Search

Objectives To compare prevalence and severity of diaper dermatitis (DD) in infants and toddlers (babies) across three countries (China, USA, and Germany), including diapered skin measures and caregiver practices. Methods A cross‐sectional study of 1791 babies (~600 from each country) was recruited at each clinical site. Based on regional toilet‐training habits, exclusively diaper‐wearing infants were recruited between ages 2‐8 months in China and 2‐18 months in the USA and Germany. DD was measured, as well as skin pH, transepidermal water loss (TEWL), and relative humidity (RH) in the diapered region. Caregiver habits were collected via a questionnaire and included information on hygienic practices. Results Diaper dermatitis was highest in the perianal area, followed by the intertriginous, genital, and buttock regions. In general, DD was significantly lower in babies in China, highest in Germany, and intermediate in the USA. This rank ordering of DD by geography was also observed in baby age 2‐8 months. The lower DD observed in China was associated with lower skin pH and TEWL on diapered skin and decreased RH in the diaper. Chinese caregivers had the highest rate of prophylactic topical product usage, the most robust cleaning of the diapered area, lack of cleansing after urine‐only diaper changes, and Chinese infants spent the least time in an overnight diaper. Conclusions These data suggest caregiver behaviors including prophylactic use of topical products, thorough cleaning after stooling and reduced time in an overnight diaper are associated with less DD, lower superficial skin pH, and enhanced skin barrier.

Collagen makes up a large proportion of the human body, particularly the skin. As the body ages, collagen content decreases, resulting in wrinkled skin and decreased wound healing capabilities. This paper presents a method of delivering type I collagen into porcine and human skin utilizing a polyvinylpyrrolidone microneedle delivery system. The microneedle patches were made with concentrations of 1, 2, 4, and 8% type I collagen (w/w). Microneedle structures and the distribution of collagen were characterized using scanning electron microscopy and confocal microscopy. Patches were then applied on the porcine and human skin, and their effectiveness was examined using fluorescence microscopy. The results illustrate that this microneedle delivery system is effective in delivering collagen I into the epidermis and dermis of porcine and human skin. Since the technique presented in this paper is quick, safe, effective and easy, it can be considered as a new collagen delivery method for cosmetic and therapeutic applications.

Pruritus is a common complication in patients with epidermolysis bullosa (EB). There is limited published data about the treatments that individuals with EB use for pruritus. The objective of the current study was to determine quantitatively which treatments individuals with EB have used for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. A questionnaire was developed to evaluate the treatments and therapies used for pruritus in patients of all ages and for all types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (-2 = relieves itch a lot, -1 = relieves itch a little, 0 = no change, 1 = increases itch a little, 2 = increases itch a lot) was used to evaluate perceived effectiveness. Patients from seven North American EB centers were invited to participate. Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean = -1.1), topical prescription corticosteroids (mean = -1.0), oils (mean = -0.9), oral hydroxyzine (mean = -0.9), topical diphenhydramine (mean = -0.9), and vaporizing rub (menthol, camphor, eucalyptus) (mean = -0.9). Systemic opioids (mean = 0.3), adherent bandages (mean = 0.3), and bleach baths (mean = 0.2) slightly increased pruritus. Randomized controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in individuals with EB.

Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB and factors that contribute to pruritus are unknown. The objective of the current study was to quantitatively identify and to characterize pruritus that EB patients experience using a comprehensive online questionnaire. A questionnaire was developed to evaluate pruritus in all ages and all types of EB. Questions that characterize pruritus were included and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. One hundred forty-six of 216 questionnaires were completed (response rate 68%; 73 male, 73 female; median age 20.0 years). Using a 5-point Likert scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), itchiness was the most bothersome EB complication (mean 3.3). The average daily frequency of pruritus increased with self-reported EB severity. Pruritus was most frequent at bedtime (mean 3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Pruritus is common in individuals with EB and can be bothersome. Future studies will need to investigate the most effective treatments given to individuals with EB for pruritus.

Background Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications. Objective We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children. Methods Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline. Results Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal. Limitations A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations. Conclusions Sildenafil can reduce lymphatic malformation volume and symptoms in some children.

Epidermolysis bullosa (EB) is a genetic condition characterized by skin fragility and blistering. There is no instrument available for clinical outcome research measurements. Our aim was to develop a comprehensive instrument that is easy to use in the context of interventional studies. Item collection was accomplished using a two-step Delphi Internet survey process for practitioners and qualitative content analysis of patient and family interviews. Items were reduced based on frequency and importance using a 4-point Likert scale and were subject to consensus (>80% agreement) using the nominal group technique. Pilot data testing was performed in 21 consecutive patients attending an EB clinic. The final score, Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa (iscorEB), is a combined score that contains clinician items grouped in five domains (skin, mucosa, organ involvement, laboratory abnormalities, and complications and procedures; maximum score 114) and patient-derived items (pain, itch, functional limitations, sleep, mood, and effect on daily and leisurely activities; maximum score 120). Pilot testing revealed that combined (see below) and subscores were able to differentiate between EB subtypes and degrees of clinical severity (EB simplex 21.7 ± 16.5, junctional EB 28.0 ± 20.7, dystrophic EB 57.3 ± 24.6, p = 0.007; mild 17.3 ± 9.6, moderate 41.0 ± 19.4, and severe 64.5 ± 22.6, p < 0.001). There was high correlation between clinician and patient subscores (correlation coefficient = 0.79, p < 0.001). iscorEB seems to be a sensitive tool in differentiating between EB types and across the clinical spectrum of severity. Further validation studies are needed.

