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Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. Mice lacking the ubiquitin ligase RNF5 exhibit attenuated activation of the unfolded protein response (UPR) components, which coincides with increased expression of inflammasome components, recruitment and activation of dendritic cells and reduced expression of antimicrobial peptides in intestinal epithelial cells. Reduced UPR expression is also seen in murine and human melanoma tumor specimens that responded to immune checkpoint therapy. Co-housing of Rnf5-/- and WT mice abolishes the anti-tumor immunity and tumor inhibition phenotype, whereas transfer of 11 bacterial strains, including B. rodentium, enriched in Rnf5-/- mice, establishes anti-tumor immunity and restricts melanoma growth in germ-free WT mice. Altered UPR signaling, exemplified in Rnf5-/- mice, coincides with altered gut microbiota composition and anti-tumor immunity to control melanoma growth.

Yellow nail syndrome is a rare disorder characterized by the triad of yellow dystrophic nails, lymphedema, and chronic lung disease. Most cases occur in adulthood, with only a few congenital or familial cases reported. The pathogenesis of yellow nail syndrome remains largely unknown. This case series, which includes both congenital and sporadic cases, aimed to elucidate the key mechanistic pathways underlying the development of this disease. Background: Yellow nail syndrome (YNS) is a rare disorder characterized by a triad of yellow dystrophic nails, lymphedema, and chronic lung disease. Most patients present in adulthood, with only a few congenital or familial cases described. The cause of YNS remains largely unknown, although defects in lymphatic vessel development are suggested to play a significant role. Objective: To elucidate the genetic mechanisms underlying YNS. Design: Analysis of genetic sequencing data and gene and protein expression studies. Setting: A tertiary care academic medical center. Patients: 6 patients with congenital YNS (cYNS) and 5 with sporadic YNS (sYNS). Measurements: Exome and genome sequencing were used to detect disease-causing variants, complemented by RNA analyses for intronic variants. Protein and gene expressions were studied by immunofluorescence staining and real-time reverse transcriptase quantitative polymerase chain reaction analyses. Results: Biallelic variants in CELSR1 (n  = 5) or likely FZD6 (n  = 1), both core molecules in the Wnt/planar cell polarity (PCP) pathway, were identified in all patients with cYNS; none of the patients with sYNS had candidate genetic variants. Immunofluorescence staining showed that CELSR1 colocalizes with lymphatic vessels in the skin but not in the lungs or the intestine. Moreover, levels of CELSR1 and FZD6 proteins were negligible to zero in patient tissues (n  = 2) compared with control tissues. Gene expression of Wnt/PCP–related genes was reduced in patients with cYNS (n = 3), and patients with sYNS (n  = 4) showed milder gene expression impairments. Limitation: Small cohort size and limited sample availability. Conclusion: Defects in PCP organization may play a major role in the pathogenesis of YNS. To the authors' knowledge, this is the first demonstration of a mechanism explaining YNS development, mainly in its congenital form but also in patients with sporadic disease. Primary Funding Source: The Prof. Baum Research Fund of Israel Lung Association. [ABSTRACT FROM AUTHOR]

Background: Viral warts are the result of keratinocyte infection caused by the human papillomavirus (HPV), usually represent as benign growths of epithelial tissue. Those afflicted often experience a notable decline in their quality of life due to these lesions, which can also lead to functional issues and physical discomfort. Laser technology has introduced novel approaches in treating viral warts, especially ablative lasers such as CO2 and Erbium‐YAG (Er:YAG) lasers. Er:YAG laser gained recognition as a safe and effective method for addressing viral warts. Nevertheless, different recurrence rates have been reported in medical literature following treatment using Er:YAG laser, ranging from 24% to 71%. This study aimed to evaluate the recurrence rate and the risk factors that might affect it following successful treatment of warts using an Er:YAG laser. Methods: A retrospective chart review analysis of all 245 patients who underwent an Er:YAG laser wart removal between January 2019 and July 2023 was conducted. The main outcomes measures were response rate and number of sessions required to get complete clearance. Results: There was an overall complete resolution rate of 71.6% at 12 months follow‐up. Four parameters were found to affect the response rate: the number of sessions until complete response, duration of the wart present before the laser treatment, smoking, and periungual wart location. Conclusion: Er:YAG laser is an effective method for treating recalcitrant warts, and different risk factors were proven to effect its efficacy. [ABSTRACT FROM AUTHOR]

