Journal of Pharmacy Practice Psoriatic Arthritis: A Review
Kathy Eroschenko, Kevin W. Cleveland and Kyle Gunter Journal of Pharmacy Practice 2009 22: 86 originally published online 14 October 2008 DOI: 10.1177/0897190008322287 The online version of this article can be found at:

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New York State Council of Health-system Pharmacists

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Psoriatic Arthritis: A Review
Kathy Eroschenko, PharmD, Kevin W. Cleveland, PharmD, ANP, and Kyle Gunter, PharmD
Psoriatic arthritis (PsA) is a seronegative inflammatory spondyloarthropathy occurring in individuals with psoriasis. Psoriasis precedes joint disease in approximately 80% of PsA cases. The clinical course of PsA varies from mild arthritis to a severe, debilitating erosive arthropathy that affects functional capacity and quality of life of patients. The incidence of PsA is gender neutral, but a significant genetic component exists. Hallmark clinical features include dystrophic nail changes in the fingers or toes, dactylitis, and enthesitis. Many drugs indicated for use in rheumatoid arthritis

Journal of Pharmacy Practice Volume 22 Number 1 February 2009 86-103 # 2009 Sage Publications 10.1177/0897190008322287 hosted at

have been found useful in the treatment of PsA, suggesting a similar immune-mediated etiology. Nonsteroidal anti-inflammatory drugs and intraarticular corticosteroids are often sufficient to manage mild PsA. Moderate to severe forms of the disease require the initiation of disease modifying anti-rheumatic drugs. Failure of two disease modifying antirheumatic drugs justifies the initiation of biologic therapy with tumor necrosis factor-a inhibitors. Keywords: psoriatic arthritis; psoriasis; drug therapy


soriatic arthritis (PsA), initially described in the 19th century, is a unique form of inflammatory arthritis commonly found in individuals with psoriasis.1,2 Psoriatic arthritis was recognized as a clinical entity separate from rheumatoid arthritis (RA) following the discovery of rheumatoid factor in 1948.2 Psoriatic arthritis was further distinguished from RA after epidemiologic and clinical studies identified different clinical courses between the two inflammatory processes.1 Unlike RA, individuals with PsA normally are seronegative for rheumatoid factor and are further distinguished from RA by five clinical presentations as defined by Taurog and colleagues: inflammation of the spine, sacroiliac, and distal interphalangeal (DIP) joints of the fingers, asymmetrical oligoarthritis, symmetrical polyarthritis, arthritis mutilans, and spondylitis.1-3

From the College of Pharmacy (KE, KWC, KG) and the College of Pharmacy, Idaho Drug Information Service (KWC), Idaho State University, Pocatello, Idaho. Address correspondence to: Kevin W. Cleveland, Idaho State University College of Pharmacy, Pocatello, ID 83209; phone: (208) 282-3785; e-mail:

Psoriatic arthritis is often preceded by the skin disorder of psoriasis and is associated with joint pain, tenderness, and stiffness.3 The core clinical features of PsA are heterogeneous and involve both the joints and skin. Although cutaneous manifestations of the disease are important, nail involvement including pitting, longitudinal ridges, and onycholysis are more characteristic of PsA.4 Other extraarticular features of PsA include oral ulcers, urethritis, and ocular inflammation, which can make it difficult to distinguish from other spondyloarthropathies.4,5 Once thought less severe than RA, PsA can be an erosive and destructive type of arthritis that affects functional capacity and the quality of life of those afflicted. Early detection and diagnosis of PsA can be difficult and structural damage often occurs prior to the emergence of clinical symptoms.4 Currently, there are no clinical markers that can predict which patients with psoriasis will ultimately be diagnosed with PsA. The pathogenesis of the disease is not fully understood but is believed to be caused by a combination of genetic factors and immunological mediators.1

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Reports of PsA prevalence have been varied due to the relatively rare nature of the condition as well as the lack of specific serological markers.6 Onset can occur at any age but a bimodal distribution of age has been observed.7 Studies have identified two clinical forms of PsA based upon the age at onset. Individuals with early onset PsA have a higher incidence of a positive family history, frequent relapses and a more deteriorative form of the disease.7 Those who develop late onset PsA have a more stable clinical course of disease with less body and nail involvement.7 Occurring equally in men and women, the prevalence of PsA has been reported to range from 0.4% to 1.2% in the general population.1,8 The exact prevalence is unknown due to lack of validated diagnostic criteria but is most common in whites and less common in other ethnic groups.1,9 Latitudes closer to the equator have been associated with a lower prevalence, possibly from the added benefits of sunlight to those afflicted with the disease.1,9 In patients with psoriasis, the prevalence ranges from 6% to 39%.6,8 Recent studies have reported that 30% of patients with psoriasis will ultimately develop PsA.6 Interestingly, only about 10% of patients with PsA manifest arthritis symptoms prior to the skin manifestations of psoriasis.9 There is a clear genetic component to PsA. First degree relatives have a 30-fold higher risk for developing psoriasis, PsA, or other spondyloarthritides compared to the general population.1 Monozygotic twins have been shown to have a concordance rate greater than 30% for PsA and over 65% for psoriasis.1 Psoriatic arthritis development has been linked to the human leukocyte antigen (HLA) class 1 alleles and the MIC-A locus, which supports a genetic component to its etiology.2 Psoriatic arthritis differs from RA, which is associated with HLA class 2 alleles.1,2 It is believed that several unlinked allelic loci are required for an individual to be susceptible to psoriasis or PsA.1 Psoriatic arthritis has been shown to not only have a social impact on those afflicted but a financial burden as well.3 Cost data is limited, but the combined direct health care costs associated with psoriasis and PsA have been assessed.3 In 1997, PsA accounted for 25% of hospitalizations and 7% of outpatient physician visits in the United States.3 More than $500 million were spent on photochemotherapy, dermatological prescriptions, and over-

the-counter items used to treat psoriasis and PsA in the United States.3 At the time the cost data were studied, the use of biological agents were not included; these agents will significantly increase prescription drug costs for PsA therapy.

Psoriatic arthritis is characterized as an autoimmune disorder, but the specific mechanisms leading to its development have not been fully elucidated.7 Several genes have been identified and are believed to be partly responsible for the disease in those who are susceptible.8 The role of environmental factors such as infection and trauma as triggers are speculated but remain unproven.8 It has been hypothesized that susceptible individuals may contract an infection or sustain an injury that triggers an autoimmune mediated reaction that leads to the expression of the disease.8 Although genetics and environmental factors cannot be controlled, an understanding of the pathophysiology of the disease may lead to the development of novel drugs to stop or reverse the progression of the disease. Whether psoriasis and PsA are one single clinical disorder or separate entities with significant common genetic and environmental triggers remains a subject of debate.8 Interestingly, the pathophysiology of skin and joint lesions in patients who suffer from psoriasis and PsA appear to be very similar.7 Both are believed to be due in part to an inflammatory reaction, autoimmunity, and activation of complement.7 The key components that play important roles surrounding the immunopathology of both disorders are T cells, macrophages, and the cytokine tumor necrosis factor alpha (TNF-a).10 Skin lesions, synovium, and synovial fluid of PsA patients contain infiltrates of T cells, B cells, macrophages, dendritic cells, monocytes, fibroblasts, and neutrophils, which contribute to the inflammation and tissue hypertrophy commonly seen in the disease.1,7,8 In particular, stimulation of CD8þ T cells leads to the production and release of cytokines that further stimulate inflammatory cells in the autoimmune cascade leading to skin lesions, cartilage loss, and bone erosion.8 The cytokines TNF-a and interleukin-1 (IL-1) have been of particular relevance due to the development of effective agents that target and block the activity of both inflammatory mediators.10

