Management of Melasma: Laser and Other Therapies-Review Study.

Melasma is a commonly occurring pigmented skin condition that can significantly affect one's appearance, described as symmetric hyperpigmentation that presents as irregular brown to gray-brown macules on various facial areas, such as the cheeks, forehead, nasal bridge, and upper lip, along with the mandible and upper arms. Due to its complex pathogenesis and recurrent nature, melasma management is challenging and the outcomes following treatment are not always deemed satisfactory. Solely treating hyperpigmentation may prove ineffective unless paired with regenerative techniques and photoprotection, since one of the main reasons for recurrence is sun exposure. Hence, the treatment protocol starts with addressing risk factors, implementing stringent UV protection, and then treatment using different strategies, like applying topical treatments, employing chemical peels, laser and light therapies, microneedling, and systemic therapy. This review aims to provide a summary of the effectiveness and safety of the frequently employed laser and light therapies for treating melasma, focusing on laser therapy as a treatment for melasma.

[COMPREHENSIVE GUIDELINES AND INDICATIONS FOR DIGITAL MONITORING OF PATIENTS AT HIGH-RISK FOR MELANOMA: A POSITION PAPER BY THE ISRAELI ASSOCIATION FOR DERMATOLOGY].

INTRODUCTION: Early detection may lead to reduced morbidity and mortality from melanoma. This study aims to establish guidelines for selecting patients suitable for digital monitoring of skin lesions. METHODS: A literature review was conducted, followed by consensus among experts appointed by the Israeli Dermatology Association. RESULTS: Two effective methods for early melanoma diagnosis were identified: Total-body photography (TBP) and digital dermoscopy. TBP involves capturing clinical images of the entire skin area for long-term monitoring (6-12 months). Digital dermoscopy focuses on close-up images of distinct lesions for short-term monitoring (3-4 months). Various risk factors for melanoma were identified, including genetic and familial factors, as well as demographic and phenotypic characteristics. Based on these risk factors and feasibility of clinical follow-up, a comprehensive list of indications for TBP was developed, categorized into three groups based on the expected level of benefit. Digital dermoscopy surveillance is recommended for patients with flat or slightly raised skin lesions showing dermoscopic features that do not definitively indicate melanoma. DISCUSSION: TBP significantly improves early melanoma detection, enhancing sensitivity and specificity while reducing unnecessary biopsies. However, due to its high cost and limited coverage by the Israeli public health care system, prioritizing patients who would benefit most from TBP is crucial. The compiled list of indications aligns with international recommendations and provides further details within the article.

To ASLO or Not to ASLO: Utility of the ASLO Test in Dermatology.

BACKGROUND: Group A Streptococcus (GAS) causes a wide spectrum of acute infections and immune-related diseases, most of which include a dermatological presentation. However, dermatological findings have a wide range of other possible etiologies. The diagnosis of GAS-related disease requires an indication of preceding GAS infection by direct culture or by measuring antistreptolysin O (ASLO) titer. OBJECTIVES: To explore the correlation between ASLO positivity and dermatological diseases. METHODS: We analyzed clinical data from all cases of patients over 18 years of age who underwent ASLO testing between the years 2016 and 2020 in the Department of Dermatology at Rambam Health Care Campus. RESULTS: Of 152 adult patients with ASLO tests, 100 had diagnoses that were potentially related to streptococcal infection. Vasculitis and psoriasis were the most suspected diagnoses. Positive ASLO test was found in 44 (29%) patients. The diagnoses showing the highest ratio of positive ASLO were psoriasis (60%), erythema nodosum (46%), skin infections (43%), Sweet syndrome (33%), and vasculitis (15%). Psoriasis types included plaque psoriasis (8 patients), guttate psoriasis (3 patients), and palmoplantar pustulosis and erythroderma (2 patients each). CONCLUSIONS: Although the applicability of ASLO for the spectrum of dermatological diseases remains unclear, our results enhance the practical relevance of the test. We showed a higher prevalence of positive ASLO tests in psoriasis and erythema nodosum cases and a lower prevalence in vasculitis. Notably, ASLO was positive in all psoriasis subtypes, suggesting high utility of the test for psoriasis.

Pigmentary Changes in a Woman With Oral Lichen Planus.

