The presentation and primary symptoms of all subtypes of epidermolysis bullosa are similar. However the age at onset, dermal layer involved, severity and extent of blistering differ [1] [3].

• Epidermolysis bullosa simplex is characterized by blistering of the intraepidermal layer, often on the palms and soles [3] [4] [12]. Internal involvement is mild. Lesions occur following a trauma to the skin and heal without scarring. It is dominantly inherited, but recessive cases have been reported [3] [10]. 
• Junctional epidermolysis bullosa has blistering at the intralamina layer. There are lethal and non-lethal forms of this subtype [6]. Lethal junctional epidermolysis bullosa is characterized by generalized blistering at birth [7]. Mucosal involvement is common. Signs include hoarse cry, cough, and other respiratory difficulties [6] [8]. These infants are at higher risk for death from sepsis or respiratory complications and most do not survive past infancy [8] [12]. Nonlethal junctional epidermolysis bullosa presents with generalized blistering without the more severe internal involvement [6] [7]. Mucous membranes may be affected resulting in strictures. Infants generally survive infancy and clinically improve with age [7]. Blisters heal with a distinctive atrophic scarring pattern [12] [14]. 
• Dystrophic epidermolysis bullosa presents at birth or early infancy with generalized blistering [3] [6]. As the child ages the pattern changes to more localized blistering [6]. With this subtype dystrophic or absent nails and dental abnormalities are common [6] [8]. Blisters heal with dystrophic scarring with milia (1 to 4mm white papules) due to damage to hair follicles [8]. Blistering of the hands and feet can be severe. This can produce pseudosyndactyly (mitten-hand deformity) [13] [15]. With age flexion contractures of the extremities are common [13]. Involvement of internal mucus membranes can result in esophageal strictures, urethral and anal stenosis, phimosis, and corneal scarring [6] [15]. Malabsorption may occur as a result of gastrointestinal involvement [6]. 
• Hemidesmosomal epidermolysis bullosa produces blistering at the lowest aspect of the basal layer where the basal epidermis fastens to the basement membrane [3] [5]. This form of the disease may be associated with muscular dystrophy or pyloric atresia [5]. It is associated with severe generalized blistering and extensive internal involvement. For most patients prognosis is poor and is usually fatal during infancy [8]. 

Patients with epidermolysis bullosa may develop blepharitis and scarring of the conjunctivae and cornea, obstruction of tear ducts, and blistering of the eyelids [1] [3]. 

The most severe forms of epidermolysis bullosa are associated with clinically significant complications that may lead to permanent disability or death [1]. Complications include the following [1] [3]:

• Immunologic abnormalities such as decreased lymphocyte production and poor nutritional status. These conditions lower resistance to infections. Patients are susceptible to developing life threatening sepsis. 
• Squamous cell carcinoma often develops in the chronic wounds or scars of epidermolysis bullosa patients. This is an invasive neoplasm and is highly metastatic. 
• Pseudosyndactyly (mitten-hand deformity) is a frequent complication resulting from extensive blistering and scarring of the fingers and toes.
• Mucus membrane complications of the gastrointestinal, respiratory, and genitourinary tracts may cause permanent damage due to scarring, strictures, stenosis and obstructions. 

• Anemia

  In one severe form, recessive dystrophic epidermolysis bullosa, chronic anemia is common. [ncbi.nlm.nih.gov]

  Complications from EB Complications include -malnutrition and anemia -infection of the blisters -problems involving the internal organs -blindness -Cell skin cancer -loss of limb function -the death rate is 87% for the first year of infants. [de.slideshare.net]

  Anemia: Patients with more severe cases of EB often suffer from chronic anemia due to iron deficiency, chronic disease, and blood loss from open wounds. [chop.edu]

  Patients with more severe disease may experience a variety of serious medical conditions including blisters in the lining of the mouth and digestive tract, poor growth and nutrition, and anemia. [cincinnatichildrens.org]

  Chronic anemia reduces energy and growth is retarded. There is little hope for life beyond 30 years. Children with EB are often referred to as Butterfly Children because their skin is as fragile as a butterfly’s wings. [ebmrf.org]

• Malnutrition

  Complications from EB Complications include -malnutrition and anemia -infection of the blisters -problems involving the internal organs -blindness -Cell skin cancer -loss of limb function -the death rate is 87% for the first year of infants. [de.slideshare.net]

  Malnutrition may result in vitamin and mineral deficient states, leading to stunted growth, affecting normal growth Scarring can result in disfigurement-like fusion of the fingers and toes. [dovemed.com]