The relationship between food and environmental allergens in contributing to eczema risk is unclear on a multiethnic population level. Our purpose was to determine whether sensitization to specific dietary and environmental allergens as measured according to higher specific immunoglobulin E (IgE) levels is associated with eczema risk in children. National Health and Nutrition Examination Survey participants ages 1 to 17 years were asked whether they had ever received a diagnosis of eczema from a physician (n = 538). Total and specific serum IgE levels for four dietary allergens (egg, cow's milk, peanut, and shrimp) and five environmental allergens (dust mite, cat, dog, Aspergillus, and Alternaria) were measured. Logistic regression was used to examine the association between eczema and IgE levels. In the United States, 10.4 million children (15.6%) have a history of eczema. Eczema was more common in black children (p < 0.001) and in children from families with higher income and education (p = 0.01). The median total IgE levels were higher in children with a history of eczema than in those without (66.4 vs 50.6 kU/L, p = 0.004). In multivariate analysis adjusted for age, race, sex, family income, household education, and physician-diagnosed asthma, eczema was significantly associated with sensitization to cat dander (odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.05, 1.4, p = 0.009) and dog dander (OR = 1.5, 95% CI, 1.2, 1.7, p < 0.001). After correction for multiple comparisons, only sensitization to dog dander remained significant. U.S. children with eczema are most likely to be sensitized to dog dander. Future prospective studies should further explore this relationship.

Background Our group's 2009 study of the integrity of the dermatology match revealed that some dermatology program directors violated National Resident Matching Program (NRMP) policy during their communications with applicants. Our group's article concluded with recommendations to change this behavior. Objective We repeated a survey of dermatology applicants to understand if dermatology program personnel behavior has changed since our group's 2009 study of the dermatology match. Methods We surveyed 2011 applicants to Department of Dermatology, Stanford University, Palo Alto, CA. The survey was anonymous and available online. Results Of applicants, 14% were asked to reveal how they intended to rank a program before match day. Of applicants, 32% felt pressured to reveal how they intended to rank programs. Of applicants, 90% were asked about interviews at other programs. Of applicants, 44% were asked about their marital status and 19% were asked if they had children or intended to have children. Limitations The response rate for applicants was 53%. Conclusion Although our previous study increased knowledge about the problems within the dermatology match, dermatology program personnel continue to violate NRMP policy. The most widespread violations are asking applicants where they will interview, asking applicants if they are married, and pressuring applicants to reveal how they intend to rank programs. We continue to recommend that programs avoid postinterview contact, and recommend that the NRMP create training videos for applicants and interviewers.

Background National Resident Matching Program (NRMP) policy outlines the conduct expected by both program directors and residency applicants. However, recent studies and personal experiences have introduced the possibility that NRMP policy is violated during the residency application process. Objective To investigate the communications that occur between dermatology applicants and dermatology programs during the residency application process. Methods From April to July 2009, we surveyed 2009 Stanford dermatology applicants, current US dermatology residents, and US dermatology program directors. The survey was anonymous and available online. The main outcome measures were the frequency and incidence of dermatology NRMP policy violations. Results Thirty-one percent of Stanford applicants and 19% of US dermatology residents felt pressured to reveal to programs how they ranked them before match day. Seventeen percent of Stanford applicants and 14% of US dermatology residents witnessed behavior that made them feel uncomfortable or that they thought was a possible ethical infraction of NRMP policy. Limitations Response rates were as follows: 43% of Stanford applicants, 46% of residents, and 61% of program directors. Conclusions Our data suggest that some dermatology program directors violate NRMP policy during their communications with applicants. The most widespread violation is pressuring applicants into revealing how they intend to rank programs. Other violations include apparent sexual discrimination and reserving NRMP positions for preselected applicants. Additional studies should be done in order to determine the incidence of dermatology applicants violating NRMP policy.

Recent discussions regarding the burden of skin disease and patient-centered medicine highlight the profound effects skin disease can have on individuals, their families, and society as a whole. Local support groups, often connected to national patient advocacy groups, can be an invaluable resource for patients, and offer physicians the opportunity to learn more about patients' disease experiences while providing adjunctive therapy for conditions such as alopecia areata and vitiligo, for which medical options are often limited. We created a support group for children with alopecia areata and their parents as a model for other diseases such as vitiligo and epidermolysis bullosa. Herein we outline the steps involved in establishing a support group, including the many resources available for patient support, steps in the recruitment of patients, topics for discussion and goals for the group, and the logistics of running a meeting. Creating this family support group was a relatively straightforward and rewarding experience for us, and we hope that other pediatric dermatologists can utilize this model for their patients.

Dystrophic EB (DEB) is a blistering skin disease caused by mutations in the gene (COL7A1) encoding type VII collagen (C7). DEB can be inherited by either dominant (DDEB) or recessive (RDEB) mechanisms. RDEB results in severe wounds and scarring, as well as extracutaneous manifestations such as esophageal strictures, chronic anemia, and pseudosyndactyly. DDEB is generally a milder form, with fewer and less severe blisters.(1)

Recessive dystrophic epidermolysis bullosa is a severe genetic blistering skin condition resulting in chronic wounds. Nonhealing wounds were treated over 8 weeks using a reconstituted natural purified type I collagen skin substitute. Chronic wounds were defined as nonhealing wounds present for longer than 6 months. For each patient, two chronic wounds were identified and randomized into a control or treatment group. Both groups received standard-of-care wound dressings. The treatment group received an additional type I collagen skin substitute. Wound size was measured at baseline and weeks 1, 4, and 8. Pain, pruritus, and burning and stinging were assessed. Wound cultures were obtained at baseline and thereafter as was considered clinically relevant. Ten subjects were enrolled; seven completed the study. Six subjects showed a positive response to the type I collagen skin substitute. Three subjects demonstrated full wound reepithelialization. Wounds treated using the collagen skin substitute showed statistically significantly greater improvement. Average scores for pruritus and pain decreased significantly. Reconstituted natural purified type I collagen skin substitutes improved the healing of chronic wounds and may be a valuable addition to the epidermolysis bullosa wound care arsenal.

The biotech industry is the usual venue of new drug development, with costs estimated between $500 million and $2 billion per drug developed (Adams and Brantner, 2006). Occasionally, members of an academic medical community may choose to develop a new drug within their own institution because they are focused on an orphan disease and/or their new therapy may lack a successful financial model. The Dermatology Department at Stanford University School of Medicine has focused on creating a successful treatment for epidermolysis bullosa since 1988. Support for this process has come from philanthropy (http://www.ebkids.org) as well as federal and state funding.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1 -corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1 -corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

Importance Describing the relationship between the availability of free prescription drug samples and dermatologists’ prescribing patterns on a national scale can help inform policy guidelines on the use of free samples in a physician’s office. Objectives To investigate the relationships between free drug samples and dermatologists’ local and national prescribing patterns and between the availability of free drug samples and prescription costs. Design, Setting, and Participants Cross-sectional study investigating prescribing practices for acne, a common dermatologic condition for which free samples are often available. The settings were, first, the offices of nationally representative dermatologists from the National Disease and Therapeutic Index (an IMS Health Incorporated database) and, second, an academic medical center clinic without samples. Participants were ambulatory patients who received a prescription from a dermatologist for a primary initial diagnosis of acne vulgaris or rosacea in 2010. Main Outcomes and Measures National trends in dermatologist prescribing patterns, the degree of correlation between the availability of free samples and the prescribing of brand-name medications, and the mean cost of acne medications prescribed per office visit nationally and at an academic medical center without samples. Results On a national level, the provision of samples with a prescription by dermatologists has been increasing over time, and this increase is correlated ( r = 0.92) with the use of the branded generic drugs promoted by these samples. Branded and branded generic drugs comprised most of the prescriptions written nationally (79%), while they represented only 17% at an academic medical center clinic without samples. Because of the increased use of branded and branded generic drugs, the national mean total retail cost of prescriptions at an office visit for acne was conservatively estimated to be 2 times higher (approximately $465 nationally vs $200 at an academic medical center without samples). Conclusions and Relevance Free drug samples can alter the prescribing habits of physicians away from the use of less expensive generic medications. The benefits of free samples in dermatology must be weighed against potential negative effects on prescribing behavior and prescription costs.

Background Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have advanced in our development of a novel diaper that delivers dermatological formulations to help protect the skin from over-hydration and irritation. Objective To determine the clinical benefits of a novel disposable diaper designed to deliver a zinc oxide and petrolatum-based formulation continuously to the skin during use. Methods All studies were independent, blinded, randomized clinical trials. Study A was conducted to confirm transfer of the zinc oxide/petrolatum (ZnO/Pet) formulation from the diaper to the child’s skin during use. Children wore a single diaper for 3 h or multiple diapers for 24 h. After the use period, stratum corneum samples were taken from each child and analysed for ZnO/Pet. Study B evaluated the prevention of skin irritation and barrier damage from a standard skin irritant (SLS) in an adult arm model. Study C evaluated skin erythema and diaper rash in 268 infants over a 4-week usage period. One half of the infants used the ZnO/Pet diaper, while the other half used a control diaper that was identical except for the absence of the ZnO/Pet formulation. Results The ointment formulation and ZnO transferred effectively from the diaper to the child’s skin during product use. Transfer of ZnO increased from 4.2 µg/cm2 at 3 h to > 8 µg/cm2 at 24 h. Exposure to the formulations directly on adult skin prior to an irritant challenge was associated with up to a 3.5 reduction in skin barrier damage and skin erythema. Greatest reductions were seen for the ZnO containing formulations. Wearing of the formulation treated diaper was also associated with a significant reduction in skin erythema and diaper rash compared to the control product. Conclusions The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper.

Objective:To review the literature addressing the care of neonatal skin.Data Sources:Computerized searches in MEDLINE and CINAHL, as well as references cited in articles reviewed. Key concepts in the searches included neonatal skin differences; neonatal skin and care practices for skin integrity; neonatal skin and toxicity; permeability; and contact irritant sensitization.Study Selection:Articles and comprehensive works relevant to key concepts and published after 1963, with an emphasis on new findings from 1993 to 1999. One hundred two citations were identified as useful to this review.Data Extraction:Data were extracted and organized under the following headings: anatomy and physiology of the skin; physiologic and anatomic differences in neonatal skin; nutritional deficiencies; skin care practices; and care of skin breakdown.Data Synthesis:Newborns’ skin is at risk for disruption of normal barrier function because of trauma. In light of available evidence about differences in neonatal skin development, clinical practice guidelines are suggested for baths, lubrication, antimicrobial skin disinfection, and adhesive removal. In addition, basic care practices are suggested for maintaining skin integrity, reducing exposure to potentially toxic substances, and promoting skin health beyond the neonatal period. Preventive care recommendations are made for reducing trauma, protecting the skin’s immature barrier function, and promoting skin integrity.Conclusions:This review generated evidence with which to create a new and comprehensive practice guideline for clinicians. Evaluation of the guideline is under way at 58 U.S. sites.

Mitochondrial DNA syndromes are an emerging class of diseases that can present at any age. Clinical findings are legion and may include renal tubulopathy, growth retardation, myopathy, seizures, and ophthalmoplegia. Mitochondrial DNA syndromes have presented with symmetric cervical lipomas, poikiloderma, and anhidrosis. We describe a child with a novel mitochondrial DNA syndrome who had poikiloderma on sun-exposed areas. We also reviewed 274 patients with mitochondrial DNA disorders for skin findings. Symmetric cervical lipomas were consistently associated with myoclonic epilepsy as part of 1 syndrome. With the exception of lipomas, skin findings were reported in 16 patients. (J Am Acad Dermatol 1998;39:819-23.)

To treat or not to treat, that is the question. Two cutaneous infections, warts and molluscum contagiosum, have evaded eradication for centuries, and the viruses continue to thrive and to expand in number despite all attempts at destruction. Meanwhile, many cases regress spontaneously. In this article, the authors review the characteristics of the viruses involved; discuss their transmission, epidemiology, and clinical manifestations; and assess the effectiveness of available therapies.

Objective: Premature infants have an ineffective epidermal barrier. The aim of this study was to investigate the cutaneous and systemic effects of preservative-free topical ointment therapy in premature infants. Study design: We conducted a prospective, randomized study of 60 infants less than 33 weeks' estimated gestational age. The treated infants received therapy for 2 weeks with twice-daily preservative-free topical ointment therapy while the control group received no topical treatment or as-needed therapy with a waterin-oil emollient. Data collection included transepidermal water loss (TEWL) measurement, skin condition evaluations, fungal and quantitative bacterial skin cultures, analysis of fluid requirements, patterns of weight loss or gain, and the incidence of blood and cerebrospinal fluid cultures positive for microorganisms. Results: We found that topical ointment therapy significantly decreased TEWL during the first 6 hours after the initial application. TEWL was decreased by 67% (p = 0.0001) when measured 30 minutes after application and 34% (p = 0.001) when measured 4 to 6 hours after application. We also observed significantly superior skin condition scores in the treated group on study days 7 and 14 (p = 0.001 and 0.0004, respectively). Quantitative bacterial cultures revealed significantly less colonization of the axilla on day 2, 3, or 4 and on day 14 (p = 0.008 and 0.04, respectively). The incidence of positive findings in blood and/or cerebrospinal fluid cultures was 3.3% in the treated group of infants versus 26.7% in the control group (p = 0.02). There was no statistical difference in the fluid requirements or patterns of weight gain or loss during the 2 weeks of the study. Conclusions: Preservative-free topical ointment therapy decreased TEWL for 6 hours after application, decreased the severity of dermatitis, and decreased bacterial colonization of axillary skin. Infants treated with ointment had fewer blood and cerebrospinal fluid cultures positive for microorganisms. These data support the use of topical ointment therapy in very premature infants during the first weeks after birth.

This article reviews in detail the pathogenesis, clinical characteristics and management of impetigo in children. Impetigo is the most common bacterial skin infection of children. Most cases of nonbullous impetigo and all cases of bullous impetigo are caused by Staphylococcus aureus. The remainder of cases of nonbullous impetigo are due to group A beta hemolytic streptococci (GABHS). GABHS colonize the skin directly by binding to sites on fibronectin that are exposed by trauma. In contrast, S. aureus colonizes the nasal epithelium first; from this reservoir, colonization of the skin occurs. Patients with recurrent impetigo should be evaluated for carriage of S. aureus. Superficial, localized impetigo may be treated successfully in more than 90% of cases with topical application of mupirocin ointment. Impetigo that is widespread or involves deeper tissues should be treated with a beta-lactamase-resistant oral antibiotic. The choice of antibiotics is affected by the local prevalence of resistance to erythromycin among strains of S. aureus, antibiotic cost and availability, and issues of compliance.

Infants of less than 32 wk gestation have a defective epidermal barrier, with increased skin permeability and transepidermal water loss (TEWL). We studied the effect of a nonadhesive semipermeable dressing on the epidermal barrier of premature infants and on fetal skin transplanted to nude mice. Fifteen infants with a mean estimated gestational age of 27.7 wk and 16 human fetal skin grafts (estimated gestational age, 23-26 wk) transplanted to eight nude mice were studied. One lower leg (or skin graft) was treated and the other left untreated as a control. In the infants, TEWL was measured on control skin and treated skin (both through the dressing and after temporary dressing removal) on d 0, 1, 2, 4, and 7. Bacterial and fungal cultures were also performed. In the mice, TEWL and skin blood flow were measured on d 0, 2, and 4. Biopsies were obtained on d 4 for a cell proliferation assay, histology, and electron microscopy. Treated infant skin showed a consistently lower bacterial number and a significantly decreased TEWL (measured through the dressing). There was also a significantly lower TEWL on the treated side, measured after temporary dressing removal, on d 1, 2, 4, and 7, documenting improved epidermal barrier function. The animal study revealed decreased TEWL and a nearly 2-fold greater d-4 keratinocyte proliferation (p = 0.01) in treated skin and decreased blood flow on d 4 in control skin (p = 0.01). There was no significant difference in the volume density of membrane coating granules or the morphology of intercorneocyte spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Pilomatricoma is a benign tumor that presents as a 3-30-mm, firm, solitary, deep, dermal or subcutaneous tumor on the head, neck, or upper extremities. The clinical diagnosis is often made by the firm, sometimes rock-hard texture of the skin. The diagnosis can be confirmed by a skin biopsy or excision of the lesion. We have recently noted that pilomatricomas appear as a black mass in the skin when the lesion is transilluminated by placing the light of a fiberoptic otoscope adjacent to the skin lesion. To our knowledge, this is the first report demonstrating preoperative diagnosis of pilomatricoma by transilluminating the lesion with an otoscope.

Multiple Spitz nevi are rare and may occur in agminated, widespread, or dermatomal distributions. Agminated Spitz nevi usually arise in children, presenting on grossly normal, hyperpigmented, or most rarely, hypopigmented skin. We present a child with Langerhans cell histiocytosis who developed bilateral agminated Spitz nevi in the inguinal area. Unusual features included the multifocal distribution, bilateral inguinal location, and co-occurrence with Langerhans cell histiocytosis.

In spite of advances in the molecular diagnosis of recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disease due to a deficiency of type VII collagen at the basement membrane zone (BMZ) of stratified epithelium, current therapy is limited to supportive palliation. Gene delivery has shown promise in short-term experiments; however, its long-term sustainability through multiple turnover cycles in human tissue has awaited confirmation. To characterize approaches for long-term genetic correction, retroviral vectors were constructed containing long terminal repeat-driven full-length and epitope-tagged COL7A1 cDNA and evaluated for durability of type VII collagen expression and function in RDEB skin tissue regenerated on immune-deficient mice. Type VII collagen expression was maintained for 1 year in vivo, or over 12 epidermal turnover cycles, with no abnormalities in skin morphology or self-renewal. Type VII collagen restoration led to correction of RDEB disease features, including reestablishment of anchoring fibrils at the BMZ. This approach confirms durably corrective and noninjurious gene delivery to long-lived epidermal progenitors and provides the foundation for a human clinical trial of ex vivo gene delivery in RDEB.

The Herlitz subtype of junctional epidermolysis bullosa (JEB-H) is a lethal genetic disorder characterized by recurrent and persistent erosions of the epithelial surfaces that heal with exuberant granulation tissue. In addition, respiratory distress, refractory anemia and failure to thrive are often seen. Mortality in the first year of life approaches 90%. JEB-H is caused by mutations in the genes that encode the protein laminin 5, a structural molecule involved in the adhesion of epidermis to dermis. There is currently no cure for JEB-H. Medical interventions treat complications but do not ultimately limit mortality. Ethical principles contend that offering comfort and company to the patient and family, not aggressive therapies, should comprise the mainstay of care for affected infants.

