Background
Methods
Multidisciplinary management of EB patients
Tissue/organ/system | Major complications | EB type/subtype* |
---|---|---|
Skin | Fluid loss | Lethal acantholytic EB, JEB-H, EBS-PA, JEB-PA |
Chronic/infected wounds | RDEB-SG, RDEB-I, RDEB-O, JEB-H, JEB-nH, EBS-AR, DEB-Pr, DDEB-G, EBS-DM | |
Exuberant granulation tissue | LOC, JEB-H, JEB-nH | |
Atrophic scars, post-inflammatory pigmentary changes | DEB, JEB, EBS | |
Poikiloderma/diffuse skin atrophy | KS | |
Excessive/hypertrophic scarring | RDEB-SG, RDEB-I, DEB-Pt, DEB-Pr, RDEB-O | |
Albopapuloid lesions | DEB | |
Milia | DEB, JEB, EBS, KS | |
Palmoplantar keratoderma | EBS, JEB-nH, KS | |
Aplasia cutis congenita | EBS-PA, JEB-PA, DEB, other JEB and EBS subtypes | |
EB nevi | JEB, DEB, EBS | |
Basal cell carcinomas | EBS-DM | |
Squamous cell carcinomas | RDEB-SG, RDEB-O, KS, JEB-nH, RDEB-I | |
Skin adnexa | Onychodystrophy, nail shedding or loss | DEB, JEB, EBS-MD, EBS-DM, EBS-PD, EBS-AR, EBS-O, KS |
Scarring alopecia | JEB-nH, RDEB-SG, JEB-H, JEB-PA, RDEB-O | |
Alopecia universalis | Lethal acantholytic EB | |
Hypotrichosis | EBS-PD | |
Oral cavity | Microstomia, ankyloglossia, obliteration of the oral vestibules | RDEB-SG, RDEB-I, RDEB-O |
Enamel hypoplasia | JEB, EBS-MD | |
Multiple caries and tooth decay | DEB, JEB | |
Periodontitis | KS | |
External eye | Corneal erosions | RDEB-SG, JEB-H, RDEB-O, RDEB-I, JEB-nH, EBS-DM, KS |
Blepharitis, corneal scarring and/or pannus formation | RDEB-SG, RDEB-I, JEB-H, RDEB-O, JEB-nH | |
Symblepharon | LOC, RDEB-SG, RDEB-I, JEB-H, JEB-nH | |
Ectropion/exposure keratitis | JEB-H, RDEB-SG, KS | |
Diminished vision/blindness | RDEB-SG | |
Conjunctival granulation tissue | LOC | |
External ear | External auditory canal narrowing/conductive hearing loss | RDEB-I |
Nose | Nare narrowing (granulation tissue) | JEB-H, JEB-nH, LOC |
Tissue/organ/system | Major complications | EB type/subtype* |
---|---|---|
Gastrointestinal tract | Pyloric atresia | JEB-PA, EBS-PA |
Esophageal stenosis/strictures/web formation | RDEB-SG, RDEB-I, KS, RDEB-O | |
Chronic constipation/fecal impaction | RDEB-SG, RDEB-I, RDEB-O, DDEB, JEB-H, JEB-nH, EBS-DM, EBS-MD | |
Gastroesophageal reflux disease | RDEB, JEB-nH, EBS-DM, EBS-MD, JEB-PA, JEB-H, DDEB | |
Anal fissures/stenosis | RDEB-SG, RDEB-I, RBED-O, KS | |
Protein-loosing enteropathy | JEB-PA, EBS-PA, JEB-H, JEB-nH | |
Colitis/diarrhea | KS, RDEB, JEB-PA | |
Genitourinary tract | Urethral strictures, meatal stenosis | JEB-H, RDEB-SG, JEB-PA, JEB-nH, LOC, KS |
Genitourinary malformations, ureteral/ureterovesical junction obstruction/stenosis, recurrent cystitis | JEB-PA, EBS-PA | |
Vulvar/vaginal scarring/strictures | RDEB-I, KS | |
Renal failure | RDEB-SG, JEB-PA, JEB-nH | |
Upper respiratory tract | Tracheolaryngeal stenosis/acute respiratory failure | JEB-H, LOC, EBS-MD, lethal acantholytic EB, EBS-DM |
Musculoskeletal system | Osteopenia and osteoporosis | RDEB-SG, RDEB-O, JEB-nH |
Limb flexion contractures | RDEB-SG | |
Digit contractures/pseudosyndactyly | RDEB-SG, RDEB-O, RDEB-I, KS | |
Mitten deformities | RDEB-SG | |
Muscular dystrophy | EBS-MD, EBS-PA | |
Hematopoietic system | Multifactorial anemia | RDEB-SG, JEB-H, JEB-PA, EBS-PA, JEB-nH, EBS-AR, EBS-DM, RDEB-O |
Heart | Dilated cardiomyopathy | RDEB-SG, JEB-nH, EBS-MD |
Endocrine | Delayed puberty, amenorrhea | RDEB-SG, RDEB-O |
Systemic complications | Sepsis | JEB-H, JEB-nH, RDEB-SG, EBS-DM |
Failure to thrive, growth retardation | JEB-H, JEB-PA, EBS-PA, RDEB-SG, JEB-nH, RDEB-O, EBS-AR, EBS-DM, RDEB-I |
General principles
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Treatment of EB patients should be performed in centres of expertise adhering to the recommendations for quality criteria issued by the European Union Committee of Experts on Rare Diseases (EUCERD) [19].
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Centres of expertise should also guarantee the continuity of care between pediatric age and adulthood [20].
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A coordinated multidisciplinary approach must be adopted (Table 3).
Physicians | Other professionals |
---|---|
Dermatologist | Specialist nurse |
Neonatologist/pediatrician/internist | Dietitian |
Pathologist | Psychologist |
Medical geneticist | Dental hygienist |
Otolaryngologist | Physical therapist |
Ophthalmologist | Occupational therapist |
(Pediatric) surgeon | Speech therapist |
Orthopedic surgeon | Social worker |
Plastic surgeon | |
(Pediatric) gastroenterologist | |
Dentist | |
(Pediatric) anesthetist | |
Endocrinologist | |
Neurologist | |
Radiologist | |
Pain relief doctor | |
Cardiologist | |
Nephrologist | |
Oncologist |
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The multidisciplinary management is centered on the patient; therefore, it is a tailored treatment for each patient.
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The multidisciplinary team should be specifically trained and regularly updated [19].
Care of the EB newborn and infant
General principles
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The first multidisciplinary care should be provided independently from the diagnostic definition of the EB type and subtype.
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Diagnosis should be performed as soon as possible in order to implement the most appropriate treatment, communicate the diagnosis and specific information to the parents. Methods and criteria for diagnosis have been regularly updated by an International Consensus Conference [1].
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The communication of the diagnosis should involve the dermatologist and the neonatologist and should be addressed to both parents. The information should be delivered gradually and adapted to the family socio-cultural level.
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A psychologist should support the family (see paragraph “Care of disease burden”).
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Caregiver education should start promptly (see paragraph “Therapeutic patient education”).
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Members of the multidisciplinary team usually involved in EB care in infancy are neonatologist/pediatrician, dermatologist, anesthetist, pathologist, medical geneticist, psychologist and specialized nurses.
General measures
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Blood sampling for complete blood count, electrolytes, C-reactive protein, urea, creatinine, total serum protein and albumin, iron, zinc, and, whenever required, blood cultures. Swabs for culture should be taken from infected wounds.
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In severely affected newborns, a venous access should be guaranteed through placement of an umbilical venous catheter. Whenever required, this will be followed by elective insertion of an indwelling central venous catheter (tunnelled external design such as Broviac catheters).
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The following measures should be adopted to prevent blistering:
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✓ the baby should not be placed systematically in an incubator unless needed for reasons such as prematurity [10]: heat and humidity can lower the threshold for blistering. An overhead heater can be used, cautiously regulated.
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✓ Naso- and oro-pharyngeal suction should be avoided. If required, a soft catheter is chosen, and minimal suction pressure exerted [31].
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✓ The use of clips should be avoided, and name band put on clothing instead of wrist.
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✓ Electrodes should be of small size; the adhesive rim should be removed allowing only the lubricated central portion to be in contact with the skin and the electrode should then be secured with a non-adhesive dressing (e.g. Mepilex®, Mölnlycke) [33].
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✓ Clip sensors should be used for pulse oximetry.
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✓ For blood pressure monitoring, thick padding is recommended before applying the blood pressure cuff.
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✓ When possible, skin-to-skin contact (kangaroo care) with parents should be encouraged.
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✓ There is no contraindication to immunization for infectious diseases.
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Skin care
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For clothing, a front-fastening babygro is easier to put on and remove. It should be turned inside out to prevent the seams from rubbing skin [31]. If available, DermaSilk® (Alpretec) underclothes and gloves can be used as they combine silk properties with the protective activity of an antimicrobial agent, in addition to being seam-free. Alternatively, Tubifast (Mölnlycke) garments and gloves can be used [10].
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Disposable nappies can be used, they should first be lined with a soft material (e.g. soft silicone contact layer or foam such as Mepitac®, Mölnlycke) in order to reduce skin rubbing from the elastic edges. Nappies with Velcro fasteners prove safer as it is less likely for the securing tapes to adhere to the skin [10, 31].
