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Sat, 12.07.25

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June 2025
Baruch Kaplan MD

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.

Meital Oren-Shabtai MD, Assi Levi MD, Daniel Mimouni MD, Hadas Prag-Naveh MD, Elena Didkovsky MD, Elisheva Pokroy-Shapira MD, Emmilia Hodak MD, Iris Amitay-Laish MD

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.

Dania Abu Assab MD, Abraham Zlotogorski MD, Vered Molho-Pessach MD

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.

Zvi Segal MD, Sharon Baum MD, Aviv Barzilai MD, Yaron Lavi MD, Michal Solomon MD

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.

Jonathan Shapiro MD, Tamar Freud PhD, Baruch Kaplan MD, Yuval Ramot MD MSc

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.

Mira Hamed MD, Amir Bieber MD, Michael Ziv MD, Guy Feraru MD, Roni P Dodiuk-Gad MD, Eran Cohen-Barak MD, Daniella Kushnir-Grinbaum MD

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.

Avner Shemer MD, Anna Lyakhovitsky MD, Eran Galili MD, Riad Kassem MD, Baruch Kaplan MD

Nail psoriasis (NP) is a common manifestation of psoriasis, affecting up to 80–90% of patients with psoriatic arthritis and up to 60% of those with cutaneous psoriasis. Isolated NP also occurs in 5–10% of cases. It significantly impacts quality of life and may indicate or precede psoriatic arthritis. In this review, we summarized the clinical features of NP, highlighting patterns of matrix and nail bed involvement, and discussed differential diagnosis with onychomycosis. We outlined current topical, intralesional, systemic, and non-pharmacological treatment options, and proposed an evidence-based approach to diagnosis and management.

Psoriasis is a chronic immuno-inflammatory skin disorder characterized by rapid keratinocyte proliferation, forming thick, red patches with silvery scales. It affects 2–3% of the population, impacting skin, nails, and joints. Pathogenesis involves genetic, environmental, and immunological factors [1]. Triggers such as infections (especially Streptococcus), skin injuries, medications, stress, and alcohol can initiate or worsen the condition [1]. Psoriasis may follow a stable course or present in cycles of flare-ups and remissions. Skin involvement may manifest in any body area but is most common on the knees, elbows, trunk, and scalp [1]. Nail involvement appears in up to 60% of those with cutaneous psoriasis and 80% of those with psoriatic arthritis (PsA), with an 80–90% lifetime incidence [2,3]. Isolated nail psoriasis (NP), defined as nail changes without cutaneous psoriasis or with limited body surface involvement (< 5%), occurs in 5–10% of patients [4,5].

Mor Gross MD, Yuval Ramot MD MSc

Psoriasis is a chronic, immune-mediated skin disease characterized by inflammatory lesions and systemic co-morbidities. Emerging evidence highlights the significant role of the microbiome in psoriasis pathogenesis. Dysbiosis of the skin and gut microbiota has been linked to increased disease severity and co-morbidities such as psoriatic arthritis and cardiovascular disease. In this review, we explored the microbiome's influence on immune responses in psoriasis and its potential as a therapeutic target. Microbial therapies, such as probiotics and fecal microbiota transplantation, hold promise for restoring microbial balance and improving outcomes. We also discuss how the microbiome modulates drug efficacy and toxicity, offering insights for personalized treatment approaches. While challenges remain in establishing causality and translating findings into clinical practice, leveraging the gut-skin axis may optimize psoriasis management and improve patient outcomes.

May 2025
Marron Daud MD, S. Nahum Goldberg MD, Dotan Cohen MD, Gili Dar MD, Shiran Levy MD, Adam Nevo MD, Jacob Sosna MD, Naama Lev-Cohain MD

Background: Coronavirus disease-2019 (COVID-19) chest computed tomography (CT) involves ground-glass opacity (GGO) and denser consolidations, which are crucial for diagnosis.

Objectives: To determine optimal window settings for characterization and detection of GGO and dense consolidation on CT imaging in COVID-19 patients using a Simplex-based approach.

Methods: The study included 54 conventional CTs of COVID patients in two phases. First, CT images of 14 patients with GGO and 4 with dense consolidation were included. Seven radiologists evaluated representative images in different windows of varied width and center. They were graded for adequacy of characterization and detection. A Simplex algorithm was used to iteratively determine the optimal window settings. Surface response maps expressing the relationship between window settings and overall reader grades were constructed. Next, the reviewers compared manufacturer recommendations to the new optimal windows found on CT images of 40 patients.

Results: Overall, 12 different window settings were evaluated over a total of 1176 reads. Optimal characterization and detection of pure GGO was seen with a center of 630 HU and width 1460 HU, producing higher grades for both detection and characterization than the manufacturer window settings (P = 0.005). Optimal windowing for dense consolidation was like manufacturer measures (-585 HU and 1800 HU). In phase 2, an overwhelming preference of 78% favoring the optimal window compared to conventional settings was found.

Conclusions: GGO lung opacities characteristic for COVID-19 can be best seen using a lower CT windowing width than the manufacturer's recommendations, unlike denser consolidations, possibly due to differences in underlying pathophysiology.

Dana Madorsky Feldman MD, Yael Laitman MSc, Dana Albagli Bsc, Jacob Korach MD, Eitan Friedman MD PhD

Background: BRCA1/BRCA2 female pathogenic sequence variant (PSV) carriers in Israel are offered semiannual cancer antigen 125 (CA125) serum level determination and transvaginal ultrasound until performing risk reducing salpingo-oophorectomy (RRSO), even with the lack of proven efficacy of these procedures in providing adequate early detection of ovarian cancer.

Objectives: To report the results of longitudinal CA125 measurements in BRCA1/BRCA2 carriers as a tool for ovarian cancer detection in a single medical center in Israel.

Methods: Asymptomatic BRCA1/BRCA2 PSV carriers attending the Meirav High Risk Clinic at Sheba Medical Center for more than 3 years were eligible. Data on specific PSV, risk reducing surgeries, and cancer diagnoses were obtained from participant records. We used chi-square and Wilcoxon-Rank tests for statistical analyses.

Results: Overall, 739 (399 BRCA1, 336 BRCA2, 4 BRCA1 + BRCA2) PSV carriers were included. Mean age at the start of follow-up was 38.96 ± 11.13 years, mean follow-up time was 7.93 ± 2.34 years, (5860.80 women/years). Most participants (490/739 [66.3%]) had stable CA125 levels (± 5 U/µl). Of participants, 61 had CA125 levels > 35 U/µl at least twice (n=42) or at least doubling of marker levels to a minimum of 20 U/µl (n=19), results that have led to further cancer defining investigations. Of these, 14 and 4 were diagnosed with breast and ovarian cancer, respectively.

Conclusions: Longitudinally stable CA125 levels were noted in most BRCA1/BRCA2 PSV carriers and elevated levels were a poor marker for ovarian cancer development.

Rawi Hazzan MD, Tarek Saadi MD, Revital Guterman RN, Ruhama Elhayany MHA, Avraham Yitzhak MD, Naim Abu-Freha MD

Background: Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. There are conflicting reports on whether colonoscopies performed during the morning shift have higher adenoma detection rates.

Objectives: To investigate the differences in polyp detection rate (PDR) in colonoscopies between morning and afternoon shifts.

Methods: In a retrospective, multicenter study involving a large cohort, we analyzed all colonoscopies conducted between 2016 and 2023 across seven endoscopy departments. The PDR was compared between morning and afternoon shifts.

Results: We included 368,997 colonoscopies: 213,795 (57.9%) performed during the morning shift and 155,202 (42.1%) during the afternoon shift. Patients undergoing colonoscopies during the morning shift were more frequently female (53.8% vs. 51%, P < 0.001) and tended to be older compared to those in the afternoon shift (average age of 56.97 ± 12.6 vs. 55.6 ± 12.9, P < 0.001). Colonoscopies conducted during the morning shift exhibited a higher cecum intubation rate (CIR) (96.7% vs. 95.6%, P < 0.001). During the morning shift, higher rates of PDR (32.9% vs. 29.9%, P < 0.001) were observed. In the multivariate analysis, after adjusting for other variables, age, male sex, polyp follow-up, fecal occult blood test, morning shift, familial history of CRC, and rectal bleeding demonstrated statistically significant associations (P < 0.001) for PDR.

Conclusions: Colonoscopies during the morning shift yielded a higher PDR and CIR than those in the afternoon. To improve this rate, endoscopists working the afternoon shift must be provided with the right conditions.

Avishag Laish-Farkash MD PhD, Ella Yahud MD, Michael Rahkovich MD, Yonatan Kogan MD, Lubov Vasilenko MD, Emanuel Harari MD, Gergana Marincheva MD, Emma Shvets MA RNS, Eli I. Lev MD, Uri Farkash MD

Background: Uninterrupted antithrombotic treatment (ATT) during cardiac implantable electronic device (CIED) implantation increases bleeding and device-related infections (DRI) risk. The wide-awake-local-anesthesia-no-tourniquet (WALANT) technique, using large-volume local anesthesia and adrenaline, is successful in hand surgeries but its potential to mitigate bleeding risk in CIED implantations remains unknown.

