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BACKGROUND Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P

Microcystic lymphatic malformation (MiLM), also known as lymphangioma circumscriptum, is a superficial collection of lymphatic vessels measuring1 cm in the largest diameter, often with a more extensive deeper malformation. It commonly presents as discrete or grouped plaques of clear or hemorrhagic vesicles classically described as "frogspawn"; however, here we describe a case of its unique presentation as firm papules on the lips of a healthy six-year-old child. These skin-colored papules in the absence of vesicles with lymphatic and/or hemorrhagic fluid may not be clinically indicative of MiLM. This case represents a diagnostic challenge due to the unique morphology of pink, fleshy papules as opposed to the clear or hemorrhagic vesicles typically observed in MiLM.

Proliferative nodules arising within congenital melanocytic nevi often present a diagnostic challenge given a close resemblance to melanoma. Several morphologic variants have been characterized. In difficult cases, ancillary molecular tests can be used to better exclude the possibility of malignant degeneration. Herein, we report a case of an unusual proliferative nodule with overlapping features of angiomatoid Spitz tumor and ancient melanocytic nevus, which demonstrated normal findings on both chromosomal microarray and a gene expression profiling assay.

Purpose To describe the spectrum of retinal vascular abnormalities in patients with phakomatosis pigmentovascularis (PPV). Design Multicenter, retrospective, noncomparative, consecutive case series. Methods Eligible patients underwent detailed retinal examination including indirect ophthalmoscopy. Ultra-widefield fundus imaging, including color fundus photography and angiography, was performed using standardized protocols, and findings were recorded and reviewed and analyzed. Participants Three patients with a clinical diagnosis of PPV are presented. Results Evaluation of all patients (n = 6 eyes of 3 patients) with widefield fluorescein angiography showed several retinal vascular abnormalities, including peripheral retinal nonperfusion (n = 3 eyes), peripheral vascular leakage (n = 3 eyes), aberrant retinal vessels (n = 1 eyes), vascular tortuosity (n = 1 eyes), and disruption of the foveal avascular zone including fovea plana (n = 3 eyes). In addition, 2 eyes demonstrated peripheral retinal vascular straightening and leakage similar to the features of familial exudative vitreoretinopathy. One of the patients was a carrier of a somatic GNA11 R183C pathogenic variant that has been associated with PPV. Conclusions Fluorescein angiography, especially with widefield capability, reveals numerous retinal vascular abnormalities in patients with PPV. Considering the association of GNA11 pathogenic variants with PPV and allied disorders, these observations may suggest a role of guanine-binding proteins (G-proteins) in retinal vascular development. Supplemental material available at www.ophthalmologyretina.org.

Pigmented epithelioid melanocytoma (PEM) represents a group of rare, heavily pigmented melanocytic tumors encompassing lesions previously designated as "animal-type melanomas" and "epithelioid blue nevi." Despite the association of multiple such tumors in the setting of Carney complex, most cases of PEM occur spontaneously as solitary neoplasms in otherwise healthy patients. PEM may arise in both children and adults, and has a known propensity to spread to the regional lymph nodes. Despite this latter finding, recurrence at the biopsy site or spread beyond the lymph node basin is exceptionally uncommon. Although the molecular basis for PEM continues to be characterized, findings to date suggest that this category of melanocytic neoplasia has genetic alterations distinct from those seen in common nevi, dysplastic nevi, Spitz nevi, and melanoma. Herein, we present an in-depth clinical, histopathologic, and molecular analysis of a case of PEM occurring on the scalp of a young African American girl found to have a novel NTRK3-SCAPER gene fusion.

Atopic dermatitis is a chronic, pruritic inflammatory disease that often disrupts sleep in severely affected children, but there are limited studies to guide clinical management of these sleep problems. Disease control is crucial in improving sleep, but additional sleep aids may sometimes be helpful in decreasing scratching during the night. This review discusses the benefits and limitations of potential therapeutic agents available to manage sleep disturbances in children with atopic dermatitis.

Harlequin ichthyosis (HI) is associated with high mortality. Early systemic retinoids are widely used, although their use remains debatable. We reported two neonates with homozygous mutations in ABCA12 consistent with harlequin ichthyosis who survived to discharge home with intensive care and without use of systemic retinoids.

Ataxia-telangiectasia (A-T) is an autosomal recessive, multisystem disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias that present in early childhood. Increased incidence of malignancy is also associated with A-T. Hematopoietic malignancies occur most commonly, with a majority being lymphoid cancers; however, there is a risk for other malignancies, such as breast, gastric, and other solid tumors. Herein, we report the case of a 28-year-old woman with A-T with melanoma.

Microcystic lymphatic malformation (also known as lymphangioma circumscriptum) presents as a collection of poorly defined, small lymphatic channels that appear as clear or hemorrhagic vesicles. Lymphangioma circumscriptum can evolve over time with various distributions and colors of the vesicles. The lesions can present clinically anywhere on the body but have a predilection for the proximal limbs, chest, and the mouth. Bleeding and crusting of the lesions can complicate the course. Rarely, infection may occur.

Poikiloderma with neutropenia is also known as “Navajo poikiloderma.” There are only a couple dozen known cases of this rare genodermatosis with autosomal recessive inheritance. Patients present with mutations in C16orf57. Both genders are equally affected. It was recently described in 2011 and found to have a predominance in the Navajo Indian population.

Basal Cell Nevus Syndrome (BCNS) (also known as Gorlin Syndrome) is a rare autosomal dominant disorder associated with basal cell skin cancers and other features. The incidence of BCNS reportedly varies from 1 in 57,000 to 1 in 256,000 [1]. The mutation associated with BCNS is in the PTCH1 gene, a tumor suppressor gene, which plays an important role during embryogenesis affecting cell proliferation, differentiation and cell fate. PTCH mutations have high penetrance but variable phenotypic expression [1].

Keratosis follicularis spinulosa decalvans (KFSD) is a genetic disorder within the family of keratosis pilaris atrophicans. It is most commonly inherited as an x-linked recessive mutation in MBTPS2 [1].

Epidermolysis bullosa simplex (EBS) is a mechanobullous disorder where the skin fragility affects the epidermis. There are both basal and suprabasal subtypes depending on where the blister occurs. It is inherited predominantly in an autosomal dominant fashion. Multiple genes have been implicated in EBS including PKP-1 and DSP for suprabasilar lesions and KRT5, KRT14, PLEC1, ITGA6, ITGB4, and DST for basilar lesions. These gene mutations correlate to proteins such as plakophilin-1, desmoplakin, keratin-5, keratin-14, plectin, alpha-6 beta-4 integrin, and dystonin, respectively [1].

Hypohidrotic ectodermal dysplasia is a rare genodermatosis that is most commonly X-linked with a mutation in the HED gene. It occurs in approximately 1:10,000 male infants.

Nonbullous congenital ichthyosiform erythroderma (CIE) is a clinical entity in the category of autosomal recessive congenital ichthyoses (ARCIs) [1]. Other diagnoses that fall within this category include lamellar ichthyosis and harlequin ichthyosis [1]. CIE is a rare condition with a prevalence of 1 in 100,000 to 200,000 individuals [2]. Nonbullous CIE can be caused by several mutations including ALOX12B, ALOXE3,CERS3, CYP4F22, LIPN, NIPAL4/ICHTHYIN, PNPLA1, TGM1, and ABCA12 [1–3] all of which encode epidermal enzymes critical to the processing of lamellar bodies. Mutations in these enzymes lead to inefficient creation of the cornified envelope and thus an impaired epidermal barrier [1].

Familial dysautonomia with anhidrosis type IV is a very rare cause of anhidrosis. It has an autosomal recessive inheritance. The diagnosis is suspected clinically in patients who present with anhidrosis and repetitive trauma; however, a histamine flare test can be performed. These patients will not produce a flare [1]. Once clinically suspected, genetic testing can confirms an abnormal NTRK1 (TRKA) gene, located on chromosome 1 [1]. This gene encodes for a neurotropic tyrosine kinase receptor type 1, which plays an important role in the nerve growth factor pathway ultimately leading to the failure to thrive of unmyelinated fibers and some small myelinated fibers [1].

Conradi-Hunermann-Happle (CHH) syndrome is a type of X-linked dominant ichthyosis. Other etiologies in this category include congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome). CHH is also known as X-linked dominant chondrodysplasia punctata. As an X-linked dominant disorder, CHH is lethal in males except for males with XXY phenotype or in the case of mosaicism. This disorder is exceedingly rare [1, 2].

Junctional epidermolysis bullosa (JEB) induces skin fragility slightly deeper in the basement membrane zone affecting the lamina lucida. It is most commonly inherited in an autosomal recessive manner. Mutations include LAMA3, LAMB3, LAMC2, COL17A1, ITGA6, ITGB4 corresponding to the proteins laminin-332, type XVII collagen, and alpha-6 beta-4 integrin.

Hyper-immunoglobulin E (IgE) syndrome (HIES) is a rare clinical entity that was first recognized by Davis in 1966 that affects 1:100,000 patients annually [1]. HIES is a primary immunodeficiency, previously called Job syndrome. It is equally prevalent in men and women (Table 1.1).

Dystrophic epidermolysis bullosa (DEB) is the most severe presentation of epidermolysis bullosa with skin fragility occurring in the sublamina densa region. DEB is the second most common presentation of EB after EBS. There are two subtypes of DEB. The first is the dominant dystrophic phenotype (DDEB) and the second is the recessive dystrophic phenotype (RDEB). Both subtypes have mutations in COL7A1, which correlates to type VII collagen.

IMPORTANCE: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. OBJECTIVES: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. EXPOSURES: Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). MAIN OUTCOMES AND MEASURES: Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. RESULTS: Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. CONCLUSIONS AND RELEVANCE: The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

Metastatic Crohn's disease is a rare cutaneous complication of primary Crohn's disease. It is a granulomatous inflammatory process, similar to the pathogenic mechanism of Crohn's disease, that occurs in sites discontiguous from the gastrointestinal tract. Metastatic Crohn's disease can precede the development of Crohn's disease by months to years, and children are more likely to present with metastatic Crohn's disease in the absence of gastrointestinal symptoms. Given that approximately 30% of individuals with Crohn's disease present in childhood, early recognition of extraintestinal manifestations of Crohn's disease such as metastatic Crohn's disease can aid in timely diagnosis and management of bowel disease. We present data from two pediatric cases of metastatic Crohn's disease recently seen at our institution in addition to the 61 reported cases of pediatric metastatic Crohn's disease in the literature. This review article will focus on the epidemiology, pathogenesis, clinical features, and histology of and treatment options for pediatric metastatic Crohn's disease.

Scabies is an infestation of Sarcoptes scabiei resulting in intensely pruritic erythematous papules tipped with hemorrhagic crusts. Current guidelines and medication labels instruct application of topical permethrin 5% cream from neck down for treatment of adult patients with scabies. Although scalp and head involvement are observed in infants, it is rare in older children and adults. Herein, we present a case of an 11-month-old patient who had scalp involvement, and required a scalp-to-toes application of permethrin. We also present a 77-year-old patient with scabies involving the head, who failed initial treatment when permethrin was applied neck down, but had subsequent resolution when it was applied scalp-to-toes. These cases provide impetus for review of current guidelines to reflect application of topical permethrin 5% cream to all external surfaces of the body including the scalp and head.

Perioral dermatitis is a common acneiform facial eruption found in both adults and children. Its variants are periorificial and granulomatous periorificial dermatitis. The etiology of perioral dermatitis remains unknown; however, topical corticosteroid use on the face commonly precedes the manifestation of this condition. There are an overwhelming number of treatment options for perioral dermatitis, and the options in children are slightly different from those in adults for both systemic medications and topical treatment. This article provides a literature review of the various applicable treatments available based on the level and quality of the evidence by the US Preventive Service Task Force. Oral tetracycline reveals the best valid evidence. However, if the patient is less than 8 years old, then this oral therapy may not be suitable. Topical metronidazole, erythromycin, and pimecrolimus also represent effective treatment choices with good evidence. Topical corticosteroid use is common in these cases and the question of whether it is a good treatment or a cause remains unanswered. Corticosteroid cream can improve the clinical picture, but there is a risk of rebound when treatment is stopped. We propose a treatment algorithm to assist dermatologists, pediatric dermatologists, and general practitioners encountering this condition.

Photodermatoses are a group of skin disorders caused by abnormal reaction to ultraviolet radiation. Photodermatoses are divided into four groups: (1) immunologically mediated photodermatoses; (2) chemical- and drug-induced photodermatoses; (3) photoaggravated dermatoses; and (4) hereditary photodermatoses. This contribution discusses differences in the approach and diagnosis of pediatric and adult patients with suspected photodermatoses, focusing on immunologically mediated photodermatoses and chemical- and drug-induced photodermatoses.

