Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are ...currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.
Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with ...CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors.
We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14.
Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed.
We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab.
Relatively small sample size.
Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.
Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because linear porokeratosis manifests in ...the lines of Blaschko representing the dorsoventral migration patterns of keratinocyte precursors, it has been suggested that postzygotic somatic mutation underlies the disease. However, no genetic evidence has supported this hypothesis to date.
To identify genetic mutations associated with linear porokeratosis.
Paired whole-exome sequencing of affected skin and blood/saliva samples from 3 participants from 3 academic medical centers with clinical and histologic diagnoses of linear porokeratosis.
Whole-exome sequencing of paired blood/saliva and affected tissue samples isolated from linear porokeratosis lesions.
Germline and somatic genomic characteristics of participants with linear porokeratosis.
Of the 3 participants, 2 were male. Participant ages ranged from 5 to 20 years old. We found a combination of a novel germline mutation and a novel somatic mutation within affected tissue in all cases. One participant had a germline heterozygous PMVK c.329G>A mutation and a somatic copy-neutral loss of heterozygosity confined to the lesional skin, while a second had a germline heterozygous PMVK c.79G>T mutation and an additional PMVK c.379C>T mutation in the lesional skin. In a third participant, there was a germline splice-site mutation in MVD (c.70 + 5G>A) and a somatic deletion in MVD causing frameshift and premature codon termination within the lesional skin (c.811_815del, p.F271Afs*33 frameshift).
Our findings suggest that linear porokeratosis is associated with the presence of second-hit postzygotic mutations in the genes that encode enzymes within the mevalonate biosynthesis pathway, and provide further evidence that the mevalonate pathway may be a potential target for therapeutic intervention in porokeratosis.
Background
Erythema multiforme (EM) is an acute condition characterized by distinctive target lesions of the skin often accompanied by mucosal ulcers. A subset of individuals experience frequent ...episodes of recurrent EM, which is rare and poorly understood, especially in children.
Objective
To characterize clinical features, laboratory findings, and treatment responses of pediatric recurrent EM.
Methods
A retrospective chart review was conducted at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin (2000‐2015) and the Mayo Clinic in Rochester, Minnesota (1990‐2015). Inclusion criterion was a diagnosis before age 18 years with recurrent EM, defined as a symmetrically distributed, fixed eruption, including target lesions, with or without mucous membrane involvement, occurring on at least three occasions. A literature review was conducted to include individuals who met the inclusion criterion.
Results
Twenty‐six patients were included, of whom 16 (62%) were male. The median age of onset was 9.1 years (range 0‐15.7 years). Nine patients (35%) required hospitalization. Herpes simplex virus testing was positive in 9 of 17 (65%) patients. Remission was achieved in 5 of 16 (31%) patients while taking suppressive antivirals. Eight patients received continuous anti‐inflammatory treatment, two (25%) of whom experienced remission.
Conclusion
This study of pediatric recurrent EM found a greater male predominance, more hospitalizations, fewer cases caused by herpes simplex virus, and a lower response to immunosuppression in children than in the general population.
Numerous studies have investigated the efficacy of intralesional immunotherapy for warts, but there are a lack of studies investigating the efficacy of alternative intralesional immunotherapies ...following failure of initial intralesional immunotherapy. In this retrospective study, we aimed to investigate the efficacy of intralesional measles, mumps, and rubella vaccine for the treatment of pediatric warts following failure of intralesional therapy with Candida antigen. Following intralesional measles, mumps, and rubella vaccine administration, 8/51 (15.5%) patients had complete resolution of their warts, 6/51 (12%) had near complete resolution, 19/51 (37%) had partial improvement, 12/51 (23.5%) had no change, and 6/51 (12%) had worsening. Although limited by retrospective nature and low sample size, our results demonstrate that intralesional immunotherapy with measles, mumps, and rubella vaccine provides an alternative therapeutic option for the treatment of recalcitrant pediatric warts in patients who fail to respond to intralesional Candida antigen.
