Israel Medical Association Journal

Background: In times of war, healthcare systems face the dual challenge of attending to the medical needs of injured soldiers and civilians as well as struggling to meet the everyday healthcare demands of civilians.

Objectives: To assess the correlation between exposure to war and the likelihood of spontaneous abortion (SAB) and to compare it to a similar period in previous years.

Methods: We conducted a retrospective study comparing the rate of SAB during war to the previous years.

Results: During the Iron Swords war, 381 patients out of 3245 (11.74%) were diagnosed with SAB, compared to 530 of 4080 (13%) in 2022, 536 of 3387 (13.8%) in 2021, and 516 of 3798 (13.6%) in 2020. The median gestational age at diagnosis was similar between the groups, with most cases identified during the first trimester. The study group exhibited a significantly higher prevalence of smoking (18.47% vs. 7.75% vs. 6.3% vs. 9.3%, P = 0.03), with no differences in the prevalence of chronic diseases and in the method of pregnancy termination.

Conclusions: Exposure to stress due to war during early pregnancy appears to have no significant impact on the rate of SAB.

Acne vulgaris is a common dermatological condition, affecting up to 85% of adolescents and increasingly observed in adults, particularly women. Its chronic nature and visible manifestations impose significant psychological and social burdens. This review provides an updated examination of acne pathogenesis that explores emerging therapeutic approaches informed by recent molecular, genetic, and microbiome research. Findings from clinical studies, molecular biology, and immunological research published in the past decade are presented in a comprehensive overview of current advancements in acne treatment. Key databases and recent consensus guidelines have been utilized to identify novel mechanisms and therapeutic innovations. Current understanding emphasizes the role of innate immunity (e.g., toll-like receptors, inflammasomes), sebocyte biology via peroxisome proliferator-activated receptors (PPAR) signaling, and strain-specific Cutibacterium acnes dynamics. Environmental and genetic factors, including androgen receptor gene polymorphisms and lifestyle contributors, influence disease expression. Emerging treatments include selective retinoids (trifarotene), PPAR modulators, interleukin-targeting biologics, probiotics, bacteriophages, and hormonal therapies with improved safety profiles. Microbiome modulation and narrow-spectrum antibiotics are gaining attention for precision management. Integrating molecular insights with clinical practice fosters a personalized, multidisciplinary approach to acne care. Future research should prioritize microbiome restoration, novel biologics, and strategies to minimize antimicrobial resistance.

Scleromyxedema is a rare, chronic cutaneous mucinosis characterized clinically by diffuse indurated plaques, numerous waxy papules, and potential for systemic involvement, including neurological, pulmonary, and gastrointestinal complications. It can significantly impact the clinical course and patient prognosis [1].

Histologically, scleromyxedema typically manifests in two main forms. The classic form, the most common variant, is characterized by dense mucin deposition within the dermis, an increase in fibroblasts, and thickened collagen. The granuloma annulare-like variant, accounting for approximately 23% of cases, mimics granuloma annulare and is characterized by interstitial granulomatous infiltration and, in some cases, palisaded granulomas within the dermis. This unusual variant presents a significant diagnostic challenge due to its overlap with other granulomatous conditions, potentially causing diagnostic delays [2].

The lack of standardized treatment regimens makes managing scleromyxedema complex. Intravenous immunoglobulin (IVIG) has emerged as a leading therapeutic option, demonstrating efficacy in controlling both cutaneous and systemic manifestations. Other options include systemic steroids, thalidomide, retinoids, and melphalan [3].

These cases underscore the challenges of recognizing the clinical and histologic variability of scleromyxedema, which may lead to a delay in the diagnosis. Early diagnosis is critical given the potential for systemic involvement (neurological, gastrointestinal, and muscular) and the association of scleromyxedema with monoclonal gammopathy of undetermined significance (MGUS), which might progress to multiple myeloma. Consequently, timely hematologic evaluation and ongoing surveillance are warranted.

Background: Silicone breast implants (SBIs) are associated with subjective and autoimmune related manifestations, ranging from reported symptoms such as depression and fatigue to diseases such as Sjögren's syndrome and systemic sclerosis.

