AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Psoriatic arthritis is a chronic inflammatory arthritis that is commonly associated with psoriasis. At least 5% of patients with psoriasis develop psoriatic arthritis. The association between psoriasis and arthritis was first made in the mid 19th century, but psoriatic arthritis was not clinically distinguished from rheumatoid arthritis (RA) until the 1960s. Precisely defining psoriatic arthritis is still difficult because of a lack of specific biologic tests. It is most commonly a seronegative oligoarthritis found in patients with psoriasis with less common but characteristic differentiating features of distal joint involvement and arthritis mutilans. Because 50% of patients with psoriatic arthritis have evidence of spondyloarthropathy, often HLA-B27 associated, psoriatic arthritis has also been classified among the seronegative spondyloarthropathies.

Pathophysiology

Psoriatic arthritis is an autoimmune inflammatory condition affecting the skin and the joints as well as the insertion sites of tendons, ligaments, and fascia. Overexpression of tumor necrosis factor (TNF)-alpha is thought to play a key role. Multiple HLA associations are known. Although psoriatic arthritis is sometimes seen in the absence of detectable skin lesions, it is thought to be more frequent in patients with severe cutaneous disease. However, the exact etiology is unknown and is probably multifactorial, including immune-mediated, genetic, and environmental causes. Environmental factors may include trauma, infection, and stress.

Frequency

United States

In the United States, psoriatic arthritis affects at least 5% of patients with psoriasis. It is thought to occur in up to 1% of the general population. Prevalence rates vary widely between studies; however, a recent random telephone survey of 27,220 US residents found a prevalence rate of psoriatic arthritis to be 0.25% in the general public and 11% among patients with psoriasis.

International

Internationally, the incidence of psoriatic arthritis is 1-40%, depending on the population studied.

Mortality/Morbidity

Psoriatic arthritis usually follows an undulating course, with flares and remissions. Significant morbidity may occur, with long-standing or mutilating disease resulting in joint destruction. Although psoriatic arthritis was originally thought to be relatively mild, as many as 40% of patients may develop erosive and deforming arthritis.

Race

The effect of race on the prevalence of psoriatic arthritis is not well studied. However, whites are known to be more commonly affected than other racial groups.

Sex

Overall, men and women are affected equally. However, a male predominance occurs in the spondylitic form, and a female predominance occurs in the rheumatoid form.

Age

Psoriatic arthritis usually develops in the fourth to sixth decades of life, but it can occur at almost any age.

CLINICAL

Section 3 of 10  

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

History

Psoriatic arthritis may appear in a variety of clinical patterns (see Physical).

• Psoriasis appears to precede the onset of psoriatic arthritis in 60-80% of patients. Occasionally, arthritis and psoriasis appear simultaneously. In addition, cutaneous eruptions may be preceded by the arthropathy.
• Joint stiffness, while not specific for psoriatic arthritis, can be a prominent symptom.
• In a patient who presents with musculoskeletal symptoms without a history of psoriasis, the diagnosis can be suspected based on a family history of psoriasis; the pattern of arthritis; and the presence of psoriasis in frequently overlooked areas, such as the umbilicus, the gluteal cleft, and the ears. Although the association between severe psoriasis and the development of psoriatic arthritis is clear, the severity of psoriasis does not appear to be related to the pattern of joint involvement.
• Factors that do increase the risk of a patient with psoriasis developing arthritis in their lifetime include the presence of nail lesions as well as more extensive skin involvement. A family history of psoriatic arthritis also increases the risk of developing arthritis.

Physical

Diagnosis of psoriatic arthritis can be problematic in the absence of overt skin lesions. Joint findings may include dactylitis (sausage digits), enthesopathy (reflecting inflammation of the insertion points of tendon into bone), tendonitis, and spondylitis. A careful physical examination, including evaluation of the scalp, the gluteal crease, the umbilicus, the axillae, and the nails, may aid in making the diagnosis of psoriatic arthritis.

