Israel Medical Association Journal

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.

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.

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.

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.

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.

Background: High prevalence of hepatitis C (HCV) among people with severe mental illness (SMI) is attributed mostly to current or past intravenous (IV) drug use. However, such history may disappear from patient files over time, especially in chronic SMI with prolonged psychiatric admissions.

Objectives: To explore HCV and SMI cross-morbidity (HCV/SMI) in a hospitalized population.

Methods: In this observational, retrospective, historical computerized study we examined prevalence, characteristics, and outcomes of patients with HCV/SMI compared to HCV alone in patients admitted to an Israeli hospital 1 January 2005 to 31 December 2020.

Results: Of 1638 eligible HCV patients, 219 (13.4%) were HCV/SMI. Significantly more native Israelis showed HCV/SMI than HCV alone (36.1% vs. 18.1%, P = 0.013) and history of IV drug use (60.3% vs. 32.4%, P < 0.001). Among Israeli natives, more Jews were SMI/HCV compared to HCV only (67.1% vs. 45%, P < 0.01). Among non-native Israelis, immigration age was lower in SMI/HCV compared to HCV only (27.97 vs. 37.23 years, P < 0.001). No differences were found in mortality or cirrhosis, although HCV/SMI patients experienced earlier mortality compared to HCV alone (61.42 ± 14.3 vs. 72.8 ± 14.6 years, P < 0.001). Cirrhosis among HCV/SMI patients was a risk factor for early mortality (hazard ratio 5.528, 95% confidence interval 3.721–8.213).

Conclusions: HCV/SMI is related to early mortality, particularly with cirrhosis. There is significantly high SMI prevalence in hospitalized HCV patients, representing a unique at-risk population. Identification during hospitalization and medical recommendations at discharge may fill the gaps.

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: Hyponatremia is common among hospitalized children, including those with community acquired pneumonia. The prevalence and severity of hyponatremia were reported to correlate with disease. However, data regarding the association between hyponatremia and causative infectious pathogens are limited and results are inconsistent.

Objectives: To investigate the associations between sodium levels, severity and causative pathogen in children with pneumonia.

Methods: A retrospective study of all children (< 18 years) hospitalized with pneumonia from 1 January 2018 to 31 December 2020. Admission sodium levels were compared to the presumed etiological pathogens, clinical parameters, and inflammatory markers.

Results: Among 751 (52% males) children, 10 (1%) had sodium levels < 130 mEq/L, 187 (25%) had mildly decreased levels 130–134 mEq/L, and the remaining 554 (74%) had normal levels 135–145 mEq/L. Sodium levels < 130 mEq/L were found in 7/236 (3%) of the patients with presumed bacterial pneumonia, in 0/20 of patients with presumed atypical-bacterial, and in only 3/495 (0.6%) of the patients with a presumed viral infection, P < 0.001. Sodium levels < 135 mEq/L conferred an odds ratio of 3.1 (95% confidence interval [95%CI] 2.1–4.3) and levels < 130 mEq/L an odds ratio of 6.8 (95%CI 1.8–33.0) for bacterial infection, P < 0.001 for both. Hyponatremia was also inversely associated with high white blood cell counts, absolute neutrophil cell counts, and C-reactive protein levels.

Conclusions: Hyponatremia was common among children hospitalized with pneumonia and was associated with elevated inflammatory markers and presumed bacterial pneumonia.

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.

Postmortem sperm retrieval allows for the procreation of biological children using the sperm of a deceased male; however, the data on how to optimize this procedure and its potential long-term effect are limited. We searched medical databases (PUBMED and Cochrane) and performed a systematic review of articles published from the databases' inception until December 2023. Case reports, case studies, and reviews reporting on and investigating the methodology and outcome of postmortem sperm retrieval were included. The primary search yielded 98 publications. After assessing eligibility and evaluating with a quality assessment tool, 17 articles remained, including 11 single case reports and 6 case series. Overall, 103 clinical cases of posthumous sperm retrieval were identified, and eight deliveries were reported. Most publications lacked information regarding the conditions to which the bodies were exposed before postmortem sperm retrieval. Moreover, sperm viability assessment was not performed routinely, and there was no examination of the potential genetic and epigenetic damage that may have occurred. Currently, there is a lack of standardization for postmortem sperm retrieval procedures. The lack of specific information regarding the potential hypoxic damage to the viable sperm cells may limit the safety of using these cells for procreation. These gaps in our current knowledge are relevant and should be expressed in the informed consent given to the potential users.

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.

Background: Chest radiograph is a standard procedure for diagnosis of pneumonia; however, interpretation shows considerable variability among observers.

Objectives: To assess the extent of agreement between pediatric residents and board-certified radiologists in interpretation of chest radiography for detection of pneumonia. To evaluate the impact of resident experience, patient age, and signs of infection on this phenomenon.

Methods: The cohort included 935 patients with suspected pneumonia admitted to the pediatric emergency department at a non-tertiary medical center in Israel 2019–2021. All patients had chest radiographs interpreted by a resident and a radiologist. Interobserver agreement was assessed using Κ and prevalence-adjusted bias-adjusted κ (PABAK) with 95% confidence intervals (95%CI). Results were stratified by resident experience (junior or senior), patient age (≤ 3 vs. > 3 years), white blood cells (≤ 15,000 vs. > 15,000 cells/ml), C-reactive protein (≤ 5 vs. > 5.0 mg/dl), and temperature (< 38.0°C vs. ≥ 38.0°C).

Results: Moderate agreement between pediatric residents and radiologists was demonstrated for diagnosis of pneumonia (κ= 0.45). After adjustment for disease prevalence, the extent of agreement increased to near-substantial (PABAK= 0.59, 95% confidence interval 0.54–0.64). The extent of agreement was higher for children over 3 years of age and in patients without clinical or biochemical features of pneumonia, especially when diagnosis of pneumonia was ruled out.

Conclusions: A second reading of chest radiographs by an experienced radiologist should be considered, particularly for patients younger than 3 years of age and in those with signs of infection and an initial diagnosis of pneumonia.