Does the Diagnostic Accuracy and Rates of Face-to-Face Visits Occurring Shortly after an Asynchronized Teledermatology Consultation Justify Its Implementation? An 18-Month Cohort Study.

INTRODUCTION: In 2019, Maccabi Health Services (MHS) rolled out the store-and-forward "Dermadetect" teledermatology consultation (TC) application. Study goal was to analyze MHS records of TCs (August 2019-February 2021) for the rate and reasons for face-to-face consultations (FTFC) occurring shortly after a TC with emphasis on FTFCs resulting in a different diagnosis for the same indication. METHODS: The records of FTFCs held up shortly after TCs were reviewed and classified into cases marked as unsuited for teledermatology, cases in which the indication differed, and cases with the same indication, which were analyzed for concordance of diagnoses. RESULTS: Dermadetect was used by 12,815 MHS beneficiaries. In 30% of cases, following FTFC occurred within the subsequent 5 months, and 901 of them occurred in the subsequent 2 weeks and were analyzed. Thirty percent were not suited for teledermatology, 15% were held for a different indication, and 55% occurred for the same indication. The diagnosis concordance between the TC and recurrent FTFC for the same indication was 97.4%, with full concordance at 68.1% and partial concordance at 29.3%. Overall, 13 patients (1.4%) of the 901 patients using the application only once had a subsequent FTFC within 2 weeks and received a different diagnosis than the one given in the TC. CONCLUSIONS: When considering the implementation of store-and-forward TC's, a 30% rate of following FTFC's during the next 5 months should be considered when planning the reimbursement model. Diagnosis discordance may be disregarded due to its low rates.

Superimposed type 2 segmental atopic dermatitis: case series and review of the literature.

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.

The relationship between atopy and allergic contact dermatitis in Israeli patients.

Introduction: 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. Aim: To explore the association between atopy and allergic contact dermatitis (ACD). Material and methods: 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. Results: 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 (p = 0.2). Additionally, 147 patients had an atopic background, of which 92 (62%) had ≥ 1 positive patch test result, compared with 55% of non-atopic patients (p = 0.2). Nickel sulphate was the most common contact allergen (13.4% of the patch test reactions). Conclusions: 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.

Genetic risk factors for antiepileptic drug-induced hypersensitivity reactions in Israeli populations.

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.

Eponyms and clinical entities from the land of Israel.

Seven eponyms have been pioneered by dermatologists in Israel: Brenner's sign, Chanarin-Dorfman syndrome, granulated sweetener packet sign, isopathic phenomenon of Sagher, lanolin paradox, Nakar-Ingber disease, and Wolf's isotopic response. In addition, there are three id reactions described by Israeli dermatologists: leishmanid, pediculid, and scabid. There is also the acronym PEMPHIGUS, which stands for the causative reasons for pemphigus. We celebrate these eponyms and clinical entities, which reflect the impressive progress made by dermatologists in Israel during the past century who have helped to build an academic, vibrant, and dynamic specialty in the Holy Land.

Effect of the Dead Sea climatotherapy for psoriasis on quality of life.

BACKGROUND: 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. OBJECTIVES: To determine the effect of the Dead Sea climatotherapy on the quality of life of patients with psoriasis vulgaris and psoriatic arthritis. METHODS: 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. RESULTS: 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. CONCLUSIONS: Dead Sea climatotherapy has a significant positive influence on the quality of life of patients with psoriasis vulgaris and psoriatic arthritis.

[What's new in 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.

[Nosology of inflammatory diseases: lessons learned from the auto-inflammatory syndromes--a focus on skin manifestations].

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.

[In vivo reflectance-mode confocal laser microscopy: basic principles and clinical and research employments in dermatology].

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.

Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

The controls of human keratin expression in situ remain to be fully elucidated. Here, we have investigated the effects of the neurohormone prolactin (PRL) on keratin expression in a physiologically and clinically relevant test system: organ-cultured normal human hair follicles (HFs). Not only do HFs express a wide range of keratins, but they are also a source and target of PRL. Microarray analysis revealed that PRL differentially regulated a defined subset of keratins and keratin-associated proteins. Quantitative immunohistomorphometry and quantitative PCR confirmed that PRL up-regulated expression of keratins K5 and K14 and the epithelial stem cell-associated keratins K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes. PRL also up-regulated K15 promoter activity and K15 protein expression in situ, whereas it inhibited K6 and K31 expression. These regulatory effects were reversed by a pure competitive PRL receptor antagonist. Antagonist alone also modulated keratin expression, suggesting that "tonic stimulation" by endogenous PRL is required for normal expression levels of selected keratins. Therefore, our study identifies PRL as a major, clinically relevant, novel neuroendocrine regulator of both human keratin expression and human epithelial stem cell biology in situ.

Increased vitamin D serum levels correlate with clinical improvement of rheumatic diseases after Dead Sea climatotherapy.

