A patient aged 3 years presents with skin fragility and sporadic blistering that her parents first noticed during infancy. The condition worsened when the patient began to crawl, and she developed extensive blistering on her elbows, knees, forearms, and feet.
The patient now appears to develop a blister anytime there is friction or trauma to the skin.
Submit your diagnosis to see full explanation.
Epidermolysis bullosa (EB) is a heterogeneous family of genodermatoses characterized by skin fragility and the formation of cutaneous and mucosal blisters in response to mild trauma, such as rubbing or scratching.
Blisters may range from small vesicles to large bullae. The distribution and depth of blisters varies depending on the subtype, although the hands and feet are common locations. Nail involvement, including features such as dystrophic or absent nails, is commonly associated with certain subtypes.
Systemic findings and internal blistering occur in some forms of EB. The onset of the disease ranges from birth to early adulthood, depending on the subtype. In contrast, epidermolysis bullosa acquisita is an unrelated autoimmune blistering disease that typically presents in late adulthood.
The three major subclasses of the EB family, epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and dystrophic epidermolysis bullosa (DEB), are classified by the depth at which skin separation occurs.
The pathogenesis of EB involves defects in the attachment of the epidermis to the dermis due to mutations in genes whose products are located either within the epidermis itself (EBS), within the basement membrane zone (JEB), or below the basement membrane zone (DEB). The location of the defective protein determines the depth of blister formation, and thus the major subclass of EB.
The three most common forms of EBS are Dowling-Meara, generalized (aka Koebner), and localized (aka Weber-Cockayne). These forms are due to mutations in the genes coding for keratin 5 or keratin 14 and display an autosomal dominant mode of inheritance.
Dowling-Meara is the most severe form of EBS, with a generalized distribution of blisters, pronounced involvement of oral mucosa, and spontaneous appearance of grouped (herpetiform) blisters on the trunk and proximal extremities.
The patient in this case likely has EBS Dowling-Meara.
All forms of JEB display autosomal recessive inheritance. The most common form, Herlitz JEB, is usually lethal in infancy or early childhood. The presence of periungual hypertrophic granulation tissue in a neonate is suggestive of this disease. Associated systemic findings include tracheolaryngeal stenosis, growth retardation, and a mixed anemia.
Key clinical features of DEB are blisters associated with secondary milia and scarring. The defective protein in this subtype of EB is Type VII, which may be inherited in an autosomal dominant or recessive manner.
After puberty, patients with recessive DEB may develop highly aggressive squamous cell carcinomas that are prone to metastasis.
Once a diagnosis of EB is suspected based on the history and physical exam, a punch biopsy should be obtained on a fresh blister. Ideally, the clinician should induce formation of a new blister by rubbing the skin.
Transmission electron microscopy and/or immunofluorescence microscopy is then performed to determine the level of skin separation, which will differentiate among EBS, JEB, and DEB. Light microscopy may rule out other diagnoses in the differential, but cannot be used alone to positively diagnose EB.
Additional genetic testing will identify the specific genetic subtype of EB, knowledge that is beneficial for genetic counseling and providing prognostic information.
Treatment of EB is mainly supportive, with the primary goals being avoiding trauma and optimizing wound healing. A multidisciplinary approach is necessary in cases associated with systemic disease.
Wound healing may be complicated by infection, foreign bodies, nutritional deficiencies, and repeated trauma.
Topical antibiotics and nonadhesive dressings (tape will cause blistering) are often used to facilitate wound healing. Surgery is indicated for complications such as the aggressive squamous cell carcinomas in recessive DEB.
Jonathan Konopinski is a medical student at Baylor College of Medicine
Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
- Goldsmith LA, Fitzpatrick TB. 2012. “Chapter 62 – Inherited Epidermolysis Bullosa.” Fitzpatrick’s dermatology in general medicine. New York: McGraw-Hill Professional.
- James W., Berger T, Elston D, and Odom R. “Chapter 27: Genodermatoses and Congenital Anomalies.” 2006. Andrews’ Diseases of the Skin: Clinical. Philadelphia: Saunders Elsevier.