Background: The underlying pathogenesis of pityriasis lichenoides et varioliformis acuta (PLEVA) remains unclear, although immunologic injury and viral etiology have been suggested. Objective: To evaluate and expand the immunophenotype of PLEVA and to search for possible viral pathogens. Methods: Formalin‐fixed, paraffin‐embedded specimens of 20 patients with PLEVA and 9 patients with common inflammatory dermatoses (ID) were studied for immunophenotyping and for human herpesvirus (HHV) 1 and 2, cytomegalovirus (CMV), HHV‐8, parvovirus B19, and Epstein–Barr virus (EBV) immunohistochemistry. The presence of HHV‐6, HHV‐7, and enteroviruses was assayed molecularly. Results: The numbers of CD8+ T cells and T‐cell intracellular antigen‐1 (TIA‐1)+ cells were statistically significantly higher in PLEVA compared to the ID group. Immunohistochemistry for human HHV‐1 and HHV‐2, CMV and HHV‐8, parvovirus B19, and in situ hybridization for EBV were all negative. There was molecular evidence for HHV‐7 in only one PLEVA case (5%). Molecular studies for HHV‐6 and enterovirus involvement were negative in all the PLEVA specimens. Conclusions: The predominant T‐cell infiltrate in PLEVA is dominated by CD8+ cells, and by increased numbers of TIA1+ cells, which may indicate a cytotoxic T‐cell damage to the epidermis. Viral presence was not detected. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis, mainly cutaneous leishmaniasis (CL), is endemic in Israel. In recent years, the diagnosis of leishmaniasis has transitioned to a molecular diagnosis. Objective: To summarize all cases of leishmaniasis and the identified species seen in Israel based on molecular diagnosis. Methods: A retrospective study was performed of patients diagnosed with leishmaniasis between January 2017 and December 2022. All five medical centers in Israel in which Leishmania diagnosis is performed were included: Soroka, HaEmek, Hadassah, Rambam, and Sheba, all utilized molecular diagnostic methods. Data on the annual number of cases, species, age, and gender were retrieved. Results: During the years 2017–2022, a total of 4168 cases of leishmaniasis were diagnosed, which corresponds with ~7/100,000 inhabitants. L. (L.) major and L. (L.) tropica accounted for 84% and 14%, respectively. During the years 2020–2021, L. (L.) infantum emerged as a new form of cutaneous disease [2.7% of cases during this period]. Visceral L. (L.) infantum was found in five cases. Imported New World leishmaniasis accounted for 1% of the cases. L. (L.) major affected more males (67%) while L. (L.) tropica commonly affected more children and caused more facial lesions. Conclusions: The mean annual number of cases during these years is ~700. The dominant species is L. (L.) major. Since 2020, cutaneous L. (L.) infantum is an emerging infection in Israel. [ABSTRACT FROM AUTHOR]

Methacrylate allergy is a common cause of allergic contact dermatitis, and its incidence has surged over the past decade. Consequently, the primary sensitizing agent, 2-hydroxyethyl methacrylate, was recently added to the European Baseline Series of contact allergens. This study aimed to assess the added value of testing for allergens included in the (Meth)Acrylate Series -- Nails, in addition to 2-hydroxyethyl methacrylate, as well as to characterize patients who may benefit from more extensive testing. A retrospective analysis of medical records of patch-tested patients was conducted between June 2013 and July 2022. Among the 3,828 patients who underwent patch testing, 396 were tested with the (Meth)Acrylate Series -- Nails; 153 (38.6%) of those patients tested positive for at least 1 acrylate. The most common hapten was 2-hydroxyethyl methacrylate (85.6%), followed by hydroxypropyl methacrylate (85.0%) and ethylene glycol dimethacrylate (80.4%). In our study, 22/153 patients (14.4%) would have been missed if tested only for 2-hydroxyethyl methacrylate. The analysis showed that including hydroxypropyl methacrylate and ethylene glycol dimethacrylate improved detection rate to 98%, rendering the use of the entire tray unnecessary in most cases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]