Ocular manifestations and outcomes of OPMD- a report from the national IsrOPMD registry.

PURPOSE: This study aims to describe the ocular manifestations, treatment, and prognosis of OPMD patients registered in the national Israel OPMD(IsrOPMD) registry. METHODS: Data was prospectively collected from patients referred to the IsrOPMD registry from January 2022 to March 2023. This included patient demographics, medical and ocular history, eye exams, eyelid evaluations, visual field exams, and orthoptic evaluations. RESULTS: 30 patients (15 males, mean age 53 years) were treated in the ocular OPMD clinic, predominantly of Bukhari descent (86.6%). The mean visual acuity was 0.06 logMAR. Twenty-one patients (70%) had eye movement problem, mostly in horizontal gaze. 6(20%) patients' complaint about diplopia. Ptosis surgery was performed in 21(70%) patients, with 17(56.7%) patients underwent frontalis sling surgery and 4(13.3%) patients undergoing levator advancement. The mean Margin reflex distance (MRD1) improved post-surgery (2.28 mm vs. 1.58 mm), but 11(36.6%) patients required more than one ptosis surgery. CONCLUSIONS: The study contributes valuable insights into the ocular aspects of OPMD. It reveals that OPMD patients often experience a range of ocular symptoms, such as ptosis, abnormalities in eye movements, strabismus, and potentially diplopia, which can significantly impact their quality of life. The findings underscore the importance of regular ophthalmological follow-up for these patients to address these symptoms effectively. The study is significant in contributing to the limited but growing knowledge about the ocular manifestations of OPMD and the management of these symptoms to improve the quality of life for patients suffering from this condition.

A Mobile Health App for Facilitating Disease Management in Children With Atopic Dermatitis: Feasibility and Impact Study.

BACKGROUND: Inadequate control of atopic dermatitis (AD) increases the frequency of exacerbations and reduces the quality of life. Mobile health apps provide information and communication technology and may increase treatment adherence and facilitate disease management at home. The mobile health app, Atopic App, designed for patients and their caregivers, and the associated web-based patient education program, Atopic School, provide an opportunity for improving patients' and caregivers' engagement and adherence to the management of AD. OBJECTIVE: This noninterventional, observational study aimed to explore the feasibility and potential impact on the management of AD in children by caregivers using the Atopic App mobile health app. METHODS: The patient-oriented eczema measure (POEM) and numerical rating scale for the grading of pruritus were used as severity scores (scale range: 0-28). The artificial intelligence model of the app was used to assess the severity of AD based on the eczema area and severity index approach. The deidentified data enabled the analysis of the severity of AD, treatment plan history, potential triggers of flare-ups, usage of available features of the app, and the impact of patient education. RESULTS: During a 12-month period, of the 1223 users who installed the app, 910 (74.4%) registered users were caregivers of children with AD. The web-based Atopic School course was accessed by 266 (29.2%) caregivers of children with AD, 134 (50.4%) of whom completed the course. Usage of the app was significantly more frequent among those who completed the Atopic School program than among those who did not access or did not complete the course (P<.001). Users who completed a second POEM 21 to 27 days apart exhibited a significant improvement of AD severity based on the POEM score (P<.001), with an average improvement of 3.86 (SD 6.85) points. The artificial intelligence severity score and itching score were highly correlated with the POEM score (r=0.35 and r=0.52, respectively). CONCLUSIONS: The Atopic App provides valuable real-world data on the epidemiology, severity dynamics, treatment patterns, and exacerbation-trigger correlations in patients with AD. The significant reduction in the POEM score among users of the Atopic App indicates a potential impact of this tool on health care engagement by caregivers of children with AD.

Cutaneous Leishmaniasis Treated with Miltefosine: A Case Series of 10 Paediatric Patients.

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.

Cutaneous Leishmaniasis Treated with Miltefosine: A Case Series of 10 Paediatric Patients.

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.

Vascular lesions in genital lichen sclerosus in pediatric patients.

BACKGROUND/OBJECTIVES: Lichen sclerosus is a rare, pruritic, mucocutaneous disease affecting mostly the anogenital area. Reports have occasionally associated lichen sclerosus with overlapping vascular lesions. This study explores this association in children. METHODS: A retrospective study was conducted in the dermatology unit of a pediatric tertiary care medical center. Electronic medical records were searched for patients diagnosed with lichen sclerosus from 2006 to 2019. Review of the cases was performed to identify overlapping vascular lesions and review the clinical course of overlap cases. RESULTS: Of 74 children diagnosed with lichen sclerosus during the study period, five (6.75%) had overlapping vascular lesions and genital lichen sclerosus. Four patients presented with reticular telangiectatic macules and patches (n = 4, 5.4%) that appeared at or shortly after disease onset; resolution occurred a few months after treatment initiation. The fifth patient presented with telangiectases that appeared more than 2 years after the onset of the first symptoms of lichen sclerosus (n = 1, 1.3%). CONCLUSION: Vascular lesions in children with genital lichen sclerosus are common and have variable clinical manifestations. Early appearance of reticular macules, patches, and papules is a variant of the disease and is followed by prompt resolution of these lesions. Pathogenesis is attributed to structural changes and repositioning of the papillary vascular plexus. These changes may be alarming to parents and therefore must be recognized by physicians to prevent unnecessary concern and investigations.

[NEUTROPHILIC DERMATOSIS OF THE HANDS ASSOCIATED WITH CHRONIC LYMPHOCYTIC LEUKEMIA].

INTRODUCTION: Neutrophilic dermatosis of the hands (NDH) is a rare localized variant of Sweet's syndrome occurring predominantly over dorsa of hands. Both Sweet's syndrome and its dorsal hand variant have been reported in association with malignancies, inflammatory bowel diseases, and drugs. We report a patient with neutrophilic dermatoses of dorsal hands associated with chronic lymphocytic leukemia (CLL).

DEGS1 variant causes neurological disorder.

Sphingolipidoses are monogenic lipid storage diseases caused by variants in enzymes of lipid synthesis and metabolism. We describe an autosomal recessive complex neurological disorder affecting consanguineous kindred. All four affected individuals, born at term following normal pregnancies, had mild to severe intellectual disability, spastic quadriplegia, scoliosis and epilepsy in most, with no dysmorphic features. Brain MRI findings were suggestive of leukodystrophy, with abnormal hyperintense signal in the periventricular perioccipital region and thinning of the body of corpus callosum. Notably, all affected individuals were asymptomatic at early infancy and developed normally until the age of 8-18 months, when deterioration ensued. Homozygosity mapping identified a single 8.7 Mb disease-associated locus on chromosome 1q41-1q42.13 between rs1511695 and rs537250 (two-point LOD score 2.1). Whole exome sequencing, validated through Sanger sequencing, identified within this locus a single disease-associated homozygous variant in DEGS1, encoding C4-dihydroceramide desaturase, an enzyme of the ceramide synthesis pathway. The missense variant, segregating within the family as expected for recessive heredity, affects an evolutionary-conserved amino acid of all isoforms of DEGS1 (c.656A>G, c.764A>G; p.(N219S), p.(N255S)) and was not found in a homozygous state in ExAC and gnomAD databases or in 300 ethnically matched individuals. Lipidomcs analysis of whole blood of affected individuals demonstrated augmented levels of dihydroceramides, dihydrosphingosine, dihydrosphingosine-1-phosphate and dihydrosphingomyelins with reduced levels of ceramide, sphingosine, sphingosine-1-phosphate and monohexosylceramides, as expected in malfunction of C4-dihydroceramide desaturase. Thus, we describe a sphingolipidosis causing a severe regressive neurological disease.

Biologic treatment of recalcitrant pediatric psoriasis: a case series from a tertiary medical center.

BACKGROUND: There is a paucity of data on the use of biologic therapy in recalcitrant pediatric psoriasis. The current study presents pediatric psoriasis cases treated with biologic agents in a tertiary referral center. METHODS: In this retrospective case series, data were collected on all patients ≤18 years old with severe psoriasis treated with biological therapy from 2010 through 2016 in a tertiary children's hospital. We included demographic data, previous systemic treatments, reason for discontinuation or switch to other systemic treatments, efficacy and side effects. RESULTS: There were 10 patients, mean age 5.75 (±3.3) years treated with biologic agents in our center; Etanercept was the most frequent biological treatment prescribed (n = 9) followed by adalimumab (n = 5) ustekinumab (n = 3) and infliximab (n = 2). Additional systemic therapy was added to the biological therapy in seven cases: Methotreaxate (n = 5), phototherapy (n = 4), cyclosporine A and colchicine (1 case each). The most common reason for discontinuation was secondary failure (5 for etanercept, 3 for adalimumab). Six patients failed one biological treatment and three patients failed two biological treatments. Four patients are still being treated with a first line biologic (Etanercept in all). Adverse events were rare. CONCLUSION: Biologic therapy is effective and safe in recalcitrant pediatric psoriasis. Larger series are needed to confirm our observation.

Risk of Attention-Deficit/Hyperactivity Disorder in Children with Atopic Dermatitis.

Atopic dermatitis (AD) is a common, chronic, inflammatory, pruritic skin disorder that affects up to 20% of the children in Western countries. Attention-Deficit/Hyperactivity disorder (ADHD) has been reported to be more frequent in children with AD. The purpose of this study was to explore the risk for ADHD in our population of patients with AD. A population-based case-control study, using the medical database of Clalit Health Services (CHS), the largest healthcare provider organization in Israel. The study included 840 patients with AD between the age of 0-18 years and 900 age and gender frequency-matched patients without AD. The proportion of ADHD in patients with AD was 7.1% as compared to 4.1% in controls. ADHD was more frequent in boys with AD (9.6% vs. 5.2%, odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.2) but not in girls with AD (4.6% vs. 2.9% OR 1.5). In multivariate analyses, AD was associated with ADHD (OR 2.1, 95% CI 1.3-3.4). The current study demonstrated an association between AD and ADHD. This report and earlier observations emphasize the need for detection and treatment of ADHD in atopic patients.

Propranolol treatment for infantile hemangioma does not increase risk of childhood wheezing.

OBJECTIVE: Propranolol is the treatment of choice for infantile hemangiomas requiring medical intervention. Although contraindicated in asthma, its bronchoconstrictive effect in infants and children has not been extensively studied. We aimed to assess the incidence of wheezing episodes in infants and children treated with propranolol for infantile hemangiomas. STUDY DESIGN: A retrospective case-control study. SETTING: a tertiary pediatric hospital. PATIENTS: All Children followed for infantile hemangioma between 2009 and 2014. Children followed conservatively served as control group and were matched 1:1 for gender and month of birth by random matching to children treated with propranolol. INTERVENTIONS: All respiratory episodes (asthma, wheezing, stridor, and pneumonia) and respiratory associated hospitalizations were recorded from hospital records, from the primary care physician visits records and pharmacy prescriptions. The main outcome measure was the incidence of respiratory episodes in the treatment and the control groups. RESULTS: A total of 1828 clinic visits were reviewed for 683 children. In addition, primary care physician visits records were available in 80% of them. Two hundred and sixteen children were treated with propranolol. Incidence of respiratory episodes and recurrent respiratory episodes was similar in the propranolol and control groups (8.3% vs 12%, P = 0.265; 3.7% vs 6.5%, P = 0.274, respectively). Time to first episode was similar in the treatment and control groups (5.03 ± 3.32 vs 4.45 ± 3.21 months, respectively, P = 0.09). Respiratory hospital admission rate was similar in both groups. CONCLUSIONS: Propranolol treatment does not exacerbate wheezing episodes in infants and children.

