A 15-month-old boy presents with a history of skin blistering since birth, primarily on his hands, feet, and the perioral face. Blisters and erosions also involve the trunk, some in an annular configuration. There is no family history of neonatal blistering or skin fragility. Over time, the patient has had a decreased number of new vesicles and bullae associated with trauma and friction but has developed thicker skin on the soles of the feet and dystrophic nails.
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Epidermolysis bullosa (EB) was first described in the 1880s. However, it was not until 1962 that a classification scheme among this group of inherited blistering diseases was developed.1 EB encompasses a group of hereditary disorders characterized by blistering of the skin upon exposure to mechanical stress. EB is traditionally divided into 3 major groups based on the level of dermoepidermal separation. These groups include EB simplex (EBS), junctional EB, and dystrophic EB. Among these 3 groups, EBS is the most frequent form of EB, with an approximate prevalence ranging from 1:20,000 to 1:50,000.
EBS-Dowling Meara (EBS-DM) is almost exclusively inherited as an autosomal dominant disorder2 that is 100% penetrant,3 and it encompasses approximately 25% of all EBS cases,4 but can also arise from spontaneous mutation. This disease is the result of mutations in either the KRT5 gene, encoding keratin 5, or the KRT14 gene, encoding keratin 14.5
Patients who have EBS-DM often present at birth with widespread, severe blistering. The hallmark feature of its presentation is intact vesicles in grouped or annular configuration. Because of this appearance, EBS-DM was initially named EB-herpetiformis, despite there being no association between this disease and herpetic infection.1 The blisters may appear spontaneously or erupt with minimal trauma due to increased skin fragility. The greatest morbidity and risk of mortality in patients with EBS-DM is in infancy, when these groups of blisters are most severe, leading to recurrent skin infections (Staphylococcus aureus and Pseudomonas aeruginosa) and septicemia (S. aureus, P. aeruginosa, Enterococcus cloacae).5 Mucosal involvement of EBS-DM can lead to interference with feeding and tracheolaryngeal compromise, which can result in infant demise.3 As these patients age, the blistering tends to improve, and the keratoderma of the palms and soles may progress.6 Other symptoms include dystrophic and discolored nails, as well as post-inflammatory hyperpigmentation or hypopigmentation at the blister site.1
Skin biopsies of vesicles and bullae will demonstrate a subepidermal blister with paucity of infiltrating inflammatory cells. In addition to standard hematoxylin and eosin staining, additional samples for transmission electron microscopy (TEM) or immunomapping are recommended. TEM findings show blistering above the skin basement membrane at the level of the basal keratinocytes. Immunofluorescence can be used to detect antibodies to keratin 5 and keratin 14 to detect and classify EBS-DM.7
When considering the diagnosis of EBS-DM, the various disease categories under the larger umbrella of epidermolysis bullosa should be considered, especially as EBS-DM often is confused with junctional or severe recessive dystrophic EB, which can only be definitively differentiated with immunomapping or TEM. Additionally, if there is no family history of blistering, congenital herpes simplex infection should be strongly considered and evaluated.1
A diagnosis of EBS-DM should be suspected in a neonate presenting with fragility of the skin manifested by blisters in annular groups or clusters, nail dystrophy, or a weak cry as a result of laryngeal involvement.3 The blisters that occur in patients with EBS-DM are more often hemorrhagic than those seen in other forms of EBS. Mucosal involvement is frequently present in severely affected neonates, which manifests as multiple oropharyngeal blisters. These blisters have the potential to seriously interfere with feeding, and the patient may require a feeding tube to ensure adequate nutrition. Once these blisters have healed, transient milia and minor scarring may be present,2 but a large majority of blisters heal without scarring.6
There is currently no curative treatment for patients with EBS-DM. The therapeutic approaches used for these patients are valuable for symptom management and infection prevention. The major underlying tenants of treatment are avoiding blistering events and ensuring proper wound care. Well-fitting clothes and shoes are essential, and patients often benefit from PT/OT. Additionally, because EBS-DM is inherited in an autosomal dominant fashion, genetic counseling should be considered or offered for those with the disease who are planning to conceive.
Our patient was biopsied as a neonate for both H&E and induced blister for immunomapping by a specialty laboratory. Genetic testing was performed to confirm mutation in KRT5 for diagnosis of EBS-DM. He is followed regularly by dermatology, gastroenterology, pediatric dentistry, or other services. Careful wound care is performed by his mother to reduce trauma-induced blistering and improve discomfort. Urea cream is used to soften nails and the plantar keratoderma. He follows with physical therapy and occupational therapy as well. The family was also given information about the Dystrophic Epidermolysis Bullosa Research Association of America for additional resources.
Joan Fernandez is a medical student, and Jessica Boulavsky, MD, is a dermatology resident at the Baylor College of Medicine in Houston.
- Fine JD. Inherited epidermolysis bullosa. Orphanet J Rare Dis. 2010;5:12.
- Yordanova I, Vassileva S, Demerjieva Z, et al. Epidermolysis bullosa
- Pfendner EG, Bruckner AL. Epidermolysis bullosa simplex. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews. Seattle: University of Washington; 1998:1993-2016. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1369/
- Bergman R, Harel A, Sprecher E. Dyskeratosis as a histologic feature in epidermolysis bullosa simplex-Dowling Meara. J Amer Acad Dermatol. 2007;57:463-466.
- Titeux M, Mazereeuw-Hautier J, Hadj-Rabia S, et al. Three severe cases of EBS Dowling-Meara caused by missense and frameshift mutations in the keratin 14 gene. J Investigat Dermatol. 2006;126:773-776.
- Chamcheu JC, Siddiqui IA, Syed DN, et al. Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys. 2011;508:123-137.
- Chan LS. Blistering skin diseases. Boca Raton, FL: CRC Press; 2009:87-90