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1.
Orphanet J Rare Dis ; 17(1): 367, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175960

RESUMO

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a serious, ultra-rare, genetic blistering disease that requires a multidisciplinary care team and lifelong, proactive disease management. To organize and optimize care, we comprehensively examined diagnoses, healthcare use, and annual costs in patients with DEB across all healthcare settings. METHODS: A retrospective study was performed using electronic health record (EHR) data from Optum Clinical Database (January 1, 2016, through June 30, 2020). Patients with an epidermolysis bullosa (EB) diagnosis between July 1, 2016, and December 31, 2019, with ≥ 6 months of baseline and 12 months of follow-up activity were included. Patients were stratified by EB type: recessive DEB (RDEB), dominant DEB (DDEB), DEB (type unknown), and EB unspecified. Demographics, comorbid conditions, and healthcare resource utilization were identified from EHR data. Cost of bandages and total medical costs (US$) were identified from linked claims data. RESULTS: A total of 412 patients were included, classified as having DDEB (n = 17), RDEB (n = 85), DEB (type unknown; n = 45), and EB unspecified (n = 265). Mean age was 38.4 years, and 41.7% had commercial insurance coverage. The most common comorbidities were mental health disorders, malnutrition, and constipation. Rates of cutaneous squamous cell carcinoma ranged from 0% (DDEB) to 4.4% (RDEB). Prescriptions included antibiotics (56.6%), pain medications (48.3%), and itch medications (50.7%). On average, patients had 19.7 ambulatory visits during the 12-month follow-up, 22.8% had an emergency department visit, and 23.8% had an inpatient stay. Direct medical costs among patients with claims data (n = 92) ranged from $22,179 for EB unspecified to $48,419 for DEB (type unknown). CONCLUSIONS: This study demonstrated the range of comorbidities, multiple healthcare visits and prescription medications, and treatment costs during 1 year of follow-up for patients with DEB. The results underscore that the clinical and economic burden of DEB is substantial and primarily driven by supportive and palliative strategies to manage sequelae of this disease, highlighting the unmet need for treatments that instead directly address the underlying pathology of this disease.


Assuntos
Carcinoma de Células Escamosas , Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Neoplasias Cutâneas , Adulto , Antibacterianos , Atenção à Saúde , Epidermólise Bolhosa/genética , Epidermólise Bolhosa Distrófica/patologia , Humanos , Estudos Retrospectivos , Neoplasias Cutâneas/complicações
2.
Clin Dermatol ; 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35988761

RESUMO

In 2013, Next Accreditation System and Milestones became the competency-based assessment framework required for all specialties accredited by the Accreditation Council for Graduate Medical Education. Dermatology residency programs implemented Milestones 1.0 in the 2013-2014 academic year. The Accreditation Council for Graduate Medical Education committed to review and revise Milestones 1.0 within 3 to 5 years. Subsequently, feedback from key stakeholders influenced the goals for revision, including reducing complexity, enhancing community engagement, and providing additional resources for programs. In 2019, the Dermatology Milestones 2.0 work group streamlined the specialty-specific patient care and medical knowledge subcompetencies. The harmonized milestones allowed for greater uniformity across specialties in systems-based practice, practice-based learning and improvement, professionalism, and interpersonal communication and skills. The work group developed a supplemental guide with specialty-specific context to help program directors, clinical competency committee members, and other faculty understand individual milestones. Dermatology Milestones 2.0 reduces the number of subcompetencies from 28 to 21. Milestones 2.0 represents an advancement in competency-based assessment for dermatology. The first year of reporting for Dermatology Milestones 2.0 is 2021.

3.
JAMA Dermatol ; 158(5): 547-551, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385065

RESUMO

Importance: Pediatric alopecia areata (AA) prevalence and incidence data are key to understanding the natural history of this medical disease. Objective: To determine the prevalence and incidence of AA in a pediatric population across time, age, sex, race and ethnicity, and geographic areas within the US. Design, Setting, and Participants: In this multicenter cohort study conducted among 5 children's hospitals, data (January 2009 to November 2020) were collected from a standardized electronic health record (PEDSnet database, version 4.0) to evaluate the incidence and prevalence of pediatric AA. The study cohort included patients younger than 18 years with at least 2 physician visits during which a diagnosis code for AA was recorded, or 1 dermatologist specialty visit for which AA was recorded. Main Outcomes and Measures: The prevalence denominator population comprised 5 409 919 patients. The incidence denominator population was 2 896 241. We identified 5801 children for inclusion in the AA cohort, and 2398 (41.3%) had 12 months or more of follow-up and were included in the incidence analysis. Results: Of 5801 patients in the AA cohort, the mean (SD) age was 9.0 (4.5) years, 3259 (56.2%) were female, 359 (6.2) were Asian, 1094 (18.9%) were Black, 1348 (23.2%) were Hispanic, and 2362 (40.7%) were White. The overall prevalence of pediatric AA was 0.11%, and the participants in the AA cohort were more often older, female, and members of a racial and ethnic minority group than the full PEDSnet population. The 11-year overall incidence rate of pediatric AA between 2009 and 2020 was 13.6 cases per 100 000 person-years (95% CI, 13.1-14.2). The incidence rate by age was normally distributed and peaked at age 6 years. Rates were 22.8% higher in female patients than male patients (15.1 cases per 100 000 person-years for females vs 12.3 cases per 100 000 person-years for males). Additionally, incidence rates were highest among Hispanic children (31.5 cases per 100 000 person-years). Conclusions and Relevance: This cohort study examined the prevalence and incidence rates of pediatric AA in the US across time, age, sex, race and ethnicity, and region from 2009 to 2020, finding a prevalence of 0.11% (doubling during the last decade) and incidence rate of 13.6 cases per 100 000 person-years. Additionally, the results identified Asian and Hispanic children as high-risk demographic subgroups who were shown to be 2 and 3 times more likely, respectively, to receive a diagnosis of AA.


Assuntos
Alopecia em Áreas , Alopecia em Áreas/epidemiologia , Criança , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Humanos , Incidência , Masculino , Grupos Minoritários , Prevalência
4.
Pediatr Blood Cancer ; 69(5): e29639, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35253347

RESUMO

Variants in RAS are known drivers of certain pediatric blood and solid cancers, including brain tumors. Though most RAS-driven cancers are thought to occur sporadically, genetic syndromes caused by germline RAS variants portend a slightly higher risk of rhabdomyosarcoma (RMS) development. Three new cases and a review of the literature demonstrate that in rare cases, certain somatic RAS variants are associated with an increased risk of RMS and that RMS development may be heralded by the presence of concomitant RAS-driven birthmarks. Further prospective studies are needed to establish incidence and recommend appropriate monitoring guidelines for patients at risk.


Assuntos
Leucemia Mieloide Aguda , Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Criança , Células Germinativas , Humanos , Rabdomiossarcoma/genética
6.
Pediatr Dermatol ; 39(2): 236-242, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35178735

RESUMO

BACKGROUND/OBJECTIVES: We evaluated the acceptance of synchronous (live video) telehealth for pediatric dermatology. METHODS: This was a prospective, single-center study of patient and dermatologist surveys paired at the encounter level for telehealth encounters with Children's Hospital Colorado Pediatric Dermatology Clinic between 21 April 2020 and 22 May 2020. RESULTS: Dermatologists were most receptive to a telehealth encounter for isotretinoin monitoring (96.6%) and non-isotretinoin acne (89.5%). In contrast, 71.8% and 58.8% of patients surveyed were open to telehealth for isotretinoin encounters and non-isotretinoin acne encounters, respectively. There was no significant correlation between patient and dermatologist satisfaction regarding a telehealth encounter (r = 0.09, CI [-0.09, 0.26], p = .34) or between patient and dermatologist preference for telehealth encounter (r = 0.07, CI [-0.11, 0.25] p = .46). Dermatologists reported needing a photo to aid their physical examination in 38/363 (10.7%) of encounters and preferred in-person examinations when an encounter would have benefitted from laboratories, procedures, dermatoscopic examination, examination by palpation, and accurate weights in infants. CONCLUSIONS: Synchronous, live-video telehealth is an effective method of healthcare delivery in certain situations for pediatric dermatology, but it does not replace in-person encounters. Families and dermatologists have different perceptions about its acceptance.


Assuntos
Acne Vulgar , Dermatologia , Telemedicina , Criança , Humanos , Lactente , Isotretinoína , Satisfação do Paciente , Estudos Prospectivos , Telemedicina/métodos
7.
Anesth Analg ; 134(4): 810-821, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34591805

RESUMO

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare epithelial disorders caused by abnormal or absent structural proteins at the epidermal-dermal junction. As a result, patients experience blisters and wounds from mild shearing forces. Some forms of EB are complicated by resultant scarring and contractures. The perioperative anesthetic management of patients with EB is complex and requires a systems-based approach to limit harm. We reviewed our experience with providing general anesthesia to patients at our tertiary EB referral center, including adverse events related to anesthetic care, outcomes in the immediate perioperative period, and details of anesthetic management. METHODS: We retrospectively reviewed the charts of all patients with EB anesthetized at the Children's Hospital Colorado between January 2011 and December 2016. A subset of pediatric anesthesiologists cared for all patients using a standardized clinical care pathway. Patient demographics, detailed anesthetic methods, immediate perioperative outcomes, and adverse events were characterized. RESULTS: Over a 6-year period, 37 patients underwent 202 general anesthetics. Most patients (75.7%) had dystrophic EB (DEB). Female patients comprised 48.6%. The majority (56.7%) traveled >50 miles to receive care, and many (35.1%) traveled >150 miles for their care. Common adaptations to care included avoidance of electrocardiogram leads (88.6%) and temperature probes (91.6%). Nasal fiberoptic intubation (n = 160) was performed, or natural airway/mask (n = 27) was maintained for most patients. Supraglottic devices were not used for airway management during any of the anesthetics. Anesthesia preparation time was longer (average 25.8 minutes [standard deviation {SD} = 12.7]) than our average institutional time (14 minutes). Succinylcholine was never used, and nondepolarizing muscle relaxants were used in only 1.5% of patient encounters. Blood was transfused in 16.3% of cases and iron infused in 24.8%. Average length of stay in the postanesthesia care unit was comparable to our institutional average (average 40.1 [SD = 28.6] vs 39 minutes). New skin or mucosal injury occurred in 8 encounters (4%), and desaturation occurred in 43 cases (21.3%). There were no major adverse events. CONCLUSIONS: By using a specialized team and a standardized clinical care pathway, our institution was able to minimize adverse events caused by the anesthetic and surgical care of patients with EB. We recommend natural airway or nasal fiberoptic airway management, meticulous avoidance of shear stress on the skin, and a multidisciplinary approach to care. Supportive therapy such as perioperative blood transfusions and iron infusions are feasible for the treatment of chronic anemia in this population.


Assuntos
Anestésicos , Epidermólise Bolhosa , Anestésicos/uso terapêutico , Criança , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/diagnóstico , Epidermólise Bolhosa/terapia , Feminino , Humanos , Ferro , Estudos Retrospectivos , Centros de Atenção Terciária
8.
J Am Acad Dermatol ; 86(5): 1063-1071, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34634382

RESUMO

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 < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSIONS: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.


Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa Simples , Epidermólise Bolhosa Juncional , Epidermólise Bolhosa , Epidermólise Bolhosa/diagnóstico , Epidermólise Bolhosa/genética , Epidermólise Bolhosa Distrófica/diagnóstico , Epidermólise Bolhosa Simples/diagnóstico , Imunofluorescência , Humanos , América do Norte , Estudos Retrospectivos
9.
Am J Med Genet A ; 185(11): 3390-3400, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34435747

RESUMO

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis caused by mutations in the gene coding for type VII collagen (COL7A1). More than 800 different pathogenic mutations in COL7A1 have been described to date; however, the ancestral origins of many of these mutations have not been precisely identified. In this study, 32 RDEB patient samples from the Southwestern United States, Mexico, Chile, and Colombia carrying common mutations in the COL7A1 gene were investigated to determine the origins of these mutations and the extent to which shared ancestry contributes to disease prevalence. The results demonstrate both shared European and American origins of RDEB mutations in distinct populations in the Americas and suggest the influence of Sephardic ancestry in at least some RDEB mutations of European origins. Knowledge of ancestry and relatedness among RDEB patient populations will be crucial for the development of future clinical trials and the advancement of novel therapeutics.


Assuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Judeus/genética , Chile/epidemiologia , Colômbia/epidemiologia , Epidermólise Bolhosa Distrófica/epidemiologia , Feminino , Genes Recessivos/genética , Humanos , Masculino , México/epidemiologia , Fenótipo , Estados Unidos/epidemiologia
10.
Pediatr Dermatol ; 38(1): 164-180, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33169909

RESUMO

Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.


Assuntos
Ictiose Lamelar , Ictiose , Adolescente , Criança , Consenso , Humanos , Ictiose/tratamento farmacológico , Retinoides
11.
Pediatr Dermatol ; 38(1): 119-124, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33247481

RESUMO

BACKGROUND/OBJECTIVES: Patients with epidermolysis bullosa (EB) require care of wounds that are colonized or infected with bacteria. A subset of EB patients are at risk for squamous cell carcinoma, and bacterial-host interactions have been considered in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the United States and Canada. Access to this resource enabled broad-scale analysis of wound cultures. METHODS: A retrospective analysis of 739 wound cultures from 158 patients from 13 centers between 2001 and 2018. RESULTS: Of 152 patients with a positive culture, Staphylococcus aureus (SA) was recovered from 131 patients (86%), Pseudomonas aeruginosa (PA) from 56 (37%), and Streptococcus pyogenes (GAS) from 34 (22%). Sixty-eight percent of patients had cultures positive for methicillin-sensitive SA, and 47%, methicillin-resistant SA (18 patients had cultures that grew both methicillin-susceptible and methicillin-resistant SA at different points in time). Of 15 patients with SA-positive cultures with recorded mupirocin susceptibility testing, 11 had mupirocin-susceptible SA and 6 patients mupirocin-resistant SA (2 patients grew both mupirocin-susceptible and mupirocin-resistant SA). SCC was reported in 23 patients in the entire database, of whom 10 had documented wound cultures positive for SA, PA, and Proteus species in 90%, 50%, and 20% of cases, respectively. CONCLUSIONS: SA and PA were the most commonly isolated bacteria from wounds. Methicillin resistance and mupirocin resistance were reported in 47% and 40% of patients tested, respectively, highlighting the importance of ongoing antimicrobial strategies to limit antibiotic resistance.


Assuntos
Epidermólise Bolhosa , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Canadá , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/tratamento farmacológico , Humanos , Mupirocina , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
13.
J Am Acad Dermatol ; 83(4): 1222-1224, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32682031
14.
JAMA Dermatol ; 156(9): 1003, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32584385
15.
Pediatr Dermatol ; 37(2): 326-332, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944391

RESUMO

BACKGROUND/OBJECTIVES: Epidermolysis bullosa (EB) comprises a group of inherited skin blistering diseases. There is currently no cure, and management includes skin protection and prevention of infection. To date, there has been no systematic investigation of home skin care practices among EB patients on a multicenter scale. METHODS: This cross-sectional, observational study included data collected from patients with EB enrolled in the Epidermolysis Bullosa Characterization and Clinical Outcomes Database (EBCCOD) who provided answers to a patient-directed questionnaire between January 1, 2017, and December 31, 2017. RESULTS: Of 202 respondents, 130 (64.4%) had dystrophic EB, 51 (25.2%) had EB simplex, 21 (7.4%) had junctional EB, 3 (1.5%) had Kindler syndrome, and 3 (1.5%) had an unspecified subtype. Seventy-eight patients reported cleansing in plain water only (39%). Of those who used an additive in their cleansing water, 75 (57%) added salt, 71 (54%) added bleach, 36 (27%) added vinegar, and 34 (26%) endorsed the use of an "other" additive (multiple additives possible). Reported concentrations of additives ranged widely from 0.002% sodium hypochlorite and 0.002% acetic acid solutions, which are thought to have negligible effects on microbes, to 0.09% sodium hypochlorite and 0.156% acetic acid, concentrations shown to be cytotoxic. One hundred eighty-eight patients answered questions regarding topical product use (93%). Of those, 131 reported topical antimicrobial use (70%). Mupirocin and bacitracin were the most commonly reported topical antibiotics (59, 58 [31.4%, 30.9%], respectively). CONCLUSIONS: These findings highlight the variety of skin care routines and frequent use of topical antimicrobials among EB patients and have potential implications for antibiotic resistance. The reported range of bleach and vinegar additives to cleansing water, including cytotoxic concentrations, emphasizes the need for clear and optimized skin cleansing recommendations.


Assuntos
Detergentes/administração & dosagem , Epidermólise Bolhosa/terapia , Higiene da Pele , Administração Tópica , Adolescente , Adulto , Criança , Pré-Escolar , Cosméticos/administração & dosagem , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Autocuidado , Adulto Jovem
16.
Orphanet J Rare Dis ; 15(1): 1, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900176

RESUMO

BACKGROUND: Little information is available regarding the burden of living with and managing epidermolysis bullosa, including the distinct challenges faced by patients with different disease types/subtypes. METHODS: A 90-question/item survey was developed to collect demographics, diagnostic data, management practices, and burden of illness information for patients with epidermolysis bullosa living in the United States. Recruitment was conducted via email and social media in partnership with epidermolysis bullosa patient advocacy organizations in the United States, and the survey was conducted via telephone interview by a third-party health research firm. Respondents aged ≥ 18 years with a confirmed diagnosis of epidermolysis bullosa or caring for a patient with a confirmed diagnosis of epidermolysis bullosa were eligible to participate in the survey. RESULTS: In total, 156 responses were received from patients (n = 63) and caregivers (n = 93) representing the epidermolysis bullosa types of simplex, junctional, and dystrophic (subtypes: dominant and recessive). A large proportion of patients (21%) and caregivers (32%) reported that the condition was severe or very severe, and 19% of patients and 26% of caregivers reported a visit to an emergency department in the 12 months prior to the survey. Among the types/subtypes represented, recessive dystrophic epidermolysis bullosa results in the greatest wound burden, with approximately 60% of patients and caregivers reporting wounds covering > 30% of total body area. Wound care is time consuming and commonly requires significant caregiver assistance. Therapeutic options are urgently needed and reducing the number and severity of wounds was generally ranked as the most important treatment factor. CONCLUSIONS: Survey responses demonstrate that epidermolysis bullosa places a considerable burden on patients, their caregivers, and their families. The limitations caused by epidermolysis bullosa mean that both patients and caregivers must make difficult choices and compromises regarding education, career, and home life. Finally, survey results indicate that epidermolysis bullosa negatively impacts quality of life and causes financial burden to patients and their families.


Assuntos
Epidermólise Bolhosa/epidemiologia , Adolescente , Adulto , Idoso , Cuidadores/estatística & dados numéricos , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto Jovem
18.
JAMA Dermatol ; 155(2): 196-203, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30586139

RESUMO

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.


Assuntos
Epidermólise Bolhosa/epidemiologia , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/patologia , Predisposição Genética para Doença/epidemiologia , Adolescente , Distribuição por Idade , Biópsia por Agulha , Canadá , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Incidência , Lactente , Masculino , América do Norte/epidemiologia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Análise de Sobrevida , Adulto Jovem
19.
Sci Transl Med ; 10(455)2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30135250

RESUMO

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors. We report that driver mutations were shared with spontaneous, ultraviolet (UV) light-induced cutaneous SCC (UV SCC) and head and neck SCC (HNSCC) and did not explain the early presentation or aggressive nature of RDEB SCC. Instead, endogenous mutation processes associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases dominated RDEB SCC. APOBEC mutation signatures were enhanced throughout RDEB SCC tumor evolution, relative to spontaneous UV SCC and HNSCC mutation profiles. Sixty-seven percent of RDEB SCC driver mutations was found to emerge as a result of APOBEC and other endogenous mutational processes previously associated with age, potentially explaining a >1000-fold increased incidence and the early onset of these SCCs. Human papillomavirus-negative basal and mesenchymal subtypes of HNSCC harbored enhanced APOBEC mutational signatures and transcriptomes similar to those of RDEB SCC, suggesting that APOBEC deaminases drive other subtypes of SCC. Collectively, these data establish specific mutagenic mechanisms associated with chronic tissue damage. Our findings reveal a cause for cancers arising at sites of persistent inflammation and identify potential therapeutic avenues to treat RDEB SCC.


Assuntos
Desaminases APOBEC/genética , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Citosina Desaminase/genética , Epidermólise Bolhosa Distrófica/enzimologia , Epidermólise Bolhosa Distrófica/genética , Mutação/genética , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Variações do Número de Cópias de DNA/genética , Reparo do DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Mutagênese/genética , Taxa de Mutação , Transcriptoma/genética
20.
J Pediatr Gastroenterol Nutr ; 67(6): 701-705, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30052567

RESUMO

OBJECTIVE: The aim of the study is to analyze a large series of esophageal balloon dilations in patients with epidermolysis bullosa (EB) to determine procedural approach and frequency of post-endoscopic adverse events (AEs). METHODS: Retrospective chart review for AE occurrence and clinical outcomes in children and adolescents with EB, age 1 to 19, who underwent esophageal dilation for esophageal stricture(s) from January 2003 to April 2016 at an academic, tertiary care, free-standing children's hospital. The primary outcome measure was occurrence of procedural AEs (defined as events occurring within 72 hours after endoscopic dilation procedure). RESULTS: A total of 231 fluoroscopy-guided esophageal balloon dilation procedures (209 anterograde, 20 retrograde, 2 both) were performed in 24 patients. Strictures were more common in the proximal portion of the esophagus with median stricture location 13 cm from the lips. From 2003 to 2012, 4.1% of dilations were retrograde. From 2013 to 2016, 20.2% of dilations were retrograde. AEs attributable to dilation occurred after 10.0% of procedures, and the most common AEs were vomiting, pain, and fever. No esophageal perforations, serious bleeding events, or deaths occurred secondary to dilation. The rate of post-dilation hospitalization was 6.9%. Dilation approach (anterograde vs retrograde) did not impact the likelihood of AEs. CONCLUSIONS: The characteristic esophageal lesion in EB is a single, proximal esophageal stricture. EB patients can safely undergo repeat pneumatic esophageal balloon dilations with minimal risk for severe complication. We observed a trend towards increased use of retrograde esophageal dilation.


Assuntos
Dilatação/métodos , Epidermólise Bolhosa/complicações , Estenose Esofágica/cirurgia , Esofagoscopia/métodos , Fluoroscopia/métodos , Adolescente , Criança , Pré-Escolar , Dilatação/instrumentação , Estenose Esofágica/etiologia , Esofagoscopia/instrumentação , Esôfago/cirurgia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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