On day-of-life 2, a 3-day-old boy who was born with no visible skin problems begins to develop erosions and bullae over both the palmar and plantar surfaces. These bullae are localized to areas of friction or trauma (eg, where electrocardiogram leads were placed). The mother’s pregnancy was normal, and the infant had been born without complications. Aside from the development of bullae, the infant has no evidence of any other medical problems. The infant’s parents are healthy and have no medical problems. No one in the infant’s family has had similar dermatologic findings.
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Epidermolysis bullosa (EB) is a rare genetic disorder defined by blister formation after minor or insignificant trauma. EB encompasses different disorders that all share a genetic mode of transmission, mechanical fragility of the skin, and blister formation. It was first described in 1870 by von Hebra and got its current name in 1886 by Koebner.1 With the advent of transmission electron microscopy in the 20th century, distinct forms of EB were first categorized into three major subtypes in 1962 by Pearson, by the skin layer affected.2 These subtypes include EB simplex (EBS), affecting the epidermis; dominant dystrophic/recessive dystrophic EB (DDEB/RDEB), affecting the uppermost papillary dermis; and junctional EB (JEB), affecting the dermoepidermal junction.2,3
The different forms of EB are caused by mutations in proteins that are localized into the specific skin regions listed above. Examples of such proteins include keratin (EBS), laminin (JEB), and type 7 collagen (DDEB/RDEB).4 All three of the major subtypes have mutations that include both autosomal recessive and autosomal dominant modes of inheritance.3 Thus, as with any genetic disorder, obtaining an in-depth family history can aid in diagnosis. Because the mutated proteins in EB are localized in different layers of skin, transmission electron microscopy and immunofluorescence antigen staining serve as the gold standard for the histologic diagnosis of inherited EB.3
The National Epidermolysis Bullosa Registry was established in 1986 by the National Institutes of Health to facilitate epidemiologic, clinical, and laboratory characterization of EB subtypes. The final estimates from this registry on prevalence and incidence from 3,271 patients were reported in 2016, finding an incidence of EB from 1986 to 2002 of 19.57 cases per 1 million live births and a prevalence of 11.07 per 1 million live births.5 The most common form of EB was EBS, followed by DDEB.5
Across the different forms of EB, the locations, frequency of skin manifestations, and severity vary widely.3 Some forms of EB are relatively mild and localized with little effect on mortality, whereas more severe types of EB can be lethal at a young age. Although the types of EB have differentiating features, it can be difficult or impossible to differentiate them clinically; thus, it is more important to be able to recognize and rule out EB rather than to try to diagnose a specific subtype. Clinically, mechanically fragile skin, erosions, and visible blisters characterize all forms of EB.3 Slight lateral or rotatory motion can often elicit blister formation, such as rotating a pencil eraser on uninvolved skin.3 Atrophic scarring after blisters are healed is also common.3 Other cutaneous findings in EB patients include dystrophic or absent nails, milia, and scarring scalp alopecia.3 Further cutaneous findings that can aid in diagnosing EB subtypes include hyperpigmented macules, peeling skin without blistering, herpetiform blisters, migratory erythema, and excessive granulation tissue.3,4
Many of the mutated proteins in EB are highly expressed in other epithelial areas, such as the eye, oral cavity, and gastrointestinal and genitourinary tracts. Common extracutaneous manifestations include corneal blisters, enamel hypoplasia, oral caries, pyloric atresia, constipation, gastrointestinal reflux disease, chronic renal failure, dilated cardiomyopathy osteoporosis, and severe multifactorial anemia.3,4 These manifestations must be closely monitored.
The differential diagnosis for neonates with blisters and erosions also includes infectious diseases such as herpes and bullous impetigo, and staphylococcal infections.3 Because it is an inherited genetic disease, genetic counseling for patients and family members is also recommended.
Currently, there are no curative therapies for any form of inherited EB. Management is focused on preventing blister formation from mechanical trauma and preventing secondary infection3,6,7; this includes padding bony surfaces and wearing loose clothing.3 Soaking/bathing in either diluted household bleach (0.5 cups of household bleach in a standard tub) or diluted acetic acid (1 part white vinegar to 20 parts water) will reduce bacterial colonization and subsequent blister infections.3,6,7 Chronic antibiotic use, such as topical mupirocin or oral antibiotics, is not recommended.3 For blisters that have already been formed, nonadhesive dressings and soft silicone dressings that incorporate absorbent foam packing can be applied.3,6,7 Dressings containing silver or iodine are also recommended to reduce infection.3,6,7 Appropriate care is also recommended for extracutaneous manifestations. This includes diligent oral hygiene, proper fluid and dietary fiber intake, and adequate nutritional intake through measurement of height, weight, and body mass index.3 All children with EB should be referred to a pediatric dermatologist for continued management and care.
Current experimental therapies for EB include gene replacement therapy, allogeneic fibroblast transplantation, bone-marrow-derived stem cell transplantation, and infusion of recombinant proteins.3,8,9
The patient in our case underwent a skin biopsy for routine histologic examination and electron microscopy, which confirmed that he had RDEB, a severe subtype of EB. The patient was referred to a specialized pediatric dermatologist for management and continued care.
Jay Patel, BS, is a medical student at Baylor College of Medicine in Houston; Arielle Gray, BS, is a medical student at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois; and Christopher Rizk, MD, is a dermatology resident at Baylor College of Medicine.
- Fine JD, Bauer EA, Gedde-Dahl T. Inherited epidermolysis bullosa: definition and historical overview. In: Fine JD, Bauer EA, McGuire J, Moshell A, eds. Epidermolysis Bullosa: Clinical, Epidemiologic, and Laboratory Advances, and the Findings of the National Epidermolysis Bullosa Registry. Baltimore, MD: Johns Hopkins University Press, 1999:1-19.
- Pearson RW. Studies on the pathogenesis of epidermolysis bullosa. J Invest Dermatol. 1962;39:551-575.
- Fine JD, Mellerio JE. Epidermolysis bullosa. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:501-513.
- Fine JD, Bruckner-Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70:1103-1126.
- Fine JD. Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the National Epidermolysis Bullosa Registry. JAMA Dermatol. 2016;152:1231-1238.
- Salavastru CM, Sprecher E, Panduru M, et al. Recommended strategies for epidermolysis bullosa management in Romania. Maedica (Buchar). 2013;8:200-205.
- Elluru RG, Contreras JM, Albert DM. Management of manifestations of epidermolysis bullosa. Curr Opin Otolaryngol Head Neck Surg. 2013;21:588-593.
- Ferrari S, Pellegrini G, Mavilio F, De Luca M. Gene therapy approaches for epidermolysis bullosa. Clin Dermatol. 2005;23:430-436.
- Cutlar L, Greiser U, Wang W. Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic epidermolysis bullosa. Exp Dermatol. 2014;23:1-6.