Objectives: To investigate whether WALANT protocol for CIED implantations reduces clinically significant pocket hematoma in patients with a high bleeding risk or is a contraindication for interrupting ATT.

Methods: We conducted a prospective, double-blind, randomized controlled trial with CIED surgery patients on uninterrupted ATT. They received WALANT protocol (lidocaine 1% with adrenaline 1:100,000) or standard protocol (lidocaine 1%). Following implantation, patients were blindly monitored in the ward and pacemaker clinic. Patients were monitored for bleeding outcomes post-implantation.

Results: Forty-six consecutive patients (73.6 ± 9 years, 72% male) were enrolled. In the WALANT group (n=24) no intra-pocket pro-hemostatic agents were needed, compared to 45% in the control group (P = 0.0002). Postoperative pressure dressings were used in 12.5% vs. 68% (P = 0.0002). WALANT patients had smaller hematoma areas (median 3.7 cm2 IQR [1–39] vs. 46 cm2 [IQR 24–76], P = 0.0004) 1-day postoperative. ATT interruption occurred in 12.5% vs. 18% (P = 0.7). Superficial skin infection rates were 4% vs. 9% (P = 0.6). No DRI occurred. No WALANT-related side effects were observed.

Conclusions: WALANT protocol in CIED implantation with uninterrupted ATT reduced pro-hemostatic agents, pressure-dressing need, and hematoma size. Larger studies are needed to assess its impact on infection rates.

Shira Gabizon-Peretz MD, Rinat Yerushalmi MD, Mordehay Vaturi MD, Inbar Nardi Agmon MD

We presented the emergent development of pulmonary hypertension and right ventricular impairment in a 64-year-old woman with metastatic breast cancer undergoing carboplatin–gemcitabine combination therapy. The patient's acute decompensation, characterized by dyspnea and desaturation, occurred 2 days after chemotherapy initiation. Clinical assessments revealed right ventricular dilation and systolic dysfunction, a rare manifestation not previously associated with the administered drugs, but which may be associated with cardiopulmonary toxicity of gemcitabine therapy. Prompt discontinuation of chemotherapy and initiation of diuretic therapy resulted in clinical improvement and resolution of the right ventricular dysfunction within several weeks. While a definitive causal link to gemcitabine remains inconclusive, this report highlights a potential and under-reported side effect, emphasizing the need for increased awareness and further investigation into the cardiopulmonary effects of gemcitabine.

Mohammad Adawi MD, Suhail Aamar MD

Fasting, a practice with deep historical roots, has gained scientific attention for its potential benefits on human health, particularly in autoimmune diseases. In this review, we explored the impact of fasting on immune function and autoimmunity. Autoimmune diseases, characterized by the immune system's attack on the body’s own tissues, are influenced by genetic, environmental, and dietary factors. Various forms of fasting (intermittent, water fasting, calorie restriction, ketogenic diets, and time-restricted feeding) affect metabolism, immune modulation, and inflammation reduction. These changes can promote autophagy, stem cell renewal, and immune system rebalancing by offering potential therapeutic effects for autoimmune conditions. Although more research is needed, fasting may serve as an adjunctive therapy for immune-mediated diseases by reducing symptoms and promoting remission. However, fasting must be approached with caution, particularly for individuals with specific autoimmune disorders. We reviewed the physiological changes during fasting, types of fasting regimens, and the clinical relevance in autoimmunity. Further studies are needed to validate these observations in patient populations.

Maguli S. Barel MD, Majeed E. Zahalka MD, Ofer M. Kobo MD MHA, Adham Zidan MD, Rami Abu Fanne MD PhD, Simcha R. Meisel MD, Ariel Roguin MD PhD

Standup paddleboard surfing (SUP) is a sports activity in which a person stands upright on a surfboard and propels the board using a single paddle. It is an emerging recreational activity that is attracting public attention and gaining popularity because it promotes fitness, strength, and improved balance. In this review, we discuss the outcomes after severe cardiac events in SUP surfers. We report on six fit individuals (five males and one female, age range 41–69 years) who experienced sudden cardiac arrest (n=3) or acute myocardial infarction occurring during SUP. Cardiopulmonary resuscitation was initiated in three patients on presentation due to ventricular fibrillation. In four patients the culprit coronary artery was the left anterior descending artery treated by percutaneous coronary intervention. All patients were discharged alive. A review of the literature showed a paucity of scientific evidence to substantiate the proposed health benefits of SUP surfing. Our cluster of acute cardiac events occurring during this activity calls for heightened public awareness to better understand the physical demand required to practice SUP. There is a need for more data regarding the cardiovascular clinical aspects of this water activity, and the risks it entails.

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