Here, we describe a case of a patient with known poikiloderma with neutropenia who developed cutaneous squamous cell carcinoma in a chronically sun-exposed area at the age of 14. To date, there is only one other report of this association. This report highlights the need for routine skin cancer screening in patients with this diagnosis as well as the importance of a correct initial diagnosis.

Bullous dermolysis of the newborn (BDN) is a subtype of dystrophic epidermolysis bullosa caused by mutations in type VII collagen resulting in disorganized anchoring fibrils and sublamina densa blister formation. Disease activity is usually confined to the first year of life, with restoration of physiologic type VII collagen localization. We report four new cases of BDN and review the utility of immunofluorescence mapping in establishing the diagnosis.

Pediatric Sweet syndrome (acute neutrophilic dermatosis) is a rare dermatosis in children characterized by painful papules or nodules and a dense neutrophilic infiltrate in the dermis on histopathology. To date, there are less than 100 cases reported in the literature. Because of the rarity of this disease, controversies in its pathogenesis, classification, clinical presentations, and treatment exist. These controversies are discussed in this chapter.

markdownabstractPediatric dermatology is a young field that combines dermatologic and pediatric skills and expertises. Knowledge of dermatology and pediatrics is necessary for optimal care of children with skin diseases. A multidisciplinary approach in which there is cooperation between dermatologists and pediatricians is essential and makes that 1 + 1 (dermatologist + pediatrician) equals 2 but is actually more than 2. This has always been the slogan of our Dutch courses in pediatric dermatology that were organized for more than 20 years. Pediatric dermatology is officially started as a subspeciality in many countries and recognized as a terminology beginning in 1972 in Mexico. The number of pediatric dermatologists started small and has been growing quickly in the last several decades. Pediatric dermatology was earlier called dermatology of the child. Since the 1980s, developments have been impressive with several specific pediatric dermatology textbooks, as well as world, European, regional, and national congresses. The interest in this field has grown, and pediatric dermatology is now an integral part of most dermatological and pediatric meetings. The (US) American Board of Medical Specialties, which oversees all medical specialties, has demanded that specific pediatric dermatology teaching criteria be included in the training of all US trained general dermatologists. In this book, subjects were chosen based on practical controversial problems in pediatric dermatology, so the content is not structured after basic classification or subgrouping of dermatological disorders but according to controversies in diagnosis and treatment of childhood dermatological disorders. It will help the authors and readers to think about and evaluate pediatric dermatology dilemmas. In this way it will help you to perform a critical and well-balanced and most evidence-based diagnosis, approach, and treatment of the disease involved.

We report a case of a 2-week-old white female who presented with large stellate atrophic skin defects on bilateral thighs and knees at birth. The pregnancy was complicated by the death of monozygotic twin at the 16th week of gestation. This represents aplasia cutis congenita with fetus papyraceus. This rare condition is defined as the congenital skin defect and intrauterine death of fetus with or without a stillborn fetus pressed flat by the growing twin (fetus papyraceus) at delivery time. Aplasia cutis congenita coexisting with fetus papyraceus has a distinctive and reproducible distribution pattern of bilateral symmetrical truncal, buttock, and thigh lesions related to fetal death during the late first to early second trimester. There are at least 44 reported cases of this disorder in the English literature. We discuss our case and review the literature.

Mastocytosis is a broad term used for a group of disorders characterized by accumulation of mast cells in the skin with or without extracutaneous involvement. The clinical spectrum of the disease varies from only cutaneous lesions to highly aggressive systemic involvement such as mast cell leukemia. Mastocytosis can present from birth to adulthood. In children, mastocytosis is usually benign, and there is a good chance of spontaneous regression at puberty, unlike adult-onset disease, which is generally systemic and more severe. Moreover, individuals with systemic mastocytosis may be at risk of developing hematologic malignancies. We describe a girl who presented to us with a solitary mastocytoma at age 5 and later developed maculopapular cutaneous mastocytosis. At age 23, after an episode of anaphylactic shock, a bone marrow examination revealed mast cell leukemia. She ultimately died despite aggressive chemotherapy and bone marrow transplantation.