Clinical Guidance

JEB generalized severe is the result of inactivating pathogenic variants on both alleles, which result in little or no functional protein . For frameshift variants, the severity may be related to where the stop codon is located and whether any functional (although truncated) protein is formed; the presence of some functional protein appears to be the most important factor in mitigating disease severity . JEB generalized intermediate generally results from amino acid substitutions and splice-junction variants, although it is difficult to generalize because of the wide phenotypic variability and range of allelic variants that have been identified .

Source: GeneReviews — "Junctional Epidermolysis Bullosa"

Diagnostic Criteria

Suggestive Findings

Junctional epidermolysis bullosa (JEB) should be suspected in individuals who have fragility of the skin with:

• Blistering with little or no trauma. Blistering may be mild or severe; however, blisters generally heal with no significant scarring.

• Significant oral and mucous membrane involvement

Note: Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally in and around the upper airway and the trachea .

Establishing the Diagnosis

The diagnosis of JEB is established in a proband with one or both of the following:

Source: GeneReviews — "Junctional Epidermolysis Bullosa"

Differential Diagnosis

Epidermolysis bullosa (EB). According to the 2014 classification system, the four major types of EB, caused by pathogenic variants in 18 different genes, are EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome (KS) . Classification into major type is based on the location of blistering in relation to the dermal-epidermal junction of skin. Subtypes are predominantly determined by clinical features and supported by molecular diagnosis. The four major types of EB share easy fragility of the skin (and mucosa in many cases), manifested by blistering with little or no trauma.

Source: GeneReviews — "Junctional Epidermolysis Bullosa"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with junctional epidermolysis bullosa (JEB), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Evaluation of the sites of blister formation, including mouth, esophagus, and airway in a child with progressive hoarseness or stridor

• Direct examination of the airway by an experienced otolaryngologist with appropriately small and lubricated instruments to determine the extent of airway compromise so that decisions regarding tracheostomy can be discussed with the family

• Evaluation for gastroesophageal reflux disease, which may cause additional trauma to the upper airway

• Evaluation for existing osteopenia through skeletal radiographs or DXA (dual-energy x-ray absorptiometry) scan

• Evaluation for cardiomyopathy by clinical evaluation and/or echocardiogram [Fine et all 2008]

• Measurements of hemoglobin and electrolytes to evaluate for anemia and electrolyte imbalance

• Skin bacterial cultures and blood cultures in clinically ill infants to decide appropriate antibiotic treatment

• Consultation with a clinical geneticist and/or genetic counselor

Note: Clinical decision making in children who manifest sign and symptoms of severe JEB with a very poor prognosis has been debated and remains difficult .

Treatment of Manifestations

Skin. The skin needs to be protected from shearing forces and caretakers need to learn how to handl...

Source: GeneReviews — "Junctional Epidermolysis Bullosa"

Clinical Guidance

Most persons with JEB cannot use ordinary medical tape or Band-Aids®. Silicone-based products provide a good substitute for tape. Poorly fitting or coarse-textured clothing and footwear can cause trauma. Activities such as hiking, mountain biking, and contact sports traumatize the skin; affected individuals who are determined to participate in such activities should be encouraged to find creative ways to protect their skin.

Source: GeneReviews — "Junctional Epidermolysis Bullosa"

Therapies Under Investigation

Several approaches to gene therapy for JEB, focused on retroviral modification of in vitro epidermal cells, have been proposed . One successful clinical trial has been conducted using transplantation of sheets of genetically modified epidermal stem cells in one affected individual with biallelic LAMB3 pathogenic variants . Animal models include intra-amniotic prenatal laminin 332 delivery in mouse and a spontaneous form of JEB in dog . The use of a variety of viral vectors, including AAV , lentivirus , and retroviruses , is being explored to correct the pathogenic variants in cells cultured from individuals with JEB in preparation for transplantation back onto severely affected sites, and shows promise for future clinical trials.

Source: GeneReviews — "Junctional Epidermolysis Bullosa"

Surveillance Guidelines

Surveillance includes the following:

• Annual complete blood counts and measurement of serum iron concentration to screen for iron-deficiency anemia

• Annual measurement of serum zinc concentration to screen for zinc deficiency

• Annual measurement of serum vitamin D

• Screening with bone mineral density scanning may detect early osteopenia and/or osteoporosis. No guidelines have been established regarding the age at which this should be initiated.

• Screening for dilated cardiomyopathy with periodic echocardiograms

• Skin examination starting in the second decade of life for wounds that do not heal, have exuberant scar tissue, or otherwise look abnormal to screen for squamous cell carcinoma. Frequent biopsies of suspicious lesions followed by local excision may be necessary.

Source: GeneReviews — "Junctional Epidermolysis Bullosa"