AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

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

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

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.
  • 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.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

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

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Lab 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 in Genetics. 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.
• 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.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Medical Care

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.

Initial treatment includes nonsteroidal anti-inflammatory drugs (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.

• 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 disease-modifying antirheumatic drugs.
• In patients with severe skin inflammation, medications such as methotrexate (MTX), retinoic-acid derivatives, and psoralen plus UV light should be considered. These medications have been shown to work for both skin and joint manifestations.
• Sulfasalazine and cyclosporine are 2 second-line agents 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 nephrotoxicity and hypertension. Combination therapy (eg, MTX/sulfasalazine, MTX/cyclosporine) may be more efficacious in some patients.
• 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.
• Etanercept is approved by the US Food and Drug Administration 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 that has been approved for the treatment of Crohn disease, ulcerative colitis, RA (in combination with MTX), ankylosing spondylitis, and psoriatic arthritis. It has shown successful results in reducing the signs and symptoms of psoriatic arthritis. However, the Food and Drug Administration 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.
• The effects of other anti-TNF medications on psoriasis and psoriatic arthritis are being studied.
• A recent randomized 6-month study by Scarpa et al (2007) showed the early use of MTX 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 MTX.² These results suggest that other therapeutic approaches capable of modifying the early course of the disease should be used.
• Several other modalities 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. Two studies showed that these reactions did not occur in patients treated with hydroxychloroquine; therefore, it is occasionally used to treat psoriatic arthritis.
• Systemic corticosteroids are usually avoided because of possible rebound of the skin disease upon withdrawal.

Surgical Care

Arthroscopic synovectomy has been effective in treating severe chronic monoarticular synovitis. Because of the enhanced tendency for fibrosis associated 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.

Diet

For people who have morning stiffness, the optimal time for taking an NSAID might 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.

Activity

• Exercise
• • Exercise is an important part of the total treatment to limit the pain and swelling of arthritis, which can make joints stiff and hard to move.
  • A directed exercise program can improve movement, strengthen muscles to stabilize joints, improve sleep, strengthen the heart, increase stamina, reduce weight, and improve physical appearance.
• Rest
• • Generally, a normal amount of rest and sleep is sufficient to decrease fatigue and reduce joint inflammation.
  • In a very few people, psoriatic arthritis may cause extreme fatigue.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

The treatment of psoriatic arthritis usually begins with NSAIDs. These include enteric-coated acetylsalicylic acid, naproxen, indomethacin, ibuprofen, diclofenac, tolmetin, meloxicam, or other NSAIDs. Enteric-coated acetylsalicylic acid and ibuprofen require frequent administration, whereas meloxicam and slow-release indomethacin may be administered in a once-daily routine, which may be preferred by some patients.

Indomethacin is the strongest of the available traditional NSAIDs, although it has significant adverse GI and CNS effects and a potential to increase blood pressure. It is best used for short-term (eg, acute) flares.

NSAIDs clearly control the mild inflammatory features of psoriatic arthritis; however, some NSAIDs may aggravate the skin psoriasis.

Drug Category: Nonsteroidal anti-inflammatory drugs

Have analgesic, anti-inflammatory, and antipyretic activities. Mechanism of action may be inhibition of COX activity and prostaglandin synthesis. Others may include inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Drug Name	Diclofenac (Voltaren, Cataflam)
Description	Inhibits prostaglandin synthesis by decreasing activity of COX, which, in turn, decreases formation of prostaglandin precursors.
Adult Dose	Persistent night pain or morning stiffness: Up to 100 mg PO qhs may help to relieve pain; not to exceed 200 mg/d
Pediatric Dose	>12 years: Administer as in adults <12 years: Not established
Contraindications	Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, high risk of bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of MTX toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts occur rarely and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia develops

Drug Name	Naproxen (Anaprox, Naprelan, Naprosyn, Aleve)
Description	For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of COX, which is responsible for prostaglandin synthesis.
Adult Dose	250-500 mg PO bid; may increase to 1.5 g/d for limited periods
Pediatric Dose	<2 years: Not established >2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of MTX toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Drug Name	Indomethacin (Indocin)
Description	Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.
Adult Dose	25-50 mg PO bid/tid 75 mg SR bid; not to exceed 200 mg/d
Pediatric Dose	1-2 mg/kg/d divided PO bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d
Contraindications	Documented hypersensitivity; GI bleeding or renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of MTX toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia develops)

Drug Name	Sulindac (Clinoril)
Description	Decreases activity of COX and, in turn, inhibits prostaglandin synthesis. Results in a decreased formation of inflammatory mediators.
Adult Dose	150-200 mg PO bid or 300-400 qd; not to exceed 400 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; patients in whom aspirin, iodides, or other NSAIDs induce hypersensitivity; GI bleed and renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of MTX toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in preexisting renal disease or compromised renal perfusion; low WBC counts occur rarely and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia develops; caution in anticoagulation defects or patients receiving anticoagulant therapy

Drug Name	Celecoxib (Celebrex)
Description	For those at risk of GI toxicity with NSAIDs. Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose for each patient.
Adult Dose	200 mg/d PO qd; alternatively, 100 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration with rifampin may decrease celecoxib plasma concentrations
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, and conditions predisposing to fluid retention; caution in severe heart failure and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate therapy when symptoms or laboratory results suggest liver dysfunction

Drug Name	Meloxicam (Mobic)
Description	Decreases activity of COX, which, in turn, inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators.
Adult Dose	7.5 mg PO qd; may increase to 15 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active GI bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of MTX toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia develops)

Drug Category: Immunosuppressant agents

Inhibit key factors in the immune system responsible for inflammatory responses.

Drug Name	Cyclosporine (Sandimmune, Neoral)
Description	Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for a variety of organs. Demonstrated to be helpful in a variety of skin disorders, especially psoriasis.
Adult Dose	2.5-5 mg/kg/d PO in divided doses
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because may increase risk of cancer
Interactions	Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve intravenous use only for patients who cannot take PO

Drug Category: Biologic therapies

Postulated mechanisms include free radical–mediated oxidative damage to DNA; decreased secretion of IL-6, IL-1 beta, IL-10, and TNF-alpha; reduced angiogenesis; induction of IFN-gamma; and IL-2 production by CD8 T cells.

Drug Category: 5-Aminosalicylic acid derivatives

Inhibit inflammatory reactions and pain by decreasing activity of COX, which is responsible for prostaglandin synthesis.

Drug Category: Tumor necrosis factor (TNF) inhibitors

TNF is a cytokine of which 2 forms have been identified with similar biological properties. TNF-alpha or cachectin is produced predominantly by macrophages, and TNF-beta or lymphotoxin is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to symptoms.

Drug Name	Adalimumab (Humira)
Description	Recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors. Indicated for reducing signs and symptoms of active arthritis in psoriatic arthritis.
Adult Dose	40 mg SC q2wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active infection
Interactions	May interfere with immune response to live virus vaccine (MMR) and reduce efficacy; MTX decreases clearance (available data do not support adjusting dose of either HUMIRA or MTX); coadministration with anakinra (an interleukin-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Causes immunosuppression; may reactivate tuberculosis infection; increases risk for lymphoma development; associated with CNS demyelination (rare); discontinue if serious infection develops; autoantibody development may occur causing lupus-like syndrome; may cause hypersensitivity reactions including anaphylaxis and hematologic adverse effects (ie, pancytopenia, aplastic anemia)

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Further Outpatient Care

• 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.

Deterrence/Prevention

• A number of medications cause an exacerbation of psoriasis; therefore, avoidance of these medications may help prevent or minimize flare-ups.
• • Lithium and withdrawal from systemic corticosteroids are well known to cause flares of disease.
  • Beta-blockers, antimalarials, and NSAIDs have also been implicated.