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Table 1. Moll and Wright Classification Scheme for PsA12,13,a
PsA Subtype DIP joint predominant Asymmetric oligoarticular Symmetric polyarticular Spondylitis predominant Arthritis mutilans Prevalence (%) 5-15 16-70 15-25 20-40 5 Definition Involves distal joints of fingers and toes; strong association with nail deformities Most common form; <5 tender, swollen joints; usually affects knee, hip, ankle, hands, feet, wrists; DIP and PIP joints of hands and feet often involved, causing enlarged ‘‘sausage’’ digits Affects multiple symmetrical pairs of joints; can be disabling; often misdiagnosed as rheumatoid arthritis; MCP joint involvement is common; psoriasis often severe Affects axial column predominantly; may occur without peripheral arthritis Aggressive, destructive form resulting in severe deformity; affects small joints of the hands and feet; associated with neck and lower back pain (sacroiliitis); causes telescoping of digits secondary to extensive bone resorption

Abbreviations: PsA, psoriatic arthritis; DIP, distal interphalangeal; PIP, proximal interphalangeal; MCP, metacarpophalangeal. a Patients must have psoriasis, an inflammatory form of arthritis, and a negative laboratory test for rheumatoid factor.

There is clear evidence that TNF-a is responsible for numerous inflammatory and biologic effects seen in PsA. Pharmaceutical agents that block the effects of this cytokine have demonstrated substantial benefit in PsA patients, further emphasizing its key role in etiology of PsA.6 The mechanisms by which TNF-a exerts its inflammatory properties are numerous. TNF-a is responsible for the upregulation of nuclear transcription factors such as nuclear factor b (NFKB), which increases the expression of numerous inflammatory molecules including cytokines and chemokines.10 Expression of dendritic, keratinocyte, and endothelial cell surface receptors such as intercellular adhesion molecules and E-selectin, responsible for recruiting leukocytes to the inflamed area, are induced by TNF-a.10 Hyperproliferation and survival of keratinocytes induced by TNF-a also contribute to common psoriatic lesions seen in many patients with psoriasis and PsA.7 Biologic effects contributing to the effects of TNF-a include the stimulation and production of metalloproteinases and other enzymes from chondrocytes and fibroblasts.10 Monocyte stimulation by TNF-a produces matrix metalloproteinases that are responsible for cartilage erosion. Chondrocyte and fibroblast stimulation leads to osteoclast maturation and activation resulting in further cartilage loss, bone erosion, and fibrosis commonly seen in late-stage PsA.8,10 Neovascularization present in the synovium and psoriatic skin lesions is caused by the upregulation of growth factors such as vascular epithelial growth factor, transforming growth factor b, and angiopoietins.6 The development of

angiogenesis around the area of destruction has been shown to occur more commonly in PsA than in RA.6,7 Inflammation also occurs secondary to upregulation of other key cytokines during T cell activation including IL-1, IL-6, IL-12, IL-15, and IL-18.6 Advances in technology has led to more awareness but current treatment algorithms for the disease are less clear.

Clinical Presentation
Joint inflammation is the primary clinical feature of PsA.11 However, because PsA is a heterogeneous disease state composed of multiple subtypes, the clinical presentation is unpredictable. Patients may present with oligoarthritis (pain and stiffness in fewer than five joints) or polyarthritis (involvement of five or more joints), and the pattern may be asymmetrical or symmetrical. The joints most often affected are the wrists, metacarpophalangeal, proximal interphalangeal, and DIP joints.5,11 Patients may also report spinal involvement manifesting as lower back pain.5 Five subtypes of PsA have been proposed: DIP joint predominant, asymmetrical oligoarticular, polyarticular, spondylitis, and arthritis mutilans (Table 1).12 Polyarticular is the most common form of early PsA, followed by oligoarticular.11,14 Polyarticular PsA typically affects peripheral joints in a symmetrical pattern.4 Oligoarticular PsA affects less than five joints in an asymmetrical pattern. Approximately 5% of patients have arthritis mutilans, the most severe and crippling subtype of PsA. Arthritis

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Table 2. CASPAR Classification of PsA2,1
The patient must have established inflammatory musculoskeletal disease and a score of three or more from the following criteria: Criterion Psoriasis Dystrophic nail changes RF negative Dactylitis Radiologic evidence As Evidenced by Current psoriatic skin or scalp disease, personal history of psoriasis, or history of psoriasis in a first or second degree relative Pitting, onycholysis, and hyperkeratosis Negative laboratory test for RF by any method except latex Current swelling of an entire finger or toe (sausage digit) or history of dactylitis Evidence of juxta-articular new bone formation on plain X-rays of hand or foot Point Score 2 1 1 1 1

Abbreviations: PsA, psoriatic arthritis; CASPAR, Classification of Psoriatic Arthritis; RF rheumatoid factor.

mutilans is characterized by shortening of digits (‘‘telescoping’’) which may coexist with ankylosis and contractures in other digits.1 The vast majority of patients with PsA will present with psoriatic skin lesions. Approximately 70% of presenting patients will have psoriatic nail dystrophy (pitting, dystrophic hyperkeratosis, yellowish discoloration of the nail margins, ridging, and/ or onycholysis). Early morning stiffness is another very common presenting complaint, with a mean subjective visual analog scale score of approximately 5 out of 10.14 Enthesitis (painful inflammation at the site of insertion of a tendon, ligament, or joint capsule fiber into bone) manifests in approximately 40% of patients at presentation; about 30% experience dactylitis of digits (inflammation of an entire finger or toe). About 10% to 15% report plantar fasciitis at the time of diagnosis—heel pain (a manifestation of enthesitis) can be severe and disabling.11,14 Although most patients present with classic psoriasis vulgaris, there is no direct correlation between skin lesion severity and the degree of joint inflammation.11 Less than 40% of patients suffering from psoriasis who have arthritic complaints recognize a link between the joint and cutaneous disorders.15 In 15% to 20% of cases, arthritic complaints precede the psoriasis, so lack of psoriatic lesions cannot definitively rule out PsA.11 Ocular complications (conjunctivitis or chronic uveitis) and late cardiac sequelae (aortic valve insufficiency) have been reported in a small percentage of patients with PsA.1,5,11 Interestingly, the five classifications of PsA are not permanent; more than 60% of patients change subtypes over the course of their illness.16,17 The subtype of PsA at the time of diagnosis does not predict the clinical outcome in the majority of patients.17

Further, the application of subtype criteria may be confounded in established PsA by the effects of disease-modifying drugs.18

