An investigation of late onset psoriasis

  • Eleni Theodorakopoulou

    Student thesis: Phd

    Abstract

    Psoriasis is a chronic, clinically heterogeneous, skin condition that affects approximately 2% of the general population. In 1985, Henseler and Christophers, classified psoriasis into early onset (EOP; age at onset smaller or equal to40 years-y) and late onset disease (LOP; age at onset >40 y). Previous research suggests that there are genetic and immunological differences between EOP and LOP. In particular, the major genetic determinant for psoriasis, the human leukocyte antigen (HLA)-Cw6 allele, occurs more frequently in EOP (55-80%) compared to LOP (15-20%) patients. Epidermal Langerhans' cells (LC) migration is also different in these 2 subtypes of psoriasis. The primary aim of this thesis was to further explore the clinical, histological and immunohistochemical (IHC) differences between EOP and LOP. We compared clinical characteristics in a total of 497 subjects, including 340 psoriasis patients (108 recruited prospectively; 76 EOP and 32 LOP, mean age of onset 20.3±9.9 and 55.6±7y respectively, and 232 retrospectively; 202 EOP and 30 LOP, mean age of onset 20.7±9.9 and 55.2±7.2y respectively) and 157 controls (mean age 66±11.2y). Information on demographics, family history of psoriasis, clinical features, treatment and co-morbidities were recorded. Patients were also assessed for health-related quality of life and psychological distress. A total of 31 psoriasis patients, greater than or equal to 50y of age, participated in the histological and IHC evaluation; 17 EOP and 14 LOP, mean age of onset 21.1±8.5 and 55.4±7.7y respectively. Skin biopsies were taken from involved (PP) and uninvolved (PN) skin and stained with haematoxylin and eosin (H&E) and IHC antibodies against various T-cell (CD3, CD4, and CD8) and LC (CD1alpha) markers. The H&E parameters (morphological and inflammatory) were graded with the use of a study specific histological score, whilst IHC positive epidermal cells were counted per microscopic field at 200X magnification. The dermal IHC infiltrate was assessed with a semi-quantitative (0-3) scale. Gender, body mass index, disease duration and severity, diagnosed hypertension and dyslipidemia were treated as covariates.The clinical data showed that LOP patients had a lower likelihood of having a positive family history of psoriasis (62% of EOP versus 35.6% of LOP patients; chi square-x2, P=0.001). In addition, patients with EOP parent(s) were 91% less likely to develop LOP than EOP (odds ratio-OR=0.093, P=0.025, 95% confidence interval-CI 0.012-0.74). Moreover, compared to LOP, EOP patients had a more severe disease (x2, P=0.021), usually requiring 3rd line treatments (x2; P=0.010). They also experienced frequent flares, following upper respiratory tract infections (x2, P=0.049). When data were segregated by age (greater than or equal to50years) and after accounting for covariates, we observed that, compared to the non-psoriasis population, LOP patients were approximately 3 times more likely to develop type 2 Diabetes Mellitus (OR=2.56, P=0.05, 95% CI 1.01-6.54), whilst, EOP subjects were 98% less likely to develop autoimmune thyroiditis (OR=0.025, P=0.02, 95% CI 0.001-0.55). Psychologically, LOP patients were found to be a clinically more anxious group compared to EOP (t-test, P=0.006). Microscopically, the results from the H&E study showed an increased total inflammatory infiltrate in LOP, PP sections compared to EOP, PP ones (t-test, P=0.028). With IHC stains, we observed that in the epidermis of LOP PP, there was a significantly higher count of CD4+ cells; mean CD4+ in LOP of 15.1 ± 6.2 versus 6.7±4.6 in EOP (Analysis of variance-ANOVA, P
    Date of Award1 Aug 2014
    Original languageEnglish
    Awarding Institution
    • The University of Manchester
    SupervisorChristopher Griffiths (Supervisor) & Richard Warren (Supervisor)

    Keywords

    • immunological differences
    • psoriasis
    • early onset
    • late onset
    • histological differences
    • clinical differences

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