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Chapter 35 Psoriatic Arthritis

Manual of Rheumatology and Outpatient Orthopedic Disorders

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Chapter 35 Psoriatic Arthritis

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Joseph A. Markenson

Clinical presentations
History
Physical examination
Laboratory studies
Differential diagnosis
Treatment
Prognosis

Psoriatic arthritis (PA) is an inflammatory arthropathy occurring in 5% to 7% of patients with psoriasis [excluding subjects who are positive for rheumatoid factor (RF) and presumably have coexisting psoriasis and rheumatoid arthritis (RA)]. Psoriasis is a common disease afflicting 1% to 2% of the general population. Dermal psoriasis usually appears in the second to third decades, but the onset of associated arthritis is usually delayed by two decades. The pathogenesis of PA is unknown, although a genetic component is evident. Concordance between monozygotic twins is higher (70%) than in RA (30%), yet the lack of complete concordance suggests that other (e.g., environmental) factors are involved. Because many lesions of psoriasis are colonized with staphylococci and streptococci, there is some thought that psoriatic arthritis may be a form of reactive arthritis in which microbial superantigens result in T cells that cross- react with human auto-antigens. Family studies suggest an extremely high (>50%) risk in first-degree relatives of patients with arthritis. The female -to-male ratio is 1:1, whereas in RA it is 3:1.

I. Clinical presentations. Five distinct patterns of PA are recognized.

1. Patients with oligoarticular disease constitute 70% of all cases of PA. It is characteristically asymmetric, affecting a large joint such as a knee and a few scattered distal interphalangeal (DIP), proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints, often in association with diffuse swelling of one or more fingers and toes ( sausage digits ).
2. Symmetric polyarthritis, which resembles RA, is the next most common pattern. Patients are usually RF-negative and constitute about 15% of all cases of PA. Constitutional symptoms such as morning stiffness and fatigue are common and tend to parallel the activity of joint disease.
3. Asymmetric involvement of distal interphalangeal joints of the hands and feet is sometimes referred to as classic psoriatic arthropathy, but this pattern appears in no more than 10% of cases of psoriatic arthritis; digits affected often have characteristic psoriatic nail changes. This pattern may evolve into the oligoarticular pattern.
4. Arthritis mutilans is a particularly disabling form, occurring in fewer than 5% of all cases of PA. The deformity, most striking in the fingers and toes, is caused by osteolysis of the affected joints.
5. Psoriatic spondyloarthritis occurs in up to 5% of patients with PA and presents with clinical and radiographic features that may be indistinguishable from those of idiopathic sacroiliitis or ankylosing spondylitis. The histocompatibility antigen HLA-B27 is found in 40% of this group .

II. History. Symptoms are highly variable according to the anatomic patterns described above. Although interphalangeal (IP) joints of the fingers and toes are most commonly affected, larger joints such as the knee and ankle may be involved.

The extraarticular manifestations such as vasculitis, lung disease, and pericarditis seen in RA are generally not seen in PA. Inflammatory eye disease does occur in up to 30% of patients with PA. Constitutional symptoms such as malaise, morning stiffness, and fever are less common and are more often seen with the symmetric polyarticular pattern. Back pain may be indicative of psoriatic spondylitis or sacroiliitis. There is an increasing awareness of an association between temporomandibular joint disease and psoriatic arthritis.

III. Physical examination reveals cardinal signs of inflammation in affected joints. IP joint involvement is often associated with a sausage appearance of the digits (dactylitis). The most common form of PA has the characteristic asymmetric skip-hit pattern of digit involvement. Psoriasis may be obvious or may manifest only as an obscure patch in the scalp or umbilicus, or as nail pitting (onychodystrophy). Arthritis usually follows well-established cutaneous or nail lesions, although some patients exhibit characteristic patterns of PA in the absence of such. Nail changes alone may not be diagnostic, but the presence of more than 20 pits is suggestive and more than 60 diagnostic of PA. With all nail changes, especially those involving the toenails, fungal and bacterial infections, which may also cause hyperkeratosis and onycholysis, should be ruled out.

IV. Laboratory studies

1. Rheumatoid factor is seen in fewer than 10% of PA patients.
2. Polyclonal hypergammaglobulinemia is occasionally present.
3. Serum complement in patients with PA tends to be higher than normal; however, this finding is of no diagnostic significance. Theoretically, elevated synovial fluid complement levels might distinguish PA from RA. Such measurements are frequently subnormal in RA.
4. Serum uric acid. In 10% to 20% of patients with psoriasis, levels of uric acid may be elevated in relation to the severity of the skin disease.
5. The erythrocyte sedimentation rate and other acute-phase reactants are elevated and parallel the activity of the arthritis.
6. Test results for antinuclear factors are usually negative.
7. Radiographic features considered classic for PA are destructive lesions involving predominantly the DIP joints of fingers and the IP joints of the toes. Bony ankylosis of the DIP joints of the hand and toes, along with bony proliferation of the base of the distal phalanx, and resorption of the tufts of the distal phalanges of hands and feet are also commonly seen. Other classic features are fluffy periostitis of large joints, pencil-in-cup appearance of DIP joints, an asymmetric joint pattern, and gross destruction of isolated small joints. Changes in the spine and sacroiliac (SI) joints may be similar to those seen in ankylosing spondylitis, but SI joint changes in PA are often unilateral, and syndesmophytes can sometimes be distinguished from those of ankylosing spondylitis.

