Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a genetic disorder characterized by skin fragility and unique oral features. AIMS: To provide (a) a complete review of the oral manifestations in those living with each type of inherited EB, (b) the current best practices for managing oral health care of people living with EB, (c) the current best practices on dental implant-based oral rehabilitation for patients with recessive dystrophic EB (RDEB), and (d) the current best practice for managing local anesthesia, principles of sedation, and general anesthesia for children and adults with EB undergoing dental treatment. METHODS: Systematic literature search, panel discussion including clinical experts and patient representatives from different centers around the world, external review, and guideline piloting. RESULTS: This article has been divided into five chapters: (i) general information on EB for the oral health care professional, (ii) systematic literature review on the oral manifestations of EB, (iii) oral health care and dental treatment for children and adults living with EB-clinical practice guidelines, (iv) dental implants in patients with RDEB-clinical practice guidelines, and (v) sedation and anesthesia for adults and children with EB undergoing dental treatment-clinical practice guidelines. Each chapter provides recommendations on the management of the different clinical procedures within dental practice, highlighting the importance of patient-clinician partnership, impact on quality of life, and the importance of follow-up appointments. Guidance on the use on nonadhesive wound care products and emollients to reduce friction during patient care is provided. CONCLUSIONS: Oral soft and hard tissue manifestations of inherited EB have unique patterns of involvement associated with each subtype of the condition. Understanding each subtype individually will help the professionals plan long-term treatment approaches.

Infantile Hemangiomas in Twins: A Prospective Cohort Study.

BACKGROUND: Twins have a higher-than-expected risk of infantile hemangiomas (IHs), but the exact reasons for this association are not clear. Comparing concordant and discordant twin pairs might help elucidate these factors and yield more information about IH risk factors. METHODS: A prospective cohort study of twin pairs from 12 pediatric dermatology centers in the United States, Canada, Argentina, and Spain was conducted. Information regarding maternal pregnancy history, family history of vascular birthmarks, zygosity (if known), and pregnancy-related information was collected. Information regarding twins (N = 202 sets) included birthweight, gestational age (GA), presence or absence of IHs, numbers and subtypes of IHs, presence of other birthmarks, and other medical morbidities. RESULTS: Two hundred two sets of twins were enrolled. Concordance for IH was present in 37% of twin pairs. Concordance for IH was inversely related to gestational age (GA), present in 42% of GA of 32 weeks or less, 36% of GA of 33 to 36 weeks, and 32% of GA of 37 weeks or more. Twins of GA of 34 weeks or less were more than two and a half times as likely to be concordant as those of GA of 35 weeks or more (odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.42-4.99; p < 0.01). In discordant twins, lower birthweight conferred a high risk of IH; of the 64 sets of twins with 10% or greater difference in weight, the smaller twin had IH in 62.5% (n = 40) of cases, versus 37.5% (n = 24) of cases in which the higher-birthweight twin was affected. Zygosity was reported in 188 twin sets (93%). Of these, 78% were dizygotic and 22% monozygotic. There was no statistically significant difference in rates of concordance between monozygotic twins (43%, 18/42) and dizygotic twins (36%, 52/146) (p = 0.50). In multivariate analysis comparing monozygotic and dizygotic twins, adjusting for effects of birthweight and sex, the likelihood of concordance for monozygotic was not appreciably higher than that for dizygotic twins (OR = 1.14, 95% CI = 0.52-2.49). Female sex also influenced concordance, confirming the effects of female sex on IH risk. The female-to-male ratio was 1.7:1 in the entire cohort and 1.9:1 in those with IH. Of the 61 concordant twin sets with known sex of both twins, 41% were female/female, 43% were female/male, and 16% were male/male. CONCLUSIONS: These findings suggest that the origin of IHs is multifactorial and that predisposing factors such as birthweight, sex, and GA may interact with one another such that a threshold is reached for clinical expression.

Upper airway complications of junctional epidermolysis bullosa.

OBJECTIVE: To assess the incidence of upper airway pathology in patients with junctional epidermolysis bullosa (JEB). STUDY DESIGN: We conducted a retrospective chart review of all patients with JEB who came to an interdisciplinary epidermolysis bullosa center at a tertiary care institution between 2004 and 2010. RESULTS: Twenty-five patients with JEB were identified, and 12 patients were seen in the otolaryngology clinic (age range, 2 months-15 years; 8 male, 4 female). Of the 12 patients, 8 underwent rigid laryngoscopy and bronchoscopy for upper respiratory tract symptoms; 7 of these patients displayed laryngeal pathology, and 5 of them underwent surgical intervention with successful resolution of symptoms. Furthermore, none of these patients had any short- or long-term complications from their surgery. A strict protocol and a precise problem-focused cold surgical technique were used in these cases to protect skin and mucus membranes. CONCLUSION: With appropriate precautions, endoscopic laryngeal surgery can be safe and effective in patients with JEB and larygnotracheal disease. Endoscopic laryngeal surgery is feasible when indicated for these patients.

Prospective study of spinal anomalies in children with infantile hemangiomas of the lumbosacral skin.

OBJECTIVE: To prospectively evaluate a cohort of patients with infantile hemangioma in the midline lumbosacral region for spinal anomalies to determine the positive predictive value of infantile hemangioma for occult spinal anomalies and to make evidence-based recommendations for screening. STUDY DESIGN: A multicenter prospective cohort study was performed at 9 Hemangioma Investigator Group sites. RESULTS: Intraspinal abnormalities were detected in 21 of 41 study participants with a lumbosacral infantile hemangioma who underwent a magnetic resonance imaging evaluation. The relative risk for all patients with lumbosacral infantile hemangiomas for spinal anomalies was 640 (95% confidence interval [CI], 404-954), and the positive predictive value of infantile hemangioma for spinal dysraphism was 51.2%. Ulceration of the hemangioma was associated with a higher risk of having spinal anomalies. The presence of additional cutaneous anomalies also was associated with a higher likelihood of finding spinal anomalies; however, 35% of the infants with isolated lumbosacral infantile hemangiomas had spinal anomalies, with a relative risk of 438 (95% CI, 188-846). The sensitivity for ultrasound scanning to detect spinal anomalies in this high-risk group was poor at 50% (95% CI, 18.7%-81.3%), with a specificity rate of 77.8% (95% CI, 40%-97.2%). CONCLUSIONS: Infants and children with midline lumbosacral infantile hemangiomas are at increased risk for spinal anomalies. Screening magnetic resonance imaging is recommended for children with these lesions.

Perioperative care of patients with epidermolysis bullosa: proceedings of the 5th international symposium on epidermolysis bullosa, Santiago Chile, December 4-6, 2008.

Epidermolysis bullosa (EB) has become recognized as a multisystem disorder that poses a number of pre-, intra-, and postoperative challenges. While anesthesiologists have long appreciated the potential difficult intubation in patients with EB, other systems can be affected by this disorder. Hematologic, cardiac, skeletal, gastrointestinal, nutritional, and metabolic deficiencies are foci of preoperative medical care, in addition to the airway concerns. Therefore, multidisciplinary planning for operative care is imperative. A multinational, interdisciplinary panel of experts assembled in Santiagio, Chile to review the best practices for perioperative care of patients with EB. This paper presents guidelines that represent a synthesis of evidence-based approaches and the expert consensus of this panel and are intended to aid physicians new to caring for patients with EB when operative management is indicated. With proper medical optimization and attention to detail in the operating room, patients with EB can have an uneventful perioperative course.

MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehicle-controlled study.

OBJECTIVE: To examine the efficacy and safety of MAS063DP (Atopiclair) cream in the management of mild to moderate atopic dermatitis in infants and children. STUDY DESIGN: One hundred forty-two patients aged 6 months to 12 years were administered MAS063DP (n = 72) or vehicle (n = 70) cream 3 times per day to affected areas and sites prone to develop atopic dermatitis. The primary endpoint for efficacy was the Investigator's Global Assessment at day 22. Secondary endpoints included Investigator's Global Assessment at other time-points, patient's/caregiver's assessment of pruritus, onset, duration of itch relief, Eczema Area and Severity Index, subject's/caregiver's assessment of global response, and need for rescue medication in the event of an atopic dermatitis flare. RESULTS: MAS063DP cream was statistically more effective (P < .0001) than vehicle cream for the primary endpoint and all secondary endpoints. Treatment discontinuation as a result of an adverse event occurred in 9.9% of patients using MAS063DP cream and 16% of patients using vehicle cream. CONCLUSION: MAS063DP cream is effective and safe as monotherapy for the treatment of symptoms of mild to moderate atopic dermatitis in infants and children.

Multicenter prospective study of ulcerated hemangiomas.

OBJECTIVE: To identify clinical features of infants with ulcerated infantile hemangiomas. STUDY DESIGN: Cross-sectional analysis was conducted within a prospective cohort study of children with infantile hemangiomas. Children younger than 12 years of age were recruited. Demographic and prenatal/perinatal information was collected. Hemangioma size, location, subtype, course, complications, and treatments were recorded. RESULTS: One thousand ninety-six patients were enrolled, and 173 (15.8%) patients experienced ulceration. Ulceration occurred in 192 (9.8%) of 1960 [corrected] total hemangiomas. Hemangiomas with ulcerations were more likely large, mixed clinical type, segmental morphologic type, and located on the lower lip, neck, or anogenital region. Ulceration occurred at a median age of 4 months, most often during the proliferative phase. Children with ulcerated hemangiomas were more likely to present to a pediatric dermatologist at a younger age and to require treatment. Bleeding occurred in 41% of ulcerated lesions but was rarely of clinical significance. Infection occurred in 16%. CONCLUSIONS: Ulceration occurs in nearly 16% of patients with infantile hemangiomas, most often by 4 months of age, during the proliferative phase. Location, size, and clinical and morphologic type are associated with an increased risk for development of ulceration.

Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics.

OBJECTIVES: To characterize demographic, prenatal, and perinatal features of patients with infantile hemangiomas and to determine the importance of these factors in predicting rates of complication and treatment. STUDY DESIGN: We conducted a prospective study at 7 U.S. pediatric dermatology clinics. A consecutive sample of 1058 children, aged 12 years and younger, with infantile hemangiomas was enrolled between September 2002 and October 2003. A standardized questionnaire was used to collect demographic, prenatal, perinatal, and hemangioma-specific data. National Vital Statistic System Data (NVSS) was used to compare demographic variables and relevant rates of prenatal events. RESULTS: In comparison with the 2002 United States National Vital Statistics System birth data, we found that infants with hemangiomas were more likely to be female, white non-Hispanic, premature (P < .0001) and the product of a multiple gestation (10.6% versus 3.1%; P < .001). Maternal age was significantly higher (P < .0001), and placenta previa (3.1%) and pre-eclampsia (11.8%) were more common. CONCLUSIONS: Infants with hemangiomas are more likely to be female, white non-Hispanic, premature, and products of multiple gestations. Prenatal associations include older maternal age, placenta previa, and pre-eclampsia. No demographic, prenatal, and perinatal factors predicted higher rates of complications or need for treatment.

Pubertal correlates in black and white girls.

OBJECTIVES: Since pubertal maturation is an important covariate in studies that evaluate physical and social changes that occur during the teen years, we examined pubertal parameters in a group of US girls. STUDY DESIGN: Black and white girls recruited at age 9 were followed annually for 10 years. Preece-Baines model 1 was used to estimate tempo and growth parameters. The temporal trend between age of menarche and onset of puberty was calculated. RESULTS: The study included 615 (77.2% prepubertal) white and 541 (49.4% prepubertal) black participants. Mean onset of puberty was 10.2 and 9.6 years in white and black girls, respectively, menarche was 12.6 and 12.0, achievement of Tanner growth stage 5 was 14.3 and 13.6, and achievement of adult height was 17.1 and 16.5 years. The Pearson's correlation coefficient between menarche and onset of puberty was .37. CONCLUSIONS: Menarche is often used as a marker for onset of puberty and for timing of puberty. Data gathered over the past 20 years suggest only moderate correlation between menarche and onset of puberty (.37-.38), which has decreased significantly during the last 50 years. This suggests the existence of both similar and unique factors that impact the age at onset of puberty and age at menarche.

Pubertal maturation in girls and the relationship to anthropometric changes: pathways through puberty.

OBJECTIVE: Patterns of pubertal maturation may have an impact on several risk factors associated with adult morbidity and mortality, such as obesity. We examined the relationship of the initial manifestation of puberty in girls with anthropometric measures, as well as age at menarche. METHODS: White females (n = 1166, ages 9 and 10 at intake) were followed with annual visits for 10 years. Physical examinations included height, weight, skinfold thicknesses, and pubertal maturation assessment. RESULTS: During the course of the study, 443 of 859 eligible females (51.6%) were observed to have asynchronous maturation in the development of puberty, that is, initial areolar/breast (thelarche pathway) or pubic hair (adrenarche pathway) development, without development of the other characteristic. Using a longitudinal regression model, significant interactions were noted between initial pubertal manifestation and years since onset of puberty on the following outcomes: sum of skinfolds thickness, percent body fat, waist-to-hip ratio, and body mass index (BMI). However, age of onset of pubertal maturation was the same in the 2 groups (10.7 years). Females in the thelarche pathway had earlier menarche (12.6 vs 13.1 years) as well as greater skinfolds, body fat, and BMI at the time of menarche. Females in the thelarche pathway also had greater body fat and BMI 1 year before puberty and throughout puberty compared with those in the adrenarche pathway. CONCLUSIONS: Females who enter puberty through the thelarche pathway, as compared with the adrenarche pathway, had greater sum of skinfold thicknesses, BMI, and percent body fat 1 year before the onset, as well as throughout, puberty. Because larger body composition and earlier age of menarche of females in the thelarche pathway parallel the epidemiologic profiles of women who are obese or at risk for obesity, these females may be at greater risk for adult obesity.