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Diagnosis of epidermolysis bullosa

Diagnosis of epidermolysis bullosa
Literature review current through: Jan 2024.
This topic last updated: Apr 07, 2023.

INTRODUCTION — Epidermolysis bullosa (EB) includes a heterogeneous group of inherited disorders with the common finding of epithelial fragility. The skin and, in some cases, the mucosa develop blisters and/or erosions in response to minimal frictional trauma. Four major EB types are recognized on the basis of the ultrastructural level of skin cleavage (figure 1):

Epidermolysis bullosa simplex (EBS; intraepidermal)

Junctional epidermolysis bullosa (JEB; intralamina lucida)

Dystrophic epidermolysis bullosa (DEB; sublamina densa)

Kindler epidermolysis bullosa (KEB; intraepidermal, intralamina lucida, and sublamina densa)

Clinical, pathophysiologic, and molecular criteria define more than 30 subtypes of EB (table 1A-D) [1,2].

This topic will discuss the diagnosis of EB. The pathogenesis, clinical features, and management of EB are discussed separately. (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features" and "Overview of the management of epidermolysis bullosa".)

WHEN TO SUSPECT EPIDERMOLYSIS BULLOSA — EB should be considered in any neonate who presents with blisters and/or erosions in the absence of another plausible etiology (eg, infection). Blistering or skin fragility may develop later in infancy or childhood, particularly related to diaper changing or crawling, and even in adulthood in milder EB subtypes. (See 'Newborns' below and "Vesicular, pustular, and bullous lesions in the newborn and infant".)

In older children and adults, scarring, milia, nail dystrophy, oral involvement, or other organ involvement may suggest the EB subtype. (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features".)

EB should also be suspected in individuals presenting with a history of recurrent blistering or erosions with onset in infancy or childhood. A family history of similar manifestations is supportive. The skin changes are usually localized to areas of trauma but are out of proportion to the degree of trauma.

DIFFERENTIATING EPIDERMOLYSIS BULLOSA FROM OTHER BLISTERING DISEASES — Differentiating EB from other blistering diseases may be difficult, especially in newborns. In older children and adults, the timing of the onset of blistering usually helps in distinguishing EB from autoimmune bullous diseases. In some cases, clinical or laboratory features may confirm a diagnosis other than EB (eg, sucking blisters or infection), but skin biopsy is generally necessary to confirm the other disorders [3].

Newborns — In neonates and young infants, congenital or acquired disorders that should be considered in the differential diagnosis of EB include:

Epidermolytic ichthyosis (bullous congenital ichthyosiform erythroderma). (See "Keratinopathic ichthyoses", section on 'Epidermolytic ichthyosis'.)

Incontinentia pigmenti (picture 1). (See "Incontinentia pigmenti".)

Aplasia cutis congenita (picture 2). (See "Aplasia cutis congenita".)

Focal dermal hypoplasia (picture 3). (See "Focal dermal hypoplasia (Goltz syndrome)".)

Congenital erythropoietic porphyria. (See "Congenital erythropoietic porphyria".)

Bullous mastocytosis (picture 4). (See "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis", section on 'Cutaneous mastocytosis'.)

Bullous pemphigoid – Bullous pemphigoid is exceedingly rare in infants. The mean age at presentation is 4.5 months. Involvement of the hands and feet is characteristic, with or without generalized blistering [4]. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid".)

Neonatal pemphigus vulgaris, pemphigus foliaceus, pemphigoid gestationis, immunoglobulin A (IgA) bullous dermatosis, and epidermolysis bullosa acquisita (transient, transplacentally acquired conditions seen in newborns born, with the exception of neonatal IgA bullous dermatosis, to mothers with the disorders) [5]. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus", section on 'Neonatal pemphigus' and "Dermatoses of pregnancy", section on 'Pemphigoid gestationis'.)

Viral and bacterial infections, including herpes simplex, bullous impetigo, and staphylococcal scalded skin syndrome (picture 5A-C). (See "Vesicular, pustular, and bullous lesions in the newborn and infant", section on 'Infectious vesiculopustular eruptions'.)

Sucking blisters (picture 6). (See "Vesicular, pustular, and bullous lesions in the newborn and infant", section on 'Sucking blisters'.)

