Epidermolysis Bullosa Clinical Presentation

Updated: May 09, 2018
  • Author: M Peter Marinkovich, MD; Chief Editor: William D James, MD  more...
  • Print
Presentation

History

Important general points include age of onset; size, frequency, and location of blisters; possible inciting factors; prior diagnostic attempts; prior therapies; and extent of pain or pruritus.

Review of systems information that can be associated with different epidermolysis bullosa (EB) subtypes includes alteration of growth or development and evidence of mucosal involvement, including oral (which is demonstrated in the image below), nasopharyngeal, ocular, genitourinary, GI, or respiratory symptoms. A family history of blistering disease is an important finding to identify.

Recessively inherited dystrophic epidermolysis bul Recessively inherited dystrophic epidermolysis bullosa; oral cavity blistering and scarring.
Next:

Physical Examination

Perform a complete physical examination with an emphasis on inspection of all skin, as well as conjunctival, oral, and genital mucosae. Evaluate the size, location, and character of blisters. Attempt to assess the general level at which lesions split. Usually, superficial blisters manifest as crusted erosions, intraepidermal blisters are flaccid and may expand under pressure, and intralamina lucida blisters are tense and heal with atrophy but no scarring. Sublamina densa blisters heal with scarring and milia formation. Assess for involvement of nails, hair, or teeth.

Epidermolysis bullosa simplex

Most epidermolysis bullosa simplex cases consist of keratin disorders characterized by intraepidermal blistering with relatively mild internal involvement. Lesions typically heal without scarring. Most commonly, these diseases are dominantly inherited, but recessively inherited cases have been reported. An epidermolysis bullosa simplex variant associated with mottled pigmentation has been described in several families.

Epidermolysis bullosa simplex, localized

Formerly termed Weber-Cockayne subtype, this is the most common form of epidermolysis bullosa simplex. Blisters usually are precipitated by a clearly identified traumatic event. They can be mild to severe and most frequently occur on the palms and soles. Hyperhidrosis can accompany this disorder. The epidermolysis bullosa simplex localized subtype is shown in the image below.

Epidermolysis bullosa simplex localized (formerly Epidermolysis bullosa simplex localized (formerly termed Weber-Cockayne subtype). This mild bullous disease is characterized by localized blistering at sites of trauma such as the feet.

Epidermolysis bullosa simplex, generalized

Generalized epidermolysis bullosa simplex is further subdivided into intermediate and severe subtypes. Both forms typically present with a generalized onset of blisters that occurs at or shortly after birth. Hands, feet, and extremities are the most common sites of involvement. Palmoplantar hyperkeratosis and erosions are common. Blisters heal with atrophy, and nails are often affected. Mucosal involvement can also take place, more commonly in the more severe subtypes. Grouped herpetiform blisters can sometimes be seen in the severe subtypes as well.

Epidermolysis bullosa simplex, generalized (former Epidermolysis bullosa simplex, generalized (formerly termed Koebner subtype). Palmoplantar blistering and hyperkeratosis are noted.
Epidermolysis bullosa simplex, generalized (former Epidermolysis bullosa simplex, generalized (formerly termed Koebner subtype). Close-up image shows hyperkeratotic papules and plaques on the palm.

Epidermolysis bullosa with muscular dystrophy

This rare epidermolysis bullosa simplex variant is characterized by generalized blistering activity, followed by onset of muscular dystrophy later in life. The degree of blistering activity does not correlate necessarily with the degree of muscular dystrophy. This disorder can sometimes be associated with pyloric atresia. Some patients can present with enamel hypoplasia.

Epidermolysis bullosa with pyloric atresia

This condition always is associated with pyloric atresia at birth and usually is accompanied by severe generalized blistering. In most patients, prognosis is poor despite correction of the pyloric atresia because the internal involvement is extensive. While this subtype typically is fatal during infancy, some patients with a milder case of the disease have survived into childhood. There is inconsistency with classification of this disorder; sometimes it is referred to as being in the simplex category, while at other times it is placed in the junctional category.

Suprabasal epidermolysis bullosa simplex

This is a group of extremely rare autosomal recessive disorders characterized by separation above the basal keratinocyte layer. In these disorders, the blister roofs are often not seen, and, instead, crusting and superficial erosions are the usual clinical presentation. Cutaneous involvement ranges from extremely mild to widespread and can sometimes take an acral distribution. Depending on the underlying molecular pathology (see Causes), extracutaneous involvement can be absent or alternatively can be associated with severe renal and respiratory disease.

Junctional epidermolysis bullosa

Junctional epidermolysis bullosa is a collection of diseases characterized by intralamina lucida blistering. Primary subtypes include a lethal subtype termed Herlitz or junctional epidermolysis bullosa letalis, a nonlethal subtype termed junctional epidermolysis bullosa mitis, and a generalized benign type termed generalized atrophic benign epidermolysis bullosa.

Severe generalized junctional epidermolysis bullosa

The severe generalized form of junctional epidermolysis bullosa is characterized by generalized blistering at birth and arises from an absence or a severe defect in expression of the anchoring filament glycoprotein laminin-332. Patients with lethal forms of junctional epidermolysis bullosa show characteristic periorificial erosions around the mouth, eyes, and nares, often accompanied by significant hypertrophic granulation tissue. Multisystemic involvement of the corneal, conjunctival, tracheobronchial, oral, pharyngeal, esophageal, rectal, and genitourinary mucosae is present. Internal complications of the disease include a hoarse cry, cough, and other respiratory difficulties. Patients with severe generalized junctional epidermolysis bullosa are at increased risk for death from sepsis or other complications secondary to the profound epithelial disadhesion, and usually they do not survive past infancy. The severe generalized subtype is shown in the image below.

Junctional epidermolysis bullosa, generalized seve Junctional epidermolysis bullosa, generalized severe (formerly termed Herlitz or letalis) subtype. This severe disease is characterized by generalized intralamina lucida blistering at birth, significant internal involvement, and a poor prognosis.

Generalized intermediate junctional epidermolysis bullosa

There is a spectrum of patients who fall into this category of nonlethal but generalized junctional epidermolysis bullosa, including those with significant mucosal involvement and those without. Those with a more marked phenotype with mucosal involvement usually have partial loss of laminin-332. These patients can still display the same periorificial erosive hypergranulation tissue as those with the severe variant, and they can also show significant oropharyngeal, esophageal, and urogenital erosions and scarring. Enamel hypoplasia can lead to tooth abnormalities, and nail dystrophy or loss of nails can occur. Even though this group of patients with significant mucosal involvement survives infancy, life expectancy is often reduced.

Another subtype in the generalized intermediate junctional category are patients with loss of the basement membrane protein BP180/collagen XVII. Generalized atrophic benign epidermolysis bullosa was the term previously used for these patients, and, as the name suggests, patients with this subtype are characterized by generalized cutaneous blistering and presenting at birth. Blistering activity is worsened by increased ambient temperature, and blisters heal with a distinctive atrophic appearance. Extracutaneous involvement is rare, with the exception of teeth, with hypoplastic enamel formation resulting in significant tooth decay. Nail dystrophies and a nonscarring alopecia are other common clinical manifestations. Individuals with generalized atrophic benign epidermolysis bullosa have the potential to bear children and have a typical life expectancy. Of note, this subtype has been shown to display phenotypic reversion, a correction of blistering occurring in localized regions, most often on the arms and other subexposed regions. [13]

Localized junctional epidermolysis bullosa

Some patients with localized junctional epidermolysis bullosa (previously termed mitis) can present with blistering predominantly localized to the intertriginous (inversa) pretibial or other regions. This is a less common than the generalized subtypes.

Dystrophic epidermolysis bullosa

This is a group of diseases caused by defects of anchoring fibrils. Blisters heal followed by dystrophic scarring. Formation of milia (1- to 4-mm white papules) results as a consequence of damage to hair follicles. These diseases are typically lifelong; however, a rare variant exists termed bullous dermolysis of the newborn, which remits after infancy.

Dominantly inherited dystrophic epidermolysis bullosa

The onset of disease usually is at birth or during infancy, with generalized blistering as a common presentation. With increasing age, an evolution to localized blistering is present. A common variant has an acral distribution and minimal oral or tooth involvement. Another variant features more extensive blistering, scarlike papules on the trunk (termed albopapuloid lesions), and involvement of the oral mucosa and teeth. Dystrophic or absent nails are common in both of these dominantly inherited dystrophic epidermolysis bullosa variants. Localized involvement to only acral or pretibial regions or nails can sometimes occur. A pruriginosa variant characterized by marked pruritus associated with wound healing has also been described.

Recessively inherited epidermolysis bullosa

This group of diseases ranges from mild to severe in presentation.

The intermediate and localized subtypes demonstrate clinical manifestations similar to the dominantly inherited forms of dystrophic epidermolysis bullosa, often showing a localized, often pretibial, acral, or inversa distribution. These less severe subtypes often involve nails but show less mucosal involvement.

Severe generalized recessive epidermolysis bullosa, as described by Hallopeau-Siemens, usually shows generalized blistering at birth and subsequent extensive dystrophic scarring that is most prominent on the acral surfaces. This can produce pseudosyndactyly (mitten-hand deformity) of the hands and feet. Flexion contractures of the extremities are increasingly common with age. Nails and teeth also are affected. Involvement of internal mucosa can result in esophageal strictures and webs, urethral and anal stenosis, phimosis, and corneal scarring. Malabsorption commonly results in a mixed anemia resulting from a lack of iron absorption, and overall malnutrition may cause failure to thrive (see Diet). Patients with severe recessively inherited epidermolysis bullosa who survive to childhood are at significant risk of developing aggressive SCC in areas of chronic erosions. Pseudosyndactyly is shown in the image below.

Recessively inherited dystrophic epidermolysis bul Recessively inherited dystrophic epidermolysis bullosa pseudosyndactyly (mitten-hand deformity) of the hands and feet.

Kindler syndrome

This is clinically characterized by epidermolysis bullosa–like blistering induced by mechanical trauma, starting at birth or in infancy. The skin heals with atrophic changes similar in appearance to junctional epidermolysis bullosa. Blistering becomes less prominent in late childhood, coincident with an increase in poikilodermatous changes on sun-exposed skin. Poikilodermatous skin can display atrophy, hyperkeratosis, telangiectasias, and areas of hypopigmentation and/or hyperpigmentation. Photosensitivity is a frequent accompanying feature. Nail changes and webbing of digits also can be seen.

Previous
Next:

Complications

Squamous cell carcinoma

Arising in chronic wounds or scars of recessively inherited epidermolysis bullosa, this form of SCC is invasive and has high metastatic potential. Other epidermolysis bullosa subtypes do not show a tendency to develop SCC.

Pseudosyndactyly (mitten-hand deformity)

This is a frequent complication in patients with recessively inherited epidermolysis bullosa but is rare in other subtypes. In this disorder, skin grows around the digits because of repeated blistering and dystrophic healing. Over time, the digits are encased in a mitten of skin. Therapeutic surgical approaches are available, but the rate of recurrence is high (see Surgical Care).

Mucosal complications

Patients with recessively inherited epidermolysis bullosa often have esophageal manifestations. Esophageal scarring secondary to repeated blistering and healing results in dysphagia from webbing, strictures, or stenosis. These complications are rare in patients with epidermolysis bullosa simplex but occur in patients with Herlitz and other nonlethal forms of junctional epidermolysis bullosa and dominantly inherited dystrophic epidermolysis bullosa. No cases of esophageal involvement have been reported in the generalized benign atrophic form of junctional epidermolysis bullosa (see Surgical Care). While patients with the Herlitz form of junctional epidermolysis bullosa have the greatest tendency for tracheolaryngeal involvement, recessively inherited epidermolysis bullosa may involve the tracheolaryngeal mucosa as well. Oral inflammation and mucosal structuring, especially on esophagus and urethra, can also be seen in Kindler syndrome.

Previous