Skill Checkup: A Student With an Inherited Blistering Condition and Painful Bullae on His Feet

William D. James, MD

Disclosures

April 12, 2021

Cutaneous squamous cell carcinoma (SCC), and more rarely mucosal SCC, are associated with certain forms of EB. EB-associated SCCs tend to arise at sites of chronic skin blistering, wounds, and scarring, unlike in the general population where chronic ultraviolet sun exposure leads to tumor development. In EB, multiple primary SCCs often occur and tumors generally behave more aggressively than conventional SCCs; therefore, clinical detection is important. EB cancers are the leading cause of death in patients with recessive dystrophic EB (RDEB), particularly the severe generalized form (RDEB-SG). Lesions that are suspicious and atypical in EB patients should be evaluated with modalities that include imaging studies and lymph node assessment, staging, and a multidisciplinary team review as appropriate and needed. Different surgical resection techniques are used in the treatment of EB patients with SCC. Radiotherapy was reported to shrink the tumor size when used neoadjuvantly. Chemotherapy is used for palliative therapy. Available therapies include the epidermal growth factor receptor inhibitors (cetuximab) and tyrosine kinase inhibitors (erlotinib) which have shown positive results but notable toxicities. Rigosertib is a RAS pathway–targeting drug that is currently in trials which have shown initial efficacy in the management of SCC associated with RDEB.

Mortality rates remain high despite aggressive tumor resection. Risk for SCC in other forms of EB is lower, tumors occur later in life, and they tend to be less aggressive. It is also important to acknowledge that many EB subtypes, especially EB simplex, are not associated with an increased risk for SCC.

Esophageal strictures are common findings in the intermediate and severe subtypes of RDEB. Intermediate RDEB, formerly known as intermediate generalized RDEB or non-Hallopeau-Siemens RDEB, is characterized by generalized distribution blisters. Clinical findings include esophageal strictures, corneal lesions, and pseudosyndactyly of the hands and feet but are less common in the intermediate form of the disease. Developmental delay and anemia are even more rare conditions in this subtype of RDEB. Severe RDEB, formerly known as severe generalized RDEB or Hallopeau-Siemens RDEB, constitutes the most severe form of DEB. It is usually associated with the complete absence of collagen VII expression. Clinical manifestations include the formation of generalized blisters throughout the body from birth, and pseudosyndactyly in the hands and feet which result in joint contractures. Other signs include chronic ulcers that are difficult to heal, milia, and nail dystrophy. Blistering occurs in the oral mucosa, in the corneal region, and in the gastrointestinal epithelium; esophageal stenosis is described in many cases. Anemia, developmental delay, and SCC associated with early death are associated with severe RDEB.

Esophageal strictures are considered a precancerous condition. They may lead to obstruction and the need for esophageal balloon dilation or surgical intervention in order to maintain the patient's nutritional needs.

Anemia, often severe, occurs in both the intermediate and severe RDEB subtypes. It is usually the result of malabsorption due to esophageal and gastrointestinal mucosal blistering, ulceration, and scarring. Iron deficiency and overall malnutrition may cause failure to thrive.

According to the European Reference Networks, patients with severe JEB (formerly severe generalized JEB) are susceptible to multiorgan dysfunction in response to infections and sepsis. Sepsis is the leading cause of death in infants with severe JEB and less frequently in severe generalized RDEB and severe generalized EBS. EB patients and caregivers should carry emergency cards. Signs and symptoms that could indicate sepsis include altered behavior or consciousness, change in urine output, widespread blistering, recent surgery, catheters, or IV lines. When patients are suspected of having sepsis, a scoring system that includes the following should be used to assess its degree:

  • consciousness level

  • respiratory rate

  • hypotension

  • temperature

  • oxygen saturation on air

  • skin changes (mottled, dusky)

Patients are treated with oxygen and IV fluids before hospital admission. Assessment tests include arterial blood gases including lactate, blood cultures, complete blood count, urea and electrolytes, creatinine, coagulation screen, urine and skin swabs for culture and sensitivity, and chest radiography. After microbiology specimens are collected, broad-spectrum IV antibiotics are administered. ICU admission is appropriate if necessary.

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