Israel Medical Association Journal

Background: The association between new-onset atopic dermatitis (AD) and the coronavirus disease 2019 (COVID-19) pandemic was scarcely documented in the literature.

Objectives: To evaluate the incidence of AD in a large nation-wide cohort over 6 years, focusing on changes in incidence following the onset of the COVID-19 pandemic.

Methods: This retrospective cohort study included all members of the largest HMO in Israel (n=4.8 million) from 2017 to 2022. Patients with newly diagnosed AD were identified using the ICD-10 code for AD (L20). Incidence rates were calculated as the number of new diagnoses per 1000 person-years. The pre-COVID period was 1/2017 to 1/2020, and post-COVID 2/2020 to 12/2022. Age-adjusted incidence rates were calculated based on the World Health Organization's standard population.

Results: The overall crude incidence of AD across the study period was 3.38/1000 person-years (PYs). From 2017 to 2022, there was a 36.97% increase in the crude incidence and a 40.44% increase in the age-adjusted incidence, with a mean annual incidence change of +6.5% and +7.1%, respectively. Both crude and adjusted annual incidence increases were significant (P < 0.001, R² = 0.98; P < 0.001, R² = 0.99, respectively). The incidence of AD at the follow-up before the COVID-19 pandemic was 3.07/1000 PYs, and after was 3.71/1000 PYs.

Conclusions: We observed a significant and nearly consistent annual increase in AD incidence from 2017 to 2022, across various sex and age groups. Further research is needed to explore the impact of the COVID-19 pandemic on rising trends in AD incidence.

Background: Ramadan, one of the core tenets of Islam, requires a rigorous fasting regimen from dawn until sunset, during which practitioners abstain from all forms of food and drink. This substantial alteration in daily habits raises pertinent questions regarding its potential implications for cardiovascular health.

Objectives: To analyze the incidence of myocardial infarction (MI) throughout the Ramadan fasting period.

Methods: We retrospectively compared the incidence of MI occurring during Ramadan with that observed during the corresponding non-Ramadan months from 2010 to 2021 using medical records of Muslim patients admitted to the Galilee Medical Center. Ramadan's timing varies from year to year. We used a 3-year comparative framework to ensure seasonal alignment.

Results: During the study period and within a well-defined geographic region, we found that among Muslims, there were 405 MIs: 201 during Ramadan and 204 during non-Ramadan periods, P = 0.282.

Conclusions: The incidence of MI during Ramadan remained stable, indicating that the fasting practice does not significantly heighten the risk of MI.

Background: Antiphospholipid syndrome (APS) is a common form of acquired thrombophilia associated with a high thrombotic risk. Fabry’s disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (GLA) gene and presents with a wide range of clinical manifestations, including a high rate of thrombosis. Previously reported, 45% of FD patients were found to have antiphospholipid autoantibodies.

Objectives: To determine the prevalence of FD in patients with APS.

Methods: We conducted a prospective study. Data were collected from 41 APS patients at our outpatient clinic at Meir Medical Center in Israel. We utilized chemical and genetic analyses to identify FD among APS patients. Dried blood spot (DBS) was used to assess GLA activity in males, and mutational analysis of the GLA gene was performed by sequencing exons and their flanking regions in women.

Results: Among 41 antiphospholipid patients, one male patient was diagnosed with FD. Gal variants were not detected in any of the tested female patients.

Conclusions: We found a low prevalence (2.4%) of FD in APS patients. Larger studies are needed to evaluate the clinical utility and cost-effectiveness of routine FD screening in this population.

A 70-year-old female with a 10-year history of dermatomyositis involving the skin, muscles, and gastrointestinal system was diagnosed based on proximal muscle weakness, typical dermatomyositis-specific rashes, elevated creatine kinase, and muscle biopsy findings consistent with dermatomyositis. Myositis-specific autoantibodies were negative.

The patient initially received treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) but experienced gastrointestinal intolerance to both methotrexate and azathioprine. Subsequently, she was managed with intravenous immunoglobulin (IVIg) for 4 years; however, due to a relapse of muscle involvement, rituximab was initiated and has been administered for the past 3 years.

Over the last year, the patient achieved remission in muscle involvement but experienced worsening dermatomyositis-specific skin manifestations, including heliotrope rash, Gottron signs, and holster sign [Figure 1A], accompanied by severe pruritus that significantly impaired her quality of life. The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score reached 17. Her skin condition remained refractory despite treatment with topical steroids and calcineurin inhibitors.

Obesity is a growing global health concern, with its prevalence contributing to the rise of multiple chronic conditions, including autoimmune diseases. In this review I explore the intricate relationship between obesity and autoimmunity, focusing on how excess adiposity can affect immune responses and promote the development of autoimmune disorders. Obesity alters adipose tissue architecture, promoting chronic low-grade inflammation and triggering the release of pro-inflammatory cytokines, which contribute to immune system dysregulation. Adipose tissue is no longer seen as merely an energy store but as an active endocrine organ that interacts with the immune system. The review delves into mechanisms such as the role of adipokines, altered T cell function, and the recruitment of immune cells to inflamed adipose tissue, which together exacerbate autoimmune risk in obese individuals. Genetic and environmental factors also play a critical role in these processes, as polymorphisms and high-fat diets have been shown to influence both obesity and autoimmune susceptibility. Last, the review explores potential therapeutic strategies, such as lifestyle interventions and targeting obesity-driven inflammatory pathways, which could mitigate autoimmunity. Understanding the connection between obesity and autoimmunity offers insights into more effective interventions for patients suffering from these intertwined conditions.

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by persistent respiratory symptoms and airflow obstruction determined by spirometry, including emphysema, chronic bronchitis, and small airway disease. Traditional treatment settings for COPD exacerbations typically involve in-hospital care. However, hospital-at-home (HaH) programs have emerged as an innovative model to provide hospital-level care at a patient's home. I synthesized available randomized controlled trials (RCTs) and compared the outcomes of COPD management in HaH and in-hospital settings. I searched for English language medical literature studies of COPD patients in HaH programs compared to in-hospital. Searches were performed in PubMed, EMBASE, Scopus, and CENTRAL. Outcomes were compared, meta-analyses were performed, and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated and I² statistic was used to measure the proportion of inconsistency in individual studies. Potential publication bias was also calculated. Seven controlled studies representing 19 sub-studies (data sets) were selected according to the inclusion criteria. The OR of the HaH and in-hospital comparison was 0.542, 95%CI 0.379–0.774, P = 0.001. The different clinical outcomes of HaH were better or similar to those at regular hospitals, but with higher patient preference (OR 0.316, 95%CI 0.198–0.506). Heterogeneity and inconsistency were small, with no significant publication bias. HaH may be recommended for COPD patients' hospitalization when needed according to the specific indications and patients matching HaH criteria.

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.

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.

Background: Prior to the coronavirus disease 2019 (COVID-19) pandemic, bronchiolitis caused by respiratory syncytial virus (RSV) was primarily observed during the winter months. Recently, however, an increase in incidence during the warmer months has been noted. This trend suggests an interaction between RSV and coronavirus, as well as the impact of public health measures, such as hand hygiene, mask-wearing, and social distancing.

Objectives: To characterize bronchiolitis cases in children under 2 years old caused by RSV during the COVID-19 pandemic in Israel from 2018 to 2022.

Methods: We conducted retrospective study by analyzing medical records of children hospitalized with bronchiolitis from January 2018 to December 2022. A comparison was made between cases before and after the first COVID-19 lockdown.

Results: A total of 922 children with bronchiolitis were studied: 276 cases occurred before the lockdown and 646 cases afterward. We found an increase in bronchiolitis frequency during the summer following the lockdown and a decrease during the winter (P < 0.0001). In addition, there was a shift in the pathogenic profile, with a notable rise in mixed infections after the lockdown (P < 0.0001). No significant differences in clinical presentation were observed between pre- and post-lockdown periods.

Conclusions: There was a change in bronchiolitis seasonality after the lockdown, with a significant increase in cases during the summer and a rise in mixed infections. Further studies are needed to assess whether this shift is a lasting consequence of the pandemic or a temporary change.

Adoration of the Shepherds is one of the favorite subjects of sacred scripture by many artists. For almost 5 centuries they have published their vision of unique moments. The largest number of paintings were completed during the 16th and 17th centuries, with approximately 160 paintings created in the 16th century and approximately 420 in the 17th century. I was able to find two publications about pathological conditions of shephards that were diagnosed by artwork analysis. They include nodular goiter in Simone Veneziano Peterzano's works (1578–1582) [1] and Down syndrome in Jacob Jordaens' artwork (1618) [2]. In one of paintings, my attention was drawn to the change in the neck of one of the members of the Holy Family, St. Joseph.