Trauma or abuse – Erosions and wounds in EB typically have uniform depth, whereas injury or burn creates erosions of varied depth within the same lesion. (See "Physical child abuse: Recognition" and "Physical child abuse: Diagnostic evaluation and management".)

Children and adults — In older children and adults, some autoimmune bullous diseases may share clinical features with EB. (See "Approach to the patient with cutaneous blisters".)

Linear IgA disease (chronic bullous disease of childhood (picture 7A-B) and adult linear IgA disease (picture 8)) (see "Linear IgA bullous dermatosis")

Epidermolysis bullosa acquisita (picture 9A-B) (see "Epidermolysis bullosa acquisita")

Bullous pemphigoid (picture 10) (see "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid")

Pemphigus vulgaris, which may mimic the acantholytic forms of EB (see "Pathogenesis, clinical manifestations, and diagnosis of pemphigus")

In these acquired disorders, the blisters usually occur near the time of presentation. In contrast, EB blistering is present at birth or begins in early infancy in most cases.

DIAGNOSTIC APPROACH — Our approach to the diagnosis of EB is generally consistent with the 2020 published guidelines [6].

Referral to an epidermolysis bullosa center — For patients with clinical manifestations suggestive of EB, referral to a specialized EB center or appropriate specialist (eg, a pediatric dermatologist and genetics professional) for precise diagnosis is recommended. Although many local laboratories are able to determine the type of EB (based on the cleavage level determined by immunohistochemistry with antibodies to type IV collagen and keratin 14), the accurate identification of the EB subtype is performed only in specialized laboratories and requires immunofluorescence mapping (IFM) with specific monoclonal antibodies targeting EB-specific proteins (table 2), transmission electron microscopy (TEM), or mutational analysis, which requires send-out testing.

Identifying and contacting the laboratory before the biopsy is performed will ensure that the specimen is obtained and processed appropriately. Information on the centers for the diagnosis and treatment of EB is available on the Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International website.

Diagnostic steps

A skin biopsy for IFM is typically the first step in the diagnosis of newly suspected EB. In resource-limited settings, immunohistochemistry with a limited panel of antibodies may be an alternative to IFM [7]. (See 'Immunofluorescence mapping' below.)

IFM is sufficient for diagnosis if it identifies the level or cleavage and the subtype; this occurs in most severe cases. If IFM is normal or fails to demonstrate the level of cleavage and/or subtype, the diagnosis can be confirmed with either TEM or mutational analysis. (See 'Transmission electron microscopy' below and 'Genetic testing' below.)

Depending on the availability and resources of the diagnostic center, mutational analysis is recommended in all patients with an established or suspected diagnosis of EB [6]. Mutational analysis can also be performed as a first-line test for EB. As an example, direct genetic testing can be performed to confirm the diagnosis in a patient from an autosomal dominant EB pedigree with a pathogenic variant already identified. In milder cases, mutational analysis may detect cases too subtle for detection by direct immunofluorescence.

In newborns presenting with skin fragility, IFM and mutational analysis should ideally be performed in parallel [6]. While a minimum of two to three weeks is required for mutational analysis results, IFM of an induced blister can be performed in a few hours or days, providing a rapid initial diagnosis and allowing for appropriate management of the newborn.

Collecting family history and creating a pedigree diagram — Obtaining a full and detailed family history with characterization of relatives going back three generations is helpful and may identify additional affected relatives. In the case of known familial mutations, targeted genetic testing to confirm the same mutation in the affected patient is usually sufficient.

The main exception to this would be if the patient's presentation differs in any way from the rest of the family (eg, more complications, earlier involvement, increased requirement for medical care), as there are unsuspected cases of mixed dominant and recessive mutations from the same gene and codominant inheritance of different gene mutations that have resulted in more severe or overlapping forms of EB [8]. In such cases, biopsies and full EB gene panel screening are required.

It is important for clinicians assessing genetic diseases, such as EB, to be able to create accurate pedigree diagrams based on information provided by the patient or family/caregivers. These diagrams are vital to having the correct information on each family. Examples of autosomal dominant and recessive pedigrees are provided in the figure (figure 2A-B). (See "Genetic counseling: Family history interpretation and risk assessment", section on 'Pedigree'.)

In recessive forms of EB, it is often cousins within these pedigrees who may have died in infancy, either from EB or an unknown condition. Early demise from cardiomyopathy may not have been appreciated as related to epidermolysis bullosa simplex (EBS), for example. Some parents may be cousins in generations removed or second-degree cousins and may even be unaware of this until such diagrams are created.

