Coronary stent restenosis and the association with allergy to metal content of 316L stainless steel.

BACKGROUND: Most intra-coronary stents in use are made of 316 L stainless steel, which contains nickel, chromate and molybdenum. Whether inflammatory and allergic reactions to metals contribute to in-stent restenosis is still a matter of debate. AIM: The aim of this study was to ascertain the relationship between metal allergy and the occurrence of in-stent restenosis. METHODS: Ninety-nine adult patients who underwent two cardiac catheterisations, up to two years apart, were included in the study. Seventy patients had patent stents at the second angiogram (patent stent group) and 29 were found to have in-stent restenosis (restenosis group). All patients underwent patch testing with the relevant metals and the 316L stainless steel plate. RESULTS: Twenty-eight (28.3%) patients were found to have an allergy to at least one metal. There was no significant difference in the prevalence of metal allergy between the patent stent group and the restenosis group (28.6 and 27.6%, respectively; p = 0.921). CONCLUSIONS: Our data do not support the theory that contact allergy plays a role in the pathogenesis of in-stent restenosis.

Noninvasive in vivo confocal laser scanning microscopy is effective in differentiating allergic from nonallergic equivocal patch test reactions.

Patch testing is the gold standard for the validation of contact dermatitis. It relies on the subjective scoring by an evaluator of the inflammatory reaction induced by an allergen applied to the skin. Equivocal reactions imply faint erythema and could represent allergic, irritant, or negative reactions. They constitute approximately 1 % of the positive reactions encountered in patch test practice. Histological evaluation of the equivocal reaction has proven helpful for the correct interpretation but is however time consuming, and its invasive nature is often unacceptable to the patient. In vivo confocal laser scanning microscopy (CLSM) is a novel, noninvasive imaging technique which permits real-time visualization of skin structures and lesions at a resolution close to that obtained by conventional histology. CLSM has been successfully applied for the differentiation between clinically clear-cut allergic and irritant patch test reactions. The objective of this study is to determine the relevance of CLSM in differentiating between allergic, irritant, and negative equivocal patch test reactions. Fifteen patients who underwent patch testing in our clinic were observed as having 20 equivocal reactions. All 20 reactions were evaluated using in vivo CLSM and compared with adjacent normal skin. In vivo CLSM evaluation revealed that 8 of the 20 equivocal reactions (40 %) showed confocal patterns consistent with the patterns encountered in positive allergic reactions. Anamnestic exposure, i.e., detailed assessment of previous related contact with these allergens, confirmed high relevance rates. In vivo CLSM is useful in differentiating between allergic, irritant, and negative equivocal patch test reactions, a differentiation that cannot be made by conventional clinical patch test reading.

Preservatives in cosmetics in the Israeli market conform well to the EU legislation.

BACKGROUND: Preservatives are important and frequent skin sensitizers, found in a wide range of products for personal and occupational use. According to the European legislation, some cosmetic ingredients are restricted in terms of quantity and a detailed list of ingredients must be present on the product or packaging. OBJECTIVES: To examine the use of preservatives in common cosmetics on the Israeli market. MATERIALS/METHODS: Sixty different Israeli brand cosmetics, including shampoos, liquid soaps, body creams and hand creams were randomly selected. Ingredient labels were examined. The products were investigated by the chromotropic acid method for release of formaldehyde and by high performance liquid chromatography for the presence of formaldehyde, DMDM hydantoin and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI content. RESULTS: All products but one contained a detailed list of ingredients printed on the package. According to labelling, the most prevalent preservatives in Israeli shampoos and liquid soaps were DMDM hydantoin and MCI/MI. Hand creams and body creams contained mainly parabens but also iodopropynyl butylcarbamate, phenoxyethanol and DMDM hydantoin. Formaldehyde in doses from 4 to 429 ppm, and DMDM hydantoin were detected in 38 and 16 (63% and 27%) of the products, respectively. MCI/MI was detected in 11 (18%) of the products, with highest prevalence in rinse- off products (55%). Excluding one hand cream which measured 106 ppm MI, the amount of formaldehyde, DMDM hydantoin, MCI/MI and MI was within the allowed concentrations by the European directive in all cases. CONCLUSIONS: In Israel, adaptation of the European directive prevails, as shown by the measurements we performed on randomly selected products.