Background: Solid organ transplant (SOT) recipients represent a particularly vulnerable group due to their reliance on immunosuppressive therapies. Previous studies indicated a mortality rate of 20%-30% among SOT recipients with coronavirus disease 2019 (COVID-19). With the advent of the Omicron variant in November 2021, characterized by milder symptoms and lower mortality rates in the general population, safety measures relaxed, potentially impacting vulnerable populations like SOT recipients.

Objectives: To investigate mortality and morbidity among hospitalized SOT recipients with COVID-19 infection during the Omicron wave.

Methods: A retrospective, propensity-matched cohort study conducted at the Rabin Medical Center, Israel, spanned from November 2021 to June 2023. Adult SOT recipients hospitalized with COVID-19 were compared to matched controls.

Results: Among 139 hospitalized SOT recipients and 209 controls, SOT recipients hospitalized with COVID-19 displayed higher in-hospital mortality (19% vs. 11%) and 90-day all-cause mortality (30% vs. 17%). In addition, the 90-day readmission rate was significantly higher among SOT recipients (43% vs. 31%). Multivariable analysis confirmed these trends, with SOT recipients exhibiting increased risk for mortality, readmission, invasive ventilation, and intensive care unit admission.

Conclusions: The heightened vulnerability of hospitalized SOT recipients during the Omicron wave was characterized by higher mortality and readmission rates compared to matched controls. Despite the perceived milder nature of the Omicron variant, SOT recipients remain disproportionately affected. Continued vigilance and targeted interventions are necessary for this population including vaccinations and adherence to preventive measures. Investigating this population’s outcomes through the changing COVID-19 variants is still warranted.

Crohn's disease patients undergoing anti-tumor necrosis factor (anti-TNF) therapy such as infliximab face potential risks from opportunistic infections. We introduce the unique case of a 66-year-old male Crohn's patient, previously in remission, presenting with gastrointestinal symptoms following a trip to the Czechia. Despite concerns of reactivated tuberculosis due to infliximab, his biopsies showed the presence of Mycobacterium simiae (M. simiae). Despite this, anti-TNF therapy was continued and resulted in clinical improvement. This is a case report of M. simiae in intestinal biopsies of an immunocompromised Crohn's patient is a clinical challenge. The findings suggest the benign colonization of M. simiae potentially influences future treatment considerations in similar clinical scenarios.

Background: Enterovirus meningitis (EM) is a common central nervous system (CNS) infection with a seasonal peak in summer and fall.

Objective: To describe the epidemiologic and clinical patterns of EM in children before (2017–2019 years) and during the coronavirus disease 2019 (COVID-19) pandemic (2020–2022).

Methods: This retrospective study included children (age 0–16 years) hospitalized in a pediatric department in Israel diagnosed with EM: January 2017–December 2019 and January 2020–December 2022. The seasonal peak for each period was defined as the maximal incidence in particular months. EM was diagnosed by reverse transcription polymerase chain reaction of cerebrospinal fluid (CSF) for enteroviruses.

Results: During the study period, EM was diagnosed in 134 cases (median age 5 months [1–51], 76 [57%] males); 72 during 2017–2019 and 62 during 2020–2022. The most common presentation was fever. C-reactive protein (CRP) was elevated in 57 cases (43%). CSF profile showed pleocytosis in 130 cases (97%) and elevated protein in 80 (60%). In the 2020–2022 group, fewer patients were febrile, CRP was higher, and CSF profile showed a higher glucose level compared to the 2017–2019 group. Seasonal peaks in 2017–2019 occurred June–August, and in 2020–2022 February–April.

Conclusions: The COVID-19 pandemic altered the clinical characteristics of EM and its seasonal peak. Clinicians should be aware of changes in epidemiological patterns of EM to make appropriate diagnoses in viral infection in order to avoid unnecessary antibiotic treatment.

Infant botulism is a rare and potentially fatal condition caused by intestinal colonization with Clostridium botulinum. Enteric toxin causes intestinal immobility and progressive descending paralysis due to the effect on acetylcholine release at the neuromuscular junction and other cholinergic nerve terminals, particularly in the gut [1].

We present a case of infant botulism, describe the characteristics of the disease, and focus on early diagnosis.

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.