A woman in her 60s presented with oral lichen planus on hands and cheeks since childhood and also present in her parent and sibling. What is your diagnosis?

miR-184 represses ß-catenin and behaves as a skin tumor suppressor.

miR-184-knockout mice display perturbed epidermal stem cell differentiation. However, the potential role of miR-184 in skin pathology is unclear. Here, we report that miR-184 controls epidermal stem cell dynamics and that miR-184 ablation enhances skin carcinogenesis in mice. In agreement, repression of miR-184 in human squamous cell carcinoma (SCC) enhances neoplastic hallmarks of human SCC cells in vitro and tumor development in vivo. Characterization of miR-184-regulatory network, suggests that miR-184 inhibits pro-oncogenic pathways, cell proliferation, and epithelial to mesenchymal transformation. Of note, depletion of miR-184 enhances the levels of ß-catenin under homeostasis and following experimental skin carcinogenesis. Finally, the repression of ß-catenin by miR-184, inhibits the neoplastic phenotype of SCC cells. Taken together, miR-184 behaves as an epidermal tumor suppressor, and may provide a potentially useful target for skin SCC therapy.

Clinical and molecular features in a cohort of Middle Eastern patients with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub-classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB-associated genes reported to date. METHODS: We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds. RESULTS: The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14-associated EBS as compared to EBS due to KRT5 mutations (p < .05). Mutations in COL17A1 and laminin 332-encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332-associated JEB (p < .05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p < .001). CONCLUSIONS: EB patients of Middle Eastern origin were found to feature specific phenotype-genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region.

Paediatric Mycosis Fungoides: Clinical Variants, Treatment Modalities and Response to Therapy.

Mycosis fungoides is a rare cutaneous lymphoma in the paediatric population. The aim of this study was to examine the epidemiological, clinical, and histological characteristics, as well as the treatment modalities and response to therapy of paediatric patients with mycosis fungoides. This retrospective cohort study reviewed the records of 37 paediatric patients treated at Rambam Medical Center, Israel, between 2013 and 2021. Extracted data included epidemiology, clinical presentation, histological reports, infiltrate clonality status, treatment modalities and response to therapy. The mean follow-up period was 60 months. All patients were diagnosed with stage IA or IB disease. Folliculotropic mycosis fungoides was the most prevalent variant (49%). Most patients were treated with phototherapy (90%), with a response rate of 85%, and a complete response rate of 55% after the first course. There were no significant differences in response to phototherapy between the folliculotropic or other variants (p = 0.072). Similarly, delayed diagnosis, atopic diathesis, clonality, phototherapy type or number of treatments, were not associated with response to therapy, while protracted phototherapy was associated with prolonged remission. In conclusion, mycosis fungoides in the paediatric population is an indolent disease with a favourable prognosis and potentially prolonged response to phototherapy.

Clinical-Epidemiological Characteristics of Hidradenitis Suppurativa: A Retrospective Cohort Study from a Tertiary Care Centre in Northern Israel.

BACKGROUND: Hidradenitis suppurativa (HS) is characterised by inflamed lesions that typically appear in apocrine-rich flexural areas. Although studies have reported clinical and epidemiological data from western countries, data from the Middle East are scarce. The aim of this study is to characterise the differences in the clinical characteristics of patients with HS of Arab and Jewish ancestry and review the clinical characteristics, the course of the disease, the comorbidities, and the response to treatment. METHODS: This is a retrospective study. We collected clinical and demographic data from patient files between 2015-2018 at the Rambam Healthcare Campus dermatology clinic-a tertiary hospital located in the north of Israel. Our results were compared to those of a previously published Israeli control group registered in Clalit Health Services. RESULTS: Of the 164 patients with HS, 96 (58.5%) were men and 68 (41.5%) were women. The average age at diagnosis was 27.5 years and the average latency between the onset and diagnosis of the disease was 4 years. We found a higher adjusted prevalence of HS in Arab patients (56%) than in their Jewish counterparts (44%). Gender, smoking, and obesity, as well as axilla and buttock lesions, were risk factors for severe HS, with no differences between ethnicities. No differences were documented in comorbidities and in response to adalimumab, with a high overall response rate of 83%. CONCLUSIONS: Our findings revealed differences between Arab and Jewish patients with HS in terms of incidence and gender predominance, while no differences were documented in comorbidities and response to adalimumab.

Pediatric Tinea Capitis: A Retrospective Cohort Study from 2010 to 2021.