Risk of sensorineural hearing loss in patients with vitiligo.

OBJECTIVE: The purpose of this study was to determine the prevalence of hearing loss and vestibular symptoms among Israeli vitiligo patients as compared with healthy controls. METHODS: 16 vitiligo patients and 16 healthy controls were enrolled in this prospective study. Vitiligo patients had undergone dermatologic evaluation and complete ENT evaluation. RESULTS: Vitiligo patients demonstrated a significantly higher prevalence of sensorineural hearing loss (SNHL) (p = 0.001). A 'notch'-shaped audiogram was the most frequent type of audiogram found among vitiligo patients (p = 0.021). Patients with mucosal involvement as the primary site of onset had a significantly more normal hearing level (p = 0.004). CONCLUSIONS: Due to the high prevalence of SNHL amongst vitiligo patients, it is recommended that these patients undergo a complete hearing evaluation, avoiding ototoxic hazards if possible.

The use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients.

OBJECTIVE: To summarise our experience of the use of medicinal maggots for the debridement of necrotic chronic wounds and to try and identify prognostic factors for debridement success and associated pain. METHOD: During the years 1996­2009, 723 wounds of 435 patients (180 females and 255 males) were treated with maggot debridement therapy (MDT) in 16 departments and units of the Hadassah Hospital in Jerusalem, Israel. Overall, 261 patients were treated during hospitalisation, while 174 were treated as ambulatory patients. In 90.5% of the patients the wounds were located on the leg, but only 48.0% had diabetic foot ulcers. The wound duration range from one to 240 months (mean=8.9; median=4 months). Sterile maggots of the green bottle fly, Lucilia sericata, were used for MDT. In 90.6% of the cases, maggots were placed directly on the wound using a cage-like dressing and left for 24 hours, while in 9.4% of the patients maggots concealed in a tea-bag like polyvinyl netting were used. The concealed maggots were left on the wound for 2­3 days. RESULTS: The number of treatments was 1­48 (mean=2.98; median=2) and the duration of the treatment varied between one and 81 days (mean=4.65; median=3). In 357 patients (82.1%) complete debridement of the wound was achieved, while in 73 patients (16.8%) the debridement was partial and in five (1.1%) it was ineffective. Increased pain or discomfort during MDT were reported in 38% of the patients. CONCLUSION: MDT is a very safe, simple and effective treatment modality for chronic wounds in ambulatory and hospitalised patients. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no additional conflicts of interest to declare.

Patients with early-onset psoriasis achieve better results following Dead Sea climatotherapy.

BACKGROUND: Plaque psoriasis has recently been divided in two types, which differ in severity and inheritance according to the age of the patient at the onset of the disease. AIM: To compare the effect of Dead Sea climatotherapy (DSC) on these two types of disease, with early vs. late onset, and to determine the impact of this treatment on the response rate. METHODS: The files of 605 patients who were suffering from plaque psoriasis were retrieved from the database of the Research Institute at the Dead Sea (RIDS) and divided in two groups, types I and II, according to whether the age at the onset of the disease was under or over 40 years, respectively. The primary outcome for the assessment of DSC was Psoriasis Assessment of Severity Index of 95 (PASI 95), which indicates that the PASI improvement percentage reached 95%. Logistical regression was used to identify the factors that related to the observed outcome. RESULTS: By the end of the study, 74% of the patients in group 1 reached PASI 95 in comparison to 62% in group 2. The 95% confidence interval for the odds ratio (OR) of the effect in group 2 in comparison to that of group 1 was [0.31, 0.99], which implies that group 1 responded better to treatment in comparison to group 2. Cut-off values for patients who were aged 30 and 20, respectively, exhibited similar trends; 75% vs. 65% and 78% vs. 68% for groups 1 and 2, respectively. CONCLUSIONS: Efficacy rates following DSC were impressively high for plaque psoriasis patients. Contrary to our hypothesis, the treatment effect was found to inversely correlate with the age of the patient at disease onset.