Objectives: To examine whether autoantibodies directed against autonomic nervous system receptors are associated with reported symptoms of dry mouth and eyes in patients with SBIs.

Methods: ELISA assays were used to evaluate a panel of 11 autoantibodies in the sera of patients with SBIs and age-matched healthy controls.

Results: Four autoantibodies (anti-angiotensin II type 1 receptor, anti-β1 adrenergic receptor, anti-muscarinic receptors M2, and anti-muscarinic receptors MR) had significantly lower median titers in SBI recipients who reported dry mouth compared to the control group (9.9 vs. 15.7, P < 0.001; 8.8 vs. 23.3, P < 0.001; 3.2 vs. 4.7, P < 0.001; and 6 vs. 8.8, P = 0.0011, respectively). Anti-muscarinic receptor M4 had significantly lower median titers in patients with SBIs who reported dry eyes compared to the control group (5.9 vs. 8.8, P = 0.0039).

Conclusions: A dysregulation of the autonomic nervous system in SBI recipients was correlated with the presence of dry mouth and dry eyes. Our results emphasize the need to further investigate the proposed involvement of the autonomic nervous system in subjective symptoms reported by SBI recipients.

Background: Behcet's syndrome (BS) is a multisystem syndrome that typically manifests as recurrent oral and genital ulcers, as well as other systemic manifestations. Few studies describing the characteristics of BS among Israeli patients have been published.

Objectives: To describe the characteristics of BS patients and to compare Jewish and Arab subpopulations.

Methods: We retrospectively reviewed electronic medical records and extracted demographic, clinical, laboratory, and medication data for each patient. We compared the Jewish and Arabic BS patients.

Results: The cohort included 98 patients. Males constituted 49 (50%); mean age at the time of diagnosis was 29.9 years; 71 (72.4%) were Arab and 27 (27.6%) were Jewish. Oral ulcers were evident in 93 patients (94.9%) and genital ulcers in 54 (55.1%). Involvement of the skin, joints, eyes, gastrointestinal tract, and neurologic and vascular systems were demonstrated among 42 (42.9%), 57 (58.2%), 47 (48.0%), 8 (8.2%), 10 (10.2%), and 15 (15.3%), respectively. HLA B51 was positive in 24 of 37 (64.9%). Pathergy was positive in 8 of 12 (66.7%). Colchicine was used in 82 (83.7%), azathioprine 47 (48%), methotrexate 16 (16.3%), apremilast 10 (10.2%), cyclosporine-A 8 (8.2%), adalimumab 26 (26.5%), infliximab 12 (12.2%), cyclophosphamide 1 (1.0%), tocilizumab 2 (2.0%), and anti-coagulation 6 (6.1%). The Arab and Jewish subpopulations were significantly different regarding male proportion, 40 (56.3%) vs. 9 (33.3%), P = 0.042.

Conclusions: BS is more common among Arabs in northern Israel, but no significant clinical or demographic differences were found except for a higher proportion of male patients among Arabs.

Background: Inflammatory and thrombotic markers play crucial roles in risk stratification for various diseases.

Objectives: To investigate the relative importance of inflammation, measured by C-reactive protein (CRP), and platelet turnover, indicated by immature platelet fraction (IPF), in predicting outcomes for patients with cardiovascular disease, coronavirus disease 2019 (COVID-19), and bacterial infections.

Methods: In this retrospective observational study, we analyzed data from 1473 individuals admitted to the Samson Assuta Ashdod University Hospital between 2018 and 2022. Patients were categorized based on CRP and IPF levels, with a focus on 280 patients in the high CRP/low IPF or high IPF/low CRP tertiles.

Results: The high CRP low IPF group demonstrated significantly higher mortality rates compared to the low CRP high IPF group (13.5% vs. 0.8%, P < 0.001). Logistic regression analysis revealed that the high CRP and low IPF combination was the strongest predictor of mortality (odds ratio 12.951, 95% confidence interval 1.409–119.020, P = 0.024).

Conclusions: The combination of inflammatory (CRP) and thrombotic (IPF) markers provides superior prognostic information compared to individual disease diagnoses in patients with cardiovascular disease, COVID-19, and bacterial infections.

