Amanda has psoriatic arthritis (PsA). Naproxen at 500 mg twice daily was of little help, so she was put on methotrexate, which was progressively increased to weekly 25 mg subcutaneously -- with limited success. On both sides, her MCP 2 and 3, knees, ankles and MTP 2, 3 and 4 remained swollen. Considering her skin condition and the number of active joints, an anti-tumour necrosis factor (anti-TNF) was suggested, with the hope that it would resolve both the arthritis and cutaneous lesions, as well as halt the progression of articular damage and improve her quality of life.
Making the case
Psoriasis is a chronic inflammatory disease of the skin, affecting about 1 million people in Canada. Its name is derived from "psora," the Greek word for scab. The association between arthritis and psoriasis was noted back in the 19th century -- indeed, up to 40% of people with psoriasis develop PsA, usually within 5-10 years after onset of the cutaneous disease. Arthritis precedes the skin lesions in about 15% of patients, and it appears simultaneously in another 20%.
PsA is progressive and erosive in 50% of cases, and it can lead to functional impairment and decreased quality of life. Patients with psoriasis have nearly 2 times the average level of comorbidities, including diabetes, gastrointestinal disorders, hepatotoxicity, hypertension and cardiac disease. They also have an increased rate of depression, suicide and alcoholism, and 72% report difficulties in their sexual life. In addition, these people often suffer discrimination in public places because their skin lesions are thought to be contagious. PsA raises the risk of death, which is even higher if the sedimentation rate is elevated or if there's radiological evidence of joint damage.
Mechanism of disease
Family investigations, genome-wide scans, human leukocyte antigen and candidate gene studies have demonstrated a genetic link with PsA, but immunologic factors and the environment also play a role. The disease is almost certainly immune-mediated, although the exact mechanism isn't well understood yet. Synovium affected by PsA shows infiltration with T cells, B cells and macrophages, and is also characterized by an upregulation of leukocyte homing receptors. Cytokine production in the synovium resembles that in psoriatic skin lesions and in the synovium with rheumatoid arthritis (RA), having predominantly a Th1 pattern.
In 1976, Wright and Mall described five clinical patterns of PsA, which can sometimes overlap: isolated interphalangeal joint involvement (see Figure); symmetric polyarthritis; asymmetric, oligoarticular arthritis; spondylitis; and arthritis mutilans. Patients may also evolve from one pattern to another.
More recently, the Classification of Psoriatic Arthritis study group (CASPAR) came up with new classification criteria for PsA. According to their definition, there must be inflammatory musculoskeletal disease -- e.g. of the joint, spine or entheses -- with three or more of the following: psoriatic nails; negative test for RF; radiological evidence of juxta-articular new bone formation; dactylitis (current or history); and finally, evidence of psoriasis, i.e. a history or family history, or current psoriasis -- which counts as two points.
Over the past decades, it's become clear that PsA leads to serious disability and increased mortality, and traditional medications haven't been effective in preventing the progression of joint damage. Ideally, coordinated therapy should be directed at both the skin and joints. A new class of biologic disease-modifying antirheumatic drugs that target specific components of the immune response offers highly efficacious disease management with fewer severe side effects than more general immunosuppressant therapies. The development of several new cell- and cytokine-specific immunomodulatory medications in the coming years should further extend our ability to treat the disease successfully.
Prompt and dramatic resolution of both arthritis and skin lesions has been observed with anti-TNF-a agents such as infliximab, etanercept and adalimumab. Many of the responding patients had long-standing disease that was resistant to all previous therapy; often, they also had extensive involvement of the skin. The effect of these drugs on radiological damage and disease progression has now been documented.
Other treatment for PsA has been based on drugs that are efficient in RA and/or in psoriasis. Although methotrexate in doses of 15-25 mg/week and sulfasalazine -- usually given in doses of 2-3 g/day -- have each been found to have clinical efficacy in controlled trials, neither one effectively halts progression of erosive joint disease. Other agents reported to benefit PsA are cyclosporine, retinoic acid derivatives and psoralen plus ultraviolet light. There's controversy regarding the effectiveness of gold and antimalarials in PsA -- both have been widely used in RA. The new antirheumatic agent leflunomide is currently being evaluated. All of these treatments require careful monitoring. Immunosuppressive therapy, including anti-TNF-a agents, methotrexate and cyclosporine, is largely contraindicated in HIV-associated PsA.
In one large prospective series, 7% of patients with PsA required musculoskeletal surgery beginning -- on average -- at 13 years disease duration. Indications for surgery are similar to those in RA, and are based on failure of medical treatment -- although there's an impression that outcomes in PsA may be less satisfactory.
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