Epithelioid Sarcoma Presenting in the Thumb of a Child.

Epithelioid sarcoma (ES) is a high-grade, soft tissue tumor of mesenchymal origin that rarely occurs in children and is often misdiagnosed as a benign entity. We present the case of a 12-year-old girl with a delayed diagnosis of ES of the left thumb. Radiological examination showed possible calcinosis from inflammation or traumatic injury. However, histopathological and immunohistochemistry studies showed findings consistent with a diagnosis of ES. She was treated with amputation of the interphalangeal joint of the left thumb. This case highlights the clinical and pathologic correlation required for the appropriate diagnosis and treatment of patients with soft tissue masses.

Continuing patient care to underserved communities and medical education during the COVID-19 pandemic through a teledermatology student-run clinic.

A virtual pediatric dermatology student-run clinic was initiated during the COVID-19 pandemic, when in-person educational opportunities were limited. The clinic's aim is to provide high-quality dermatologic care to a diverse, underserved pediatric patient population while teaching trainees how to diagnose and manage common skin conditions. In our initial eight sessions, we served 37 patients, predominantly those with skin of color, and had a low no-show rate of 9.8%. This report describes the general structure of the clinic, goals, and the patient population to provide an overview of our educational model for those interested in similar efforts.

Pediatric mastocytosis.

PURPOSE OF REVIEW: The current article highlights recent developments in the field of pediatric cutaneous mastocytosis. Mastocytosis is a spectrum of conditions that range from fleetingly benign to aggressively malignant. Through recognizing the natural progression of disease, the role of biomarkers and mutational analysis, treatment and risk of triggers, physicians can confidently stage, counsel and manage patients with pediatric cutaneous mastocytosis. RECENT FINDINGS: Many lesions of cutaneous mastocytosis are chronic with some resolving around the mid-teenage years. KIT mutations are found in the majority of pediatric cutaneous mastocytosis but are not correlated with prognosis. Serum tryptase levels may be elevated in pediatric cutaneous mastocytosis patients without systemic mastocytosis. Pimecrolimus, omalizumab and tyrosine kinase inhibitors are effective treatment options. The low risk of NSAIDs and vaccinations has been characterized and epinephrine autoinjectors are rarely utilized in the pediatric cutaneous mastocytosis patient. SUMMARY: Pediatric cutaneous mastocytosis is a heterogeneous disease with good outcome overall. Organomegaly, elevated tryptase levels and the presence of KIT mutation in peripheral blood may aid in the decision to pursue bone marrow biopsy. The armamentarium of treatments has expanded and better understanding of the significance of triggers and vaccination safety allows the clinician to thoughtfully counsel and allay anxiety around pediatric cutaneous mastocytosis.

Pemphigus-like eruption as a complication of molluscum contagiosum treatment with imiquimod in a 5-year-old girl.

Pemphigus and pemphigus-like reactions can be triggered by a variety of medications including topical therapies, such as imiquimod. While the association between imiquimod and pemphigus-like reactions has been reported in adults, this is the first report of a generalized reaction beyond the site of imiquimod application in a child. The mechanism by which this occurs may be through a unique pathway, separate from the classic antibody-mediated pathway. Our patient had a full recovery without recurrence after cessation of the inciting drug.

Two Cases of Chronic Candidiasis in Keratitis-Ichthyosis-Deafness Syndrome.

Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis that typically results from mutations of the GJB2 gene or, less commonly, the GJB6 gene. Patients with KID syndrome are at higher risk of malignancy and infections. Here, we present 2 patients with KID syndrome who developed verrucous plaques. Given that patients with KID syndrome are at high risk of developing squamous cell carcinoma, biopsies were performed. Both cases revealed histologic findings of marked papillomatous epidermal hyperplasia with numerous fungal spores and pseudohyphae in the stratum corneum. For one case, daily oral fluconazole was initiated. The patient demonstrated dramatic resolution of his foot plaques over the course of 2 years. These cases highlight that, for the dermatopathologist, chronic fungal infection should be sought for verrucous plaques in patients with KID syndrome as, if present, this finding may alter treatment and quality of life.

Subcutaneous granuloma annulare involving the scalp.

Subcutaneous granuloma annulare (SGA) is an uncommon subtype of granuloma annulare. There are few reports of this entity solely affecting the scalp. We report a case of biopsy-proven SGA in a 21-month-old boy with six asymptomatic, rock-hard scalp nodules.

Determinants of laminin polymerization revealed by the structure of the α5 chain amino-terminal region.

The polymerization of laminin into a cell-associated network--a key step in basement membrane assembly--is mediated by the laminin amino-terminal (LN) domains at the tips of the three short arms of the laminin αßγ-heterotrimer. The crystal structure of a laminin α5LN-LE1-2 fragment shows that the LN domain is a ß-jelly roll with several elaborate insertions that is attached like a flower head to the stalk-like laminin-type epidermal growth factor-like tandem. A surface loop that is strictly conserved in the LN domains of all α-short arms is required for stable ternary association with the ß- and γ-short arms in the laminin network.

The biomechanical properties of the skin.

BACKGROUND: The skin possesses unique biochemical properties that allow it to protect and conform to the body that it covers. Elements constituting the dermis-collagen and elastin-primarily afford these properties. OBJECTIVES: To define these properties and explore their relevance with regard to aging skin and dermatologic surgery. MATERIALS AND METHODS: In the first part of this review, the determinants of mechanical properties of the skin will be outlined, through an extensive review of the literature. General physical properties that explain the behavior of skin will be defined, and diseases that manifest the extremes of those properties will be discussed. In the second half of this discussion, the surgical implications of skin biomechanics will be reviewed. RESULTS: Emphasis will be placed on understanding how dermatologic surgeons may optimally use skin properties to produce the best cosmetic and functional outcomes possible. CONCLUSION: Understanding of the biomechanical properties of skin is paramount to obtain the best cosmetic outcomes in dermatologic surgery.

Hidradenitis Suppurativa in Pediatric Patients.

Hidradenitis suppurativa is a chronic inflammatory skin disorder primarily affecting apocrine gland-bearing areas, including the axillae, groin, and buttocks. It is reported in up to 2% of Western populations and with increasing incidence in children and adults. Nearly one-third of hidradenitis suppurativa cases occur in pediatric patients and nearly half of patients endorse initial symptoms in childhood. To date, there are few clinical studies and guidelines for pediatric hidradenitis suppurativa. Here, we review the epidemiology, clinical presentation, comorbidities, and management of pediatric hidradenitis suppurativa. We discuss barriers contributing to delays in diagnosis and the significant physical and emotional impact of the disease on children and adolescents.

Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan.

Dystroglycan is a ubiquitously expressed cell adhesion protein. Its principal role has been determined as a component of the dystrophin-glycoprotein complex of muscle, where it constitutes a key component of the costameric cell adhesion system. To investigate more fundamental aspects of dystroglycan function in cell adhesion, we examined the role of dystroglycan in the dynamics and assembly of cellular adhesions in myoblasts. We show that beta-dystroglycan is recruited to adhesion structures and, based on staining for vinculin, that overexpression or depletion of dystroglycan affects both size and number of fibrillar adhesions. Knockdown of dystroglycan increases the size and number of adhesions, whereas overexpression decreases the number of adhesions. Dystroglycan knockdown or overexpression affects the ability of cells to adhere to different substrates, and has effects on cell migration that are consistent with effects on the formation of fibrillar adhesions. Using an SH3 domain proteomic screen, we identified vinexin as a binding partner for dystroglycan. Furthermore, we show that dystroglycan can interact indirectly with vinculin by binding to the vinculin-binding protein vinexin, and that this interaction has a role in dystroglycan-mediated cell adhesion and spreading. For the first time, we also demonstrate unequivocally that beta-dystroglycan is a resident of focal adhesions.

Nonpharmacologic management of common skin and psychocutaneous disorders.

Data supporting the effectiveness of nonpharmacologic psychocutaneous techniques continues to accumulate. These interventions are used for the treatment of common and psychocutaneous skin conditions. They are most commonly used as adjuncts to traditional therapies. This article will review the data on the effectiveness of hypnosis, biofeedback, psychotherapy, meditation, support groups, guided imagery and progressive muscle relaxation, and psychotherapy.

Structural Basis for the Acceleration of Procollagen Processing by Procollagen C-Proteinase Enhancer-1.

Procollagen C-proteinase enhancer-1 (PCPE-1) is a secreted protein that specifically accelerates proteolytic release of the C-propeptides from fibrillar procollagens, a crucial step in fibril assembly. As such, it is a potential therapeutic target to improve tissue repair and prevent fibrosis, a major cause of mortality worldwide. Here we present the crystal structure of the active CUB1CUB2 fragment of PCPE-1 bound to the C-propeptide trimer of procollagen III (CPIII). This shows that the two CUB domains bind to two different chains of CPIII and that the N-terminal region of one CPIII chain, close to the proteolytic cleavage site, lies in the cleft between CUB1 and CUB2. This suggests that enhancing activity involves unraveling of this chain from the rest of the trimer, thus facilitating the action of the proteinase involved. Support for this hypothesis comes from site-directed mutagenesis, enzyme assays, binding studies, and molecular modeling.

Crystal Structure of the Heterotrimeric Integrin-Binding Region of Laminin-111.

Laminins are cell-adhesive glycoproteins that are essential for basement membrane assembly and function. Integrins are important laminin receptors, but their binding site on the heterotrimeric laminins is poorly defined structurally. We report the crystal structure at 2.13 Å resolution of a minimal integrin-binding fragment of mouse laminin-111, consisting of ∼50 residues of α1ß1γ1 coiled coil and the first three laminin G-like (LG) domains of the α1 chain. The LG domains adopt a triangular arrangement, with the C terminus of the coiled coil situated between LG1 and LG2. The critical integrin-binding glutamic acid residue in the γ1 chain tail is surface exposed and predicted to bind to the metal ion-dependent adhesion site in the integrin ß1 subunit. Additional contacts to the integrin are likely to be made by the LG1 and LG2 surfaces adjacent to the γ1 chain tail, which are notably conserved and free of obstructing glycans.

Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity.

Heparin/heparan sulfate (HS) glycosaminoglycans are required for Slit-Robo cellular responses. Evidence exists for interactions between each combination of Slit, Robo and heparin/HS and for formation of a ternary complex. Heparin/HS are complex mixtures displaying extensive structural diversity. The relevance of this diversity has been studied to a limited extent using a few select chemically-modified heparins as models of HS diversity. Here we extend these studies by parallel screening of structurally diverse panels of eight chemically-modified heparin polysaccharides and numerous natural HS oligosaccharide chromatographic fractions for binding to both Drosophila Slit and Robo N-terminal domains and for activation of a chick retina axon response to the Slit fragment. Both the polysaccharides and oligosaccharide fractions displayed variability in binding and cellular activity that could not be attributed solely to increasing sulfation, extending evidence for the importance of structural diversity to natural HS as well as model modified heparins. They also displayed differences in their interactions with Slit compared to Robo, with Robo preferring compounds with higher sulfation. Furthermore, the patterns of cellular activity across compounds were different to those for binding to each protein, suggesting that biological outcomes are selectively determined in a subtle manner that does not simply reflect the sum of the separate interactions of heparin/HS with Slit and Robo.

Vesicles and pustules in the neonate.

Vesicles and pustules in the neonate can be due to common or life threatening conditions. Recognizing key clinical features and understanding when and how to workup the various different vesiculopustular eruptions that occur in the neonatal period is vital. A rapid diagnosis of an infectious cause of a neonatal vesiculopustular eruption can be life-saving.