Severe congenital ichthyosiform dermatosis in CHIME syndrome successfully treated with ixekizumab.

Coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, conductive hearing loss, and epilepsy (CHIME) syndrome is a rare autosomal recessive neuroectodermal disorder caused by PIGL gene mutations. There is emerging literature to support the use of interleukin-17 (IL-17) antagonists in the treatment of certain ichthyosiform dermatoses. Here, we report a case of severe ichthyosiform dermatosis in a child with CHIME syndrome who was recalcitrant to multiple topical medications and dupilumab. This is the first reported case of successful treatment of congenital ichthyosiform dermatosis in a CHIME syndrome patient with ixekizumab, an IL-17A antagonist.

JAK Inhibitors: A New Weapon in the Skin Care Providers' Arsenal.

A number of chronic skin diseases, such as vitiligo and alopecia areata, are historically resistant to or respond poorly to treatment. Additionally, disorders such as atopic dermatitis and psoriasis have subtypes that are inadequately treated by current medications. Lastly, in the field of dermatology there are a number of conditions, some genetic (such as Darier's disease and Hailey-Hailey disease) and others caused by aberrant inflammatory responses (macrophage-driven conditions such as sarcoidosis and autoimmune conditions such as localized scleroderma) where effective treatments have been limited to date. A new class of anti-inflammatory medications that inhibit the Janus Kinase-Signal transducer and activator of transcription pathway (JAK-STAT) show great promise in providing new and effective treatment of these formerly recalcitrant conditions. This brief review will cover inhibitors of the JAK-STAT pathway (JAK inhibitors) currently approved for use in treating dermatologic diseases including several very recently approved medications. It will also touch on additional conditions under study or where early reports of efficacy are promising.

Leprosy (Hansen's disease): An Update and Review.

Leprosy (Hansen's disease) is caused by infection with bacilli of the Mycobacterium leprae complex. It is considered an exotic and rare diagnosis in Missouri. Past leprosy patients diagnosed locally have typically acquired it in areas of the world where leprosy is endemic. However, a recent case in a native Missourian that appears to be locally acquired suggests that leprosy may now be endemic in Missouri, possibly due to the expanded range of its zoonotic vector, the nine-banded armadillo. Health care providers in Missouri should be aware of how leprosy manifests and suspected cases referred to centers such as ours for evaluation and early institution of appropriate treatment.

Accelerating Care Through ECHO: Case Examples from the Field.

In this article, we describe three life-changing patient cases demonstrating high-quality and timely care they received in their communities, thanks to the Show-Me ECHO project. Early autism diagnosis, a potentially deadly tumor manifesting as a benign-looking rash, a recalcitrant case of hepatitis C: rural and underserved Missourians now have access to state-of-the-art care through their local providers receiving interdisciplinary telementoring on evidence based practices.

Uveitis Following Treatment of Verruca Vulgaris with Intralesional Candida Antigen.

This is a first literature report of a case of uveitis along with severe systemic symptoms following verruca vulgaris treatment with intralesional Candida antigen. We believe the Candida injection was causative.

Cornoid Lamella-Like Structures in HIV-Associated Epidermodysplasia Verruciformis: A Unique Histopathologic Finding.

Epidermodysplasia verruciformis (EV) is an uncommon inherited skin condition with increased vulnerability to widespread infection by certain human papillomavirus types, resulting in extensive verruca plana-like papules coalescing to large confluent plaques. Since the AIDS epidemic starting in the 1980s, an acquired type of EV has been described in patients infected with human immunodeficiency virus. The histopathologic features of EV consist of papillated epidermal hyperplasia with hypergranulosis and a distinct bluish-gray color in the large human papillomavirus-infected keratinocytes in the stratum granulosum. The authors present a case of HIV-associated EV with a unique histopathologic finding of multiple cornoid lamella-like structures. To the authors' knowledge, this finding has not been previously described in the literature.

Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFß pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.

Care of the newborn with ichthyosis.

Mendelian disorders of cornification (ichthyosis; MeDOC) often present in the neonatal period with little warning to providers or parents. This report reviews the majority of ichthyoses with congenital findings. The neonatal presentation of many MeDOC often differs from the later phenotype because of the changes in the skin that occur with transition from an intrauterine to extrauterine environment. While differentiation of ichthyosis subtypes in the neonatal period is difficult, there are certain phenotypic groups within which these neonates fall, recognition of which can guide initial work up and treatment. For this report, these are categorized as: exuberant vernix; collodion baby/harlequin ichthyosis (HI); ichthyosiform erythroderma; blistering; and normal skin/xerosis phenotypes.

Climate change and pediatric skin health.

Children are known to disproportionately bear the health impacts of climate change, particularly children living in impoverished areas. Owing to their developing physiology and immature metabolism, distinct exposure behaviors, and reliance on adults for care and protection, children are uniquely susceptible to the adverse effects of our warming planet. Herein, we summarize the known impacts of climate change on pediatric skin health, including its effects on atopic dermatitis, vector-borne and other infectious diseases, nutritional deficiencies, and psychodermatoses.

Genodermatoses with malignant potential.

The hereditary nature of some forms of cancer was recognized long ago. Over time, recognition of associated findings led to the delineation of numerous hereditary cancer syndromes. Many of these syndromes also have cutaneous manifestations, the recognition of which can lead to their early identification. Recognition of these syndromes allows vigilant surveillance and preemptive treatment, which can dramatically impact the risks of morbidity and mortality for affected patients. The rise of rapid and accurate genetic testing now allows the early identification of asymptomatic at risk family members so that monitoring can be initiated as early as possible. The dermatologist plays a critical role in early identification of these syndromes and, in many cases, their treatment. This review summarizes many known hereditary cancer syndromes with cutaneous findings, their etiology, identification, evaluation, and management. Importantly, this is an ever evolving topic and new findings and syndromes will continue to be recognized. The dermatologist must be always alert to ensure they are detected.

Cutaneous Drug Eruptions in Pediatrics-A Primer.

Cutaneous adverse drug reactions (ADRs) are commonly seen in the pediatric population in both inpatient and outpatient settings and are important to identify, evaluate, and appropriately manage. Early recognition and proper classification of a cutaneous drug reaction allows the clinician the ability to narrow in on a culprit drug and determine whether the medication is safe to continue. This review discusses the clinical presentation, categorization, and management of cutaneous ADRs in the pediatric population. [Pediatr Ann. 2020;49(3):e132-e139.].

Diagnosis, diagnostic confidence, and management concordance in live-interactive and store-and-forward teledermatology compared to in-person examination.

Teledermatology studies have examined diagnostic concordance between live-interactive (LI) and in-person examinations (IP); and between store-and-forward (SF) and IP examinations. However, no studies have looked simultaneously across all three care delivery modalities, and few have measured management concordance and diagnostic confidence of the dermatologist. The purpose of this study was to compare LI and SF modalities with IP with respect to diagnostic and management concordance and to compare physician diagnostic confidence across the three modalities. Four dermatologists, in random rotation among all three care modalities, examined 110 new patients. Confidence was rated on a Likert scale from 1 to 5 (5 = total confidence; 1 = no confidence). Identical diagnoses were given to the patient by examiners from all three examination modalities in 70/110 patients (64%). More identical diagnoses were given for IP and LI examinations than for IP and SF examinations (80% vs. 73%); however, the difference was not statistically significant (p = 0.13). The highest self-reported confidence rating was given for 87% of IP examinations, 59% for LI, and 54% for SF. Diagnostic confidence ratings for SF and LI were not significantly different from each other (p = 0.50); however, diagnostic confidence ratings for LI and SF were both statistically lower than IP (p < 0.0001). Dermatologists were more confident with IP examination than either form of teledermatology. The percent of diagnostic and management agreement among IP, LI, and SF modalities was high.

Experimental BPA Exposure and Glucose-Stimulated Insulin Response in Adult Men and Women.