  This may result in developmental trauma, malnutrition, infection, or even death. Resources for Epidermolysis Bullosa (EB) EB Promise - For all families adopting a child with Epidermolysis Bullosa [rainbowkids.com]

  Not only does EB affect the external skin, but also the lining of the mouth and throat, the eyes and digestive system, leading to malnutrition, anaemia, intolerable itch and pain.4 No cure Current treatment is focused on wound care which involves daily [amrytpharma.com]

  This scarring can cause chewing and swallowing problems that lead to malnutrition and slowed growth. [healthline.com]

• Crying

  "I started today crying, and will get into my bed crying," she admitted. Actor Colin expressed his admiration for Emma, saying he couldn't get his head around how "amazing" he found her to be. [web.archive.org]

  Infants and children with the disease often develop a hoarse cry, cough, and other breathing problems. They are prone to developing fevers, often lose their fingernails and toenails, and have poorly-formed tooth enamel. [counsyl.com]

  When an infant’s lungs are affected, he or she will have a distinctive, hoarse sounding cry, and may have a persistent cough and trouble breathing. [disabilitybenefitscenter.org]

  Internal complications may produce a hoarse cry, cough and respiratory difficulty. There is risk of death from sepsis or other complications due to epithelial dysfunction, and they usually die in infancy. [patient.info]

• Nail Abnormality

  Symptoms of the condition, such as abnormal nails, thickened skin on the palms or feet, and blistering, typically appear in infancy or childhood. However, the condition can manifest at any age. EB varies from minor to fatal. [fulgentgenetics.com]

  Nail abnormalities along with multiple cutaneous bullae and erosions were a prominent early physical finding in this cohort, with 6 of 10 patients overall developing nail dystrophy (n = 3), anonychia (n = 1), or subungual erosions (n = 3) within several [jamanetwork.com]

  abnormalities, leading to classification as mitis form. [scielo.br]

  Nail abnormalities were common in all types of epidermolysis bullosa. Of note, patients with epidermolysis bullosa simplex had fewer oral cavity and dental problems than patients with other disease types. [ojrd.biomedcentral.com]

• Wound Infection

  Many children with EB die at a young age due to infection, nutrition deficiencies or other causes. Historically, treatment has addressed the symptoms, including prevention of pain, wounds, infection and itching. [bmt.umn.edu]

  The most significant problems in severe forms of EB are the life-long presence of blistering, wound infections and partially chronic wounds resulting in pain, scarring and immobility. [amrytpharma.com]

  […] properties that helped heal infected wounds.[9] Moreover, honey was used as a topical ointment. [en.wikipedia.org]

  Surveillance Surveillance for infection and proper wound healing is indicated. Agents/Circumstances to Avoid Excessive heat may exacerbate blistering and infection in EBS. [ncbi.nlm.nih.gov]

  Critically colonized and infected wounds To early diagnose a critically colonized or infected wound the following parameters and features should be considered: ✓ wound history: several week duration, recent size extension and exudate increase; ✓ wound [ojrd.biomedcentral.com]

• Hoarseness

  Infants and children with the disease often develop a hoarse cry, cough, and other breathing problems. They are prone to developing fevers, often lose their fingernails and toenails, and have poorly-formed tooth enamel. [counsyl.com]

  When an infant’s lungs are affected, he or she will have a distinctive, hoarse sounding cry, and may have a persistent cough and trouble breathing. [disabilitybenefitscenter.org]

  Internal complications may produce a hoarse cry, cough and respiratory difficulty. There is risk of death from sepsis or other complications due to epithelial dysfunction, and they usually die in infancy. [patient.info]

  The condition can also affect the lungs, resulting in hoarseness, cough and other respiratory complications. Most cases of junctional epidermolysis bullosa are very severe. [disability-benefits-help.org]

  […] unusually shaped nails Thickened skin on the palms of the hands and soles of the feet Small white bumps on the skin Itchy, painful skin Skin that appears unusually thin Difficulty swallowing (caused by blisters in the mouth and throat) Constipation Hoarse-sounding [chop.edu]

• Failure to Thrive

  For some types of EB, the internal mucosa is also affected: nutrition can be compromised, resulting in osteoporosis, and general failure to thrive: quite young children can depend on gastrostomies or require highly specialised diets. [debra-international.org]

  […] to thrive, anemia, infectious and respiratory complications, etc. [orpha.net]

  Sepsis, respiratory failure and failure to thrive are the main causes. [ 26 ] Some subtypes, especially the milder EB forms, improve with age. [ 3 ] [patient.info]

  […] to thrive, esophageal strictures and debilitating hand and foot deformities Diagnosis: usually requires focused lab testing, such as transmission EM (gold standard), immunofluorescence antigen mapping or immunohistochemical staining with EB specific [pathologyoutlines.com]

• Dysphagia

  Rare case of dysphagia, skin blistering, missing nails in a young boy. World J Gastrointest Endosc, 7 (2015), pp. 154-158 [5] Z. Djuric, A. Nagorni, D. Zivanovic. [revistagastroenterologiamexico.org]

  Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland. [ncbi.nlm.nih.gov]

  Since early childhood, he has been on a diet of milk shakes, baby food, etc. because of dysphagia. [pubs.rsna.org]

  […] the soles of the feet scalp blistering, scarring and hair loss (scarring alopecia) thin-appearing skin (atrophic scarring) tiny white skin bumps or pimples (milia) dental problems, such as tooth decay from poorly-formed enamel difficulty swallowing (dysphagia [skinhealthinstitute.org.au]

• Heart Disease

  diseases, a study suggests. [epidermolysisbullosanews.com]

  There is also a strong environmental component to many of them (e.g., blood pressure). asthma autoimmune diseases such as multiple sclerosis cancers ciliopathies cleft palate diabetes heart disease hypertension inflammatory bowel disease intellectual [en.wikipedia.org]

  Common known causes of death in DEB patients include squamous cell carcinoma, sepsis, pneumonia, respiratory failure, failure to thrive, renal failure, heart disease, stroke, and auto-accidents. [nature.com]

• Dental Caries

  Regular dental visits are required for EB patients as good oral hygiene is essential, especially in patients with DEB and JEB, who are more prone to developing dental caries. [news-medical.net]

  Extracutaneous 4 manifestations include: dystrophy or absence of nails, sparse head hair or alopecia, excessive dental caries, microstomia, mouth ulcers, lingual tip fixation to the floor of the oral cavity, pseudosyndactylia, syndactylia and deformities [revistanefrologia.com]

  The psychological intervention required during the dental treatment of these patients is also presented. Uniterms: Epidermolysis bullosa. Oral manifestations. Dental caries. [scielo.br]

  Many patients with epidermolysis bullosa develop dental caries despite good care, because of enamel erosion.Oral candidiasis often occurs and can be treated with an anticandidal medication. [symptoma.com]

  Good dental hygiene and regular dental checks are recommended. Many patients with JEB and DEB develop dental caries because of enamel defects. Oral mucosal involvement can accompany severe forms of JEB and DEB. [patient.info]

• Tooth Loss

  Severe forms of the recessive subtype may lead to eye damage, tooth loss, blistering inside the mouth and gastrointestinal tract, and fusing together of the fingers or toes. There is also a high risk of developing skin cancer. [niams.nih.gov]

  Peri- and intraoral blisters, ankyloglossia, microstoma, dental enamel hypoplasia, tooth dysplasia, excessive caries, premature tooth loss, and tooth misalignment have been described(6). [medichub.ro]

• Blister

  Blisters heal with a distinctive atrophic scarring pattern. Dystrophic epidermolysis bullosa presents at birth or early infancy with generalized blistering. As the child ages the pattern changes to more localized blistering. [symptoma.com]

  The distribution, extent and severity of skin blistering will be dependent on the particular subtype of EB. In milder forms of EB the blistering may be confined only to the hands and feet and usually heals without leaving scars. [dermcoll.edu.au]

  Infants have blistering with loss of skin all over their bodies. Fingernails are usually lost and mucosal surfaces throughout the body blister and can develop scars. [aocd.org]

  Wound care Blisters should be popped with a sterile needle as this will make your child feel more comfortable and will stop the blisters from getting bigger. Once popped, the roof of the blister should be left on the skin to improve healing. [rch.org.au]

  Blistering begins at birth or shortly afterwards. Much of the skin is covered in blisters and there is extensive internal blistering. [stanfordchildrens.org]

• Skin Disease

  Epidermolysis Bullosa Hereditaria definition Epidermolysis Bullosa Hereditaria refers to a group of rare, hereditary skin diseases. [dermis.net]

  Abnormalities Congenital Abnormalities Skin Diseases, Genetic Genetic Diseases, Inborn Skin Diseases Skin Diseases, Vesiculobullous Collagen Diseases Connective Tissue Diseases [clinicaltrials.gov]

  Jonathan Pitre, 17, of Russell, Ont., suffered from epidermolysis bullosa, or EB, a painful and deadly skin disease. Jonathan, who worked diligently at raising awareness of the disease, has died. [cbc.ca]

  Learn about this topic in these articles: formation In skin disease: Distribution …hereditary blistering disorders collectively called epidermolysis bullosa owe their distributions to local trauma; lesions that show a predilection for the elbows, knees [britannica.com]

  Skinzy - The AI-based app for skin disease prediction 2016-07-06 Skin Disease And Treatment Skin Disease And Treatment 2019-02-02 Skin Doctor - All Skin Diseases and Treatment Skin Disease with Overview, prevention, diagnosis and treatment with photo [apkgk.com]

• Alopecia

  These patients had generalized cutaneous findings, including milia, atrophicscarring, nail dystrophy, and scalp alopecia, which have been classically attributed to either junctional or dystrophic EB. [jamanetwork.com]

  […] friction deformity or loss of fingernails and toenails (nail dystrophy) internal blistering, including on the vocal cords, oesophagus and upper airway skin thickening on the palms and the soles of the feet scalp blistering, scarring and hair loss (scarring alopecia [skinhealthinstitute.org.au]

  Extracutaneous 4 manifestations include: dystrophy or absence of nails, sparse head hair or alopecia, excessive dental caries, microstomia, mouth ulcers, lingual tip fixation to the floor of the oral cavity, pseudosyndactylia, syndactylia and deformities [revistanefrologia.com]

  Other characteristic features of this condition include alopecia, malformed fingernails and toenails, and irregular tooth enamel. [ghr.nlm.nih.gov]

  Darker Skin Tones Skin care secrets Hair care Hair loss Diseases & Conditions Acne Dark spots Dry skin Light spots Razor bumps Caring for Black hair Scalp psoriasis Weaves & extensions Central centrifugal cicatricial alopecia Frontal fibrosing alopecia [aad.org]

• Oral Blisters

  Cutaneous manifestations Blisters ranging from small to large bullae Erosions Hemorrhagic crusts Chronic wounds Scars Contractures Extracutaneous findings Mouth Microstomia Dental decays Bleeding gums Ankyloglossia Oral ulcers Eyes Erosions/blisters Keratitis [clinicaladvisor.com]

  One key limitation is lethality, a likely consequence of severe oral blistering ( SI Fig. 7 ). [dx.doi.org]

  There has historically been a higher incidence in women.[4] Signs and symptoms[edit] Pemphigus vulgaris most commonly presents with oral blisters (buccal and palatine mucosa, especially), but also includes cutaneous blisters. [en.wikipedia.org]

• Pachyonychia

  Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients. 61 24 Bolling MC...Jonkman MF 21375516 2011 26 Botulinum toxin in the treatment of sweat-worsened foot problems in patients with epidermolysis bullosa simplex and pachyonychia [malacards.org]

  […] bullosa mitis Juvenile elastoma Keratoderma areata Keratoderma due to Dowling-Meara type epidermolysis bullosa simplex Keratoderma plantare sulcata Keratoderma with deafness Keratoderma with mental retardation and spastic paraplegia Keratoderma with pachyonychia [icd9data.com]

  Plakoglobin PKP1 Plakophilin 1 DSC3 Desmocollin 3 DSG3 Desmoglein 3 Hyperkeratotic disorders with skin fragility Intraepidermal Keratinopathic ichthyoses Autosomal dominant KRT1, KRT10, KRT2 Keratin 1, 10, 2 Autosomal recessive KRT10 Keratin 10 Intraepidermal Pachyonychia [onlinelibrary.wiley.com]

  Botulinum toxin in the treatment of sweat-worsened foot problems in patients with epidermolysis bullosa simplex and pachyonychia congenita. [ncbi.nlm.nih.gov]

DNA analysis for mutations is the definitive test for diagnosis of epidermolysis bullosa and the classification of subtype by identifying the underlying molecular defect [2] [4] [5]. 

Laboratory tests

Biopsy of the lesions can further identify the subtype and level of dermal involvement [10] [13]. Procedures for this evaluation include [13]:

• Routine light microscopy cannot be used to make a diagnosis of epidermolysis bullosa, but is useful to exclude other diagnoses [13]. 
• Electron microscopy is the standard for determining the severity of the disease, identifying morphology, and determining subtype [10]. 
• Immunofluorescent microscopy indicates the level of the blistering and the molecular defect [13].
• Bacterial cultures are indicated for poorly healing wounds or wounds that appear infected.

Patient history should include [1] [3]:

• Age of onset
• Size, frequency, and location of blisters
• Inciting factors
• Prior treatment
• Extent of pain or pruritus

A complete physical examination with inspection of all skin, conjunctival, oral, and genital mucosae should be done on any patient suspected of having epidermolysis bullosa [1] [3]. This should include evaluation of the size, location, and character of blisters [3]. The character of the lesions varies by subtype and the layer of dermal involvement [3]:

• Superficial blisters present as crusted erosions
• Intraepidermal blisters are flaccid and expand under pressure
• Intralamina lucida blisters are tense and heal with atrophy but no scarring
• Sublamina densa blisters heal with scarring and milia formation

Imaging

Upper GI series or endoscopy may be useful to evaluate gastrointestinal abnormalities secondary to strictures [3].

Prenatal diagnosis

Reliable prenatal diagnosis is now possible. Diagnostic tests for epidermolysis bullosa include prenatal testing based on a better understanding of the genes responsible for the disease [2] [7] [9]. DNA for prenatal diagnosis can be obtained as a chorionic villi sample as early as the ninth week of gestation. A Western blot analysis of amniotic fluid drawn after the eleventh week [7] [9].

There is currently no preventive or curative therapy for epidermolysis bullosa. Molecular therapies, protein and gene therapy are being researched and are at the preclinical stage [1] [2] [12]. The goal of gene therapy is to provide genes that will restore normal protein production and solutions to the skin fragility found in patients with epidermolysis bullosa [2] [12]. Gene therapy for Epidermolysis bullosa has been used and shown to be effective in small clinical trials.

These new treatment modalities may provide engineered tissue grafts produced by recombinant methods containing the missing or defective proteins, especially type VII collagen, are applied directly to blistered skin [13 ][14].

Further clinical trials are currently underway. In one, bone marrow transplantation is used for the delivery of corrective skin cells. Patients undergo bone marrow ablation and immunosuppression before transplantation of healthy marrow [2] [13], therefore the procedure is not without risk.

Current treatment and management of epidermolysis bullosa is supportive [15]. The goal of therapy is effective wound care to prevent infection, scarring, and sepsis [1] [3]. Beyond this is the prevention, early identification, and repair of damage and dysfunction resulting from extensive blistering [1] [3].

Wound care and healing is complicated by many factors including traumatic injury, skin fragility, exposure to bacteria, nutritional status, tissue anoxia, and aging [1]. Optimizing wound healing in patients with epidermolysis bullosa involves controlling all of these factors.

Blisters should be treated aggressively with wound and nutritional management [1]. Regular whirlpool therapy can help with gentle cleansing and debridement of wounds [3]. This should be followed by sterile dressings using semiocclusive non-stick materials [1]. Never apply tape to the skin of patients with Epidermolysis bullosa [1] [2]. Take great care to avoid trauma to the skin that will cause additional blistering [1].

Gastrointestinal blistering causes some of the most disabling complications of Epidermolysis bullosa. Pain, dysphagia, mal-absorption, and malnutrition can result from these complications. Management of the lesions may include the use of phenytoin and oral steroid solutions to reduce the symptoms [1] [3].

Oral mucosal involvement can accompany severe forms of epidermolysis bullosa. Good oral and dental hygiene is essential; gentle tooth brushing, routine dental care, avoidance of harsh mouthwashes, normal saline rinses, gently cleansing of mucosal surfaces [1] [3]. Many patients with epidermolysis bullosa develop dental caries despite good care, because of enamel erosion [1].
Oral candidiasis often occurs and can be treated with an anticandidal medication [3].

Ocular complications, corneal abrasions, conjunctivitis, corneal scarring, are also common in patients with epidermolysis bullosa [1]. Corneal erosions can be treated with antibiotic ointments and cycloplegic agents to reduce ciliary spasm and provide comfort. Ocular lubricants may also reduce irritation [3].

Chronic forms may be treated with short-term high doses of systemic corticosteroids and a other immunosuppressants to reduce the severity of blister formation [11]. However long-term steroid therapy is contraindicated because it suppresses the body’s defense against infection. Some research has shown success with colchicine, dapsone, infliximab and immunoglobulin [11].

Surgery may be required to repair damage done by repeated blistering and scarring as a result of Epidermolysis bullosa. Surgical management can include the following [1] [3]:

• Esophageal dilation to relieve strictures
• Reconstruction of Mitten deformity of the hands
• Excision of invasive, aggressive squamous cell carcinoma
• Skin equivalent grafts: allografts, from non-related donors [15] are an effective short-term therapy for chronic nonhealing wounds [15]

Considerations for nutritional management include the following [1] [3]:

• Increased needs: Skin involvement and healing require increased caloric and protein intake. Nutritional deficiencies inhibit wound healing. 
• Oropharyngeal and gastrointestinal lesions affect nutrition of patients with epidermolysis bullosa.

Epidermolysis bullosa is a genetic disease and there are no drugs to correct or cure the underlying molecular defects. No drugs improve the symptoms of epidermolysis bullosa significantly or consistently [1].

Antibiotics, topical, oral, and intravenous, are used routinely to treat and prevent infection. The specific medication is adjusted according to the causative bacterium.

Genetic counseling is beneficial for families and siblings of patients with inherited epidermolysis bullosa that are considering children. Education of patient and family members is essential. Prenatal testing along with appropriate counseling has become an integral part of clinical management [9].

Epidermolysis bullosa simple tends to have a good prognosis. However, the disease can occasionally be severe, especially during the neonatal period [1] [3] [10].

Epidermolysis bullosa simplex, dystrophic epidermolysis bullosa and milder forms of junctional epidermolysis bullosa may not affect a patient's life expectancy [1] [3].

Infection is the leading cause of death at all ages [8]. Neonates, in particular, with extensive skin involvement may die as a result of overwhelming sepsis [9] [10]. Extensive areas of skin involvement cause the loss of this barrier to pathogens [3].

Squamous cell carcinoma often occurs with epidermolysis bullosa. This is an aggressive cancer and a significant cause of death in patients with this disease [1] [4].

The milder forms of epidermolysis bullosa are lifelong diseases. Some subtypes improve with age [3].

Epidermolysis bullosa is a group of severe, inherited blistering disorders which often results in death during infancy [7]. Over the last 25 years there have been major advances in prenatal testing for inherited skin disorders [8] [9]. Since 2000 many advances have been made in the understanding of epidermolysis bullosa due to the identification of the genetic mutations responsible for its pathogenesis [6] [10].

Onset of epidermolysis bullosa is at birth or shortly after [8]. Mild cases of epidermolysis bullosa simplex may remain undetected until adulthood or occasionally remain undiagnosed [3].

Epidermolysis bullosa subtypes are classified according to skin morphology [1] [3] [6]. The 4 major categories include [3] [6]:

• Epidermolysis bullosa simplex (intraepidermal skin separation)
• Junctional epidermolysis bullosa (skin separation in lamina lucida or central basal membrane)
• Dystrophic epidermolysis bullosa (sublamina dermal basal membrane separation)
• Hemidesmosomal epidermolysis bullosa (separation at the lowest aspect of the basal keratinocyte layer)

Approximately 92% of cases are epidermolysis bullosa simplex, 5% dystrophic epidermolysis bullosa, 1% junctional epidermolysis bullosa, and 1% hemidesmosomal epidermolysis bullosa. The rest are unclassified [7].

Epidermolysis bullosa acquisita is a recently identified, rare acquired form of the disease [11]. This variant presents in adulthood causing chronic disease [5] [11].

Epidermolysis bullosa simplex is generally associated with little or no extracutaneous involvement, while the more severe junctional, dystrophic, and hemidesmosomal forms may produce significant multi-organ system involvement [6].

Junctional epidermolysis bullosa has the highest risk during infancy with an estimated mortality rate of 87% during the first year of life [8]. The major cause of death is due to infection and subsequent sepsis [5] [8].

In patients with epidermolysis bullosa who survive childhood, the most common cause of death is metastatic squamous cell carcinoma [8].

The incidence of epidermolysis bullosa is reported to be 50 cases occur per 1 million live births [1] [8]. However, mild cases of epidermolysis bullosa simplex may not be identified and reported. This affects the reported incidence of the disease [1]. 

Incidence has been reported to be much lower in some parts of the world; in Japan 7.8 cases per million live births, and in Croatia 9.6 cases per million live births [8].

The overall annual mortality rate is 0.103 deaths per 100, 000 population [8]. The mortality rate is highest during infancy [1] [3].
The mortality rate is much higher among blacks (0.192 death per 100 000) than whites (0.025 per 100 000) [8].

The continuous renewal of human epidermis is mediated by stem cells contained in the epidermal basal layer and in hair follicles [12]. The skin and mucus membranes have a complex basilar membrane made up of specialized keratin-containing intermediate filaments that connect one layer of the dermis to another [12]. Many intracellular proteins, including plectin, laminin 5 and laminin 6, and type VII collagen [7] [13], bind these anchoring filaments to anchoring fibrils. Anchoring fibrils are critical for stable adherence of the epidermis to the underlying dermis [8] [9]. Aberrations in this network, due to genetic abnormalities, result in fragility of the skin [2] [12].

Epidermolysis bullosa occurs due to keratin gene mutations that interfere with keratin filament production [14]. Mutations of the genes coding for these essential proteins are the cause of the disease [7] [14]. As many as 10 genes have been identified as responsible for epidermolysis bullosa [3] [14]. These proteins are critical for epidermal-dermal adherence [13].

Mal-attachment of the dermal layers allows slippage of the skin layers that cause the blistering and fragility that characterize the disorder. The specific gene mutation and resulting protein deficiency determine the layer of dermis involved and variations in the symptoms of the subtypes [2].

The one variant in which the pathogenesis is different is epidermolysis bullosa acquisita (EBA) [11]. This variant is acquired rather than inherited. Autoimmunity against type VII collagen protein is thought to be the cause [11].

The incidence of epidermolysis bullosa cannot currently be prevented. Research is aimed at the identification of therapeutic interventions, including gene therapy, recombinant protein infusions, intradermal injection of allogeneic fibroblasts, and stem cell transplantation [1] [15]. New therapies may eventually lead to a cure for this disease [1] [3].

Today what can be done is prevention of the complications and deformities associated with the disease. The development of blisters can in part be reduced by [1] [3]:

• Preventing trauma to the skin
• Padding of limbs
• Soft mechanical diet

Strictly aseptic wound care and early identification and treatment of infections can prevent life-threatening sepsis [3].

The development of prenatal testing can be of benefit to families at risk of having children with epidermolysis bullosa in the absence of a cure [4] [9].

Epidermolysis bullosa (EB) refers to a group of genetic disorders characterized by fragility and blistering of the skin in response to mechanical injury [1] [2]. There are multiple variants of the disease with similar presentations and common, but not identical, pathogenesis [3] [4]. Most forms are autosomal dominant inherited, however some variants have been identified as autosomal recessive and at least one as an acquired disorder [2] [5].

Classification of epidermolysis bullosa is based on symptoms, severity, and the level of tissue separation within the cutaneous basilar membrane zone [2]. The most common subcategories include simplex, hemidesmosomal, junctional and dystrophic variants [2] [6].

The blistering of epidermolysis bullosa may be localized or generalized and may be associated with abnormal wound healing [1]. In some instances there is involvement of the mucus membrane lining the internal organs [6].

The extensive blistering and superficial tissue loss in epidermolysis bullosa may result in infection, sepsis, and death. Neonates and early infants are at highest risk [3]. Other complications of the disorder are scarring, and strictures, obstructions and deformities due to scarring [4].

What is epidermolysis bullosa?

Epidermolysis bullosa is a group of genetically inherited disorders. They are characterized by extremely fragility and blistering of the skin resulting from minimal trauma. It is divided into three sub-types according to severity of symptoms, presentation, and layer of dermis involved. The more severe forms present at birth or early infancy and are often fatal. Milder cases may not present until later and, though not curable, can be managed medically.

What are the symptoms?

The primary symptoms of epidermolysis bullosa are skin fragility and blistering. The characteristics of the blisters and area of involvement varies depending on the subtype of the disease.
Blistering and skin damage can occur on any skin surface and usually involves mucous membranes as well. Mucosal involvement can affect the mucous lining of the mouth, nose, throat, eyes, urinary tract, reproductive system gastrointestinal tract, or respiratory system. Damage can cause scarring, obstruction, strictures, and deformities of the involved structures.

What causes epidermolysis bullosa?

Epidermolysis bullosa is caused by an inherited mutation of a gene responsible for the production of one of several proteins. These proteins are necessary for the construction of filaments that connect one layer of the dermis to another. Without these filaments the layers slip resulting in damage to the tissue and blister formation.

Who gets epidermolysis bullosa?

Epidermolysis bullosa is usually a autosomal, dominant or recessive, disorder, which means that fetuses inherit the gene mutation from their parents. It is a very rare condition, occurring in only 5 infants for every 100,000 live births. A few cases of acquired Epidermolysis bullosa have been reported. These individuals do not present until much later in life.

How is it diagnosed?

Epidermolysis bullosa is diagnosed by DNA analysis and the presence of one of the specific gene mutations. The disease is suspected by the clinical symptoms. Biopsy and electron microscopic examination of the blisters help determine the specific subtype. The disease can be diagnosed prenatally by chorionic villi or amniotic fluid testing.

How is epidermolysis bullosa treated?

Epidermolysis bullosa is treated symptomatically to provide comfort and prevent complications such as infection, scarring, stricture, obstruction, and deformity. There are techniques currently being researched to correct the underlying gene mutations. These include recombinant DNA and stem cell techniques.

What are the complications?

The complications of epidermolysis bullosa include:

• Infection and subsequent sepsis
• Strictures of the esophagus
• Scarring of the trachea and respiratory tract
• Scarring and strictures of the stomach and intestinal tract
• Scarring and deformities of the hands and feet

How can it be prevented?

The symptoms of epidermolysis bullosa are treated to prevent the complications of infection and deformity. Management should include:

• Aseptic careful treatment of blisters to prevent infection
• Antibiotics both oral and topical
• Care to prevent skin trauma
• Physical therapy to prevent contracture deformities
• Corticosteroids during acute exacerbations

1. Fine JD. Inherited Epidermolysis bullosa: past, present, and future. Ann N Y Acad Sci. Apr 2010;1194:213-22.
2. Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of Epidermolysis bullosa. Matrix Biol. Feb 1999;18(1):29-42.
3. Sawamura D, Nakano H, Matsuzaki Y. Overview of Epidermolysis bullosa. J Dermatol. Mar 2010;37(3):214-9.
4. Pfendner E, Rouan F, Uitto J. Progress in Epidermolysis bullosa: the phenotypic spectrum of plectin mutations. Exp Dermatol. Apr 2005;14(4):241-9.
5. Pulkkinen L, Uitto J. Hemidesmosomal variants of Epidermolysis bullosa: Mutations in the a6b4 integrin and the 180-kD bullous pemphigoid antigen/type XVII collagen genes. Exp Dermatol .1998;7:46-64.
6. Fine JD, Eady RA, Bauer EA, et al. The classification of inherited Epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. Jun 2008;58(6):931-50.
7. Marinkovich MP, Meneguzzi G, Burgeson RE, et al. Prenatal diagnosis of Herlitz junctional Epidermolysis bullosa by amniocentesis. Prenat Diagn. Nov 1995;15(11):1027-34.
8. Fine JD, Eady RA, Bauer EA, et al. The classification of inherited Epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. Jun 2008;58(6):931-50.
9. Fassihi H, Eady RA, Mellerio JE, Ashton GH, Dopping-Hepenstal PJ, Denyer JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years' experience. Br J Dermatol. 2006;154(1):106-13. 
10. McGrath JA, Ishida-Yamamoto A, Tidman MJ, Heagerty AH, Schofield OM, Eady RA. Epidermolysis bullosa simplex (Dowling-Meara). A clinicopathological review. Br J Dermatol. May 1992;126(5):421-30.
11. Ishii N, Hamada T, Dainichi T, Karashima T, Nakama T, Yasumoto S,et al. Epidermolysis bullosa acquisita: What’s new? Journal of Dermatology. 2010; 37: 220–230. 
12. Mavilio F, Pellegrini G, Ferrari S, Di Nunzio F, Di Iorio E, Recchia A, Maruggi G, et al. Correction of junctional Epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. 2006;12(12):1397-402. 
13. Woodley DT, Keene DR, Atha T, Huang Y, Ram R, Kasahara N, Chen M. Intradermal injection of lentiviral vectors corrects regenerated human dystrophic Epidermolysis bullosa skin tissue in vivo. Mol Ther. 2004;10(2):318-26. 
14. Woodley DT, Keene DR, Atha T, Huang Y, Lipman K, Li W, et al. Injection of recombinant human type VII collagen restores collagen function in dystrophic Epidermolysis bullosa. Nat Med. 2004;10(7):693-5. 
15. Falabella AF, Valencia IC, Eaglstein WH, Schachner LA. Tissue-engineered skin (Apligraf) in the healing of patients with Epidermolysis bullosa wounds. Arch Dermatol. 2000;136(10):1225-30.