Trichoepitheliomas commonly appear as sporadic solitary lesions or, more rarely, as multiple lesions that are often dominantly inherited. We describe an 8-year-old boy with multiple facial papules that coalesced into a large plaque. This presentation of multiple trichoepitheliomas may represent an unusual type of nevus.

The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene therapy widely available clinically.

The primary goals of preventing and treating diaper dermatitis include keeping the skin dry, protected, and infection free. Frequent diaper changes with the superabsorbent disposable diapers may be the best tactic for infants' skin, if not the environment. Also, the more time that infants spend without diapers, the less dermatitis they experience, but a practical balance must be struck. Gentle cleansing and barrier creams are beneficial, and candidal infection must be treated. Finally, any recalcitrant diaper dermatitis must be further investigated to uncover underlying disease (Fig. 6).

We conducted a 6-week randomized, blinded study that compared mometasone furoate 0.1% cream, applied once daily, and hydrocortisone 1.0% cream, applied twice daily, in 48 children with moderate to severe atopic dermatitis. Mometasone furoate, a moderate-potency steroid, produced significantly greater improvement than the low-potency hydrocortisone used twice daily. The difference in therapeutic response was particularly evident in patients with involvement of more than 25% of their body surface area. Morning plasma Cortisol levels were assayed before treatment, after 1 week of therapy, and at the end of the clinical trial. Plasma Cortisol levels were transiently suppressed in one child who was treated with hydrocortisone and in none of the children treated with mometasone.

Amino acid compositions of skin samples from young and old subjects and from age-matched donors with dry skin syndrome (xerosis) were examined. The amino acid contents of the free amino acid (FAA) fraction, soluble hydrolysate (SH) fraction, and whole cell hydrolysate (WCH) were determined. The greatest differences were observed between the FAA compositions of the young and old normal subjects. Xerosis did not appear to affect the amino acid compositions of samples from young subjects as much as old subjects. Overall, the effect of aging on the amino acid contents was more pronounced than the effect of xerosis. The amino acid composition of the FAA showed a high degree of similarity to filaggrin, whereas the WCH showed a similarity to keratin.

We describe a patient with the keratitis, ichthyosis, and deafness (KID) syndrome who also had a generalized cytomegalovirus infection. Patients with the KID syndrome are susceptible to not only bacterial and fungal infections, but also to viral infections.

An experimental transplantation model using human fetal skin was applied to approach the question of the embryologic origin of human Merkel cells. Palmar and plantar skin from five fetuses, between 8 and 11 weeks of estimated gestational age (EGA), was xenografted to subcutaneous beds of nude mice. After 4 or 8 weeks of growth, biopsies were taken from these xenografts and examined for the presence of Merkel cells, using immunocytochemistry with antibodies specific for simple epithelial-type cytokeratins and neuron-specific enolase (NSE) as well as using electron microscopy. Skin from the same fetuses at the time of transplantation was screened in the same way. In all fetuses, no (or very scarce) epidermal Merkel cells were detected at the transplantation time, but in all cases abundant epidermal Merkel cells of apparent human origin were found after 4 or 8 weeks in xenograft culture. Dermal nerve fibers, as recognized by neurofilament antibodies, were scarce or essentially absent in the xenografts. These results indicate that Merkel cells regularly develop in epidermis dissected and xenografted in an early fetal stage, although the dissection implies the interruption of the dermal nerves. The results strongly support the notion of the origin of Merkel cells from epidermal precursor cells. The apparent absence of dermal Merkel cells and dermal nerve fibers in the xenografts suggests that the presence of dermal sensory nerve fibers may be required for the dropping off of epidermal Merkel cells into the upper dermis, which occurs in normal fetal development.

A murine monoclonal antibody (ECS-1) was prepared from BALB/c mice immunized with trypsinized cultured human foreskin keratinocytes. The antibody showed a pattern suggestive of intercellular staining on the nucleated layers of normal human epidermis, adult palm, mouse lip epidermis, and cultured human keratinocytes. ECS-1 stained human fetal skin by 9 weeks estimated gestational age. ECS-1 reacted with a 35 kD protein extracted from neonatal foreskin epidermis and cultured human keratinocytes. The protein required Nonidet P-40 or sodium dodecyl sulfate and mercaptoethanol for solubilization. ECS-1 induced epidermal cell detachment which was enhanced by complement. ECS- 1 shares characteristics with human pemphigus antibodies.

Thirty-five human fetal skin (HFS) grafts were transplanted to nude mice for 7 to 70 d and evaluated histologically with 64 biopsies. The estimated gestational ages (EGS) of the grafts at the time of the transplantation ranged from 8 to 19 weeks. The maturation of the engrafted fetal skin was evaluated by assessing epidermal, dermal, and appendage development. Within the nude mouse, the HFS demonstrated progression in stratification and maturation of the epidermis. The dermis increased in depth, adding fibrovascular stroma and adipose tissue. The appendages demonstrated invagination, differentiation, and progression of organogenesis. Subcutaneously placed grafts showed the same rate of HFS development as HFS in utero. The grafts transplanted to the surface of the nude mice and exposed to air demonstrated an acceleration of development. We conclude that HFS transplanted to the nude mouse is an effective in vivo model for maintaining and altering HFS maturation.

Four neonates had solitary, congenital, rapidly growing, spontaneously ulcerating tumors of the face, trunk, and extremities. No extracutaneous involvement was found, and all lesions spontaneously involuted. Mononuclear cells of the cutaneous infiltrate were Langerhans'cells. These findings expand the spectrum of congenital self-healing reticulohistiocytosis.

An immune reaction to wheat protein has been previously proposed to explain the pathogenesis of dermatitis herpetiformis. In order to detect and characterize antibodies to gluten in human sera, we developed an enzyme immunoassay for class-specific antibodies. Results of this assay in 49 patients with dermatitis herpetiformis were compared with those of 38 normal control subjects, 11 patients with celiac disease, and 6 small-bowel bypass patients. IgA antibodies to gluten were significantly more frequent in dermatitis herpetiformis sera (28/49) than in normal control sera (4/38). IgG antibodies to gluten were significantly more frequent in both celiac disease (10/11) and dermatitis herpetiformis (16/49) sera than in control (5/38) sera. Dermatitis herpetiformis sera also had an increased prevalence of IgM antibodies to gluten (19/49). Small-bowel bypass patients demonstrated no antibody to gluten. Antibodies to gluten in dermatitis herpetiformis objectively mark a state of immune reactivity to wheat protein and may be involved in the genesis of the cutaneous IgA immune deposits and the skin disease.

A wide spectrum of histopathologic changes has been reported to occur within epidermal nevi. We saw two patients with warty nevoid lesions in which histopathologic features of incontinentia pigmenti, verrucous phase, were present. The diagnosis of incontinentia pigmenti was excluded because both patients were male, lacked a preceding vesicular stage, and did not demonstrate other features of the disorder.

Sulconazole nitrate 1% cream applied twice daily was compared with its vehicle in the treatment of 229 patients with chronic moccasin-type tinea pedis confirmed by positive results of a potassium hydroxide preparation. At admission in this randomized, double-blind, parallel multicenter trial, 131 patients had positive dermatophyte cultures; Trichophyton rubrum was identified in 121 (92%). After 4 weeks of treatment, patients were examined and, if necessary, were treated for an additional 2 weeks. Sulconazole cream was significantly more effective than the vehicle in the treatment of chronic T. rubrum tinea pedis; 57% of patients were cured by sulconazole, compared with 13% cured with the vehicle. Relapse rates, assessed 2 weeks after the end of treatment, were significantly lower in patients treated with sulconazole than in those receiving vehicle (27% vs 71 %). The 103 patients with moccasin-type tinea pedis whose cultures were not positive for T. rubrum achieved similar results.

Many of the morphologic and biochemical changes that occur during human fetal skin development have been described, yet there has been little experimental analysis of the processes that regulate the development of human fetal skin. This is due in part to difficulties in culturing human fetal epidermal keratinocytes. We have successfully cultured fetal keratinocytes in two different in vitro systems; in a serum-free keratinocyte growth medium (KGM) on tissue culture plastic and cocultured with dermal fibroblasts as spheroidal aggregates. To characterize these fetal keratinocytes in vitro we have assessed their ability to express several markers of epidermal differentiation. Human fetal keratinocytes grown on plastic in KGM stratify and express some of the components of the differentiated epidermis, such as involucrin and the high molecular weight keratins. However, these keratinocytes co-express keratins and vimentin and do not form a structured basement membrane. More characteristics of fetal skin are preserved in mixed aggregates of epidermal keratinocytes and dermal fibroblasts, including epidermal stratification, synthesis of basement membrane components, tissue-specific expression of intermediate filaments, involucrin, and expression of high molecular weight keratins. The maintenance of human fetal epidermal keratinocytes in these two in vitro systems and their ability to express many differentiated characteristics suggests that these cultures will be valuable for studies of the molecular mechanisms that regulate the regionally specific differentiation of the human fetal epidermis.

No dermatologic disorder poses so little threat to health and physical cotnfort and yet is so emotionally devastating as alopecia areata. Fortunately, the rate of spontaneous remission is high; nevertheless, management is problematic because of the considerable cosmetic disability imposed by extensive and visible hair loss, and the unpredictability of response to accepted therapeutic agents. Indeed, opinions vary as to whether or not any of the currently employed therapeutic modalities is effective, and there is remarkable diversity in approach to the patient with this problem. This symposium includes two lengthier articles on alopecia areata as well as several shorter commentaries on management by dermatologists with a special interest in this disorder.

Human fetal skin was evaluated for sequential and regional development of several epidermal antigens. Indirect immunofluorescent methods were used to detect laminin, bullous pemphigoid antigen, pemphigus antigen, and anchoring fibril antigens identified by monoclonal antibodies AF1 and AF2. Eighty-three human fetal skin biopsies from 32 human fetuses were examined. The fetuses examined ranged from estimated gestational age (EGA) of 7-38 weeks. Laminin was present in the basement membrane zone of all the fetal tissues examined. Bullous pemphigoid antigen developed first in the palm and sole, 9 weeks EGA, and was present in all other sites by 17 weeks EGA. Pemphigus antigen was present by 11 weeks EGA. AF1 and AF2 staining was not present until 26 weeks EGA, AF1 and AF2 stained epidermal basal cells in addition to the basement membrane zone area. Comparison of human fetal skin development with basal cell carcinoma identified similarities between basal cell carcinoma and early fetal development.

Two anti-keratin monoclonal antibodies, Kab-2 and Kab-3, with specificities for different epitopes of type II (basic) human epidermal keratins, were produced. These antibodies had different immunofluorescent staining patterns on human fetal epidermis. Western blots and solid phase RIA showed both antibodies bound to 65- 67-kD basic keratins (K1 and K2) extracted from foreskin epidermis. Competitive binding studies with the two Kab antibodies and other anti-keratin monoclonal antibodies showed that Kab-2 and Kab-3 recognized related epitopes, distinct from the epitopes recognized by other anti-keratin antibodies AE-1, 2, and 3 Kab-2 and epitopes were epitopes were distinguished by differences in their reactivity with peptides generated by Staphlococcus aureus V8 protease digestion of the K1 keratin; the antibodies recognized both common and unique peptides. Western blots of cyanogen bromide digests of the K1 keratin showed that both Kab antibodies reacted with a 30-kD fragment of the molecule presumed to be the N-terminal CNBr peptide. We interpret these data to indicate that in tissues, portions of the N-terminal region of the K1 keratin are differentially available for reaction with these monoclonal antibodies and that morphologic differences in staining with monoclonal antibodies to the same molecule can reflect epitope specificity or epitope availability related to supramolecular organization.

Basement-membrane-zone (BMZ) components are altered in basal-cell carcinoma (BCC). Electron microscopy has identified areas of normal, discontinuous, or absent BMZ components in human BCC [13, 15, 26]. In the present study, we used new monoclonal antibodies to the anchoring fibrils to study this component of the BMZ. Skin tumors of 11 patients with BCC (10 nodular, 1 superficial) and the palmar pit of a patient with basal-cell nevus syndrome were examined [10] for bullous-pemphigoid antigen (BPA), laminin, and anchoring-fibril antigens recognized by monoclonal antibodies AF1 and AF2 [4, 5]. A wedge of tumor (1 2 mm) was frozen in optimal cutting temperature (OCT) compound (Lab-Tek Products, Naperville, IL, USA) and stored at -70~ until assayed. Fourmicron-thick sections were cut using a Tissue-Tek-II cryomicrotome and placed on gelatin-prepared slides. The tissue sections were air-dried for 20 rain before staining. AF1 and AF2 murine monoclonal antibodies to anchoring fibrils [4, 5] were used as undiluted hybridoma-cell supernatants. Human bullous-pemphigoid serum from a patient in whom the diagnosis had been confirmed by direct and indirect immunofluorescence

A double-blind, vehicle-controlled comparison of two glucocorticosteroid ointments demonstrated that once-daily therapy for psoriasis was effective. After 3 weeks of once-daily therapy, psoriasis subjects treated with betamethasone dipropionate (BD) ointment or diflorasone diacetate (DD) ointment showed statistically significant (p less than 0.01) improvement compared to subjects using vehicle alone.

Prevention or modification of the onset of atopic dermatitis has been difficult to document through prolonged breast feeding or delayed introduction of solid foods. Dietary management of established atopic dermatitis is not routinely indicated for the majority of patients. Dietary management of atopic dermatitis should not be continued indefinitely. Gradual reintroduction of the offending food(s) is often appropriate. The foods most commonly avoided in the management of atopic dermatitis are cow's milk, wheat, eggs, and nuts. Severe or prolonged dietary restrictions should not be instituted without full consideration of their impact on the patient's general health.

Recent advances in neonatal care have greatly decreased mortality and morbidity in premature infants. Those who survive, however, often have significant cutaneous abnormalities. This has led to enhanced understanding and care of the premature infant's skin. Future dermatologic research may develop methods both to control epithelial maturation and to deliver therapy through the skin.

Bullous mastocytosis (diffuse cutaneous mastocytosis) is a rare form of mast cell disease that begins during the first month of life and causes extensive blisters that mimic scalded skin syndrome or bullous erythema multiforme. Discrete pigmented macules, papules, and nodules arc absent and the characteristic leathery induration of skin may not develop until 6 months of age. Skin biopsy shows a subepidermal blister with mast cells at the base. The most serious complications are gastrointestinal hemorrhage and shock. The symptoms of bullous mastocytosis may be modified by a number of new therapeutic agents.