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Whether individuals with atopic diseases have a different risk of contact allergy compared to those who are non-atopic is controversial and data are conflicting.To explore the association between atopy and allergic contact dermatitis (ACD).This retrospective cross-sectional study included 301 patients referred to a tertiary clinic to evaluate ACD. Demographic details including personal and familial mucosal or cutaneous atopic status were recorded. Patch tests were tailored to their clinical presentations and relevant exposures.At least 1 positive patch test reaction was observed in 177 patients (59% of the study cohort), of which 52% had a history of atopic diseases, compared with 44% of patients with a negative patch test result (We identified a positive tendency for atopic diseases among individuals with ACD and vice versa. Our study supports the aggregate data from previous studies despite the non-significant differences between the study and control groups. However, further research performed in larger populations of patients is necessary to evaluate the real association between atopy and ACD on a solid basis. Our results indicate the necessity of systematic patch testing in patient setups with atopic background and chronic dermatitis.

Jonathan Bar,1 Sari Godlewicz,2 Arieh Ingber,2 Eli Sprecher,1,3 Dan Slodownik1,3 1Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Sackler School of Medicine, Tel – Aviv University, Tel-Aviv, IsraelCorrespondence: Dan SlodownikTel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 6423906, IsraelTel +972 3-6973585Fax +972 3-6974998Email dans@tlvmc.gov.ilBackground: Chronic spontaneous urticaria (CSU) is a common debilitating condition. Although not completely understood, the main pathomechanism involves autoimmune-related mast-cell degranulation. Patch test (PT) is the gold standard for the diagnosis of type IV cutaneous hypersensitivity. The relevance of PT to the diagnosis of CSU is debatable.Objective: We aimed at determining the role of PT in selected patients with CSU.Methods: In this retrospective study, we reviewed cases of patients referred for patch testing at our clinic. We compared results of patients with CSU (n = 134) and patients with suspected allergic contact dermatitis (n = 680; control group).Results: Among patients in the CSU group, 3% of patients had relevant reactions to PT, indicating that contact allergen avoidance resulted in resolution of all skin findings. Metals and textile dyes were the most relevant allergens. No significant differences were found between the groups with regard to the percentage of patients with positive PT and hapten reaction profiles. Patients from the CSU group were significantly older (4.1 years on average, P < 0.05), consisted of more females, and were less likely to have atopic trait (46% vs 58%, P< 0.05).Conclusion: In some of patients, PT may assist in determining the cause of CSU.Keywords: chronic spontaneous urticaria, patch test, contact dermatitis

Generalized acquired dermatoses can seldom manifest more prominently or exclusively along the lines of Blaschko. Six individuals with segmental atopic dermatitis (AD) have been reported to date. We present three additional cases of segmental cutaneous manifestations superimposed on generalized AD, and review the relevant literature.

Background and objectives Allergic contact dermatitis is a common dermatosis among military personnel. Given the unique military demands, it is not surprising that shoe dermatitis and textile dermatitis are common. Our study aimed to compare the clinical and demographic parameters between military personnel and civilians evaluated for the suspicion of shoe and textile dermatitis in a tertiary clinic in Israel. Methods This retrospective cross-sectional study included 295 patients who were referred to a tertiary clinic for evaluation because of suspected shoe or textile dermatitis. Eighty-eight of the patients were soldiers. The patch tests were tailored according to the clinical presentation and relevant exposures. Results The 2 populations differed in several parameters. The duration of the dermatitis was longer in the civilian group. The atopy rate was significantly higher among military conscripts. The patch test reactivity and multiple patch test reactivity were lower in the army group. Dermatitis seen in the military group tended to be more widely distributed. Conclusions Distinctive demographic and exposure patterns explain the differences observed between the 2 study groups. It is not surprising that irritant dermatitis is more common among military personnel, given the extreme military demands and higher atopy rate among soldiers.

Hypopigmentation may be a clinical presentation of infectious and parasitic diseases, including pityriasis versicolor, leprosy, onchocerciasis, endemic treponematoses, and syphilis. A presentation of these diseases with an emphasis on skin manifestations is discussed.

A group of skin diseases that occur specifically in pregnant women. The following diseases will be discussed in depth: Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP), Pemphigoid Gestationis (PG), Impetigo Herpetiformis (IH), Prurigo of Pregnancy (Besnier), Pruritic Folliculitis of Pregnancy and Linear IgM Dermatosis of Pregnancy. The nomenclature and the specificity of these diseases is not clear and causing confusion. The purpose of this chapter is to set and simplify this group of unique skin conditions.

Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.

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.

The human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA-B*15:02 and HLA-A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens-Johnson syndrome (SJS)- and toxic epidermal necrolysis (TEN)-related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab-Muslim donors, 81 individuals of known origin carried the HLA-B*15:02. Among them, 66 were Jews of India-Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA-A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS- or TEN-related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug-induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA-B before treatment with carbamazepine or phenytoin.

Pregnancy is frequently associated with major skin changes. Some of these changes are attributed to pregnancy-specific dermatoses, which often are overlooked and misdiagnosed by physicians. We discuss four major pregnancy-specific dermatoses: pemphigoid gestationis; pruritic urticarial papules and plaques of pregnancy; prurigo of pregnancy; and pruritic folliculitis of pregnancy. Accurate diagnosis and management is crucial, not only to alleviate symptoms, but also to estimate correctly the risk for the fetus.

BACKGROUND Atopic dermatitis (AD) has an appreciable effect on quality of life. Improving the quality of life of AD patients is a priority. OBJECTIVE This study aimed to evaluate the impact of Dead Sea climatotherapy (DSC) as a treatment of AD and its influence on the quality of life of these patients. METHODS Forty-nine adult patients with AD treated during the years 2009-2010 at the Deutsches Medizinisches Zentrum Medical Center participated in this prospective study. Climatotherapy was administered in accordance with a computer-designed protocol and included gradually increased sun exposure after a sea bath. Severity of AD was evaluated using the Scoring Atopic Dermatitis (SCORAD) index. Patient quality of life was evaluated using Skindex-29. Statistical analysis was performed using a paired t test and Wilcoxon and Mann-Whitney U tests. RESULTS After treatment, the mean SCORAD value improved by 39 points (P < 0.001). The overall Skindex-29 score improved by a mean value of 33 points (P < 0.001). The pretreatment SCORAD, duration of AD, and maximal daily sun exposure predicted the posttreatment SCORAD values. Pretreatment Skindex-29 and patient age predicted the posttreatment Skindex-29 in a multiple linear regression model. CONCLUSIONS Dead Sea climatotherapy provides an effective treatment modality for AD by improving the patient's skin condition and quality of life.

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 1996–2009, 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 2–3 days. Results: The number of treatments was 1–48 (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.

Background Dead Sea climatotherapy is a proven and useful option for the treatment of plaque psoriasis. However, combination with methotrexate treatment has not been studied. Objective We sought to evaluate the added benefit of Dead Sea climatotherapy in patients with psoriasis vulgaris receiving methotrexate treatment and compare their results with those of patients not receiving this therapy. Methods In this retrospective comparative study, 40 patients with psoriatic vulgaris were recruited at the Deutsches Medizinisches Zentrum Medical Center in Ein Bokek, Israel, between 2003 and 2005. Twenty (50%) patients were also treated with methotrexate (group 1), and 20 (50%) patients were not (group 2). A five-item scale, equivalent to Psoriasis Area and Severity Index (PASI) scores, was used to evaluate clinical response. Logistic regression using an exact method was performed on demographic and clinical parameters. Results Ten (50%) patients in group 1 and 13 (65%) patients in group 2 were totally plaque free on leaving the Dead Sea. Five (25%) patients in group 1 and four (20%) patients in group 2 were almost cleared (50% clearance, 50%–94% PASI improvement) at the end of Dead Sea climatotherapy (adjusted OR 1.43; 95% CI 0.2–16.6). Conclusion Dead Sea climatotherapy did not show better results in patients treated simultaneously with methotrexate. No side effects were observed from this combination therapy. However, the study design and the small sample size do not allow conclusions about methotrexate withdrawal before natural phototherapy.

IntroductionBullous dermatoses are characterized by skin blisteringresulting from local injury with breakdown of tissue integrityand fluid accumulation within specific layers of the skin.These disorders are traditionally classified into subcorneal,suprabasal, and subepidermal blistering by the specificlocationofthesplitintheepidermis[1, 2]. Of special interestis the group of autoimmune blistering diseases that comprisea wide spectrum of clinical presentations and are mediatedby pathogenic antibodies targeting specific adhesion mole-cules responsible for cutaneous homeostasis and integrity[3]. Diagnosis is based on the clinical picture, histology,direct and indirect immunofluorescence, immunoblotting,immunoprecipitation and immunoelectron microscopy [4, 5].Though crucial for accurate diagnosis and for selection ofspecific therapy, these techniques are cumbersome, time-consuming and unlikely to be widely available, leavingblister level determination by classical histology a keydiagnostic procedure in intraepidermal and subepidermalblistering diseases.Reflectance confocal microscopy (RCM) is a novel,noninvasive imaging technique which permits real timevisualization of cellular components in the skin at aresolution compatible with that of conventional histology[6]. RCM detects single back-scattered photons directlyfrom illuminated living tissue without prior preparation ofthe examined skin. A small pinhole in the front of thedetector allows imaging at high resolution. Contrast inconfocal images is provided by the differences in refractiveindex among the cellular organelles and structures. Melaninacts as a contrast agent in pigmented epithelia [7]. With thecurrent technology, in vivo RCM imaging is limited to adepth of approximately 300 µm which includes the entireepidermis, the papillary dermis and the upper reticulardermis. It is of interest that the depth of RCM imaging canbe increased by using the so-called “optical clearing”approach, and experimental studies utilizing gold nano-particles and osmotically active immersion liquids asoptical clearance agents have indeed increased the imagingdepth of RCM up to three times [8–11]. However, theseexperimental approaches have not yet been incorporatedinto clinically useful RCM technology. Since contrast in theimages is primarily provided by melanin, RCM has mainlybeen useful in the diagnosis of pigmented cutaneous tumorssuch as melanoma and nevi [12], and nonmelanoma skincancers [13, 14]. The use of RCM has also been reported inthe diagnosis of a variety of inflammatory skin disordersincluding psoriasis [15], contact dermatitis [16, 17], vitiligo[18], cutaneous lupus erythematosus [19, 20], folliculitis[21], and photoaging [22]. In a recent paper, Angelova-Fischer et al. [23] demonstrated the use of RCM in thediagnosis of subcorneal blisters in two patients withpemphigus foliaceus in which the dark nonrefractive blistercavity was readily visible against a background of bright

Summary 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.

Contact dermatitis (CD) is a common itchy inflammatory skin disease. It is the most common skin disease in industrialized societies. In a recent study the incidence rates of CD was found to be 13.4 % and the point prevalence was found as 20.1 % (Mortz, Bindslev-Jensen and Andersen Br, J Dermatol 2013;168(2):318–25). There are two main types of CD: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Most cases are ICD (80 %). ICD is a non-immune non specific reaction caused by direct injury to the skin by strong irritants like: strong acids and alkalis. ACD is an immune mediated delayed type hypersensitivity reaction induced by many materials (allergens) like: metals, preservatives, perfumes, rubber, resins, dyes and many more. This type of CD appears only in patients that previously were sensitized to these materials (Ale and Maibacht, Expert Rev Clin Immunol 2010;6(2):291–310). Patch tests are used to identify the culprit allergens. In this article we will discuss the issues of contact dermatitis and patch testing in pregnancy.

Despite the use of powerful insecticides and the prodigious efforts of parents and health providers, successful control of head louse infestations remains unattainable in most countries. The main r...

Background Allergic contact cheilitis may appear after exposure to different substances, including dental materials, toothpastes, cosmetics, foods and medications. Objective To compare the rate of toothpaste allergy between patients with and without cheilitis and to examine the yield of our proposed toothpaste patch test kit for use in patients with cheilitis. Methods A patch test kit containing 11 substances used in toothpastes was formed. The study sample consisted of 44 patients, 24 with cheilitis (study group) and 20 with contact dermatitis but without cheilitis (control group). Results Eleven patients in the study group (45%) were found to be allergic to toothpaste, compared to only one patient (5%) in the control group (p Conclusion The rate of toothpaste allergy among patients with cheilitis might be higher than previously reported. Patch-testing with our toothpaste series is recommended in the evaluation of cheilitis.

