How is EB Treated?

Because EB involves many systems of the body, parents and health professionals must take a 'team approach' , to the treatment of an EB patient. Intense and total patient care often must be provided, particularly for young and growing children. The severe forms of EB require hours of intensive nursing care that in many ways is similar to that given to burn patients. Much of this care is often provided by the parents; however, the education of all people who have contact with the patient is essential. These people may include the primary care physician (often a pediatrician), the dermatologist, the nurse, the pediatric dentist, the specialist in gastrointestinal (digestive) diseases, the dietitian or nutritionist, the plastic surgeon, the psychologist or social worker, and the genetic counselor, as well as teachers, relatives, baby sitters, and others.

So far, research has not yet found a cure for epidermolysis bullosa or a treatment to completely control any form of EB. However, many complications can be lessened or avoided through early intervention. Many persons with milder forms have minimal symptoms and may require little or no treatment.

In all cases, treatment of EB is directed towards the symptoms and is largely supportive. This care should focus on prevention of infection, protection of the skin against trauma, attention to nutritional deficiencies and dietary complications, minimization of deformities and contractures, and the need for psychological support for the entire family.

Supportive Care

The following list of suggested methods of care has been compiled from several sources and addresses all forms of EB. Because suggestion may not pertain to every form of EB, discretion and experimentation will guide the parents and the physician in choosing those methods that apply.

Skin Care and Wound Healing

Protection of the Skin

In EB, even slight friction can produce blisters, so minimal and gentle handling is absolutely necessary. A cool environment, avoidance of overheating, and skin lubrication to reduce friction can help lessen blister formation. A water or air mattress padded with foam may help reduce friction, as will a soft fleece covering or percale sheet placed over the mattress. Sheepskin is excellent for padding car seats, infant seats, or other hard surfaces. The young child with moderate or severe EB should never be picked up under the arms, but should be lifted from the bottom and the back of the neck and carried on soft, nonirritating material.

Clothing must be made of soft, nonirritating fabric, easy to put on, and simple in design. Socks and mittens can be used to prevent the infant from rubbing his hands and feet and scratching his face. It may not be advisable to use a diaper on a baby with severe EB; instead a pad can be placed under the buttocks and the diaper area left uncovered. When a diaper is used, the area must be kept dry and clean.

Skin Care and Bandaging

The purposes of good skin care and bandaging are to reduce the incidence of infection, assist healing of involved areas, and serve as a protective cushioning against friction. The best times for skin and dressing changes are following a bath, after a lesion has been cleansed, or before bedtime. Prior to dressing changes analgesia may be given for comfort as ordered by physician. Daily cleansing may include a bath with mild soaps or cleansers. For infant bathing some caregivers may choose to cleanse limited areas at a time to keep the child from losing their body temperature.

Helpful wound care hints:

• Always wash hands before starting.
• Do not pull off any soiled dressings or clothing that may be sticking to the skin. Soak off in warm water. The physician may suggest adding an antibacterial agent to the water.
• Release fluid in blisters by cutting a small slit on the side of the blister using a sterile scissor or scalpel blade. Many people prefer to puncture the blister in several places with a sterile needle.
• May keep the blister roof intact upon the wound.
• To help drain the fluid and dry the blister, wet soaks can be placed over punctured blister.
• If prescribed by the doctor, an antibiotic ointment may be applied.
• Nonadherent dressings or other dressing recommended by the doctor can be placed over the open areas. A soft, rolled type of gauze or netting can be used to secure the dressings in place. Loose ends can be secured with paper tape. NEVER apply tape directly to the skin. In milder or localized EB, it is preferable to leave the area open to the air. If desired, a non adherent dressing can be placed over an oozing wound.

The Art of Wound Healing

The importance of good wound care cannot be stressed enough. Due to the nature of Epidermolysis Bullosa, blistering and open wounds compromise the integrity of the skin, which is the first line of defense against infection. As soon as a break in the continuity of skin occurs, the healing process begins. In order to effectively treat a wound we must keep in mind that EB wounds are all in various stages of healing and that those wounds may require different treatments to optimize the wound bed for healing.

What happens during wound healing?

• Clotting is one of the first in a series of reactions. It occurs to reduce blood loss.
• The warmth, redness and swelling that appears is due to leakage of fluid into the wound.
• White blood cells called Leukocytes and Macrophages gang up to destroy bacteria.
• Macrophages stimulate growth factors and other important materials that are necessary for the formation of scar tissue.
• Epithelial (skin) cells travel across the wound to prepare for closure.
• The formation of new collagen, blood vessel formation and pulling together of tissue occurs to reduce the size of the wound.
• The last phase of healing involves the reorganization of collagen to maximize tensile strength of the affected area

The stages of wound healing among each wound may differ somewhat leading to variations in wound treatment. For instance wounds with minimal drainage may require additional moisture to enhance healing. Some wounds may drain heavily and require more absorptive dressings or an increase in the frequency of changes to help manage the drainage. Each wound has its own personality. Keeping that in mind may help when choosing wound products that may optimize healing. The parents and caregivers usually become the wound care experts.

Opening blisters

It is important to understand that if the blister is left intact, it can grow bigger and create a larger wound. It may be helpful to pat the blister gently with an alcohol pad prior to popping with either a sterile needle, sterile scissors or sterile lancet. Gently pierce the side of the blister and allow the fluid to drain onto a sterile gauze. After the blister is popped, the blister roof may be left intact. After popping the blister you may cover with a sterile non-adherent dressing.

Prevention of infection

Any open area on the skin or mucous membranes is a potential site for infection. The best way to prevent infection is to keep the area clean. Gentle cleansing of the skin, various anti-biotic ointments and soaks may be ordered by the physician. Remember it is always important to wash hands before and after wound care. It is important to note that over use of topical antibiotics may increase chances of resistant strains of bacteria. Mild topical antibiotics may be rotated every two to four weeks to discourage bacterial resistance.

Signs of infection may include the following. Redness surrounding the wound, or a red streak that spreads toward a more central part of the body, unexplained fever or chills, evidence of pus or yellow drainage or crusting on wound surface or draining from EB wound. A fever may or may not be present. The physician may obtain a wound culture. A wound culture is done by gently swabbing the open area with a long cotton tipped applicator to see what bacteria grows on the wound surface. These culture results are helpful in order for the physician to determine the best course of treatment. Treatments may include various topical soaks and /or antibiotic ointments that reduce bacterial growth upon the wound. Fever is an indicator that there is systemic infection. This usually warrants a visit to the physician for oral antibiotic therapy. In some instances systemic infection may require a hospital visit for intravenous antibiotic therapy. Soiled wounds and wounds covered with antibiotic ointment may need to be cleansed prior to culturing in order to increase the accuracy of the culture result. Itchy skin (pruritus) may be caused by infection, sensitive nerve endings or healing. Scratching of the area will cause further damage to the wound bed. Consult physician about medications to manage itch.

Monitor nutritional status

Factors such as poor nutritional intake, possible mal absorption of nutrients and anemia can contribute to poor wound healing. (Need for vitamins, minerals and trace elements needs to be determined by physician and dietitian).

Dry wounds

If the wound is desiccated (dried out) the use of various ointments (as ordered by physician) in conjunction with non-adherent dressings, contact layers or hydrogels may allow a better environment for healing. Remember, maintaining a moist environment will enhance re-epithelialization (repair of damaged skin) on the wound bed. In addition, many of these dressings have been shown to be less traumatic to the wound upon removal. In some instances people with EB Simplex have found it helpful to allow their wounds to dry out, preferring not to moisten or cover them. Different situations warrant different treatments, and what works well for some individuals doesn’t always work for others. More importantly some dressings may be referred to as non-adherent yet they may react differently on an EB wound so please monitor carefully.

Moderately draining wounds

If a wound is wet and the drainage sits on the wound too long, the skin in that area may become over-hydrated, irritated (macerated). In such instances foam dressings may be helpful since they have the ability to wick away drainage. Some of these types of dressings may stay on the wound for a couple of days. In the presence of infection the physician may modify the frequency of dressing changes.

Heavily draining wounds

These wounds may require more absorbent dressings (Breakaway, Exudry) to wick away some of the excess drainage/moisture. The frequency of dressing changes may need to be modified in the presence of infection and if there is heavy drainage.

Non-healing wounds

In some instances wounds remain for a long time and the very properties that stimulate healing have relinquished to causing further breakdown and even more inflammation. For these chronic ulcerations it is important to seek advice from your physician to rule out the possibility of pathology (disease) within the wound. If there is no pathology of the wound, the physician may suggest a wound covering device, such as grafts or bioengineered skin (eg. Apligraf, Organogenesis Canton MA) to give the wound a jump start toward healing.

Listed below are some wound care products that some people affected with EB have found helpful:

Note: Many of the dressings listed below are prescribed by the physician after evaluation of wounds. Please review appropriate use of the product prescribed with your physician. This is just a small list of the various wound care products helpful to some people affected with EB.

Some of the companies listed below do not sell products directly to customers, so please check with your distributor.

Direct Medical Inc. is one distributor among many that sells some of the various wound care products listed below. Customer service telephone number is 1-800-659-8037. (www.ebdressings.com).

Contact Layers:

These dressings are made up of a single layer, non-adherent woven mesh like material. Contact layers sit on the base of a wound protect against trauma during dressing changes and allow for the passage of exudate through the holes onto an outer secondary dressing. (Exudate is fluid consisting of proteins and cellular debris that has escaped from blood vessels onto tissue surfaces).

Contact layers can be used as primary dressings for many types of wounds. One of the benefits of using contact layers is the fact that they can stay on the wound bed for several days without disturbing the newly healed skin. Depending on the condition of the wound, the surrounding skin and the presence of infection, the physician may modify the frequency of dressing changes.

N-Terface and Conformant 2 are made of a high density polyethylene. Mepitel is made of a silicone safetac material.

• Mepitel Molnlycke Health Care (1-877-460-5888 ext. 1107) (www.MepitelforEB.com)
• N-Terface Winifield Laboratories, Inc (1-800-527-4616)
• Conformant 2 Smith & Nephew (1-800-876-1261) (www.snwmd.com)

Impregnated Gauze:

The gauze dressings listed below are impregnated with either Vaseline or Aquaphor. They can be used as primary or secondary dressings.

• Vaseline Gauze Kendall Health Care (www.kendallhq.com)
• Aquaphor Gauze Smith & Nephew (1-800-876-1261)
• Smith and Nephew (www.snwmd.com)
• Xeroform Kendall Health Care (www.kendallhq.com)

*Please note Xeroform dressing contains a medication called Bismuthtribromophenate. Please consult physician prior to using . It may not be appropriate for infants and children.

"Direct Medical Inc. is one distributor among many that sells the products listed above. Customer service number is 1-800-659-8037. Website is (www.ebdressings.com)."

Non Adherent Gauze:

Provides a non-stick covering for the wounds.

• Telfa (Composite) Kendall Health Care (www.kendallhq.com)

Specialty Absorptive Dressings:

These dressings provide a non shearing, non-adherent, absorbent environment that allows for the wicking away of drainage. They can be utilized on wounds with mild or heavy drainage.

Breakaway’s first layer is known as a non-adherent, contact layer (N Terface) which stays on the wound. The outer more absorbent layer can be removed while the contact layer remains in place for visualization of the wound’s progress.

Exudry has two non adherent wound contact layers which helps to prevent friction and shear. The drainage is wicked away into an absorbent layer.

These dressings can also be used to provide a cushion/padding for crib, playpen, high chair and play areas.

• Breakaway Winfield Laboratories (1-800-527-4616)
• Exudry Smith & Nephew (1-800-876-1261) (www.snwmd.com)

Foams:

These dressings are non-adherent and absorbent. Most foams provide insulation and a moist environment. Foam dressings are used on wounds with light to heavy amounts of drainage. Please keep in mind if the dressing becomes saturated with drainage, it could irritate the surrounding skin. May consider use of foams for heavier draining, non-infected wounds.

Depending on the condition of the wound, the surrounding skin and the presence of infection, the physician may modify the frequency of dressing changes.

*Careful, make sure the correct side of the dressing is put against the wound. (Not indicated for dry superficial wounds)

• Mepilex Molnlycke Health Care (877-460-5888, ext.1107) (www.MepitelforEB.com)
• Cutinova Foam Smith & Nephew (1-800-876-1261) (www.snwmd.com)
• Allevyn Smith & Nephew (1-800-876-1261) (www.snwmd.com)

Polyurethane Foam Dressings:

• Lyofoam ConvaTec (1-800-422-8811)
  (Not indicated for dry superficial wounds)

Hydrogels:

Hydrogels may be in the form of either a gel, impregnated into gauze or in the form of a hydrated sheet dressing. Basically made up of glycerin or water. They hydrate wounds providing a moist environment enhancing re-epithelialization. Maybe kept in the refrigerator to provide a cooling and soothing effect on painful wounds. Hydrogels may be helpful as primary or secondary dressings to a varied number of wounds. They are not usually recommended for wounds with heavy exudate. Please note in some instances hydrogels may dehydrate if not covered appropriately. Please review product application carefully.

• Vigilon Bard (www.bardmedical.com)
• Normlgel Molnlycke Health Care (877-460-5888, ext.1107) (www.ebdressings.com)
  (Please note Normlgel contains normal saline, has been known to sting.)

Hydrofiber Wound Dressing:

A sterile, absorbent pad made from sodium carboxymethylcellulose fibers. When applied to a wound creates a gel after coming into contact with wound exudate. This provides a moist environment. Helps reduce damage of newly forming tissue upon removal. Should only be used on moderately to heavily draining wounds. Not indicated for dry (non-draining) wounds. Depending on the condition of the wound, the surrounding skin and the presence of infection, the physician may modify the frequency of dressing changes.

• Aquacel ConvaTec (1-800-422-8811)

Collagen Dressings:

These dressings stimulate the development of new tissue, organization of granulation tissue and helps to form collagen fibers which induce healing upon the wound bed.

May be used in conjunction with other non adherent dressings for partial or full thickness wounds, they require a secondary dressing. They are absorbent, conform to the wound surface and maintain a non-adherent, moist environment. Collagen dressings may be used on wounds with minimal to heavy exudate in infected or noninfected wounds. May be used in combination with topical agents.

• Kollagen-Medifil Biocore Medical Technologies (1-888-689-5655) (www.biocore.com)
• Kollagen-Skin Temp Sheets Biocore Medical Technologies (1-888-689-5655) (www.biocore.com)

Gauze:

Cotton mesh interwoven material used for cleansing and covering. They are available in different forms such as rolls, pads as well as various length and widths.

Elastic Retention Gauze:

Stretch mesh material helps anchor bandages to appropriate areas on limbs and trunk.

• Promed Elastic Net ProMed, Inc. (1-800-888-6143)

SNOGG soft 1:

Was introduced to us by Napier Quill in England.

This comfortable, cohesive, low allergy bandage has been known to be helpful in anchoring non-adherent dressings to areas such as fingertips. (May order from Direct Medical Inc. 1-800-659-8037. (www.ebdressings.com).

Simply apply your non-adhesive dressing over the wound then cover with SNOGG. May change once a day or as needed.

Cleansers (mild):

• Cetaphil mild non soap cleanser
• Dove mild soap

Ointments:

• Aquaphor, A&D and Vaseline are non-medicated topicals that when used alone, or on a dressing, help maintain a moist environment on wound bed. When used on dressings it helps to prevent them from sticking to the wound.

Antibiotic Ointments:

• Bacitracin and Polysporin are mild over the counter topical antibiotics.
• Bactroban (strong antibiotic ointment needs a physician’s prescription).

The additional products listed below have been known to be helpful to some people affected with EB:

• Pressure relief products such as gel sheeting promote a cool and soft environment in the shoe or other areas of pressure. (Keep in mind not for direct application to open wounds, it is for pressure relief.) (Silipos 800-229-4404). May call for a catalog.
• Since high environmental temperatures have been known to induce blistering, keeping cool is very helpful. (Air conditioner)
• Pedors and weeBors are shoes made for sensitive feet. (www.pedors.com) or call toll free 1-800-750-6729 for a brochure.
• Comfort Socks for Sensitive skin: These seamless socks are made of a teflon material that reduces friction. You may visit their website at (www.sensitivefeet.com) - phone number is (503) 245-0105.

Itching and Epidermolysis Bullosa

In many instances, people affected with Epidermolysis Bullosa may suffer with itchy skin or pruritus. Itching may be due to a number or reasons such as healing during periods of rest, irritation caused by a wound infection and/or sensitivity from exposed nerve tissue. It is helpful to minimize discomfort to avoid further trauma to the skin caused by rubbing and scratching.

Some of the interventions listed below, have been found helpful by some parents of EB children and some adults affected with EB:

• Eliminate wool and rough garments
• Launder clothing and linens in mild detergent.
• Keep a cool environment (Air conditioner)
• Wash with mild soaps such as Dove or mild cleansers such as Cetaphil.
• Have questionable wounds evaluated by a physician. If there is evidence of infection physician may perform a wound culture and determine a course of treatment that may include topical and/or systemic antibiotics.
• Apply cool compresses. (Use caution especially with infants since widespread application of soaks may cause temporary decrease in the body’s core temperature.)

Please consult physician about the following treatments and medications. Though some of these may be sold over the counter it is important to consult with the physician for specific application of product, dosages, possible interactions and side effects.

• Hydrogel dressings. Since a major component of many of these dressings is water, they may help soothe and cool wounds. May be refrigerated (minimum of 1 hour) to help reduce localized discomfort. Please note that a higher room temperature may cause hydrogel to evaporate at a faster rate. Be careful, in some instances they can dry out and stick to the wound. If this occurs, gently soak dressing off to reduce trauma during removal. Hydrogels are not usually indicated for heavily draining wounds. Frequency of the dressing change will need to be determined by the physician; it will depend on the condition of the wound.
• Burow’s solution/Domeboro powder are drying agents (astringents). Diluting the medication as directed, and then applying it on a compress upon the draining wound, may dry up the wound. This may be used on infected wounds to reduce bacterial growth (it may or may not help with the itch). Skin irritation has been noted if dilutions are not correct. Concentration of the diluted agent changes over time, so it is best used within the first few hours of being made.
• Epsom Salts, normal saline and/or vinegar dilutions have been known to be soothing to skin irritations.
• Localized bacterial infections such as pseudomonas may be treated with (vinegar) dilutions.
• Topical Bactroban ointment has been used to treat various staphyloccocal infections.
• Application of non-medicated ointments such as Aquaphor, Vaseline and/or A&D may decrease the dryness of healed and healing skin. Some people prefer moisturizers such as Lubriderm. (Since most of these are greasy it may be helpful to apply at bedtime.)
• Antihistamines such as Benadryl, Atarax, Periactin, Zyrtec and Claritin. These medications have been known to be helpful in reducing itch. Please note some antihistamines may cause drowsiness, dry mouth and increased appetite. It is important to note that the way individuals react to certain medications vary from person to person. Some individuals may experience nervousness and/or irritability.
• Doxepin Hydrocholoride. Although no formal clinical studies have been done with regards to pruritus (itchy skin) in EB patients and the use of this antidepressant, some patients have found that in low doses this medication has been helpful in reducing the itch. This medication may cause drowsiness and dry mouth as well. Please note, the use of Doxepin cream is not recommended for people affected with EB since over absorption of the medicated cream is a concern.
• People affected with EB may want to avoid topical preparations such as Benadryl and Caladryl since they are common sensitizers. Sensitizers have the potential to cause an allergic reaction. You may also want to avoid using preparation such as Benzocaine and Lanacaine since they have the potential to cause skin reactions.

For additional information about itch, infection and wound care please refer to "General Guidelines to the Routine Mangement and Care of Inherited EB".

Genetic Counseling

Genetic counseling provides and interprets medical information based on expanding knowledge of human genetics. A genetic counselor will work with a couple to review their family history and explore the likelihood of recurrence of EB in subsequent children or relatives. Often the genetic counselor is a physician who will participate in the diagnosis, examine family members and provide ongoing medical care. In other instances, a geneticist (someone with an advanced degree in human genetics) may work with the child's pediatrician, dermatologist, or primary physician. The counselor, perhaps with close family advisors, such as a minister, priest or rabbi, can help a family make informed decisions about child- bearing and help them cope with the impact of a genetic disorder. Genetic counselors and social workers often work together to ensure that patients and families receive all the services and benefits to which they are entitled.

Prenatal Diagnosis for Epidermolysis Bullosa

By Ellen Pfendner
Dr. Ellen Pfendner Ph.D, Clinical Laboratory Manager, DebRA Molecular Diagnostics Laboratory, Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 408 BLSB, 233 South 10th Street, Philadelphia, PA 19107, 215-503-2176.

In 1993 mutations in the collagen 7 gene, the gene involved in dystrophic EB (DEB), were identified and the first prenatal diagnosis was performed for a family with a DEB child. Since that time over 100 successful prenatal diagnosis have been performed in the US as well as a large number in the UK. Today, a small fetal sample can be obtained by either chorionic villus sampling or amniocentesis, which is performed in the physician’s office and shipped to the DebRA Diagnostic Laboratory where mutations studies can begin on the fetal DNA, extracted from these samples. The perinatologist will determine which prenatal test to do and what time frame to perform the testing. Prenatal diagnosis can tell whether the fetus is affected with EB, unaffected but a mutation carrier or unaffected and not a carrier. This can allow parents to make family planning choices and be prepared for the birth of an affected child by choosing the type of hospital for delivery and the support they will need after birth. Prenatal diagnosis can also relieve anxiety, when parents know early in pregnancy that their baby is unaffected.

It is important to realize that prior knowledge of the mutations found in a particular family is necessary to ensure a correct and timely prenatal diagnosis result. If the mutations are known in a family, the prenatal diagnosis usually only takes one week to complete. Since mutation detection can take up to several months to complete, depending upon the family, it is very important to know the mutations in advance of a pregnancy.

Before mutation testing and subsequent prenatal diagnosis can be performed, the type of EB in a particular family member must be determined. This can be achieved through studies of a skin biopsy taken from the affected family member. The skin sample is then sent to a laboratory, usually at the National EB Registry, where electron microscopy and immunofluorescence can be performed to identify the proteins missing and the level at which blister formation occurs in the skin of the patient. These skin biopsy studies will determine the type of EB the patient has and by identifying the skin protein that is affected in the patient, along with the symptoms the patient has, the candidate genes for mutation studies can be determined. At least ten different genes are involved in the three forms of EB. By determining the type of EB, the number of genes that must be studied for mutation detection in a particular family can be narrowed down from ten to as few as one for DEB, two for EB Simplex and four for JEB. Use of biopsy results along with patient symptoms, have also allowed scientists to identify two genes involved in JEB with pyloric atresia and one in EB Simplex with muscular dystrophy.

After the type of EB is determined, the mutation studies can begin. It is often believed that mutation studies must be used to diagnose EB, but that is not their primary role. Mutation detection is a very expensive and labor intensive method that is not always able to identify mutations in all patients. Mutation studies are most useful in determining the EB inheritance pattern in most families and to provide the basis for prenatal diagnosis in future pregnancies in a given family. To begin mutation studies, a family physician or dermatologist will arrange to have blood drawn from the patient as well as parents and sent to the diagnostic Laboratory. DNA will be extracted from the blood samples and from this DNA mutation studies will be performed. This process may take several months to complete and involves screening methods and direct DNA sequencing of the candidate genes in the patient and other family members. Once the family mutations are identified the risk to a future fetus can be determined and when a pregnancy occurs, DNA taken from the fetus can be studied for the presence of these mutations.

Finally, prenatal diagnosis, like any other laboratory procedure, is not 100% accurate. Very infrequently, new mutations can occur or recombination between chromosomes can lead to a faulty predication. While there is also the possibility of laboratory error, the laboratory takes great precautions to ensure this does not happen. In general, prenatal diagnosis is a safe and effective method to determine whether the fetus has EB and has been used for eight years to predict pregnancy outcome for many families who are coping with this devastating disease.

Other Health Care Problems

The following material describes a variety of problems that can be associated with EB. It is important to bear in mind, however, that not all of these problems occur in each EB patient. Some will have none or a few; others may have nearly all of these.

Nutritional Concerns

Good nutrition is essential for all children, but may be more difficult to achieve for a child with a chronic disease such as epidermolysis bullosa.

Nutritional research on EB is in an early stage. However, knowledge gained from working with people with similar conditions, such as skin ulcers or burns, can be helpful for people with EB. Patients with skin ulcers or burns need increased protein and calories. Thus, a person with EB also may need to increase both calories and protein, depending on the severity of the disease. These extra nutritional demands on the body are due to tissue regeneration, fluid replacement and protein loss associated with blistering.

Attention to the nutrition of the child may be important from the beginning. Immediately after birth, fluid and protein loss, which may cause chemical imbalances, can be a major complication in recessive and some dominant types of EB. Unless the baby requires isolation for medical reasons, closeness of the mother and child should be encouraged and will help make early feedings successful. Oral or breast feedings can begin as soon as the sucking reflex is demonstrated, unless the doctor indicates otherwise. If the infant has difficulty sucking because of blisters in the mouth, use a preemie nipple (a soft nipple having holes large enough to permit milk to drop into the mouth), a rubber-tipped medicine dropper or a syringe. Powdered nutritional amplifiers, which can add calories and protein, are now available that can be mixed with mother's milk, and there are formulas that have higher than average calorie and protein concentrations. Follow the physician and/or dietitian's instructions in the use of such products and in the selection of an appropriate formula.

When the child is about six months old and pureed food has been introduced, it can be helpful to add extra liquid to the pureed food to facilitate swallowing in those who have mouth blisters. Hot drinks or foods can be irritating; if so, beverages and foods should be served lukewarm, at room temperature, or cold.

Dysphagia (difficulty in swallowing) can be a major complication, as EB can cause blistering in the mouth and/or the esophagus. A parent should watch when hard-crusted foods such as toast or crackers are introduced in the child's diet to see if they provoke blistering or a problem when swallowing. Acidic foods and drinks can also be irritating when an ulcer in the mouth is active; therefore, tomatoes and citrus juices may need to be avoided. If the child can tolerate milk, whole milk can be enriched by adding an "instant breakfast" mix or flavorings. A "fortified milk" can be prepared by adding nonfat dry milk powder to whole milk. "Fortified" milk can be served plain, flavors added or used to make sauces, cream soups, warm, not hot cereals, mashed potatoes, milkshakes, custards, puddings, and cocoa; it can be used in any recipe calling for milk to add extra calories and protein. If milk is not tolerated, liquid nutritional supplements may be recommended. These can be purchased at a pharmacy upon advice of a physician and/or dietitian. Most liquid supplements can be used in recipes such as custards, puddings, and soups and are available in a variety of flavors. It is wise to interchange products and flavors to offer variety so the child will not become bored. Some have found it helpful to start and complete each feeding with a cool, not cold, good tasting liquid including ice cream or cool liquid frozen yogurt.

Even when a child with EB does not have oral blistering or swallowing problems, he or she may need supplements of high-calorie, or high-protein drinks or of vitamins, minerals and trace elements.

The physician should be consulted as to whether a supplement is needed and, if so, the amount to be prescribed. Large doses of vitamins and minerals (megadoses) are not recommended. Caution should be exercised in terms of any diet or supplement that promises miraculous results. Such approaches are often attractive to parents of children with chronic diseases, but such alternatives to a varied, nutritious diet can result in malnutrition.

Esophageal stricturing may be experienced by the more severely affected individual. Scarring within the esophagus can reduce the size of the lumen, causing difficulty in the passage of food, even liquids. Many times children will experience episodes of food impaction with the expectoration of copious amounts of mucous. Though this problem is usually of no immediate danger to the child's airway it is always helpful to contact the physician when in question. Poor toleration or the refusal to eat compromises nutritional status. Studies may be ordered by the gastroenterologist to assess the need for treatments such as esophageal dilatation. Dilatation is a procedure done under light sedation that incorporates the use of a small balloon to increase the size of the esophageal opening.

In instances where esophageal stricturing is so severe, dilatation may not be helpful, a gastrostomy tube or gastric button device may be indicated to increase the individual’s nutritional intake. A gastrostomy tube is inserted to an opening (stoma) into the stomach for the delivery of nutrients, fluids and medications. The procedure is usually done by a surgeon or a gastroenterology surgeon. In many instances feedings through the gastrostomy tube are given overnight using a pump. (Please note the head of the bed should be slightly elevated when infants/ children are receiving feedings.)

The use of gastrostomy tubes may be helpful in the nutritional management of infants and small children in EB who do not have esophageal involvement but need nutritional enhancement intake for growth purposes and wound healing.

If naso gastric tubes are used it is usually short term due to risks of esophageal erosions and infection.

Gastroesophageal reflux is the back up of stomach acid into the esopohagus in many instances this may cause discomfort and reduce desire to feed.

Symptoms of gastroesophageal reflux may include:

• Cranky and pushing away bottle after a few minutes of feeding.
• Reluctance to feed.
• Coughing.
• Milk may be present in mouth between feeds.

If gastroesophageal reflux is suspected it is helpful to consult a Pediatric Gastreonterologist. Physician may order various diagnostic tests such as endoscopy, pH testing and/or various radiographic studies to rule out the presence of reflux.

Interventions may include the following:

• Feeding with head slightly elevated.
• Physician/ Gastroenterologist may prescribe various medications that decrease gastric acid production. ( Some medications that control acid reflux are sold over the counter, however, since dosages vary it is important to consult with physician prior to using over the counter medications.)

Lactose Intolerance

Lactose intolerance (or more properly, lactase deficiency, a condition in which enzyme production is insufficient to digest lactose, the sugar in milk products) has been observed in some children with EB. Milk can be treated with a commercial enzyme product called Lact Aid which, if added to a quart of milk, breaks down the sugar lactose and the milk can then be tolerated. Some stores also sell milk that has already been treated with the enzyme and is therefore more easily digested. In addition, in yogurt most of the lactose is broken down and thus is usually well tolerated Lactose-free formulas and liquid supplements are also available. Your physician and/or dietitian can help you in the selection of an appropriate product.

Constipation:

Constipation is difficulty passing stool. Contributing factors may include discomfort during the passage of stool caused by blistering in the anal margin, suppression of bowel movements due to pain and a diet low in fiber and fluids.

Symptoms of constipation may include:

• Reluctance to feed
• Loss of appetite
• Abdominal discomfort
• Abdominal bloating

Goal: Soften stool to reduce discomfort and constipation.

Constipation may be due to:

• Erratic eating patterns, low fluid and fiber intake.
• Soft tissue injury in mouth, trouble chewing, swallowing, problems with dentition, esophageal scarring and/or webbing all contribute to poor dietary intake of fiber containing foods such as cereals, breads, fruits and vegetables.
• Most iron supplements have been known to contribute to constipation.
• Since the gastrocolonic reflex is stimulated by ingestion of food, avoidance of eating, apathy and loss of appetite worsen the nutritional status.
• Extensive blistering leads to increased fluid requirements.

Interventions may include the following:

• Input by a pediatric dietitian/nutritionist many times can be helpful in formulating a dietary regimen that reduces constipation and/or fecal impaction.
• For infants it may be helpful to offer fluids such as cooled boiled water. If you want to add flavor, try one teaspoon of fruit juice in 100 milliliters of water.
• Liquid enteral formulas like Pediasure with fiber may improve gastro-intestinal function.
• Offer fruits such as prunes, pears, peaches and apricots.
• Prepare foods in forms that are easier to swallow such as broth, pureed meats, vegetables and fruits.
• Some have found it enjoyable to liquefy depitted fruits and freeze them into the form of an ice pop.
• Try not to sieve foods, it will decrease the fiber content.

Below is a list of various medications used for constipation. Please consult physician prior to using any medications. Though some of these may be sold over the counter it is important to check with the physician for specific dosages, possible interactions and side effects.

• Stool softeners such as (Docusate Sodium) allow for easier passage of stool.
• Hyperosmotic laxatives such as (Lactulose) and osmotic agents such as (Miralax) help move water into intestines, soften stool and stimulate peristalsis.
• Stimulant laxatives such as (Senekot, Bisacodyl) stimulate peristalsis allowing for the movement of feces through the intestines.
• Psyllium containing bulk laxatives such as (Metamucil)when in contact with water produces a lubricating gelatinous bulk which promotes peristalsis and natural elimination.
• Fiber and bulk laxatives need to be taken with good amounts of fluid in diet to mobilize the bulk through the intestines.
• Discuss different types of iron supplementation with physician. Some iron complexes were found to be less irritating to the gastrointestinal tract than others.
• If a medication for constipation is prescribed by a physician, it is helpful to administer them regularly to avoid worsening of the problem.

Sometimes a child may be fecally impacted, but have diarrhea. If laxatives and stool softeners are discontinued (due to the diarrhea) this will worsen the problem. Consult your child’s physician when in doubt.

Hard stools lodged in the large intestine (fecal impaction) usually requires a hospital visit. Fecal impaction is usually seen on abdominal xray.

Anemia

Many children with EB become anemic due to a chronic loss of blood from blisters and open skin lesions and perhaps due to poor ingestion and absorption of blood-building substances. Specific treatment for iron deficiency anemia is often necessary. Many children have to keep taking supplemental iron even after the anemia has been corrected to prevent it from occurring again. Many commercial nutritional supplements contain iron. Use iron supplements only when recommended by the physician. An adequate intake of protein is also important.

Scarring, Contractures and Syndactyly:

Though scarring may occur in rare instances in other types of EB it is important to keep in mind that these manifestations are more likely to occur in a person affected with Recessive Dystrophic Epidermolysis Bullosa.

Repeated friction and trauma on hands and feet causes blistering, in the more severe forms of EB, these blisters heal causing scarring, side to side fusing or webbing together of fingers and toes (syndactyly).

Contractures ( shortening of the skin ) of the hands and feet may also contribute to loss of function. Flexion contractures can occur on joints in the feet, knees and hips. Muscle atrophy (weakening) develop as a result of disuse of a joint. Scarring may decrease opening of mouth (microstomia). Scarring may limit movement of the tongue (ankyloglossia).

Interventions may include the following:

• Wrapping in between digits using strips of contact layers such as Mepitel (Molnlycke Health Care) and/or impregnated gauze such as Vaseline gauze (Kendall) may help delay the process of webbing.
• Whenever possible during the day, infants should be encouraged to discover and manipulate their hands to allow for better movement. Due to the possibility of rubbing and potential injury this should be done under supervision. During night time hands may be re-wrapped.
• Some people have found it helpful to use splints during the night to reduce chance of contractures. Splinting varies with age of person affected. Splints are made using a very heat labile moldable material.
• Consult with an Occupational therapist. They are very helpful in creating programs of activity that optimize hand function. The OT may be helpful in teaching methods of wrapping that allow for range of motion of fingers and hands. Ask the OT about range of motion exercises that you can perform on your infant/child throughout the day. Specially designed equipment such as scissors and pencils with foam padding reduce discomfort while children participate in arts and crafts.
• If the function of the hand is impaired it is advisable to consult with either a Plastic Surgeon or a Hand Surgeon. The Surgeon will determine if it is in fact necessary to perform surgery or to wait. The surgical procedure involves separating the fused digits and releasing contractures while under anesthesia. Skin grafts or various bioengineered skin products may be used to cover wounds and/or donor sites. Hand splints are used to help keep fingers separated and hands in extended position post surgically. Careful instructions for post care should be given by the surgeon. Healing usually takes several months for this reason, only one hand is done at a time.
• The child with EB should be encouraged to be as active as possible, and physical therapy is often beneficial. Swimming is a good form of exercise for children with EB.
• If child has difficulty speaking and/or eating parents may consult with a speech therapist. Mouth and tongue excercises can help improve speech. (Early intervention programs provide occupational therapists, speech therapists and physical therapists for children under three years of age. For more information contact early intervention in your state.)

Dental Problems

The infant or young child should begin to see the dentist (or pediatric dentist, if available) shortly after the teeth begin to emerge through the gums. Regular visits will ensure the most preventive care. When the teeth begin to appear, they should be brushed gently with a small, soft multi- tufted toothbrush. Discourage the child from eating sweets. If the water supply is not fluoridated, the dentist may suggest the use of nonirritating fluoride supplements. Some recommend oral swishes after the feeding at the completion of the meal to protect the dentition.

Eye Problems

Because many of the tissues of the eyes develop from the same fetal tissue as the skin, the eyes can be involved in EB, particularly in the dystrophic forms of EB. The cornea (the clear outer layer) and the conjunctiva (the mucous membrane covering the eyeball and the underside of the lids) can be damaged. Symptoms are pain, excessive formation of tears or discharge.

The goal of therapy for this problem is to protect the eye from irritation by increasing the amount of moisture. Eye drops can be useful as can lubrication with a specially prescribed antibiotic ointment. It may be helpful to put the ointment on the eye and patch it for a day or so.

Immunizations

Every child, including those with epidermolysis bullosa, should receive the normal immunization shots.

Please consult with physician if child is receiving steroid therapy or other immunosuppressive agents. Physician may reschedule live attenuated vaccinations such as Varicella and MMR for a later date if child is receiving immunosuppressive agents.

What Does the Future Hold For a Patient With EB?

As described earlier, EB can range from a relatively mild condition to a severely disabling, and sometimes fatal, disease. Patients with milder forms may have periods of "temporary disability," but can lead a relatively normal life. In more severe forms, EB can be emotionally and physically devastating and cause the person to be disabled and deformed. Proper care and family support, however, can greatly enhance the quality of life for EB patients.

Despite the physical problems the disorder can cause, there is no impairment of intelligence.

There are many psychological problems that patients with EB must learn to cope with: the teasing of classmates, the stares from others, the jokes, the loneliness of being different. Many patients overcome these problems with the support of well-informed, caring parents and friends. As all children do, those with EB need love and acceptance.

Children's tissues become less delicate with age; many forms of EB begin to lessen to some degree as the child gets older. Patients given good, consistent, and intensive care early on have the best chances of doing well.

Support Groups

When one or more children in a family has a chronic disease that requires constant or almost around-the-clock care, the entire family is affected. Family therapy or support groups can:

• Help each member of the family accept and deal with long-term chronic illness;
• Help relieve guilt;
• Make it easier to cope with the child's and the parents' feelings;
• Make a difference because the parents, attitude can affect the way a child copes, handles his own care, and interacts socially with peers and people in general.
• Help to deal with siblings and spouses, feelings.

Click on (Support Groups) for a listing of DebRA support groups.

What Can Research Tell us About EB?

By Alan Moshell MD, Skin Diseases Program Director - National Institutes of Arthritis and Musculoskeletal and Skin Diseases.

Research in Epidermolysis Bullosa and related areas are being supported by the National Institute of Arthritis and Musculoskelatal and Skin Diseases, other components of the federal government’s National Institutes of Health, and voluntary agencies such as DebRA of America.

Essentially all forms of hereditary Epidermolysis Bullosa are due to structural molecule abnormalities in the skin. These molecules may either be present but abnormal in structure, or greatly reduced or absent. Skin has two principal layers, the outermost layer known as the epidermis and the lower layer known as the dermis. The area where these layers come together is called the basement membrane zone. The molecules involved and abnormal in Epidermolysis Bullosa are located either in the bottommost portion of the epidermis, the basal layer, within the basement membrane zone, or in the uppermost part of the dermis.

Under the microscope, skin from patients with the simplex or epidermal forms of EB develop blisters within the basal layer of the epidermis. In most of these forms of EB the abnormality is in a molecule called keratin which forms the internal structure of the basal cell. The abnormalities in these proteins result in a weakness in the cells and they disintegrate under mechanical stress resulting in the blister in this area.

The basement membrane zone of skin is a very molecule rich area with many molecules involved in the attachment of the epidermis above to the dermis below. Defects in quite a number of these molecules have been associated with the junctional forms of Epidermolysis Bullosa. The most severe forms are usually associated with defects in a molecule called laminin 5. Less severe forms of the disease may be associated with a variety of other molecules found in this area.

The dystrophic forms of EB, both recessive and dominant, are usually due to defects in a molecule of the upper dermis called collagen VII. Under the electron microscope, this molecule forms a structure called anchoring fibrils. In the recessive form of the disease, the defect is usually more severe than in the dominant form of the disease.

A variety of techniques have been developed and used over the years to visualize these molecules and assist in the diagnosis of patients with hereditary blistering diseases. Electron microscopic techniques along with immunofluorescence and immunoelectromicroscopy were the mainstays of research until these specific genes for these various molecules were identified. With the identification of the genes, it is now possible to specifically and directly examine the various potential genes involved and identify specific defects in individual patients and in families. This allows for both a much more specific diagnosis and for the further studies now ongoing to correlate specific gene defects with the protein abnormalities that they produce. These investigations will allow a better understanding of exactly how the molecules function and make interventions designed to strengthen these molecular interactions or bypass them by getting other molecules to take their place possible. These studies are still in their infancy but therapeutically useful approaches can result from these investigations.

With the specific genes known, it is possible to very accurately perform prenatal diagnoses on infants at risk to assist those families who want such information in making decisions. There is also research making use of this technology as part of in vitro fertilization to select embryos that do not contain the abnormal gene for implantation in an attempt to assure normal offspring in families at risk without the need for abortions.

In addition, there is investigation of gene therapy approaches for the treatment of these diseases. These are still at the preclinical stage meaning that the baseline studies have been done proving feasibility but as yet no human trials have resulted. Human trials are to be expected in the near future but when and even if this approach ever proves feasible as a corrective therapy for any form of Epidermolysis Bullosa is still an open question.

Much of science is unpredictable. There is no way to know when and from where useful approaches will be forthcoming. Basic research advances are constantly reshaping science and its application. The cardinal objectives are to understand the basic underlying mechanism that lead to this distressing disabling disease and to develop therapies directed at correcting these mechanisms or developing interventions that improve the resistance to blistering by other means.

NEW EB Parents