V. Differential diagnosis

1. Reiter's syndrome. The cutaneous lesions of Reiter's syndrome resemble pustular psoriasis. Reiter's syndrome usually affects large joints in an oligoarticular fashion and infrequently involves the DIP joints or produces sausage digits. Both illnesses may be associated with spondyloarthritis. The incidence of HLA-B27 is higher in Reiter's syndrome than in PA. Radiographically, Reiter's syndrome may demonstrate periostitis of the plantar surfaces of the calcaneus, metatarsal bones, or ankles. In PA, periostitis is usually limited to the long bones.
2. Gout. Acute psoriatic monarthritis can resemble but should be differentiated from gout by the absence of monosodium urate crystals in the synovial fluid. Hyperuricemia may occur in up to 20% of patients with skin psoriasis but is uncommon during acute flares of PA. In contrast to monarticular PA, acute gouty arthritis usually resolves completely in 1 to 2 weeks, even if untreated.
3. Rheumatoid arthritis is the most difficult entity to differentiate from PA. Distal and asymmetric IP joint involvement and the absence of RF support the diagnosis of PA. The presence of skin psoriasis and onychodystrophy helps distinguish PA from RA. (Patients with symmetric arthritis and psoriasis who are positive for RF are usually considered to have coexistent RA and psoriasis.) Subcutaneous nodules are absent in PA. The radiographic features (see section IV.G ) may help differentiate PA from RA.
4. Human immunodeficiency virus (HIV) infection. PA is more aggressive in patients with HIV infection, which suggests a pathogenesis different from that of RA. (HIV depletes CD4+ T cells and RA is almost absent in HIV patients, unlike PA, which is a CD8+ T- cell disease). However, the incidence of skin disease (psoriasis) is not greater than in the normal population. HLA-associated antigens are similar and appear in the same frequency as in non “HIV-infected patients with PA (HLA-Bw38, -Bw39, and -Cw6). In contrast, in HIV-associated Reiter's disease, the frequency of HLA-B27 can be higher than 75%.

VI. Treatment. The management goals and therapeutic efforts applied to PA and RA have similar features. However, nonsteroidal antiinflammatory drugs (NSAIDs) are used as the base therapy in many PA patients, whereas combined disease-modifying antirheumatic drugs (DMARDs) are now used early in RA treatment.

1. Physical therapy is used as an adjunct to drug therapy to help preserve joint range of motion and minimize muscle weakness.
2. Drug therapy is aimed at decreasing inflammation of synovial tissue to allow maintenance of joint function. NSAIDs are the drugs of choice. Therapeutic options follow in order of use.
   1. Nonsteroidal antiinflammatory drugs. The reader is referred to Appendix E for a more complete discussion of the agents listed below.
      1. Ibuprofen (600 mg four times daily), naproxen (250 to 500 mg twice daily), fenoprofen (300 mg four times daily), ketoprofen (75 mg three times daily), and flurbiprofen (100 mg three times daily) are other propionic acid derivatives that are applicable to the treatment of PA.
      2. Indomethacin (200 mg/d) in divided doses is usually an effective antiinflammatory agent for both spondyloarthritis and peripheral arthritis.
      3. Sulindac (200 mg twice daily), an NSAID much like indomethacin, requires less frequent dosing and may be associated with less gastrointestinal intolerance.
      4. Piroxicam is a long-acting NSAID given in a single daily dose of 20 mg.
      5. Diclofenac (75 mg twice daily) is effective but requires monitoring with liver function tests.
      6. Nabumetone (1,000 to 2,000 mg/d) is well tolerated and may be associated with fewer gastric ulcers, although the same degree of gastric intolerance is noted as with the above-mentioned NSAIDs.
      7. Arthrotec (50 to 75 mg twice daily), a combination tablet of diclofenac and misoprostol, may be used for patients at high risk for gastrointestinal side effects.
   2. Disease-modifying antirheumatic drug therapy and combination therapies
      1. Gold salts . A course of aurothiomalate is indicated for the treatment of progressive, severe PA, especially when the disease resembles RA. A full course usually starts with sequential weekly IM injections of 10, 25, and then 50 mg until a total dose of 1,000 mg has been achieved. If successful, monthly maintenance injections of 50 mg are given indefinitely. The efficacy of auranofin (20 mg/d PO) in RA approaches that of injectable gold preparations. It has not been systematically evaluated as treatment for PA; however, this author has had moderate success with it in treating patients with PA. (The toxicity of gold preparations and relevant laboratory surveillance are discussed in Chapter 28.)
      2. Antimalarial therapy has been associated with exfoliative skin reaction in persons with psoriasis; however, recent studies have concluded that such drugs can be used safely and that they have the potential for inducing remission of PA. Hydroxychloroquine (200 mg/d for 1 month followed by 400 mg/d) is recommended. Hydroxychloroquine therapy probably should be considered when PA fails to respond to NSAIDs or gold.
      3. Sulfasalazine has been used in the treatment of RA (see Chapter 28), and trials of PA are in progress. It is effective as a second-line drug with an onset of action later than that of NSAIDs and before that of gold. Side effects are mainly gastrointestinal intolerance and skin rash.
      4. Immunosuppressive drugs. Oral or parenteral methotrexate is an extremely effective therapy for both the arthritic and skin manifestation of psoriasis. Evidence now exists in RA that liver biopsy is not necessary, and an algorithm has been developed to follow toxicity. Opinions are divided regarding whether toxicity to methotrexate is different in PA, and a biopsy must still be performed. This author, however, is following the American College of Rheumatology recommendations for monitoring liver toxicity in RA. A dosage of 7.5 to 25.0 mg/wk (maximum dosage, 50 mg/wk) is usually successful in suppressing cutaneous and articular manifestations of psoriasis. A commonly employed oral regimen consists of a series of three doses (2.5 to 10.0 mg each) administered at 12-hour intervals during a 36- hour period each week. The drug is hepatotoxic, and authorities recommend a liver biopsy at a cumulative dose of 1,500 mg. Careful monitoring of liver function tests, complete blood counts to detect bone marrow suppression, and chest radiographs to detect methotrexate-induced pulmonary infiltrates are mandatory.
      5. Corticosteroid therapy has limited application in the management of PA. For patients with oligoarticular disease, in which disability results from involvement of one or a few joints, intraarticular steroid therapy may be preferred to systemic use of antiinflammatory drugs. Topical corticosteroids are useful for psoriatic skin disease. Oral corticosteroids should be avoided if possible because of increased relapses and flares, particularly skin disease, when doses are adjusted.
      6. Preliminary open trials with retinoid (etretinate) suggest that it is beneficial at a mean daily maintenance dose of 30 mg. Results are seen usually between 6 weeks and 3 months. The mechanism of action is unknown. Etretinate cannot be used in women of childbearing age. Side effects include mucocutaneous lesions, proximal arthralgias and myalgias, and extraspinal calcifications.
      7. Cyclosporin A has been used with efficacy in patients with severe PA refractory to other treatments . Careful observation of serum creatinine levels and blood pressure monitoring are mandatory.
      8. Photochemotherapy with methoxypsoralen and long-wave ultraviolet A light (PUVA) will benefit a group of nonspondylitic patients with synchronous joint and skin flares.
      9. Reconstructive surgery is of value in patients with end-stage joint destruction. Procedures employed and indications are similar to those for RA (see Chapter 28 and Chapter 54).

VII. Prognosis. The prognosis for patients with PA varies according to the anatomic pattern. The severity of arthritis tends to parallel the severity of skin disease. Most patients have mild episodic disease affecting only a few joints. For these, the prognosis is generally favorable. In approximately 5% of patients, severe disabling and deforming arthritis develops. The axial spondyloarthropathy of PA is associated with many of the same extraarticular manifestations seen in idiopathic ankylosing spondylitis (uveitis, cardiac disease, conduction defects, aortitis), and these features may significantly contribute to morbidity. Complications of therapy, especially oral corticosteroids, have been the largest contributing factor to mortality in several large series.

Bibliography

Arnett FC, et al. Psoriasis and psoriatic arthritis: association with human immunodeficiency virus infection. Rheum Dis Clin North Am 1991;17:59.

Green L, et al. Arthritis in psoriasis. Ann Rheum Dis 1981;40:366.

Grekin RC, et al. Retinoids in the treatment of psoriasis: monotherapy and combinations. Dermatol Clin 1984;2:439.

Kammer G, et al. Psoriatic arthritis: a clinical, immunologic and HLA study of 100 patients. Semin Arthritis Rheum 1979;9:75.

Moll JMH, Wright V. Psoriatic arthritis seminar. Arthritis Rheum 1978;3:55.

Perlman GG, et al. Photochemotherapy and psoriatic arthritis. Ann Intern Med 1979;91:717.

Wright V. Psoriatic arthritis: a comparative study of rheumatoid arthritis and arthritis associated with psoriasis. Ann Rheum Dis 1961;20:123.

Books@Ovid
Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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