SCORAD 75: a new metric for assessing treatment outcomes in atopic dermatitis.

OBJECTIVE: The scoring atopic dermatitis (SCORAD) is a well-established severity-scoring tool for atopic dermatitis (AD). Dead Sea climatotherapy (DSC) is a natural selective balneo-phototherapy utilized for many years to treat severe AD. The study's goal was to evaluate the impact of DSC on AD patients through assessment of SCORAD scores and to identify parameters associated with greater improvement. METHODS: The files of 78 European patients (37 male patients and 41 female patients, mean age 37.8 years) with AD undergoing DSC were included in this retrospective study. Three sub-groups were delineated based on disease severity (as determined using the SCORAD). Demographic and clinical parameters as well as treatment characteristics--maximal and cumulative sun exposure doses--were recorded. SCORAD values were again recorded for assessment of treatment response. SCORAD 75 was defined as ≥75% decrease in SCORAD values following therapy. Statistical analysis including logistic regression models was used in multivariable analysis. RESULTS: After an average of 30 days of treatment, mean SCORAD values dropped from 50.5 to 11 (76.7%, P<0.001). 64.1% of all patients, regardless of sub-group, reached SCORAD 75, whereas 78.9% of patients with severe disease achieved this result. In a multivariate logistic regression, factors associated with achieving SCORAD 75 were maximal sun exposure, family history of AD and age at disease onset (P=0.002, P=0.009 and P=0.040 respectively). CONCLUSION: Dead Sea climatotherapy is a particularly effective treatment method for the sub-population of adults with severe AD. The SCORAD 75 can be useful for defining sub-populations in which treatment is more likely to be successful.

Tropism of herpes simplex virus type 1 to nonmelanoma skin cancers.

BACKGROUND: Current treatments for nonmelanoma skin cancer include surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy, local chemotherapy and application of immunomodulators such as imiquimod. However, all have a 5-year recurrence rate of 1-40%. Gene therapy for the treatment of skin cancers is a promising new approach, as delivery of the vectors to the skin is simple and safety issues can be properly addressed. OBJECTIVES: To develop an ex-vivo organ culture system for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tumours, and to test the feasibility of applying oncolytic viruses to these tumours. METHODS: We first optimized conditions for the maintenance of BCC and SCC tissues in organ culture, and demonstrated viability of the tissues ex vivo for 3-7 days. The tropism of two potential oncolytic viral vectors, herpes simplex virus type 1 (HSV-1) and adenovirus (AD), was next evaluated. RESULTS: Immunohistological analysis revealed that HSV-1 targeted tumour cells that expressed p63 and did not express keratin 15 or keratin 14 markers of keratinocytes. Further examination indicated that uninfected BCC and SCC tissues express two isoforms of p63 mRNA, and HSV-1 infection specifically enhanced expression of the TAp63 isoform. Furthermore, following infection, both HSV-1 and AD induced apoptosis in the BCC and SCC cells as indicated by the induction of activated caspase-3. CONCLUSIONS: The results indicated a specific pattern of viral tropism to skin cancer cells that are critical for maintenance of the tumour. This new experimental system should aid in the analysis of new therapeutic modalities, such as oncolytic viruses, for future treatment of these skin tumours.

Dead Sea climatotherapy for vitiligo: a retrospective study of 436 patients.