BACKGROUND: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms. OBJECTIVES: To assess the effectiveness of climatotherapy at the Dead Sea on the production of vitamin D in Norwegian patients suffering from various rheumatic diseases and to investigate possible associations between increased vitamin D serum levels, musculoskeletal symptoms and disease severity. METHODS: Sixty Norwegian patients who came to the Dead Sea area for 21 days of medical rehabilitation were divided into three groups according to their diagnosis: chronic pain syndromes, i.e., low back pain or fibromyalgia (Group 1, n=33); rheumatoid arthritis (Group 2, n=16); and osteoarthritis (Group 3, n=11). Serum 25-hydroxyvitamin D (25-OH-D) levels were determined at arrival and prior to departure. The treatment protocol included daily sun exposure (climatotherapy), bathing in the Dead Sea and mineral spring water (balneotherapy), mud applications and fitness classes. RESULTS: 25-OH-D serum levels increased significantly from 71.3 +/- 26.6 nM at arrival to 89.3 +/- 23.2 nM prior to departure (P < 0.001). Adjusted for the initial levels of pain (assessed by a visual analog scale) and disease severity, a direct correlation was observed between increased 25-OH-D serum levels and pain reduction (P = 0.012) and reduction of disease severity (P = 0.02). CONCLUSIONS: Climatotherapy at the Dead Sea induces significant changes in vitamin D. Increased 25-OH-D serum levels are associated with reduced musculoskeletal pain and disease severity.

Role of Patch Testing in Chronic Spontaneous Urticaria.

BACKGROUND: 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.

A Population-based study of Toenail onychomycosis in Israeli children.

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.

Effects of virtual reality immersion and audiovisual distraction techniques for patients with pruritus.

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's t tests 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.

Fluorescence imaging for the demarcation of basal cell carcinoma tumor borders.

BACKGROUND: Basal cell carcinoma (BCC) is a common malignancy accounting for 80% of all nonmelanoma skin cancers. Mohs micrographic surgery (MMS) is considered superior to alternative treatments, but the procedure is time consuming and costly. Alternative simpler techniques to facilitate accurate tumor demarcation are therefore in demand. Fluorescence imaging following application of 5-aminolevulinic acid is a noninvasive diagnostic technique that gives rapid information about the superficial extent of the skin tumor. OBJECTIVE: To ascertain whether fluorescence imaging improves the clinical tumor border assessment by investigating the consistency between tumor size determination by MMS, clinical assessment, and fluorescence imaging. METHODS: Eighteen patients with histologically verified nodular BCCs on the face scheduled for MMS were included in the study. The night before the surgical procedure, 5-aminolevulinic methyl ester cream was applied to the lesion. The following morning, tumor borders were determined clinically (clinical size), after illumination with Wood's light (fluorescence size), and by the tumor defect left on the skin surface following removal of the MMS specimen (Mohs size). RESULTS: The median tumor sizes were 93.05 mm2 (Mohs size), 61.05 mm2 (clinical size), and 72.75 mm2 (fluorescence size). The interclass correlation coefficients between Mohs size and fluorescence size was 0.984 and Mohs size and clinical size was 0.752. CONCLUSION: Tumor border estimation by fluorescence imaging and clinical assessment underestimate the genuine tumor size determined by MMS; however, the fluorescence size showed a higher degree of consistency with the Mohs size than did the clinical size.

Textile and Shoe Allergic Contact Dermatitis in Military Personnel.

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.

Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation.

BACKGROUND: Human beta-mannosidosis, a rare disorder of oligosaccharide catabolism, results from a deficiency of beta-mannosidase activity. So far, mutational analysis has been performed in only seven families and revealed 11 mutations in the MANBA gene which encodes the enzyme beta-mannosidase. OBJECTIVES: We report here a 36-year-old Arab female with beta-mannosidosis who presented with mental retardation and multiple angiokeratomas. We describe in this patient a novel null mutation and review the previously reported MANBA gene mutations and their clinical correlations. METHODS: Histopathology, ultrastructural analysis, and enzyme assays were performed. Sequencing of cDNA and genomic DNA analysis was conducted in a search for a mutation in the MANBA gene. RESULTS: Histopathology of a skin biopsy specimen from the patient showed the characteristic findings of angiokeratoma. Electron microscopy showed cytoplasmic vacuolation. Enzymatic activity of beta-mannosidase in the patient's serum, leukocytes, and fibroblasts was less than 1% of control values. Sequencing of the MANBA cDNA revealed a G-->A transition in exon 6 at nucleotide position c.693, resulting in the formation of a stop codon (W231X). LIMITATIONS: Only one family was studied. CONCLUSIONS: A new case of human beta-mannosidosis is presented and the first MANBA gene mutation from Arab ancestry is reported. Reviewing the reported MANBA gene mutations does not reveal a clear genotype-phenotype correlation. The importance of angiokeratoma corporis diffusum as the clue to the diagnosis of beta-mannosidosis and other lysosomal storage diseases is emphasized.

Langerhans cell receptors.

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.