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Epidermolysis Bullosa, or EB, is a rare genetic connective tissue disorder that affects 1 out of every 20,000 births in the United States (approximately 200 children a year are born with EB). 

There are many genetic and symptomatic variations of EB, but all share the prominent symptom of extremely fragile skin that blisters and tears from minor friction or trauma. The list of complications and secondary illnesses can be long and requires multiple interventions from a range of medical specialists. EB affects both sexes and all racial and ethnic groups equally. 

There is no treatment or cure, but researchers are making tremendous strides in developing therapies. The current standard of care is supportive, which includes daily wound care, pain management, and protective bandaging. 

There are 4 major types —EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler. On this page, you will find information on the 4 major EB types and their associated subtypes. 

Simplex

EB Simplex, or EBS, encompasses all subtypes of EB having mechanical fragility confined to the epidermis.

EBS-loc

EBS, localized (EBS-loc) 

EBS, localized, formerly called EBS, Weber-Cockayne, is generally the mildest form of EBS, and is characterized by skin blistering that begins anytime between childhood and adulthood and is usually limited to the hands and feet, but blistering can occur anywhere where enough friction or trauma is present. Later in life, skin on the palms of the hands and soles of the feet may thicken and harden.   

Noted Clinical Symptoms 

Blistering of the palms & soles of feet, Keratoderma (palms & soles), and oral cavity soft-tissue abnormalities. 

EBS-gen sev

EBS, generalized severe (EBS-gen sev)  

EBS, generalized severe, formerly called EBS, Dowling-Meara, is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth, and blisters may appear in clusters. Blistering is present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles. Improvement occurs during mid-to late childhood.  

Noted Clinical Symptoms 

Generalized blistering with relative sparing of palms & soles of feet, arciform (“herpetiform”), EB nevi, keratoderma, atrophic scarring, dystrophic or absent nails, milia, anemia, growth retardation, oral cavity soft-tissue abnormalities, constipation, respiratory tract involvement, and uncommon death related to EB by age 30. 

EBS- gen intermed

EBS, generalized intermediate (EBS-gen intermed)  

EBS, generalized intermediate, previously known as EBS, Koebner, generalized other, or non-Dowling Meara, is also most often diagnosed at birth. Generalized blistering is seen on all parts of the body and is generally more widespread than in EBS-loc, but milder than in EBS-gen sev.  

Noted Clinical Symptoms 

Generalized blistering, dystrophic or absent nails, milia, atrophic scarring, keratoderma, oral cavity soft-tissue abnormalities, ocular issues, EB nevi, and malignant melanoma. 

Other EBS Subtypes
EBS with mottled pigmentation (EBS-MP)

EBS-MP is a rare form of EBS. Blistering may begin at birth, and the skin has a mottled appearance (darker and lighter colored sports of skin). Their skin may seem to age more quickly and bruise easily. EBS-MP is caused by a mutation in the keratin-5 gene (KRT-5) and is inherited in an autosomal dominant fashion.  

Noted Clinical Symptoms  

Generalized blistering, mottled or reticulate brown pigmentation, potential for dystrophic or absent nails and/or keratoderma. 

EBS, migratory circinate (EBS-migr)

EBS-migr is a basal subtype of EBS characterized by belt-like areas of erythema (superficial reddening of the skin) with multiple vesicles and small blisters at the advancing edge of erythema.  

Noted Clinical Symptoms  

Generalized blistering, migratory circinate erythema, brown post-inflammatory hyperpigmentation, and dystrophic or absent nails. 

EBS, autosomal recessive K14 (EBS-AR K14)

Most forms of EBS are caused by an autosomal dominant inheritance, but in rare cases, autosomal recessive inheritance has been seen, and often results in less severe symptoms.  

Noted Clinical Symptoms  

Generalized & anogenital blistering, oral soft-tissue abnormalities, gastrointestinal issues (constipation), genitourinary tract involvement, growth retardation, dystrophic or absent nails, caries (cavities), anemia, ichthyotic plaques, and EB nevi (rare). 

EBS with muscular dystrophy (EBS-MD) 

Onset of blistering in those with EBS-MD is usually as early as birth, but muscular dystrophy manifests between infancy and adulthood. Blisters are often hemorrhagic and heal with mild atrophic scarring. Slowly progressive weakness of the head and limb muscles appears between the first year and the fourth decade of life and may confine the patient to a wheelchair. Additional neurological symptoms (ptosis, oculobulbar muscle weakness and fatigability) indicative of a myasthenic syndrome have been described in some patients.  