Screening for Brain Involvement in Infants with Multifocal Cutaneous Infantile Hemangiomas.

BACKGROUND: Multifocal (≥5) infantile hemangiomas (IHs) are known as a risk factor for extracutaneous involvement. Liver is the most commonly involved organ, but involvement of other systems has also been reported. This study aims to describe the characteristic findings in a group of infants with multiple cutaneous hemangiomas, with emphasis on intracranial involvement. METHODS: A retrospective case series study was carried out in a pediatric dermatology unit of a tertiary pediatric medical center. Patients diagnosed with multiple cutaneous IHs from 2006 to 2015 were identified by a computerized search. Clinical data were retrieved from the medical charts. RESULTS: A total of 60 infants (37 females and 23 males) were identified for analysis. Forty-four brain ultrasounds were recorded and reported as normal. One patient out of the 44 was later diagnosed with a small asymptomatic hemangioma seen on a brain MRI/MRA done for another indication. CONCLUSION: Brain hemangiomas may present as an asymptomatic incidental finding in infants presenting with multifocal cutaneous and liver IHs. The single case reported in our study emphasizes the low prevalence and the benign course expected. Therefore, routine ultrasound screening for brain involvement is probably unnecessary for this population.

Propranolol induced hypoglycemia.

ince 2008, propranolol has become the first line therapy for infantile hemangiomas. Due to the fact that infantile hemangiomas are the most common vascular tumors of infancy, the use of systemic propranolol has been dramatically increased in the last few years. The reported adverse effects of propranolol in the treatment of infantile hemangiomas included symptomatic hypoglycemia. In this review we will summarize those reports and will offer guidelines for prevention of hypoglycemia secondary to propranolol therapy.

Thiamine deficiency in infancy: long-term follow-up.

BACKGROUND: In 2003, several hundred Israeli infants risked thiamine deficiency after being fed a soy-based formula deficient in thiamine. Approximately 20 patients were seriously affected, and three of them died. We report the clinical presentation of acute encephalopathy in 11 children and the long-term sequelae of eight children who initially survived. PATIENTS: In the acute phase, six had bulbar signs, five had ophthalmologic signs and two had phrenic neuropathy. Three of the five patients with cardiac involvement had cardiomyopathy and died in the acute phase. One patient presented with a complete atrioventricular block. RESULTS: In the long-term, one patient, who was in a chronic vegetative state, died after 6 years. Seven children exhibited mental retardation and motor abnormalities, six developed severe epilepsy, two early kyphoscoliosis, and one patient remained with a complete atrioventricular block. CONCLUSIONS: Infants who survive severe infantile thiamine deficiency have serious residual motor and cognitive sequelae as well as epilepsy.

Juvenile mycosis fungoides: cutaneous T-cell lymphoma with frequent follicular involvement.

BACKGROUND: The literature on mycosis fungoides (MF) in children/adolescents is sparse. OBJECTIVE: We sought to evaluate the characteristics of juvenile MF in a large cohort. METHODS: Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively. RESULTS: There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA. LIMITATIONS: Relatively short follow-up is a limitation. CONCLUSIONS: This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear.

Efficacy and safety of propranolol for the treatment of infantile hemangioma: a presentation of ninety-nine cases.

BACKGROUND: Propranolol is highly effective in the treatment of infantile hemangioma (IH), but important clinical and pharmacological data are lacking. OBJECTIVE: The aims of the present study were to evaluate the efficacy of propranolol for the treatment of IH, to identify favorable prognostic factors in propranolol-treated IH, and to evaluate the safety of propranolol for the treatment of IH. METHODS: Clinical data were recorded from the electronic files and digital photographs of 99 patients with IH attending a tertiary pediatric medical center (2008-2011). Findings were evaluated by regression in volume and color changes. RESULTS: The male-to-female ratio was 1:4. Age at treatment initiation was 9.4 ± 10.1 months; 15% of the treated hemangiomas were beyond the proliferative phase (17-54 months). The propranolol starting dose was 2 mg/kg/day. Duration of the treatment was 8.5 ± 3.2 months. All but 1 patient responded to treatment. A longer treatment course was required for segmental and deep hemangiomas. Mild side effects occurred in 32% of patients. Recurrence occurred in 13% of patients. CONCLUSION: Lesions located on the face are better responders when treatment is started early. Treatment should continue up to age 12-15 months, with a longer course for segmental or deep hemangiomas.