Background: Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF).

Objectives: To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF).

Methods: We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i.

Results: Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury.

Conclusions: In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by hamartomatous polyps throughout the gastrointestinal tract, with an estimated prevalence of 1 in 100,000 individuals. While most cases follow an autosomal dominant inheritance pattern, some are caused by de novo mutations [1].

The age of onset for JPS is typically during childhood or adolescence, with a mean age at diagnosis of 18.5 years [2]. A major concern in JPS is the increased risk of colorectal cancer (CRC), requiring close lifelong surveillance. The cumulative lifetime risk for CRC ranges from 38% to 68%, with a mean age at diagnosis between 34 and 44 years [3].

Although juvenile polyps were initially considered to have low malignant potential, studies have identified two pathways of carcinogenesis in JPS: progression from hamartomatous polyps to adenoma and then to adenocarcinoma or direct transformation of hamartomatous polyps into adenocarcinoma. The management of JPS is tailored to each patient's specific manifestations and clinical presentation. The primary treatment goal is to prevent morbidity associated with gastrointestinal polyps, such as bleeding and intestinal obstruction.

We summarized the role of lung ultrasound for diagnosing and monitoring various pediatric respiratory diseases. We began with an overview of the basics of the tool, followed by describing its use in conditions such as pneumonia, pleural effusion, bronchiolitis, atelectasis, pneumothorax, bronchiectasis, and interstitial lung disease. We highlighted the sensitivity and specificity of lung ultrasound for the various diseases described. Furthermore, we included a comparison of this modality to other commonly used imaging techniques.

The potential influence of seasonal variations on vasculitis is unclear. Emerging evidence has suggested that seasonal factors may play a role in the onset of vasculitis. We extracted data from the electronic medical records at Clalit Health Services (CHS), Israel's largest health maintenance organization. We identified patients older than 18 years of age with new onset of giant cell arteritis (GCA), ANCA-associated vasculitis, immunoglobulin A (IgA) vasculitis, and Behçet's disease from 2007 to 2021. We constructed a time series of new vasculitis cases per month and explored the potential impact of seasonality on the disease onset. Our cohort included 4847 patients, including 2445 with GCA, 749 with ANCA-associated vasculitis (AAV), 547 with IgA vasculitis, and 1106 with Behçet's disease. We observed a decreased risk of GCA in September (relative risk [RR] 0.84, [95% confidence interval] 95%CI 0.72–0.98) and a significant reduction in AAV incidence in August (RR 0.68, 95%CI 0.48–0.96). For IgA vasculitis, an elevated risk was noted in February (RR 1.58, 95%CI 1.02–2.45), while Behçet's disease showed an increased risk in January (RR 1.25, 95%CI 1.02–1.55). No association was found between any specific season and the onset of vasculitis for any of the studied conditions. Our study results indicate that the onset of vasculitis conditions may be influenced by environmental factors associated with seasonality.

I read with great interest the comprehensive and interesting paper by Hazzan and colleagues in the Israel Medical Association Journal (IMAJ) [1]. The authors examined the difference in the results between morning and afternoon shifts of colonoscopy procedures. Not to my surprise, they found that more polyps were found in the morning shifts than in those in the afternoon. I believe, as do the authors, that the higher quality of the colonoscopy, the better its efficacy in detecting polyps and preventing colorectal cancer (CRC).

Background: Mycosis fungoides (MF) combined with photosensitive/autoimmune diseases has been reported, yet there are limited data regarding the therapeutic considerations in these patients, specifically phototherapy, a mainstay skin-directed treatment (SDT), being a relative or complete contra-indication.

Objectives: To outline therapeutic considerations for patients with MF who had also been diagnosed with photosensitive/autoimmune diseases.

Methods: We conducted a retrospective analysis of patients with MF who were treated at our center between January 2008 and December 2024with photosensitive/autoimmune diseases, especially collagen vascular diseases (CVD) or autoimmune bullous diseases (AIBD),

Results: Eight patients were diagnosed with MF at a median age of 39 years. Seven had early-stage (4-IA, 3-IB) and one had Sézary syndrome. Six early-stage MF patients were diagnosed with lupus erythematosus (LE, 4) or AIBD (2) and were treated with SDT (topical corticosteroids/chlormethine gel), systemic retinoid or methotrexate. A patient with resistant early-stage MF and discoid LE was treated with electron beam and interferon. One patient who presented with variegate porphyria and localized MF was treated with electron beam. The patient with Sézary syndrome had inclusion body myositis. He was treated with low-dose total skin electron beam, methotrexate, extracorporeal photopheresis, and subsequently with romidepsin. After a median of 8 years, no stage progression of MF was observed. The Sézary syndrome patient achieved down-staging and was at stage IB. There was no aggravation of the co-morbidity in any of the patients.

Conclusions: Effective management of MF and associated photosensitive or autoimmune co-morbidities underscore the need for individualized treatment strategies in patients with these unique dual diagnoses.

Background: Ectodermal dysplasia-syndactyly syndrome (EDSS) is a rare form of ectodermal dysplasia caused by biallelic mutations in NECTIN4 (PVRL4) gene.

Objectives: To identify new and rare mutations of the NECTIN4 gene in two unrelated families with EDSS.

Methods: Six patients from two unrelated families were diagnosed with EDSS. Next generation sequencing and Sanger sequencing were performed on DNA extracted from peripheral blood from affected and unaffected individuals from the families. We performed a literature search to identify previously reported cases of EDSS.

Results: A homozygous c.680A>G p.His227Arg mutation in NECTIN4 was found in five affected members of both families. One patient was found to be compound heterozygous for the latter mutation and for another novel missense mutation in NECTIN4 (c.79+1G>A). Both mutations affect the extracellular domain of nectin-4. A literature search identified only 13 reported families affected by this rare disorder.

Conclusions: We described two families with six affected members presenting with EDSS caused by two novel NECTIN4 mutations. We also reviewed the current available data on EDSS in the medical literature.

Background: Radiofrequency-skin interaction is considered self-limited for treating acquired pigmentation such as melasma. Alternatively, skin perforation with microneedling radiofrequency (MNRF) may increase skin bioavailability for depigmenting-mediated ingredients or drugs for the treatment of melasma.

Objectives: To examine the clinical feasibility of topical tranexamic acid (TA) mediated with MNRF-assisted transepidermal delivery in patients with mixed melasma.

Methods: The study protocol included 14 women with centrofacial or malar pattern of distribution of melasma (skin types II-VI; age 35–48 years). Patients underwent four treatments at 3-week intervals between treatments. Treatment protocol included non-insulated MNFR (Intensif, EndyMed Ltd, Caesarea, Israel) followed by TA (hexakapron 4%) solution application. The improvement was evaluated based on clinical photographs (Quantificare, Biot, France) and modified Melasma Area and Severity Index (mMASI) scores. Baseline Photographs were analyzed 3 months after the last treatment.

Results: In 13 patients (93%), mMASI scores were significantly lower after 3 months (mean 3.6) than at baseline (5.22). In one patient, mMASI was higher at 3 months compared to baseline. Overall, mMASI improved by 31% (P < 0.01). Physician and patient satisfaction was high. Minimal adverse reactions were recorded.

Conclusions: MNRF-assisted transepidermal delivery with topical TA is a safe and effective modality for the treatment of melasma.

Background: Identifying drug–drug interactions (DDIs) in dermatology can be cumbersome and time-consuming using traditional methods.

Objectives: To explore the potential of ChatGPT-4o, an artificial intelligence (AI)-based chatbot, to streamline the identification process.

Methods: ChatGPT-4o was tasked with assessing DDIs among commonly prescribed dermatological medications. The accuracy and reliability of the chatbot's outputs were compared against established references for 43 interactions.

Results: ChatGPT-4o successfully identified all evaluated interactions. It accurately described the interaction effects in 42 cases, with only one example of misdescription.

Conclusions: The findings highlight the potential of ChatGPT to serve as an effective and efficient alternative for identifying and understanding DDIs in dermatology, despite one noted error that emphasizes the need for ongoing verification against trusted references. Further research is needed to validate its use across a broader range of medications and clinical scenarios.