Israel Medical Association Journal

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.

Chronic cough is a common clinical symptom with a broad differential diagnosis, including respiratory, gastrointestinal, and neurological causes. A rare yet important cause is Arnold’s nerve reflex (ear-cough reflex) and triggered by stimulation of the auricular branch of the vagus nerve. We present the case of a 77-year-old man with a persistent dry cough and no significant medical history other than mild hypertension. The patient reported paresthesia in his left ear and noted that his cough was often triggered by touching the ear. A comprehensive physical and neurological examination, including otoscopy, was performed. Examination revealed cerumen impaction covering the posterior wall of the left external ear canal. Removal of the cerumen immediately triggered a cough but resulted in complete resolution of symptoms within one day. This case emphasizes the importance of considering Arnold’s nerve reflex as an underlying cause of chronic cough. A thorough physical examination, particularly otoscopy, is essential for accurate diagnosis. Understanding the neuropathic basis of the ear-cough reflex provides insights into targeted management including neuromodulator therapy.

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).

This special dermatology issue of IMAJ (June 2025) highlights cutting-edge research, innovative therapeutic approaches, and comprehensive reviews that contribute significantly to advancements in dermatologic practice. Key themes include novel genetic insights, innovative treatments for pigmentary disorders such as melasma, seasonal variations affecting diagnostic procedures, practical management strategies for psoriasis, sophisticated surgical techniques, microbiome research, and the potential of humanized mouse models in dermatological studies.

The following is the text of a letter to the editor of Lancet, which the editor-in-chief recently notified us of his decision not to publish

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: Allergic contact dermatitis (ACD), a prevalent skin disorder marked by delayed hypersensitivity reactions to specific allergens, is commonly diagnosed through patch testing. Previous studies have indicated lower rates of positive patch tests in summer months compared to winter months.

Objectives: To investigate whether there is a difference in the proportion of positive patch test results between summer and winter months.

Methods: A retrospective study was performed on 1128 patients, with 14 individuals undergoing two tests each, resulting in a total of 1142 patch tests. The tests were conducted at a major tertiary referral center between 2016 and 2020. The data set encompassed patient demographics and comprehensive patch test results.

Results: Of the 1142 tests conducted, 808 (70.8%) yielded a positive response. The most frequently administered test series was the European standard series, conducted for 1135 (99.3%) of the tests, with 559/1135 (49.2%) showing positive results, followed by the cosmetics series (394/1120, 35.1%) and fragrances series (61/118, 51.7%). No statistically significant difference was observed in the proportion of positive patch tests between summer and winter months (313/419, 74.7% vs. 175/245, 71.4%, respectively; P-value = 0.35). There was no statistically significant difference in the rate of testing each specific series between the summer and winter months, except for the fragrances series.

Conclusions: We found no significant difference in the positive patch test rates between the summer and winter months. Therefore, patch testing can be reliably conducted during the summer without an increased risk of false-negative results.

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.

Anifrolumab is a monoclonal antibody approved by the U.S. Food and Drug Administration in 2021 for the treatment of moderate-to-severe systemic lupus erythematosus (SLE) (excluding renal or neurological involvement). The drug inhibits the type 1 interferon receptor. Its safety and efficacy were evaluated through three placebo-controlled studies [1]. Clinical studies have demonstrated the beneficial effects of anifrolumab as an adjunct to standard therapy for SLE with cutaneous manifestations. Common side effects include upper respiratory tract infections, infusion-related reactions, herpes zoster, and hypersensitivity phenomena. Importantly, no serious skin reactions have been previously associated with the use of anifrolumab [2].

To the best of our knowledge, this is the first reported case of drug-induced bullous pemphigoid (DIBP) following treatment with anifrolumab.

Exercise-induced hematomas are a common condition that are caused by mechanical rupture of small blood vessels in the skin resulting in accumulation of blood in the extracellular space in the dermis. These hematomas often lead to diagnostic dilemmas in dermatological practice as they may resemble other conditions. The term talon noir (black heel) was coined to describe these hematomas as they are often blackish in appearance.

The clinical findings of subcorneal acral hematomas typically include the appearance of a bruise or a discolored purplish patch on the skin [Figure 1A] but may appear also as a black or brownish patch, raising a differential diagnosis of a melanocytic lesion. In this case series we illustrate an unusual presentation of acral hematomas that mimics melanocytic lesions.