Background An inverse correlation between serum 25-hydroxyvitamin D concentration and atopic dermatitis (AD) severity has been suggested. Objective To determine if a statistically significant ...relationship exists between serum 25-hydroxyvitamin D concentration and AD severity. Methods A cross-sectional study was conducted of patients with AD who were 1 to 18 years of age. An objective Severity Scoring of Atopic Dermatitis (SCORAD) and a serum 25-hydroxyvitamin D concentration were measured for each subject. Statistical analysis was performed using appropriate univariate tests and multivariable models. Results Ninety-four of 97 enrolled subjects were included in the analysis. Vitamin D deficiency (25-hydroxyvitamin D <20 ng/mL) was present in 37 subjects (39%), insufficiency (25-hydroxyvitamin D 21-29 ng/mL) in 33 (35%), and sufficiency (25-hydroxyvitamin D ≥30 ng/mL) in 24 (26%). The correlation between 25-hydroxyvitamin D concentration and SCORAD was not significant ( r = –0.001; P = .99). A multivariate model showed that a lower serum 25-hydroxyvitamin D concentration was significantly associated with age 3 years or older ( P < .0001), black race ( P < .0001), and winter season ( P = .0084). Limitations Limitations of this study include the inability to control for natural sunlight exposure, vitamin D intake, and AD treatment; in addition, only a single time point was captured. Conclusions Serum 25-hydroxyvitamin D concentration is not significantly correlated with AD severity in our pediatric population.
Abstract Down syndrome (DS) is associated with many dermatological conditions, including hidradenitis suppurativa, folliculitis, and alopecia areata. Despite the high incidence of skin conditions in ...this population, there are no quality of life (QoL) studies in the dermatology literature focused on patients with DS or their caregivers. The frequently used QoL assessment tool, the Dermatology Life Quality Index (DLQI), has yet to be studied in this population. This study addresses these disparities by capturing how various skin conditions affect the QoL of people with DS and their caregivers and assessing the utility of the DLQI.
Hyper‐IgE syndromes (HIES) are a heterogeneous group of rare primary immunodeficiency diseases classically characterized by the triad of atopic dermatitis, and recurrent cutaneous and pulmonary ...infections. Autosomal dominant, loss‐of‐function STAT3 pathogenic variants are the most common genetic cause, which lead to deficiency of Th17 lymphocytes, impaired interferon gamma production, and IL‐10 signal transduction, and an unbalanced IL‐4 state. Dupilumab, a monoclonal antibody to the IL‐4a receptor, inhibits both IL‐4 and IL‐13, and has been shown to improve atopic dermatitis and other manifestations of HIES including asthma and allergic bronchopulmonary aspergillosis. We present a pediatric patient with HIES who presented predominantly with eosinophilic folliculitis, recurrent cutaneous infections, and other non‐eczematous findings and achieved sustained clearance with dupilumab.
Infantile hemangioma Holland, Kristen E; Drolet, Beth A
The Pediatric clinics of North America,
10/2010, Letnik:
57, Številka:
5
Journal Article
Recenzirano
Infantile hemangiomas (IHs) are the most common soft tissue tumors of childhood. The wide spectrum of disease has made it difficult to predict need for treatment and has made it challenging to ...establish a standardized approach to management. This article provides the reader with an up-to-date discussion of IH, identifying features of this condition which predict need for treatment as well as associated complications and reviewing management.
We report recessive mutations in the gene for the latent transforming growth factor-β binding protein 4 (LTBP4) in four unrelated patients with a human syndrome disrupting pulmonary, ...gastrointestinal, urinary, musculoskeletal, craniofacial, and dermal development. All patients had severe respiratory distress, with cystic and atelectatic changes in the lungs complicated by tracheomalacia and diaphragmatic hernia. Three of the four patients died of respiratory failure. Cardiovascular lesions were mild, limited to pulmonary artery stenosis and patent foramen ovale. Gastrointestinal malformations included diverticulosis, enlargement, tortuosity, and stenosis at various levels of the intestinal tract. The urinary tract was affected by diverticulosis and hydronephrosis. Joint laxity and low muscle tone contributed to musculoskeletal problems compounded by postnatal growth delay. Craniofacial features included microretrognathia, flat midface, receding forehead, and wide fontanelles. All patients had cutis laxa. Four of the five identified LTBP4 mutations led to premature termination of translation and destabilization of the LTBP4 mRNA. Impaired synthesis and lack of deposition of LTBP4 into the extracellular matrix (ECM) caused increased transforming growth factor-β (TGF-β) activity in cultured fibroblasts and defective elastic fiber assembly in all tissues affected by the disease. These molecular defects were associated with blocked alveolarization and airway collapse in the lung. Our results show that coupling of TGF-β signaling and ECM assembly is essential for proper development and is achieved in multiple human organ systems by multifunctional proteins such as LTBP4.
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