Pediatric tinea capitis displays a wide range of prevalence, with significant variability among populations. We retrospectively extracted the medical records of 456 pediatric patients diagnosed with tinea capitis during the years 2010-2021, from the dermatology outpatient clinics in two tertiary medical centers. Three species were isolated in 90% of patients: T. tonsurans, M. canis, and T. violaceum. While T. tonsurans presented a six-fold increase in incidence during the years 2019-2021, M. canis maintained stable incidence rates. Furthermore, terbinafine was the most efficient antifungal agent against T. tonsurans, achieving complete clinical clearance in 95% of patients, as compared to fluconazole (68%) and griseofulvin (38%) (p < 0.001). The mycological cure was recorded in 61/90 (68%) of patients with available data, at an average of 10 weeks. For patients with M. canis, griseofulvin and fluconazole were equally efficient (73% and 66%, respectively) (p = 0.44). Kerion was described in 36% and 14% of patients with T. tonsurans and M. canis, respectively, (p < 0.001). In conclusion, since 2019, there has been a significant increase in the prevalence of T. tonsurans, establishing this pathogen as the most common cause for tinea capitis in our population. Our data suggest that terbinafine is effective and presents high cure rates for tinea capitis in the pediatric population.

Arginyl-tRNA-protein transferase 1 (ATE1) promotes melanoma cell growth and migration.

Arginyl-tRNA-protein transferase 1 (ATE1) catalyses N-terminal protein arginylation, a post-translational modification implicated in cell migration, invasion and the cellular stress response. Herein, we report that ATE1 is overexpressed in NRAS-mutant melanomas, while it is downregulated in BRAF-mutant melanomas. ATE1 expression was higher in metastatic tumours, compared with primary tumours. Consistent with these findings, ATE1 depletion reduced melanoma cell viability, migration and colony formation. Reduced ATE1 expression also affected cell responses to mTOR and MEK inhibitors and to serum deprivation. Among putative ATE1 substrates is the tumour suppressor AXIN1, pointing to the possibility that ATE1 may fine-tune AXIN1 function in melanoma. Our findings highlight an unexpected role for ATE1 in melanoma cell aggressiveness and suggest that ATE1 constitutes a potential new therapeutic target.

Validation of the psoriasis epidemiology screening tool (PEST) and the new early arthritis for psoriatic patients (EARP) in pediatric population: pilot study.

OBJECTIVE: Juvenile psoriatic arthritis (JPsA) is a severe inflammatory arthritis, which is associated with psoriasis in most cases. While there are few validated screening tools for diagnosis of arthritis for adult patients with psoriasis, those screening tools were never evaluated in children. The aims of this study were to evaluate two screening tools among pediatric patients with psoriasis. METHODS: Thirty-nine patients with the diagnosis of psoriasis completed two screening questionnaires: The Psoriasis Epidemiology Screening Tool (PEST) questionnaire and the new Early Arthritis for Psoriatic Patients (EARP) questionnaire. All patients were evaluated by a rheumatologist for the diagnosis of JPsA, and the accuracy of the two questionnaires was compared. RESULTS: The 4/39 (10.1%) patients diagnosed with JPsA had a PEST questionnaire score of ≥ 3, compared to a median PEST score of the patients without the diagnosis of JPsA of 0 (0-2). Thus, both the sensitivity and specificity of the PEST in diagnosing JPsA were 100%. For the EARP questionnaire, 8/39 patients had a screening questionnaire score of ≥ 3, suggestive of JPsA, four were true positive, and four false positive. Thus, the sensitivity and specificity of EARP in diagnosing JPsA were 100% and 89%, respectively. CONCLUSION: Both the PEST and EARP questionnaires were easy to use and had high sensitivity for the diagnosis of JPsA in the pediatric population with psoriasis. The PEST questionnaire had a higher specificity than the EARP. KEY POINTS: • EARP and PEST are good screening tools for diagnosis of arthritis in pediatric population with psoriasis.

Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination.

is missing (Short communication).

Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation.

Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations.

Histopathological Findings in Nail Clippings With Periodic Acid-Schiff-Positive Fungi.

BACKGROUND: Periodic acid-Schiff (PAS) staining of nail clippings is an adjunct diagnostic tool for onychomycosis. OBJECTIVE: To detect histopathological findings as clues to the presence of PAS-positive (+) fungal elements in nail clippings. METHODS: Four hundred sixteen consecutive nail clippings suspected of onychomycosis were stained with hematoxylin and eosin, and with PAS stains. All cases were studied histopathologically. The clinical files of the cases with neutrophils were reviewed. RESULTS: PAS+ staining for fungi were demonstrated in 159 (38%) of the nail clippings. Neutrophils, parakeratosis, plasma globules, and bacteria were observed in 43 (27%), 108 (67%), 80 (50%), and 80 (50%) of the PAS+ cases, respectively, and in 17 (6%), 109 (41%), 84 (32%) and 140 (54%) of the PAS- cases, respectively (P < 0.01). Neutrophils showed by far the highest specificity (93%), although with low sensitivity (27%) for the presence of PAS+ fungi. Among the 43 PAS+ and 17 PAS- specimens with neutrophils, only 1 (2.3%) and 3 (17%) had overt psoriasis, respectively. CONCLUSION: Neutrophils in nail clippings may serve as a clue for onychomycosis. PAS staining with neutrophils is not necessarily associated with psoriasis.