Other important information is the region and type of community of origin of the ancestors (eg, small villages, tribes). Descendants that have migrated to another country may not be aware of being related, although they originate from a small gene pool, which increases the chance of a recessive disease.

SKIN BIOPSY — Patients with suspected EB should undergo a skin biopsy of an induced blister for immunofluorescence mapping (IFM). Transmission electron microscopy (TEM) may be necessary if IFM is inconclusive or normal. Although TEM may not be necessary in some cases, it is most practical to perform biopsies for both studies at the same time. IFM and TEM identify the level of skin cleavage, morphologic alterations of epithelial adhesion structures in the basement membrane zone, and defective expression of adhesion proteins at the dermal-epidermal junction [9].

Routine histology of an EB lesion typically shows a noninflammatory, intra- or subepidermal blister and is not helpful in establishing the EB type. However, routine histology may be useful in order to exclude other etiologies of bullous or erosive lesions, particularly in the neonate. (See "Vesicular, pustular, and bullous lesions in the newborn and infant".)

Obtaining biopsies for epidermolysis bullosa diagnosis — Proper technique is critical when biopsying for EB diagnosis since submission of suboptimal specimens (eg, due to no blister, no epidermis, or re-epithelialization) is a relatively common reason why IFM and/or TEM cannot be performed or do not yield a diagnosis. Accurate interpretation of IFM and TEM requires examination of fresh blisters. When blisters are more than 12 hours old, proteolytic antigen degradation and/or re-epithelialization under the roof of the blister may result in artifactual cleavage planes [10]. However, a biopsy of unaffected, nonrubbed skin may be required in patients with extreme mechanical skin fragility (a characteristic feature of recessive EB). In these patients, performing a punch biopsy may be sufficient to induce the cleavage plane necessary for diagnosis [9].

Induction of a fresh blister – A fresh blister is usually induced in an area of skin that is clinically uninvolved but adjacent to a site where the patient usually blisters. The palms and soles should be avoided because the increased skin thickness in these areas makes the identification of the cleavage site difficult. To avoid unnecessary repetition of the procedure, it is important that the fresh blister is induced, ideally by a clinician with expertise in EB.

Administration of topical anesthetics (such as eutectic mixture of local anesthetics [EMLA] under occlusion) before local anesthesia should be avoided because topical anesthetics may induce artificial blistering, especially in the epidermis.

After identifying the biopsy site, the area is prepared in a sterile manner and outlined. A cotton swab, pencil eraser, or gloved finger or thumb may be used to induce a blister. Firm, downward pressure is applied to the skin, and traction is then exerted by rubbing or twisting (at least 180 degrees each way) until erythema is produced (the biopsy site is recleaned after the blister is induced) (picture 11) [9]. The amount of friction necessary to induce a subclinical blister may vary from patient to patient, but the development of erythema at the site is a good endpoint. For newborns or infants, a reasonable rule of thumb is to rub the selected area at least 20 times.

For patients with milder skin fragility, up to two minutes of induced friction can be necessary to induce the blister. It may be helpful to ask older children or adults with milder skin fragility to perform an activity that induces a fresh blister before a clinic appointment for biopsy.

Punch biopsy – Biopsies are performed at least five minutes after the induction of erythema to allow for the development of a microscopically identifiable blister. The biopsy site is cleaned with an antiseptic solution (povidone iodine stings less than alcohol) and draped. Two separate biopsies from adjacent sites are taken. Most laboratories prefer punch biopsies over shave biopsies because punched specimens are easier to orient and embed for frozen sections. Approximately one-third to one-half of each biopsy should include the induced blister, with the remaining portion composed of unaffected skin. If blistering is present, check the upper part of the biopsy tool to make sure any roof material is included with the specimen and not left in the biopsy tool.

A larger biopsy may be split in two, but this procedure is not recommended since it might separate the epidermis from the dermis with loss of the diagnostic cleavage plane.

Biopsies should be sent to a laboratory experienced in the diagnosis of EB [11]. Identifying and contacting the laboratory before the biopsy is performed will ensure that the specimen is obtained and processed appropriately. Information on the centers for the diagnosis and treatment of EB is available on the Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International website.

Handling of specimens – For IFM, a 3 or 4 mm biopsy is immersed immediately in Michel's transport medium (ammonium sulfate, N-ethyl-maleimide, magnesium sulfate, potassium citrate buffer, and distilled water; the correct pH buffering is important) [12]. It is essential to avoid contamination of the IFM sample with formalin or TEM fixative to preserve antigen expression. If an autoimmune blistering disease is in the differential diagnosis, the same sample can be tested for direct immunofluorescence by the same laboratory. (See "Approach to the patient with cutaneous blisters", section on 'Direct immunofluorescence'.)

For TEM, a 2 or 3 mm biopsy is placed in 2.5% glutaraldehyde solution (glutaraldehyde buffered by 0.1 M sodium cacodylate, pH 7.4) and stored at 4°C (39.2°F) before shipping overnight at either room temperature or with a cold pack if ambient temperatures are greater than 37°C (98.6°F).

Immunofluorescence mapping — Immunofluorescence mapping (IFM) of induced blisters has superseded TEM as the diagnostic investigation of choice for EB because of its wide availability, rapid turnaround time, lower cost, and higher degrees of sensitivity and specificity [11,13]. IFM effectively functions as an assay of protein expression in the skin, which may better predict overall disease severity than mutational analysis. IFM also demonstrates protein expression in areas of revertant mosaicism, a relatively common phenomenon in junctional epidermolysis bullosa (JEB) and recessive dystrophic epidermolysis bullosa (RDEB) [14-16], and in cases of splicing mutations [17].

Identification of major epidermolysis bullosa types – Blister mapping by IFM is performed in many local laboratories and involves the use of a limited number of antibodies directed against basement membrane antigens, including:

Bullous pemphigoid antigen 1 (bullous pemphigoid antigen 230 [BP230])

Laminin 332

Type IV collagen

Keratin 14

These antibodies map the corresponding antigens in relation to the blister and allow for the diagnosis of three of the four major EB types [18]. Patients with suspected Kindler epidermolysis bullosa (KEB) should undergo mutational analysis. (See 'Genetic testing' below.)

In epidermolysis bullosa simplex (EBS), in which blistering occurs within the epidermis, all these antibodies will stain only the floor of the blister (except anti-keratin 14, which can stain both the blister roof and floor due to lysis of the basal keratinocytes).

In JEB, in which blistering occurs within the lamina lucida, anti-laminin 332, anti-BP230, and anti-keratin 14 will stain the roof of the blister (if present), whereas anti-collagen IV will stain the floor.

In dystrophic epidermolysis bullosa (DEB), all antibodies will stain only the roof of the blister, indicating that the cleavage plain is below the lamina densa.

Identification of epidermolysis bullosa subtypes – The diagnosis of the EB subtype by IFM is performed in specialized laboratories and involves the use of panels of specific monoclonal antibodies that target EB-specific proteins of the dermal-epidermal junction. A panel of EB-specific monoclonal antibodies and their corresponding proteins is shown in the table (table 2).

The determination of the patient's underlying molecular defect is based upon the staining intensity (normal, reduced, or absent) of EB-specific proteins. Absent or attenuated staining of specific proteins is diagnostic for a specific EB subtype. As an example, in severe RDEB, the staining of type VII collagen is absent, whereas in other generalized or localized subtypes of DEB, the expression of type VII collagen may be reduced or variable (table 3) [18].

Transmission electron microscopy — Transmission electron microscopy (TEM) has historically been the initial diagnostic test for EB [19]. However, several drawbacks limit its widespread use now that IFM is available: It is time consuming, labor intensive, expensive, operator dependent, potentially more subjective in its interpretation, and available only in a few specialized centers. However, TEM may be helpful for determining the level of skin separation and is used in some instances to confirm or refine the diagnosis obtained by IFM [20]. As an example, in milder forms of EB (particularly those inherited in a dominant manner), IFM may be normal, whereas TEM can identify microsplits and other ultrastructural abnormalities at the dermal-epidermal junction.

TEM utilizes a magnification of 3000 to 30,000x, which allows for the visualization of the level of skin cleavage and morphology of the structural components of the dermal-epidermal junction, including keratin intermediate filaments, hemidesmosomes, and anchoring fibrils. TEM is of particular use in diagnosing EBS, generalized severe (formerly called Dowling-Meara), a subtype of EBS. In this form of EB, IFM may show no abnormality, except an intraepidermal split, whereas TEM demonstrates the characteristic aggregation of keratin intermediate filaments in the basal keratinocytes [20]. (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features", section on 'Epidermolysis bullosa simplex'.)

