EB Simplex in Depth

Epidermolysis bullosa (EB) is a rare genetic disorder that causes skin and mucous membrane fragility. It comprises a clinically and genetically heterogeneous group of disorder characterized by spontaneous or contact/friction–induced blistering. EB is classified into 4 types–simplex, junctional, dystrophic, and Kindler syndrome–and 30 sub-types. The disease is caused by defects in proteins implicated in dermal-epidermal adhesion. To-date, at least 19 genes have been characterized and more than 1000 mutations identified, thus making it a very diagnosis disorder.

 

Clinical Classification of EB

 

EBS Suprabasal- Skin fragility syndromes: 

Acral Peeling Skin Syndrome (APSS) [Protein- Transgluminase 5]

common features: characterized by painless peeling of the top layer of skin. The term "acral" refers to the fact that the skin peeling in this condition is most apparent on the hands and feet. Occasionally, peeling also occurs on the arms and legs. The peeling is usually evident from birth, although the condition can also begin in childhood or later in life. Skin peeling is made worse by exposure to heat, humidity and other forms of moisture, and friction. The underlying skin may be temporarily red and itchy, but it typically heals without scarring. Acral peeling skin syndrome is not associated with any other health problems.

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EBS Superficialis (EBSS) [Protein- unknown]

common features:  milia and atrophic (indented) scarring, as well as involvement of oral and/or ocular surfaces. the presence of blisters and the absence of spontaneous continual exfoliation or peeling.

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Lethal Acantholytic EBS (EBS- acanth) [Protein- Desmoplaskin, Plakoglobin]

common features: characterized by generalized oozing erosions, usually in the absence of blisters.

 

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Desmoplaskin Woolly Hair Syndrome [Protein- Desmoplaskin] 

 
common features: hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused; Cardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.

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Plakoglobin Deficiency [Protein - Plakoglobin]

common features:  mild skin involvement, thickening of the skin on the palms of the hands and soles of the feet and arrhythmogenic heart disease.

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Ectodermal Dysplasia Syndrome [Protein Plakophilin 1]

common features:  manifests with skin fragility, palmoplantar keratoderma, abnormal hair growth, and nail dystrophy and, in some but not all cases, with defective sweating

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EBS Basal- More common type of EBS

 Localized EBS (EBS-loc) [Protein- Keratin 5 or Keratin 14]

common features: most common form;  rarely present at birth and usually appear when the child begins to crawl or walk; characterized by blisters confined to the palms and soles and, in some cases, by oral erosions or blisters during infancy. Lesions can be present in any part of the body as a result of skin trauma.

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Generalized Intermediate EBS (EBS-gen intermed) [Protein- Keratin 5 or Keratin 14]

common features:  usually present at birth or within the first days of life; presents with non-herpetiform blisters (not in clusters); anemia and growth retardation are uncommon in this subtype.

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Generalized Severe EBS (EBS- gen sev) [Protein- Keratin 5 or Keratin 14]
 

common features: a less frequent subtype;  present at birth with widespread skin loss; usually associated with marked morbidity and mortality during the neonatal period or early infancy. Its most distinctive feature is the formation of intact blisters grouped in an arch-shaped or clustered distribution (herpetiform). Patients with this form usually develop skin thickening on the palms and soles, giving rise to keratosis that may resolve on reaching adulthood. Some patients have nail distrophy atrophic scarring, milia, mucosal involvement (laryngeal stenosis), anemia, and delayed growth.  

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EBS with Mottled Pigmentation (EBS-MP) [Protein- Keratin 5]

common features: blistering may begin at birth; have a mottled appearance of the skin; may bruise more easily and the skin may seem to age more quickly.  

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Migratory Circinate EBS (EBS-migr) [Protein- Keratin 5]

common features: appears to be phenotypically milder than EBS-generalized severe; is characterized by belt-like areas of erythema with multiple vesicles and small blisters at the advancing edge of erythema. Lesions appear from birth primarily on hands, feet and legs. Nails and mucosa were not affected. The lesions healed with brown pigmentation, but without scarring. 

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KLHL24 EBS [Protein-Keratin 14] 

common feature: wide spread blistering can occur;
alopecia (a condition that causes hair to fall out in small patches);  follicular and cutaneous atrophy (reduced hair follicles and
sebaceous glands) and most significantly-
Dilated cardiomyopathy- a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting.

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K14 Recessive EBS (EBS-AR) [Protein- Keratin 14]

common features: characterized by generalized or, less frequently, localized acral (hands, feet, fingers, toes) blistering.

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EBS with Muscular Dystrophy (EBS-MD) [Protein- Plectin 1]

common features: generalized blistering associated with muscular dystrophy.

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EBS with Pyloric Atresia (EBS-PA) [Protein- Plectin, Alpha4Beta6]

common features:  generalized severe blistering with widespread congenital absence of skin and pyloric atresia.

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Ogna EBS (EBS-Og) [Protein- Plectin]

common features: characterized by sometimes widespread, primarily acral blistering.

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Recessive EBS BP230 Deficiency (EBS-AR BP230) [Protein- antigen-1 BP230]

common features:  mild, predominantly acral, trauma-induced skin fragility, resulting in blisters. Blisters mostly affect the feet, including the dorsal side, and are often several centimeters big.

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Recessive EBS Exophilin 5 Deficiency (EBS-AR exo 5) [Protein Exophilin 5]

 common features: mild, generalized trauma-induced scale crusts and intermittent blistering, sometimes combined with erosions and bleeding, recovering with slight scarring and post-inflammatory hyperpigmentation. Clinical symptoms improve with age.

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