SPANX Control of Lamin A/C Modulates Nuclear Architecture and Promotes Melanoma Growth.

Mechanisms regulating nuclear organization control fundamental cellular processes, including the cell and chromatin organization. Their disorganization, including aberrant nuclear architecture, has been often implicated in cellular transformation. Here, we identify Lamin A, among proteins essential for nuclear architecture, as SPANX (sperm protein associated with the nucleus on the X chromosome), a cancer testis antigen previously linked to invasive tumor phenotypes, interacting protein in melanoma. SPANX interaction with Lamin A was mapped to the immunoglobulin fold-like domain, a region critical for Lamin A function, which is often mutated in laminopathies. SPANX downregulation in melanoma cell lines perturbed nuclear organization, decreased cell viability, and promoted senescence-associated phenotypes. Moreover, SPANX knockdown (KD) in melanoma cells promoted proliferation arrest, a phenotype mediated in part by IRF3/IL1A signaling. SPANX KD in melanoma cells also prompted the secretion of IL1A, which attenuated the proliferation of naïve melanoma cells. Identification of SPANX as a nuclear architecture complex component provides an unexpected insight into the regulation of Lamin A and its importance in melanoma. IMPLICATIONS: SPANX, a testis protein, interacts with LMNA and controls nuclear architecture and melanoma growth.

Neonatal Autoimmune Subepidermal IgG/IgA Blistering Disease With Severe Laryngeal and Esophageal Involvement: A Report of a Case and Review of the Literature.

Neonatal autoimmune subepidermal blistering disease is rare. Mucosal involvement is more common in neonatal linear immunoglobulin A (IgA) bullous dermatosis. We describe a neonate with subepidermal cutaneous blistering disease with severe laryngeal and esophageal involvement leading to acute respiratory distress. Histopathology demonstrated a subepidermal blister with neutrophils and eosinophils at the dermal base. Collagen IV was detected at the dermal floor, and direct immunofluorescence showed linear IgG, IgA, and C3 deposits at the basement membrane zone. The patient demonstrated markedly increased serum levels of anti-BP180 NC16A and anti-BP230 IgG antibodies (Abs) but failed to show anti-LAD-1 IgA Abs. His healthy mother showed serum anti-LAD-1 IgA Abs but did not show anti-BP180 and anti-BP230 Abs. The neonate responded promptly to systemic corticosteroid therapy. A review of the literature detected 11 cases of neonatal subepidermal blistering disease with linear IgA deposits. Nine of these cases demonstrated coexisting linear IgG deposits, often with C3. Respiratory compromise was present in most of the cases. Neutrophils and eosinophils were commonly present in the inflammatory cell infiltrates. Besides our case, 2 cases of neonatal IgG/IgA subepidermal blistering disease with esophageal involvement were previously described. IgA Abs were present in the sera of both cases. Anti-LAD-1 IgA Abs were detected in the mother's serum of our case alone, but IgA Abs do not cross the placenta. Our case was consistent with neonatal IgG/IgA pemphigoid. Neonatal IgG/IgA subepidermal blistering disease may be associated with severe laryngeal and esophageal involvement leading to respiratory compromise. Expedited diagnosis and prompt treatment are warranted.

Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance.

Among the hallmarks of melanoma are impaired proteostasis and rapid development of resistance to targeted therapy that represent a major clinical challenge. However, the molecular machinery that links these processes is unknown. Here we describe that by stabilizing key melanoma oncoproteins, the ubiquitin ligase RNF4 promotes tumorigenesis and confers resistance to targeted therapy in melanoma cells, xenograft mouse models, and patient samples. In patients, RNF4 protein and mRNA levels correlate with poor prognosis and with resistance to MAPK inhibitors. Remarkably, RNF4 tumorigenic properties, including therapy resistance, require the translation initiation factor initiation elongation factor alpha (eIF2α). RNF4 binds, ubiquitinates, and stabilizes the phosphorylated eIF2α (p-eIF2α) but not activating transcription factor 4 or C/EBP homologous protein that mediates the eIF2α-dependent integrated stress response. In accordance, p-eIF2α levels were significantly elevated in high-RNF4 patient-derived melanomas. Thus, RNF4 and p-eIF2α establish a positive feed-forward loop connecting oncogenic translation and ubiquitin-dependent protein stabilization in melanoma.