Arteriovenous malformations as a presenting sign of PTEN hamartoma tumor syndrome: A case series.

High-flow vascular malformations have been associated with multiple syndromes including capillary malformation-arteriovenous malformation (CM-AVM) syndrome, hereditary hemorrhagic telangiectasia syndrome, and less commonly, phosphatase and tensin homolog hamartoma tumor syndrome (PHTS). We present a series of three patients with clinically challenging complex AVMs who were found to have underlying PHTS. In all patients, diagnosis was delayed, and the presence of the AVM prompted sampling and genetic testing for PHTS in the absence of other clinical features of the condition. This series highlights the importance of screening for PHTS in the setting of high-flow vascular malformations.

Use of dupilumab for atopic dermatitis in young transplant patients-A case series of 3 patients.

Patients who undergo solid organ transplantation are at an increased risk of developing atopic dermatitis, potentially due to long-term use of calcineurin inhibitors which results in a shift towards the Th2 immune response. The effectiveness and safety of dupilumab for atopic dermatitis in posttransplant patients is not established. Previous reports of dupilumab use in posttransplant patients have been in adult patients. In this series, we report three young posttransplant patients treated successfully with dupilumab.

Transition of care in patients with epidermolysis bullosa: A survey study.

There are little published data on the transition of care in EB. We conducted a survey study recruiting EB patients from the Dystrophic EB Research Association (debra) website and centers caring for high numbers of EB patients in the United States and internationally from Sept 17, 2019 to Nov 3, 2021. The majority of participants had not discussed the transition of care with their healthcare providers, nor the healthcare needs to be required as an adult. Ongoing pediatric subspecialty care was reported by 12% of adults, most commonly in pediatric dermatology. Identified barriers to transition included the perceived lack of adult providers' knowledge about EB patient healthcare needs. The results suggest the need for transition guidelines, early discussions with families about transition, and practical information for the adult providers accepting care.

Conradi-Hünermann-Happle syndrome associated with severe hypocalcemia in a newborn.

Conradi-Hünermann-Happle syndrome is rare X-linked dominant syndrome associated with stippled epiphyseal calcifications, congenital cataracts, Blaschkoid ichthyosiform scaling, and follicular atrophoderma. This case describes a novel finding of hypocalcemia and hypoparathyroidism in an infant with Conradi-Hünermann-Happle syndrome.

Worsening ulceration of infantile hemangioma after initiation or escalation of propranolol.

For infantile hemangiomas (IH) requiring treatment, including those in high-risk locations or in the setting of ulceration, oral propranolol is first-line therapy. Here, we present three cases of infantile hemangioma with worsening ulceration following initiation or escalation of oral propranolol at standard doses.

Successful management of an arteriovenous malformation with trametinib in a patient with capillary-malformation arteriovenous malformation syndrome and cardiac compromise.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

Cutaneous findings in Fanconi anemia.

BACKGROUND: Fanconi anemia (FA) is a genetic disorder that results in bone marrow failure, physical abnormalities, and solid organ malignancies. The diagnosis of FA is often delayed because the early disease characteristics have not been well established. OBJECTIVE: To outline the spectrum of cutaneous findings seen in patients with FA. METHODS: A cross-sectional study in which patients with FA received a full-body skin examination. Patient characteristics are summarized with mean (SD) for continuous and count (%) for categorical variables. Poisson regression and logistic regression models were used to examine the relationships between pigmentary changes and patient characteristics. RESULTS: At least 1 cutaneous pigmentary alteration was present in 96.8% of patients, most arising before the teenage years. The most common finding was café-au-lait macules. Other findings included hypopigmented macules, skin-fold freckle-like macules, extensive sun-exposed freckling, and both hypopigmented and hyperpigmented pigment macules. LIMITATIONS: Patients received a single assessment, so the number of pigmentary changes could not be assessed over time. CONCLUSIONS: Characteristic morphology of FA includes faint and ill-defined café-au-lait macules, hypopigmented skin-fold freckle-like macules and the concurrence of hypopigmented and hyperpigmented macules. The recognition of these findings could aid clinicians in making earlier diagnoses.

Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

THE demographics and trends in pediatric melanoma in the United States: An analysis of the National Cancer Database.

BACKGROUND/OBJECTIVE: Relative to adults, rates of melanoma are lower in children. Due to its rarity, it is difficult to assess the incidence, trends, and outcomes of this malignancy. Much of our understanding comes from single institution or regional cancer registries which may not be large enough to detect subtleties in the burden of pediatric melanoma. METHODS: Data from the 2004 to 2016 National Cancer Database were analyzed; this database captures approximately 70% of all cancer diagnoses in the United States. RESULTS: Our analysis consisted of 1903 cases. A majority were White (89.8%), the mean age was 12.4 years, and the ratio of females: males was 1.2:1.0. The most common anatomic location was the trunk (31.1%). Between 2004 and 2016, a decreasing trend in the number of new melanoma cases was observed. Comparing histologic subtype by age, there was an increased percentage of nodular and epithelioid and spindle cell tumors in the pre-teen children and a greater percentage of superficial spreading tumors in teenagers. Overall, a majority of cases were stage 0 or I (56.9%), with relatively few stage IV cases (2.0%). A 5-year all-cause survival of greater than 90% was observed for stage I-III tumors, with stage IV tumors having a 5-year all-cause survival of 34.4%. CONCLUSION: Comparable to previous studies, pediatric melanoma occurred most often in Whites, females, and adolescents. However, we detected a decreasing trend in new cases, noted differences between histologic subtype and age, and observed a 5-year all-cause survival rate of greater than 90% for stage I-III tumors.

An outbreak of acute hemorrhagic papules on the posterior neck in children during the COVID-19 pandemic.

Within a two-week timespan in April 2020, multiple children presented with hemorrhagic macules, papules, and erosions localized to the posterior neck and occipital scalp. All of these patients were children of health care workers, with at least one confirmed COVID-19 exposure. The unique lesional morphology and the timing of onset led to SARS-CoV-2 antibody testing for all and biopsy of one child. Biopsy ultimately confirmed these lesions were consistent with arthropod bites, which coincided with an unprecedented surge in local populations of Simulium tuberosum, a biting gnat.

Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series.

BACKGROUND: Systemic sirolimus (rapamycin) has recently been found effective in treating complex vascular anomalies by reducing the size and associated complications. Many vascular anomalies have a cutaneous component, and thus, we sought to determine whether topical administration of sirolimus may be an effective therapy, as data on the use of topical sirolimus are limited. OBJECTIVE: We reviewed the efficacy and tolerability of topical formulations of sirolimus in the treatment of various simple and combined vascular malformations and tumors. METHODS: Eighteen patients with any vascular anomaly treated exclusively with topical sirolimus were retrospectively reviewed. RESULTS: Eleven patients had combined venous lymphatic malformations, three had tufted angiomas, two had a lymphatic malformation, one had a venous malformation, and one had a verrucous venous malformation. All (100%) patients reported some degree of improvement and 50% of patients reported marked improvement in one or more symptoms, most commonly blebs and lymphatic drainage, and bleeding. LIMITATIONS: The retrospective nature, small number of patients, and differences in topical preparations limit the broad application of the results. CONCLUSION: Topical sirolimus appears to be a safe and useful non-invasive therapy that is well-tolerated in the treatment of the cutaneous portion of a variety of vascular anomalies.

The incidence of pediatric malignant soft tissue tumors of the skin and subcutaneous tissue.

Soft tissue tumors are a known, albeit uncommon, cause of cutaneous malignancy in children. Little is known about which types and how frequently these tumors initially present in the skin or subcutis of children. Using data from the 2000-2014 SEER-18 database, we have identified 12 malignant soft tissue tumor types, which initially presented in the skin or subcutis of children in over 50% of cases.

Cutaneous Reactions in Children Treated with the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase Inhibitor Trametinib for Neural Tumors.

BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway is a target for the treatment of a growing number of malignancies. The cutaneous reactions to medications that inhibit this pathway have not been described in children. METHODS: A retrospective chart review was completed for eight children with neural tumors treated with the MAPK extracellular signal-regulated kinase inhibitor trametinib. All children were evaluated by a pediatric dermatologist with documentation of cutaneous findings. RESULTS: All patients had at least two separate skin reactions while on treatment with trametinib. Common skin findings included xerotic dermatitis, bacterial folliculitis, acneiform eruptions, paronychia, and hair thinning. No child needed to discontinue use of trametinib due to cutaneous toxicities. CONCLUSIONS: Cutaneous reactions are common in children receiving trametinib. Identification of these reactions is the initial step in establishing treatment guidelines that will minimize skin eruptions and subsequent interruption of trametinib treatment.

Toxic Epidermal Necrolysis in Recessive Dystrophic Epidermolysis Bullosa following Bone Marrow Transplantation.

A 3-year-old child with recessive dystrophic epidermolysis bullosa treated with bone marrow transplantation subsequently developed body-wide epidermal detachment distinct from his epidermolysis bullosa. Toxic epidermal necrolysis was diagnosed by examination and skin biopsy. Although graft-vs-host disease was considered, he had no features of this diagnosis by laboratory studies or skin biopsy, and he improved without addition of further immune suppressants. Throughout the episode, the patient was maintained on cyclosporine A, a component of his transplant regimen, and also a reported therapy for toxic epidermal necrolysis. He had full recovery. Re-epithelialization occurred in a unique folliculocentric pattern, which we postulate was related to the patient's mesenchymal stem cell infusion, received as an adjunct to his marrow transplantation.

Congenital hemangiomas.

Congenital hemangiomas are rare solitary vascular tumors that do not proliferate after birth. They are characterized as either rapidly involuting congenital hemangiomas (RICHs) or noninvoluting congenital hemangiomas (NICHs) based on their clinical progression. NICHs have no associated complications, but are persistent. RICH, while usually asymptomatic, may ulcerate or bleed early in their presentation, but involute quickly during the first few months of life. Hepatic RICHs are not associated with cutaneous RICHs, but may result in high-output cardiac failure due to arteriovenous or portovenous shunting. In the following review, the clinical characteristics and current management specific to congenital hemangiomas is discussed.