Pulse corticosteroid therapy for alopecia areata in children: a retrospective study.

BACKGROUND/OBJECTIVE: Alopecia areata may occur at any age, though usually before the age of 20 years. Treatment often consists of systemic steroids administered as high-dose bolus infusions. This study sought to investigate the effectiveness and side effects of intravenous high-dose pulse corticosteroids in children with alopecia areata and to identify prognostic factors for successful treatment. METHODS: Patients treated with pulse corticosteroids for alopecia areata in 2001-2008 at the day care unit of a tertiary pediatric medical center were identified by computerized file search and clinical treatment and outcome data were collected. RESULTS: The sample included 24 children (16 female, 8 male) with a mean age of 8.5 ± 4.6 years at diagnosis; 8 (33%) had multifocal disease,10 (42%) multifocal disease with ophiasis, 4 (17%) alopecia totalis and 2 (8%) alopecia universalis. Nail involvement was noted in 9 patients (38%). Mean duration of disease was 22 ± 27 months. Patients were treated with 8 mg/kg body weight intravenous methylprednisolone on 3 consecutive days at 1-month intervals. After a mean of 5.65 ± 1.95 courses, 9 patients (38%) had a complete response, 7 (29%) a partial response and 8 (33%) no response. Of the 16 responders, 13 (81%) relapsed at 9.5 ± 12 months after the last course; 3 patients had side effects, none of which were severe. Three positive prognostic factors were identified: short disease duration (≤6 months), younger age at disease onset (<10 years) and multifocal disease (as opposed to severe, diffuse variants). CONCLUSIONS: Careful patient selection is necessary to achieve maximal benefit from pulse corticosteroid treatment for alopecia areata in children.

Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.

Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.

Clinical and histopathologic spectrum of alopecia mucinosa/follicular mucinosis and its natural history in children.

BACKGROUND: Some authorities consider alopecia mucinosa (AM)/follicular mucinosis (FM) to invariably represent mycosis fungoides (MF). This understanding of AM/FM derives from observations in adults. OBJECTIVES: We sought to explore the clinicopathologic features and natural history of pediatric AM/FM. METHODS: Medical records were searched for children given the diagnosis of AM/FM from 1998 through 2009. Diagnosis of AM/FM was defined as the presence of well-demarcated hairless plaques with follicular prominence plus an abundance of mucin on histopathologic examination. RESULTS: Forty children with a clinical diagnosis of AM/FM were identified. Nine did not meet the inclusion criteria. In the 31 remaining cases (16 boys, 15 girls) the mean age at onset was 9 ± 3.5 years. Histopathologic examination showed folliculotropism in 28 patients (90%) and epidermotropism in 15 (48%). Twelve cases fulfilled the International Society of Cutaneous Lymphomas (ISCL) diagnostic criteria for early MF. The histopathologic findings were typical of MF in only in two of these cases. T-cell receptor gene rearrangement was positive in 3 of 6 (50%) of tested samples, one in a patient who fulfilled the ISCL criteria for early MF. Mean duration of follow-up was 6.2 ± 3.7 years. All skin lesions resolved and none persisted or recurred. Hodgkin lymphoma was diagnosed 6 months after diagnosis of AM/FM in one patient. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Although some pediatric cases meet the diagnostic criteria for MF, AM/FM cannot be regarded unequivocally as early follicular MF in this age group. We suggest the current diagnostic criteria for early MF should exclude children with AM/FM. Long-term follow-up of children with AM/FM is nevertheless warranted.