eMedicine World Medical Library

Psoriatic Arthritis

Last Updated: January 7, 2005
Synonyms and related keywords: psoriasis, arthritis, skin disease, bone disease, rheumatism, rheumatoid arthritis, psoriatic arthropathy, arthritis mutilans, arthropathia psoriatica, psoriatic spondylitis, asymmetrical seronegative oligoarticular arthritis, dactylitis, sausage digits, pencil-in-cup radiograph, opera-glass hand

  AUTHOR INFORMATION  

Author: Anwar Al Hammadi, MD, Staff Physician, Department of Dermatology, McGill University

Coauthor(s): Peter D Gorevic, MD, Professor and Chief, Division of Rheumatology, Mount Sinai School of Medicine

Anwar Al Hammadi, MD, is a member of the following medical societies: American Academy of Dermatology

Editor(s): Kristine M Lohr, MD, Associate Chief, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology, University of Tennessee School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Herbert S Diamond, MD, Chairman, Department of Internal Medicine, Professor of Medicine, Temple University School of Medicine, Department of Internal Medicine, Western Pennsylvania Hospital; Alex J Mechaber, MD, FACP, Director of Clinical Skills Program, Assistant Professor, Department of Internal Medicine, Division of General Internal Medicine, University of Miami School of Medicine; and Arthur Weinstein, MD, Associate Chairman of Medicine and Director, Professor of Medicine, Georgetown University Medical Center, Section of Rheumatology, Washington Hospital Center
  INTRODUCTION  

Background: In 1964, the American Rheumatism Association listed psoriatic arthritis as a clinical entity. However, diagnostic criteria have not been agreed upon, and several proposed definitions have stressed separate features of this multifaceted disease.

The high frequency of distal joint involvement in psoriatic arthritis compared to rheumatoid arthritis and arthritis mutilans (as an unusual but characteristic manifestation) have received special attention. The great variety of clinical manifestations were framed in the definition suggested by Moll and Wright in 1973, ie, "An inflammatory arthritis associated with psoriasis, usually with a negative sheep cell agglutination (SCA) test, ie, rheumatoid factor."

Other more detailed criteria have been suggested. Psoriatic arthritis, a term used by the American Rheumatism Association, is widely accepted.

Pathophysiology: Psoriatic arthritis is an autoimmune disease with known human leukocyte antigen (HLA)–associated risk factors. Psoriatic arthritis affects the ligaments, tendons, fascia, and joints. It occasionally develops in the absence of detectable psoriasis, and it may occur at higher frequencies when skin involvement is more severe, especially when pustular psoriasis is present, although recent studies suggest that this may not be valid.

Frequency:

  • In the US: Psoriasis affects 2.5% of the white population of North America, but it is less prevalent in the African American and Native American populations. Psoriatic arthritis affects 5-8% of patients with psoriasis.

    Recent survey results indicate approximately 1 million US adults have psoriatic arthritis. This figure is significantly higher than researchers had previously believed, and suggests many people with psoriasis, a related skin disease, may not be aware they have psoriatic arthritis. (This is according to a new study conducted by the National Psoriasis Foundation [NPF].)

  • Internationally: Estimates of the frequency of psoriatic arthritis in patients with all types of psoriasis vary widely according to the nature of the diagnostic criteria and ascertainment used, but most fall into the range of 5-8%. Considering the frequency of psoriasis to be 1-3%, the prevalence of psoriatic arthritis in the general white population ranges from 0.05-0.24%, a value approaching half that of seropositive rheumatoid arthritis.

Mortality/Morbidity: The course of psoriatic arthritis usually is characterized by flares and remissions. Arthritis mutilans is recognized as a typical but unusual form of psoriatic arthritis. Earlier studies have reported that psoriatic arthritis results in joint destruction and severe disability in a large proportion of patients. Of patients observed in a large outpatient psoriatic arthritis clinic, 7% required musculoskeletal surgery.

Race: Psoriatic arthritis is more common in white persons than in persons of other races.

Sex: Men and women are affected equally; but, in the subsets of psoriatic arthritis, male predominance occurs in the spondylitic form, whereas female predominance occurs in the rheumatoid form.

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

History: The following list details the 5 patterns of psoriatic arthritis involvement:

  • Asymmetrical oligoarticular arthritis
    • Until recently, this was thought to be the most common type.
    • Usually, the digits of the hands and feet are affected first, with inflammation of the flexor tendon and synovium occurring simultaneously, leading to the typical "sausage" appearance (dactylitis).
    • Usually, fewer than 5 joints are affected at any one time.
  • Symmetrical polyarthritis
    • Recently, this rheumatoidlike pattern has been recognized as one of the most common types. The hands, wrists, ankles, and feet may be involved.
    • It is differentiated from rheumatoid arthritis by the presence of distal interphalangeal (DIP) joint involvement, the relative asymmetry, the absence of subcutaneous nodules, and a negative test result for rheumatoid factor. This condition generally is milder than rheumatoid arthritis, with less deformity.
  • Distal interphalangeal arthropathy
    • Although DIP joint involvement is considered classic and unique to psoriatic arthritis, it occurs in only 5-10% of patients, primarily men.

    • Involvement of the nail with significant inflammation of the paronychia and swelling of the digital tuft may be prominent, occasionally making appreciation of the arthropathy more difficult.
  • Arthritis mutilans
    • Resorption of bone (osteolysis) with dissolution of the joint, observed as the "pencil-in-cup" radiographic finding, leads to redundant overlying skin with a telescoping motion of the digit.

    • This "opera-glass hand" is more common in men than in women and is more frequent in early-onset disease.
  • Spondylitis with or without sacroiliitis
    • This occurs in approximately 5% of patients with psoriatic arthritis and has a male predominance.
    • Clinical evidence of spondylitis, sacroiliitis, or both can occur in conjunction with other subgroups of psoriatic arthritis.
    • Spondylitis may occur without radiologic evidence of sacroiliitis, which frequently tends to be asymmetric, or it may appear radiologically without the classic symptoms of morning stiffness in the lower back. Thus, poor correlation can exist between symptoms and radiologic signs of sacroiliitis.
    • Vertebral involvement differs from that observed in ankylosing spondylitis. Vertebrae are affected asymmetrically, and the atlantoaxial joint may be involved with erosion of the odontoid and subluxation.
    • Unusual radiologic features may be present, such as nonmarginal asymmetric syndesmophytes (characteristic), paravertebral ossification, and, less commonly, vertebral fusion with disk calcification.
  • Juvenile psoriatic arthritis
    • Juvenile psoriatic arthritis accounts for 8-20% of childhood arthritis and often is monoarticular at onset.

    • The mean age of onset is 9-10 years, with a female predominance. The disease usually is mild, although occasionally it may be severe and destructive, progressing into adulthood.

    • In 50% of children, the arthritis is monoarticular, and DIP involvement occurs in a similar percentage.

    • Tenosynovitis is present in 30% of children, and nail involvement is present in 71%, with pitting being the most common but least specific finding.

    • In 47% of children, disordered bone growth with resultant shortening may result from involvement of the unfused epiphyseal growth plate by the inflammatory process.

    • Sacroiliitis occurs in 28% of children and usually is associated with HLA-B27 positivity.

    • Although the presence of HLA-B8 may be a marker of more severe disease, HLA-B17 usually is associated with a mild form of psoriatic arthritis.

    • Children have a higher frequency of simultaneous onset of psoriasis and arthritis than adults, with arthritis preceding psoriasis in 52% of children.
  • Psoriatic arthritis may be present with or without obvious skin lesions; with minimal skin involvement such as the scalp, umbilicus, or intergluteal cleft; or with only nail malformations. Psoriasis usually precedes arthritis (occasionally by as many as 20 y); however, in as many as 15-20% of patients, arthritis appears before the psoriasis. If the latter is the case, a family history of psoriasis may reveal a hereditary pattern.

  • Initial symptoms may be acute. When localized to the foot or toe, symptoms may be mistaken for gout. Alternatively, patients may experience only stiffness and pain with few objective findings.

Physical: Recognition of the patterns of joint involvement as described in History is essential to the diagnosis of psoriatic arthritis.

  • Recently, the possibility that less joint tenderness occurs with psoriatic arthritis than with rheumatoid arthritis has been emphasized.
  • The term enthesopathy or enthesitis, reflecting inflammation at tendon or ligament insertions into bone, may be seen in psoriatic arthritis as in other spondyloarthropathies. This is observed more often at the attachment of the Achilles tendon and the plantar fascia to the calcaneus with the development of insertional spurs.
  • Dactylitis with sausage digits is seen in as many as 35% of patients.
  • Skin involvement includes the following:
    • Arthritis generally is not considered to correlate strongly to any particular type of psoriasis or to the severity of the skin disease. However, in one study, arthritis was noted more frequently in patients with severe skin disease, whereas in another, pustular psoriasis was associated with more severe psoriatic arthritis.
    • In patients presenting with an undefined seronegative polyarthritis, looking for psoriasis in hidden sites such as the scalp (where psoriasis frequently is mistaken for dandruff), perineum, intergluteal cleft, and umbilicus is extremely important.
    • A diagnosis of psoriatic arthritis may be missed because of an inadequate physical examination.
  • Nail involvement includes the following:
    • Onycholysis, transverse ridging, and uniform nail pitting are 3 features of nail involvement that should be noted. A direct correlation exists between the number of pits and the diagnostic significance. When skin and joint disease begin simultaneously, nail involvement frequently is present at onset.
    • Involvement of DIP joints correlates moderately well with psoriasis in adjacent nails, although this is not an invariable association.
    • Nails are involved in 80% of patients with psoriatic arthritis but in only 20% of patients with uncomplicated psoriasis.
    • Severe deforming arthritis of the hands and feet frequently is associated with extensive nail involvement.
    • Fungal infection of the nails is the main consideration in the differential diagnosis in a patient with a seronegative polyarthritis.
  • Extraarticular features include the following:
    • Extraarticular features are observed less frequently in patients with psoriatic arthritis than in those with rheumatoid arthritis. In psoriatic arthritis, a predilection exists for synovitis to affect flexor tendon sheaths with sparing of the extensor tendon sheath; both commonly are involved in rheumatoid arthritis. Subcutaneous nodules are rare in patients with psoriatic arthritis. If nodules are present in a patient who has psoriasis and arthritis, particularly if the rheumatoid factor titer is positive, they suggest the coincidental occurrence of psoriasis and rheumatoid arthritis.
    • Ocular involvement may occur in 30% of patients with psoriatic arthritis, including conjunctivitis in 20% and acute anterior uveitis in 7%. In patients with uveitis, 43% have sacroiliitis and 40% are HLA-B27–positive. Scleritis and keratoconjunctivitis sicca are rare.
    • Inflammation of the aortic valve root, which may lead to insufficiency, has been described in 6 patients with psoriatic arthritis and is similar to that observed more frequently in ankylosing spondylitis and Reiter syndrome. Occasionally, patients may develop secondary amyloidosis.

Causes: The pathogenesis of psoriatic arthritis remains unknown, but much information has been gathered. In addition to the genetic influences, environmental and immunological factors are thought to be prominent in the development and perpetuation of the disease. The de novo development or exacerbation of psoriasis and psoriatic arthritis in patients with human immunodeficiency virus (HIV) infection and CD4 deficiency remains controversial.

Psoriasis may remit following allogeneic bone marrow transplantation and may exacerbate with interferon-alfa treatment for hepatitis C.

  • Genetics
    • Approximately 40% of patients with psoriasis or psoriatic arthritis have a family history of these disorders in first-degree relatives. The exact mechanism of the association between HLA and psoriatic arthritis is not clear.
    • HLA-B13, HLA-B17, HLA-B39, and Cw*0602 are found to occur with increased frequency in both psoriasis and psoriatic arthritis when compared to the general population.
    • Psoriatic arthritis shows an increased frequency of HLA-B7 and HLA-B27 and a lower frequency of HLA-DR7 and Cw7.
    • HLA-B27 in the presence of HLA-DR7, HLA-DQ3 in the absence of HLA-DR7, and HLA-B39 are predictors for disease progression, whereas HLA-B22 is protective.
    • Certain immunoglobulin genes also have been suggested to be associated with psoriatic arthritis.
    • Genome scan studies have demonstrated associations with genetic markers.
    • In psoriasis, linkages with loci on 17q, 4q, and 6p have been reported in whole genome scans, with the strongest evidence for linkage on 6p. Recent studies in psoriatic arthritis have demonstrated associations with genetic markers. These include a tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism and class I major histocompatibility complex (MHC) chain-related gene A.
  • Immunologic factors
    • The pathologic process of skin and joint lesions in psoriatic arthritis is an inflammatory reaction, and evidence also exists for autoimmunity, perhaps mediated by complement activation. The inflammatory nature of the skin and joint lesions in psoriatic arthritis is demonstrated by synovial-lining cell hyperplasia and mononuclear infiltration, resembling the histopathologic changes in rheumatoid arthritis. However, synovial-lining hyperplasia is less, macrophages are fewer, and vascularity is greater in psoriatic arthritis compared with rheumatoid arthritis synovium.
    • The cytokine profile in psoriatic arthritis reflects a complex interplay between T cells and monocyte macrophages. Th1 cytokines (eg, TNF-alpha, interleukin-1 beta, interleukin-10) are more prevalent in psoriatic arthritis than in rheumatoid arthritis, suggesting that these 2 disorders may result from a different underlying mechanism.
    • Antiepidermal keratin and anticytokeratin 18 antibodies have been found in the sera of patients with psoriasis and psoriatic arthritis. Several studies have shown a significant reduction in the number and percentage of CD4+ T cells in the peripheral blood, whereas they are found throughout the skin lesions and synovium.
    • Dendritic cells have been found in the synovial fluid of patients with psoriatic arthritis and are reactive in the mixed leukocyte reaction; the inference is that the dendritic cells present an unknown antigen to CD4+ cells within the joints and skin of patients with psoriatic arthritis, leading to T-cell activation.
    • Fibroblasts from the skin and synovia of patients with psoriatic arthritis have an increased proliferative activity and the capability to secrete increased amounts of interleukin-1, interleukin-6, and platelet-derived growth factors. Several studies suggest that cytokines secreted from activated T cells and other mononuclear proinflammatory cells induce proliferation and activation of synovial and epidermal fibroblasts.
    • Psoriatic plaques in skin have increased levels of leukotriene B4. Injections of leukotriene B4 cause intraepidermal microabscesses, suggesting a role for this compound in the development of psoriasis.
  • Infections
    • The temporal relationship between certain viral or bacterial infections and the development or exacerbation of psoriasis or psoriatic arthritis suggests a possible pathogenetic role for these organisms.
    • Pustular psoriasis is a well-described sequela of streptococcal infections. However, the response to streptococcal antigens by cells from patients with psoriatic arthritis is not different from that of cells from patients with rheumatoid arthritis, making the role of Streptococcus species in psoriatic arthritis doubtful.
    • Psoriasis and psoriatic arthritis have been reported to be associated with HIV infection and to be prevalent in some HIV-endemic areas. Although the prevalence of psoriasis in patients infected with HIV is similar to that in the general population, patients with HIV infection usually have more extensive erythrodermic psoriasis and patients with psoriasis may present with exacerbation of their skin disease after being infected with HIV.
  • Trauma: A few studies have reported the occurrence of arthritis and acroosteolysis after physical trauma in patients with psoriasis.
  DIFFERENTIALS  

Gout
Osteoarthritis
Reactive Arthritis and Reiter Syndrome
Rheumatoid Arthritis
Septic Arthritis


Other Problems to be Considered:

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


  WORKUP  

Lab Studies:

  • No specific diagnostic tests are available for psoriatic arthritis. Diagnosis of the disease is made based on clinical and radiologic criteria in a patient with psoriasis.
    • Immunoglobulin M (IgM) rheumatoid factor in serum usually is absent. However, in 33% of patients, immunoglobulin G (IgG) antiglobulins have been detected in serum. When IgM rheumatoid factor positivity is studied in a group of patients with psoriatic arthritis and a similar comparison is undertaken in an age-matched and sex-matched normal population, rheumatoid factor positivity generally is found to be comparable in both groups.
    • The erythrocyte sedimentation rate may be elevated in patients with active psoriatic joint disease, but elevations higher than 100 mm/h (Westergren method) are uncommon. Severe skin and joint disease may be associated with a mild normochromic normocytic anemia and leukocytosis. Acute phase reactants, such as alpha2-macroglobulin, may be increased.
    • Antinuclear antibody titers in psoriatic arthritis do not differ from those of age-matched and sex-matched control populations. In 10-20% of patients with generalized skin disease, the serum uric acid concentration may be increased and, on occasion, may predispose to acute gouty arthritis. Low levels of circulating immune complexes have been detected in 56% of patients with psoriatic arthritis but do not appear to parallel disease activity.
    • The associations of psoriatic arthritis with HLA-B17, HLA-B13, and HLA-B27 were described under Genetics. Serum immunoglobulin A levels are increased in two thirds of patients with psoriatic arthritis and in one third of patients with psoriasis. Levels of IgM tend to increase with severe disease, but IgG levels usually are not elevated.
    • Synovial fluid is inflammatory, with cell counts ranging from 5,000-15,000/mm3 and with more than 50% of cells being polymorphonuclear leukocytes. Within the synovium, the infiltrate consists predominantly of T lymphocytes. Synovial fluid complement levels are either within reference ranges or increased, and glucose levels are within reference ranges.

Imaging Studies:

  • Radiological features have helped to distinguish psoriatic arthritis from other causes of polyarthritis. In general, the common subtypes of psoriatic arthritis, such as asymmetric oligoarthritis and symmetric polyarthritis, tend to result in only mild erosive disease. Early bony erosions occur at the cartilaginous edge, and cartilage initially is preserved with maintenance of a normal joint space.
  • Juxtaarticular osteopenia, which is a hallmark of rheumatoid arthritis, is minimal in psoriatic arthritis. Asymmetric erosive changes in small joints of the hands and feet are typical of psoriatic arthritis and have a predilection (in decreasing order) for DIP, proximal interphalangeal (PIP), metatarsophalangeal, and metacarpophalangeal (MCP) joints.
  • Erosive disease frequently occurs in patients with either DIP involvement or progressive deforming arthritis and may lead to subluxation and, less commonly, bony ankylosis of the joint. Erosion of the tuft of the distal phalanx, and even the metacarpals or metatarsals, can progress to complete dissolution of the bone. Although this form of acroosteolysis is not diagnostic, it is very suggestive of psoriatic arthritis. The pencil-in-cup deformity observed in the hands and feet of patients with severe joint disease usually affects the DIP joints but also may involve the PIP joints.
  • CT scan of the sacroiliac joint may be a sensitive method of visualizing involvement in patients with spondylitis or sacroiliitis.
  • Recent studies have indicated that MRI may be a sensitive method for demonstrating typical enthesopathic pathology of psoriatic arthritis, particularly in the hands and feet.

Other Tests:

  • Traditional methods of monitoring patients with rheumatic conditions include clinical assessment for joint inflammation or damage and radiographic evaluations. The radiologic scoring methods for evaluating peripheral joints in psoriatic arthritis were developed for patients with rheumatoid arthritis. A study validated the original Steinbrocker method, a modified Steinbrocker method, and the Larsen method for assessment of radiographs in patients with psoriatic arthritis. The latter 2 methods now can be used to assess disease progression in patients with psoriatic arthritis.
Histologic Findings: The histopathology of psoriatic synovitis is similar to that observed in other inflammatory arthritides, with a notable lack of intrasynovial immunoglobulin and rheumatoid factor production and a greater propensity for fibrous ankylosis, osseous resorption, and heterotopic bone formation.

  TREATMENT  

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

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

  • Intraarticular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients.
    • Use disease-modifying drugs in individuals whose arthritis is persistent. If the skin disease is well controlled with topical medication, the joint disease can be treated with a variety of second-line or cytotoxic drugs.

    • Intramuscular administration of gold has been used in the past but has been supplanted by newer disease-modifying antirheumatic drugs.
  • In patients with severe skin inflammation, medications such as methotrexate (MTX), retinoic-acid derivatives, and psoralen plus ultraviolet light (PUVA) should be considered. These medications have been shown to work for both skin and joint manifestations.
  • Sulfasalazine and cyclosporine are 2 second-line agents that have received particular attention in the management of psoriatic arthritis. Although these drugs may control the acute inflammation in psoriatic arthritis, they have not been helpful in arresting the progression of clinical and radiologic damage. Thus, the disease must be treated earlier or better drugs are necessary to prevent the damage that may ensue as a result of psoriatic arthritis.
    • Cyclosporine appears to be an effective agent for the treatment of psoriasis and psoriatic arthritis.

    • The major concern with cyclosporine is its toxicity, especially nephrotoxicity and hypertension. Combination therapy (eg, MTX/sulfasalazine, MTX/cyclosporine) may be more efficacious in some patients.
  • Anti–TNF-alpha therapy, such as etanercept (Enbrel) and infliximab (Remicade) has reportedly been used in treatment of psoriatic arthritis. Etanercept was recently approved by the US Food and Drug Administration.

  • Several other modalities have been tried in psoriatic arthritis, including vitamin D-3, bromocriptine, peptide T, and fish oils, but their efficacy remains to be proven.

  • Antimalarials, particularly hydroxychloroquine (Plaquenil), usually are avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. Two studies showed that these reactions did not occur in patients treated with hydroxychloroquine; therefore, it is used occasionally.

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

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

Diet: For people who have morning stiffness, the optimal time for taking an NSAID might be after the evening meal and again upon awakening. Taking NSAIDs with food can reduce stomach discomfort. All NSAIDs are capable of damaging the mucous layer and causing ulcers and GI bleeding when taken for long periods. Cyclooxygenase-2 (COX-2) selective inhibitors are associated with a lower incidence of gastric ulcers.

Activity:

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

  MEDICATION  

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

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

Several selective COX-2 inhibitors, such as celecoxib and rofecoxib, have been developed and may be the optimal agents in patients at risk for GI toxicity with NSAIDs. NSAIDs clearly control the mild inflammatory features of psoriatic arthritis; however, some NSAIDs may aggravate the skin psoriasis.

Drug Category: Nonsteroidal anti-inflammatories -- Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action may be inhibition of COX activity and prostaglandin synthesis. Other mechanisms also may exist, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.
Drug Name
Ibuprofen (Motrin, Ibuprin, Advil, Excedrin IB) -- DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose 400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose 20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Contraindications Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or 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; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy
Drug Name
Diclofenac (Voltaren, Cataflam) -- 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 qhs may help to relieve pain; not to exceed total daily dose of 200 mg
Pediatric Dose >12 years: Administer as in adults
<12 years: Not established
Contraindications Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, and those 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 persistent leukopenia, granulocytopenia, or thrombocytopenia develops
Drug Name
Naproxen (Anaprox, Naprelan, Naprosyn, Aleve) -- 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 occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug
Drug Name
Indomethacin (Indocin) -- Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.
Adult Dose 25-50 mg PO bid/tid
75 mg SR bid; not to exceed 200 mg/d
Pediatric Dose 1-2 mg/kg/d divided PO bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d
Contraindications Documented hypersensitivity; GI bleeding or renal insufficiency.
Interactions Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of MTX toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy B - 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 persistent leukopenia, granulocytopenia, or thrombocytopenia develops)
Drug Name
Sulindac (Clinoril) -- 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 occur rarely and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia develops; caution in anticoagulation defects or patients receiving anticoagulant therapy
Drug Name
Celecoxib (Celebrex) -- For those at risk of GI toxicity with NSAIDs. Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose for each patient.
Adult Dose 200 mg/d PO qd; alternatively, 100 mg PO bid
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration with rifampin may decrease celecoxib plasma concentrations
Pregnancy B - 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 lab results suggest liver dysfunction
Drug Name
Meloxicam (Mobic) -- 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 persistent leukopenia, granulocytopenia, or thrombocytopenia develops)
Drug Name
Valdecoxib (Bextra) -- Second-generation COX-2 inhibitor that offers a very rapid onset and prolonged efficacy. Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, valdecoxib does not inhibit COX-1 isoenzyme, decreasing GI toxicity.
Adult Dose 10 mg PO qd
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions Coadministration with fluconazole may cause increase in valdecoxib plasma concentrations; coadministration with rifampin may decrease valdecoxib plasma concentrations
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Category D in third trimester of pregnancy; abdominal pain, nausea, and diarrhea may occur; 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 lab results suggest liver dysfunction
Drug Category: Immunosuppressants -- Inhibit key factors in the immune system responsible for inflammatory responses.
Drug Name
Methotrexate (Rheumatrex) -- Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction. Adjust dose gradually to attain satisfactory response.
Adult Dose 2.5 mg/wk PO/IM initially; administer 3 doses over a 24-h period, then titrate to as high as 25 mg/wk depending on response
Pediatric Dose Not established
Contraindications Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) can increase plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines
Pregnancy D - Unsafe in pregnancy
Precautions Monitor CBCs monthly and liver and renal function every 1-3 mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts occur; fatal reactions reported when administered concurrently with NSAIDs
Drug Name
Cyclosporine (Sandimmune, Neoral) -- Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-versus-host disease for a variety of organs. Demonstrated to be helpful in a variety of skin disorders, especially psoriasis.
Adult Dose 2.5-5 mg/kg/d PO in divided doses
Pediatric Dose Administer as in adults
Contraindications Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because may increase risk of cancer
Interactions Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Pregnancy C - 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 enzymes; 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
Etanercept (Enbrel) -- Acts by binding and inhibiting TNF, the cytokine that contributes to inflammatory and immune responses.
Adult Dose 25 mg SC twice weekly
Pediatric Dose 0.4 mg/kg SC; maximum single dose 25 mg
Contraindications Documented hypersensitivity, sepsis, and concurrent live vaccination; reactivation of tuberculosis; possible drug-induced lupus
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in impaired renal function and asthma; discontinue administration if a serious infection develops; adverse effects may include pain at injection site, localized erythema, rash, UTI symptomatology, GI upset, nausea, vomiting, rhinitis, and cough
Drug Category: 5-Aminosalicylic acid derivatives -- Inhibit inflammatory reactions and pain by decreasing activity of COX, which is responsible for prostaglandin synthesis.
Drug Name
Sulfasalazine (Azulfidine, EN-Tabs) -- Acts locally in colon to decrease the inflammatory response and systemically inhibits prostaglandin synthesis. Loading dose is not necessary.
Adult Dose 1 g PO tid/qid initially; titrate to 2-4 g/d in divided doses depending on response
Pediatric Dose <2 years: Not established
>2 years: 40-60 mg/kg/d PO in 3-6 divided doses; follow by maintenance dose of 20-30 mg/kg/d divided qid
Contraindications Documented hypersensitivity to sulfa drugs or any component; GI or GU obstruction
Interactions Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and MTX
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in patients with renal or hepatic impairment, blood dyscrasias, urinary obstruction, or G-6-PD deficiency
  FOLLOW-UP  

Further Outpatient Care:

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

Deterrence/Prevention:

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

Complications:

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

Prognosis:

  • Until recently, psoriatic arthritis generally had been considered a milder disease than rheumatoid arthritis. The following factors influence the degree of severity:
    • Clinical subset (eg, arthritis mutilans, symmetric polyarthritis)
    • Early age of onset
    • Severity of skin involvement
    • Female sex
    • Family history of arthritis
    • Presence of HLA-DR7
  • New evidence suggests that psoriatic arthritis may be as disabling and destructive as rheumatoid arthritis when the appropriate comparisons are made; thus, treatment should be aggressive in those individuals with progressive joint disease.

Patient Education:

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

Special Concerns:

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

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

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