Paediatric-onset lymphomatoid papulosis: results of a multicentre retrospective cohort study on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce. OBJECTIVES: To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP. METHODS: This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0-14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0-19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP.

Lymphomatoid papulosis is a very rare skin condition caused by an abnormal increase in white blood cells (called 'lymphocytes') in the skin. The condition rarely affects children, so most of the scientific data published about this disease focuses on adults. This study involved 12 academic dermatology centres in Europe, the Middle East and North America, and gathered data from about 87 children who presented with symptoms of lymphomatoid papulosis before the age of 19 years. The aim of this study was to better describe this disease in the paediatric population and discuss its treatment options and evolution. We found that the presentation of the disease in children is roughly the same as in adults. Safe and effective treatment options exist. The disease is not life threatening, but it requires investigation by a dermatologist, both to make a careful diagnosis and to monitor it as sometimes associated cancers that originate from blood cells can occur, mostly on the skin.

Cutaneous Reactions in Pediatric Patients Treated with MEK Inhibitors: A Retrospective Single-Center Study.

INTRODUCTION: Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency, and severity in a cohort of pediatric patients. METHODS: We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications. RESULTS: Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with a combination of trametinib and B-Raf proto-oncogene serine/threonine-protein kinase inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia, and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded. CONCLUSIONS: Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents.

Paradoxical Psoriasiform Skin Eruption in Pediatric Patients with Inflammatory Bowel Disease Treated with TNFα Inhibitors.

BACKGROUND: Tumor necrosis factor α inhibitors (TNFαI)-induced psoriasiform eruptions are a well-known phenomenon among adults. However, data are limited regarding this reaction in children. OBJECTIVES: To describe in pediatric patients with inflammatory bowel diseases (IBD), the clinical characteristics of TNFαI-induced psoriasiform eruptions and the outcomes of various therapeutic options. METHODS: We reviewed the medical charts of pediatric patients (aged <18 years old) with IBD who developed TNFαI-induced psoriasiform eruptions during 2006-2022. RESULTS: Among 454 patients with IBD treated with TNFαI, 58 (12.8%) were diagnosed with TNFαI-induced psoriasiform eruptions, of whom 51 were included in the study. The female to male ratio was 1:1.3. The median age at skin eruption was 14.1 [interquartile range, 12.11-16.05] years. The median elapsed time to eruption appearance was 15 [interquartile range, 7-24] months after initiation of the treatment. All the patients were treated with topical steroids and 17 (33%) needed systemic treatment (phototherapy, methotrexate or acitretin). Sixteen patients (31%) needed to stop TNFαI treatment due to an intractable eruption. Female patients, patients with inflammatory alopecia and patients who were treated with methotrexate or phototherapy were more prone to stop TNFαI. CONCLUSIONS: TNFαI-induced psoriasiform eruptions are common in pediatric patients with IBD. The eruption may appear months or even years after treatment initiation. Almost one-third of the described patients had to replace their treatment due to a recalcitrant cutaneous eruption. This indicates that a multidisciplinary approach is required for effective management.

Verrulyse Methionine® as Monotherapy in Children and Adolescents With Common Warts.

BACKGROUND: Common cutaneous non-genital viral warts are a common skin infection with significant morbidity in the pediatric population. Although various therapeutics are available, many of them necessitate recurrent patient visits and may be associated with significant irritation and pain. Verrulyse Methionine® (VM), a nutritional supplement, was previously suggested as a non-invasive treatment option for the disease. OBJECTIVE: To assess the response to oral VM supplement as a monotherapy in a cohort of children and adolescents with multiple, non-genital viral warts after failing previous treatments. METHODS: We reviewed medical records of pediatric patients (<18 y/o) with viral warts treated with VM between 2010 and 2021. RESULTS: Among 25 patients with multiple verrucae vulgaris lesions who failed previous treatments, 14 (56%) had complete or almost-complete response to VM within 4 months, after an average of 18 months of active disease prior to VM treatment initiation. None of the 4 patients with verruca plana had response to VM treatment. Favourable cosmetic results were found in responders, and no adverse events were recorded. CONCLUSION: Response rates in our cohort are comparable to those reported in the literature for destructive local therapeutics for viral warts. Thus, our data suggest that VM may be considered for children with multiple verrucae vulgaris, providing a painless and non-invasive therapeutic option for this common disease.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. OBJECTIVE: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. METHODS: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. RESULTS: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1). CONCLUSIONS: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

Treating pediatric cutaneous Leishmania tropica with systemic liposomal amphotericin B: A retrospective, single-center study.

Leishmania tropica (L. tropica) cutaneous leishmaniasis (CL) is associated with high morbidity and low response rate to therapy, especially in pediatric patients. Intravenous (IV) liposomal amphotericin B (LAmB) has been used off-label as a treatment for L. tropica CL for many years. However, data regarding its efficacy and safety in children is lacking. In order to evaluate the efficacy and safety of IV LAmB for treating pediatric patients with L. tropica, we retrospectively reviewed electronic medical records of 24 children who were diagnosed with L. tropica CL and treated with IV LAmB during 2014-2020, at a tertiary medical center in Israel. Fourteen (58%) completed the treatment protocol and 10 (42%) experienced an infusion-related adverse event (IRAE) leading to treatment termination. Complete response was noted in 6/14 (43%) patients, while 8/14 (57%) failed to respond. Lower response rate was noted in lesions involving the mid-facial area. The relatively low response rate is speculated to result from a low dose of LAmB, short follow-up period, and difficult to treat anatomic locations. The observation of a lower response rate for mid-facial lesions should be validated in larger cohorts. The highrisk of IRAE should be considered in physician decisions regarding this treatment.

Psoriasis and Renal Disorders: A Large-Scale Population-Based Study in Children and Adults.

BACKGROUND: Psoriasis is a systemic disease with associated comorbidities. An association between renal diseases and psoriasis has previously been reported in adult patients, but little is known about renal diseases in pediatric patients. OBJECTIVE: To determine whether there is an association between psoriasis and renal comorbidities in adult and pediatric patients. METHODS: This cross-sectional study analyzed the database of the largest health care maintenance organization in Israel. Logistic regression was used to calculate odds ratios to compare 68,836 psoriatic patients and 68,836 controls with respect to renal comorbidities. RESULTS: In adults, an inverse association emerged between psoriasis and dialysis (OR, 0.69; 95% CI, 0.58-0.83) and kidney transplantation (OR, 0.60; 95% CI, 0.43-0.83), a positive association with other kidney diseases (OR, 1.09; 95% CI, 1.05-1.13), and no association between psoriasis and chronic kidney disease (OR, 1.03; 95% CI, 0.98-1.09). Comparing 9,127 pediatric patients and 9,478 controls, no association was found between psoriasis and renal comorbidities, chronic kidney disease (OR, 0.90; 95% CI, 0.33-2.48), dialysis (OR, 2.06; 95% CI, 0.19-22.69), kidney transplantation (OR, 0.34; 95% CI, 0.04-3.29), or other kidney diseases (OR, 0.98; 95% CI, 0.79-1.23), even after a multivariate analysis adjusting for putative confounders. CONCLUSION: As opposed to adult patients, pediatric patients with psoriasis were not shown at risk of kidney diseases.

Epidemiologic features and risk of scarring in pediatric patients with kerion celsi.

BACKGROUND: Kerion celsi represents the inflammatory extreme of tinea capitis, as a delayed hypersensitivity reaction to the causative dermatophyte. Data regarding prevalence, trends in pathogens, and risk factors for scarring are limited. OBJECTIVE: The main objective of the study is to assess clinical and epidemiologic features of children with kerion celsi and risk factors for scarring. METHODS: We reviewed medical records of pediatric patients with kerion celsi treated between January 2006 and July 2020. RESULTS: Among 80 patients, the prevalence of permanent alopecia was 27.5%. Patients with remaining alopecia presented to our clinic at a mean 1.3 months earlier than those with complete response to treatment (2.2 ± 2.1 and 3.4 ± 4.8, respectively; p < .05). Patients of Ethiopian ethnicity were more represented than in the general population; however, scarring was observed in only 11% (p = 0.08). Outcomes did not differ by pathogen, antifungal treatment prescribed, duration of treatment, or the use of prednisone or antibiotics. CONCLUSIONS: Scarring alopecia is a common complication of kerion celsi. Host innate immune response, pathogen virulence, and treatment timeline should be considered as possible variables affecting risk of scarring in the future studies.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

Trametinib for orbital plexiform neurofibromas in young children with neurofibromatosis type 1.

INTRODUCTION: Plexiform neurofibromas (PNF) in neurofibromatosis type 1 (NF1) are usually diagnosed in childhood and can grow rapidly during this period. In 10% of patients, PNF involve the orbital-periorbital area and may cause visual problems including glaucoma, visual loss from amblyopia (deprivational, strabismic, or refractive), optic nerve compression, or keratopathy. Ptosis, proptosis, and facial disfigurement lead to social problems and decreased self-esteem. Complete surgical removal involves significant risks and mutilation, and regrowth after debulking is not uncommon. Inhibitors of the RAS/MAPK pathway have recently been investigated for their activity in PNF. We administered the oral MEK inhibitor trametinib to five young children with NF1 and PNF of the orbital area, with visual compromise and progressive tumor growth; and followed them clinically and by volumetric MRI. METHODS: Treatment was initiated at a mean age of 26.8 months (SD ± 12.8) and continued for a median 28 months (range 16-51). Doses were 0.025 mg/kg/day for children aged > 6 years and 0.032 mg/kg/day for those aged < 6 years. RESULTS: Volumetric MRI measurements showed a reduction of 2.9-33% at 1 year after treatment initiation, with maximal reductions of 44% and 49% in two patients, at 44 and 36 months, respectively. No change in visual function was recorded during treatment. One child reported decreased orbital pain after 2 weeks; and another, with involvement of the masseters, had increased ability to chew food. Toxicities were mostly to skin and nails, grades 1-2. CONCLUSIONS: Trametinib can decrease tumor size in some young children with orbital PNF and may prevent progressive disfigurement.

The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex.

Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to "ash-leaf like" hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.

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.

Cutaneous presentations of omphalomesenteric duct remnant: A systematic review of the literature.

BACKGROUND: Disorders of the umbilicus are commonly seen in infancy, including hernias, infections, anomalies, granulomas, and malignancies. Meticulous inspection of the umbilicus at birth might reveal a persisting embryonic remnant, such as an omphalomesenteric duct (OMD), manifested by a variety of cutaneous signs, such as an umbilical mass, granulation tissue, or discharge. OBJECTIVE: To systematically review the available data regarding the presence and management of OMD remnant with cutaneous involvement to suggest a practical approach for diagnosis and treatment. METHODS: A systematic review of the literature evaluating OMD anomalies presenting with cutaneous symptoms was performed. In addition, an index case of an 11-month-old patient is presented. RESULTS: We included 59 publications reporting 536 cases; 97% of the patients whose age was noted were infants (mean age 11 months). In 7.5% of the cases, diagnosis was established only after treatment failure. In 6.4% of patients, nonlethal complications were reported, and in 10.3%, the outcome was death, partly due to delayed diagnosis or mismanagement. LIMITATIONS: Limited quality of the collected data, reporting bias. CONCLUSION: OMD is relatively rare; however, the clinician must consider this remnant while examining patients with umbilical abnormalities because mismanagement could cause severe morbidity and mortality.

An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis.

BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking because the underlying molecular basis is poorly understood. OBJECTIVE: We sought to characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsy specimens from 21 genotyped patients with ichthyosis (congenital ichthyosiform erythroderma, n = 6; lamellar ichthyosis, n = 7; epidermolytic ichthyosis, n = 5; and Netherton syndrome, n = 3) using immunohistochemistry and RT-PCR and compared them with specimens from healthy control subjects, patients with atopic dermatitis (AD), and patients with psoriasis. Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); transepidermal water loss; and pruritus. RESULTS: Ichthyosis samples showed increased epidermal hyperplasia (increased thickness and keratin 16 expression) and T-cell and dendritic cell infiltrates. Increases of general inflammatory (IL-2), innate (IL-1ß), and some TH1/interferon (IFN-γ) markers in patients with ichthyosis were comparable with those in patients with psoriasis or AD. TNF-α levels in patients with ichthyosis were increased only in those with Netherton syndrome but were much lower than in patients with psoriasis and those with AD. Expression of TH2 cytokines (IL-13 and IL-31) was similar to that seen in control subjects. The striking induction of IL-17-related genes or markers synergistically induced by IL-17 and TNF-α (IL-17A/C, IL-19, CXCL1, PI3, CCL20, and IL36G; P < .05) in patients with ichthyosis was similar to that seen in patients with psoriasis. IASI and IASI-E scores strongly correlated with IL-17A (r = 0.74, P < .001) and IL-17/TNF-synergistic/additive gene expression. These markers also significantly correlated with transepidermal water loss, suggesting a link between the barrier defect and inflammation in patients with ichthyosis. CONCLUSION: Our data associate a shared TH17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17-targeting strategies.

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.

Diagnosis, treatment, and long-term outcomes of pediatric pemphigus: a retrospective study at tertiary medical centers.

BACKGROUND: Pediatric pemphigus is a rare bullous disease that represents a diagnostic and therapeutic challenge;  evidence on patients' response to various treatments and long-term surveillance data are lacking. We aimed to investigate pediatric pemphigus patients' characteristics, diagnosis, therapeutics, response, and long-term follow-up. METHODS: This is a retrospective study of all pemphigus patients aged <18 years, diagnosed between 2000 and 2023, from three tertiary medical centers in Israel. The diagnosis was confirmed by positive immunofluorescence. RESULTS: Twelve pediatric pemphigus patients were included (mean age 10.7 ± 4.3 years, male:female ratio 1:1). Mean diagnostic delay was 11.1 ± 12.6 months (range 1.8-36 months). Most patients had pemphigus vulgaris with mucosal involvement (58.3%). First-line treatment for all patients included systemic corticosteroids (sCS), with a treatment duration (including tapering down) of 28 ± 18.4 months. Hospitalization did not yield better outcomes. Only three patients achieved sustained complete response with sCS treatment (25.0%), and the rest required additional therapeutics, most commonly rituximab. Rituximab showed a good safety profile and therapeutic response. Follow-up was recorded up to 18.1 years after diagnosis (mean: 5.6 years). Three of five patients with information available more than 5 years after the pemphigus diagnosis still exhibited disease symptoms. CONCLUSIONS: Pediatric pemphigus is associated with a significant diagnostic delay. While sCS can induce remission in most patients as a first-line treatment, long-term disease control requires additional immunomodulators. Long-term follow-up reveals a chronic yet mostly benign disease course in this population and advocates for the use of rituximab in pediatric pemphigus patients.

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.

New insights into associated co-morbidities in patients with cutaneous T-cell lymphoma (mycosis fungoides).

Studies of associated cancer in patients with mycosis fungoides (MF) have focused primarily on secondary cancers in North American and European populations. This study investigated the association between MF and malignancies, anxiety and depression in the Israeli population. Data on Israeli patients with MF and age- and gender-matched controls were collected from a database of population- based cohort (683 patients; 1,700 controls) and an institution- based cohort (343 patients; 846 controls) and analysed by univariate and multivariate methods. MF was significantly associated with Hodgkin's lymphoma in both cohorts (multivariate odds ratio (OR) 7.83, univariate OR ∞, respectively); acute leukaemia (multivariate OR 10.1, first cohort) and lung cancer (multivariate OR 10.15, second cohort). MF was significantly associated with anxiety and depression (multivariate OR 1.59, OR 1.51, respectively in first cohort). The current study provides support to the associations between MF and other cancers: Hodgkin's lymphoma, acute leukaemia and lung cancer. The study also emphasizes the association between MF and anxiety and depression.