Psoriasis : : Studies of phenotype at onset and of associated cardiovascular morbidity

Abstract: Psoriasis is a complex inflammatory skin disorder, affecting 2-3% of the population in the western world. The etiology of psoriasis is not yet known. However it is likely that its pathogenesis involves interplay between multiple genetic and environmental triggers. The aim of this thesis was to study psoriasis phenotypes at disease onset, to explore putative precipitating factors and to investigate cardiovascular morbidity in psoriasis. Firstly, we established the Stockholm Psoriasis Cohort (SPC), comprising 400 adults (<15 yr) with first-time incidence (<1 yr) of psoriasis disease: 74 had guttate psoriasis and 326 primarily had plaque psoriasis. Different environmental factors were implicated in different phenotypes: guttate psoriasis was associated with younger age and recent infection (84%), while the predominating factor associated with the onset of plaque psoriasis was a recent distinct life crisis (46%). Secondly, we examined whether or not the prevalence of streptococcal infections in guttate and plaque phenotypes varies in HLA-Cw'0602 positive and negative individuals. Three hundred and seventy five individuals, either with guttate (n=68) or plaque (n=307) psoriasis, derived from the SPC, and a total number of 285 matched controls were included in the study. The study showed that, regardless of phenotype, the prevalence of streptococcal throat infections is double among HLA-Cw'0602 positive psoriatics compared with HLA-Cw'0602 negative patients. No increased prevalence of streptococcal infection was noted among control individuals. Thirdly to assess the risk for cardiovascular death among psoriasis patients, we used Swedish nation-wide registries to follow up both inpatients and outpatients with psoriasis for cardiovascular mortality. In a cohort of 8991 psoriatic inpatients, followed until 1995, cardiovascular mortality was 50% greater compared with the general population. There was a gradual increase in risk with increasing duration of follow-up, and with increasing number of admissions. The relative risk of death from cardiovascular disease was highest among patients who were admitted at a young age, whereas psoriasis outpatients had no increase in risk. The underlying pathogenesis for such a correlation remains unclear. However multiple factors including systemic inflammation, oxidative stress, aberrant lipid profile and concomitant established risk factors have been discussed. Fourthly, to assess the blood lipid profile in patients with psoriasis at the initial stage of the disease, 200 patients derived from the SPC were investigated, comparing plasma concentrations of lipids, lipoproteins and apolipoproteins with those of matched controls. Psoriasis patients manifested significant dyslipoproteinemia. Specifically, patients had significantly higher cholesterol concentrations in the verylow-density and high-density lipoprotein fractions compared with controls. Adjustment for established environmental risk factors did not affect the results.