Prevalence: 1/1x106 live births. Fragility of the skin that form bubbles when subjected to a force of friction or shear, or minor trauma. More than 20 forms have been described. A group of international experts has classified them into 4 types according to the layer of the skin where the erosion or the bubble appears: basal layer (simple epidermolysis), clear layer (stratum lucidum) (junctional epidermolysis), dense layer (dystrophic epidermolysis), or several levels (Kindler syndrome). It is very difficult to make an accurate diagnosis (electron microscopy, immunofluorescence, mutations) in the neonatal period.

There are specifically:

-         simple bullous (EB Simplex) or epidermolytic (or intraepidermal) epidermolyses: onset at birth or during the neonatal period except the localized form that appears in childhood. PHP1 and DSP genes are involved in the suprabasal forms and KRT5, KRT14, PLEC1, ITGA6 and ITGB4 genes in basal forms.

-        junctional epidermolysis (Lamina lucidolytic EB) : autosomal recessive transmission. Onset at the neonatal period, except for the late form which starts in adulthood; the genes involved are LAMA3, LAMB3, LAMC2, COL17A1, ITGB4 and ITGA4.

Here are the different types:

• dystrophic  or dermatolytic (Dermolytic EB) epidermolysis: the most serious forms of EB. autosomal dominant or recessive transmission of a mutation in the COL7A1 gene; onset: neonatal or during infancy  blisters heal leaving atrophic scars and contractures;  oral, pharyngeal and esophageal (stenosis) lesions, pseudosyndactyly, corneal erosions. Chronic pain related to the blisters and treatments (cfr burned patients). Malnutrition and esophageal stenoses often necessitate the use of a gastrostomy (ideally by laparoscopic approach).

• Kindler syndrome (Mixed EB): rarest form; autosomal recessive transmission of a mutation of the KIND1 or FERMT1 gene (20p12. 3) coding for kindline-1, a protein that links the actin cytoskeleton to the extracellular matrix; neonatal onset; bullae all over the whole body surface; progressive improvement with age, but secondary keratoderma and discrete interdigital webbing; photosensitivity; few or no extracutaneous lesions: colitis, esophagitis; early and severe periodontitis, pitted amelogenesis imperfecta of variable severity, gingival hyperplasia; sometimes cicatricial microstomia; vital prognosis is relatively good.
  Increased risk of skin carcinoma (basal cell carcinoma).

Anesthetic implications: 

echocardiography to detect any dilated cardiomyopathy (by dietary deficiency in selenium and/or carinitine, chronic anemia, iron overload); the dystrophic forms as well as the simple ones due to a mutation of the KHLH24 gene are at increased risk.

Risk of difficult intubation; microstomia, trismus, ankyloglossia. Frequent dental decay. Risk of laryngeal lesions anywhere alongside the glottis. Risk of esophageal stenosis.

For all forms, there is extremely fragile skin and mucous membranes (except the nasal mucosa): avoid any friction or shear as this causes the formation of blisters. Desinfection by dabbing. No adhesive, no ECG electrodes except if the skin is protected by Mepiform® Mepilex® or Mepitel®. The interposition of a hydrophilic gel plate (such as those used to ensure a good skin conduction during defibrillation: 3M® Defib pads 2346N) between the ECG electrodes or diathermy plate has been used with success. Difficult venous access. No diathermy plate (prefer bipolar coagulation). In general, there is a chronic use of ointments containing cortisone: risk of adrenal insufficiency, osteoporosis. If possible: IV induction; if inhalatory induction, oral premedication to avoid any hyperexcitation; cover the face mask with petrolatum or KY soaked compresses; careful lubrication of laryngoscope blades, gloves, laryngeal mask etc. in case of blisters: pierce them with a sterile needle. Avoid skin infiltration with local anesthetic (for dental care e.g.) as the mechanical effect is similar to a shear but regional blocks (axillary, epidural, spinal anesthesia) have been used with success. Use non-adhesive dressings type Aquacel® Mepiform® or Mepitel®. Avoid plaster, suppositories, lollipops. A silicone spray TrioNiltac® can be used to remove the dressings.

For junctional forms: respiratory impairment (25% of cases) is generally linked to severe forms and associated with gastroesophageal reflux. The Herlitz type presents the highest risk for complications: the risk of laryngeal stenosis is ± 40 % at the age of 6 years. It presents as weak and hoarse voice, stridor, respiratory distress. It can however be treated endoscopically but it is not uncommon to have to perform a tracheostomy.

For dystrophic forms: difficult intubation (opening of the mouth limited by retractile scars); it seems preferable to use the nasal route to intubate (wuth a well lubricated tube softened in hot water) because the endonasal epithelium is of respiratory origin and more resistant to shear forces.

An experimental treatment based on Beremagene Geperpavec gel (a gene therapy that uses the herpes virus type 1 as a vector) is showing promising results in these forms.

The affected skin surface and the metabolic needs required by healing can result in a loss of fluids, hypoproteinemia and malnutrition, with pharmacological consequences. 

The intranasal route has been used successfully to obtain rapid analgesia.

The importance of the pain and itching is very variable. Pruritus is often resistant: try anti- histaminics, tricyclic antidepressants, pregabalin, ondansetron, methylnaltrexone, lidocaine gel.

In case of epidermolysis bullosa simplex, daily use, for 15-20 minutes long dressingg changes, of an equimolar mixture of oxygen and nitrous oxide has proved effective for several months and without producing adverse effects if vitamin B12 supplementation and regular monitoring of blood levels of folic acid and vitamin B12 is provided.

Website: www.debra-international.org.uk

References : 

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Updated: April 2024