An educational programme for patients with psoriasis and atopic dermatitis: a prospective randomized controlled trial.

BACKGROUND: Patient education in addition to standard treatment, with the aim of affecting care through courses, is a relatively new concept in dermatology. Here we introduce a randomized controlled trial (RCT) regarding a previously described 12-week educational programme for chronic skin diseases. OBJECTIVES: The primary objective of the RCT was to measure the effect of an educational programme on disease severity and quality of life in patients with psoriasis or atopic dermatitis. METHODS: We recruited 50 patients from Ghent University Hospital. Patients with diagnosed psoriasis or atopic dermatitis were randomized (1 : 1) to the intervention or control group. The clinical outcome was measured by two blinded observers using the Psoriasis Area and Severity Index (PASI), Scoring Atopic Dermatitis or the Eczema Area and Severity Index. Quality of life was measured by dermatology-specific quality-of-life questionnaires. There was a follow-up period of 9 months. RESULTS: We found that disease severity and quality of life improved significantly for patients with psoriasis (n = 29) but not for patients with atopic dermatitis (n = 21) at 3 months. Patients in the intervention group showed a significant reduction in mean PASI (P = 0·036), mean Dermatology Life Quality Index (P = 0·019) and mean Psoriasis Disability Index (P = 0·015), compared with the control group at 3 months. This improvement continued for at least 6 months, i.e. 3 months after the intervention, but was lost at follow-up after 9 months. CONCLUSIONS: Evaluating this form of educational programme, by means of a single-centre RCT, indicates its added value in the longer term management of psoriasis.

Clinical significance of Koebner phenomenon in vitiligo.

BACKGROUND: The clinical significance of Koebner phenomenon (KP) in vitiligo with respect to disease activity and course is still debatable. Recently, a new classification was introduced for the assessment of KP. OBJECTIVES: To evaluate the new assessment method for KP in clinical practice and to determine its clinical significance, both with respect to the clinical profile, course of vitiligo and treatment response. METHODS: Seven hundred patients with generalized vitiligo were included in this observational cohort study. KP was classified according to the new classification system into different subtypes [KP1, by history; KP2A and KP2B, by clinical examination (A, lesions on friction areas; B, linear, artefactual lesions)]. RESULTS: KP1 was positive in 34·1% of the patients, 66·3% were KP2A positive and 15·1% showed KP2B. The body surface area (BSA) was significantly (P < 0·001) higher in the presence of any KP subtype and more disease activity was found in KP1-positive and KP2B-positive patients. An earlier age at onset and elevated risk of further depigmentation despite treatment were observed in all KP-positive groups. In KP2A- and KP2B-positive patients, depigmentation of wrists/ankles was more common. In the KP2A-positive group, a significantly higher prevalence of thyroid disease was found while autoimmune diseases were less prevalent in KP2B-positive patients. CONCLUSION: The new assessment method for KP, taking into account both history and clinical examination, seems to be a useful and valuable tool for assessing KP in daily practice. Our results support the hypothesis that KP may function as a clinical parameter to assess and predict the clinical profile and course of vitiligo.

Serum plakophilin-3 autoreactivity in paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a malignancy-associated autoimmune disease in which circulating autoantibodies recognize various polypeptides that constitute the desmosomes and hemidesmosomes of epithelial structures. OBJECTIVES: To determine whether PNP is associated with autoreactivity against the armadillo-repeat-containing plakophilin-3 (PKP3) protein. METHODS: HEK293 cells were transiently transfected with either a pEF6/myc-His or a pEGFP-N2 construct, both encoding human PKP3 (protein products of 85 kDa and 115 kDa, respectively). Protein lysates were made in Laemmli buffer. The proteins were separated by gel electrophoresis, transferred to filters and probed with five PNP sera, four pemphigus vulgaris sera, two pemphigus foliaceus sera, five bullous pemphigoid sera, one cicatricial pemphigoid serum and one linear IgA dermatosis serum. A mouse monoclonal anti-PKP3 antibody raised against a 20-amino acid peptide of human PKP3 was used as a positive control. RESULTS: Autoreactivity against both 85-kDa and 115-kDa recombinant PKP3 protein products was detected in all five PNP sera and in one pemphigus vulgaris serum. None of the sera of patients with basement membrane zone bullous diseases reacted with the PKP3 protein products. The presence of autoantibodies against PKP3 in PNP sera was subsequently confirmed in human epidermal lysate blots. CONCLUSIONS: This is the first report of PKP3 reactivity in bullous disorders, which was present in all the PNP sera tested. The presence of PKP3 reactivity in one patient with pemphigus vulgaris is not unexpected as the desmosome is also targeted in this disease.

Identifying targets for topical RNAi therapeutics in psoriasis: assessment of a new in vitro psoriasis model.

Diseases of the skin are amenable to RNAi-based therapies and targeting key components in the pathophysiology of psoriasis using RNAi may represent a successful new therapeutic strategy. We aimed to develop a straightforward and highly reproducible in vitro psoriasis model useful to study the effects of gene knockdown by RNAi and to identify new targets for topical RNAi therapeutics. We evaluated the use of keratinocytes derived from psoriatic plaques and normal human keratinocytes (NHKs). To induce a psoriatic phenotype in NHKs, combinations of pro-inflammatory cytokines (IL-1α, IL-17A, IL-6 and TNF-α) were tested. The model based on NHK met our needs of a reliable and predictive preclinical model, and this model was further selected for gene expression analyses, comprising a panel of 55 psoriasis-associated genes and five micro-RNAs (miRNAs). Gene silencing studies were conducted by using small interfering RNAs (siRNAs) and miRNA inhibitors directed against potential target genes such as CAMP and DEFB4 and miRNAs such as miR-203. We describe a robust and highly reproducible in vitro psoriasis model that recapitulates expression of a large panel of genes and miRNAs relevant to the pathogenesis of psoriasis. Furthermore, we show that our model is a powerful first step model system for testing and screening RNAi-based therapeutics.