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Particular attention should be paid to avoid friction when handling the baby: he/she should be nursed on neonatal incubator mattress, and lifted by sliding hands below the mattress or using the sheet [10]. To handle the naked infant, the nurse/caregiver should roll the baby away, place one hand behind his/her neck and head and the other one behind his/her buttocks, let the baby roll back and then lift him/her [31, 32] (Figure 1).
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Adhesive tapes must be avoided. Soft silicone fixation tapes providing atraumatic removal (e.g. Mepitac®) are recommended to secure devices such as electrodes, catheters, tubes, and probes. For removal they should be rolled out gently rather than lifted.
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Silicone Medical Adhesive Removers (SMARs), such as Appeel® (CliniMed) or Niltac®, should be used to remove electrodes or accidentally applied tapes or dressing/clothing adhered to wounds. If SMARs are not available, liquid and white soft paraffin in equal parts facilitate atraumatic removal [10, 34, 35].Regular bathing in tepid to slightly warm water is recommended (Figure 1), the frequency will be adapted to each case. If the infant presents crusted lesions, an emollient/oil-based cleanser should be used, while infected wounds should be treated with an antiseptic (e.g. containing 0.1% chlorhexidine). After bathing, the skin should be dried by gentle padding with a towel.
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Principles for blister, aplasia cutis congenita and wound treatment are similar to those applying to children and adults (see paragraph “Wound care”).
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Aplasia cutis congenita and blistering involving hands or feet or digit degloving following delivery require specific dressing in order to prevent early digit fusion [10]. The separation should be performed by using easily modelled dressings, such as soft silicone foams (e.g. Mepilex® or Mepilex Lite®), which are cut into strips (Figure 1). If advanced dressings are not available, paraffin-impregnated gauzes can be used, and should also be cut into thin strips. Attention should be paid to keep the first finger extended and separated from the rest of the hand.
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The diaper area is constantly subject to handling, exposed to urine, feces and to the diaper occlusion effect. We prefer to treat the less exuding erosions with paraffin-impregnated gauzes, replaced at each nappy change. Alternatively, a soft silicone primary wound dressing (e.g. Mepitel®) or hydrogel-impregnated gauzes (e.g. Intrasite® Conformable, Smith & Nephew) can be used. In more exuding lesions, an antiseptic and silicone foams (e.g. Mepilex® or Mepilex®Transfer) are indicated.
Feeding modalities
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In less severely affected newborns breast-feeding is possible: soft paraffin can be applied on the nipple and breast as well as on the infant face and lips to reduce friction from rooting reflex [31]. The mother should be trained to handle the baby and breast feed him. When breast-feeding proves traumatic, oral feeding remains the best option, also allowing to add supplements in malnourished infants.
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Commercially available teats should be softened with warm boiled water. The teat hole can be enlarged or extra holes may be created to facilitate sucking. Lips can be protected with petroleum jelly to avoid the skin sticking to the teat [31].
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A few infants may require naso-gastric feeding. A small soft polyurethane tube fixed for few weeks will minimize internal damage and reduce the trauma [31].
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For nutritional principles see paragraph “Nutritional aspects”.
Follow-up
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The infant should be discharged home when the general health condition is stable and the parents are adequately educated and confident to care for their baby. This decision is taken jointly by the dermatologist and neonatologist/pediatrician. The involvement of social workers and psychologists in the organization of the discharge is helpful.
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A first follow-up visit with a specialized team (usually: dermatologist, pediatrician, EB nurse, psychologist) will be organized in one or two weeks for severe EB subtypes (e.g. Dowling-Meara EBS, JEB and recessive DEB). It should comprise a complete clinical examination (skin/mucosae, nutrition, pain, etc.), dressing, and evaluate and pursue the therapeutic education of the parents. If the infant care is correctly performed the next appointment should be in one month, then every three months during infancy. In mild EB subtypes the follow-up visits will be every 3–6 months.
EB care from childhood to adult
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reduced patient compliance to care and claim for self-care;
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chronic pain;
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presence of chronic wounds and their susceptibility to infection;
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risk of cancer development;
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chronic itching;
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anemia and malnutrition secondary to oral and gastrointestinal involvement and chronic wounds, in turn negatively interfering with wound healing;
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psychological problems related to both disease acceptance and social relationship (school, hobbies, job, etc.).
General principles
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The members of multidisciplinary team vary upon the EB type and patient and family needs. In mild EBS subtypes (e.g. localized and generalized non-Dowling-Meara EBS), the dermatologist ensures the follow-up with the help of a specialized nurse. In severe EBS forms (such as Dowling-Meara EBS or EBS with muscular dystrophy), JEB and generalized DEB subtypes the core members are the dermatologist and the pediatrician supported by the EB nurse and dietician. Other specialists (ophthalmologist, dentist, digestive surgeon, psychologist, physiotherapists, etc.) are involved depending on disease complications.
