.

Recognition of the patterns of joint involvement is essential to the diagnosis of psoriatic arthritis. (See Overview of Psoriatic Arthritis, above.)

Less joint tenderness possibly occurs with psoriatic arthritis than with RA.

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 (seen in the image below) is seen in as many as 35% of patients.

Diagnosis is also suggested by asymmetrical joint involvement, dactylitis, the absence of RF, and DIP involvement in the absence of osteoarthritis.

When localized to the foot or toe, the symptoms of psoriatic arthritis may be mistaken for gout.

Skin involvement

Scaly, erythematous plaques; guttate lesions; lakes of pus; and erythroderma are all types of psoriatic skin lesions that may be seen in the context of psoriatic arthritis.

In one study, as previously mentioned, arthritis was noted more frequently in patients with severe skin disease.

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.

Nail involvement

The presence of Beau lines, leukonychia, onycholysis, oil spots, subungual hyperkeratosis, splinter hemorrhages, spotted lunulae, transverse ridging, cracking of the free edge of the nail, and uniform nail pitting all support the diagnosis of psoriatic arthritis, especially in DIPs. In fact, psoriatic nail changes may be a solitary finding in patients with psoriatic arthritis. (Nail pitting is shown below.)

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

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 tendon sheaths 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. Possible ocular findings also include iritis.

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.

The following disorders can mimic the symptoms of psoriatic arthritis:

Gout

Osteoarthritis

Reactive arthritis

Rheumatoid arthritis

Septic arthritis

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

Lupus erythematosus

This condition can produce a rash similar to a psoriatic rash. Usually, the arthritis associated with lupus is not as deforming as that associated with psoriasis arthritis

Secondary syphilis

Secondary syphilis can also cause a rash similar to a psoriatic rash. An arthropathy can be associated with syphilis, but this entity occurs years after the skin lesions have cleared in an untreated patient.

Ankylosing spondylitis

This condition can produce back pain similar to that associated with psoriatic arthritis but without the associated peripheral arthropathy or skin lesion.

No specific diagnostic tests are available for psoriatic arthritis.^[25] 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 to track the activity of the disease by measuring inflammation. An elevated ESR is usually found in approximately 40% of patients with psoriatic arthritis. (An ESR of greater than 15 mm/h, along with medication use before the first clinical visit, evidence of radiologic damage, and absence of nail lesions, has been associated with increased mortality in 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 genetic associations of psoriatic arthritis are discussed in Etiology, above.

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.

Table. Comparison of Expected Laboratory Values in Psoriatic Arthritis and Rheumatoid Arthritis (Open Table in a new window)

Radiologic features have helped to distinguish psoriatic arthritis from other causes of polyarthritis. In general, the common subtypes of psoriatic arthritis, such as asymmetrical oligoarthritis and symmetrical 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 RA, is minimal in persons with psoriatic arthritis. Asymmetrical 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. (See the images below.)

Erosive disease frequently occurs in patients with either DIP involvement or progressive deforming arthritis and may lead to subluxation and, less commonly, to bony ankylosis of the joint.

Erosion of the tuft of the distal phalanx, and even of the metacarpals or metatarsals, can progress to complete dissolution of the bone. Although this form of acro-osteolysis 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.

Go to Imaging of Psoriatic Arthritis for complete information on this topic.

Traditional methods for monitoring patients with rheumatic conditions include, along with clinical assessment for joint inflammation or damage, radiographic evaluations.

Radiography shows a combination of erosion (unlike in ankylosing spondylosis) and bone growth (unlike in RA) in affected joints.^[26] The following radiographic abnormalities are suggestive of psoriatic arthritis:

• Pencil-in-cup deformity (seen in the image below)Arthritis mutilans (ie, "pencil-in-cup" deformities).
• Joint-space narrowing in the interphalangeal joints, possibly with ankylosis
• Increased joint space in the interphalangeal joints as a result of destruction
• Fluffy periostitis
• Bilateral, asymmetrical, fusiform soft-tissue swelling
• Unilateral or symmetrical sacroiliitis
• Large, nonmarginal, unilateral, asymmetrical syndesmophytes (intervertebral bony bridges, seen in the image below) in the cervical, thoracic, and lumbar spine, often sparing some of the segments Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Courtesy of Bruce M. Rothschild, MD.

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 the 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.

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be useful for detecting early signs of joint synovitis.

MRI is particularly sensitive for detecting sacroiliitic synovitis, enthesitis, and erosions; it can also be used with gadolinium to increase sensitivity. MRI may show inflammation in the small joints of the hands, involving the collateral ligaments and soft tissues around the joint capsule, a finding not found in persons with RA.

Ultrasonography has a somewhat undefined, but emerging, role in the diagnosis and management of psoriatic arthritis, including the ability to differentiate synovitis and enthesitis, accurately and objectively monitor disease activity, and accurately deliver local therapy.

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.

The treatment of psoriatic arthritis is directed at controlling the inflammatory process. Although no clear correlation exists between the skin and joint inflammation in every patient, the skin and joint aspects of the disease often must be treated simultaneously.

Based on evidence from systematic literature reviews and expert opinion, the European League Against Rheumatism (EULAR) recently developed 10 treatment recommendations, 5 overarching principles, and a research agenda for psoriatic arthritis.^[27] Also see EULAR Recommendations.

Medical treatment regimens include the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). Although traditional therapy has consisted of NSAIDs and local corticosteroid injections, with DMARDs being reserved for NSAID-resistant cases, the finding that 40% of patients may develop erosive and deforming arthritis suggests that early, more aggressive treatment with DMARDs may be warranted.

DMARDs include methotrexate, sulfasalazine, cyclosporine, and leflunomide, as well as biologic agents, such as the anti–TNF-alpha medications.^[28]

In patients with severe skin inflammation, medications such as methotrexate, retinoic-acid derivatives, and psoralen plus ultraviolet (UV) light should be considered. These agents have been shown to work on skin and joint manifestations.

Intra-articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use disease-modifying drugs in individuals whose arthritis is persistent. If the skin disease is well controlled with topical medication, the joint disease can be treated with a variety of second-line or cytotoxic drugs. Intramuscular administration of gold has been used in the past but has been supplanted by newer DMARDs.

Nonsteroidal anti-inflammatory drugs

Initial treatment includes NSAIDs for joint disease and topical therapies for the skin. In many patients, this approach is sufficient to control disease manifestations, although some patients have a worsening of psoriasis with NSAIDs. In these patients, a drug belonging to a different family of NSAIDs should be used.

Methotrexate

A randomized, 6-month study by Scarpa et al (2007) showed that the early use of methotrexate in patients with early psoriatic arthritis markedly improved tender and swollen joints and/or entheses. However, no significant difference was found after 3 months of treatment with NSAIDs or methotrexate.^[29] These results suggest that other therapeutic approaches capable of modifying the early course of the disease should be used.^[30]

Patients receiving long-term, high cumulative doses of methotrexate therapy can be monitored using serial liver function tests (LFTs). Liver biopsy should to be considered if LFT values are persistently elevated. Pro-collagen 3 N-terminal peptide (PIIINP) is a new, alternate test; however, Lindsay et al reported that PIIINP frequently showed elevated values despite normal liver biopsy results.^[31]

Sulfasalazine and cyclosporine

Sulfasalazine and cyclosporine are 2 second-line DMARDs that have received particular attention in the management of psoriatic arthritis. Although these drugs may control the acute inflammation in persons with psoriatic arthritis, they have not been helpful in arresting the progression of clinical and radiologic damage. Thus, the disease must be treated earlier or better drugs are necessary, to prevent the damage that may ensue as a result of psoriatic arthritis.

Cyclosporine appears to be an effective agent for the treatment of psoriasis and psoriatic arthritis. The major concern with cyclosporine is its toxicity, especially its nephrotoxicity, and hypertension.

Combination therapy (eg, methotrexate/sulfasalazine, methotrexate/cyclosporine) may be more efficacious in some patients.^[32]

Biologic agents

The use of biologic response modifiers that target TNF and other cytokines represents an advance in the treatment of several diseases involving autoimmune mechanisms. Several such agents have been developed, in the form of either soluble fusion proteins (eg, etanercept) or monoclonal antibodies (eg, infliximab, adalimumab), which have shown considerable efficacy in the treatment of rheumatoid arthritis (RA) and other autoimmune diseases.^[33]

Etanercept is approved by the US Food and Drug Administration (FDA) for (1) treating adult patients (age ≥18 y) with chronic, moderate to severe plaque psoriasis; (2) reducing the symptoms and signs of moderate to severe polyarticular-course juvenile RA and ankylosing spondylitis; and (3) reducing the signs and symptoms and inhibiting the progression of structural damage associated with psoriatic arthritis. Therefore, etanercept may be an effective and safe alternative monotherapy for the treatment of psoriatic arthritis.

Infliximab (Remicade) is another TNF-neutralizing agent. It has been approved for the treatment of Crohn disease, ulcerative colitis, RA (in combination with methotrexate), ankylosing spondylitis, and psoriatic arthritis. It has shown successful results in reducing the signs and symptoms of psoriatic arthritis.^[34]

However, the FDA has issued safety warnings for infliximab concerning worsening heart failure in patients with moderate to severe congestive heart failure and opportunistic infections, such as tuberculosis, histoplasmosis, listeriosis, and pneumocystosis.

In a study completed by the Psoriatic Arthritis Study Group, patients with psoriasis and psoriatic arthritis who were receiving stable doses of methotrexate were found to benefit from the addition of 1 or more courses of intramuscular alefacept, a T-cell inhibitor via a human LFA3 Fc fusion protein that blocks the interaction between CD2 on T cells and LFA-3 on antigen-presenting cells. Further benefit in psoriatic arthritis was apparent after a second course of alefacept, and no additional toxicity was observed.^[25]

Golimumab is an FDA-approved human TNF-alpha antibody that is given every 4 weeks as a subcutaneous injection at doses of 50 mg and 100 mg. It has been shown to significantly improve symptoms of psoriatic arthritis.^[2]

Other new biological agents in clinical trials include certolizumab pegol, a PEGylated Fab' fragment of an anti–TNF-alpha monoclonal antibody. Certolizumab pegol has shown promising results in the treatment of RA and may be applicable for treating psoriasis and psoriatic arthritis in the future.

Phase II studies of the biologic agent ustekinumab, which is directed against IL-12 and IL-23, suggest that it is effective in alleviating the symptoms of psoriasis and psoriatic arthritis.^{[13, 35]}

Other agents

Several other agents have been tried in persons with psoriatic arthritis, including vitamin-D3, bromocriptine, peptide T, and fish oils, but their efficacy remains to be proven.

Antimalarials, particularly hydroxychloroquine (Plaquenil), are usually avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. However, 2 studies showed that these reactions did not occur in patients who were treated with hydroxychloroquine; therefore, this drug is occasionally used to treat psoriatic arthritis.

Systemic corticosteroids are usually avoided because of possible rebound of the skin disease upon withdrawal.

Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis. Because of an enhanced tendency for patients to develop fibrosis in association with this therapy, anti-inflammatory and physical therapy measures aimed at improving range of motion are important adjuncts to this intervention. Joint replacement and forms of reconstructive therapy are occasionally necessary.

Currently, no prospective studies are addressing surgical intervention in patients with psoriatic arthritis. Patients in severe pain or with significant contractures may be referred for possible surgical intervention. Treatment should be aimed at pain relief or increasing the patient's function.

Hip and knee joint replacements have been successful, for the most part, in patients with psoriatic arthritis. Arthrodesis and arthroplasty have also been used on joints, such as the thumb PIP joint. The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention.

Because of the diffuse soft-tissue involvement that is associated with psoriatic arthritis, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand.

For arthritis mutilans, surgical intervention is usually directed toward salvage of the hand. Combinations of arthrodesis, arthroplasty, and bone grafts to lengthen the digits may be used. The goal is to maintain the pinch mechanism of the thumb and the first 2 fingers.

If the patient's physiatrist feels uncomfortable with prescribing medications for psoriatic arthritis, referral to a rheumatologist with more experience with these agents may be advisable. The physiatrist may then concentrate on functional restoration of the patient. Referral to a surgeon should be considered for appropriate patients.

Children with juvenile psoriatic arthritis should be examined by an ophthalmologist annually to check for the several forms of eye inflammation usually associated with various forms of juvenile arthritis.

Given the complexity of DMARD therapy, patients with psoriatic arthritis should be followed simultaneously by a rheumatologist and physiatrist. In addition, consultation with an orthopedic surgeon is warranted for individuals who may benefit from joint replacement, arthrodesis, or contracture release.

For people who have morning stiffness, the optimal time for taking an NSAID may be after the evening meal and again upon awakening. Taking NSAIDs with food can reduce stomach discomfort. Any NSAID can damage the mucous layer and cause ulcers and GI bleeding when taken for long periods. Cyclooxygenase (COX)–2 selective inhibitors are associated with a lower prevalence of gastric ulcer formation.

The rehabilitation treatment program for patients with psoriatic arthritis should be individualized and should be started early in the disease process. Such a program should consider the use of the following:

• Rest - Local and systemic
• Exercise - Passive, active, stretching, strengthening, and endurance
• Modalities - Heat, cold
• Orthotics - Upper and lower extremities, spinal
• Assistive devices for gait and adaptive devices for self-care tasks - Including possible modifications to homes and automobiles
• Education about the disease, energy conservation techniques, and joint protection
• Possible vocational readjustments

With regard to the first item above, prolonged rest should be avoided to prevent the deleterious effects of immobility. In a very few people, psoriatic arthritis may cause extreme fatigue.

Acute phase

Encourage rest as indicated. Splints may be used for rest and pain relief, especially for the hands, wrists, knees, or ankles. Cold modalities should be used to decrease inflammation and assist with pain relief. Joints should not be moved beyond the limit of pain; passive movements should be limited at this time. Education should be completed during this phase, with topics including the disease itself, the importance of rest, the exercise program, joint protection, energy conservation, and weight loss, if appropriate.

Subacute and long-term phase

Isometric exercises are begun, with progression to active movement. Gradual range-of-motion (ROM) exercises include passive and active exercises; areas with subluxation should not be forced passively. Heating modalities, including moist heat packs, paraffin wax, diathermy, and ultrasound, can be used to decrease pain; heat therapy should be performed just prior to performance of ROM exercises.

Institute gait activities, with the patient bearing weight as tolerated, with or without an assistive device. Gentle stretching should be gradually introduced. If pain persists beyond 2 hours after therapies, then the intensity should be decreased. If a joint is swollen, then no resistive exercises should be performed through full ROM.

For patients with axial spine involvement, spine extension exercises help with flexibility and strength. ROM exercises should be performed, but not in patients with increased pain.

If the patient has sausage toes, extra-depth shoes with a high toe box should be considered to protect the foot. With pain in the toes, such shoes should have a rocker-bottom modification to alleviate forces during the toe-off phase in the gait cycle. The patient may also benefit from arch supports if plantar fascitis is a problem.

Heat and cold treatments can temporarily relieve pain and reduce joint swelling. Examples of treatments include soaking in a warm tub or placing a warm compress or cold pack on the painful joint.

Specific outpatient follow-up care is required for individuals with psoriatic arthritis who undergo surgical repair of their joints. In most cases, conservative treatment is successful and completed in an outpatient setting. Physical and/or occupational therapy is usually recommended, in addition to medications, to minimize pain and stiffness. (See Physical Therapy in Psoriatic Arthritis, above.)

A number of medications can exacerbate psoriasis; therefore, avoidance of these medications may help to prevent or minimize flare-ups. Lithium and withdrawal from systemic corticosteroids are well known to cause disease flare-ups.

Other drugs that have been implicated include beta blockers, antimalarials (although, as previously mentioned, evidence suggests that hydroxychloroquine does not exacerbate skin lesions), and NSAIDs. If skin lesions worsen with an NSAID, switch to a different family of NSAID.

Prevention includes rest and exercise. Joint protection, including splints, braces, and other supports, may be helpful. No definitive prevention exists, because this is a chronic disease that can wax and wane.

Education is an important component of the patient's treatment plan, because he or she must be able to manage the symptoms of psoriatic arthritis and be comfortable with self-treatment strategies. Physical therapists provide education and an exercise program developed for each individual patient. Completing the wrong kind of exercise or overexertion can be harmful for patients with psoriatic arthritis.

Instructing patients with psoriatic arthritis in methods of joint protection is necessary and becomes part of the therapy process. Patients need to pace themselves and take adequate rest breaks from activity. Other examples of joint protection include wearing splints on the affected joints, using proper body mechanics and lifting techniques, and incorporating assistive devices or adaptive equipment into the patient’s activities of daily living.

For patient education information, see eMedicine's Psoriasis Center and Arthritis Center, as well as Psoriatic Arthritis, Psoriasis, Types of Psoriasis, Understanding Psoriasis Medications, and Nail Psoriasis.