BACKGROUND: Virtual reality immersion (VRI), an advanced computer-generated technique, decreased subjective reports of pain in experimental and procedural medical therapies. Furthermore, VRI significantly reduced pain-related brain activity as measured by functional magnetic resonance imaging. Resemblance between anatomical and neuroendocrine pathways of pain and pruritus may prove VRI to be a suitable adjunct for basic and clinical studies of the complex aspects of pruritus.OBJECTIVES: To compare effects of VRI with audiovisual distraction (AVD) techniques for attenuation of pruritus in patients with atopic dermatitis and psoriasis vulgaris.METHODS: Twenty-four patients suffering from chronic pruritus – 16 due to atopic dermatitis and eight due to psoriasis vulgaris – were randomly assigned to play an interactive computer game using a special visor or a computer screen. Pruritus intensity was self-rated before, during and 10 min after exposure using a visual analogue scale ranging from 0 to 10. The interviewer rated observed scratching on a three-point scale during each distraction program.RESULTS: Student’sttests were significant for reduction of pruritus intensity before and during VRI and AVD (P=0.0002 and P=0.01, respectively) and were significant only between ratings before and after VRI (P=0.017). Scratching was mostly absent or mild during both programs.CONCLUSIONS: VRI and AVD techniques demonstrated the ability to diminish itching sensations temporarily. Further studies on the immediate and late effects of interactive computer distraction techniques to interrupt itching episodes will open potential paths for future pruritus research.

Langerhans cells (LC) are a subtype of dendritic cells, which reside in the epidermis. LCs are antigen-presenting cells that originate in bone marrow and enter the epidermis through blood vessels. LCs exhibit a variety of antigen receptors that are able to respond to a wide range of antigens. Within the last two decades, these receptors have been the subject of considerable research. This article focuses on the rapidly growing body of knowledge with respect to the functions of LC receptors.

Summary 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-α target genes, matrix metalloproteinases and NFκB 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.

Monilethrix is a structural defect of the hair shaft usually inherited in an autosomal dominant fashion and caused by mutations in the hHb1, hHb3, and hHb6 keratin genes. Autosomal recessive inheritance in this disease has been sporadically reported. We encountered 12 Jewish families from Iraq, Iran, and Morocco with microscopic findings of monilethrix, but with no evidence of vertical transmission. Since no mutations were found in these three hair keratin genes, we examined nine chromosomal regions containing gene clusters encoding skin and hair genes. On chromosome 18q, a common haplotype in the homozygous state was found among all seven Iraqi patients, but not in 20 controls (P

Mathias proposed 7 criteria for establishing occupational causation and aggravation of contact dermatitis (Mathias, J Am Acad Dermatol 1989, 20, 842-848). 4 of the 7 criteria must be positive to conclude occupational dermatitis. In order to evaluate the validity of these criteria, we re-examined 19 patients (17 male and 2 female) with contact dermatitis, who had given a positive answer to at least 4 of the criteria and had either exchanged their workplace or stopped working. We re-evaluated them, 2-5 years later, for the presence of contact dermatitis. 14 of 19 patients (74%) reported that their dermatitis had cleared after they had left their previous workplace. Only 5 patients still suffered from dermatitis, 2-5 years later. 3 of these 5 patients could have been exposed to the causative allergens in their new workplace. We conclude that the Mathias criteria are useful to assess occupational contact dermatitis.

During the last years, a growing number of inherited skin disorders have been recognized to be caused by abnormal function of desmosomal proteins. In the present study, we describe the first female individuals affected with the ectodermal dysplasia/skin fragility syndrome (MIM604536), a rare autosomal recessive disease due to mutations in the PKP1 gene encoding plakophilin 1, a critical component of desmosomal plaque. One patient was shown to carry a homozygous splice site mutation in intron 4. The second patient displayed a homozygous recurrent mutation affecting the acceptor splice site of intron 1. Both mutations were associated with intraepidermal separation, widening of intercellular spaces, and abnormal desmosome ultrastructure, and were found to result in the absence of immunoreactive plakophilin 1 in the epidermis of the affected individuals. These two cases emphasize the role of molecular genetics in the assessment of congenital blistering in newborns and illustrate the importance of proper desmosomal activity for normal epidermis development and function.