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A regular follow-up is required to evaluate skin and mucosal conditions, general health status, and specific problems encountered by the patient and his/her caregivers. Follow-up planning should be performed taking into account the EB type, disease complications, family and patient compliance and specific complains. After childhood, EBS and mild DEB patients are generally seen by an EB specialist once a year; JEB and generalized RDEB should be seen at least twice a year. More frequent follow-up visits (e.g. every month) are required for the most severe patients in order to fasten wound healing and to early diagnose and treat squamous cell carcinoma.
General measures
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Monitoring of severe EBS variants (e.g. Dowling-Meara EBS or EBS with muscular dystrophy), JEB, and generalized RDEB subtypes comprises at follow-up visits: a complete blood count, electrolytes, total serum protein and albumin, iron, iron-binding capacity, ferritin, erythrocyte sedimentation rate, C-reactive protein, liver function tests, urea, creatinine and, if required, zinc, selenium, folate and vitamins (A, B6, C, D and E) [22, 39]. Swabs for culture should be taken from infected and critically colonized wounds, as blood cultures in case of sepsis suspicion.
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Patient adherence to therapy should be regularly checked. Caregiver and patient compliance and experience should be always taken into account in designing the care plan.
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Immunization schedule for infectious diseases should be regularly continued. Chicken pox vaccination is recommended.
Direct skin protection
| • Protect vulnerable skin sites, (e.g. knees and elbows) with soft silicon contact layers, silicon sheets or strips (e.g. KerraPro®) or thick padding |
• Use gloves when the child begins to crawl/walk and lifelong during sports or hobbies (e.g. DermaSilk® or Tubifast®) | |
• Avoid hard shoes with internal seams, tight clothes and clothes with raised seams, tags in contact with the skin | |
• Use protective padding for shoes, such as a poron insole or orthotic device | |
• Pad the frame at the nose bridge and over the ears of eye glasses | |
Other measures
| • Ensure that toys are frequently cleaned and in soft material without traumatic angles |
• Prefer hobbies and sports at low risk of skin trauma (e.g. adapted gym, swimming, ping-pong, reading, singing, playing music, electronic toys and informatics) | |
• House air conditioning and other cooling measures in hot climates |
Skin care
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Regular patient follow-up by the dermatologist comprises the assessment of the entire body including the scalp, external ear, genital/anal area, oral cavity and nostrils.
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A dermatological management is necessary in all types of EB and skin lesions.
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An appropriate analgesia should be performed before any procedure, such as bathing or dressing (see paragraph “Pain management”).
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For the hygiene, a mild antiseptic cleanser (e.g. chlorhexidine 0.1% or polyhexanide, sodium hypochlorite 5–10 ml in 5 L of water, acetic acid ≤0.25%) should be used for extended and/or critically colonized/infected lesions [39, 41]. An emollient/oil-based cleanser should be chosen for xerotic skin and hyperkeratotic or crusted lesions.
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Bathing frequency depends on the type of dressing and lesion characteristics: in case of infected wounds or dressings which stick to the lesions (e.g. paraffin-impregnated gauzes) bathing should be performed every other day; when advanced dressings are employed bathing can be delayed until once a week.
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Daily use of emollients and moisturizing products is strongly recommended for xerotic skin in order to reduce blistering, pain and itching [31].
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Regular photoprotection is mandatory in patients affected by KS who present photosensitivity.
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Courses of topical keratolytic agents (e.g. urea, salicylic acid, ammonium lactate) are helpful to treat palmoplantar hyperkeratosis and/or keratoderma [40]. Their concentration depends on the patient age, rhythm of application, treatment duration and local tolerance. Particular caution is required for young children.
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Hyperhidrosis, frequent in EBS patients, should be treated in order to reduce/prevent blistering and itching. Corn flour is an inexpensive and easily available remedy [10, 40], other absorbent powders (e.g. Zeasorb®, Stiefel Laboratories) may also be useful. An additional option is iontophoresis [43]. Furthermore, the use of botulinum toxin may be considered for severe plantar hyperhidrosis [43, 44]. Silver-lined or Dermasilk socks keep feet dry and comfy, provide anti-friction action and reduce the risk of bacterial overgrowth [10, 40].
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No specific treatment is required for milia.
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Mucosal care:
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Oral management should adhere to the recently published best practice guidelines for oral health care in EB [9].
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Conjunctiva should be regularly lubricated, in particular in JEB or RDEB patients, with lanolin and preservative-free eye drops or gels, e.g. containing hyaluronic acid, polyethylene/propylene glycol or carbomer [45].
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Nasal lubricants are more frequently indicated for JEB or RDEB patients; regular ointment containing vitamin E or simply petroleum jelly can be helpful.
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Wound care
Dry to lightly exuding wounds
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Non adhesive soft silicone or lipido-colloid contact layers [e.g. Mepitel®, Adaptic® touch (Systagenix), Urgotul® (Urgo Medical), Silflex® (Advancis Medical)], thin polyurethane-soft silicone foams (e.g. Mepilex® Lite), and hydrogels (e.g. Intrasite® Conformable) appear to be the most suitable in these lesions [8, 10, 46, 51]. Hydrogel dressings should be changed daily or as soon as they become dry. The other types could be changed every 3–4 days.
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The dressing choice depends on the affected site: e.g. flexible dressings should be used mainly for the folds. Soft bordered materials [e.g. Mepilex® Border, Alleyvn® Gentle Border (Smith & Nephew)] easily adapt to the different skin sites but they may be too sticky and thus require a primary contact layer in order to protect fragile skin [10].
Heavy exuding wounds
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Heavy exuding wounds present a high risk of infection and require specific dressings. Either hydrofiber dressings (e.g. Aquacel®, Convatec) or soft silicone foam with super-absorbers (e.g. Cutimed® Siltec, BSNmedical), able to absorb the abundant exudates, should be preferred. Soft silicone foams [e.g. Mepilex®, Mepilex® Transfer, and Advazorb Silflo® (Advancis Medical)] and polymeric membranes (PolyMem®, Ferris Mfg. Corp.) are also indicated [8, 10, 46, 51]. The soft silicone foams are also suited for digits and folds. On the other hand, PolyMem® is not easily retained on the wounds and requires a secondary dressing to hold in place. Also Mepilex® Transfer needs a secondary dressing to absorb exudates.
Critically colonized and infected wounds
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To early diagnose a critically colonized or infected wound the following parameters and features should be considered:
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✓ wound history: several week duration, recent size extension and exudate increase;
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✓ wound bed: presence of debris, dead slough, friable tissue and bad smelling;
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✓ wound margins and surrounding skin: oedema, erythema, higher temperature than the healthy skin.
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In the presence of the above mentioned criteria, swabs for culture should be taken after washing the lesion with normal saline and then the treatment should be started based on clinical features [41].
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In case of lesions at risk of infection, the use of lipid-stabilized hydrogen peroxide cream (Crystacide®) has been proposed [41]. An aqueous solution of eosin (2%) is employed in some countries with the aim to reduce the exudate, keeping in mind that it has no antiseptic properties. In other countries, medical-grade honey in ointments (e.g. Mesitran S®, Medloc) or dressings (e.g. Algivon®, Advancis Medical; Medihoney®, Derma Sciences) are available and used with the aim to reduce the risk of infection and promote wound debridement [10, 41, 52, 53].
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The use of silver-containing creams (e.g. silver sulfadiazine) or dressings (e.g. Mepilex®AG; Urgotul®silver/SSD; PolyMem®silver, Aquacel®Ag) has been advocated [10, 41]. However, there is no clear evidence that silver-containing products can prevent wound infection or improve healing rates of leg ulcers [52] and references herein]. Importantly, silver plasma level should be checked in case of large surface and/or prolonged treatment because of the risk of silver absorption and related toxicity [54, 55]. In children, the use of silver-containing products should be very limited in time and treated surface.
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The dressings for infected wounds are the same used for heavy exuding wounds, but they should be changed daily.
Topical agents
| • Restrict the use to critically colonized and infected wounds |
• Prefer agents which do not have a systemic formulation (e.g. fusidic acid, mupirocin) | |
• Use for short periods and rotate to avoid resistances and sensitizations | |
• Consider retapamulin as a second line treatment for resistant Gram positive bacteria | |
Systemic agents
| • Administer in multiple infected lesions |
• Start early in malnourished and/or non compliant patients and in infants | |
• Prescribe antibiotics according to the result of culture | |
• Prefer narrow spectrum antibiotics |
Hyperkeratotic and crusted lesions
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Warty and crusted lesions require an accurate treatment and follow-up because they are itchy and can mask an underlying squamous cell carcinoma. The crusts and hyperkeratosis should be regularly removed. Frequent application of emollient creams and bathing twice a week are indicated to this purpose.
Exuberant granulation tissue
General remarks
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The dressings of all types of wounds should be checked daily and the change frequency modified based on wetting and smelling.
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Paraffin-impregnated gauzes (e.g. Jelonet®, Smith & Nephew) or medicated gauzes (e.g. Fitostimoline® containing an aqueous extract of Triticum vulgaris, or Connectivine®, Fidia, containing hyaluronic acid) can be used when advanced dressings are not available [8, 10]. They require a secondary dressing and should be changed on a daily basis, increasing wound manipulation, pain and indirectly also the risk of infection. These products adhere to the wound bed. In order to reduce pain and trauma, dressing removal requires prolonged soaking with distilled water or saline solution or bathing [8, 10].
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In RDEB patients, finger and toe dressing should be regularly performed as described for the neonatal period, to delay digit fusion and pseudosyndactyly [10].
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Tubular bandages of various sizes and heights according to the affected body area (e.g. Elastomul®, Tubifast® or Self-fix®) should be used for dressing retention to prevent slipping and further trauma. Tight bandages must be avoided as they can induce blistering by rubbing the skin [8, 10]. If available, Dermasilk® or other specifically designed garments, without silver, can also be useful to retain the dressings in place.
Itch management
General measures
| • Bathing in tepid water with syndet/oil cleanser and skin hydration with emollients |
• Overheating and dry environment avoidance | |
• Relaxation techniques and patient education to cope with the vicious itch–scratch cycle | |
Therapeutic options
| • Short courses of topical mid-potency steroids |
• Sedating antihistamines (e.g. hydroxyzine) and/or tricyclics with anti-H1 antihistaminic action (doxepin) as first-line treatment* | |
• Low-dose gabapentin (Neurontin®) or pregabalin (Lyrica®) as second-line treatment | |
• Anti-inflammatory agents (e.g. cyclosporine, thalidomide or topical tacrolimus) to be cautiously considered as third-line treatment only in severe cases** |
Management for surgical procedures
General principles
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Surgery in general anaesthesia should be limited to strictly necessary procedures and organized jointly by the surgical team (surgeon, anaesthesiologist and nurse) and the EB team coordinator.
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Whenever necessary and feasible, the different surgical treatments should be performed at one time in order to reduce the risks linked to anaesthesia.
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A tailored management should be planned for each patient after a careful evaluation.
General measures
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When a surgical procedure in general anesthesia is planned, a multidisciplinary re-assessment should be performed a week or two ahead of the surgery date to verify the general health conditions of the patient [33].
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Blood sampling should be performed before surgery to evaluate and treat anemia.
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Before the procedure, the surgical team, including the anaesthesiologist and the case manager, should clearly explain the possible problems and complications linked to the procedure, paying particular attention to those related to EB disease.
Specific measures
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Anxiolytic administration can be helpful in the pre-operative stage.
Procedure | Measures to be adopted |
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Operating table
| • Place an anti-decubitus mattress and cushion on the table |
• Use the sheet to lift the infant and move him/her to the operating table; older patients should move themselves | |
• Pad trauma-exposed sites (e.g. chin, occiput, elbows, heel, hands, feet) | |
Premedication
| • Administer oral premedication 45 minutes prior surgery in order to reduce/prevent: |
✓ Patient anxiety (midazolam 0.5 mg/kg) | |
✓ Oral secretion (atropine 40 mcg/kg) | |
✓ Gastro-esophageal reflux (ranitidine 1 mg/kg) | |
✓ Vomiting (metoclopramide 150 mcg/kg) | |
• Prefer intravenous induction in presence of intravenous line, otherwise inhalational anaesthesia. In the latter case, protect the face from the mask with silicon foam (e.g. Mepilex®) or a water-based lubricant. | |
• Protect the eyes with a moisturizing ophthalmologic gel and the eyelids with moistened gauzes | |
Patient monitoring
| • Use tape with a silicon contact layer (Mepitac®) to fixe all tubes (e.g. endotracheal tube) and catheters |
• Lubricate all tubes with a water-based lubricant | |
• Remove the adhesive part of electrodes allowing only the lubricated central portion to be in contact with the skin; then secure with a non adhesive dressing (e.g. Mepilex ®) | |
• Use clip sensors for pulse oximetry | |
• Use a lubricated disposable thermometer | |
• Pad the skin with cotton or advanced dressings under the blood pressure cuff | |
• Use bipolar diathermy to avoid a monopolar pad | |
• Avoid carefully all kinds of trauma and friction for the entire duration of surgery | |
Intubation
| • Evaluate microstomia, esophageal strictures and prominent incisors in RDEB* patients who need intubation |
• Prefer fiberoptic-assisted intubation to laryngoscopy in case of difficult intubation | |
Recovery room
| • Administer a moderate sedation before emergence to avoid cutaneous lesions due to irritability |
• Perform tracheal aspiration gently using soft and small tubes |
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After surgery, the intravenous line should be kept in place as long as possible to be used for transfusion, perfusion or other systemic therapy (iron, albumin, antibiotics).
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Fiberoptic intubation appears to be a good technique to minimise frictional trauma and to reduce the risk of blistering, whilst safely securing the difficult airway [67].
Pain management
General principles
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Pain is acute, chronic and related to procedures (e.g. bathing, dressing, surgical procedures, etc.). Psychological pain and anxiety contribute constantly to worsen organic pain.
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Acute pain is mainly due to newly-onset mucosal lesions (cornea, oral cavity, oesophagus, anus or larynx and trachea).
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Chronic pain includes inflammatory, neuropathic and bone pain.
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The general conditions and nutritional status affect the severity of chronic pain.
