OVERVIEW: What every practitioner needs to know
Are you sure your patient has epidermolysis bullosa? What are the typical findings for this disease?
Epidermolysis bullosa (EB) presents with blisters/bullae on the skin in response to minimal trauma. The typical location is on friction-prone areas such as hands, feet, knees, and elbows.
The severity and extent of the blistering depends on the type of EB (see below). The presence of blisters can lead to pain itching and affect daily activities and quality of life.
There are four major types of EB that result from protein abnormalities affecting the dermoepidermal junction. Lack of production, or production of proteins that are structurally abnormal, leads to fragility of the skin and separation of the skin layers. The clinical presentation, severity, and overall prognosis depends on the level of the split within the dermoepidermal junction.
Epidermolysis bullosa simplex (EBS) results from abnormal production of the proteins that make the desmosomal and hemidesmosomal unit (keratin 5, 14, plectin). Other rare variants of EBS may involve transglutaminase 5, desmoplakin, plakoglobin, plakophilin 1, integrin, exophilin 5, and bullous pemphigoid antigen-1. These mutations lead to blistering above the basement membrane. Most of the forms are autosomal dominantly inherited. Its clinical manifestations are primarily skin related of various severity depending on the EBS subtype. Overall, these patients have a better prognosis than do those with the other forms of EB; long-term survival is unaffected.
Junctional epidermolysis bullosa (JEB), is the result of abnormal proteins (laminin 332, integrin, collagen XVII) that are present at the basement membrane. The most severe subtype, called generalized severe JEB, is characterized by severe skin and mucosal blistering that leads to mortality within the first few years of life. The other forms (generalized intermediate, localized) have milder presentations and are compatible with long-term survival.
Dystrophic epidermolysis bullosa (DEB) is the result of collagen VII mutations that create a split below basement membrane. As the split is lower, the resulting blisters are deeper and heal with scarring. There are two major subtypes, dominant DEB (DDEB) and recessive DEB (RDEB). The recessive forms produce lifetime blistering, significant extracutaneous findings, and decreased survival, particularly in the generalized forms.
Kindler syndrome (KS) is the result of fermitin family homolog 1 (kindlin-1) mutations. It is characterized by blistering at multiple levels within the basement membrane and unique clinical features from other EB types, such as photosensitivity. KS is autosomal recessively inherited. KS produces significant skin findings (blistering is more common in children than in adults) and extracutaneous findings (including oral cavity abnormalities, GI tract abnormalities, pseudosyndactyly). Long-term survival is not commonly affected.
Blisters ranging from small to large bullae
Ear, Nose, Throat
Blisters leading to hoarseness, airway obstruction
Conductive hearing loss
Constipation due to perianal blistering/fissuring
Malabsorption leading to vitamin and mineral deficiencies
Chronic renal failure
Dilated cardiomyopathy (multifactorial)
Anemia (multifactorial: iron deficiency, blood loss through the skin, chronic inflammation)
Osteoporosis (immobility, poor nutrition, skin not exposed because of bandages)
What other disease/condition shares some of these symptoms?
Infections (viral, herpes; bacterial; streptoccocus group A/B, staphylococcus species)
Immunoblistering disorders (mother typically affected)
Inherited skin disorders (bullous ichthyosis, epidermolytic hyperkeratosis, porphyria, incontinentia pigmenti)
Infections (herpes, varicella, bullous impetigo, staphyloccoccal scaled skin syndrome, bullous tinea)
Immunoblistering disorders (linear IgA dermatosis, pemphigus, bullous pemphigoid, EB acquisita)
Systemic lupus erythematosus
What caused this disease to develop at this time?
EB is an inherited disorder
It can be autosomal dominant or autosomal recessive
There are at least 14 different types of missing proteins responsible for one of the three major described types
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Light microscopy—level of the defect
Electron microscopy— to identify level of the split and morphologic characteristics of the dermoepidermal structures
Immunofluorescence antigen mapping (IFM)—most sensitive in identifying and quantifying the missing protein
Would imaging studies be helpful? If so, which ones?
Imaging studies are not useful.
Confirming the diagnosis
Rule out other entities with viral and bacterial studies.
Skin biopsy establishes the diagnosis offers some insight into the prognosis, depending on the protein affected (e.g., degree of staining for laminin 332 on immunophenotyping may be predictive of severe, generalized JEB (no staining), or localized variant of JEB [some staining]).
Molecular diagnosis confirms the diagnosis of EB as well as the type and subtype. It can help the clinician with long-term prognosis and can help families with prenatal testing.
If you are able to confirm that the patient has epidermolysis bullosa, what treatment should be initiated?
There is no curative treatment for EB. The goals of management are to prevent blistering, recognize and manage complications and improve quality of life.
Avoidance of sticky tapes and probes directly on the skin (use soft silicone fixation tape to secure devices and use a silicone medical adhesive remover)
Prevention of blistering in the neonatal/infantile period (gentle handling, invert clothing so the seams are on the outside, place monitor probes on silicone dressings instead of on the skin, remove elastic layer of the diaper, use soft silicone nipples for feeding to prevent oral blisters, use “egg crate” mattress or sheepskin on beds)
Prevention of blistering in childhood (soft leather shoes, protective pads around knees, avoid sticky dressings)
Management of open blisters (the fluid can lead to further blistering and causes pain; need to drain fluid by opening the blister with a sterile needle leaving the blister roof intact)
Management of skin wounds
Nonstick silicone dressings
Avoid daily dressing changes to minimize trauma
Exudative wounds require two layers of dressings (contact mesh layer and a secondary dressing to absorb exudate; only the top layer is replaced as needed, the contact one can be left in place for up to 1 week) or a foam dressing
Chronic wounds are colonized with bacteria; use antimicrobial agents topically or silver dressings
Secure dressing in place using a burn net
Avoid routine use of topical antibiotics, particularly the ones with potential sensitization (neomycin, bacitracin)
Soaking in a bathtub may help with the removal of dressings; salt and a cupful of bleach added to the water are helpful in decreasing the skin colonization
Routine bacterial skin swabs are not helpful as they reflect bacterial colonization
Fever, increasing exudate, increasing local pain are indicative of bacterial infection and require systemic antibacterial treatment
Minimize pain (nonstick dressings, cover open areas, remove dressings in the tub after soaking)
Use opioids (morphine) before dressing changes and any other painful procedures (blood investigations)
Use physical methods (ice packs) to decrease itching
Use sedating antihistamines for itch control
Management of Anemia (depending on the level requires iron supplementation and transfusions)
Ensuring Optimal Nutrition
Ensure caloric needs are met
Provide G-tube feedings if oral intake is restricted
Esophageal dilatation for strictures
Management of Constipation
Management of Vitamin/Mineral Deficiencies
Calcium and vitamin D supplementation
Zinc, carnitine, selenium supplementation depending on the blood levels
Anticipatory Guidance of Complications
Blood investigations yearly or more frequently depending on the symptoms (e.g., complete blood count, iron studies; calcium, phosphate, vitamin D, zinc, carnitine, and selenium determinations; erythrocyte sedimentation rate; C-reactive protein, urea, creatinine, and electrolyte levels)
Bone densitometry (Dexa) scan yearly
Electrocardiogram, echocardiogram yearly
Urinalysis, abdominal ultrasonography
What are the possible outcomes of epidermolysis bullosa?
Prognosis of EB depends on the type and subtype. Generally, EBS, generalized, intermediate JEB, localized JEB, dominant forms of DEB (DDEB), and KS are associated with a better prognosis than is generalized, severe JEB and generalized, severe or generalized, intermediate recessive DEB (RDEB). Mortality in childhood is related to sepsis, airway compromise, and dilated cardiomyopathy, whereas in adulthood it is due to invasive squamous cell carcinoma. The cumulative mortality by age 15 years is 60% for JEB and 8% for recessive DEB.
What causes this disease and how frequent is it?
Genetics are the cause of this disease. The exact prevalence is unknown.
How do these pathogens/genes/exposures cause the disease?
This is a genetic disorder leading to partial or complete loss of structural proteins that are essential for the integrity of the basement membrane, leading to skin fragility.
What complications might you expect from the disease or treatment of the disease?
Failure to thrive
Squamous cell carcinoma
Are additional laboratory studies available; even some that are not widely available?
How can epidermolysis bullosa be prevented?
What is the evidence?
There is anecdotal evidence only; studies are currently underway.
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Ongoing controversies regarding etiology, diagnosis, treatment
Because of the rarity of the disease and the wide spectrum of severity, there are no uniform guidelines of care. In addition, most of the recommended “ideal” dressings are not widely available or affordable. New therapies aimed at correction of the genetic defect are being attempted at present.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has epidermolysis bullosa? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has epidermolysis bullosa, what treatment should be initiated?
- What are the possible outcomes of epidermolysis bullosa?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- What complications might you expect from the disease or treatment of the disease?
- Are additional laboratory studies available; even some that are not widely available?
- How can epidermolysis bullosa be prevented?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment