PSORIATRIC ARTHRITIS

PSORIATIC ARTHRITIS

Baron Jean Luis Alibert first described psoriatic arthritis (PsA) in 1818. Since then, a variety of terms have been used to describe this type of arthritis.

Much time and effort have been invested in determining whether PsA is truly a separate entity from other arthropathies, and the debate has not yet been resolved completely.

PsA appears to deserve its own classification; it is a chronic inflammatory arthritis that affects people with psoriasis.  

PATHOPHYSIOLOGY

As its name implies, psoriatic arthritis (PsA) is a disease that affects the joints in patients with psoriasis.

PsA is a chronic inflammatory arthritis that affects the synovium, but it also may be associated with the skin manifestations that accompany psoriasis and with occasional ocular symptoms.

FREQUENCY

Approximately one third of psoriatic patients develop joint manifestations.

The prevalence of psoriatic arthritis is 1-40%, depending on the population studied.  

MORTALITY/MORBIDITY

While no direct mortality linked to psoriatic arthritis has been identified, significant morbidity is associated with the loss of function because of pain and deformity.

SEX

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

• Females are more commonly affected with the symmetrical polyarthritis that resembles rheumatoid arthritis (RA) and the juvenile form.

• A preponderance of males has been noted in the type of PsA that affects the axial spine, for which the male-to-female ratio is 3:1.

AGE

Age of onset for psoriatic arthritis is usually 30-55 years. In the juvenile form, the age of onset is 9-11 years.

CLINICAL

HISTORY

• Psoriasis precedes arthritis in 60-80% of patients.

• The duration between the onset of psoriasis and the onset of arthritis is usually less than 10 years, but it can vary.

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

• In those patients who present without obvious skin manifestations, a positive family history of psoriasis may be a key to making the diagnosis of psoriatic arthritis (PsA). In such cases, the clinician should search for hidden signs of psoriasis in areas of the skin that are not readily visible, such as the scalp, ears, umbilicus, and anus.

• Symptoms consist of joint pains, morning stiffness, and onychodystrophy (ie, oncolysis, pitting of the nails).

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

o   Evidence indicates that PsA is more frequent in patients with severe psoriasis than in those with milder cases. While this is true, no evidence indicates that the severity of the psoriasis relates to the pattern of joint involvement.

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

PHYSICAL

Psoriatic arthritis (PsA) manifests in a variety of forms, with 5 classic patterns originally being described by Wright in 1959. Peripheral joint disease occurs in 95% of the patients, and, in the other 5%, axial spine involvement occurs exclusively.  

• Asymmetrical oligoarthritis

  • This is the best-known pattern of PsA; it occurs in up to two thirds of all patients with PsA.

  • It is characterized by asymmetrical involvement of fewer than 4 joints.

    • The most common manifestation of this condition is involvement of a large joint (eg, the knee), with scattered involvement of the distal interphalangeal (DIP), proximal interphalangeal (PIP), or metatarsophalangeal joints.  

  • Sausage digits may be evident on presentation and pitting edema in the distal extremities.

• Symmetrical polyarthritis

  • This is also called referred to as the distal predominant form of arthritis.

    • It involves the wrists, small joints of the hands and feet, ankles, knees, and elbows and is very difficult to distinguish from rheumatoid arthritis.  

  • This form occurs in approximately 25% of patients with PsA and is slightly more common in females than in males.

  • Test findings for rheumatoid factor (RF) generally are negative, which helps to differentiate this form of PsA from other conditions.

  • If a patient has psoriasis and symmetrical polyarthritis, look for the characteristic clinical features of PsA (eg, dactylitis, enthesis, DIP or sacroiliac joint involvement) or radiologic evidence to make the diagnosis.

• Arthritis mutilans

  • This is a rare form of PsA that occurs in 1-5% of patients.

    • Osteolysis of the phalanges and metacarpals occurs, resulting in telescoping of the digits or opera-glass deformity. Redundant skin over resorbed joints may be present.  

  • This type of arthritis can be extremely disabling, especially with destruction of the digits.

• Juvenile PsA

  • This form of PsA is a chronic inflammatory arthritis that occurs before age 16 years and is accompanied by the skin manifestations of psoriasis.

  • Making a definitive diagnosis may be difficult because the arthritis may precede any rash.

  • Approximately 50% of patients with PsA have a family history indicating a familial incidence of the condition, which may aid in making the final diagnosis.

  • Usually, 1-5 joints are affected in an asymmetrical pattern.

  • The median age of onset is 4.5 years in girls and 10 years in boys.

  • The most commonly affected joints are the large joints, followed by the PIP joints of the hands and feet and then the DIP joints.

• Spondylitis

  • This occurs in up to 40% of patients with PsA. Spondylitis often does not cause symptoms, but it may manifest as mild back pain despite significant findings on radiographs.

  • Random involvement of the axial spine is characteristic, unlike with ankylosing spondylitis, which affects the lumbar spine first and then progresses toward the cervical spine.

  • Spondylitis may follow 1 of 2 patterns, as follows:

    • The first type is characterized by involvement of the axial spine alone. Radiologic evidence shows sacroiliitis and nonmarginal and asymmetrical syndesmophytes. The lumbar spine is the most commonly affected area. Enthesopathic erosions also may be observed, often at the insertion of the Achilles tendon into the calcaneus.

    • The second type of spondylitis is characterized by an overlap of involvement of the spinal and peripheral joints.

• Extra-articular features associated with PsA

  • The typical skin lesion is a well-demarcated, erythematous plaque with silver white scales; however, such lesions may lack silvery scales on flexor surfaces. Typically, the skin lesions of psoriasis are present for approximately 10 years prior to the onset of the arthropathy.

  • Nail changes include pitting, onycholysis, hyperkeratosis, yellowing, and transverse ridging (Beau lines); fungal nail diseases should be excluded. Nail changes are seen in up to 87% of patients with PsA, compared with 40-45% of patients with psoriasis alone.

  • Eye disease is associated with PsA. Conjunctivitis occurs in 20% of patients; iritis occurs in 7% (more with axial involvement).

CAUSES

At this time, no single causative agent has been identified to account for the findings associated with psoriatic arthritis (PsA). The following theories attempt to explain the causes of this condition.

• Genetic predisposition

  • Evidence suggests that PsA may be affected by genetic factors, but it follows a polygenetic inheritance pattern. This theory is supported by the strong family history of psoriasis seen in patients.

  • Note that a 70% concordance rate is recognized between monozygotic twins, indicating that other factors are at play besides the genetic component.

  • Certain HLA antigens have been found to be predicative of disease progression.

• Environmental factors

  • Because some evidence suggests that infectious agents (eg, streptococci, staphylococci) may have a role in the pathogenesis of psoriasis, they also may be involved in PsA.

  • The theory of environmental factors playing a role involves a process of superantigens reacting with autoantigens.

• Immunologic components

  • Increasing evidence points to the activation of lymphocytes as a key component of disease pathogenesis. These cells secrete cytokines, which begin a cascade of reactive changes in the skin and joints.

  • The theory of immunologic involvement is also supported by the fact that immunosuppressive agents are successful in treating PsA.

LABORATORY STUDIES

• No laboratory studies can confirm the presence of psoriatic arthritis (PsA).

• HLA testing can assist in the prognosis of disease progression.

• Nonspecific elevation of the erythrocyte sedimentation rate may occur. Elevated serum uric acid levels have been observed in 10-20% of patients, especially those with severe skin disease.

• Rheumatoid factor (RF) findings may be positive in up to 13% of PsA patients. Testing for RF can aid in diagnostic considerations, but it does not definitively differentiate PsA from rheumatoid arthritis.

• Synovial fluid analysis typically reveals inflammatory cells with an increased number of neutrophils, usually 2,000-15,000/µL. Much higher counts can be seen in persons with larger effusions.

IMAGING STUDIES

• Radiography - This shows a combination of erosion (unlike in ankylosing spondylosis) and bone growth (unlike in rheumatoid arthritis [RA]) in affected joints. The following changes may be seen:

  • • Pencil-in-cup deformity: This is tapering of the proximal phalanx as a result of bony erosion and bone growth in the distal phalanx.  

• • Joint-space narrowing in the interphalangeal joints, possibly with ankylosis

  • Increased joint space in the interphalangeal joints as a result of destruction

  • Fluffy periostitis

  • Bilateral asymmetrical fusiform soft tissue swelling

  • Unilateral or symmetrical sacroiliitis

  • Large, nonmarginal, unilateral, asymmetrical syndesmophytes (intervertebral bony bridges) in the cervical, thoracic, and lumbar spine, often sparing some of the segments. 

  • Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the joints

  • These imaging tests may be useful for detecting early signs of joint synovitis.

  • MRI is particularly sensitive for detecting sacroiliitic synovitis, enthesis, and erosions; it can also be used with gadolinium to increase the sensitivity.

  • MRI may show inflammation in the small joints of the hands, involving the collateral ligaments and soft tissues around the joint capsule, a finding not found in persons with RA.

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

HISTOLOGIC FINDINGS

Histologic findings from patients with psoriatic arthritis are synovium hyperplasia, polymorphonuclear infiltration early in the disease, and then mononuclear cells later, with cartilage erosion and pannus formation.

TREATMENT

PHYSICAL THERAPY

The rehabilitation treatment program for patients with psoriatic arthritis should be individualized.

The treatment should be started early in the disease process.

Such a program should consider use of the following:

v  Rest (local and systemic) - Prolonged rest should be avoided to prevent the deleterious effects of immobility.

v  Exercise (passive, active, stretching, strengthening, and endurance)

v  Modalities (heat, cold)

v  Orthotics (upper and lower extremities, spinal)

v  Assistive devices for gait and adaptive devices for self-care tasks - These include possible modifications to homes and automobiles

v  Education about the disease, energy conservation techniques, and joint protection

v  Possible vocational readjustments

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

v  Subacute and long-term phase - Isometric exercises are begun, with progression to active movement. Gradual range-of-motion (ROM) exercises include passive and active exercises; areas with subluxation should not be forced passively. Heating modalities, including moist heat packs, paraffin wax, diathermy, and ultrasound, can be used to decrease pain; this should be performed just prior to performance of ROM exercises. Institute gait activities with the patient bearing weight as tolerated, with or without an assistive device. Gentle stretching should be gradually introduced. If pain persists beyond 2 hours after therapies, then the intensity should be decreased. If a joint is swollen, then no resistive exercises should be performed through full ROM.

For patients with axial spine involvement, spine extension exercises help with flexibility and strength.

ROM exercises should be performed, but not in patients with increased pain. If the patient has sausage toes, extra-depth shoes with a high toe box should be considered to protect the foot.

With pain in the toes, such shoes should have a rocker-bottom modification to alleviate forces during the toe-off phase in the gait cycle. The patient may also benefit from arch supports if plantar fascitis is a problem.

OCCUPATIONAL THERAPY

As in other inflammatory arthropathies, therapies for psoriatic arthritis are based on the patient's symptoms.

Paraffin baths or splinting individual finger joints can be used for pain relief, but these therapies do not change the course of the disease. Stress the importance of joint protection.

SURGICAL INTERVENTION

Patients in severe pain or with significant contractures may be referred for possible surgical intervention.

Treatment should be aimed at pain relief or increasing the patient's function.

Hip and knee joint replacements have been successful, for the most part, in patients with PsA.

Arthrodesis or arthroplasty has been used for joints such as the thumb PIP joint. The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention.

• Because of the diffuse soft tissue involvement associated with the disease, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand.

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

OTHER TREATMENT

For acute flare-ups of a small number of joints, intra-articular steroid injections may be helpful in the short term. Avoid injecting through the psoriatic lesions because they may be colonized with staphylococci or streptococci. If the only access to a joint is through a psoriatic lesion, take care to clean the skin thoroughly prior to injection.

MEDICATION

While symptom management should not be minimized, the advent of disease-modifying antirheumatic drugs (DMARDs) has significantly transformed the treatment of psoriatic arthritis (PsA).

The most common medications are etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade). The first 2 medications are

injected subcutaneously, while the last medication is given by intravenous infusion.

Older DMARDs that have been reported efficacious for PsA include sulfasalazine, auranofin, methotrexate (MTX), leflunomide, cyclosporine A, and azathioprine. The utility of these agents is somewhat marginal compared with the newer DMARDs.

Traditional treatment of PsA included symptomatic relief with anti-inflammatory and analgesic medications.  

This therapy includes oral nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid injections into joints and around inflamed tendons. If joint injection with corticosteroids fails to control pain after 2 injection sessions, this commonly is considered the criterion to institute DMARD therapy.

Systemic steroid therapy typically is avoided because of the risk of exacerbating the dermatologic component of psoriasis after withdrawal of the steroids.

DRUGS AND DOSAGE

MECLOFENAMATE (Meclomen)

Decreases activity of cyclooxygenase, which results in decreased formation of prostaglandin precursors.

Adult - Mild to moderate pain: 50 mg PO q4-6h, not to exceed 400 mg/d

RA: 200-400 mg/d PO divided tid/qid

METHOTREXATE (Folex PFS, Rheumatrex)

Acts primarily on rapidly dividing tissues like those found in PsA. May affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).

          Adjust dose gradually to attain satisfactory response.

Adult - 5-25 mg PO q7d

CYCLOSPORINE (Sandimmune, Neoral)

Can block an early step in T-cell activation; also has a direct anti-inflammatory activity by inhibiting release of immune mediators from tissue mast cells, basophils, and PMN leukocytes.

Symptomatic improvement in skin and joint manifestations usually seen in 2-8 wk.

Adult - 2-5 mg/kg PO may be effective while limiting adverse effects

HYDROXYCHLOROQUINE SULFATE (Plaquenil)

Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and complement-dependent antigen-antibody reactions.

Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

Adult - 200-400 mg PO q24h

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Eye examinations recommended q6mo because of possible retinal pigmentation (if this occurs, discontinue medication); caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children; perform periodic (q6mo) ophthalmologic examinations; test periodically for muscle weakness

SULFASALAZINE (Azulfidine, EN-tabs)

Combination of sulfapyridine and 5-aminosalicylic acid (mesalamine). Metabolized to its active components, sulfapyridine and mesalamine, by bacteria in the colon.

When given as sulfasalazine, a larger quantity of sulfapyridine and mesalamine reach the colon than when these agents are administered as single agents.

Once sulfapyridine and mesalamine reach the colon, the beneficial effects result primarily from the anti-inflammatory properties of mesalamine.

The anti-inflammatory mechanism of mesalamine is believed to occur, at least in part, through the inhibition of arachidonic acid metabolism in the bowel mucosa by inhibition of cyclooxygenase. This effectively diminishes the production of prostaglandins, thereby reducing colonic inflammation. Production of arachidonic metabolites appears to be increased in patients with inflammatory bowel disease.

Mesalamine also inhibits leukotriene synthesis, possibly through inhibition of lipoxygenase. This action has been suggested as a major component of the drug's anti-inflammatory effects.

Inhibition of colonic mucosal sulfidopeptide leukotriene synthesis and chemotactic stimuli for PMN leukocytes may also occur.

Enteric-coated tab may be of benefit in patients who cannot take uncoated sulfasalazine tab because of GI intolerance; as opposed to NSAIDs, a therapeutic response is not observed immediately but can be seen in 4 wk (12 wk treatment may be required in some patients).

Adult

0.5-1 g/d PO for first wk; increase by 500 mg/d each wk to a maintenance dose of 2 g/d, which may be given in 2-3 divided doses.

INFLIXIMAB (Remicade)

Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor.

Mix with 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 PsA.

Adult

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)

PROGNOSIS

• Prognosis is generally good for psoriatic arthritis, with most symptoms controlled with medications, but 25% of patients may have progressive disease.

PATIENT EDUCATION

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

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