Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects.

BACKGROUND: Darier disease (DD) is a rare genodermatosis caused by heterozygous mutations in the ATP2A2 gene. It has been associated with neuropsychiatric manifestations. OBJECTIVES: To investigate the genetic basis of Israeli patients with DD, and its association with the neuropsychiatric phenotype. METHODS: A cohort of 32 families comprising 74 affected individuals and 13 unaffected family members was recruited from the Haemek Dermatology Department and other dermatology clinics in Israel. The individuals were evaluated by detailed questionnaires, physical examination and genetic analysis. The main outcome measures were genetic mutations, psychiatric profile and their association. RESULTS: Twenty-three mutations in ATP2A2 were scattered over the entire gene, 14 of them novel. Two families shared the same mutation. Twenty-one patients (28%) had a history of psychiatric disorders, most of them mood disorders. Another seven patients (9%) were highly suspected of having a psychiatric disorder; 21 (28%) reported suicidal thoughts and five (7%) had attempted suicide. The psychiatric phenotype demonstrated inter- and intrafamilial variability, and was not associated with disease severity, family history of psychiatric disease or mutation location. CONCLUSIONS: The cohort demonstrated genetic heterogeneity with no mutation cluster along the gene, and a high prevalence of psychiatric disorders. Although no clear genotype-phenotype correlation was found, the results point to a major effect of genetic background on psychiatric phenotype, together with other modifiers.

Impact of antipsoriatic therapy on endothelial function.

BACKGROUND: Endothelial function (EF) impairment is one of the first events in the process of atherosclerosis, which is known to be associated with psoriasis. Nevertheless, the effect of antipsoriatic treatments, some of them with atherogenic risks, on cardiovascular morbidity and EF is still unclear. OBJECTIVES: To investigate the effect of short-term antipsoriatic treatments on EF values as a potential marker of their effect on cardiovascular morbidity. METHODS: EF was evaluated in 26 patients with moderate-to-severe psoriasis by measuring microvascular blood flow, expressed as the reactive hyperaemia index (RHI), before and after phototherapy (8 weeks) or systemic antipsoriatic treatment (12 weeks). RESULTS: Antipsoriatic intervention was effective (46% achieving ≥ 75% improvement in Psoriasis Area and Severity Index), while the average RHI did not improve during the study (1·73 ± 0·48. vs. 1·66 ± 0·35, average difference -0·12 ± 0·43, not significant). Patients with baseline preserved EF exhibited a decline in RHI (difference -0·2 ± 0·4, P = 0·053), while patients with abnormal baseline RHI presented nonsignificant RHI improvement (RHI difference 0·1 ± 0·2). CONCLUSIONS: There was no positive effect on EF of short-term antipsoriatic treatment. It is possible that a longer period of treatment and EF evaluation would uncover a positive endothelial effect, especially in patients with baseline abnormal EF.

Learning disabilities in Darier's disease patients.

BACKGROUND: Neuropsychiatric features and intellectual difficulties have been reported in studies of Darier's disease. Learning disabilities have never been reported or evaluated systematically in these patients. OBJECTIVE: To assess the prevalence of learning disabilities in 76 patients with Darier's disease, and cognitive functioning in 19 of them. METHODS: The data were collected by two methods: a questionnaire, as part of a larger study on the clinical characteristics of 76 patients; and neuropsychological measures for the assessment of learning disabilities in 19 of them. RESULTS: Thirty-one of the 76 patients reported learning disabilities (41%) and 56 (74%) reported a family history of learning disabilities. Significant differences were found between the 19 patients evaluated on cognitive tasks and a control group of 42 skilled learners on subtraction and multiplication tasks. Six (32%) of the 19 were identified as having reading difficulties and five (26%) exhibited low performance on the Concentration Performance Test. All patients had general cognitive ability in the average range. CONCLUSIONS: Findings suggest an association between Darier's disease and learning disabilities, a heretofore unreported association, pointing to the need to obtain personal and family history of such disabilities in order to refer cases of clinical concern for further study.

Bacteriological aspects of Darier's disease.

BACKGROUND: There are no established data on the prevalence of bacterial colonization of lesional skin, nares and perineum in Darier's disease (DD), or its contribution to the clinical manifestations of the disease. OBJECTIVE: To determine the prevalence of bacterial colonization of lesional skin and Staphylococcus aureus (S. aureus) in nares and perineum in 75 patients with DD, the association of these parameters with disease and patient characteristics, and the features of the bacterial skin infection in this group. METHODS: Medical interviews and physical examinations were performed. Bacteria were isolated from swabs taken from lesional skin, nares and perineum. RESULTS: S. aureus was isolated in 68%, 47% and 22% of lesional skin, nares and perineum cultures respectively. Subjects with positive S. aureus culture from lesional skin and/or nares had a statistically significant higher percentage of skin area affected and a more severe disease than patients with negative culture. Thirty of the 75 patients (40%) recalled bacterial skin infection, most often on the chest. CONCLUSIONS: Patients with DD have high prevalence of S. aureus colonization in lesional skin and nares, with a correlation between disease severity and extent of the colonization. Further studies examining the consequences of S. aureus eradication in those sites may establish the need for S. aureus lesional skin and nares colonization screening and eradication as part of the treatment of DD exacerbations.

Health-related quality of life among Darier's disease patients.

BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder characterized by persistent eruption of hyperkeratotic papules. The effect of DD on quality of life (QOL) has been assessed in only one study, which found no correlation between the Dermatology Life Quality Index (DLQI) score and clinical severity of the disease. The correlation between health-related quality of life (HRQL) and other diseases and patient characteristics has not been studied. OBJECTIVES: To examine the HRQL of patients with DD and to evaluate the association between HRQL scores and disease and patient characteristics. METHODS: A total of 74 DD patients completed three QOL questionnaires: DLQI, EQ-5D, and one specially designed for the study. The data reported in this study were collected as part of a larger study on the clinical characteristics of DD; the socio-demographic and clinical data were used in the statistical analysis of the current study. RESULTS: Mean DLQI was 5.41 ± 5.57 and the mean EQ-Visual Analogue Scale (VAS), was 70.84 ± 19.25. DLQI and EQ-VAS were significantly associated with skin area affected, disease severity, age at onset of DD and a seborrhoeic distribution pattern of DD. Stepwise linear regression showed skin area affected to be the most significant variable in the predication of DLQI (beta = 0.183; SE = 0.04; P < 0.001), and disease severity the most significant variable in the predication of EQ-VAS (beta = -9.15; SE = 3.21; P < 0.006). CONCLUSIONS: Darier's disease has a negative impact on HRQL of patients and the HRQL is associated with various disease characteristics, mainly skin area affected and clinical severity.

Pregnancy outcomes in women with moderate-to-severe psoriasis.

BACKGROUND: The association between psoriasis and pregnancy outcomes has not been adequately examined, although psoriasis onset is common in the reproductive period. OBJECTIVE: To evaluate the association between moderate-to-severe psoriasis and pregnancy complications. METHODS: A retrospective, matched cohort study of 68 deliveries in 35 women with moderate-to-severe psoriasis compared to 237 deliveries in 236 women without psoriasis randomly selected after matching for age, parity and gestational age. RESULTS: The psoriasis patients had higher mean of past spontaneous (0.42±0.58 vs. 0.26±0.63, P=0.002) and induced (0.32±0.60 vs. 0.06±0.25, P=0.001) abortions than controls. They had a higher percentage of pregnancy-induced hypertensive diseases (7.4% vs. 2.1%, P<0.05) and premature rupture of membranes (16% vs. 5.5%, P<0.008). Newborns to women with psoriasis had higher birth weight (3375±543 g vs. 3247±460 g, P=0.03), increased percentage of large-for-gestational age (24% vs. 12%, P=0.02), and macrosomia (13% vs. 4.2%P=0.02). In multivariate analysis, moderate-to-severe psoriasis was an independent risk factor for previous spontaneous abortions, induced abortions, premature rupture of membranes (PROM), and newborn macrosomia. CONCLUSION: Moderate-to-severe psoriasis is associated with spontaneous and induced abortions, pregnancy-induced hypertensive diseases, premature rupture of membranes, large-for-gestational age newborns, and macrosomia.