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The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.

Background: In recent years propranolol has become the treatment of choice for infantile hemangiomas (IHs). There is broad variation in the approach to propranolol initiation in clinical practice. This retrospective study explored the effectiveness of routine pre-treatment ECG in screening infants being considered for systemic treatment with propranolol., Methods: All patients seen in the outpatient pediatric dermatology clinics at Oregon Health and Sciences University (OHSU) and The Mayo Clinic Rochester (MCR), as well as those seen in multidisciplinary vascular anomalies clinics, who had ECGs obtained prior to planned initiation of propranolol for treatment of IH from 2008 to 2013, were identified. A total of 162 patients were included in the study., Results: We found that 43% (69) of routine ECGs were read as abnormal, leading to 28 formal consultation appointments with pediatric cardiologists. After either formal consultation or informal discussion with cardiology, no patients with initially "abnormal" ECGs were ultimately excluded from treatment with propranolol based on routine ECG findings. Additionally no patients in our cohort experienced an adverse effect during treatment that could have been predicted or prevented by ECG prior to initiation of the propranolol., Conclusion: Our findings suggest that routine ECG may not be necessary or helpful in the vast majority of patients treated with propranolol for IHs., (© 2016 Wiley Periodicals, Inc.)

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections., (© 2013 Wiley Periodicals, Inc.)

PHACE syndrome represents the association of large infantile hemangiomas of the head and neck with brain, cerebrovascular, cardiac, ocular, and ventral or midline defects. Cardiac and cerebrovascular anomalies are the most common extracutaneous features of PHACE, and they also constitute the greatest source of potential morbidity. Congenital heart disease in PHACE is incompletely described, and this study was conducted to better characterize its features. This study of the International PHACE Syndrome Registry represents the largest central review of clinical, radiologic, and histopathologic data for cardiovascular anomalies in patients with PHACE to date. Sixty-two (41%) of 150 subjects had intracardiac, aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian artery was the most common cardiovascular anomaly (present in 31 (21%) of 150 subjects). Coarctation was the second most common anomaly, identified in 28 (19%) of 150 subjects, and can be missed clinically in patients with PHACE because of the frequent association of arch obstruction with aberrant subclavian origin. Twenty-three (37%) of 62 subjects with cardiovascular anomalies required procedural intervention. A greater percentage of hemangiomas were located on the left side of the head and neck in patients with coarctation (46% vs 39%); however, hemangioma distribution did not predict the presence of cardiovascular anomalies overall. In conclusion, PHACE is associated with a high risk of congenital heart disease. Cardiac and aortic arch imaging with detailed assessment of arch patency and brachiocephalic origins is essential for any patient suspected of having PHACE. Longitudinal investigation is needed to determine the long-term outcomes of cardiovascular anomalies in PHACE., (Copyright © 2013 Elsevier Inc. All rights reserved.)

PHACE syndrome is the association of large segmental facial hemangiomas and congenital anomalies, such as posterior fossa malformations, cerebral arterial anomalies, coarctation of the aorta, eye anomalies, and sternal defects. To date, the reported cases of PHACE syndrome have been sporadic, suggesting that PHACE may have a complex pathogenesis. We report here genomic copy number variation (CNV) analysis of 98 individuals with PHACE syndrome as a first step in deciphering a potential genetic basis of PHACE syndrome. A total of 3,772 CNVs (2,507 duplications and 1,265 deletions) were detected in 98 individuals with PHACE syndrome. CNVs were then eliminated if they failed to meet established criteria for quality, spanned centromeres, or did not contain genes. CNVs were defined as "rare" if not documented in the database of genomic variants. Ten rare CNVs were discovered (size range: 134-406  kb), located at 1q32.1, 1q43, 3q26.32-3q26.33, 3p11.1, 7q33, 10q24.32, 12q24.13, 17q11.2, 18p11.31, and Xq28. There were no rare CNV events that occurred in more than one subject. Therefore, further study is needed to determine the significance of these CNVs in the pathogenesis of PHACE syndrome.

Background: The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction., Objective: To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations., Methods: This was a cross-sectional study. Dermatological surveys were designed by the authors and were completed by parents of mutation-positive individuals with CS at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatological examinations were performed by the authors at the CSFN conferences., Results: Cutaneous papillomas were reported in 33 of the 46 (72%) participants, with age of onset ranging from infancy to 22years. Individuals with CS are more likely than patients with cardiofaciocutaneous syndrome (CFC) to present with cutaneous papillomas (72% vs. 5%, P<0·001) and palmoplantar keratoderma (76% vs. 36%, P<0·001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (9% vs. 90%, P<0·001) or keratosis pilaris (33% vs. 80%, P=0·001). This study also identified that loose, redundant skin on the hands and feet, 'stippled' dermatoglyphs (pachydermatoglyphia) on the fingertips (eight of 26, 31%) and acanthosis nigricans (17 of 46, 37%) are frequent features of CS., Conclusions: While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatological features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Although measuring test compliance in a pediatric neuropsychological evaluation is important, increasing demands on clinicians' time and the need for efficiency during assessments may make it difficult to routinely include effort testing. This study investigated whether performance on Trial 1 of the Test of Memory Malingering (TOMM) is predictive of overall performance in children and adolescents with neurological disorders. Participants included 53 children and adolescents between six and 19 years (mean age = 12.4, SD = 4.1) who were followed through a neurology clinic at a tertiary care hospital. Several cutoff scores were examined, with the goal of maximizing positive predictive (accurate detection of failure on the TOMM) and negative predictive (accurate detection of passing the TOMM) values. Every participant who scored ≥36 on Trial 1 (n = 50) went on to pass the TOMM. This study is the first step in providing evidence that performance on Trial 1 might be used as a quick screening measure of overall performance on the TOMM in children and adolescents. Further research on this topic is warranted., (© The Author 2011. Published by Oxford University Press. All rights reserved.)

Objective: The objective of this study was to investigate minor hockey coaches' knowledge base of sport-related concussions., Design: Cross-sectional survey., Setting: Subjects independently completed the written survey at preseason organizational meetings., Participants: One hundred seventy-eight active coaches spanning 5 age levels (ages 5-15 years). Coaches reported 2.62 ± 3.73 years of coaching experience., Main Outcome Measures: Resources where coaches obtained information about concussions, perceptions of variables associated with concussions, knowledge level of issues associated with concussions, and decision-making practices., Results: Newspapers and magazines were the most frequent source of information regarding concussions, yet were rated as not very helpful. Family physicians were less frequently sought but were rated as most helpful. A majority of coaches reported limited knowledge about concussions but rated this knowledge as being important. There was a significant relationship between head coaching experience and concussion knowledge [R = 0.09, F3,156 = 4.41, P = 0.005]. Most coaches demonstrated a good knowledge base of common issues associated with concussions, and a majority of individuals correctly identified return-to-play practices., Conclusions: A majority of minor hockey coaches correctly recognized and understood issues related to sport-related concussions. Results suggested that knowledge translation through various formal and informal sources has had a positive effect. However, a majority of coaches reported having limited knowledge about concussions yet consider it an important topic.

Context: Monitoring of subjective symptoms is the foundation of all sport concussion management programmes. The purpose of this study is to examine methodological variables that impact symptom reporting during baseline testing., Objective: To investigate how the administration method of a concussion assessment tool (self-report vs interview) affects the report of symptoms., Design, Setting and Participants: This was a cross-sectional, semi-randomized study of 117 athletes., Main Outcome Measurements: Subjects completed the Post-Concussion Scale during pre-season evaluations., Results: A two-factor ANOVA revealed a significant difference in total symptom scores (p = 0.02) and number of endorsed symptoms (p = 0.02) across administration modes. Athletes had a greater total symptom score and reported a greater number of symptoms in the self-administration condition than in the interview condition. Furthermore, there was a significant difference in symptom reporting across interviewer gender. Athletes endorsed more symptoms when the interviewer was a woman., Conclusions: Because the method of collecting symptoms, as well as interviewer gender, can impact test results, self-report measures may be a better way of obtaining consistent results. Clinicians and researchers should be aware that both the nature and extent of symptom reporting is greater when using questionnaires than when athletes are interviewed.

Porokeratotic eccrine ostial and dermal duct nevus and a similar condition, porokeratotic eccrine and hair follicle nevus, are rare disorders of keratinization with eccrine and hair follicle involvement. We describe the clinical features in 5 patients, all of whom had widespread skin involvement following the lines of Blaschko. Two patients presented with erosions in the newborn period as the initial manifestation of their disease; one had an associated structural anomaly, unilateral breast hypoplasia; and one adult had malignant transformation in the nevus with development of multifocal squamous cell carcinomas. Three patients had histologic involvement of both acrosyringia and acrotrichia. Based on the observation of overlapping histologic features, we propose the name "porokeratotic adnexal ostial nevus" to incorporate the previously described entities porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

Background and Purpose: Transient ischemic attack (TIA) patients may deteriorate rapidly. MRI is being increasingly used to assess such patients. One possible mechanism of neurological worsening is the presence of perfusion abnormalities. We sought to identify what proportion of TIA patients had evidence of perfusion abnormalities on MRI., Methods: TIA patients were prospectively enrolled and had a MRI completed as soon as possible. The images were assessed for the presence of perfusion abnormalities., Results: Sixty-nine TIA patients were enrolled, and 62 had perfusion imaging. In 56 patients (81%), the symptoms had resolved before imaging. In 21 patients (33.9%), there was evidence of a perfusion abnormality defined by relative mean transit time delay. In 12 patients (19.4%), the perfusion abnormality was present despite having complete resolution of neurological symptoms. We found no relationship between the presence of a perfusion abnormality and the clinical outcome., Conclusions: A proportion of TIA patients have perfusion abnormalities evident on MRI.

An 11-month-old infant girl presented with right-sided features of aplasia cutis congenita of the scalp, unilateral epibulbar dermoids, eccentric pupil, coloboma of the right upper eyelid, and depigmentation of the fundus surrounding the right optic nerve. These findings were similar to the oculoectodermal syndrome reported by other clinicians and researchers.

Incontinentia Pigmenti is an X-linked dominant neurocutaneous disorder with central nervous system manifestations in 30% of cases, including seizures and mental retardation. Ischemic or hemorrhagic cerebrovascular accidents have been reported rarely in incontinentia pigmenti. Chart review and literature search was performed following identification of the index case. We describe a patient with incontinentia pigmenti who developed bilateral cerebrovascular accidents in the neonatal period, with resultant severe neurologic sequelae. This is the second reported case of bilateral cerebrovascular accidents in a patient with incontinentia pigmenti. This finding may be secondary to cerebrovascular anomalies, similar to those observed in the retina. Recognition of cerebrovascular accidents as a complication of incontinentia pigmenti will hopefully lead to earlier recognition and treatment.

Background: Granuloma gluteale infantum is a skin disorder of controversial etiology manifested clinically by oval reddish-purple granulomatous nodules on the gluteal surfaces and groin areas of infants. Similar granulomas are noted in adults and the elderly and are referred to as granuloma gluteale adultorum and diaper area granuloma of the aged, respectively. Occlusion from diapers, paper napkins, plastic pants, detergents, starch, powder, halogenated steroids, candidal infection, and urine and feces are postulated as possible etiologies., Objective: We report a case of a 40-year-old woman presenting with a 3-year history of multiple, painful, closely set, red-purple, oval, smooth, firm papules and nodules in the genitocrural area. The development of the lesions was associated with prolonged use of topical benzocaine. Histology of the lesions was consistent with granuloma gluteale infantum. Gram stain and culture of representative tissue did not demonstrate bacterial or fungal organisms. The lesions significantly improved with discontinuation of topical benzocaine. Patch testing of skin to determine allergic contact hypersensitivity to benzocaine was negative., Conclusion: We propose that topical benzocaine preparations may play a role in the pathogenesis of granuloma gluteale adultorum, independent of contact sensitization to benzocaine.

Cyclic neutropenia (CN) is a rare hematologic disorder characterized by regular cycling of the absolute neutrophil count and a symptom complex presenting during the neutropenic nadirs. Despite the profound cyclic neutropenia, most patients have a benign course of recurrent fever, malaise, oral ulceration, and minor skin and upper respiratory tract infections. Recurrent infections, inflammation, and ulcers can lead to significant chronic morbidity. Severe dental disease is common, pregnancy complications are increased, and overwhelming infections, bowel necrosis, and mortality, although rare, are potential sequelae. We report a 10-year-old boy with a classical presentation of CN that had remained undiagnosed for 10 years. The difficulty in diagnosing this unusual disorder is highlighted. Treatment with daily recombinant granulocyte colony-stimulating factor (rG-CSF) resulted in a complete clearing of symptoms and a significant increase in quality of life. The excellent clinical response of CN to rG-CSF, in the absence of major adverse effects, is strongly demonstrated by this case and supports rG-CSF as a first-line therapy for CN. The physiologic and adverse effects of rG-CSF use in CN and other neutropenic disorders, including potential leukemic induction, are reviewed. The need for long-term follow-up to investigate the effects of chronic hematopoietic stimulation by rG-CSF is emphasized.

Background: Onychomycosis is an increasing problem with limited therapeutic options., Objective: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis., Methods: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis., Results: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity., Conclusion: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.

Eight patients were treated for perianal streptococcal dermatitis. The condition previously was described as perianal cellulitis, a term that is confusing in light of the clinical features and distinctive appearance of the disorder.

Improvements in surgical techniques and prosthetic devices and the establishment of prosthetic clinics have altered the outlook for the amputee. A cooperative effect on the part of professionals looking after amputee patients, as carried out in these clinics, offers the best means of recognition and treatment of difficulties as they arise. Until the "bionic man" becomes a reality, amputees will continue to have skin problems. In describing a number of illustrative cases, we have attempted to: (a) renew interest in these problems; (b) demonstrate the value of the group approach; and (c) encourage the participation of interested dermatologists in the prosthetic clinic team to facilitate earlier recognition and treatment of troublesome skin disorders in the amputee.