Noted Clinical Symptoms  

Generalized blistering, dystrophic or absent nails, keratoderma (punctate or focal), atrophic scarring, oral soft-tissue abnormalities, enamel hypoplasia, granulation tissue/stenosis in the respiratory tract, anemia, growth retardation, and risk of death related to EB by age 30. 

EBS with pyloric atresia (EBS-PA) 

EBS-PA affects the skin and digestive tract. Most often, blisters occur over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. People with EB-PA are also born with pyloric atresia, which is an obstruction of the lower part of the stomach (the pylorus). This obstruction prevents food from emptying out of the stomach into the intestine. Signs of pyloric atresia include vomiting, a swollen (distended) abdomen, and an absence of stool. Pyloric atresia is life-threatening and must be repaired with surgery soon after birth.  

Because the symptoms of EB-PA are so severe, many infants with this condition do not survive beyond the first year of life. In those who survive, the condition may improve with time; some affected individuals have little or no blistering later in life.  

Noted Clinical Symptoms  

Generalized blistering, pyloric atresia of the gastrointestinal tract, anemia, growth retardation, oral soft-tissue abnormalities, widespread congenital absence of skin, malformed pinnae and nasal alae, joint contractures, cryptorchidism, atrophic scarring, and risk of death related to EB by age 30. 

EBS-Ogna (EBS-Og)

EBS-Ogna is a basal subtype of EBS characterized by sometimes widespread, primarily acral blistering.  

Noted Clinical Symptoms  

Acral blistering (but may be widespread), onychogryphosis, potential tendency to bruise. 

BS, autosomal recessive-BP230 deficiency (EBS-AR BP230)

Noted Clinical Symptoms  

Acral blistering and dystrophic or absent nails. 

EBS, autosomal recessive – exophilin 5 deficiency (EBS-AR exophilin 5)

Noted Clinical Symptoms  

Generalized blistering & crusts, and mild mottled pigmentary changes. 

Junctional

Junctional EB, or JEB, includes all subtypes of EB in which blisters develop within the mid portion or junction, the so-called lamina lucida, of the skin basement membrane zone (BMZ). 

JEB-loc

JEB, Localized (JEB-loc) 

JEB, Localized, not previously named nor classified, is a subtype of JEB characterized by localized blistering, and dystrophic or absent nails. Symptoms seen in other subtypes of JEB, such as atrophic scarring, granulation tissue, and scalp abnormalities, are not seen in this subtype.  

Noted Clinical Symptoms  

Localized blistering, dystrophic or absent nails, enamel hypoplasia, excessive carries (cavities), and milia. 

JEB- gen sev

JEB, generalized severe (JEB- gen sev)  

JEB, generalized severe, formerly called JEB, Herlitz, is a severe subtype of JEB. From birth or early infancy, affected individuals have blistering over large regions of the body. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. As a result, many affected children have chronic malnutrition and slow growth. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a buildup of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing.  

Other complications of Herlitz JEB can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement, and hair loss (alopecia). Because the signs and symptoms of Herlitz JEB are so severe, infants with this condition usually do not survive beyond the first year of life.  

Noted Clinical Symptoms 

Generalized blistering, granulation tissue, anemia, growth retardation, oral soft-tissue abnormalities, enamel hypoplasia, excessive carries (cavities), dystrophic or absent nails, death related to EB, atrophic scarring, gastrointestinal tract issues, ocular issues, respiratory tract issues, genitourinary tract issues, scalp abnormalities, and milia.

JEB-gen intermed

JEB, generalized intermediate (JEB-gen intermed) 

JEB, generalized intermediate, formerly called JEB, non-Herlitz, is a milder form of JEB. Blistering may be limited to the hands, feet, knees, and elbows, and it often improves after the newborn period. Other characteristic features of this condition include alopecia, malformed fingernails and toenails, and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. This subtype is typically associated with a normal lifespan.  

Noted Clinical Symptoms  

Generalized blistering, dystrophic or absent nails, enamel hypoplasia, atrophic scarring, milia, EB nevi, oral soft-tissue abnormalities, excessive carries (cavities), potential gastrointestinal tract, genitourinary tract, ocular, and respiratory tract issues, anemia, growth retardation, granulation tissue, and rare risk of squamous cell carcinoma or death related to EB by age 30. 

Other JEB Subtypes
JEB with pyloric atresia (JEB-PA)

Some infants born with JEB have been observed to have pyloric atresia, which is an obstruction of the lower part of the stomach (the pylorus). This obstruction prevents food from emptying out of the stomach into the intestine. Signs of pyloric atresia include vomiting, a swollen (distended) abdomen, and an absence of stool. Pyloric atresia is life-threatening and must be repaired with surgery soon after birth.  

Generalized blistering, ulcerations of skin and mucous membranes is usually evident at birth. Blistering may be mild to severe. Erosions on finger and toenails, nail dystrophy or absence of nails may be evident. Erosions and loss of hair (alopecia) upon the scalp and granulation tissue around mouth and nares may occur. There may be some scarring and thinning of the skin on affected areas (atrophic scarring). Warmer climates can exacerbate blistering.  

The infant may suffer complications such as infection, dehydration, electrolyte imbalances, respiratory, gastrointestinal, and/or genitourinary tract involvement. These complications may lead to death.  

Noted Clinical Symptoms 

Generalized blistering, dystrophic or absent nails, atrophic scarring, excessive carries (cavities), gastrointestinal tract issues (plyloric, duodenal, or anal atresia), multiple congenital genitourinary abnormalities, acquired genitourinary abnormalities, rudimentary ears, large areas of aplasia cutis (possible), ocular issues, anemia, growth retardation, and risk of death related to EB. 

JEB, late onset (JEB-LO) 

JEB-LO is a subtype of JEB is characterized by blistering of primarily the hands and feet starting in childhood.  

Noted Clinical Symptoms 

Blistering, milia, atrophic scarring, dystrophic or absent nails, hyperhidrosis, absent dermatoglyphs, mild keratoderma, oral soft-tissue abnormalities, and enamel hypoplasia. 

JEB with Respiratory and Renal Involvement (JEB-RR)

JEB-RR is a rare subtype of JEB characterized by congenital nephrotic syndrome, interstitial lung disease, mild skin fragility, fine and spare scalp hair, eyebrows, and eyelashes, nail dystrophy, distal onychosis, delayed reepithelization, healing with residual erythema. This subtype involves no scarring nor mucosal involvement.  

Noted Clinical Symptoms 

Blistering on legs & buttocks, respiratory and renal involvement at or shortly after birth, skin features within the first months of life, anemia, growth retardation, congetical nephrotic syndrome, severe respiratory distress, interstitial pneumopathy, dystrophic or absent nails, erosions, and risk of death related to EB within the first months of life. 

JEB, Inversa (JEB-inv)

JEB, Inversa is a rare severe subtype of JEB characterized by blistering and erosions confined to intertriginous skin sites (where two areas of skin may touch or rub together), the esophagus, and vagina.  

Noted Clinical Symptoms 

Intertriginous blistering, atrophic scarring, dystrophic or absent nails, gastrointestinal tract issues, increased frequency of carries (cavities), oral soft-tissue abnormalities, and enamel hypoplasia.

JEB-LOC syndrome

LOC syndrome is a subtype of JEB characterized by an altered cry in the neonatal period and by aberrant production of granulation tissue which, in particular, affects the upper airway tract, conjunctiva and periungual/subungual sites.  

Noted Clinical Symptoms 

Blistering with erosions (especially on face & neck), dystrophic or absent nails, soft-tissue abnormalities involving the Larynx, Conjunctival ocular issues, eyelid granulomas, symblepharon, respiratory tract involvement, enamel hypoplasia granulation tissue, milia, caries (cavities), anemia, growth retardation, risk of death related to EB by age 30.

Dystrophic

Dystrophic EB, or DEB, includes all EB subtypes in which blistering occurs within the uppermost dermis. Dominant Dystrophic EB (DDEB), and Recessive Dystrophic EB (RDEB) are the two clinical Major subtypes of DEB. The targeted protein in all subtypes of DEB is Collagen VII. 

DDEB-gen

DDEB, generalized (DDEB-gen) 

DDEB, generalized, formerly called DDEB, Pasini or Cockayne-Touraine, tend to be milder than the recessive forms of Dystrophic EB, with blistering often limited to the hands, feet, knees, and elbows. The blisters heal with scarring, but it is less severe. Most affected people have malformed fingernails and toenails, and the nails may be lost over time. In the mildest cases, abnormal nails are the only sign of the condition.  

RDEB-gen sev

RDEB, generalized severe (RDEB-gen sev)  

RDEB, generalized severe, formerly called RDEB, Hallopeau-Siemens, is the most severe, classic form of the RDEB. Affected infants are typically born with widespread blistering and areas of missing skin, often caused by trauma during birth. Most often, blisters are present over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Additional complications of progressive scarring can include fusion of the fingers and toes, loss of fingernails and toenails, joint deformities (contractures) that restrict movement, and eye inflammation leading to vision loss. Additionally, young adults with this form of EB have a very high risk of developing a form of skin cancer called squamous cell carcinoma, which tends to be unusually aggressive and is often life-threatening.  

Noted Clinical Symptoms  

Generalized blistering, milia, atrophic scarring, dystrophic or absent nails, anemia, growth retardation, oral soft-tissue abnormalities, excessive carries (cavities), pseudosyndactyly, gastrointestinal tract issues, EB nevi, granulation tissue (common in chronic wounds), scalp abnormalities, glomerulonephritis, renal amyloidosis, lgA nephropathy, CRF, cardiomyopathy, delayed puberty, osteoporosis, and increased risk of squamous cell carcinoma and/or death related to EB by age of 30. 

RDEB-gen intermed

RDEB, generalized intermediate (RDEB-gen intermed)  

RDEB, generalized intermediate, formerly called RDEB, non-Hallopeau-Siemens or RDEB, generalized other, is a subtype of DEB characterized by generalized cutaneous and mucosal blistering that is not associated with severe deformities. This form of the condition is somewhat less severe than the classic type and includes a range of subtypes. Blistering is limited to the hands, feet, knees, and elbows in mild cases, but may be widespread in more severe cases. Affected people often have malformed fingernails and toenails. RDEB-gen intermed involves scarring in the areas where blisters occur, but this form of the condition does not cause the severe scarring characteristic of RDEB-gen sev. 

Noted Clinical Symptoms  

Generalized blistering, dystrophic or absent nails, milia, atrophic scarring, gastrointestinal tract issues, increased frequency of caries (cavities), ocular issues, EB nevi, keratoderma, granulation tissue (uncommon), anemia, growth retardation, increased risk of squamous cell carcinoma and/or death related to EB by age of 30. 

RDEB-inv

RDEB, inversa (RDEB-inv)  

RDEB, inversa is rare subtype of DEB characterized by blisters and erosions which are primarily confined to intertriginous skin sites, the base of the neck, the uppermost back, and the lumbosacral area.  

Noted Clinical Symptoms  

Intertriginous, acral, lumbosacral, and axial blistering; dystrophic or absent nails, gastrointestinal tract issues, genitourinary tract issues, oral soft-tissue abnormalities, milia, atrophic scarring, external auditory canal stenosis, and pseudosyndactyly. 

Other DDEB Subtypes (rare variants)
DDEB, acral (DDEB-ac) 

DDEB, acral is a very rare subtype of DEB characterized by blistering confined primarily to the hands and feet. In the case of DDEB, acral, the disease is inherited in an autosomal dominant manner. 

DDEB, pretibial (DDEB-pt)

DDEB, pretibial is a rare form of DEB, in which characteristic blisters and skin erosions develop predominantly on the front of the lower legs (known as the "pretibial region"). In some affected people, the feet, hands and/or nails may also be affected. Healing of the blisters is generally associated with hypertrophic scarring. In the case of DDEB, pretibial, the disease is inherited in an autosomal dominant manner. 

Noted Clinical Symptoms 

Pretibial blistering of the hands, feet, fingers, and toes; milia, atrophic scarring, dystrophic or absent nails, lichenoid papules or plaques, atrophic plaques, oral soft-tissue abnormalities, ocular issues, risk of squamous cell carcinoma by age 30. 

DDEB, pruriginosa (DDEB-pr)

DDEB pruriginosa is a rare subtype of DEB characterized by generalized or localized skin lesions associated with severe, if not intractable, pruritus. In the case of DDEB, pruriginosa, the disease is inherited in an autosomal dominant manner.  

Noted Clinical Symptoms  

Generalized or localized blistering, milia, atrophic scarring, dystrophic or absent nails, severe pruritus (itching), oral soft-tissue abnormalities, ocular issues, risk of squamous cell carcinoma by age 30, anemia, and growth retardation. 

DDEB, nails only (DDEB-na)

DDEB, nails only Dystrophic epidermolysis bullosa, nails only, is a rare subtype of DEB that shows no blistering and that is characterized by dystrophic or absent nails.  

Noted Clinical Symptoms 

Dystrophic or absent nails 

DDEB, bullous dermolysis of the newborn (DDEB-BDN)

In this rare form of DDEB, newborns may develop blisters over a large area after birth, which then heal relatively rapidly. These babies should be observed and treated just like all other newborns with EB. After a few weeks, blister formation may occur very rarely or stop and become clinically inactive.

Noted Clinical Symptoms  

Blistering may have generalized distribution, milia, atrophic scarring dystrophic or absent nails, and oral soft-tissue abnormalities. 

Other RDEB Subtypes
RDEB, localized (RDEB-loc) 

RDEB, localized is a rare form of DEB, characterized by blistering predominantly of the hands and feet. Those with RDEB, localized experience symptoms typical for DEB such as blisters, milia, atrophic scarring, and dystrophic or absent nails.  

Noted Clinical Symptoms 

Blistering (hands & feet), milia, atrophic scarring, dystrophic or absent nails, oral soft-tissue abnormalities, ocular issues, keratoderma (rare), potential increased risk of squamous cell carcinoma over the age of 30. 

RDEB, pretibial (RDEB-pt)

RDEB, pretibial is a rare form of DEB, in which characteristic blisters and skin erosions develop predominantly on the front of the lower legs (known as the "pretibial region"). In some affected people, the feet, hands and/or nails may also be affected. Healing of the blisters is generally associated with hypertrophic scarring. In the case of RDEB, pretibial, the disease is inherited in an autosomal recessive manner.  

Noted Clinical Symptoms  

Pretibital blistering of the hands, feet, fingers, and toes; milia, atrophic scarring, dystrophic or absent nails, lichenoid papules or plaques, atrophic plaques, oral soft-tissue abnormalities, ocular issues, risk of squamous cell carcinoma by age 30. 

RDEB, pruriginosa (RDEB-pr)

RDEB pruriginosa is a rare subtype of DEB characterized by generalized or localized skin lesions associated with severe, if not intractable, pruritus. In the case of DDEB, pruriginosa, the disease is inherited in an autosomal recessive manner. 

RDEB, centripetalis (RDEB-ce)

Noted Clinical Symptoms 

Pretibial blistering (fingers & toes), dystrophic or absent nails, milia, atrophic scarring, granulation tissue, and oral soft-tissue abnormalities. 

Kindler

Kindler Syndrome, which was added to the EB classification in 2008, describes a specific entity which is characterized by the presence of clinical phenotypic features unique EB (most notably photosensitivity) and blistering that arises in multiple levels within and/or beneath the BMZ, rather than within a discrete plane, as occurs in all other EB types. There are no known subtypes of Kindler Syndrome. 

Noted Clinical Symptoms 

Generalized blistering, atrophic scarring, dystrophic or absent nails, keratoderma pseudosyndactyly (or digital tapering), poikilioderma, photosensitivity, skin atrophy, bone abnormalities (rare), oral soft-tissue abnormalities (gingival hyperplasia), colitis (may be severe), esophagitis, esophageal strictures, urethral strictures, ectropion, increased risk of squamous cell carcinoma over the age of 30, and death related to Kindler syndrome (uncommon). 

EB Schematic

Where in the skin do blisters develop?  

The level of the skin in which blisters develop is dependent on which type of EB the person has. On the right is a schematic representation of the epidermis, the skin basement membrane zone, the location of specific proteins pertinent to the pathogenesis of epidermolysis bullosa (EB), and the level in which blisters develop in different EB types.


The scheme depicts the cell layers of the epidermis, the basal keratinocytes, and above them the suprabasal keratinocyte layers (spinous and granular layers), which are covered by the horny layer (pink). The epidermis is attached to the dermis by the bilayered basement membrane consisting of lamina lucida and lamina densa (red bar). On the left, the level of blister formation is indicated. 

Level of Blister Formation by Major EB Type:   

  • In EB simplex (EBS) suprabasal, the blisters form within the middle/upper epidermal layers, depending on which protein is mutated.   
     
  • In EBS basal, the cleavage plain is within the basal keratinocytes.  
     
  • In junctional EB (JEB), the separation takes place within the lamina lucida.  

 

  • In dystrophic EB (DEB), the separation takes place within the sublamina densa region within the uppermost dermis.   
     
  • In Kindler syndrome (KS), cleavage can occur within the basal keratinocytes, at the level of the lamina lucida or below the lamina densa.