BACKGROUND: Vitiligo is an acquired idiopathic skin disorder characterized by depigmented macules and patches. Despite many therapies available today, treatment of vitiligo remains a challenge. Preliminary reports cite encouraging results for Dead Sea Climatotherapy (DSC) in vitiligo patients. OBJECTIVE: To evaluate the efficacy of DSC in 436 patients suffering from vitiligo. METHODS: Files of 436 vitiligo patients, who were treated by DSC between the years 1997 and 2005 at the Deutsches Medizinisches Zentrum (DMZ) Medical Center, were retrieved for analysis. Climatotherapy, including gradually increased sun exposure following a sea bath, was administered in accordance with a computer-designed protocol. Age at vitiligo onset, skin phototype, skin involvement, duration of disease, as well as timing and duration of DSC were recorded. Logistic regression was used to estimate the effect of each one of the parameters analysed on the treatment's success. RESULTS: Following treatment, 3.9% of patients demonstrated total or significant repigmentation (defined by more than 50% repigmentation in more than 50% of the lesions); 81.4% showed good repigmentation; 13.1% showed no repigmentation but their vitiligo spots were pink-colored and 1.6% appeared not to be affected at all by DSC. Patient response to the treatment was inversely proportional to the size of the affected area. A negative correlation was found between duration of the vitiligo and the clinical short-term response to DSC. In addition, the longer the stay at the Dead Sea the better was the result. CONCLUSION: Climatotherapy at the Dead Sea is an effective treatment modality for vitiligo. Disease duration and severity, as well as length of treatment, were the main factors found to favourably influence the clinical response.

Well being, psychopathology and coping strategies in psoriasis compared with atopic dermatitis: a controlled study.

BACKGROUND: There is a vast literature describing the association between psoriasis, atopic dermatitis (AD) and psychological distress. Some of these studies were uncontrolled and others used non-dermatological diseases as control, but only a few used chronic skin diseases as controls. OBJECTIVE: To compare well being, psychopathology and coping strategies of psoriatic, AD and healthy controls in a prospective case-control study. METHODS: Thirty-seven psoriatic patients and 31 AD patients were recruited from the Hadassah Ein Karem Hospital, Jerusalem, Israel, outpatient and inward clinic. The participants in the control group were 31 healthy workers and volunteers with no dermatological diseases from Kaplan Hospital, Rehovot, Israel. We used self-report questionnaires [Mental Health Inventory (MHI) and Adjustment to Chronic Skin Diseases Questionnaire (ACSD)], a projective technique (Hand Test) and assessment tools (Clinical Global Impression). RESULTS: Psoriatic patients experienced reduced well being (P = 0.007) and more anxiety and depression (P = 0.018) than normal controls. Psoriatic patients also displayed more severe psychopathology (P = 0.039) a more passive attitude towards life, and loss of meaning in life (P = 0.001) as measured by the projective technique compared with AD patients and normal controls. CONCLUSIONS: We propose two explanations, derived from the psychological and the psycho-neuro-immunological domains. First, greater mental distress in psoriasis is because of the greater stigma it bears compared with AD. Alternatively, we hypothesize that the psoriatic inflammatory process may possibly have a direct central nervous system effect.

A novel treatment of contact dermatitis by topical application of phospholipase A2 inhibitor: a double-blind placebo-controlled pilot study.

Phospholipase A2 hydrolyzes membrane phospholipids releasing arachidonic acid and lysophospholipids. These are key precursors of inflammatory mediators, such as prostaglandins, leukotrienes, thromboxanes and PAF, in numerous inflammatory/allergic diseases, including skin inflammation. Accordingly, inhibition of PLA2 has long been postulated as a potentially potent anti-inflammatory therapy. In the present study we tested the effect of a novel PLA2 inhibitor on contact dermatitis in human subjects. A double-blind, placebo-controlled pilot study was conducted on contact dermatitis patients (n = 11) treated with the inhibitor-containing topical preparation (1% cream). Disease severity was assessed by physicians assessment before treatment (day 0) as well as after 14-days and 30-days. Patients treated with 1% PLA2 inhibitor-containing cream showed a 69.9% reduction in disease score while placebo-treated patients showed a reduction of 36.5% with p = 0.0024. The clear improvement in the disease score of inhibitor-treated patients supports the involvement of PLA2 activity in skin inflammation and the therapeutic prospective of its inhibition.

Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin-like growth factor-binding protein-7 after phototherapy.

BACKGROUND: Phototherapy is an effective therapy for psoriasis. The molecular mechanisms underlying its efficacy are not yet understood. OBJECTIVES: To compare the expression profiles of psoriatic epidermis in patients before and after undergoing phototherapy with the purpose of expounding the molecular mechanisms underlying the efficacy of this therapeutic modality. METHODS: Patients with psoriasis were investigated before and after full courses of phototherapy: three patients completed 3 weeks of heliotherapy at the Dead Sea; three patients received narrowband ultraviolet B (NB-UVB) for a total of 20-27 treatments. Epidermal samples were analysed using oligonucleotide microarrays. Our microarray results led us to explore further and to quantify a specific gene, insulin-like growth factor-binding protein-7 (IGFBP7), using real-time quantitative reverse transcriptase-polymerase chain reaction assays and immunohistochemical protein expression. RESULTS: We identified 315 genes modulated by phototherapy: the expressions of 248 genes (142 up; 106 down) were changed by Dead Sea treatment, 116 (71 up; 45 down) by NB-UVB and 49 (37 up; 12 down) were modulated regardless of treatment. The differentially changed genes include S100 calcium-binding proteins, dendritic cell markers, tumour necrosis factor-alpha target genes, matrix metalloproteinases and NFkappaB target genes. We also found that IGFBP7 mRNA and protein were significantly underexpressed in psoriatic compared with normal epidermis, and that phototherapy significantly increased their expression. CONCLUSIONS: IGFBP7 is underexpressed in psoriatic epidermis but is inducible by UVB.

The UVB-induced gene expression profile of human epidermis in vivo is different from that of cultured keratinocytes.

In order to obtain a comprehensive picture of the molecular events regulating cutaneous photodamage of intact human epidermis, suction blister roofs obtained after a single dose of in vivo ultraviolet (UV)B exposure were used for microarray profiling. We found a changed expression of 619 genes. Half of the UVB-regulated genes had returned to pre-exposure baseline levels at 72 h, underscoring the transient character of the molecular cutaneous UVB response. Of special interest was our finding that several of the central p53 target genes remained unaffected following UVB exposure in spite of p53 protein accumulation. We next compared the in vivo expression profiles of epidermal sheets to that of cultured human epidermal keratinocytes exposed to UVB in vitro. We found 1931 genes that differed in their expression profiles between the two groups. The expression profile in intact epidemis was geared mainly towards DNA repair, whereas cultured keratinocytes responded predominantly by activating genes associated with cell-cycle arrest and apoptosis. These differences in expression profiles might reflect differences between mature differentiating keratinocytes in the suprabasal epidermal layers versus exponentially proliferating keratinocytes in cell culture. Our findings show that extreme care should be taken when extrapolating from findings based on keratinocyte cultures to changes in intact epidermis.

[The use of tacrolimus in dermatology].

This article aims to review the literature on the use of tacrolimus in dermatology. We tried to focus on the local application of tacrolimus. The local application of tacrolimus is known to be effective for several skin diseases, especially atopic dermatitis. Since the major action site of tacrolimus is activated T-lymphocytes, the drug showed efficiency mostly in inflammatory dermatological diseases including psoriasis, lichen planus, alopecia areata and pyoderma gangrenosum. Tacrolimus lacks most of side effects of local steroids and seems to have better results for short and long term application. We presume that tacrolimus will be widely used on skin diseases, especially when it becomes less expensive.