Israel Medical Association Journal

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.

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].

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.

Over the past decade, the introduction of humanized mouse models, especially the transplantation of full-thickness human skin with autologous immune cells onto severe combined immunodeficient (SCID) mice, has transformed pre-clinical dermatology. These composite grafts vascularize and reinnervate within days, retain normal human architecture, evade graft-versus-host disease, and faithfully recapitulate complex cutaneous conditions such as psoriasis, atopic dermatitis, alopecia areata, androgenetic alopecia, vitiligo, pemphigus, and even intrinsic skin aging. Because the grafts respond to murine neuro-endocrine stress pathways yet remain immunologically human, investigators can track how psychological stress, cytokine networks, or targeted drugs shape disease onset, flare, and resolution in a living mini-patient. Unlike conventional murine models, which often capture only a single disease facet and vary by strain, humanized xenografts predict clinical efficacy, metabolism, and toxicity with far greater fidelity, enabling the discovery of pivotal mechanisms (e.g., vascular endothelial growth factor A-driven rejuvenation of aged skin [VEGF-A], voltage-gated potassium channel [Kv1.3], blockade in psoriasis, and alopecia areata) and accelerating the rational design of therapies from Janus kinase (JAK) inhibitors to neurokinin-1 receptor (NK-1R) antagonists. Although access to donor tissue and the need for pathogen-free facilities remain practical hurdles, these models now represent the gold standard for bridging bench and bedside in cutaneous research and for de-risking novel dermatologic and anti-aging interventions before they enter human trials.

Mohs micrographic Surgery (MMS) is a specialized surgical technique for removal of skin tumors. It achieves the highest cure rates of any available treatment. At the same time, it spares healthy tissue and thus provides superior cosmetic and functional results. The technique is indicated mainly for tumors on the head and neck. Other bodily areas including the trunk and extremities have been found to be indications for MMS as well. These indications have been defined by a collaborative work of major dermatology and dermatologic surgery organizations. Knowledge of these indications, in particular on areas other than the head and neck, is prudent for appropriately managing these tumors.

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy. Recent advances, particularly in beta-blocker therapy, have significantly improved the management of IHs. Early identification and treatment of IH may help reduce morbidity and associated complications. In this review, experts in pediatric dermatology in Israel who have experience in treating IH formulated national guidelines for the diagnosis and treatment of IHs, providing evidence-based recommendations for selecting appropriate therapeutic approaches. These Israeli national guidelines provide a structured approach to the diagnosis and treatment of IH, emphasizing early referral, appropriate treatment selection, and careful monitoring. The guidelines serve as a critical resource for pediatricians and dermatologists, ensuring optimal patient outcomes while minimizing complications.

Pott’s Puffy tumor (PPT) is a rare complication of frontal sinusitis, involving a subperiosteal abscesses with associated osteomyelitis of the frontal sinus anterior table. It mainly affects children and adolescents but can also occur in adults. It presents with localized forehead swelling, pain, fever, headache, and sometimes intracranial complications like epidural or subdural abscesses [1,2]. The standard treatment for PPT typically involves surgical drainage under general anesthesia and broad-spectrum intravenous antibiotics. During the coronavirus disease 2019 (COVID-19) pandemic (March–June 2020), delayed surgeries and resource limitations led to the use of minimally invasive techniques [3] such as needle aspiration without general anesthesia. In this study, we present three adult PPT cases from Nottingham University Hospitals, United Kingdom, treated with early abscess aspiration during this period.

We conducted retrospective study of PPT cases presented during the early COVID-19 pandemic. Following patients’ consent, case notes were reviewed for baseline demographics, previous treatments, presenting symptoms, and examination findings.