Complications

• Until recently, psoriatic arthritis was generally believed to be a mild disease, with severe joint deformity and destruction (called arthritis mutilans) occurring in only approximately 5% of patients. This severe condition usually occurs in the small joints of the hands and feet. Some reports now suggest that arthritis mutilans may occur in as many as 16% of patients and that it may be as severe as rheumatoid arthritis (RA).
• Atlantoaxial subluxation with attendant neurological complications can occur. Rarely, patients with psoriatic arthritis may develop aortic insufficiency.

Prognosis

• Until recently, psoriatic arthritis generally had been considered a milder disease than RA. The following factors influence the degree of severity:
• • Clinical subset (eg, arthritis mutilans, symmetric polyarthritis)
  • Early age of onset
  • Severity of skin involvement
  • Female sex
  • Family history of arthritis
  • HLA marker: Patients with HLA-B39 and HLA-B27 in the presence of HLA-DR7 are more likely to experience disease progression, while those with HLA-B22 or HLA-DQw3 in the presence of HLA-DR7 may be protected from disease progression.
  • ESR of greater than 15 mm/h, medication use before the first clinical visit, evidence of radiologic damage, and absence of nail lesions: These factors have been associated with increased mortality.
• New evidence suggests that psoriatic arthritis may be as disabling and destructive as RA when the appropriate comparisons are made; thus, treatment should be aggressive in those individuals with progressive joint disease.

Patient Education

• Patients may visit the Web sites of the Arthritis Foundation or the National Psoriasis Foundation for more information on their disease.
• For excellent patient education resources, visit eMedicine's Psoriasis Center and Arthritis Center. Also, see eMedicine's patient education articles Psoriatic Arthritis, Psoriasis, and Nail Psoriasis.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Special Concerns

• 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.

FURTHER READING

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

For additional information, see Medscape’s Psoriasis Resource Center and Arthritis Resource Center.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Media file 1:  Severe fixed flexion deformity of the interphalangeal joint.
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Media file 2:  Comparison between sites of involvements in both hands and feet in psoriatic arthritis and rheumatoid arthritis.
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Media file 3:  Psoriatic arthritis involving the distal phalangeal joint.
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Media file 4:  Swelling and deformity of the metacarpophalangeal and distal interphalangeal joints in a patient with psoriatic arthritis.
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Media file 5:  Psoriatic arthritis involving the distal phalangeal joint.
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Media file 6:  Severe psoriatic arthritis involving the distal and proximal interphalangeal joints.
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Media file 7:  Asymmetric arthritis pattern of psoriatic arthritis (fixed flexion deformity).
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Media file 8:  Arthritis mutilans, a typically psoriatic pattern of arthritis, which is associated with a characteristic "pencil-in-cup" radiographic appearance of digits.
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Media file 9:  Psoriatic arthritis involving the distal phalangeal joint.
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Media file 10:  Arthritis mutilans (ie, "pencil-in-cup" deformities).
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Media type:  X-RAY

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

1. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: Development of new criteria from a large international study. Arthritis Rheum. Jul 26 2006;54(8):2665-2673. [Medline].
2. Scarpa R, Peluso R, Atteno M, Manguso F, Spano A, Iervolino S, et al. The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate. Clin Rheumatol. Nov/2007;Ahead of print:[Medline].
3. Andrews BS, Lowe NJ. Therapy of psoriatic arthritis. In: Practical Psoriasis Therapy. 2^nd ed. St. Louis, Mo: Mosby-Year Book; 1993:239-55.
4. Bruce I, Gladman DD. Psoriatic Arthritis: Recognition and Management. BioDrugs. 1998;9:271.
5. Calzavara-Pinton PG, Franceschini F, Manera C, Zane C, Prati E, Cretti L, et al. Antiperinuclear factor in psoriatic arthropathy. J Am Acad Dermatol. Jun 1999;40(6 Pt 1):910-3. [Medline].
6. Cather JC, Abramovits W, Menter A. Cyclosporine and