Psoriatic arthritis was identified as a distinct clinical entity by the American Rheumatism Association in 1964.19 However, there are no established diagnostic criteria for PsA.20 The Moll and Wright classification criteria (Table 1) have traditionally been used for the identification of PsA subtypes.12 A new diagnostic scheme has been proposed by the Classification of Psoriatic Arthritis (CASPAR) study group (Table 2).21 The CASPAR diagnostic criteria have been criticized recently due to heavy emphasis on radiographic evidence which is only evident late in the disease course, thus limiting the criteria’s usefulness in early diagnosis.22 Other diagnostic criteria for PsA have been proposed, with sensitivities ranging from 56% to 99%, but none have been widely accepted.15,19,20,23 In the absence of a clear consensus on diagnostic criteria for PsA, the clinician must rely upon a cluster of signs and symptoms characteristic for PsA, while ruling out other rheumatic diseases that may mimic PsA (Table 3). An empiric diagnosis of PsA is most often made when a patient with psoriasis presents with inflammatory arthritis. There are many overlapping signs and symptoms among several rheumatic disorders, especially early in the disease course. Although there are no specific laboratory tests to confirm the PsA diagnosis, several blood tests are often performed to rule out differential diagnoses. Erythrocyte sedimentation rate (ESR) and C-reactive protein levels are generally assessed; elevated results indicate the presence of

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Table 3. Differential Diagnosis of Psoriatic Arthritis4,5,24,25
Rheumatoid Factor Present (%) <10

Inflammatory Component* Psoriatic arthritis Yes

Distribution Pattern Asymmetric (16-70%), generally affecting 1-3 joints**, DIP joints (5-15%) or symmetric (25%) Symmetric involvement of MCP, PIP, and MTP joints Variable—DIP joints commonly involved; Heberden’s nodes possible Symmetric joint involvement Large joints (typically lumbar region); occasional MCP, PIP, MTP joint involvement Typically monoarticular inflammation of first metatarsophalangeal joint

Axial Involvement Unilateral sacroiliitis (5%), axial column (20-40%) Cervical

Enthesitis Common (19%)

Dactylitis Yes (50%)

Female:Male Ratio 1:1

Rheumatoid Arthritis Osteoarthritis








Cervical and lumbar



1:1 to 2:1

Systemic lupus erythematosus Ankylosing spondylitis

Yes Yes

80-90 No

No Yes (bilateral sacroiliitis)

No Common

No No

10:1 1:10







Abbreviations: DIP, distal interphalangeal; PIP, proximal interphalangeal; MTP, metatarsophalangeal; MCP, metacarpophalangeal. a Manifested by elevated erythrocyte sedimentation rate and C-reactive protein level. b Typically knee, hip, ankle, hands, feet, wrist.

inflammation. About 40% to 60% of patients with PsA have an ESR that is abnormally high.11 Unfortunately, an elevated ESR is common of any inflammatory arthritis during the early stages and therefore is not useful for differentiating between them. A negative rheumatoid factor (RF) test makes the diagnosis of rheumatoid arthritis much less likely, but a positive RF may occur if the patient suffers from rheumatoid arthritis and PsA concurrently.5 A weakly positive RF can also occur in approximately 10% of patients with PsA.4 Diagnosis is particularly difficult in the 15% to 20% of patients with PsA who do not exhibit psoriasis.1 In these patients, radiographic findings typical of PsA may be the only way to reach a definitive diagnosis.4,11 An assessment of hidden psoriatic lesions in the umbilical area, ears, and hairline should be performed in these patients. Elevated serum uric acid levels may indicate the presence of gout, but active skin turnover seen in psoriasis may also result in high uric acid levels. The absence of

uric acid crystals in the joint are required to rule out a diagnosis of gout.11 Although there is no single pattern of arthritis that is characteristic, the presence of nail lesions, asymmetric sacroiliitis, dactylitis, or enthesitis in a patient suspected of having PsA should result in a high index of suspicion.4,5 Psoriatic nail lesions occur in up to 90% of patients suffering from PsA compared to 40% of patients with psoriasis alone, and these lesions have been strongly associated with the development of PsA.1,11

Drug Therapy
With the introduction of biologic agents, drug therapy for PsA has evolved significantly (Table 4). Most of the currently available agents were originally approved for use in RA but have proven to be beneficial in other autoimmune disorders. Initial therapy for PsA patients involves the use of

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Table 4.
Drug Class and Agent

Drugs and Monitoring Parameters10,26,27,28
Monitoring Parameters and Special Considerations Signs and Symptoms GI pain, dyspepsia, black tarry stool, increased bleeding and bruising GI pain, dyspepsia, increased signs of bleeding and bruising Laboratory Monitoring CBC, serum creatinine

Adult Dosage Range

NSAIDs Various noncyclooxygenase Lowest effective selective anti-inflammatory dosage Cox-2 inhibitors Celecoxib

200-400 mg po qd

CBC, liver function tests, serum creatinine, weight gain, edema

DMARDs Methotrexate

5-7.5 mg po weekly

Sulfasalazine Lefluonimide Biologic Therapies Infliximab

1 g po bid or tid 100 mg qd po for 3 days followed by 20 mg/day 3 or 5 mg/kg iv at weeks 0, 2, and 6, followed by every 8 weeks

GI symptoms, stomatitis, rash, Liver function tests annually, alopecia, jaundice WBC and platelet counts monthly Liver function tests GI intolerance, rash, nausea, vomiting GI symptoms (diarrhea), hypertension, alopecia, rash Infusion related anaphylaxis, infection, screen for nonmelanoma skin cancer in patients with a history of phototherapy Injection site reactions, infection Injection site reactions, infection Baseline CBCa and chem panelb (repeat CBC every 2-6 months), PPD Baseline CBCa and chem. panelb (repeat CBC every 2-6 months), PPD Baseline CBCa and chem. panelb (repeat CBC every 2-6 months), PPD CD4 þ T-lymphocyte counts at baseline, prior to initiation and every 2 weeks during treatment


25 mg sq twice weekly or 50 mg sq weekly 40 mg sq every other week



15 mg im weekly for 12 weeks, Injection site reactions, infection may repeat 12 weeks after last treatment

Abbreviations: NSAIDs, nonsteroidal anti-inflammatory agents; DMARDs, disease modifying anti-rheumatic drugs; qd, once a day; tid, three times a day; bid, twice a day; po, per ose (by mouth); sq, subcutaneous; im, intramuscular; CBC, complete blood count; CD4, cluster of differentiation 4 on T-lymphocytes; GI, gastrointestinal; PPD, purified protein derivative (tuberculosis skin test). a CBC should include platelet count. b Chem panel should include basic electrolytes, liver function tests and serum creatinine.

nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease modifying anti-rheumatic drugs (DMARDs).

Nonsteroidal Anti-inflammatory Drugs and Celecoxib
Although there are limited data to support the use of NSAIDs in PsA, these drugs are commonly used to treat mild cases.29-31 Their usefulness is limited to patients with minimal joint involvement and little to no disability or structural damage.29 Nonsteroidal anti-inflammatory drugs may be used for symptomatic

relief to decrease pain as well as reduce swelling and joint tenderness. These agents have no effect on rashes and do not alter disease progression. There have been reports of exacerbation of psoriasis after treatment with ibuprofen and indomethacin.32 The sole clinical trial that assessed the utility of NSAIDs in PsA was a 4-week randomized, controlled dose-ranging study.30 Eighty patients with PsA were randomized to receive placebo or 100, 200, or 400 mg nimesulide orally daily. After 4 weeks, significant reductions in arthritic symptoms, morning stiffness, and pain severity compared to placebo were reported for the groups receiving 200 and 400 mg nimesulide daily. Psoriasis symptoms remained unchanged.