Twenty-three female and 2 male subjects, documented to be sensitive to nickel by history and diagnostic patch testing, were pierced with American Iron Steel Institute (AISI) 316L stainless-steel ear piercing post assemblies (The Ear Piercing Manufacturers of Europe, UK), AISI 316L having a specification that includes a nickel content of between 10 and 14%. After piercing, the subjects were examined on days 7, 14, 30 and 42. Seven of the ear piercing post assemblies collected at random from the subjects at the end of the study and 10 unused post assemblies selected at random were analysed for nickel content and release. None of the nickel-sensitive patients showed signs of nickel dermatitis during the study. The nickel content of the ear piercing post assemblies collected from patients was reported as being between 11.5 and 12.9%, and the calculated rate of nickel release was below the detection limit of the method, thus recorded at 2/week. By comparison, the nickel content of the unused post assemblies was reported to be between 9.93 and 10.5%, and the calculated rate of nickel release was between 0.11 and 0.21 (mean: 0.15) µg/cm2/week. These results suggest that the AISI 316L stainless-steel ear piercing post assemblies do not elicit adverse reactions to nickel in previously sensitized subjects.

Objective. This is a retrospective analysis of malignant melanoma of the female genital tract, focusing on the high local recurrence rate of this tumor. Methods. All women treated for malignant melanoma of the genital tract were identified through the archives of the Hadassah University Hospital. The medical records and the pathological specimens were reviewed and reevaluated. Results. From 1986 to 2002, nine cases were diagnosed and treated at Hadassah. Seven had vulvar melanoma and two had vaginal melanoma. Sixty-six percent (6/9) of the patients had more than one focus of melanoma, either apparent at their initial diagnosis (3/9) or developed during follow up (3/9). Most of the recurring lesions were melanoma in situ. In one patient multiple nodular melanomas were detected. Atypical melanocytic hyperplasia was found in an otherwise normal mucosa in four patients. Three had experienced multiple recurrences. All patients were treated by radical local excisions with (3/9) or without (6/9) elective groin lymph node dissection. Three patients with locally recurring melanoma within the genital tract required two to five sessions of repeated surgical excisions. Conclusion. It is suggested that melanoma of the genital tract is the result of a multifocal disorder of the melanocytes within the mucosa. The increased local recurrence rate reflects an inherent abnormality of melanocytes. It is not attributed to surgical failure in controlling the disease. Insistent and even radical surgical excision is recommended, especially for patients whose prospects for prolonged survival are improved.

BACKGROUND/AIMS: The lack of a suitable, validated animal model for the comparison of the pharmacological effectiveness of known and potential moisturizers in the treatment of "dry skin syndrome" led us to develop such an in vivo model. METHODS: "Dry skin syndrome" was induced in guinea pigs by daily application of 2% sodium lauryl sulphate (SLS) in deionized water on one of the two shaved flanks for three consecutive days. After ascertaining skin dryness, that side was treated with an agent for 6 days. The in vivo humectant effect was measured by a Corneometer CM 825(R), erythema was measured by a Mexameter MX 16(R). In some cases histological studies were carried out. RESULTS: The treatment with the 2% SLS led to a consistent "dry skin syndrome" for 2 weeks. Glycerol, Vaseline, urea and ammonium lactate treatments validated the model, since the Corneometer CM 825(R) readings of the treated dry side was equal to that of the control untreated side after 1 week of treatment. Mexameter MX 16(R) measurements showed abolishment of the erythema by glycerol only. Histological study showed that SLS treatment creates acanthosis that is partially reversed by Vaseline and fully reversed by glycerol treatment. CONCLUSION: The guinea pig dry skin model is a relevant model of the human "dry skin syndrome". The instrumental results combined with the histological findings indicate that erythema measurements are relevant for the determination of curative effect.

Onychomycosis is widespread in the adult population, but considered to be rare in children. A number of studies in recent years show a rise in the prevalence of toenail onychomycosis in children. Of these, only a few were population-based. Here, we present a comprehensive cross-sectional population-based survey of toenail onychomycosis in primary school children in Israel. The survey included 1148 children, 598 boys, and 550 girls aged 5 to 14 from primary schools in the Jerusalem vicinity. Each child underwent a physical examination and completed a personal questionnaire, which provided background information of predisposing factors. The survey shows a prevalence of 0.87% of toenail onychomycosis. Although this figure is too small for statistical analysis, some important conclusions could be drawn: prevalence increased with age: boy/girl ratio was 2.2; the dominant etiologic agent was Trichophyton rubrum followed by Trichophyton mentagrophytes and Candida albicans. Infections were probably transferred from adults via the environment to children. Infected children came from different socio-economic backgrounds. This condition should be considered in the differential diagnosis of nail diseases in children.

