Osteoporosis and bone health in pediatric patients with epidermolysis bullosa: A scoping review.

Nutritional compromise, low levels of vitamin D, chronic inflammation, abnormal growth, and physical inactivity affect bone metabolism and compromise long-term bone health in individuals with epidermolysis bullosa (EB). The result is a high risk for osteopenia, osteoporosis, and pathologic fractures, but this important consequence of EB has been the focus of few investigations. Our scoping review found 21 publications that assessed the current understanding and clinical practices for monitoring of osteoporosis and its treatment in EB. Recommendations summarized from 13 of these publications include early nutritional and weight assessments before 2 years of age; bloodwork every 6-12 months starting at birth; Tanner stage assessments every 6 months to detect any pubertal delay; DEXA scans starting at age 6 years with repeated scans every 1-2 years, except in mild cases; and vitamin D supplementation of 80-320 IU daily for children 0-7 years and 720 IU for patients >8 years.

Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa.

BACKGROUND: Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB. RESULTS: Due to the lack of high-quality evidence, a consensus methodology was followed. An initial survey exploring patient preferences, concerns and symptoms related to anemia was sent to EB patients and their family members. A second survey was distributed to EB experts and focused on screening, diagnosis, monitoring and management of anemia in the different types of EB. Information from these surveys was collated and used by the panel to generate 26 consensus statements. Consensus statements were sent to healthcare providers that care for EB patients through EB-Clinet. Statements that received more than 70% approval (completely agree/agree) were adopted. CONCLUSIONS: The end result was a series of 6 recommendations which include 20 statements that will help guide management of anemia in EB patients. In patients with moderate to severe forms of EB, the minimum desirable level of Hb is 100 g/L. Treatment should be individualized. Dietary measures should be offered as part of management of anemia in all EB patients, oral iron supplementation should be used for mild anemia; while iron infusion is reserved for moderate to severe anemia, if Hb levels of > 80-100 g/L (8-10 g/dL) and symptomatic; and transfusion should be administered if Hb is < 80 g/L (8 g/dL) in adults and < 60 g/L (6 g/dL) in children.

Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases.

Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care-based interventions. Opioid-based therapies underpin pain care in EB; however, they are unable to provide adequate analgesia in a significant proportion of patients. Cannabinoid-based medicines (CBMs) have been studied increasingly for pain conditions of various aetiologies and pose as a novel dimension for pain care in EB. We present three patients with EB who were prescribed pharmaceutical-grade sublingually administered CBMs comprising tetrahydrocannabinol and cannabidiol. All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake.

Birmingham epidermolysis severity score and vitamin D status are associated with low BMD in children with epidermolysis bullosa.

Bone status impairment represents a complication of generalized forms of epidermolysis bullosa (EB); however, the prevalence and the main determinants of this event in localized forms remain poorly defined. Birmingham epidermolysis bullosa severity (BEBS) score and 25-hydroxyvitamin D levels are strongly associated with low bone mass, suggesting that vitamin D may play a potential beneficial role in bone health. Further longitudinal studies are needed in order to confirm this hypothesis. INTRODUCTION: Bone status impairment represents a complication of generalized forms of EB; thus, we aimed to estimate the prevalence of low bone mass, to examine mineralization differences in various EB subtypes and to identify the most important determinants of bone impairment in children with either generalized or localized EB. METHODS: An observational study of 20 children (11 males; mean age ± standard deviation, 11.7 ± 3.9 years) with EB was performed. Clinical history, physical examination, laboratory studies, X-ray of the left hand and wrist for bone age, and dual energy X-ray absorptiometry scans of the lumbar spine were obtained. Areal bone mineral density (aBMD Z-scores) and bone mineral apparent density were related to the BEBS score. RESULTS: Areal BMD Z-score (mean -1.82 ± 2.33, range, -7.6-1.7) was reduced (<-2 SD) in 8 patients (40%), whereas aBMD Z-score adjusted for bone age was low in 7 patients (35%). BEBS score and 25-hydroxyvitamin D serum levels were the most important elements associated with aBMD (P = 0.0001 and P = 0.016, respectively). A significant correlation between the aBMD Z-score and area of skin damage, insulin-like growth factor-1, C-reactive protein, and sodium serum levels was also found. CONCLUSIONS: Low aBMD can be considered a systemic complication of EB, primarily associated with BEBS score and 25-hydroxyvitamin D levels. Therefore, longitudinal evaluation of bone status is ongoing in these patients to define whether vitamin D supplementation would prevent, or at least reduce, bone status impairment.

Enfermedad de Hailey-Hailey recalcitrante con buena respuesta a terapia fotodinámica / Refractory Hailey-Hailey Disease That Responded Well to Photodynamic Therapy

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Evaluation of Treatments for Pruritus in Epidermolysis Bullosa.

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.

Pain care for patients with epidermolysis bullosa: best care practice guidelines.

BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a group of rare disorders that have multi-system effects and patients present with a number of both acute and chronic pain care needs. Effects on quality of life are substantial. Pain and itching are burdensome daily problems. Experience with, and knowledge of, the best pain and itch care for these patients is minimal. Evidence-based best care practice guidelines are needed to establish a base of knowledge and practice for practitioners of many disciplines to improve the quality of life for both adult and pediatric patients with EB. METHODS: The process was begun at the request of Dystrophic Epidermolysis Bullosa Research Association International (DEBRA International), an organization dedicated to improvement of care, research and dissemination of knowledge for EB patients worldwide. An international panel of experts in pain and palliative care who have extensive experience caring for patients with EB was assembled. Literature was reviewed and systematically evaluated. For areas of care without direct evidence, clinically relevant literature was assessed, and rounds of consensus building were conducted. The process involved a face-to-face consensus meeting that involved a family representative and methodologist, as well as the panel of clinical experts. During development, EB family input was obtained and the document was reviewed by a wide variety of experts representing several disciplines related to the care of patients with EB. RESULTS: The first evidence-based care guidelines for the care of pain in EB were produced. The guidelines are clinically relevant for care of patients of all subtypes and ages, and apply to practitioners of all disciplines involved in the care of patients with EB. When the evidence suggests that the diagnosis or treatment of painful conditions differs between adults and children, it will be so noted. CONCLUSIONS: Evidence-based care guidelines are a means of standardizing optimal care for EB patients, whose disease is often times horrific in its effects on quality of life, and whose care is resource-intensive and difficult. The guideline development process also highlighted areas for research in order to improve further the evidence base for future care.

Bullous skin lesions in a jaundiced infant after phototherapy: a case of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria is a rare autosomal recessive disorder of porphyrin metabolism in which the genetic defect is the deficiency of uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues, leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity, and mutilating skin lesions. We discuss a female infantile case who was admitted for jaundice; bullous lesions appeared on her trunk during phototherapy in the neonatal period. The skin biopsy findings were consistent with epidermolysis bullosa. Due to persistent hepatosplenomegaly and cholestasis, metabolic tests and liver biopsy were performed. During the follow-up, hemolytic anemia and red urine were detected. The levels of porphyrin metabolites were determined at high concentrations in plasma, stool and urine analysis, which were suggestive of congenital erythropoietic porphyria.

Oral health care for patients with epidermolysis bullosa--best clinical practice guidelines.

OBJECTIVE: To provide the users with information on the current best practices for managing the oral health care of people living with EB. METHODS: A systematic literature search, in which the main topic is dental care in patients with Epidermolysis Bullosa, was performed. Consulted sources, ranging from 1970 to 2010, included MEDLINE, EMBASE, CINAHL, The Cochrane Library, DARE, and the Cochrane controlled trials register (CENTRAL). In order to formulate the recommendations of the selected studies the SIGN system was used. The first draft was analysed and discussed by clinical experts, methodologists and patients representatives on a two days consensus meeting. The resulting document went through an external review process by a panel of experts, other health care professionals, patient representatives and lay reviewers. The final document was piloted in three different centres in United Kingdom, Czech Republic and Argentina. RESULTS: The guideline is composed of 93 recommendations divided into 3 main areas: 1) Oral Care--access issues, early referral, preventative strategies, management of microstomia, prescriptions and review appointments 2) Dental treatment: general treatment modifications, radiographs, restorations, endodontics, oral rehabilitation, periodontal treatment, oral surgery and orthodontics, and 3) Anaesthetic management of dental treatment. CONCLUSIONS: A preventive protocol is today's dental management approach of choice.

The challenges of meeting nutritional requirements in children and adults with epidermolysis bullosa: proceedings of a multidisciplinary team study day.

This is a report of a study day held in London on 3 March 2010 to discuss measures with which to meet the nutritional requirements of patients with epidermolysis bullosa (EB). Members of national and international multidisciplinary teams (MDTs) caring for patients with EB attended this event. The study day focused on four challenging aspects of management intimately associated with nutritional status in EB, necessitating close cooperation between MDT members: iron-deficiency anaemia, gastrostomy placement and feeding, muscle mass and mobility, and dental health. The study day provided a unique forum for dietitians, doctors, nurses, physiotherapists, psychologists, psychotherapists, dentists, dental hygienists and occupational therapists to share knowledge and debate problems common to all who strive to promote best practice in this rare and complex group of conditions.

Dilated cardiomyopathy in epidermolysis bullosa: a retrospective, multicenter study.

Dilated cardiomyopathy (DC) has been reported in severe epidermolysis bullosa (EB) subtypes. Poor nutritional status, low carnitine levels, selenium deficiency, chronic iron overload, drugs and viral etiology have been proposed as potential contributors. This was a retrospective, descriptive, multicenter study describing EB patients that developed DC, and determining potential pre-disposing risk factors. Fifteen patients were enrolled in the study; 11 of them were male subjects (73%). Eighty-seven per cent of the participants had dystrophic EB and 13% had junctional EB. Mean age at diagnosis of DC was 12.18 +/- 4.99 years. Chronic anemia was diagnosed in 13 of 15 patients (86.7%). Sixty per cent of patients had prior red blood cell transfusions. At diagnosis, selenium levels were low in 55% of the patients (n = 11) and total carnitine levels were low in 45% of the patients (n = 11). Systolic function was moderately impaired, with a mean shortening fraction of 19.38% (SD = 5.04, n = 8). After a mean follow-up period of 6.3 +/- 4.8 years, six patients were alive without being on any medications (40.0%), two were alive on medications (13.3%) and seven had died (46.7%). Limitations of the study was that it was a retrospective chart review with relatively small sample size. Retrospective chart review, relatively small sample size. This study substantiates the association between DC and EB. Currently, there is no single risk factor identified in EB patients that leads to DC. Further prospective studies are needed.

Dilated cardiomyopathy in epidermolysis bullosa.

Dilated cardiomyopathy (DC) is a rare but potentially fatal complication of epidermolysis bullosa. No clear cause for it has been identified, but iron overload, low carnitine, low selenium, concomitant viral illness, chronic anemia, and medications have been proposed as possible contributors to the development of DC in reported cases. Early detection allows for medical treatment that delays clinical progression and prolongs survival.

Osteopenia and osteoporosis in epidermolysis bullosa.

Patients with the more severe forms of epidermolysis bullosa (EB) are at risk of developing osteopenia, osteoporosis and fractures. The cause is likely to be multifactorial and includes reduced mobility, a generally proinflammatory state, poor nutrition and hormonal factors. Monitoring this group with dual energy X-ray absorptiometry (DEXA) scans and plain radiographs is necessary to detect these changes. Data are lacking about the optimal approach to managing poor bone health in EB, although it seems that encouraging mobility, supplementation of calcium and vitamin D where necessary, with the addition of a bisphosphonate when there is evidence of fractures, may be helpful.

Deep sedation with intravenous infusion of combined propofol and ketamine during dressing changes and whirlpool bath in patients with severe epidermolysis bullosa.

Continuous i.v. infusion of propofol, or propofol plus ketamine for deep sedation and analgesia was carried out in two patients with severe epidermolysis bullosa (EB) during extensive dressing changes and deep whirlpool baths. Intermittent small doses of narcotics were given as supplement for pain relief as needed. Both patients had typical features of severe EB, including extremity contractures, severe digit deformity, difficult airways, extensive blisters and broken skin with denuded areas and severe wound infections. SpO(2) was roughly estimated by holding the probe around the earlobe periodically and no other monitors could be applied because of the skin conditions and the settings of the procedures. Retrospective anesthesia record review showed that the combined propofol and ketamine infusions provided satisfactory sedation with significantly reduced narcotic requirements compared with propofol alone. There were no noticeable side effects when ketamine was added. Ketamine appears to be a good addition to propofol and narcotics to provide sedation and analgesia when there are great concerns for respiration depression, apnea, difficult pain management and potential unstable hemodynamics during dressing changes and whirlpool baths in severe EB patients.

Nutritional support for children with epidermolysis bullosa.

Epidermolysis bullosa (EB) comprises a rare group of genetically determined skin blistering disorders characterized by extreme fragility of the skin and mucous membranes, with recurrent blister formation. The cornerstones of management are control of infection, wound management, pain relief, promotion of optimal nutritional status and mobility, surgical intervention and provision of the best possible quality of life. There is currently no cure for EB and, throughout life, those with the more severe types are at risk of significant nutritional compromise which impacts negatively on health and overall quality of life. Nutritional support is an important facet of holistic care and the dietetic challenges can be considerable. This paper describes some of the issues involved in optimizing the nutritional status of children with this disorder.

Dilated cardiomyopathy complicating a case of epidermolysis bullosa dystrophica.

A child with epidermolysis bullosa dystrophica, recessive type (EBDR) developed significant anemia at 9 years of age and was treated with long-term transfusion therapy. At age 17 he had symptoms of congestive heart failure secondary to dilated cardiomyopathy. Treatment with digoxin and vasodilators for the past year has failed to improve his cardiomyopathy significantly. Chronic iron overload and secondary hemosiderosis may have contributed to his problems, and we propose that chelation therapy be used in any child receiving long-term transfusion therapy.

Care of the hand in recessive epidermolysis bullosa.

Epidermolysis bullosa refers to a group of disorders whose common feature is blistering of the skin. This paper deals specifically with the loss of motion and digital function resulting from the recessive dystrophic type of epidermolysis bullosa in five young patients aged 3 to 11 years. Indications for surgery and preoperative planning are discussed. Special management considerations included skin care, the need for dietary supplements, and a preference for ketamine anesthesia. Epidermal degloving, full release of contractures, the use of split-thickness skin grafts, and immobilization and suspension of the hand by means of a traction bow without the use of other dressings constituted the important operative points. Postoperative treatment emphasizes wound care, splinting, and gradual mobilization of the joints. Long-term use of a splint to provide gentle digital separation helped prevent early recurrence of webbing. All the patients obtained increased joint motion and enhanced hand function as a result of their treatment.