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.

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.

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.

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.

Sensory processing patterns of adults with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) has been associated with sensory hypersensitivity in children. OBJECTIVE: To examine the sensory profile of adults with AD using a standardized questionnaire that measures sensory processing and related behaviours in daily living. METHODS: Thirty-two patients aged 18-53 years with AD and 32 healthy, sex- and age-matched control subjects completed the Adolescent/Adult Sensory Profile (AASP). Severity of AD was assessed by the Severity Scoring of Atopic Dermatitis (SCORAD). RESULTS: Patients with AD showed higher sensory sensitivity and avoidance than the controls, mainly in the tactile, vestibular, visual and auditory modalities. CONCLUSIONS: Adults with AD may suffer from sensory hypersensitivity. Additional studies should examine the influence of the peripheral and the central nervous system on sensory hypersensitivity. Better understanding of the sensory impairment of patients with AD may help improving treatment strategies for the disease.

Cat scratch disease encephalopathy in an immunocompetent patient.

Cat scratch disease (CSD) is typically a self-limited regional lymphadenopathy in children and young adults that is caused by Bartonella henselae. The majority of CSD cases resolve spontaneously; however, many systemic complications have been described. We report an unusual case of CSD presenting as an epitrochlear arm mass and complicated by encephalopathy. Identification of B. henselae DNA in the affected lymph node and cerebrospinal fluid confirmed the diagnosis of CSD. Systemic antibiotic therapy was administered and the patient improved without any neurological deficit.

Onchocerciasis in Israel.

A 15-year-old boy with onchocerciasis had severe generalized pruritus of five months' duration. He had been born and raised in Ethiopia and had emigrated to Israel one year earlier. A biopsy specimen of an area of depigmentation on the right thigh disclosed microfilaria of Onchocerca volvulus in the dermis. The discovery of an unusual disease in a nonendemic area is an example of the increased complexity of differential diagnosis resulting from the ease of travel from one geographic region to another.

Maternal mortality in an Israeli hospital: a review of 23 years.

In spite of great strides in obstetrics, maternal mortality has been completely eliminated. Possible changes in the causes of mortality are examined for three periods of time (1954-1961, 1962-1971 and 1972-1976). The overall incidence was 3.6/10 000, changing through the three periods from 4.9 to 4.3 and finally to 3.0/10 000. Vascular accidents were the cause of death in almost one third of the cases, emerging as the most important etiologic factor. Older age and higher parity did not seem to influence the incidence of obstetric deaths. Cesarean section was involved in ten of 23 cases in which the death was directly related to the pregnancy and delivery. In six patients there was a rupture of the uterus. The number of preventable deaths has decreased steady, but research into the problem of vascular accidents and dampening of the enthusiasm for cesarean sections may further improve the situation.

PIP: Despite scientific advances in obstetrics, maternal mortality is still a serious problem in many countries. This paper analyzes the causes of maternal mortality in Kaplan Hospital since its opening in 1954 up to 1976. 27 women died during this period; total number of deliveries was 63,997. The period was divided into 3: 1954-61, with a mean number of deliveries of 2386 per year; 1962-71, with a mean number of deliveries of 2308 per year; and 1972-76, with a mean number of deliveries of 4244/year. Maternal mortality for the 1st period was 4.9/10,000; in the 2nd, 4.3/10,000 and in the last, 3.0/10,000. Confidence limits based on the Poisson distribution method was used to test for statistical significance. Causes of direct maternal death included: 1) vascular accidents (amniotic fluid embolism and disseminated intravascular clotting) which accounted for almost 1/3 of all cases; 2) infection; 3) EPH gestosis or toxemia of pregnancy; 4) hemorrhage; and 5) anesthesia. Indirect causes of death included cardiac cases, followed by pulmonary embolism, cerebrovascular andirenal diseases, in decreasing order of importance. Older age and parity did not affect incidence of obstetric deaths. This report indicates a definite decline in maternal mortality for the 3 periods. The decline was attributed to liberal use of better antibiotics, emphasis on aseptic techniques, better antenatal care and well-equipped operating theaters. Nevertheless, vascular accidents remain the major direct cause of maternal deaths. Further research should be done on vascular accidents and its prevention; a healthy respect for the use of ceasarian sections may also be helpful in reducing further maternal deaths.

[Herpes zoster treated with acyclovir].

During the past 5 years, 99 patients with herpes zoster were hospitalized and followed. Age, sex, localization of rash, complications, duration of hospitalization and treatment were analyzed. Most patients were in their 6th and 7th decades. Cranial nerve involvement was frequent (35%). A generalized rash was more common in those with immunodeficiency. Acyclovir (Zovirax) inhibited to some extent the spreading of the rash and reduced the frequency of herpetic neuralgia. Our findings are in accord with those in the literature.

Nail disorders in patients with chronic renal failure and undergoing haemodialysis treatment: a case-control study.

BACKGROUND: Few controlled studies have compared nail disorders in patients with chronic renal failure (CRF) and haemodialysis (HD)-dependent individuals with a healthy population. OBJECTIVE: The aim of this study was to compare the prevalence of nail disorders in patients with CRF and patients undergoing HD treatment with a healthy population, and evaluate the relationship between nail changes and various demographic, medical and laboratory parameters in these groups. METHODS: In this case-control study we recruited 73 patients affected with CRF, 77 patients undergoing regular HD and 77 healthy individuals. All patients were examined for the presence of nail disorders. Various parameters [age, gender, type of kidney disease, regular medications, duration of renal failure and HD, dialysis efficacy (Kt/v), haemoglobin, neutrophil count, calcium, phosphorus, albumin, creatinine, urea, alkaline phosphatase and parathyroid hormone (PTH) levels] of the patients were determined by multivariate analysis and compared. RESULTS: Forty-four patients (60.3%) with CRF and 48 patients (62.3%) undergoing HD treatment had at least one type of nail pathology. The most common nail alterations found in patients with CRF and those undergoing HD were absence of lunula (AL) and half-and-half nails (HHN), respectively. Prevalence of nail disorders among patients with CRF was influenced significantly by PTH level (P = 0.03). In the HD group, male sex, age above 65 years and comorbidities (diabetes mellitus, hypertension and heart failure) were significantly associated with nail pathologies. CONCLUSION: Patients with CRF and those undergoing HD therapy have higher rates of nail disorders when compared to a healthy population. Efficient HD does not improve nail changes.

Epidemiological and clinical manifestations of patients hospitalized with brown recluse spider bite.

BACKGROUND: Necrotic arachnidism represents a common health problem and standard treatments are usually safe and effective. OBJECTIVE: The aim of this study was to review documented Loxosceles species spider envenomations and identify the natural history of affected patients. METHODS: A retrospective single-centre study included 52 patients with necrotic arachnidism hospitalized in the dermatology department between 1997 and 2004. We examined the relationship between the epidemiological, clinical and laboratory parameters and degree of lesion severity, length of hospitalization and time to complete healing. RESULTS: The bites occurred predominantly in rural areas, 67% between April and August. Only 35% of the patients sought medical care within 24 h post bite. Most bites were of the extremities (67%). Time to complete healing ranged from 14 days to more than 8 weeks (mean, 4.8 weeks). A marked relationship was found between age, comorbidities, lesion severity and time to complete healing (P < 0.01). Duration of hospitalization was significantly longer in patients with severe thigh lesions (P < 0.02). CONCLUSIONS: Loxosceles species spider bites frequently induce necrotic, slowly healing ulcers on the fatty areas of the body. Early, appropriate systemic therapy may provide clinical benefit.

Minocycline-induced cutaneous hyperpigmentation: confocal laser scanning microscope analysis.

BACKGROUND: Minocycline has a characteristic yellow-green fluorescent emission. This fluorescence has been previously demonstrated only in type 1 minocycline-induced skin hyperpigmentation. OBJECTIVE: To investigate whether the fluorescence can be detected in other types of minocycline-induced cutaneous hyperpigmentation, and to study the possible mechanisms. METHODS: Biopsies of pigmented and nonpigmented skin from 3 patients with different types of skin hyperpigmentation induced by minocycline were analysed by light microscopy and Confocal Laser Scanning Microscope (CLSM). RESULTS: A yellow-green fluorescence was observed in the hyperpigmented skin of two patients with type 2, and one patient with type 4 minocycline-induced cutaneous hyperpigmentation. No fluorescence was detected in the non-pigmented skin. CONCLUSION: Minocycline can possibly serve as a fluorescent probe in the diagnosis of all types of minocycline-induced cutaneous hyperpigmentation.

Third trimester induction of labor with fetal death in utero.

Labor was induced in 64 women in the third trimester, after antepartum fetal death. In 26 patients, hypertonic saline solution was instilled into the uterus; in 24, surgical rupture of the membranes, followed by oxytocin, was tried, and in 14, induction was by amniotomy only. A definite advantage of the last two methods was shown, the mean induction delivery interval being 22.55, 8.96 and 7.20 hours, respectively. Considering also the possible dangers of hypertonic saline solution, the simple method of amniotomy is preferred.