Epidermolysis Bullosa

Genetic disorder characterized by cutaneous blistering and scarring following minor trauma.

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More than 20 different subtypes of the disease are grouped into three main categories: epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), and junctional epidermolysis bullosa (JEB).

Seems to vary widely, depending on the country, from as high as 1:12,500 in the United States and 1:17,000 in the United Kingdom to 1:300,000 in Canada. The incidence of DEB and EBS is approximately 2 in 100,000, for each of them.

DEB has two modes of transmission that are autosomal dominant and more frequently autosomal recessive. EBS is inherited as an autosomal dominant trait. JEB form is an autosomal recessive trait.

In EBS, skin separation occurs at the level of mid basal cells and is most commonly associated with mutations affecting the genes responsible for keratins 5 and 14. The molecular background of JEB is highly variable and most likely represents a collection of different diseases. The separation of the skin layers with blister formation occurs in the lamina lucida. The responsible mutations have been assigned to the genes coding for the laminin 5 subunits, collagen XVII, and α6 and β4 integrin. DEB is associated with mutations in the gene coding for collagen type VII (COL7A1), which is a protein that anchors the lamina densa within the superficial dermis.

Based on the clinical features of blisters and scarring associated with minor trauma of the skin, oropharynx, and esophagus.

In general, patients are very sensitive to touch because frictional or shearing forces damage their skin and lead to blistering and scarring. These blisters can be very painful (and sometimes itchy) and often are present at birth or shortly thereafter. Application of direct pressure (without shearing forces), such as related to blood pressure measurement, is not as damaging. Affected patients may present with severe syndactyly of their fingers and toes (so-called “pseudosyndactyly” or “mitten deformity”) and contractures of their limbs caused by scarring as a consequence of the disease. Depending on the type of epidermolysis bullosa, onychodystrophy and repeated loss of fingernails and toenails are common. At later stages, mutilation of the extremities may occur. Involvement of the oral mucosa leads to microstomia, narrowed nasal apertures, and esophageal strictures with poor oral feeding. Constipation may result from poor feeding but also from anal blister and fissure formation associated with painful and therefore retained defecations. Eyelid retraction (entropium and symblepharon) can lead to corneal abrasion. Skin bullae render patients more prone to infection and anemia secondary to bleeding from the lesions.

Junctional Epidermolysis Bullosa: Herlitz Type (Lethal Type): This most common form of JEB is caused by the absence or a defect in the anchoring filament glycoprotein laminin 5 in the skin. It is also the most severe form commonly affecting the mouth and pharynx, including the larynx, resulting not only in feeding difficulties and hoarse voice but also in potentially life-threatening respiratory distress. Death as a result of respiratory distress and/or sepsis (favored by poor nutritional state) originating from skin infections often occurs before age 2 years. Scalp involvement is characteristic for this type of JEB, as is onychodystrophy with excessive granulation leading to bulbous enlargement of the finger tips (“drumstick fingers”). Anemia is a frequent finding.

Non-Herlitz Type: Initially similar to Herlitz type of JEB; however, the frequency and severity of blister formation decrease with increasing age.

JEB with Pyloric Atresia: This rarest from of JEB is associated with a poor prognosis. Death often occurs in the first year of life.

Epidermolysis Bullosa Simplex: Weber-Cockayne Type: Milder variant of EBS that usually starts in early childhood and most often is limited to hands and feet. The lesions tend to heal quickly, although infections are a common complication often resulting in delayed wound healing. The nails are unaffected.

Dowling-Mara Type: This form has an extremely wide range of clinical appearance, ranging from only mild symptoms to early neonatal death. The blisters are often hemorrhagic. In contrast to the Weber-Cockayne type, this type is not limited to hands and feet, although they are the most commonly affected sites and later result in keratoderma palmoplantaris. Enoral and laryngeal involvement interfering with feeding and/or breathing is frequently seen in these patients.

Koebner Type: Blister formation most often starts in the first months of life. The blisters usually heal quickly, and secondary infections are less common than in other forms of EB. The frequency of blisters seems to decrease as the children become older and onychodystrophy is not a feature of this type.

Dystrophic Epidermolysis Bullosa: Probably the type most common in patients presenting for surgery. Chronic poststreptococcal glomerulonephritis secondary to skin infections and nephrotic syndrome secondary to renal amyloidosis have been described in these patients. Some of the lesions may turn into squamous cell carcinomas later in the evolution of the disease (usually in the third and fourth decades of life) and are the main cause of death in DEB patients surviving into adulthood.

Obtain a complete blood count because many of the patients are anemic as a result of poor nutrition and frequent trauma. Renal function should be evaluated if there are anyconcerns about renal involvement. Assess mouth opening (microstomia), check tongue (scarring), neck mobility (contractures), and status of the teeth (pain associated with tooth brushing may result in poor dental hygiene). Peripheral vascular access can be extremely difficult because of scarring and/or mutilation. Rarely, epidermolysis bullosa is associated with muscular dystrophy, characterized by progressive muscle weakness or Myasthenia Gravis. A possible association with cutaneous Porphyrias has been reported.

The main anesthetic management point to remember is to use a nontouch technique to prevent induction of blisters. Venous access can be difficult to obtain, and securing the intravenous cannula is an issue because dressing can cause blistering. Therefore use of Vaseline gauzes over and around the cannula followed by a light bandage around the insertion site is recommended. Monitoring can cause new bullae, and care must be taken to avoid adhesive electrode pads directly on the skin whenever possible and to wrap the underlying skin with Vaseline gauze before applying the blood pressure cuff. Needle electrodes for the electrocardiogram have been used successfully instead. Airway management can be difficult because of scarring around the mouth (microstomia) and of the tongue, so a padded (air-cushion type, if possible) and well-lubricated (Vaseline) face mask and laryngoscope blade must be used. Difficult airway management is associated with a higher risk of new bullae formation. In severe cases, fiberoptic intubation is needed because of restricted mouth opening. Oral intubation is preferred, and an endotracheal tube half to one size smaller than predicted should be used. Hoarse voice may be an indicator for laryngeal bullae/scarring, also potentially requiring a smaller endotracheal tube. Again, endotracheal tube securing may be complicated, and suturing it in place is often the best choice. The lips should be well lubricated too, especially where they come in contact with the endotracheal tube. Laryngeal mask airway use with few complications from new bullae formation has been reported. In addition, tracheal lesions do not appear to occur frequently after intubation (may be explained by respiratory columnar epithelium instead of squamous epithelium). Oropharyngeal suctioning should be avoided or done under direct vision only (also to check for new bullae before extubation) because it can easily cause bullae formation. Regional anesthesia is not contraindicated if the skin over the region is unaffected, but use of a sterile technique is imperative because these patients are prone to infections. Avoid rubbing the skin for disinfection; use a spray such as aqueous chlorhexidine instead. Finally, because of esophageal scarring, affected patients are at higher risk for regurgitation and aspiration, so antacid prophylaxis is recommended prior to surgery. Esophageal involvement also leads to malnutrition as a result of poor feeding and sometimes requires correction prior to elective surgery. Infections are more common because of the broken epidermal barrier and should be treated prior to the patient going to the operating room. Blood for transfusion should be easily available in the operating room, particularly if the hemoglobin level already is borderline. Administering a sedative premedication prior to taking young children to the operating room may be wise to prevent them from struggling during induction, which may lead to new bullae formation. Be very careful while positioning these patients because inappropriate handling may cause new bullae formation. Ideally, the patient should position him/herself on a well-padded operating table. Corneal abrasions are common among affected patients secondary to scarring of the eyelids with poor coverage of the cornea, so lubricant eye ointment and Vaseline gauzes should be applied. However, in small children, eye ointment resulting in blurred vision may trigger eye rubbing with new blister formation postoperatively. Avoid nasopharyngeal, esophageal, or rectal temperature probes. These patients are often already in significant pain preoperatively, which will be even worse postoperatively. Adequate pain relief is mandatory. Regional anesthesia is an elegant and effective way to achieve this goal; however, not all procedures are suitable for this approach. The oral and rectal routes may not be options in these patients (dysphagia and anal blisters/fissures, respectively), leaving the intravenous route as the only option. Patient-, parent-, or nurse-controlled analgesia has been used successfully in these cases.

Avoid using succinylcholine in patients with associated muscular dystrophy. Some patients seem to be very sensitive to nondepolarizing muscle relaxants, so titration under the control of a peripheral nerve stimulator (Caveat: use needle electrodes instead of self-adhesive) is recommended. Perioperative steroid stress coverage may be necessary for patients on long-term oral steroids. Atropine preoperatively has been recommended to reduce oral secretions, particularly in sedated and spontaneously breathing patients. Drugs to be avoided in the presence of porphyria are given under Porphyrias.

Adams-Oliver Syndrome (AOS): Very rare inherited disorder characterized by defects of the scalp associated with multiple scarred and hairless areas that usually have dilated blood vessels directly under the skin. Scalp defects are present at birth. The extremities are either short (hypoplastic fingers and toes) or characterized by absent hands and lower legs. Congenital heart defect must be ruled out.

Aplasia Cutis Congenita: Most often inherited disorder with circumscribed or more extensive skin lesions that may also involve underlying tissues. Neurologic and cardiac anomalies have been described in these patients.

Erythema Multiforme (EM): Acute mucocutaneous hypersensitivity reaction of variable severity characterized by symmetrical skin eruptions, with or without mucous membrane lesions.

Danbolt-Closs Syndrome: Inherited vesiculobullous disorder characterized by intermittent simultaneous occurrence of diarrhea and bullous dermatitis (dry lesions surrounding the mouth, ears, nose and eyes, but also affecting the fingers, feet, and knees) and failure to thrive in premature babies. In children, periorificial lesions of the face and anogenital region. Alopecia and absence of eyebrows, eyelashes, and thymus are common.

Pemphigus: Rare autoimmune blistering disease that affects the skin and mucous membranes. Patients have circulating antibodies to an intercellular cement substance of the basal membrane.