Published data on the prevalence of onychomycosis in psoriasis patients compared with healthy controls are controversial, We therefore conducted a prospective study of toenail onychomycosis, among 113 psoriatic and 106 healthy non-psoriatic subjects, selected from the normal population in the Jerusalem area in the period 2003-05. The results revealed a prevalence of 47.6% toenail onychomycosis among psoriatic patients, compared with 28.4% in normal controls (p=0.0054). Both gender and age affected the prevalence of onychomycosis in both psoriatic and healthy controls, with a higher prevalence in male and elderly subjects. The type and duration of psoriasis were also found to have an impact on the prevalence of onychomycosis. However, the body area involved did not affect the prevalence of onychomycosis in psoriatic patients. Approximately the same percentages of dermatophytes and yeasts were found in psoriatic patients as in healthy controls. However, a higher percentage of moulds was found in psoriatic patients.

Background: Low-dose heparin devoid of anticoagulant activity inhibits T-lymphocyte heparanase activity, which is crucial in T-cell migration to target tissues. Objective: The purpose of this study was to assess the efficacy of low-dose enoxaparin (Clexane), a low-molecular-weight heparin, as monotherapy in lichen planus. Methods: Included in the study were 10 patients with widespread histopathologically proven lichen planus (LP) associated with intense pruritus of several months' duration. Patients were given 3 mg enoxaparin, subcutaneously once weekly; three patients received four injections, and seven patients received six injections. Results: In nine patients the itch disappeared within 2 weeks. Within 4 to 10 weeks in eight of these patients, there was complete regression of the eruption with residual postinflammatory hyperpigmentation; in one patient, there was marked improvement. In one patient, no effect was observed. Of the four patients who also had oral LP, only one showed improvement. No side effects were observed in any of the patients. Conclusion: These findings indicate that enoxaparin may be a simple, effective treatment for cutaneous LP. (J Am Acad Dermatol 1998;38:564-8.)

Total chromium levels were determined in 38 detergents and 12 bleaches on the market in Israel (45 locally produced, 5 imported). The samples were analyzed by Zeeman-corrected graphite furnace atomic absorption spectrophotometry. Chromium levels were higher than 5 ppm in 28 (56%) of the 50 products, from 1 to 5 ppm in 16 (32%), and lower than 1 ppm in only 6 (12%). Among the 5 imported products, only 1 had a chromium level below 1 ppm and the other 4 (1 from Germany, 3 from the USA) had high levels. Since a most 90% of the detergents and bleaches examined contained chromium levels higher than 1 ppm, it is concluded that these consumer products may be the cause of the high incidence of chromium sensitivity in Israel.

Contact dermatitis is one of the leading causes of occupational morbidity and absenteeism and has become an intolerable cause of missed workdays and health problems in the Israeli military. The aim of this study was to determine the rate of contact dermatitis in maintenance and clerical workers, the common allergens causing it, and the background of atopy in the subjects in order to design preventive measures. Medical records of all recruits to the Israel Defense Forces from 2000 to 2003 were reviewed for contact dermatitis. The 102 cases found were further assessed for job assignment, atopic background, and allergens. Of the 102 cases, 60 had irritant contact dermatitis and 42 had allergic contact dermatitis, of which 33 (78.6%) were maintenance workers, mainly mechanics. 13 soldiers in the maintenance job category (39%) and 2 soldiers in the clerical group (22.2%) had atopic background. There were 55 positive reactions in patch tests, 25 of them to oil and cooling fluids, with 14.5% attributed to methylchloroisothiazolinone/methylisothiazolinone) (Kathon CG). Atopy was found to be a risk factor for allergic contact dermatitis in our study and should be screened for in job assignment procedures in the military. Oil and greases contain significant allergens, especially their preservatives.

Objective To test the efficacy of tri-herbal combination on atopic dermatitis in a randomized, placebo-controlled trial. Methods Forty-nine patients were included for 2 weeks of treatment. Patients were followed until week 8. Results The response to the real medication was significant in objective and subjective parameters. Patients maintained partial remission until the end of follow-up. The placebo-treated group had a similar response without a significant difference. Conclusions Treatment with tri-herbal combination for atopic dermatitis does not differ from treatment with placebo.

It is well known that quality of life is an integral part in the outcome evaluation process of psoriasis treatment. Very few studies, however, examined the effect of climatotherapy at the Dead Sea on quality of life of such chronically ill patients.To determine the effect of the Dead Sea climatotherapy on the quality of life of patients with psoriasis vulgaris and psoriatic arthritis.A total of 119 patients participated in an observational prospective study carried out at the Deutsches Medizinisches Zentrum clinic, a medical skin care center specializing in climatotherapy. The patients completed questionnaires (Skindex-29) to quantify their quality of life at different time points: the day of arrival, the day of departure, and 3 and 6 months after the end of treatment.Marked improvement in the quality of life scores was measured between the time of arrival to time of departure and to 3 months after the end of treatment.Dead Sea climatotherapy has a significant positive influence on the quality of life of patients with psoriasis vulgaris and psoriatic arthritis.

Reflectance-mode confocal scanning laser microscopy is a novel, non-invasive imaging technique which permits real time visualization of cellular components in the skin at a resolution close to that of conventional histology. It has been widely used in the diagnosis of both benign and malignant tumors of the skin. In recent years it was also employed in the investigation of a variety of inflammatory and infectious skin conditions. The non-invasive nature of the procedure allows examination of multiple lesions and/ or repetitive sampling of one lesion over time, making it an excellent tool for followup and for monitoring treatment outcome in medical and cosmetic dermatology. This review summarizes the main indications for the use of this novel technique in clinical and experimental dermatology.

Skin diseases have been the focus of many innovations in the last decade. These innovations are mainly in the classification of skin diseases (primarily due to the dramatic development of research into the genetics of skin diseases, but not only because of this element), a new understanding of the processes underlying various diseases, improvements in diagnosis and innovations in drug treatment. In the current issue of "Harefuah", we review some advances in the field of skin diseases discovered in recent years. We review psoriasis as a multi-system disease, describe new insights into polyarteritis nodosa, parapsoriasis, autoinflammatory syndromes, and pustular psoriasis of pregnancy (impetigo herpetiformis). We also describe the new immunotherapy for metastatic melanoma. Dermatology aLso has new technological developments, especially the in vivo reflected mode confocal laser microscopy. We describe in detail the use of this technique in dermatology.

Auto-inflammatory diseases were first described more than 10 years ago as inherited disorders, characterized by recurrent flares of inflammation due to an abnormality in the innate immune system. The understanding of the underlying pathogenic mechanisms of these disorders, and especially the fact that they are mediated by IL-1 secretion by stimulated monocytes/macrophages, facilitated significant progress in patient management. IL-1 inhibitors are especially effective, and indeed, a brief and complete response to IL-1 inhibition is probably one of the best signs of auto-inflammation. Cutaneous manifestations are frequent in the monogenic auto-inflammatory syndromes, and a careful analysis of those findings reveals that they are almost always the consequence of neutrophilic skin infiltration. The neutrophilic dermatoses are, therefore, the cutaneous manifestations of those disorders. Even when the neutrophilic dermatoses occur outside the setting of genetically determined auto-inflammatory disorders, they probably also result from auto-inflammatory mechanisms. The distinction between auto-inflammation and autoimmunity is essential for the proper treatment of the patients. Auto-inflammation will almost always respond to IL-1 inhibition, while immunospressors will not be beneficial. The aim of the current paper is to review these two sub-groups of inflammatory diseases, focusing on their cutaneous manifestations, and highlighting the connection between these syndromes and inflammation in general.

Non-melanoma skin cancers (NMSC) are the most common malignancies in caucasians worldwide. Insulin-like growth factor-binding protein-7 (IGFBP7) was suggested to function as a tumor suppressor gene in several cancers, and to play a role in the proliferation of keratinocytes. A-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cells. A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function. Two editing sites were identified within the IGFBP7 transcript. To evaluate the expression and editing of IGFBP7 mRNA in NMSC compared to normal epidermis. We examined the expression and mRNA editing level of IGFBP7 in 22 basal cell carcinoma (BCC), 15 squamous cell carcinoma (SCC), and 18 normal epidermis samples that were surgically removed from patients by the Mohs Micrographic Surgery procedure. We studied the effect of IGFBP7 editing on an immortalized HaCaT keratinocyte cell model. IGFBP7 mRNA is over expressed in BCC and SCC compared to normal epidermis. Moreover, the IGFBP7 transcript is highly edited in normal epidermis, but its editing is significantly reduced in BCC and SCC. The edited form of IGFBP7 can inhibit proliferation and induce senescence in cultured keratinocytes. This study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin.