Dystrophic EB

4 Dystrophic EB
4.1 What is the Cause of Dystrophic EB?
4.2 How is Dominant Dystrophic EB Inherited?
4.3 Dominant Dystrophic EB or DDEB
4.4 Transient Bullous Dermatosis of the Newborn (TBDN)
4.5 How is Recessive Dystrophic EB Inherited?
4.6 Recessive Dystrophic EB or RDEB
4.7 Recessive Dystrophic EB Inversa
4.8 Common Manifestations of Dystrophic EB
4.9 Rare Manifestations of Dystrophic EB
4.10 Skin Cancers and Dystrophic EB

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4.1 What Is The Cause Of Dystrophic EB?

Through research it is now known that the genes that carry the instructions necessary to produce the proteins in the basement membrane zone of the skin, are faulty. This results in incorrectly formed anchoring fibrils, deeming them unable to perform their normal role as a 'stable interweave' between the dermal and epidermal layers of the skin.

Mutation (a change in the genetic material) occurs within the collagen VII gene, which encodes the protein of the anchoring fibril. Anchoring fibrils hold together the two layers of skin. As a result, there is a lack of adherence and disruption of the skin when any friction or trauma occurs to an area. Where the two layers separate there is a blister. Blistering in the various types of dystrophic EB causes scarring.

There are two major types of DEB:

  • Dominant Dystrophic Epidermolysis Bullosa
  • Recessive Dystrophic Epidermolysis Bullosa
    ( Major subtypes of RDEB are listed below.)
  • Recessive Dystrophic Epidermolysis Bullosa- Hallopeau Siemens
  • Recessive Dystrophic EB-non Hallopeau Siemens
  • Recessive Dystrophic EB inversa

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4.2 How is Dominant Dystrophic Epidermolysis Bullosa Inherited?

DDEB is an autosomal dominant condition. One parent of an affected person will usually also have the condition. It is possible for DDEB to appear 'sporadically' (to appear for the first time in a person who has no other affected family member). Anyone who has DDEB whether male or female, can pass the condition on to his or her children. Each time a pregnancy occurs, there is a 1 in 2 chance that the child will inherit DDEB.

Electron microscopic evaluation reveals skin separation at the level of the sub lamina densa of the basement membrane zone, with normal or decreased
number of anchoring fibrils.

Mutations are noted in the genes encoding collagen VII either the gene from the mother or from the father. The change that results, decreases the functioning of the anchoring fibrils, but does not eliminate the anchoring fibrils.

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4.3 Dominant Dystrophic Epidermolysis Bullosa

There is usually generalized blistering noted at birth. Blistering may be generalized or appear only on the hands, feet, elbows or knees: this is usually due to mechanical trauma. Rarely does scarring cause immobility and deformity of the hands and feet. Small cysts or milia are seen at sites of scarring. There may be mild involvement of the mucous membranes, nails may be thick, dystrophic or destroyed. Some affected by this form of EB may note the presence of small, firm flesh colored or white skin elevations that appear spontaneously on the trunk and extremeties of their body, that are called albopapuloid lesions.

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4.4 Transient Bullous Dermatosis of the Newborn

(TBDN) appears to be a form of DDEB noted by blistering and skin fragility that appears from changes in the collagen VII gene. For reasons unknown the problem seems to correct itself during infancy.

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4.5 How is Recessive Dystrophic Epidermolysis Bullosa Inherited?

RDEB is an autosomal recessive inherited condition. This means both parents are carriers, yet they are unaffected. When each parent has a copy of the altered gene, there is a 1 in 4 chance or 25% that the child will be affected. Unfortunately, there is no test to detect carriers for RDEB. We are made aware that the parents are carriers after their child is born.

Electron microscopic evaluation reveals skin separation at the level of the sub lamina densa, with absence of anchoring fibrils in RDEB-HS.

There are reduced or occasionally abnormal appearing anchoring fibrils in RDEB-nHS.

Mutations in RDEB are found in both the motherÂ’s and the fatherÂ’s gene encoding collagen VII.

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4.6 Recessive Dystrophic Epidermolysis Bullosa

Although in some cases this form of EB can be mild with generalized blistering, typically the recessive forms of EB tend to be more severe. Onset is usually at birth with areas of missing skin. Generalized blistering then scarring can occur on skin surfaces and mucous membranes. Scarring may limit range of motion of extremities. Fusion of fingers and toes and contractures cause deformity and loss of function.

In some cases there is relatively mild blistering on hands, feet, elbows, and knees; these cases are very similar to dominant dystrophic EB. However, recessive dystrophic epidermolysis Bullosa typically is characterized as follows:

Blistering onset is at birth or soon afterwards. In some cases, nearly all skin surfaces and mucous membranes (from mouth to anus) are covered by blisters. Large areas may be devoid of skin. There is widespread scarring and deformity. Fingers and toes may become immobile. With recurrent scarring, fingers and/or toes may fuse together. Hands and arms may become fixed in a flexed position with resulting contractures. There is usually loss of the nails of the fingers and toes. Teeth may be malformed and delayed in appearing through the gums. Because routine dental care can raise blisters, many persons with RDEB have a higher than normal incidence of cavities. Blistering on the mucosal surfaces often cause scarring within the mouth and gastrointestinal tract. The ingestion of food may be limited due to microstomia (inability to fully open mouth due to scarring and contractures of the perioral region), painful swallowing, difficulty chewing, (due to poor dentition) esophageal webbing. In many cases chronic malnutrition, growth retardation and anemia may ensue. Involvement of the eyes can include eyelid inflammation with adhesions to the eyeball, as well as inflammation of the cornea or the conjunctiva (the mucous membrane covering the eyeball and the underside of the lids).

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4.7 RDEB inversa

RDEB inversa is a rare subtype of RDEB, blistering is noted on intertriginous (areas where skin rubs on skin i.e. axilla and groin) Lumbosacral areas may be affected as well.

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4.8 Common Manifestations of DEB

Since EB varies in severity these manifestations may or may not be experienced by the individual affected.

  • Generalized blistering.
  • Absent or dystrophic nail - Presence of a rough, thick or changed finger or toenail.
  • Milia - tiny skin cysts.
  • Atrophic scarring - Depressions in skin as a result of thinning in
    epidermis or or dermis.
  • Anemia - A reduced amount of red blood cells, volume of red blood cells, amount of hemoglobin. Hemoglobin is the oxygen carrying portion of the red blood cell. The heme aspect of hemoglobin, is the iron compound that makes up the pigment part of the hemoglobin molecule. It is more common in the severely infected individual (RDEB Hallopeau Siemens). In some instances anemia may occur in (DDEB, RDEB non-Hallopeau-Siemens and RDEB inversa).
  • Growth retardation is more common in a severely affected individual (RDEB Hallopeau Siemens). In some instances this may occur in (DDEB, RDEB non-Hallopeau-Siemens and RDEB inversa).
  • Problems with the soft tissue inside the mouth.
  • Ocular (eye) involvement is more common in severely affected individuals (RDEB-HS). In some instances this may occur in (RDEB non-HS
    and RDEB inversa).
  • Dental caries - Presence of cavities. This is more common in (RDEB-HS and RDEB inversa).
  • Gastrointestinal tract: Involvement of the GI tract may include blisters in the mouth, esophagus and/or anal margins. (Problems may exist in those with DDEB however it is more commonly seen in RDEB.)
  • Pseudosyndactyly - Fusion of fingers and/or toes. This manifestation is more common in the severely affected individual (RDEB HS, RDEB non-HS
    and RDEB inversa).

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4.9 Rare Manifestations of DEB
  • Granulation tissue - Capillary formation during tissue healing. Would be a rare occurrence in a person affected with either form of DEB. (This manifestation may be seen in a person severely affected with Junctional EB.)
  • Enamel hypoplasia - Underdeveloped enamel upon the teeth. This is more prevalent in patients with JEB.
  • Respiratory tract involvement. Rare occurrences have been noted in the more severely affected individual.
  • Genitourinary tract involvement. Rare occurrences involving the GU tract such as urethral stenosis and/or scarring have been reported.

For additional information about DEB you can view the Revised classification system for Inherited epidermolysis Bullosa (http://www.daklex.com/).

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4.10 Skin Cancers and Dystrophic Epidermolysis Bullosa

It is important to note that skin cancers usually react differently in a patient with EB. The more severely affected individual (RDEB) appears to be more at risk for developing squamous cell carcinoma. These localized skin cell tumors have the ability to grow faster and spread to other areas of the body more rapidly then they would on a less compromised individual. Patients and caregivers need to examine skin carefully for any changes. It is important to perform self examinations of your skin at home. Many times it is helpful to have family members look at areas that are not often viewed by the affected individual, such as the back or upon the scalp. Mirrors can be helpful in detecting growths on the back of trunk and extremities when you are self examining.

Any suspicious lesions, moles or markings should be evaluated by a dermatologist. Yearly full body exams are usually recommended, however, in some instances your dermatologist may modify the frequency of skin exams.

  • Squamous Cell Carcinoma and Recessive Dystrophic EB: The incidence of squamous cell carcinoma is more common in the severely affected individual, RDEB Hallopeau-Siemens. There have also been reports of Squamous Cell Carcinoma in patients with RDEB non Hallopeau- Siemens.
  • Squamous Cell Carcinoma and Dominant Dystrophic Epidermolysis Bullosa: It is a rare occurrence for the person affected with DDEB to develop squamous cell carcinoma.
  • Melanoma and Dystrophic EB: Rare occurrences of melanoma have been reported in Dominant Dystrophic EB and Recessive Dystrophic EB.
  • Basal Cell Carcinoma and Dystrophic EB: Rare, but has been reported in a small percentage of individuals with Dominant Dystrophic EB.

Changes in skin that warrant visit to physician for prompt evaluation
include the following: