A disease severity scale for systemic sclerosis: development and testing.

OBJECTIVE: To develop and test a severity scale for individual organ involvements in systemic sclerosis (SSc, scleroderma). METHODS: An international study group completed the following tasks: (1) developed a glossary of terms including all pertinent variables for 9 potentially affected organ systems; (2) collected prospective data to determine the feasibility and practicality of each proposed variable; (3) revised the initial list of variables; (4) determined the association of each variable with mortality (a proxy for morbidity) using 579 patients in an existing comprehensive longitudinal scleroderma databank; (5) developed a severity grading scale for each organ system by discussion and consensus; and (6) externally validated the scale using an independent group of 680 patients from the same databank. RESULTS: Nine organ-specific severity scales were developed from 0 (no documented involvement) to 4 (endstage disease). The data required for scale completion are relatively easy and practical for all physicians to obtain. CONCLUSION: This preliminary severity scale will be useful for assessing disease severity status in individual patients both at one point in time and longitudinally. The severity scale will assist in the design and conduct of clinical trials and the comparison of study populations with one another. The scale will serve as a framework for developing a scleroderma disease activity index.

Sustained vasoconstriction associated with daily cyclosporine dose in heart and lung transplant recipients: potential pathophysiologic role of endothelin.

Transient decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) have been associated with each daily dose of cyclosporine (CYA) in patients with renal allografts. We examined the differential dose effects of CYA on native renal function in 24 recipients of heart or lung transplants (treated with 7.3 +/- 0.5 mg/kg/day [mean +/- SEM]) and in seven patients with psoriasis (treated with 4.2 +/- 0.7 mg/kg/day). GFR and RPF were measured by urinary inulin and para-aminohippuric acid clearances 2 hours before the morning CYA dose and for 6 hours after. The age of heart and lung transplant recipients at renal study (2 months after transplantation) was 47 +/- 2.0 years. Their serum creatinine levels rose from 80 +/- 4.0 mumol/L during the first week after transplantation to 120 +/- 4.0 mumol/L at renal study (p < 0.0001). Their GFR and RPF were decreased before the CYA dose at 64 +/- 2.4 and 340 +/- 16 ml/min per 1.73 m2 and did not vary during the study. In comparison, the age of patients with psoriasis was 51 +/- 4.6 years at renal study (24 +/- 4.0 months after CYA treatment). Their serum creatinine levels rose from 80 +/- 4.0 mumol/L before treatment to 100 +/- 10 mumol/L at renal study (p = 0.07). Transient decreases of their baseline GFR and RPF (85 +/- 7.4 and 380 ml/min per 1.73 m2) with a nadir occurring during the first 2 hours of CYA ingestion were observed together with the recovery of these parameters toward baseline by the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic nephrotoxicity in psoriatic patients treated with low-dose cyclosporine.

Chronic nephrotoxicity is a major complication in high-dose cyclosporine treatment. We examined the glomerular filtration rate, renal plasma flow, and kidney biopsies of 15 psoriatic patients treated with low-dose cyclosporine (< or = 5 mg/kg/d) for 30 months (25 to 35 months) 1 month after drug withdrawal. The mean (95% confidence interval) age of the patients in the study was 44 years (38 to 50 years). Their serum creatinine levels pretreatment and at the time of the study were 0.94 mg/dL (0.85 to 1.0 mg/dL) and 1.2 mg/dL (1.1 to 1.3 mg/dL). Seven patients had a decreased glomerular filtration rate and four of them also had a reduced renal plasma flow, below the 2.5 percentile of normal. Four patients had moderate tubulointerstitial scarring and arteriolopathy, while the remaining patients had mild structural abnormalities. The severity of acute nephrotoxicity during treatment and chronic structural injury were highly correlated (r = 0.81; P < 0.0003). Recurrent episodes of severe acute nephrotoxicity (defined as reversible increase of serum creatinine > 90% of baseline value) was a marker for moderate chronic nephrotoxicity. No correlation was found between chronic structural injury and patient age, sex, pretreatment creatinine level, blood pressure (pretreatment or during treatment), cyclosporine dose and treatment duration, and cyclosporine blood levels. In seven patients continued on cyclosporine for another 12 months (10 to 14 months), repeat studies showed no interval changes. Despite 40 months (30 to 51 months) of treatment, all but one of these seven patients (with previous hypertension and atherosclerotic vascular disease) had mild functional and structural abnormalities. None had any severe acute nephrotoxicity at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Representation of preferences in decision-support systems.

The recommendations of computer-based decision-support systems depend on the preferences of an expert on which the model is based. Often, these preferences are represented only implicitly, rather than explicitly, in the system. Decision-theoretic preference models that explicitly represent the preferences of the decision maker provide numerous advantages for decision-support systems. In this paper, we describe these advantages. The creation and refinement of decision-theoretic preference models, however, remains a difficult task. We describe an accurate and efficient method for determining the preferences of domain experts and for refining the model that captures those preferences. In this preference-assessment method, we simulate decisions common in the expert's area. We then infer the preferences of the expert from the choices that she makes on the simulated decisions, and use the preference information to refine the model automatically.

Fluorescence assay to monitor phagocytosis by bloodclot derived polymorphonuclear leucocytes. 2. Study of patients with psoriasis and the effect of exposing leucocytes to psoriatic skin scales.

Comparisons of phagocytic parameters were carried out by a recently developed fluorescence test which is reproducible, simple and fast. Phagocytosis by polymorphonuclear leucocytes (PMNs) obtained from patients with psoriasis was compared with that of healthy individuals. Psoriatic skin scales, non-sterile and sterile, were tested for stimulatory effect on PMNs and compared with the effect of normal skin scrapings. Results confirm enhanced phagocytosis of bacteria by PMNs from patients with psoriasis over that of PMNs from healthy volunteers. Furthermore, the supernatant fluid from suspensions of psoriatic skin scales, non-sterile and sterile, stimulated PMNs activity.

Pilot study of etretinate in psoriatic arthritis.

A 2-center pilot study compared clinical and laboratory outcomes in 40 patients with psoriatic arthritis before and after treatment for 8 to 24 weeks with the vitamin A derivative, etretinate. The number of tender joints fell from 22.0 +/- 8.75 before treatment to 11.44 +/- 8.50 after treatment (p = .000). The duration of morning stiffness was 101.95 +/- 62.45 min before therapy and 44.53 +/- 82.10 min after treatment (p = 0.0004). Similar highly clinically and statistically significant improvement was seen in all clinical outcome measures and in the erythrocyte sedimentation rate. Primarily mucocutaneous side effects were seen in 39/40 patients and resulted in treatment termination before 24 weeks in 9 patients.

Psoriatic arthritis (PSA)--an analysis of 220 patients.

Since 1978, 220 patients with psoriatic arthritis have undergone detailed study at the Women's College Hospital in Toronto, Canada. Clinical, radiological and biochemical data were subjected to computer analysis in order to determine clinical-biochemical correlations within subsets of patients with psoriatic arthritis. Our findings indicate a spectrum of disease patterns and severity. Overall, we found a 40 per cent incidence of deforming, erosive arthropathy, with 17 per cent of patients having five or more deformed joints. ARA stage 3 and 4 radiological joint change occurred in 28 and 14 per cent respectively, and 11 per cent of patients had ARA Class III or IV functional impairment. The asymmetric oligoarthritis previously reported to account for the majority of cases of psoriatic arthritis was not a dominant pattern in our own experience, occurring in only 28 per cent of the series. Polyarthritis was the most common joint pattern, present in 61 per cent with symmetric and asymmetric patterns occurring equally. Our experience suggests that polyarthritis, symmetric or asymmetric, is a more common presentation of the disease than is generally acknowledged. Furthermore, the frequency of deforming destructive arthropathy challenges the concept of psoriatic arthritis as a benign arthropathy.

HLA antigens in psoriatic arthritis.

HLA antigen frequencies were studied in 158 patients with psoriatic arthritis, and compared to those of 101 patients with uncomplicated psoriasis and 243 healthy controls. The HLA antigens B16, B17, B27, B39 and Cw6 were associated with psoriatic arthritis. No associations between DR antigens and psoriatic arthritis were demonstrated. However, the subset of patients with rheumatoid-like arthritis demonstrated an increase in DR4. Uncomplicated psoriasis patients had higher frequencies of B17, Cw6 and DR7 than patients with psoriatic arthritis, while B7 and B27 correlated with development of arthritis. HLA-B27, Cw2 and DRw52 were associated with back involvement, whereas B38 and B39 were associated with polyarthritis. HLA-B7, B13 and DR7 correlated with milder disease in patients with psoriatic arthritis.

Impaired antigen-specific suppressor cell activity in psoriasis and psoriatic arthritis.

Antigen specific suppressor cell activity of peripheral blood mononuclear cells was investigated in 20 patients with psoriatic arthritis and 18 patients with uncomplicated psoriasis and compared to that of 27 age- and sex-matched healthy controls and 18 patients with osteoarthritis. Topical skin therapy and nonsteroidal anti-inflammatory medications were allowed but patients who had taken disease suppressive, immunosuppressive, cytotoxic, and systemic steroid therapy were excluded. The results demonstrate reduced suppressor cell activity (SCA) in patients with psoriatic arthritis compared to normal controls (54.8% +/- 4.9 vs 68.4 +/- 2.8, p less than 0.005). Similarly, the response of patients with uncomplicated psoriasis was significantly lower than normal (50.1 +/- 4.9 vs 67.3 +/- 3.0% p less than 0.005). Five of the 20 patients with psoriatic arthritis and 7 of the 18 patients with uncomplicated psoriasis demonstrated SCA of more than 2 SD below the normal mean. The SCA of patients with osteoarthritis was normal. The plaque forming cell (PFC) response of patients with psoriatic arthritis and uncomplicated psoriasis was not different from those of the normal controls or of patients with osteoarthritis. There was no correlation between impaired suppression and disease activity or therapy.

A randomized comparison of three conventional modes of treatment of psoriasis of the scalp.

Three conventional treatments of scalp psoriasis were compared in a randomized, blind, uncontrolled clinical trial in 30 patients at a psoriasis day-care centre. Triple gel (the sequential application of Keralyt, Estar, and Topsyn gels), 10 percent salicylic acid in Sofsyn oil, and 10 percent salicylic acid in mineral oil were compared. There were no statistically significant differences among the three treatments in terms of clinical efficacy. Therefore, on the basis of lowest cost and highest patient acceptance, 10 percent salicylic acid in mineral oil is the preferred treatment.

An educational program for psoriatics: an evaluation.

Patients with psoriasis referred to the Dermatology Service at Women's College Hospital and satisfying certain criteria relating to percentage body involvement, age, and the absence of serious coincident conditions were assigned at random to three weeks of day care and education at the Psoriasis Education and Research Centre (PERC) or to the Dermatology Service at Women's College Hospital (WCH) for normal hospital care. On admission, all study patients received normal history and physical examinations and were photographed by a standardized procedure that provided an accurate estimate of type and extent of body involvement. A functional history was taken from PERC patients that provided information concerning their ability to cope at home, at work, and socially; the extent and appropriateness of their self-care practices; and their knowledge concerning the pathophysiology and etiology of psoriasis and the names and actions of the medications they were using. Individualized patient education programs were designed with reference to the medical and functional information and implemented in the three weeks of day care. Photographic assessment and the functional history were repeated at three weeks, six months and twelve months. Hospital patients were reassessed at six and twelve months and a functional history was taken at six months. The functional status of PERC and hospital patients was compared at six months. The results of this study reinforced the belief that in the case of psoriasis, education coupled with treatment is more effective than treatment alone.

Mycetoma caused by Nocardia madurae.

Actinomycotic mycetoma was diagnosed in a woman from Jamaica living in Ontario. This is the first case reported in Canada in which the infection was caused by Nocardia madurae. Despite oral therapy with trimethoprim-sulfamethoxazole, local excision of newly appearing nodules was required periodically for clinical improvement. Laboratory procedures were modified to aid in identification of pathogenic actinomycetes.