Scaly, erythematous plaques; guttate lesions; lakes of pus; and erythroderma are all types of psoriatic skin lesions that may be seen in the context of psoriatic arthritis. Nail pitting, Beau lines, leukonychia, onycholysis, oil spots, subungual hyperkeratosis, splinter hemorrhages, spotted lunulae, and cracking of the free edge of the nail all support the diagnosis of psoriatic arthritis, especially of the distal interphalangeal (DIP) joint type. In fact, psoriatic nail changes may be a solitary finding in patients with psoriatic arthritis.

Systemic symptoms are usually limited to ocular involvement, which affects 30% of patients with psoriatic arthritis. Ocular findings may include conjunctivitis, iritis, episcleritis, and keratoconjunctivitis sicca. Aortic insufficiency has also been reported.

Diagnosis is also suggested by the following: asymmetric joint involvement, DIP involvement in the absence of osteoarthritis, dactylitis, and absence of rheumatoid factor (RF) and subcutaneous nodules.

• Clinical patterns of arthritis
• • Asymmetric oligoarthritis occurs in as many as 70% of patients with psoriatic arthritis. As many as 4 large joints are affected, often with acute scattered involvement of the metatarsophalangeal, proximal interphalangeal, and DIP joints. Sausage digits due to inflammation of the flexor tendons and synovium and pitting edema of the distal extremities may be observed.
  • DIP joint involvement occurs in approximately 5-10% of patients with psoriatic arthritis. One or several DIP joints may be involved. Periarticular swelling and acute inflammation with warmth and rubor may occur. DIP joint involvement and concomitant nail involvement with acute paronychia is a characteristic picture.
  • Symmetric psoriatic arthritis of the small joints of the hands and the feet, the knees, and the elbows usually follows a mild course and is difficult to distinguish from RA. RF seronegativity, a history of psoriasis, the presence of DIP involvement, and characteristic radiographic findings all support a diagnosis of symmetric polyarthritis. This form affects as many as 25% of patients.
  • Arthritis mutilans is a rare form of psoriatic arthritis occurring in 5% of patients with psoriatic arthritis. Osteolysis of the phalanges and the metacarpals causes a telescoping motion of the digits, noted as opera-glass deformity or pencil-in-cup radiographic findings. Fever may accompany arthritis mutilans.
  • Spondylitis occurs in about 5% of patients with psoriatic arthritis and is often asymptomatic. Radiographic evidence of sacroiliitis may be present in as many as 20% of patients. The axial spine may be involved alone or in conjunction with peripheral joints. The vertebrae are asymmetrically affected. Atlantoaxial joint involvement may lead to subluxation. Male patients are more frequently affected than female patients.
• Psoriatic nail lesions, soft tissue thickening above the terminal phalanx, and radiologic involvement of the phalanx with periosteal reaction and bone have recently been described under the term psoriatic-onycho-pachydermo-periostitis (POPP). POPP must be differentiated from other forms of psoriatic arthritis, especially the DIP joint type. A periosteal reaction of the terminal phalanx in the absence of DIP joint involvement is characteristic of POPP. In addition, pain and soft tissue thickening is more common in POPP. Nail disease is common to both POPP and DIP psoriatic arthritis. The nails of the great toes are involved in most reported cases of POPP.
• Juvenile psoriatic arthritis is usually mild and often monoarticular. Tenosynovitis and nail involvement are common. Sacroiliitis is associated with HLA-B27 positivity. When unfused epiphyses are inflamed, disordered bone growth and foreshortening can result. Children have a higher frequency of simultaneous onset of psoriasis and psoriatic arthritis.
• Other associations
• • First described by Chamot et al in 1987, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by variable bone changes (hyperostosis, arthritis, aseptic osteomyelitis) of the chest wall, sacroiliac joints, and long bones. Dermatologic manifestations include palmoplantar pustulosis, hidradenitis suppurativa, pustular psoriasis, dissecting cellulitis of the scalp, Sweet syndrome, and Sneddon-Wilkinson disease. Skin and osseous involvement may occur simultaneously or be separated by as long as 20 years.
  • The number of diagnosed cases of psoriasis and psoriatic arthritis has risen dramatically in sub-Saharan Africa in association with the escalating epidemic of HIV infection. Although HIV infection is not known to affect the incidence of psoriasis, it may significantly exacerbate otherwise limited disease. The evolution of mild psoriasis to erythroderma in the setting of a flare-up of psoriatic arthritis may be a sign of HIV infection.

Causes

Although the exact cause of psoriatic arthritis is unknown, genetic, environmental, immunologic, and vascular factors contribute to one's predisposition.

• Genetic factors
• • Approximately 40% of patients with psoriasis or psoriatic arthritis have first-degree relatives who are affected. The sibling occurrence risk is about 8%. Although concordance rates of psoriatic arthritis in twins are not yet known, a 65-72% concordance rate of psoriasis exists between monozygotic twins, compared with a 15-30% concordance for dizygotic twins. A 65-72% concordance exists between monozygotic twins compared with a 15-30% concordance for dizygotic twins.
  • The following HLA associations have been elucidated:
    • Early-onset psoriasis - HLA-Cw6, HLA-B57, HLA-DR7, and HLA-B17
    • Psoriatic arthritis - HLA-B7 and HLA-B27
    • Psoriasis and psoriatic arthritis - HLA-Cw6, HLA-B13, HLA-B17, and HLA-B39
    • Ankylosing spondylitis - HLA-B27
    • Protective - HLA-B22
  • TNF-alpha promoter polymorphisms are also thought to be associated with psoriatic arthritis.
• Environmental factors: Although trauma and infection are thought to play a role in the etiology of psoriatic arthritis, no conclusive evidence exists to support this notion. Infection-mediated molecular mimicry is theorized to play a pathogenic role through immunologic factors.
• Immunologic factors: Much evidence suggests that a T-cell–mediated process drives the pathophysiology of psoriasis and psoriatic arthritis. Activated T cells may contribute to the enhanced production of cytokines found in synovial fluid. Th1 cytokines (eg, TNF-alpha, interleukin (IL)–1-beta, IL-10) are more prevalent in psoriatic arthritis than in RA. Monocytes also play a role in psoriatic arthritis and are responsible for the production of matrix metalloproteinases, which may mediate the destructive changes in the joints of patients with psoriatic arthritis.
• Vascular factors: Slight differences exist in the vascular patterns of joints in psoriatic arthritis compared with those of RA, suggesting possible different pathogenic mechanisms of these diseases.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Gout
Osteoarthritis
Rheumatoid arthritis
Septic arthritis

WORKUP

Section 5 of 10  

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

Lab Studies

• Psoriatic arthritis is a chronic inflammatory condition for which no specific laboratory tests are available. The diagnosis is based primarily on clinical and radiographic findings. The main differential diagnosis is RA.

  Comparison of Expected Laboratory Values in Psoriatic Arthritis and RA

  Laboratory studies	Psoriatic arthritis	Rheumatoid arthritis
  Erythrocyte sedimentation rate	Elevated ( <100)	Elevated ( <100)
  RF	Negative	Positive (85% of patients)
  Antinuclear antibody	Negative	Positive (30% of patients)
  C-reactive protein	Elevated	Elevated
  Synovium	WBC count 5-15,000/µL, 50% polymorphonuclear leukocytes	WBC count 2,000/µL

Imaging Studies

• The following radiographic abnormalities are suggestive of psoriatic arthritis:
• • Paramarginal erosions without osteopenia
  • Fluffy periosteal bone formation
  • Bony ankylosis
  • Pencil-in-cup deformity
  • Acro-osteolysis
  • Asymmetric sacroiliitis
  • Large, nonmarginal, nonconsecutive syndesmophytes

TREATMENT

Section 6 of 10  

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

Medical Care

The goal of treatment is to improve the patient's quality of life and range of motion, to suppress inflammation, and to minimize the eventual development of destructive joint disease. Surgical intervention in the case of severe joint involvement is occasionally necessary. Regular exercise and an adequate amount of rest are central in the management of psoriatic arthritis.

Medical treatment regimens range from nonsteroidal anti-inflammatory drugs (NSAIDs) to disease-modifying antirheumatic drugs (DMARDs) to newer biologic therapies, such as the anti-TNF-alpha medications. Although traditional therapy has consisted of NSAIDs and local corticosteroid injections, with DMARDs being reserved for NSAID-resistant cases, the finding that 40% of patients may develop erosive and deforming arthritis suggests that early, more aggressive treatment with DMARDs may be warranted.

• NSAIDs are a first-line therapy for joint disease. They may be used in combination with topical therapy for skin involvement. In some cases, NSAIDs may cause worsening of skin involvement, in which case, a different family of NSAIDs should be used.
• The most widely used DMARDs are methotrexate (MTX), sulfasalazine, and cyclosporine. These are safe and effective in treating active peripheral arthritis but are not effective in treating axial disease. In addition, no controlled studies have evaluated their efficacy in preventing radiologic joint damage. Combining MTX with cyclosporine or sulfasalazine, as is seen in the treatment of RA, may be more effective in some patients.
• Etanercept (Enbrel) is a biologic agent that inhibits TNF-alpha and has efficacy for treating psoriatic arthritis. It is a fusion protein of the TNF receptor bound to human immunoglobulin G1 (IgG1) Fc domain. Etanercept has been shown to prevent bony erosions and was approved by the US Food and Drug Administration (FDA) for psoriatic arthritis in early 2002. It has been available for therapy for RA for many years and has a good safety profile. Two other TNF-alpha inhibitors, infliximab (Remicade) and adalimumab (Humira), are also now approved by the FDA to reduce signs and symptoms of active arthritis in patients with psoriatic arthritis. Infliximab also has been shown to prevent bone erosions. Alefacept, a T-cell inhibitor, has also recently been demonstrated to improve signs and symptoms of psoriatic arthritis when used in combination with MTX.
• Mycophenolate mofetil (CellCept), an immunosuppressive agent widely used in organ transplantation and gaining favor in treating autoimmune and inflammatory skin disorders, may be effective in treating psoriatic arthritis. However, larger controlled studies are needed to prove its efficacy.
• Antimalarials are generally avoided in patients with psoriatic arthritis for fear of exacerbating psoriatic skin lesions. However, 2 case series describing 50 and 31 patients treated with hydroxychloroquine (Plaquenil) found that no patients had exacerbations of their skin lesions. Given the lack of controlled trials, use of this therapy is not encouraged.
• Systemic corticosteroids are generally avoided because of possible withdrawal-induced rebound of skin disease.

MEDICATION

Section 7 of 10  

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

Although indomethacin is the strongest of the available traditional NSAIDs, it is best used for short-term treatment of acute flare-ups because of its GI and CNS adverse effects and its potential to increase blood pressure.

COX-2 inhibitors may be the optimal agents in patients at risk for GI toxicity with NSAIDs.

MTX and cyclosporine are effective in treating both skin disease and joint disease, while sulfasalazine is only effective in treating joint disease. The main limitation of MTX is hepatotoxicity, but liver biopsy may not be necessary in patients receiving very low doses of MTX. The main limitation of cyclosporine is renal toxicity.

Etanercept (Enbrel) is approved by the FDA for psoriatic arthritis. It has been available for therapy for RA for many years and has a good safety profile as to the risk of infection and malignancy. Infliximab (Remicade) and adalimumab (Humira) are monoclonal anti-TNF antibodies that are also now approved by the FDA to treat psoriatic arthritis. Both etanercept and infliximab are also approved for the treatment of psoriasis, which can be an advantage in patients with concurrent arthritis and skin disease.

Drug Category: Nonsteroidal anti-inflammatory drugs

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action may be inhibition of COX activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions, may also exist.

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 total daily dose of 200 mg
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; persons at 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 - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; 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 leukopenia, granulocytopenia, or thrombocytopenia persists

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 - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; 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 rarely occurs, 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 PO divided 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 - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; 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 leukopenia, granulocytopenia, or thrombocytopenia persists)

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 - Safety for use during pregnancy has not been established.
Precautions	Category D in third trimester of pregnancy; 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 rarely occur and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if leukopenia, granulocytopenia, or thrombocytopenia persists; 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 plasma concentrations because of inhibition of celecoxib metabolism; coadministration with rifampin may decrease plasma concentrations
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; 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 - Safety for use during pregnancy has not been established.
Precautions	Category D in third trimester of pregnancy; 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 leukopenia, granulocytopenia, or thrombocytopenia persists)

Drug Category: Immunosuppressant agents

These agents inhibit key factors in the immune system that are 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 UV-B 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 - Safety for use during pregnancy has not been established.
Precautions	Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzyme levels; may increase risk of infection and lymphoma; reserve IV 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 Name	Infliximab (Remicade)
Description	Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Mix in 250 mL normal saline for infusion over 2 h. Must use with low-protein–binding filter (<1.2 µm). Indicated to reduce signs and symptoms of active arthritis in patients with psoriatic arthritis and to help prevent bone erosions.
Adult Dose	5 mg/kg IV infusion at 0, 2, and 6 wk as induction regimen; then, 5 mg/kg q8wk for maintenance IV infusion must be administered over at least 2 h; must use infusion set with in-line, sterile, nonpyrogenic, low-protein–binding filter (pore size <1.2 µm)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; more cases of lymphoma were observed in TNF-alpha blockers compared with control groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections

Drug Name	Adalimumab (Humira)
Description	Recombinant human IgG1 monoclonal antibody specific for human 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 adalimumab 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 - Usually safe but benefits must outweigh the risks.
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 lupuslike syndrome; may cause hypersensitivity reactions, including anaphylaxis and adverse hematologic effects (ie, pancytopenia, aplastic anemia)

Drug Category: 5-Aminosalicylic acid derivatives

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

FOLLOW-UP

Section 8 of 10  

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

Deterrence/Prevention:

• Medications to avoid when possible include beta-blockers, antimalarials (although hydroxychloroquine has been shown to not exacerbate skin lesions), lithium, systemic steroids, and NSAIDs (If skin lesions worsen with an NSAID, switch to a different family of NSAID.).
• Prevention includes rest and exercise. Joint protection, including splints, braces, and other supports, may be helpful. No definitive prevention exists because this is a chronic disease that can wax and wane.

Complications:

• Spondylitis resulting in atlantoaxial subluxation with resultant neurologic complications can occur. Therapy may limit possible disability.

Prognosis:

• Psoriatic arthritis is often mild, with involvement of only a few joints. Treatments with immunomodulatory medicine can be successful for patients with severe disease.

Patient Education:

• For excellent patient education resources, visit eMedicine's Psoriasis Center and Arthritis Center. Also, see eMedicine's patient education articles Psoriatic Arthritis, Psoriasis, Types of Psoriasis, Understanding Psoriasis Medications, and Nail Psoriasis.
• Excellent information for patients can be found at the following Web sites:
• • Arthritis Foundation
  • The National Psoriasis Foundation
  • University of Missouri Health Care
  • The Merck Manual of Diagnosis and Therapy - Arthritis associated with spondylitis
  • MEDLINEplus - Psoriatic arthritis

MULTIMEDIA

Section 9 of 10  

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

Media file 1:  Severe psoriatic arthritis showing involvement of the distal interphalangeal joints; distal flexion deformity; and telescoping of the left third, fourth, and fifth digits due to destruction of joint tissue.
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Media type:  Photo

Media file 2:  Psoriatic arthritis showing nail changes, distal interphalangeal joint swelling, and sausage digits.
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Media type:  Photo

REFERENCES

Section 10 of 10

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

• Antoni C, Krueger GG, de Vlam K, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. Aug 2005;64(8):1150-7. [Medline].
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Article Last Updated: Jan 26, 2007