Diagnostic accuracy of IFM and TEM analysis — A few studies have evaluated the accuracy of transmission electron microscopy (TEM) and immunofluorescence mapping (IFM) in the diagnosis of EB [13,21,22].

In a study that used genetic testing as the gold standard for the diagnosis of EB in 33 patients, the sensitivity and specificity of TEM were 71 and 81 percent, respectively, and the sensitivity and specificity of IFM with an expanded panel of 13 monoclonal antibodies were 97 and 100 percent, respectively [13].

Another single-center study assessed the diagnostic accuracy of IFM and TEM using genetic testing as the gold standard in 87 patients (19 with EBS, 21 with JEB, 44 with DEB, and 1 with KEB) [23]. The sensitivity and specificity of IFM were 84 and 100 percent for EBS, 100 and 100 percent for JEB, and 100 and 100 percent for DEB, respectively. For TEM, the sensitivity and specificity were 95 and 100 percent for EBS, 100 and 100 percent for JEB, and 100 and 100 percent for DEB, respectively.

GENETIC TESTING — With the advent of next-generation sequencing (NGS), which allows for querying multiple genetic targets in parallel and has reduced overall genetic testing cost and turnaround time, genetic testing can be considered a first-line test for EB. It is desirable to obtain and store a venous blood sample at the initial visit (or consultation in the neonatal unit) to allow subsequent deoxyribonucleic acid (DNA) extraction. Ideally, a blood sample is obtained in an ethylenediaminetetraacetic acid (EDTA) tube and sent to a genetics laboratory for genomic DNA extraction and storage. Many laboratories are able to work with as little as 2 or 2.5 mL of blood. Contacting the laboratory to discuss feasibility and requirements before obtaining the specimen is advised.

Targeted NGS with the known EB genes and those of associated disorders of skin fragility can efficiently identify EB pathogenic variants [24]. NGS can also be used for whole exome sequencing or whole genome sequencing, followed by targeted filtering. Sanger sequencing is used to confirm new pathogenic variants identified with NGS. (See "Next-generation DNA sequencing (NGS): Principles and clinical applications".)

Genetic testing is strongly recommended in all patients to confirm the exact EB diagnosis, following the identification of the candidate genes by immunofluorescence mapping (IFM) and/or transmission electron microscopy (TEM).

Genetic testing is also indicated in families with a severely affected child if prenatal diagnosis or preimplantation genetic testing (PGT) are planned for subsequent pregnancies.

Genetic testing, where available, is recommended as part of the initial evaluation in the following scenarios [6]:

In newborns with clinical features suggestive of EB who are the first affected members in the family. Since EB subtype and inheritance pattern are not clear and a precise diagnosis is important to evaluate the prognosis and for genetic counseling, NGS can be used to detect postzygotic mosaicism in a variety of tissues in unaffected parents [25].

In patients with suspected Kindler epidermolysis bullosa (KEB). The identification of the mutations in the FERMT1 gene is the diagnostic gold standard for KEB, since IFM for kindlin-1 is unreliable [26]. (See "Kindler epidermolysis bullosa", section on 'Diagnosis'.)

In patients with milder forms of dystrophic epidermolysis bullosa (DEB; eg, localized recessive dystrophic epidermolysis bullosa [RDEB]; de novo, dominant epidermolysis bullosa simplex [EBS] or dominant dystrophic epidermolysis bullosa [DDEB]) in whom the diagnosis is not possible on the basis of the clinical phenotype, and TEM or IFM findings are inconclusive. Family history is not useful in these cases because parents are not affected, and other siblings may be unaffected as well [27].

In cases where other family members are affected with EB but the clinical phenotype in the patient is different (eg, more severe blistering, increased need for medical intervention).

The sensitivity of mutation analysis ranges from 60 to 95 percent and depends upon the affected gene and the techniques used for analysis [28-30]. Data from one commercial laboratory show a sensitivity of 99 percent in patients with biopsy-proven EB.

PRENATAL DIAGNOSIS AND PREIMPLANTATION GENETIC TESTING

Prenatal diagnosis – Prenatal diagnosis is increasingly sought by families with children affected by the most severe forms of EB, including recessive dystrophic epidermolysis bullosa (RDEB), severe junctional epidermolysis bullosa (JEB; formerly termed Herlitz JEB), and EB with pyloric atresia. (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features".)

Mutational analysis is the standard of care for prenatal diagnosis and has superseded the techniques involving the ultrastructural examination of fetal skin biopsy samples. Before any prenatal test, DNA samples from both parents and any affected siblings are analyzed for causative mutations. This initial screening determines the pattern of inheritance and establishes the reliability of the prenatal test [31].

For prenatal diagnosis, fetal DNA is obtained from chorionic villi (in the first trimester of pregnancy) or amniotic cells (after 15 weeks) and analyzed for mutations. (See "Chorionic villus sampling" and "Diagnostic amniocentesis".)

The validity of DNA-based prenatal diagnosis is high. In one series of 144 pregnancies at risk for EB, the outcome was discordant from the prediction in only three cases (2 percent) [32].

Preimplantation genetic testing – Preimplantation genetic testing (PGT) is a highly specialized procedure available in a limited number of centers worldwide and more commonly in the United States. In this procedure, genetic testing is performed three days after in vitro fertilization, at the 6 to 10 cell stage [31]. The genetic diagnosis is performed on a single cell, and suitable embryos can be transferred to the uterus on day 4 or 5 of development. A PGT protocol for severe JEB has been developed, validated, and successfully used in a clinical case [33].

An overview of PGT, including a discussion of limitations and safety, is presented separately. (See "Preimplantation genetic testing".)

SPECIALIZED LABORATORIES FOR EPIDERMOLYSIS BULLOSA DIAGNOSIS — Information on specialized centers for the diagnosis of EB is available on the Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International website.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Epidermolysis bullosa".)

SUMMARY AND RECOMMENDATIONS

Major types of epidermolysis bullosa – Four major types of epidermolysis bullosa (EB) are recognized on the basis of the ultrastructural level of skin cleavage: epidermolysis bullosa simplex (EBS; intraepidermal), junctional epidermolysis bullosa (JEB; intralamina lucida), dystrophic epidermolysis bullosa (DEB; sublamina densa), and Kindler epidermolysis bullosa (KEB; intraepidermal, intralamina lucida, and sublamina densa) (figure 1). Clinical, pathophysiologic, and molecular criteria define more than 30 subtypes of EB (table 1A-D). (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features".)

When to suspect epidermolysis bullosa – EB should be suspected in individuals with a history of recurrent blistering or erosions following mild trauma and in neonates presenting with blisters and erosions without other plausible etiology (eg, infection), especially if family history is positive for similar manifestations. (See 'When to suspect epidermolysis bullosa' above and 'Differentiating epidermolysis bullosa from other blistering diseases' above.)

Diagnostic approach

Skin biopsy for immunofluorescence mapping – Skin biopsy for immunofluorescence mapping (IFM) of a freshly induced blister is the first-line approach for the diagnosis of EB in most cases. Identifying and contacting the laboratory before the biopsy is performed will ensure that the specimen is obtained and processed appropriately. Information on centers for the diagnosis and treatment of EB is available on the Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International website.

IFM allows for the identification of the level of skin cleavage, morphologic alterations of epithelial adhesion structures in the basement membrane zone, and defective expression of specific protein components for identification of the subtype of EB. (See 'Immunofluorescence mapping' above and 'Transmission electron microscopy' above.)

Genetic testing – Mutational analysis may be considered as a first-line diagnostic test for EB, but cost and availability need to be reviewed in the decision-making process. Mutational analysis is recommended to confirm the EB diagnosis and is critical in patients with suspected KEB, when the inheritance pattern is not clear, in families with a severely affected child, or when prenatal or preimplantation genetic testing (PGT) is planned. Information on specialized centers for the diagnosis of EB is available on the DEBRA International website. (See 'Prenatal diagnosis and preimplantation genetic testing' above and 'Specialized laboratories for epidermolysis bullosa diagnosis' above.)

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  33. Fassihi H, Liu L, Renwick PJ, et al. Development and successful clinical application of preimplantation genetic haplotyping for Herlitz junctional epidermolysis bullosa. Br J Dermatol 2010; 162:1330.
Topic 15452 Version 31.0

References

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