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Evaluation of pain is mandatory and should address all the above mentioned components. It can be difficult in particular in children. Pain evaluation scales and frequency are the same used for non-EB patients and vary according to the patient age and on-going procedures.
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An EB expert should examine and listen attentively to the patient and his family in order to design the individual therapeutic strategies.
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An early adequate management of the physical pain is mandatory in order to reduce also the psychological pain component and to promote patient compliance.
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An early and regular psychological support for patients and families can contribute to the global efficacy of pain management.
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Unfortunately, in some cases, both pharmacological and psychological management strategies do not achieve complete pain control.
General measures
Pain related to nursing procedures
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Bathing and dressing should be performed in a room equipped with all the necessary materials prepared in advance and close at hand (Figure 1). Non-pharmacological treatments based on cognitive-behavioural techniques are essential. A quiet and relaxing environment is helpful (music, films, pacifier dipped in glucose solution, etc.). The caregiver should provide contact, caresses and sweet words. Hypnosis can be useful in older children and adults.
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Topical anaesthetics (xylocaine, lidocaine-prilocaine) are recommended before the care of painful tense blisters or wounds and venipuncture. However, the total dose should be limited to prevent the risk of seizures and methemoglobinemia.
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Paracetamol is the first choice for mild pain and short procedures. In more severe pain and complex procedures, opioids are indicated (from codeine to oxycodone and morphine). Opioid side effects include constipation, pruritus and rarely respiratory failure. The development of tolerance leads to dose increase with risk of addiction [70‐74].
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Meopa® (nitrogen monoxide-oxygen mixture) can be helpful in most severe pain both in children and adults. Its use is restricted to the hospital setting and limited in time.
Chronic pain
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General measures are essential (e.g. music, yoga, relaxation techniques, hypnosis, etc.). In most cases, they need to be combined with analgesics. Paracetamol is usually the first-line treatment, followed by opioids (codeine, morphine, etc.). Non steroid anti-inflammatory drugs (NSAID) should be cautiously administered in patients with chronic/severe infections.
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A neuropathic pain component can be managed with pregabalin (Lyrica®) or gabapentin (Neurontin®) [73]. Tricyclic antidepressants, e.g. amitriptyline, are an alternative treatment.
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The daily analgesic dose should be distributed over 24 hours and increased before any care procedure.
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Bone pain, usually observed in severe RDEB, is due to abnormal bone mineralization, in turn related to poor nutrition, reduced mobility and chronic inflammation. Therefore, the improvement of nutritional status and physiotherapy contribute to reduce pain. Biphosphonates are useful to decrease bone pain, but their administration can be limited by perfusion difficulties and side effects (e.g. mandible osteonecrosis).
Acute pain
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Reassure the patient and his family.
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Administer adequate analgesic therapy (frequently opioids) or increase the dose of the ongoing treatment.
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Local anaesthesia may be useful in case of painful constipation due to anal erosions or fissures. Botulinum toxin for anal sphincter relaxation may represent a valid alternative.
Psychological pain
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Acute and chronic pain induce psychological pain since the first days of life.
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An inadequate pain control during procedures may cause a vicious circle with a memorization of the physical pain, and then anticipation and psychological distress increasing the physical pain at each procedure. Relaxation techniques, psychological support and pharmacological treatment should be provided.
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Psychological support should be reinforced during adolescence. A latent depression is not exceptional in the most severe forms and appropriate treatments have to be administered.
Nutritional aspects
General principles
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The evaluation of patient growth, performed according to international standards (weight for length < 2 years; body mass index > 2 years), can be hampered by fixed contractures.
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The nutritional support should start early, especially in severe generalized subtypes.
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Dietetic advices, aimed to increase energy and protein content of oral food, should be addressed continuously to patients and their families.
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All factors affecting the quality of nutrition need careful management and follow-up: trauma related to hard food, dental caries and periodontal inflammation, gastro-oesophageal reflux, oesophageal strictures, inflammatory bowel disease, anal fissures and constipation, etc.
General measures
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Proteins and energy
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Nutritional procedures: nasogastric and gastrostomy feeding
Physical therapy and rehabilitation
Early diagnosis of squamous cell carcinoma (SCC)
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whole-body physical examination, including the scalp, oral mucosa and genital area, every 6 months in RDEB and adult JEB patients;
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more frequent follow-up in presence of chronic hyperkeratotic or warty wounds;
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multiple excisional biopsies in case of crusted-warty skin lesions or chronic wounds unresponsive to proper treatments;
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early and wide excision of the lesion in case of histologically confirmed carcinoma.
Management of intercurrent or associated cutaneous diseases
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represent a diagnostic challenge due to atypical presentation (impetigo, scabies, etc.);
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worsen EB course, due to the development of pruritus and risk of infection (e.g. atopic dermatitis, scabies, VZV infection, impetigo, etc.);
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need an adapted management which should take into account the presence of EB lesions and the increased risk of percutaneous absorption. Some topical products may indeed cause irritation and toxicity (e.g. topical treatment for cutaneous parasitic infestations, such as benzyl benzoate, permethryne).
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Pruritus onset/worsening in EB patients should foster investigation for parasitic infestation such as scabies and lice.
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Pruritus in associated cutaneous diseases should be treated as described for pruritus in EB patients (Table 6) in order to prevent worsening of EB lesions.
Therapeutic patient education
Principles
| • Should be addressed to the patient, his/her family and caregivers |
• Should be delivered individually or in group | |
• Should be adapted to the EB subtype, patient age, socio-cultural milieu and compliance | |
• Should be delivered by specialized nurses with the support of the members of the multidisciplinary team and the psychologist | |
• Should be performed orally and gradually, complemented by the release of information sheets for the patient and his/her family/caregivers | |
Contents
| • Should at first clearly communicate the diagnosis, disease course and complications |
• Should give clear explanations on the need of an adapted genetic counselling | |
• Should train the patient and his/her family/caregivers on the management of cutaneous and extracutaneous manifestations | |
• Should educate the patient and his/her family/caregivers to early recognize infection signs and atypical aspects of the chronic wounds, and to consequently request a rapid evaluation by a dermatologist | |
• Should provide training on the life style in order to prevent disease worsening |
Care of disease burden
General principles
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Whenever possible, the transfer of the newborn to the centre of expertise should be performed when also the mother is able to move, avoiding disruption of the close parent-infant relationship or even the infant refusal.
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A gradual and multistep delivery of information on diagnosis and prognosis can reduce the psychological trauma. Particular caution should be taken to avoid culpability feelings in the parents.
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The involvement of both parents in the education process may facilitate their coping with the disease, reduce couple difficulties and reinforce their relationship.
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The parents should be accompanied in the educational process of the affected child, at the same time ensuring that the child progressively acquires as much autonomy as possible.
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The participation of the entire family can reduce the risk that non affected siblings feel neglected by the parents.
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A psychological support to the patient and his family is frequently needed and should be integrated in the multidisciplinary management process.
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Monitoring of the emotional status of the patient and/or his family and early diagnose psychological distress require yearly appointments with a psychologist even in absence of specific symptoms.
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The psychologist should be involved early when the newborn parents manifest signs of persisting distress.
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Indications to the provision of psychological and psychotherapeutic support to the patient and family members are summarized in Table 9.
Family members
| • Fear to breastfeed or handle the newborn and/or infant refusal |
• Lack of self-confidence or inadequacy feeling in coping with the disease | |
• Anxiety to be left alone with the disease | |
• Depression or disease refusal by one the two parents | |
• Altered relationship of the couple (e.g. lack of interest in carrying out activities as a couple, loss of intimacy, negative impact on sexuality, etc.) | |
• Culpability feelings and inability to take care of the non-affected children | |
• Discomfort feelings or depression of the siblings | |
Patient
| • Stress or depression related to the visibility of disease manifestations and the feeling of being different |
• Chronic pain exacerbated by daily care procedures | |
• Chronic itching resistant to therapy | |
• Stress or depression due to limitations in daily activities and social life | |
• Lack of compliance and adherence to treatment, particularly in | |
• Adolescence and adulthood |
Continuity of care
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a detailed referral form must be delivered and addressed to the primary care physician (pediatrician or general practitioner). It must report the diagnosis and the care given during hospitalization, describe the treatment plan for patient home care, the follow-up schedule and report the contact details of the EB team coordinator or his/her delegate from the center of expertise (e.g. specialized nurse) and, whenever available, of hotlines/call centres for emergency or urgent professional information;
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whenever foreseen by national laws, a certificate stating the diagnosis and a treatment plan must be addressed to the relevant public health authority in order to ensure free-of-charge care and provision of needed drugs, dressings and devices;
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depending on the national laws, ad hoc certificates must also be addressed to the public health service in order to guarantee homecare by specialized nurses, and if necessary also psychological support, physical therapy, occupational therapy, assistance by social workers, etc.;
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in countries where specialized EB nurses are not available, ad hoc training of the community health nurses is recommended;
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information sheets should be provided to the family/caregiver (relatives, friends, teachers, colleagues, etc.) in order to promote an adequate relationship with the patient, to explain the impact of the disease on daily activities and QoL (education, work, household chores, life management);
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information about the opportunity to get in touch with the patient association, if present in the country, should be released as detailed below.
The relationship with the patient association
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Patients should be informed about the presence of the patient association in their country and the interest to become a member.
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Patient associations contribute to improve patient access to information, reference centres, and social services.
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They also facilitate contact between patients and sharing experience regarding daily life.
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In some countries, they provide financial support and/or fund nurse home care and/or organize vacations for patients and families.
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Finally, they can contribute to promote professional training and research.