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Mild gastrointestinal disturbances were reported in 15% of the study population that received nimesulide. It should be noted that hepatotoxicity secondary to nimesulide use has been reported; this agent is not available in the United States.32 Gastrointestinal side effects characteristic of all NSAIDs may limit their use in some patients.29 The frail elderly patients and patients with a history of peptic ulcer disease may benefit from combination therapy with a gastroprotective agent such as misoprostol or a proton pump inhibitor.33 The cyclooxygenase-2 (COX-2) selective inhibitor celecoxib may have less gastrointestinal effects than traditional NSAIDs. To determine the efficacy and safety of celecoxib in the treatment of PsA, a 3-month double-blind, placebo-controlled trial was conducted with 608 patients suffering from PsA flares.31 Participants were randomized to receive placebo, 200 or 400 mg celecoxib orally daily. After 2 weeks, significantly more patients in the 200 and 400 mg celecoxib groups achieved relief from arthritic symptoms and pain compared to the placebo group. The analgesic effect of celecoxib was still evident at 6 weeks, but there were no differences between either of the treatment groups and the placebo group with respect to arthritic symptoms. At 3 months there were no differences relative to placebo, suggesting that celecoxib may only be useful for short-term induction of PsA flare remission.31 The short-term utility of celecoxib may extend to other NSAIDs. In a 6-week trial that compared 0.25 to 0.5 mg/kg etritinate to 1600 mg ibuprofen orally daily in 40 patients with PsA, 19 of 20 patients in the ibuprofen group dropped out.34 Lack of efficacy was cited as the primary reason for withdrawal. The 1-month nimesulide study may not have been long enough to see this reduction in effectiveness over time.30 Longer trials assessing the efficacy of NSAIDs in PsA are warranted.

while topical steroids may be used to treat psoriasis. Low dose oral therapy may be instituted when NSAIDs do not adequately control polyarticular inflammatory symptoms or if side effects secondary to these agents become intolerable. Systemic corticosteroids must be used with caution, however, because of a significant adverse effect profile that includes osteoporosis, reduced glucose tolerance, immunosuppression, cataracts, and avascular necrosis. Once initiated, systemic corticosteroids are often maintained long-term; withdrawal of these agents has been associated with worsening of psoriasis.33 For this reason, some experts consider psoriasis a contraindication for the use of systemic corticosteroids.32 Patients with oligoarticular disease (or those with otherwise well-controlled polyarticular PsA who have one or two persistently inflamed joints) may benefit from periodic intraarticular corticosteroid injections.29 These agents work well for short-term improvement in peripheral arthritis, particularly in the hip joint and sacroiliitis.36 Intraarticular injection of corticosteroids do not generally lead to the serious adverse effects seen with oral administration due to minimal systemic absorption from the intraarticular space; however, care must be taken to assure strict aseptic technique and to avoid injection of joints surrounded by psoriatic plaques.32

Disease Modifying Antirheumatic Drugs
Methotrexate. Moderate to severe manifestations of PsA unresponsive to oral NSAID or intraarticular corticosteroid anti-inflammatory therapies require initiation of DMARD treatment.6,11 Methotrexate (MTX) has been used as standard therapy for PsA treatment since 1964 because of its beneficial effects on both arthritis and psoriatic skin disease.33,37,38 Methotrexate interferes with DNA synthesis and cellular replication by inhibiting dihydrofolate reductase, has a high affinity for tissues with high proliferation rates (eg, neoplasms, bone marrow, and psoriasis), and exhibits immunosuppressive effects. Although methotrexate has shown benefit in rheumatoid arthritis, the exact mechanism of action in PsA is unclear. A small study that recruited 33 patients recently diagnosed with psoriatic arthritis attempted to quantify the effects of methotrexate.39 Patients received 5 to 15 mg of methotrexate orally, once per week for a mean of 2.2 years. Partial or complete remission of both arthritis and psoriatic skin lesions was reported

The use of corticosteroids in PsA is empiric; there are no clinical trials in the literature that have assessed the efficacy or safety of these agents in PsA. Despite the lack of evidence-based data, the use of corticosteroids in PsA is common and widespread.32,35 Corticosteroids may be administered orally, as intraarticular injections, or topically. Oral or intraarticular corticosteroids are common therapeutic agents for the treatment of arthritic flares,

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in 94% of the patients. No hematologic, renal, or hepatic adverse effects were reported. A retrospective analysis compared radiological outcomes in patients with PsA who received methotrexate therapy for 2 years with matched PsA controls who did not receive methotrexate.40 There were no differences between groups, suggesting that methotrexate does not alter disease progression. Another retrospective trial compared 87 patients who received either oral methotrexate or intramuscular gold for the treatment of PsA.41 Although both agents were well tolerated, the likelihood of a positive clinical response was approximately 9 times greater for methotrexate compared to gold. Methotrexate has the potential to cause liver damage, blood dyscrasias, and bone loss. One small retrospective study reported the results of 40 patients with PsA who received a mean oral methotrexate dosage of 11.2 mg once per week over an average duration of 34 months.42 Thirty-eight participants reported a good or excellent subjective response to therapy. Two patients discontinued methotrexate because of leukopenia and stomatitis. Liver function tests were elevated in 11 patients, and liver biopsies revealed 1 patient with cirrhosis. Mild adverse drug reactions within 3 months of methotrexate initiation were reported in approximately 85% of 104 patients with PsA; blood dyscrasias, CNS side effects, and infections required discontinuation in 5 patients.43 Liver function test increases were temporary, mild, and reported to be independent of methotrexate dose. Although hepatic adverse effects do not appear to be a significant concern, methotrexateinduced hepatotoxicity does occur 2.5 to 5 times more commonly in patients with psoriasis compared to RA.44 Some authors have cautioned against longterm methotrexate therapy in patients who are heavy alcohol users.33 Methotrexate is 90% renally excreted unchanged, therefore caution is also warranted in immunocompromised patients and those with renal dysfunction.33 Methotrexate dosage should be reduced by approximately 50% in patients with a creatinine clearance less than 45 mL/min and avoided if the creatinine clearance is less than 20 mL/min.33 Long-term administration of low dose methotrexate was not reported to affect bone density in patients with RA or PsA.45

Cyclosporine. Like methotrexate, the immunosuppressant cyclosporine is a DMARD that is capable

of treating both skin and joint disease.46 A 6-month open label clinical trial assessed the efficacy of cyclosporine in 55 patients with PsA. Patients received a mean oral dose of 2.7 mg/kg/day. A 50% reduction in psoriasis symptom scores was achieved after 6 weeks, while a similar reduction in arthritic complaints occurred after 6 months of treatment. Four patients withdrew from the study because of renal dysfunction, hypertension, and gastroenteritis. Another small open trial achieved similar results.47 Oral cyclosporine at a mean dosage of 3.26 to 4.8 mg/kg/day resulted in a 65% improvement in skin symptom scores after 2 weeks and significant improvement in arthritic symptoms from baseline after 10 weeks. The maximum arthritis treatment effect was observed after 18 weeks. The long-term efficacy of low dose cyclosporine was assessed in a prospective, nonrandomized study that enrolled 60 patients with severe PsA.48 After 2 years, cyclosporine therapy resulted in significant clinical improvement in all patients compared to baseline. Seven patients withdrew secondary to adverse events. Common side effects included hypertrichosis, hypertension, nephrotoxicity, gastrointestinal intolerance, and neurological disturbances. Cyclosporine appears to be an effective agent for psoriasis and PsA. However, the lack of a placebo control in the trials discussed above and the relapsing/remitting nature of PsA make interpretation difficult.46-48 Combination therapy with methotrexate and cyclosporine was assessed in a double-blind placebocontrolled trial in 72 patients with active PsA who had failed to achieve a complete response to methotrexate alone.49 All patients continued methotrexate therapy (15 mg orally once per week or less if unable to tolerate a higher dose) throughout the 1-year trial. Participants were randomized to receive either placebo or 2.5 to 4 mg/kg/day oral cyclosporine in addition to methotrexate. Significant clinical improvements from baseline in some arthritis indices occurred in both groups. Significant improvements in swollen joint count, psoriasis symptoms, and synovitis were reported in the group that received cyclosporine plus methotrexate compared to methotrexate alone. No improvement was noted in quality of life or pain scores in either group over the course of the trial. Adverse events occurred more frequently in the combination therapy group; frequent side effects attributed to cyclosporine included nausea, headache, paresthesias, and hypertension. The clinical improvements noted in both groups highlight the

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necessity for appropriate placebo controls in PsA trials. A 1-year head-to-head prospective randomized trial compared the efficacy and safety profiles of cyclosporine to methotrexate in 35 patients with PsA.50 One group received cyclosporine dosed at 3 to 5 mg/kg/day orally while the other received 7.5 to 15 mg of oral methotrexate per week. After 1 year both groups had improved significantly from baseline but there were no differences between groups in terms of clinical improvement. The group that received methotrexate experienced a significant increase in liver enzymes compared to the cyclosporine group. Cyclosporine has a less favorable side effect profile compared to methotrexate, making it a second-line DMARD choice. Although the rate of withdrawal due to lack of efficacy is similar to that of other DMARDs, patients taking cyclosporine are less likely to continue long-term treatment because of its adverse effect profile.51 The most common side effect resulting in cyclosporine discontinuation is hypertension.51

PsA were randomized to receive 3 mg/kg/day of oral cyclosporine, 2000 mg/day of oral sulfasalazine plus symptomatic therapy, or symptomatic therapy. Symptomatic therapy consisted of NSAIDs, acetaminophen, and/or 5 mg or less of prednisone daily. After 6 months, the mean pain and psoriasis index scores were significantly lower in the cyclosporine group compared with the other two groups. Other indices of arthritis were statistically significantly in favor of cyclosporine compared to symptomatic therapy alone. When the sulfasalazine plus symptomatic therapy group was compared to symptomatic therapy alone, only the spondylitis symptoms were significantly reduced in the group that received sulfasalazine. These results confirm the superiority of cyclosporine over sulfasalazine and suggest that sulfasalazine should be reserved as a third-line agent behind cyclosporine and methotrexate.

Sulfasalazine. Sulfasalazine is an aspirin derivative commonly used in the management of ulcerative colitis and RA. Unlike methotrexate and cyclosporine, several well-designed randomized controlled clinical trials have assessed the effectiveness of sulfasalazine in the treatment of PsA.52-55 Heterogeneous study designs and outcome measures hinder direct comparisons. However, a meta-analysis revealed that sulfasalazine is statistically superior to placebo with respect to improvements in pain, ESR, tender joint score, and patient global assessment.56 In contrast to its established benefits in treating peripheral arthritis, sulfasalazine does not appear to alleviate axial PsA symptoms or cutaneous disease.37,57 Further, it remains unclear if the clinical response seen in PsA is dose-dependent.33 The most common adverse effects secondary to sulfasalazine are gastrointestinal intolerance, dizziness, and liver toxicity.52-55,57 The degree of clinical benefit induced by sulfasalazine compared to other DMARDs has been questioned.33 A prospective open clinical trial compared the efficacy and tolerability of three treatment regimens: sulfasalazine plus symptomatic therapy, cyclosporine monotherapy, and symptomatic therapy alone.58 Ninety-nine patients with

Leflunomide. Leflunomide is a selective pyrimidine synthesis inhibitor that acts as an immunomodulator by decreasing T lymphocyte activation. Based on demonstrated clinical efficacy in RA, two trials have been conducted with leflunomide in patients with PsA.59,60 A small open study assessed the effectiveness of oral leflunomide (dosed 100 mg daily for 3 days followed by 20 mg/day) in 10 patients with PsA who had failed previous therapies with methotrexate, sulfasalazine, and cyclosporine.59 After leflunomide treatment for 6 to 8 months, mild to moderate improvement was reported in pain, joint swelling, and physical activity. No difference was reported from baseline in either pustular or plaquetype psoriatic lesions. A larger 6-month randomized placebo-controlled trial recruited 190 patients with active PsA and psoriasis.60 Patients received placebo or oral leflunomide dosed at 100 mg daily for 3 days followed by 20 mg daily. At the end of the trial, approximately 60% of the treatment group was classified as responders compared to 30% of the control group. Significant improvements were also noted for cutaneous psoriatic lesions and quality of life scores for leflunomide compared to the placebo control. Diarrhea and elevated liver function tests were seen more frequently in the treatment group, but no serious cases of hepatotoxicity were reported. The lack of head-to-head trials with other DMARDs makes it difficult to place leflunomide appropriately in a therapeutic algorithm for PsA. However, this agent appears to treat both arthritic

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and cutaneous symptoms of PsA with a favorable side-effect profile.

Other Agents
Other immunomodulators that have been investigated for the treatment of PsA include colchicine, fludarabine, and gold.61-64 A prospective, placebocontrolled, double-blind crossover trial reported no clinical benefit in 25 patients with PsA who received 0.6 to 1.8 mg colchicine orally daily compared to placebo control.61 The effectiveness of fludarabine, a halogenated adenosine analog, was assessed in a small, placebo-controlled trial in 15 patients with active PsA.62 Patients who received intravenous fludarabine at a dosage of 30 mg/m2 monthly for 4 months exhibited marked peripheral lymphopenia but there were no statistically significant differences in clinical response between groups. A prospective, placebo-controlled trial compared intramuscular and oral gold therapies in 82 patients with PsA.64 Significant clinical improvements were reported for intramuscular gold therapy, but not for the oral form. A large 6-month placebo-controlled trial reported that oral gold had only a minor therapeutic advantage over NSAIDs alone.63 Oral gold worsened psoriasis in a small number of patients.

Biologic Therapies
Numerous advancements in the understanding of the pathogenesis of PsA has led to the development of agents able to target TNF-a, one of the most influential cytokines in the inflammatory cascade. Failure of two adequate trials of standard DMARDs (methotrexate, sulfasalazine, cyclosporine, or leflunomide) indicates the need for initiation of one of the currently available biological agents.65

Infliximab is currently approved for the treatment of Crohn’s disease, RA, PsA, ankylosing spondylitis, and ulcerative colitis. This chimeric human/mouse monoclonal antibody binds to TNF-a directly, inhibiting its inflammatory and biologic activity.6,7,26,27 The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) was a 16-week randomized placebo-controlled two-phase trial that assessed the efficacy of infliximab in 104 patients with PsA who had failed prior therapy with at least

one DMARD.66 During the first 16-week phase of the trial patients were randomized to receive 5 mg/kg infliximab or placebo intravenously at weeks 0, 2, 6, and 14. The second phase was an open-label trial in which all patients received 5 mg/kg intravenous infliximab every 8 weeks for 12 months. There was a statistically significant improvement in psoriatic and articular symptoms in patients treated with infliximab when compared to placebo. Infliximab treated patients reported statistically significant improvements in dactylitis and enthesitis symptoms at week 16 when compared to placebo treated patients. Adverse effects were similar in both phase 1 and phase 2 of the study with respect to adverse events, treatment related adverse effects, severe adverse effects, infusion associated adverse effects, and serious adverse effects. No patients contracted any serious opportunistic infections during the study; there were no reports of autoimmune, cytopenic or neurologic adverse events.66 IMPACT 2 was a 24-week phase III prospective, randomized, placebo-controlled study conducted in a larger patient population with active PsA and psoriasis.67 This trial evaluated the safety and efficacy of infliximab using multiple skin and joint disease assessments. Two hundred patients with active PsA unresponsive to previous therapies were randomized to receive intravenous placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 14, and 22. Infliximab-treated patients had statistically significant improvements in skin and joint disease assessments when compared to placebo. As seen in IMPACT 1, statistically significant improvement was reported in the treatment group for dactylitis and enthesitis symptoms compared to placebo treated individuals.66,67 Infliximab was well tolerated and the incidence of adverse effects, serious adverse events, infection, or infusion type reactions were similar between treatment groups. There were no reports of opportunistic infection, autoimmune, neurologic, or anaphylaxis reported in any patients taking infliximab. Combination therapy with methotrexate was attempted in a group of 26 patients with PsA resistant to multiple DMARDs.68 Clinical improvement was progressive, with the majority of patients experiencing good clinical benefit. After 54 weeks of combination therapy, infliximab was discontinued. The clinical improvement lasted 2 to 6 months with methotrexate monotherapy. Both IMPACT trials demonstrated the efficacy and safety of infliximab in patients with PsA and

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psoriasis.66,67 Although adverse effects were similar between placebo and infliximab treated patients, adverse effects can be serious and should be anticipated with the use of infliximab. Avoidance of this medication in immunocompromised patients is warranted. Development of human antichimeric antibodies (HACA) during the course of therapy for some patients has been noted in some patients due to the murine component of this drug.7 Problems associated with this include loss of treatment effect and the rapid development of antibodies in those individuals who stop the agent and later restart the medication.7 Development of HACA has been diminished with concomitant use of MTX; however, duration or magnitude of response remains unclear.27

compared to placebo. Radiographic assessments of disease progression demonstrated a decrease in the mean annualized rate of change in the etanercept group versus placebo. Etanercept was well-tolerated and adverse effects were similar between groups. Both infliximab and etanercept have demonstrated a definite benefit in PsA therapy.71 However, the ease of subcutaneous administration of etanercept allows patients to self-administer doses, thus avoiding a physician office visit for an infusion. Self-administration may potentially enhance patient adherence to therapy.

Adalimumab is a recombinant human IgG monoclonal antibody specific for TNF-a, which exerts its effect by prevention of TNF-a binding to cell surface receptors.72 Numerous studies have proven its effectiveness in the treatment of PsA.72-76 The Adalimumab Effectiveness in Psoriatic Arthritis (ADEPT) trial was carried out to determine the safety and effectiveness of adalimumab in patients with moderate to severe PsA.72,73 In this 24-week randomized, double-blind, parallel group, placebo-controlled trial, 313 patients received either subcutaneous adalimumab 40 mg every other week or placebo. The adalimumab treatment group reported significant improvements at week 24 for pain, physical functioning, disease activity scores, and quality of life measures compared to the control group. Adalimumab was effective in improving both joint and skin manifestations of PsA. Statistically significant improvements in radiographic progression were also noted for the treatment group compared to placebo. Adverse effects were similar between the adalimumab and placebo groups throughout the 24-week trial. Patients were allowed to continue in an open label study which further evaluated adalimumab treatment for an additional 24 weeks.74 The results following the second 24-week trial continued to demonstrate the safety and efficacy of adalimumab in PsA when compared to placebo. Adalimumab demonstrated a continued decrease in radiographic progression while improving both physical and dermatological complaints. There are limited data comparing TNF inhibitors to DMARD therapies. However, a 6-month observational study in 526 patients with PsA compared TNF inhibitors directly against methotrexate.77 After

Etanercept is a recombinant human soluble TNF receptor composed of the extracellular portion of human p75 fused to the Fc portion of human IgG; this agent binds TNF-a, preventing it from activating to surface receptors.7 Numerous short-term and long-term trials have been conducted to determine its usefulness, safety, and efficacy in PsA and psoriasis patients. A 12-week randomized, double-blind, placebo-controlled trial consisting of 60 individuals evaluated the use of subcutaneous etanercept 25 mg twice weekly compared to placebo.69 Improvements in skin and articular symptoms were evaluated after 12 weeks. At the conclusion of the trial, etanercept-treated patients reported statistically significant improvements in skin and arthritis symptoms when compared to placebo-treated individuals. Injection site reactions were the most reported adverse effect reported in the etanercept group when compared to placebo. This trial established etanercept as an alternative therapeutic choice when treating patients with PsA and psoriasis. Another 24-week trial further demonstrated the safety and efficacy of etanercept in the treatment of PsA. Two hundred five patients with PsA were randomized to receive placebo or etanercept 25 mg subcutaneously twice weekly.70 Following the 24 weeks, 168 patients were enrolled to receive etanercept in an open-label study in a 48-week extension. Efficacy outcomes included improvement of skin and joint symptoms, safety, and benefit of the medication on radiographic disease progression. All individual parameters for arthritis activity were decreased in patients receiving etanercept when

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adjustment for differences in baseline disease activity scores, the patients who received TNF inhibitors improved to a greater extent with respect to pain assessments, global disease activity scores, fatigue, and quality of life measures compared to those who received methotrexate.

Alefacept is a recombinant fusion protein that works by blocking T cell activation and facilitates apoptosis of memory T-cells.78 This agent was the first biologic agent approved for plaque psoriasis. A 12-week randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of alefacept in patients with PsA taking concomitant methotrexate.78 Patients were randomized to receive alefacept 15 mg intramuscularly once weekly or placebo in conjunction with a stable oral methotrexate dose of 10 to 25 mg per week. Statistically significant reductions in skin lesions and tender and swollen joint counts were reported for patients receiving alefacept plus methotrexate compared to placebo plus methotrexate. Adverse effects were similar between groups with serious adverse events occurring in 1.6% of the alefacept group. These adverse events (metrorrhagia, rectocele, and emphysema) were later determined to be unrelated to the study drug. There were no opportunistic infections or malignancies observed.

or methotrexate while on efalizumab or placebo therapy. Following 12 weeks, joint assessments performed in the treatment group were not significantly different when compared to placebo. Side effects were comparable between groups. Efalizumab did not prove effective in treating PsA but did not worsen symptoms. Further studies need to be conducted to determine if this agent is useful in PsA.

Nontraditional Therapies
Ultraviolet light therapy is a mainstay of treatment for psoriatic skin lesions. Ultraviolet B (UVB) radiation at wavelengths between 295 and 313 nm have been used for many years in the treatment and remission induction of psoriasis and other dermatoses.81 Recent innovations in light therapy include narrow-band UVB (NB-UVB) fluorescent lamps that emit a narrow peak around 311 to 312 nm and the combined use of psoralen and ultraviolet A radiation (PUVA). Narrow-band UVB has been demonstrated to be superior to broad-band UVB, and is considered first-line therapy for psoriasis.82 Although PUVA has produced superior results both in terms of efficacy and remission time, this therapeutic option remains second-line for patients unresponsive to NB-UVB because of increased risks for phototoxic reactions and other adverse drug reactions such as nausea and cataracts.81 There is a paucity of literature regarding the use of phototherapy for the treatment of PsA. Extracorporeal photochemotherapy has been attempted, with equivocal results.83,84 This process involves the photoactivation of 8-methoxypsoralen by ultraviolet A light. After photoactivation, the psoralen compound crosslinks the DNA present in lymphocytes; the injured white cells are then infused back into the patient. Extracorporeal photochemotherapy with 8-methoxypsoralen was attempted in 5 patients resistant to conventional therapies for PsA.83 In contrast to a rather dramatic reduction in lymphocyte viability, proliferation and mitogen response noted in vitro, there was only slight to moderate clinical improvement in arthritic symptoms reported in 4 of the 5 patients. Psoriatic skin lesions remained unresponsive to extracorporeal photochemotherapy. In another small trial, 8 patients with PsA received extracorporeal photochemotherapy for 12 weeks

Onercept and Efalizumab
Onercept, a human recombinant TNF receptor, and efalizumab, a human antibody against CD11a, were evaluated for safety and efficacy in PsA with disappointing results.79,80 Onercept was withdrawn by the manufacturer due to two reported cases of sepsis resulting in the death of 1 patient. Although the use of biologic agents predispose individuals to these risks, the manufacturer believed the overall risk/ benefit of the drug did not warrant continuation of onercept in further studies.7,79 Efalizumab is approved for use in psoriasis but has not proven to be effective in PsA. In a phase II randomized, double-blind, placebo-controlled trial patients were given efalizumab 1 mg/kg weekly or placebo for 12 weeks and followed for an additional 12 weeks in an open label study.80 Patients were required to be on at least one concomitant therapy with either an NSAID, corticosteroid, sulfasalazine,

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followed by photophoresis in combination with PUVA for 12 more weeks.84 One half of the patients experienced a marked improvement in arthritic complaints that lasted at least 1 year after the termination of therapy. Larger trials are warranted to determine if a longer treatment duration or combination therapy with PUVA can achieve reproducible long-term results in PsA.

improvement was reported in patients’ global impression scores in the group that received seal oil the end of the trial. No other clinical variables were different between the groups. The usefulness of fish oil for the treatment of PsA remains to be determined.

Mycobacterium Vaccae Silicic Acid
Silicic acid is a compound that contains the elements silicon, hydrogen, and oxygen. The colloidal form of this acid has been used orally and topically for the treatment of aged skin, fragile hair, and brittle nails in women.85 The effects of combined oral and topical therapy with colloidal silicic acid was assessed in a randomized, double-blind study in 30 patients with chronic plaque-type psoriasis.86 Twelve of the 30 suffered from concomitant PsA. All participants were randomized to receive either 10 mL silicic acid gel (Silicol) or placebo gel orally 3 times daily. Psoriatic lesions were treated topically with the same formulation 3 times daily. After 3 months joint pain scores in the 4 patients with arthropathy in the treatment group declined by almost 50% from baseline; no improvement was noted in the control group. Larger controlled trials should be conducted to validate these results. Remission in psoriasis symptoms as well as improvement in atopic dermatitis have been noted following intradermal administration of the nonpathogenic organism Mycobacterium vaccae prepared as a heat-killed suspension for injection.91,92 As a result, a double-blind, placebo-controlled trial was conducted to assess the usefulness of this immunomodulation therapy in 36 patients with PsA.93 Patients were randomized to receive two intradermal injections of 50 mcg of heat-killed Mycobacterium vaccae or placebo. After 6 months, there were no significant differences between groups in terms of arthritic symptoms. However, visual analog pain scores were significantly lower in the treatment group compared to the control group.

The Dead Sea region in Israel attracts patients from considerable distances with a variety of rheumatic complaints for balneotherapy (mud packs and sulfur bath soaks).94 The combination of balneotherapy and soaking in Dead Sea water are believed to alleviate arthritic symptoms.94 Two clinical trials have been conducted assessing the usefulness of balneotherapy in patients with PsA.95,96 In the first study, 166 patients with psoriasis and PsA received a regular regimen of bathing in Dead Sea water and sun exposure.95 The treatment group also received mud packs and sulfur baths, while the control group received no additional therapy. Statistical improvement from baseline was reported for most arthritis indices in both groups. Significant improvement from baseline was reported for reduction of spinal pain and range of lumbar spine movement in the treatment group, but not for the control group. However, this may have been an artifact of sample size since there were 20 patients in the control group compared to 146 in the treatment group. There may not have been enough participants in the control group to avoid type II error.

Fish Oil
The relatively low incidence of PsA in the Eskimo population and limited evidence of the beneficial effects of omega-3 fatty acids in chronic plaque psoriasis led to the hypothesis that fish oil may have a role in the treatment of PsA.87,88 Two clinical trials have evaluated the usefulness of fish oil in PsA.89,90 The potential benefit of a combination of evening primrose oil and fish oil was assessed in 38 patients with PsA.89 Participants were randomized to receive either 12 primrose oil/fish oil capsules (Efamol MarineTM) or 12 placebo capsules daily for 9 months. No clinical improvement was documented in the treatment group, either in terms of arthritic symptoms or NSAID usage. A second double-blind controlled trial compared the effects of seal oil to soy oil in 43 patients with PsA.90 Patients received dietary supplements containing either seal or soy oil orally for 2 weeks. At the end of the trial, a significant, albeit modest,

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The second trial evaluated 42 patients with PsA who were randomized to receive either regular bathing at the Dead Sea with sun exposure (standard therapy) or standard therapy plus treatment with mud packs and sulfur baths.96 After four weeks both groups experienced similar improvement in arthritic symptoms. There were statistically significant improvements in the group that received standard therapy plus balneotherapy compared to the group that received standard therapy for number of tender/swollen joints, inflammatory neck and back pain, and improvement over time.

Health Maintenance
Although there are no established guidelines or consensus regarding immunization in patients with PsA, it makes sense that these patients are at increased risk for infection when taking immunosuppressive therapies.97 There has been a documented increase in tuberculosis (TB) in patients treated with infliximab, etanercept, and adalimumab; the package inserts for infliximab and adalimumab recommend skin testing for TB prior to initiating treatment.98,99 TNF-a is required for the development of granuloma tissue, so activation of latent Mycobacterium tuberculosis infection may be a class effect of all TNF blockers.28 Both the National Psoriasis Foundation and the CDC have recommended TB testing prior to starting treatment with any TNF-a neutralizing agent.99,100 Efalizumab and alefacept have not been associated with the development of TB; however, most rheumatologists perform baseline TB skin testing prior to initiating these agents as well.28 Those patients testing positive for TB should obtain a confirmatory chest radiograph. If the radiograph is negative, the patient should be referred to an appropriate specialist for treatment of latent TB.28 The National Psoriasis Foundation has developed guidelines for vaccinations in patients receiving biologics for psoriasis.28 It is recommended that all patients be brought up to date with all immunizations in agreement with current immunization guidelines101 prior to initiating treatment with biologic agents. Once immunosuppressive therapy has begun, vaccination with live attenuated vaccines (MMR, oral polio, intranasal influenza, varicella, typhoid, yellow fever, and BCG) should be avoided. It is generally accepted that patients receiving 20 mg

prednisone (or prenisone equivalent) daily or less as sole immunosuppressive agent are an exception to this rule. Whenever possible, inactivated and component (acellular or subvirion) vaccines should be given preference over live vaccines (for example, injectible influenza vaccination should be administered instead of intranasal live flu vaccine). Patients with PsA who were treated with etanercept mounted a similar serologic response rate to the 23-valent pneumococcal vaccine compared to those receiving placebo.97 A 2-fold increase in titer to at least two antigens was achieved by 67% of patients, suggesting that patients treated with biologics may be able to respond appropriately to vaccination.97 There is one report that states patients attending rheumatology outpatient clinics who are taking current immunosuppressant drugs do not receive optimal rates of influenza and pneumococcal immunization.102 Raising patient awareness in combination with more aggressive immunization strategies on the part of the health care team may be required to assure timely administration of appropriate immunizations.102

Physical exercise is beneficial in many chronic conditions characterized by a progressive loss in activity levels, such as fibromyalgia and multiple sclerosis. Unfortunately, there is a paucity of data documenting potential beneficial effects of exercise in PsA. A single clinical trial evaluated the effects of strength training in 39 patients with recent-onset rheumatoid arthritis or PsA.103 The treatment group participated in a progressive dynamic strength training program while the control group maintained their normal physical activity level. Compared to the control group, significant improvements were reported in the treatment group for maximal muscle strength, arthritis indices, ESR, and quality-of-life indices after 6 months. Erosive joint changes occurred in both groups, but were less evident in the treatment group. This trial103 suggests that exercise may be beneficial early in the course of PsA; however, the inclusion of rheumatoid arthritis patients in the study group makes interpretation of the data less clear for patients with PsA. Larger studies with more limited inclusion criteria as well as data on the effects of exercise later in the disease course are needed to justify exercise recommendations in this patient population.

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The treatment of PsA depends upon the severity and clinical features of both psoriasis and arthritis.10 The therapeutic challenge lies in the selection of an optimal drug therapy or combination of therapies that alleviate arthritis, enthesitis, dactylitis, axial disease, and psoriatic skin lesions while minimizing side effects and maximizing quality of life.6 Milder forms of PsA may be managed with NSAIDs and intraarticular corticosteroid injections for the arthralgias, and phototherapy or topical corticosteroids for the skin manifestations.8 Data regarding the long-term efficacy of celecoxib are lacking; this agent should only be considered in patients with a history of ulcers. Patients with moderate to severe joint involvement should receive a DMARD such as methotrexate, cyclosporine, sulfasalazine, or leflunomide.8 Combination therapy may be considered.65 Methotrexate, cyclosporine, and leflunomide all have beneficial effects on both skin and joint disease. Sulfasalazine, on the other hand, has not been proven effective in patients with significant skin and nail disease.10 Although evidence-based data exist only for sulfasalazine and methotrexate in PsA, the choice of DMARD is often based on clinical experience and toxicity profile.56 Methotrexate use is limited by its potential to cause hepatotoxicity; this agent should not be used in patients who consume considerable quantities of alcohol. Cyclosporine use is limited by drug-induced nephrotoxicity and hypertension. None of the currently available DMARDs slow the radiographic progression of PsA.32 Failure of two courses of DMARDs justifies initiation of biologic therapy.65 TNF-a inhibitors have shown a dual benefit in targeting not only the arthritis component of the disease but also in treating the psoriatic lesions that often accompany PsA.3 Infliximab is the only drug that has been proven useful for the treatment of dactylitis.104 If one anti-TNF agent is not initially beneficial, loses efficacy, or if toxicity occurs, switching to a different agent in this class has been recommended.105

1. Taurog JD. The spondyloarthritides. In: Fauci AS, Langford CA, eds. Harrison’s rheumatology. New York, NY: McGraw-Hill; 2006:139-156.

2. Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(suppl 2):ii14-ii17. 3. Bergman MJ. Social and economic impact of inflammatory arthritis. Postgrad Med. 2006 May;Spec No:5-11. 4. Furfaro N. Diagnostic signs and symptoms of psoriatic arthritis. Dermatol Nurs. 2006 October; suppl:7-9, 22. 5. Feinstein D, Lawrence B. The complexity of the differential diagnosis for the inflammatory arthritides. Postgrad Med. 2006 May;Spec No:12-23. 6. Mease P. Psoriatic arthritis update. Bull NYU Hosp Jt Dis. 2006;64:25-31. 7. Gladman DD. Traditional and newer therapeutic options for psoriatic arthritis: an evidence-based review. Drugs. 2005;65:1223-1238. 8. Myers WA, Gottlieb AB, Mease P. Psoriasis and psoriatic arthritis: clinical features and disease mechanisms. Clin Dermatol. 2006;24:438-447. 9. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370:263-271. 10. Mease P. Current treatment for psoriatic arthritis and other spondyloarthritides. Rheum Dis Clin North Am. 2006;32(suppl 1):11-20. 11. Gladman DD. Psoriatic arthritis. In: Harris Ed, Budd RC, Genovese MC, et al, eds. Kelley’s Textbook of Rheumatology. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005. 12. Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum. 1973;3:55-78. 13. Zachariae H. Prevalence of joint disease in patients with psoriasis. Am J Clin Dermatol. 2003;4:441-447. 14. Kane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatol. 2003;42:1460-1468. 15. Gladman DD, Shuckett R, Russell ML, Thorne JC, Schachter RK. Psoriatic arthritis (PSA): an analysis of 220 patients. Q J Med. 1987 Feb;62(238):127-141. 16. Gladman DD. Natural history of psoriatic arthritis. Baillieres Clin Rheumatol. 1994;8:379-394. 17. Jones SM, Armas JB, Cohen MG, Lovell CR, Evison G, McHugh NJ. Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumatol. 1994;33:834-839. 18. Kane D, Stafford L, Bresnihan B, FitzGerald O. A classification study of clinical subsets in an inception cohort of early psoriatic peripheral arthritis: ‘DIP or not DIP revisited.’ Rheumatology (Oxford). 2003;42: 1469-1476. 19. Blumberg BS, Bunim JJ, Calkins E, Pirani CL, Zvaifler NJ. ARA nomenclature and classification of arthritis and rheumatism (tentative). Arthritis Rheum. 1964;7:93-97. 20. Helliwell PS, Taylor WJ. Classification and diagnostic criteria for psoriatic arthritis. Ann Rheum Dis. 2005;64(Suppl 2):ii3-ii8.

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