Bari B. Cunningham

MORPHEA AND LOCALIZED SCLERODERMA IN CHILDREN

Localized scleroderma refers to a diverse spectrum of disorders that involve fibrosis of the skin. Children are more likely than adults to develop localized forms of scleroderma. This condition may have devastating effects on growth and development such as limb asymmetry, flexion contractures, and psychological disability. The pathogenesis of localized scleroderma is unknown but its possible relation to Borrelial infection is discussed. This article reviews associated laboratory and radiologic abnormalities, and discusses implications for monitoring disease activity. There is no universally effective therapy for this idiopathic condition and therapy is limited. A rationale for treatment based on disease subtype and severity is provided.

Identifying potential regulators of infantile hemangioma progression through large-scale expression analysis: a possible role for the immune system and indoleamine 2,3 dioxygenase (IDO) during involution.

Hemangiomas are benign endothelial tumors. Often referred to as hemangiomas of infancy (HOI), these tumors are the most common tumor of infancy. Most of these lesions proliferate rapidly in the first months of life, and subsequently slowly involute during early childhood without significant complications. However, they often develop on the head or neck, and may pose a significant cosmetic concern for families. In addition, a fraction of these tumors can grow explosively and ulcerate, bleed, or obstruct vision or airway structures. Current treatments for these tumors are associated with significant side effects, and our knowledge of the biology of hemangiomas is limited. The natural evolution of these lesions creates a unique opportunity to study the changes in gene expression that occur as the endothelium of these tumors proliferates and then subsequently regresses. Such information may also increase our understanding of the basic principals of angiogenesis in normal and abnormal tissue. We have performed large-scale genomic analysis of hemangioma gene expression using DNA microarrays. We recently identified insulin-like growth factor 2 as a potentially important regulator of hemangioma growth using this approach. However, little is known about the mechanisms involved in hemangioma involution. Here we explore the idea that hemangioma involution might be an immune-mediated process and present data to support this concept. We also demonstrate that proliferating hemangiomas express indoleamine 2,3 dioxygenase (IDO) and discuss a possible mechanism that accounts for the often slow regression of these lesions.

Epithelioid blue nevus occurring in children with no evidence of Carney complex.

We report two pediatric patients who had biopsies of solitary lesions diagnosed as epithelioid blue nevi. Histologically these lesions had wedge-shaped, heavily pigmented infiltrates extending to the subcutaneous fat. The infiltrate was composed of spindled and polyhedral cells that were nevomelanocytic cells with nuclear pleomorphism. Also noted were pigmented globular cells interpreted as melanophages. These lesions have the same characteristics as those blue nevi occurring in patients with Carney complex. More recently, adult patients have been identified with similar nevi, but without evidence of Carney complex. To our knowledge, pediatric patients with epithelioid blue nevi, but no evidence of Carney complex have not been described previously.

Epstein-barr virus-associated genital ulcers : An under-recognized disorder

Abstract:  Infectious mononucleosis is the best‐known syndrome associated with primary Epstein–Barr virus infection. Although a variety of cutaneous and mucosal manifestations are recognized in infectious mononucleosis, genital ulcers have only rarely been described. We describe an otherwise healthy 14‐year‐old girl in whom painful genital ulcers developed during an episode of serologically‐confirmed primary Epstein–Barr virus infection. Clinical, serologic, and histopathologic evaluation failed to disclose evidence of any other etiologic explanation for her lesions. The patient remains well, without recurrence. To date, only 13 instances of genital ulceration in females attributable to Epstein–Barr virus infection have been reported.

Use of the Cotton Swab Method in Diagnosing Tinea Capitis

Objective. To evaluate the accuracy of the cotton swab technique for identifying fungal infections of the scalp. The purpose of the study was: 1) to compare the cotton swab technique with the toothbrush method, a popular and reliable means for obtaining specimens; and 2) to ascertain if transport of a specimen, entailing variable transport duration and conditions, impairs the sensitivity and specificity of the technique. Materials and Methods. Part 1 consisted of a prospective, investigator-blinded comparison analysis. Fifty children with scalp findings suspicious for tinea capitis were cultured using both techniques: the toothbrush and cotton swab. Ninety-six culture results were obtained for analysis. The second part of the study consisted of a prospective comparison analysis of cotton swab culture results obtained from samples plated immediately after collection in the physicians office as compared with samples transported to outside laboratories for processing. Thirty-one children with presumed tinea capitis were cultured twice with the cotton swab technique; one sample was immediately plated onto fungal medium and the other sent to an outside lab, the selection of which was dictated by the patients insurance plan. A total of 62 samples were obtained; 58 sample results were used for analysis. Results. In part 1 of the study, 60% of the 48 children analyzed had positive fungal cultures. Eighty percent of these wereTrichophyton species. There was 100% agreement in the results obtained; all patients with positive results using the toothbrush method were also positive when the cotton swab method was used. Similarly, there was complete concordance in laboratory results from the second part of the study. Fifty percent of the 28 children analyzed had positive cultures; 86% grew Trichophytonspecies. All patients who had positive cultures from those samples plated in-office also had positive results from the outside laboratory samples. Conclusions. The cotton swab technique is an easy, atraumatic, inexpensive, and reliable means to evaluate patients with suspected tinea capitis. The method remains sensitive and specific even when transport of these specimens is required and processing is thus delayed. This painless technique requires little technical expertise and can be rapidly performed with a standard cotton tip applicator. It should prove an invaluable aid to practitioners in evaluating patients with possible fungal infections of the scalp.

SCALP syndrome: Sebaceous nevus syndrome, CNS malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis: A distinct syndromic entity

Nevus sebaceus syndrome (SNS) is a constellation of nevus sebaceus with extracutaneous findings, including the ophthalmologic nervous, and musculoskeletal systems. Didymosis aplasticosebacea is a recently described entity consisting of aplasia cutis congenita and nevus sebaceus, implying twin spotting (didymosis). We describe a neonate with a nevus sebaceus on the scalp and a limbal dermoid on her left eye. Contiguous with the nevus sebaceus was a giant congenital melanocytic nevus and numerous areas of membranous aplasia cutis congenita. We propose the acronym SCALP (nevus sebaceus, central nervous system malformations, aplasia cutis congenita, limbal dermoid, pigmented nevus) to summarize the unique features of this case and review the two similar cases in the literature.

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC(-/-) background. XPC(-/-) cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk.

A practical approach for the use of oral isotretinoin for infantile acne.

Abstract:  Infantile acne is a rare occurrence. It is more common in boys and predominately occurs on the cheeks in infants between the ages of 1 and 16 months. Clinically, the lesions range from comedones to inflammatory papulopustules to cysts. Successful therapies include topical tretinoin, benzoyl peroxide and topical and oral erythromycin. For more serious cases, oral isotretinoin (Accutane) has been reported to successfully treat recalcitrant infantile cystic acne. We describe two additional patients with infantile cystic acne treated successfully with oral isotretinoin. The dose of isotretinoin used ranged from 0.2 mg/kg/day to 1.5 mg/kg/day. The treatment duration varied from 5 to 14 months. Careful monthly monitoring is recommended because of the many side effects reported with isotretinoin. Practical tips for the administration of oral isotretinoin in infants are reviewed.

What is Standard of Care in the Evaluation of Elastosis Perforans Serpiginosa? A Survey of Pediatric Dermatologists

Abstract:  Elastosis perforans serpiginosa is a rare chronic dermatosis characterized by extrusion of altered elastic fibers through the epidermis. It often occurs in association with a variety of connective tissue disorders, and may develop following penicillamine therapy; however, it may also present without comorbidities. There are currently no well‐established protocols for the investigation of possible associated disorders in patients who present with elastosis perforans serpiginosa. We describe three patients with idiopathic elastosis perforans serpiginosa seen at our clinic and review the standard of care among 31 pediatric dermatologists surveyed who have cared for such a patient within the last 2 years. Based upon the results of our survey, we conclude that most pediatric dermatologists limit their evaluation of such patients to a thorough patient history and physical examination. This limited approach may be a sufficient evaluation in affected patients who are otherwise healthy.

5% 5‐Fluorouracil Cream for Treatment of Verruca Vulgaris in Children

Abstract:  Warts are a common pediatric skin disease. Most treatments show only modest benefit, and some are poorly tolerated because of pain. 5‐fluorouracil interferes with deoxyribonucleic acid and ribonucleic acid synthesis, and is used to treat genital warts in adults. Efficacy, safety, and tolerability of topical 5% 5‐fluorouracil for treatment of common warts were examined in an open‐label pilot study with pediatric patients. Thirty‐nine children who have at least two hand warts applied 5% 5‐fluorouracil cream (Efudex, Valeant Pharmaceuticals International) once or twice daily, under occlusion for 6 weeks. Assessment of treatment response and side effects was performed at baseline, treatment completion, and 3‐ and 6‐month follow‐ups. Hematology measures, liver function tests, and medication blood levels were reassessed at treatment completion. Eighty‐eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5‐fluorouracil. At 6 month follow‐up, 87% of complete responders had no wart recurrence. Topical 5% 5‐fluorouracil is a safe, effective, and well‐tolerated treatment for warts in children.