CONTEXT: Human cross-sectional and animal studies have shown an association of the chemical bisphenol A (BPA) with insulin resistance, type 2 diabetes, and other metabolic diseases, but no human experimental study has investigated whether BPA alters insulin/C-peptide secretion. DESIGN: Men and postmenopausal women (without diabetes) were orally administered either the vehicle or a BPA dose of 50 µg/kg body weight, which has been predicted by US regulators (Food and Drug Administration, Environmental Protection Agency) to be the maximum, safe daily oral BPA dose over the lifetime. Insulin response was assessed in two cross-over experiments using an oral glucose tolerance test (OGTT; experiment 1) and a hyperglycemic (HG) clamp (experiment 2). Main outcomes were the percentage change of BPA session measures relative to those of the control session. RESULTS: Serum bioactive BPA after experimental exposure was at levels detected in human biomonitoring studies. In the OGTT, a strong positive correlation was found between hemoglobin A1c(HbA1c) and the percentage change in the insulinogenic index (Spearman = 0.92), an indicator of early-phase insulin response, and the equivalent C-peptide index (Pearson = 0.97). In the HG clamp study, focusing on the later-phase insulin response to a stable level of glucose, several measures of insulin and C-peptide appeared suppressed during the BPA session relative to the control session; the change in insulin maximum concentration (Cmax) was negatively correlated with HbA1c and the Cmax of bioactive serum BPA. CONCLUSIONS: This exploratory study suggests that BPA exposure to a dose considered safe by US regulators may alter glucose-stimulated insulin response in humans.

Childhood viral exanthems.

Many viral infections exhibit cutaneous lesions. Recognition of the exanthems associated with these infections and the broader clinical scenarios in which they occur can lead to more rapid diagnosis and appropriate treatment for affected patients.

Extreme pain from brown recluse spider bites: model for cytokine-driven pain.

IMPORTANCE: Bites from the brown recluse spider (BRS) can cause extreme pain. We propose cytokine release as a cause of the discomfort and a central mechanism through glial cell upregulation to explain measured pain levels and time course. OBSERVATIONS: Twenty-three BRS bites were scored at a probable or documented level clinically, and an enzyme-linked immunosorbent assay was used to confirm the presence of BRS venom. The mean (SD) pain level in these cases 24 hours after the spider bite was severe: 6.74 (2.75) on a scale of 0 to 10. Narcotics may be needed to provide relief in some cases. The difference in pain level by anatomic region was not significant. Escalation observed in 22 of 23 cases, increasing from low/none to extreme within 24 hours, is consistent with a cytokine pain pattern, in which pain increases concomitantly with a temporal increase of inflammatory cytokines. CONCLUSIONS AND RELEVANCE: These findings in BRS bites support the hypothesis of cytokine release in inflammatory pain. A larger series is needed to confirm the findings reported here. The extreme pain from many BRS bites motivates us to find better prevention and treatment techniques.

Newborn skin care.

Many organ systems undergo significant and rapid changes during the transition from an intrauterine to an extrauterine environment, especially those which serve as interfaces between the infant and the external environment. Historically the skin care methods employed during and after this period of rapid physiologic change have been derived from individual anecdotal experience or cultural tradition, rather than evidence-based or pathomechanistically derived data. While research in this area has historically been limited, it is increasing in scope and volume, and recent work has shed light on the changes experienced by the cutaneous organ during this period of transition. This increased understanding has driven new recommendations in skin care protocols for newborn infants and neonates.

New findings in genodermatoses.

New technologies are accelerating the pace at which genetic defects leading to inherited skin disease are elucidated. Translation of these genetic discoveries into new therapies for patients with inherited skin diseases has not been as rapid but the pace is now accelerating. This article summarizes recent findings in genetic skin diseases, the scope of advances being made, the role of new DNA analysis technologies in these discoveries, as well as highlighting some examples of how an understanding of the genetic cause of inherited skin diseases can lead to therapeutic interventions for patients.