Treatment of psoriatic arthritis

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Treatment of psoriatic arthritis

MARTA LUCIA CUI~LLAR GUSTAVO CITERA LUIS R. ESPINOZA

The importance of an early and adequate treatment of psoriatic arthritis (PsA) has received better recognition in the past few years. It is now well established that PsA can be disabling, and that significant functional limitation can occur in approximately 11% of patients; up to 20% of these may have a more severe form of the disease, mostly with damage to five or more joints.

Recent developments in the pathogenesis, epidemiology, immunogenetic and clinical characteristics of PsA have facilitated an improvement of our understanding of its prognosis and therapeutic management.

An ascertainment of the potential role of growth factors, the underlying inherent functional abnormality of fibroblasts, the coincident occurrence of human immunodeficiency virus (HIV) infection with psoriasis and PsA, the evidence of T-cell activation and of the role of metabolites of the arachidonic acid pathway has contributed to an understanding of the pathogenic mechanisms at play and lends support to the use of anti- inflammatory and immunomodulatory agents (Gottlieb et al, 1987; Aguilar et al, 1989; Vasey et al, 1989). The need for concomitant treatment of skin involvement was emphasized in a recent study on joint complaints in patients with psoriasis, which confirmed that articular activity may parallel skin activity (Stern, 1985; Zanolli and Wikle, 1992). The newly proposed simplified criteria for the classification of psoriatic arthropathy into three groups allows a better identification of patients with a poor prognosis, and also introduces an easier classification for treatment evaluation (Wright, 1989; Helliwell et al, 1991a).

Other developments include studies that attempt to establish the outcome of PsA by the use of clinical and functional measurements. The Arthritis Impact Measurement Scales (AIMS) was found to be a valid instrument for use in PsA (Ciaran et al, 1992); objective measures of disease activity, in search for disease markers, have been studied (Helliwell et al, 1991b) using laboratory variables. An attempt has been made to associate prognosis with certain human leukocyte antigens (Gladman et al, 1987); in this regard, a subgroup of patients with polyarticular involvement that may follow a deforming and progressive course has been identified (Gladman et al, 1990; Torre Alonso et al, 1991). Evidence that actively inflamed joints in patients

Baillibre' s ClinicaI Rheumatology-- 483 Vol. 8, No. 2, May 1994 Copyright �9 1994, by Bailli6re Tindall ISBN 0-7020-1820-1 All rights of reproduction in any form reserved

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with PsA are less tender than in those with rheumatoid arthritis helps the clinician in the clinical evaluation of patients with PsA (Buskila et al, 1992).

Treatment of PsA includes pharmacological, rehabilitative and surgical reconstructive therapies with concomitant skin management. Patients with PsA with an extensive rash, erythrodermic psoriasis or generalized pustular psoriasis will need systemic therapy, including the use of methotrexate, cyclosporin A, 1,25-dihydroxyvitamin D3 and etretinate. However, most patients respond to the use of oral non-steroidal anti-inflammatory drugs (NSAIDs). In a recent study approximately 80% of patients were found to require the use of a NSAID (Gladman and Espinoza, 1992), with control of joint symptomatology in approximately 30%.

In general, patients with PsA respond well to most NSAIDs, although there is a lack of well-controlled studies in the literature. Also, in contrast to rheumatoid arthritis, salicylates seem to be less effective in PsA than the newer NSAIDs. A variety of NSAIDs has been used, including indo- methacin, piroxicam, diclofenac, naproxen and tiaprofenic acid (Zbojanova et al, 1974; Scarpa et al, 1989). The response to NSAIDs of patients with PsA with spondylitic involvement is not well established. Few studies have addressed this issue, although there is evidence suggesting that phenyl- butazone and/or oxyphenbutazone are equally effective, as in ankylosing spondylitis (Roberts et al, 1976). Of interest, NSAIDs in ointment prep- aration (diclofenac) were shown to be as effective as the oral preparation (Shakhtmeister and Kamennykh, 1990). In terms of side-effects, these appear to be no different from those seen in the treatment of rheumatoid arthritis. Early on, there was some concern about exacerbation of the underlying psoriatic rash with the use of NSAIDs and other anti- inflammatory agents (Meyerhoff, 1983; Reshad et al, 1983); however, larger studies have not been able to confirm this observation (Scarpa et al, 1989). NSAIDs should be given at full dosage, and for a minimum of 4-6 weeks, to evaluate their efficacy fully. At times it may be necessary to try more than one NSAID before deciding that this group of agents is not effective.

SLOW-ACTING ANTIRHEUMATIC DRUGS

Persistent clinical disease activity, or the presence of severe deforming inflammatory joint involvement despite an adequate trial of NSAIDs, requires the use of slow-acting antirheumatic drugs (SAARDs). It is not well established, however, which SAARD should be used first. The benefit: toxicity ratio, skin effect and cost are variables that need to be taken into consideration before making a final selection. An interesting observation that needs further confirmation is the finding that patients with PsA with antinuclear antibody (ANA) positivity require treatment with SAARDs more frequently than ANA-negative patients with PsA. Of 60 patients with juvenile PsA, 16 had severe persistent articular disease and required SAARDs. Fifty per cent of them had polyarticular onset and 44% were ANA positive. In the group of patients without SAARD treatment (44), 18% had polyarticular onset and only 7% had positive ANA. In addition, 21

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patients had systemic steroid therapy at some point, for joint symptoms in 18 cases (Shore and Ansell, 1982).

A variety of agents has been used, including methotrexate, antimalarials, gold compounds, sulphasalazine and penicillamine. Other therapeutic modalities such as vitamin D3 derivatives, retinoids, somatostatin, azathio- prine, cyclosporin A and PUVA (psoralen plus ultraviolet A) have also been used, but most studies lack appropriate controls.

ANTIMETABOLIC AGENTS

Antimetabolic agents, such as the folate antagonist methotrexate, the purine analogue 6-mercaptopurine (6-MP), azathioprine (converted to 6-MP in the liver) and the pyrimidine analogue 6-azauridine (azaribine), have all been used for the treatment of psoriasis (Kravete and Balsam, 1961; Vogler and Olansky, 1970) and psoriatic arthritis. Both 6-MP (Baum et al, 1973) and azaribine (Levine and Paulus, 1976) have been shown to be effective in psoriasis and PsA; however, the toxicity ratio is too high. With the advent of methotrexate, these components are no longer used.

AZATHIOPRINE

In an early report of the treatment of PsA with azathioprine, Feldges and Barnes (1974) studied a small group of patients taking 2.5 mgkg -1 day -1 and found that nine out of ten patients had an excellent or good response. Improvement of both inflammatory skin and joint involvement was observed. In another double-blind controlled study of 3 m g k g - l d a y -1 azathioprine in patients with rheumatoid arthritis and PsA (18 and 6 patients respectively), marked improvement was seen in four and moderate in two patients with PsA (Levy et al, 1972). This clinical response to azathioprine therapy in patients with PsA was similar to that obtained in those with rheumatoid arthritis. More recently, the efficacy and safety of azathioprine was confirmed in patients with PsA (Le Quintec et al, 1990). Treatment was started with a dose of 2-2.5 mg kg -1 day -1. A beneficial effect was observed after a mean duration of therapy of 43 days. Treatment was discontinued if remission occurred or after 18 months; in case of recurrence, treatment was started again at the lowest effective dose. The mean duration of remission after discontinuation of therapy was 18 (range 0-93) months.

METHOTREXATE THERAPY

Methotrexate has long been recognized as an effective therapeutic agent for psoriasis. It is also a safe and effective preparation in the therapy of PsA. Early studies using the oral preparation aminopterin (Gubner et al, 1951) and parental methotrexate (O'Brien et al, 1962; Black et al, 1964) demon- strated a favourable response of both articular and cutaneous involvement

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with relatively low toxicity. Intra-articular methotrexate therapy is not effective however (Hall et al, 1978). The importance of early treatment was emphasized by Kragballe et al (1982) in a retrospective study of 59 psoriatic patients treated with methotrexate, 22 of whom were virtually asympto- matic after 1-11 years of treatment. Results, however, in a prospective controlled multicentre, double-blind placebo study using low-dose metho- trexate did not show significant differences with placebo except for the physician's assessment (Willkens et al, 1984). The total number of patients enrolled (16), and doses used, were small and, more importantly perhaps, patients were evaluated after only 12 weeks of therapy. The duration of therapy needs to be emphasized, as shown by a recent study (Zachariae and Zachariae, 1987). These authors reported dramatic improvement with low- dose methotrexate in 28 patients with PsA treated for 1 year. We have recently reported our experience with this drug in patients with PsA (Espinoza et al, 1992). A total of 40 patients were treated prospectively with oral methotrexate. There were 24 men and 16 women with a mean age of 47.2 years. The mean duration of PsA was 12 (range 1-36) years at the time of inclusion in the study. Twenty-four patients developed PsA after the onset of the cutaneous manifestations, eight had simultaneous onset of skin and joint disease, the arthritis preceded psoriasis in five, while in three it was unknown. Thirteen patients presented with oligoarthritis (three also had spondylitis) and the remaining 27 had a polyarticular distribution (seven also with spondylitic involvement). The mean duration of oral methotrexate therapy was 34 (range 6-132) months, the average dose being 11.2 (range 5-25) mg per week. Fifteen patients (38%) had an excellent response, it was good in 23 (58%) and poor in only two (5%). Skin involvement was observed in 100% of patients before methotrexate therapy. Following therapy, a marked improvement was noted, including resolution of rashes in 36 cases (90%). Characteristic nail involvement, including pitting, onycho- lysis and dystrophy were seen prior to methotrexate therapy in 36 patients. After treatment, complete resolution of psoriatic nail involvement was seen in 18 of 36 (50%). In the other 50%, partial resolution was observed. Pitting involvement disappeared in every patient taking methotrexate therapy, with most patients responding after 6-12 months of therapy.

The only laboratory change observed during methotrexate therapy was an improvement of the erythrocyte sedimentation rate in most patients with a good clinical response.

Most patients tolerated methotrexate well; in only two did it have to be discontinued because of side-effects, for leukopenia in one and stomatitis in the other. Liver function test abnormalities were seen in 11 patients but were severe (two- to three-fold increments in the levels of bilirubin, amino- transferase and/or other enzymes) in only two. These abnormalities resolved when the methotrexate dose was reduced. Liver biopsies were performed in six patients during treatment and in one before and during methotrexate therapy. The mean + SD cumulative dose of methotrexate when the biopsy was first performed was 1736.6 + 1.222.2 mg and the mean + so duration of treatment at the time of biopsy was 55.4_+ 34.2 months. Except for one patient, there was no evidence of cirrhosis or inflammation. Indeed, no

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changes were observed in the histopathology of those with repeated biop- sies. Methotrexate was continued in one patient with cirrhosis, not due to methotrexate, without further deterioration of liver chemistry and/or histo- pathology. This study confirms the efficacy of methotrexate in PsA and, more importantly, its relative lack of serious side-effects.

Specific tests indicative of liver fibrogenesis in patients with PsA treated with methotrexate are not available. Levels of the serum aminoterminal propeptide of type III procollagen may be used as an indicator of the process that may lead to hepatic fibrosis in patients treated with methotrexate, but it is also increased in patients with psoriasis and arthritis without liver abnormalities (Zachariae et al, 1991). There is a need for such a test in view of the sporadic occurrence of severe liver cirrhosis requiring transplantation in three patients receiving high doses of methotrexate, in excess of 30-35 mg per week for several years, and under no supervision (Gilbert et al, 1990).

Methotrexate has become the SAARD of choice for many, including our group. The usual dose is 7.5-15 mg per week, given as a single dose or divided into two doses taken 12 h apart on the same day. The dosage can be increased to 25-30 mg per week until improvement occurs, and then it should be tapered down to a maintenance dose that varies from patient to patient, but tends to be somewhat higher, 5-15 mg per week, than the maintenance dose used in rheumatoid arthritis. The most frequent side- effects are gastrointestinal, including abdominal pain and stomatitis. One major advantage of methotrexate is the lack of evidence of oncogenesis, and also its efficacy in suppressing both cutaneous and articular involvement.

GOLD COMPOUNDS

Chrysotherapy has been used in the treatment of PsA for many years, and several studies have reported its efficacy (Kammer et al, 1979; Scarpa et al, 1989). Richter et al (1980) studied retrospectively 27 patients treated with sodium aurothiomalate over 10 years. They found that 22 patients had a very good response; all of their patients had a rheumatoid arthritis-like disease, and nine had adverse effects that necessitated discontinuation of the drug. Five of these patients experienced a possible exacerbation of the psoriasis and four developed gold-induced skin eruption. The overall incidence of toxic reaction of 44% is not very different from that in patients with rheumatoid arthritis (Richter et al, 1980). Photosensitivity and exacerbation of under- lying psoriatic rash appear to be unique side-effects to psoriatic patients, however. The efficacy of gold in the therapy of PsA is similar to that seen in rheumatoid arthritis (Wright and Moll, 1971; Dorwart et al, 1978).

The recommended dosage of parenteral gold for PsA is similar to that used in rheumatoid arthritis, 50 mg per week up to a maximal total dose of I g, followed by a maintenance therapy with 50 mg per month.

Oral gold treatment has also been used in PsA (Dequeker et al, 1984; Tumiati et al, 1986). A recent multicentre double-blind study comparing auranofin and placebo found auranofin more effective than placebo, but not much more effective than NSAIDs (Carette et al, 1989). In another study,

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the efficacy of auranofin was compared to that of parenteral gold thiomalate in a placebo-controlled double-blind four-centre trial in 82 patients. It showed that intramuscular gold was safe and more effective than the oral compound (Palit et al, 1990).

ANTIMALARIAL THERAPY

The use of antimalarial agents for the treatment of PsA remains contro- versial. A decrease in inflammatory disease activity following antimalarial therapy has been reported (Gladman et al, 1992), but to date no prospective double-blind controlled study has been published. Exacerbation of under- lying psoriatic skin involvement, followed by improvement upon cessation of antimalarial treatment, including chloroquine and hydroxychloroquine, has long been recognized (Olsen, 1981; Luzar, 1982; Slagel and James, 1985). There are now, however, recent reports showing that this undesirable secondary effect is infrequent and does not constitute a contraindication to the use of antimalarials (Kammer et al, 1979; MacKenzie and Scherbel, 1980; Sayers and Mazanec, 1992; Gladman et al, 1992).

SULPHASALAZINE THERAPY

In the past several years, some uncontrolled studies have demonstrated a good clinical response of patients with PsA to treatment with sulphasalazine. In a 1-year open study of sulphasalazine in 34 patients, a favourable response was observed in 67%, and 26% had a very good response. Patients with spondylitis or symmetrical subtypes of arthritis responded well, and eight discontinued the drug because of adverse secondary reactions (Farr et al, 1988). In a subsequent study, the same group reported the results of their double-blind placebo-controlled study in 30 patients with PsA. Once again, they confirmed their previous observation, with five patients experiencing a good clinical response and seven a partial response; 20% were not able to complete the study because of secondary effects (Farr et al, 1990). Further- more, skin involvement improved in three patients, worsened in four and did not change in six. A beneficial effect of sulphasalazine for the psoriatic skin involvement has also been shown by others (Gupta et al, 1990a; Newman et al, 1991; Dougados et al, 1992). Unpublished observations, however, from the European-Australian Spondyloarthropathy Group seem to indicate that sulphasalazine may not be as efficacious as previously reported, and that its use in patients with PsA is complicated by a high prevalence of gastro- intestinal intolerance.

RETINOID THERAPY

Synthetic retinoids or vitamin A derivatives have been shown to be effective in the treatment of psoriasis and PsA. Three compounds are available: isotretinoin, etretinate and acitretin. The last is a derivative of etretinate

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with a short half-life of only 2 days, compared with 120 days for etretinate; for this reason acitretin is potentially less teratogenic. Otherwise, it has the same therapeutic activity and side-effects as etretinate.

Etretinate is used in psoriasis and other disorders of keratinization for its ability to interfere with proliferative activity and keratinocyte differen- tiation, and also because of its anti-inflammatory activity, especially affect- ing chemotaxis (Fritsch, 1992). Etretinate has been used in PsA since the early 1980s (Rosenthal, 1982; Fritsch et al, 1985; Chieregato and Leoni, 1986; Ciompi et al, 1988). In a recently published report, 40 patients with PsA were enrolled in a two-centre pilot study with etretinate (Klinkhoff et al, 1989) for 8-24 weeks. Clinical and laboratory outcome measures improved significantly, with maximal improvement seen at 8 weeks. Adverse effects (mucocutaneous) resulting in discontinuation of drug therapy were seen in nine patients. A limiting factor for the use of retinoid therapy is the high prevalence and seriousness of adverse side-effects. Secondary effects of oral retinoids tend to be constant and occur early during the course of therapy. The most common side-effects are mucocutaneous, such as dryness of skin, oral and nasal mucosa, pruritus, alopecia, cheilitis and palmar dermatitis; toxic effects are rare, mostly idiosyncratic, late in presentation and dependent also on the total cumulative dose. The toxic effects may involve the liver, bone, muscle and ligaments. Bone pain secondary to periostitis and calcification of muscle and ligament are not unusual. Headache with or without intracranial hypertension, decreased night vision and an increase in serum lipid levels have all been reported. Teratogenicity, the principal secondary effect, is not strictly dose related and contraception is recommended for 2 years following therapy with etretinate (Saurat, 1992).

CYCLOSPORIN A

The efficacy of cyclosporin A in the therapeutic management of psoriasis and PsA is well established (Ellis et al, 1986; Marks, 1986; Steinsson et al, 1990; Gupta et al, 1990b; Donnelly and Doyle, 1992). In a recently published study, 13 patients receiving cyclosporin A therapy were followed for 5 years (Donnelly and Doyle, 1992). At the start of therapy, the mean

1 1 dose of cyclosporin A was 5.96mgkg- day- and the mean creatinine clearance rate was 92 ml/min. At i year of therapy the mean cyclosporin A dose was 3.62mgkg -I day -1 and the creatinine clearance rate 65 ml/min. Six patients developed a rise in the serum creatinine level by over 50% of the pretreatment value and three were withdrawn from therapy, secondary to nephrotoxicity. When the drug was discontinued after 2 years of therapy, renal toxicity persisted. Four patients remained on cyclosporin at 5 years, with a mean dose of 2.46 mg kg -1 day -1. Suppression of cutaneous psoriatic involvement persisted at these low doses, but the same did not occur with the arthritic symptoms, with three patients requiring the addition of azathio- prine to control the arthritis.

Discontinuation of cyclosporin therapy is usually followed by exacerbation

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of both psoriatic skin and joint involvement (Gupta et al, 1990b). This, with high incidence of secondary effects (liver function abnormalities and the possibility of lymphoma), underscores the need for long-term studies, and also for the use of the drug only in cases of refractory PsA.

VITAMIN D DERIVATIVES

Based on the immunomodulatory effect of 1,25-dihydroxyvitamin D3 and its effects on psoriasis (Smith et al, 1988; Morimoto et al, 1989), a 6-month open-label study in ten patients with PsA receiving 2 Ixg oral 1,25-dihydroxy- vitamin D3 was conducted (Huckins et al, 1990). A significant clinical improvement was observed in the tender joint count and physician global impression. This study is interesting because of the low incidence of secondary effects (hypercalciuria), but additional trials will be necessary. Vitamin D may have immunoregulatory effects that ameliorate inflammatory articular disease.

1,25-(OH)2 D3 potentiates the inhibitory effect of cyclosporin A on helper T cells from patients with rheumatoid arthritis, inhibits T-lymphocyte mitogenesis, and also alters to a varying degree lymphokine production (Rigby et al, 1987).

SOMATOSTATIN THERAPY

The role of human growth hormone in patients with psoriasis is controversial (Weber et al, 1981). However, treatment of psoriatic patients with the growth hormone inhibitor somatostatin has been shown to be effective in ameliorating the skin lesions of psoriasis (Weber et al, 1982; Buskila et al, 1991). Excellent results were observed in 20 patients with erythrodermic psoriasis, and the acute arthropathy present in six of the patients also improved (Vernier et al, 1988).

In another study, a group of 18 patients with PsA was treated for 48 h with an infusion of somatostatin, 250 txg/h diluted in a 5% glucose solution. Beneficial effects on both skin and joint involvement were seen immediately after treatment in eight patients, a milder clinical response in four, and no response in four. Two patients were removed from the study because of significant side-effects during infusion of the drug. The beneficial effects were more pronounced 15 days after treatment. In addition, patients with erythrodermic and large-plaque psoriasis and polyarticular inflammatory involvement responded better (Matucci-Cerinic et al, 1988). In a more recent study from the same group, the therapeutic effect of the combination of gold salts and somatostatin was evaluated. The analgesic activity of this combination was found to be remarkable (Matucci-Cerinic et al, 1992).

ZINC THERAPY

Preliminary evidence with the use of oral zinc sulphate for the therapy of PsA is promising. This is of particular interest in view of the low

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toxicity: efficacy ratio seen with this agent. In an early study, a double-blind cross-over trial in 24 patients with PsA showed that most tolerated this preparation well and nine reported improvement in the joint count during zinc sulphate therapy compared with when they were receiving placebo (Clemmensen et al, 1988). Evaluation of zinc sulphate as a SAARD was made in an open uncontrolled study of 20 patients (Frigo et al, 1988). Significant beneficial clinical and laboratory response was observed in this study. However, a similar study failed to reveal a significant clinical response to zinc sulphate, while restoration of neutrophil chemotaxis to normal values was observed (Leibovici et al, 1990). Additional studies are needed to assess fully the beneficial effects of zinc sulphate in psoriatic patients.

D-PENICILLAMINE THERAPY

Limited information on the use of D-penicillamine therapy for PsA is avail- able. Accumulated evidence, however, suggests that D-penicillamine may be as effective in patients with PsA as in those with rheumatoid arthritis. In addition, side-effects, including myasthenia gravis and pemphigus vulgaris, are identical to those seen in rheumatoid arthritis (Roux et al, 1979; Price and Gibson, 1986).

CORTICOSTEROID THERAPY

The use of steroids in PsA is worthy of consideration. They should be used only in special circumstances such as cases of severe inflammatory joint involvement. It should always be kept in mind that PsA can relapse in spite of this medication. Flare-up of psoriatic skin involvement may occur during reduction of steroid dosage, and erythrodermic rash is a secondary effect. The topical use of steroids, however, is effective in controlling skin involve- ment. Furthermore, their intra-articular use in patients with monarticular or oligoarticular involvement can be of great benefit. Special care should be taken to prepare the skin to minimize the likelihood of infection into the joint. In children with PsA steroids should be used with great caution because children do not respond well to steroids and, more importantly, the incidence of side-effects is very high.

COLCHICINE THERAPY

There are two published studies on the use of colchicine in the treatment of PsA. The first was an uncontrolled study that reported a beneficial effect of this drug in the treatment of patients with psoriasis, some of them with arthralgia (Wahba and Cohen, 1980). The second was a placebo-controlled double-blind cross-over study of 15 patients with PsA that could not be controlled for analgesic or NSAID treatment. Twelve patients completed 16 weeks, with 1.5 rag/day colchicine found to be more effective than placebo.

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The cutaneous psoriatic rash did not improve, and the most common secondary effects were gastrointestinal intolerance, with two patients with- drawing from the study (Seideman et al, 1987). A recently completed prospectively controlled study did not find colchicine to be useful in the treatment of psoriatic arthritis (McKendry et al, 1993).

PHOTOCHEMOTHERAPY WITH METHOXYPSORALEN (PSORALEN PLUS ULTRAVIOLET A, PUVA)

The effects of photochemotherapy on arthritis was evaluated in 27 patients with psoriasis (Perlman et al, 1979). Patients were divided into spondylitic and non-spondylitic subgroups. A good response to PUVA treatment with a 49% improvement in peripheral joint activity was observed in the non- spondylitic group. Skin improvement was also seen in these patients. In contrast, spondylitic patients did not exhibit improvement of either psoriasis or arthritis. In another study, five patients with psoriasis and arthritis were treated with photopheresis (Wilfert et al, 1990). Patients experienced slight to moderate clinical improvement of articular involvement, but cutaneous lesions showed only minimal change. Further studies are required to confirm these results.

DIETARY SUPPLEMENTATION WITH POLYUNSATURATED ETHYL ESTER LIPIDS

The anti-inflammatory effect of dietary supplementation using polyunsatu- rated ethyl ester lipids was reported to benefit patients with psoriasis and PsA (Lassus et al, 1990).

Polyunsaturated ethyl ester lipids (Angiosan) were administered to 80 patients with psoriasis; 34 had PsA. They found this therapy moderately effective as monotherapy for psoriasis. In addition, patients with PsA experienced improvement of joint pain as measured by a visual analogue scale. At base-line, 18 patients had severe joint pain, ten had moderate and six had mild joint pain. After 8 weeks' treatment, two patients had severe, four moderate and 17 mild joint pain. These findings, although very preliminary, are promising.

USE OF BIOLOGICAL AGENTS: INTERFERON-,,/

Interferon -/(IFN--/) has been used in the treatment of PsA, but its efficacy remains to be determined. IFN-',/was given for 28 days to 24 patients with PsA (Fierlbeck and Rassner, 1990) in a placebo-controlled double-blind randomized study and 56 patients were treated in an open study for 9 months. IFN-"y (100 txg) was administered daily subcutaneously. In the first group the Ritchie index improved significantly compared with placebo, while in the second group some patients experienced improvement during

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the first 3 months of therapy. After that period, however, no further improvement was seen and a deterioration was noticed with continuing treatment. Similar findings have also been seen in patients with rheumatoid arthritis treated with IFN-~/.

Polyarthritis and acute plantar fasciitis have developed during treatment of psoriasis with intramuscular recombinant human IFN--y for 10-12 weeks. Resolution of the arthritis promptly followed discontinuation of this therapy (O'Connell et al, 1992).

PEPTIDE T THERAPY

Peptide T has been shown to be effective in a few patients with psoriasis and PsA (Wetterberg et al, 1987; Marcusson and Wetterberg, 1989). Peptide T is a synthetic octapeptide identical to a segment of the envelope glycoprotein (gp120) of the HIV. This compound is of interest, in view of the increased prevalence of psoriasis and PsA in patients with HIV infection.

MISCELLANEOUS THERAPEUTIC MODALITIES

Multiple therapeutic procedures, including razoxane (Atherton et al, 1980), plasmapheresis (Grivet et al, 1989), tetracosactrin (Chichenina and Rakkmatov, 1988), antibiotics (Caperton et al, 1990), Hz-receptor antagonists (Nielsen et al, 1991), anti-CD4 monoclonal antibodies (Herzog et al, 1989), monokine release inhibitor, allogeneic bone marrow transplan- tation, bromocriptine and radioactive synovectomy (Will et al, 1992), have been reported to be of some benefit in the management of PsA. Most reports are anecdotal, and further prospective controlled studies are needed to establish their usefulness.

SURGERY AND REHABILITATIVE MANAGEMENT

The indications for surgical procedures and rehabilitative management are similar to those for any other chronic inflammatory articular disorder.

Synovectomy may be used in highly selected cases, especially in patients with only a few joints affected. Reconstructive surgery, including total joint replacement, is indicated for patients with incapacitating and deforming forms of arthritis. There is some concern, however, about wound infection. It has been shown that patients with PsA are at increased risk of infection; therefore, special attention should be given to the use of topical cortico- steroids when total joint arthroplasty is considered (Lambert and Wright, 1979; Stern et al, 1989). The use of methotrexate or any other immuno- suppressive agent should be discontinued at least 2 weeks before operation and restarted 1-2 weeks after surgery.

The incidence of postoperative fibrosis and/or ankylosis in patients with PsA is no different from that in patients with other chronic arthritides.

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Rehabilitation therapy should be considered in every patient with PsA. It should be aimed to maximize the potential for normal physical and emotional activities. Depending on the degree of active synovitis and the type and site of joint involvement, a combination of exercise, rest and selective immobilization is advisable. Hydrotherapy or local heat (dia- thermy) facilitate implementation of exercise therapy in the recovery phase. Cryotherapy in the form of cold ice packs, ethyl chloride or fluoromethane sprays, hydrotherapy, or ice massage is more beneficial when joint inflam- mation is present. In the presence of enthesitis, cryotherapy also becomes very helpful.

In patients with spondylitic or axial involvement, physical measures, such as exercise designed to stretch the paravertebral musculature, and advice against adopting a kyphotic posture are recommended. The most important intervention is aimed at the preservation of a normal upright posture. It should also be kept in mind that the spine in patients with PsA with spondylitic involvement is often osteoporotic and therefore prone to fracture with minimal trauma. Therapy to prevent osteoporosis should be part of the overall medical management, and prolonged bed-rest should be avoided as much as possible. In addition, contact sports and heavy physical activity should be avoided, and swimming encouraged.

The use of orthotic devices including splints, sticks, crutches and walkers is advisable to improve both the working capacity of a given joint and ambulation (Gerber, 1985).

Significant disability in patients with PsA can occur, although it tends to be less severe than that seen in those with rheumatoid arthritis. Its prevention demands early initiation of the comprehensive therapeutic medical management outlined above.

SUMMARY

The treatment of psoriatic arthritis has acquired relevance in the past few years because of advances and better understanding of the pathogenetic mechanisms implicated in the disease, and also because of recognition that this disorder is not a benign disease as was previously thought. The general principles of management for any inflammatory arthritis, including pharmacological, surgical and rehabilitative treatment, are to be used, with concomitant therapeutic management of skin involvement.

Non-steroidal anti-inflammatory drugs constitute the mainstay of pharmacological therapy for most patients, with a good clinical response observed in 75-85%. Early use of remittive agents, especially methotrex- ate, is indicated in patients with a poor response to NSAIDs or those with polyarticular and progressive joint involvement. Patients who are refrac- tory to conventional therapy should be considered for newer and potentially more toxic therapeutic modalities such as cyclosporin A and retinoids.

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R E F E R E N C E S

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