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Epidermolysis Bullosa is a rare genetic skin disorder. One thing to describe its rareness is that a doctor or a nurse can be working a lifetime and never bump into this condition. It is estimated that about 10,000 Americans, mostly kids, have some form of EB. With modern medical care, some with the worse kinds of EB can live into their thirties. Unfortunately, by this age most will succumb to a particularly aggressive skin cancer (Squamous Cell Carcinoma) that is somehow touched off by EB. Of these 10,000 effected, less than 300 have the same kind as Nicky’s (he has the Hallopeau-Siemens subtype because of the webbing and contracting of his fingers and toes), making the RDEB form so rare than only one out of every one million babies is born with it.
The skin is made up of a number of different layers. The outer is called the epidermis; the inner layers are the dermis.”Bullosa” is simply the name for a blister and “lysis” means breakdown. Hence, Epidermolysis Bullosa means the breakdown and blistering of the epidermis.
Forms of EB
The skin is comprised essentially of two layers – the thin outer layer called the”epidermis” and the thicker inner layer called the “dermis”. There are three basic forms of EB. The “Simplex”, “Junctional” and”Dystrophic”.
On the Simplex the blistering is at basal cell level or above, on the Junctional the blistering is at the lamina lucida level, and on the Dystrophic the blistering is below the lamina densa level. Which means that, upon injury, the simplex’s wound is not as deep as the dystrophic’s one, although it is easier to obtain. The Junctional in its “Herlitz” form is unfortunately the lethal kind. Most babies born with this form will not survive to see their first birthday, mainly because all their internal organs are also effected, meaning they blister. Also the wounds do not heal well if at all. The Non-Herlitz form acts much like a combination of the simplex/dystrophic, tending to be a lot more like the simplex, since it is non-scarring (for the mostp art-although there are some scars), and the blisters tend to be small.
The severeness of the simplex and dystrophic forms varies a lot individually. The mildest forms are causing only a little trouble, and maybe only in summertime, when the most severe cases are severely disabling and life threatening.
Nicky has a moderatly severe form (Recessive Dystrophic – Hallopeau-Siemens subtype), his hands are severely involved and had to have surgeries to release the contractures and the webbing that were present. His mouth is a mess, he throws up blood every now and then, he has macrostomia and lingual adhesions. He also has a g-tube to supply nutrition to him.
Here is a handy table, courtesy of the National EB Registry, of the forms of EB known at the present time.
|Major EB Type||Major EB Subtype||Protein / gene systems involved|
|EB simplex (EBS)(“epidermolytic EB”)||EBS,Weber-Cockayne (EBS-WC)||K5, K14|
|EBS, Kvbner(EBS-K)||K5, K14|
|EBS, Dowling-Meara(EBS-DM)||K5, K14|
|EBS with musculardystrophy (EBS-MD)||plectin|
|Junctional EB(JEB)||JEB, Herlitz(JEB-H)||laminin-5|
|JEB, non-Herlitz(JEB-nH)||laminin-5; typeXVII collagen|
|JEBwith pyloric atresia (JEB-PA)||a6b4 integrin+|
|Dystrophic EB(DEB) (“dermolytic EB”)||DDEB||type VIIcollagen|
|RDEB,Hallopeau-Siemens (RDEB-HS)||type VIIcollagen|
|RDEB,non-Hallopeau-Siemens (RDEB-nHS)||type VIIcollagen|
How is Epidermolysis Bullosa Inherited?
How different are the different forms of EB?
First there are the three main types: Simplex, Junctional, and Dystrophic. The severity varies widely, with only a handful of true subtypes. Then there are the unknown ones, the mutants. And the ones where the parents carry the genes for two different types or subtypes of EB and the child has it. There are dominant strains and recessive strains and even ones that are acquired late in life. Each manifests itself a bit differently from the next. Even the subtypes in each type vary widely. For example: Under dystrophic one finds Transient Bullosa of the Newborn. It goes away by one year of age. And then there is Hallopeau-Siemens. Severe scarring, mittening, synthetic syndactilly, GI track involvement, blisters as big as a fist, many will develop Squamous cell carcinoma, anemia, growth retardation. Some forms get better as the patient ages, mostly the Simplex forms, and some patients don’t get any older…
The need to wrap is as diverse as the types. The mild forms and many of those especially that are at the higher levels of the skin that do not scar and often have only very tiny little blisters do not need to wrap. The air is great and beneficial. Many forms blister only in restricted areas like feet and hands. Some of the more involved forms, however, the Hallopeau-Siemens, Herlitz, some bad areas of Simplex Dowling Meara, NEED to be wrapped.
There is another diversity that I would place in here and that is the difference in the way we all wrap and the perception of what wrapping is. One person may roll some Kerlix loosely around a limb a few times and call it wrapped. Another may take many hours to get every inch, each individual finger, from neck to toe, wrapped with different layers and kinds of bandage. So much in this area varies according to the individual case and yes, experimenting is necessary to see what works for you.
What is the History of the Disorder?
The first reported cases of blistering diseases that would fall into the EB umbrella, were initially noted in the late 1800, starting from about 1870. It wasn’t until 1908 that at least one major dermatology textbook published in English used the term Epidermolysis Bullosa to describe patients with congenital blistering. For more onthe history of EB, please refer to the Debra International website .
What causes EB?
EB is the name of a group of disfiguring conditions, caused by defects in any one of the genes that code for critical skin proteins. A number of different types of proteins, including collagen and keratin, are woven together to give skin its remarkably tough, yet flexible, properties. When any one of these proteins is bad, the weave is no good and the skin can literally fall apart with the slightest touch, causing painful blistering. The type of collagen that is defective inN icky’s form (Recessive Dystrophic, or RDEB) is type VII. This is an important component of the anchoring fibrils in skin, which are responsible for keeping the epidermis firmly attached to the dermis. In EB patients these anchoring fibrils are weak because the code for the gene that produces collagen (glue) is defective. Any part of the body containing collagen VII can be affected including the skin, nails, eyes, mouth, teeth, esophagus and gastrointestinal track.
Does EB impair intelligence?
Not at all. Many EB children actually excel in school because they are not easily distracted and it is one thing that they can actually do.
How hard is it to take care of a newborn with EB?
Babies with EB are very hard to care for not only because of how fragile babies’ skin is in general, but also because they scratch and hit themselves, they fall, they can get blisters from just being picked up, from the diaper, etceteras. Even crawling and walking can bevery painful for them. Having a new baby with EB is challenging, painful and a full time job.
What are some of other side effects?
Patients with EB may lose their nails. This occurs because nails are made from the same cellular components that are disrupted in EB. Malnutrition is often seen because of the protein loss through blisters and the extra used for skin repair. Calories go to wound healing first, then growth. A common concern of most patients is blistering in the mouth and esophagus. They can only eat mushy/liquid foods, or, at the very least, chew their food extremely well. If blisters appear in the esophagus it can obstruct the passage of food, hence cause severe malnutrition. Malnutrition is another huge concern for EB patients because it can disrupt the growth of important organs, and some EB patients have died from a weak heart, which was caused by the malnutrition, this has concern many of the doctors, so they have decided that every working inside the hospital has to go through cpr training toronto just in case they are in presence of heart stroke. The choking of blood is, in some patients, a frequent occurrence. The blood comes from either a “popped” blister in the throat or esophagus, or from broken vessels/skin upon vomiting.
Some patients have severe deficiencies in Iron, which, if not treated or if cannot be treated can cause death. One other area of concern is the possibility of deformity on hands and feet after they have been injured, like the fingers contracting and webbing together for example. This is due to the fact that if the fingers get too much scar tissue (syndactilly)this skin does not “grow” like normal skin, hence the fingers and/or toes get “trapped” into that skin impairing the normal growth of the hand, and that is why the fingers get pulled into the palm of the hand. There is also a high incidence of Skin Cancer in severely effected areas (SquamousCell Carcinoma). Infections are common due to the quantity of open wounds at any given time.
Some of the general daily treatments include meticulous wound care and a high protein- high calorie diet. Other treatments may include: hand and/or feet operations for releasing of fusion of digits, biopsies and removal of skinc ancers, esophageal transplant due to scarring and narrowing of the throat, oral surgeries for special dental needs, iron supplements, shots or blood transfusions to treat anemia, and periodic antibiotics to fight infection.
Is EB lethal?
Of the currently known types of EB, only two are considered lethal. Junctional Herlitz is deadly to the newborn and young. It involves the insides; small intestines, gallbladder, urethra and kidneys along with the nasal, oral, pharynx, esophagus, etc… They commonly pass away within a few weeks of birth, some for a few months, rarely to adolescence. Recessive Dystrophic EB-Hallopeau-Siemens (Gravis) is the other. There are some variants in this form, but basically all scar and mitten in. This synthetic syndactilly will start quite young. The mucosa at the two ends of the GI tract are involved, i.e.: mouth, esophagus, anal and vaginal. Eyes and teeth are affected. Anemia is common. Many with this form do not absorb iron orally, and need transfusions of enhanced blood. Puberty is delayed, if ever reached, because the body is so busy using up all of it’s limited resources to heal. Growth is delayed for the same reasons. Few people with this form get over 80 lbs ever. One simplex form can be deadly to newborn up to 20 months- Letalis variant Dowling Meara variant, however with modern medical care only 1% of newborn with this condition succumb to it. This is a form that improves with age and puberty. It is often confused with RDEB at birth because it does have a lot of similar symptoms. Milia, common to RD is also found in this form of Simplex. A lot of blistering at birth is common. Nail dystrophy, oral blistering, esophageal involvement. DM even has a bit of flexure contracting sometimes, while not mittening, could confuse in early days. If there is a lot of blistering at birth, death would not be unheard of from causes like infection. In earlier days (the early 90s is considered the dark ages when it comes to EB) very little was know about the subtypes. If it was serious, it was seen as RDEB. There was little or none known about the genetic/DNA end of this disease, so those tests were obviously not available.
How do you get EB?
Different forms of EB are inherited differently. Simplex and Dominant Dystrophic are categorized as being Dominant conditions, hence if the parent has it, he/she has a 50% chance of passingit on to their children. If the parents are healthy, then it was a fluke at conception.
Recessive Dystrophic and any form of Juntional on the other hand, is inherited from both mom and dad. They both are healthy carriers of the same genetic defect. In other words, they both have a recessive gene for EB in their DNA. It is impossible to detect this prior to a child being born with EB because in most cases there is no evidence of the disorder in either family, therefore no way of knowing in advance. And even if there was a doubt, no test is currently available to know if someone is a carrier. It is impossible, at this time, to find out if any of us is a “healthy carrier” of “something”. Two healthy carriers of a disorder like EB have a 25% chance of having a child effected with that disorder, a 50% chance of having a child that is a healthy carrier, and a 25% chance of having a child that is a healthy non-carrier. We each carry about seven defective genes that could potentially cause a disease. But each cell in the body contains two copies of every gene, and the backup copy usually rescues us from the disease. In such a case, the defective gene is said to be recessive; one must inherit two defective copies of that gene for it to cause trouble. If you have only one copy of a recessive gene, it lies dormant, waiting to be passed along to the next generation. In some genetic diseases, however, the presence of only one defective gene will cause the disorder. This type of trait is said to be dominant. Some forms of EB, however, are new “spontaneous” mutations, meaning they are not inherited. The parents can have other children without risking giving their newborn EB again. What is a “spontaneous”mutations, you may ask? A spontaneous mutation in any EB candidate gene (i.e. keratins 1 or 14, plectin, laminin5 chains, integrins A6/B4 or typeVII or XVII collagen) means that the DNA mistake occurred sometime “after” the egg and sperm got together and not before. The mutation was not inherited from the parents. Thus, when the embryo is developing, one ofthe cells of this new life has acquired a genetic mistake in one of the EB candidate genes that was not present in parental cells. This mutant embryonic cell then creates millions of daughter cells that have incorporated the DNA mistake into tissues–like the skin–in the fetus. When the baby is born, skin fragility is manifested based on this genetic mistake which can be passed-down through subsequent generations in a dominant or recessive pattern, depending on the mistake and whether this mistake was incorporated into gametes (eggs or sperm of the fetus). Bythis logic, presumably all DNA mutations that are inherited arose spontaneously at some earlier time.
Can EB be cured/treated?
It was only 1993 that the gene that causes Dystrophic EB was located. At the present time there has been some success with Bone Marrow Transplants at the University of Minnesota with young RDEB patients, especially for those with a sibling donor. At Stanford they are working on Genetically altered Skin Grafts for the Junctional & Dystrophic forms. They will take the cells from the person with EB, correct the faulty gene, grow the new “gene corrected” healthy skin in the lab, and graft it onto the original EB donor. It will not be rejected because it is the donor’s own skin.No more blisters in that area!!!! Please remember that the Docs at Stanford are working solely on the funds fromthe EBMRF.
What is Pre-Implantation Genetic Diagnosis?
In order to help parents that are carriers of EB and are at risk of having another effected child, a few centers have started a procedure called “Preimplantation Genetic Diagnosis” or PGD. PGD brings together two cutting edge medical technologies, genetic analysis and in-vitro fertilization (IVF). Because the eight cells are virtually identical, one cell can be plucked off without harming the baby that subsequently grows from the embryo. This cell is then subjected to genetic analysis. The first step is to drop the cell into a test tube containing an enzyme called polymerize, whose job it is to copy DNA. Up to a million copies of the DNA in the cell are made. With plenty of material in hand, doctors then use other enzymes to chop the DNA into manageable bits, which are then sorted for genetic defects. Tests exist for about 450 genetic diseases, including the test developed by Dr. Christiano for the Epidermolysis Bullosa gene. The objec tis to detect which eggs are effected by EB or are carriers of the disorder, and then implant only the remaining healthy embryos back in the womb.
Is EB contagious?
People affected by EB are from all races and cultures and in either sex. It’s not contagious. It’s perfectly safe to shake hands, hug and kiss a person with EB, you can’t get it yourself because EB is an inherited disorder.
More info about the blisters in EB patients.
When people hear the word blistering, they think they know what it’s like to have EB because everyone gets a blister sometimes. But blisters in EB are very different and also there are a lot more them and all of the time. Even in mild cases of EB the blisters are much bigger than normally experienced and the amount of pain is increased. In the severe cases the wounds become very large and look like serious burns. Also the scars that come after are similar. Normally blisters arise only from very heavy and long-lasting friction, but in EB they arise from the simplest everyday actions, from clothing friction, from wearing eyeglasses, from handling simple everyday objects, even from normal eating. Blisters in EB also develop in amazing speed and if they are not punctured, they will continue to spread leaving large sore areas which will take weeks or even months to heal. EB can also affect your lifestyle, but it doesn’t necessarily do. Many people with EB live perfectly normal and fulfilling lives and at the same time look after their skin and health efficiently. Of course severe form of EB causes disability and restricts a person’s life, but a human being is very adaptable and since EB is always from birth, it’s not as difficult as you could imagine. However, you shouldn’t diminish one’s suffering, and this is always very personal experience and depends a lot of the severity of EB.