Epidermolysis Bullosa Commands Aggressive Tx

Anemia treatments include combinations of oral iron supplements, blood transfusions, parenteral iron infusions, and erythropoietin. Patients taking oral iron supplements should be advised to take them between meals and without milk to improve absorption. The ferrous form is more soluble and better absorbed; however, this advantage comes at the cost of more side effects (such as constipation). The ferric form is less soluble and has fewer side effects, but leads to a slower response.

Poor compliance rates with oral iron supplements often result from dysphagia and constipation. However, poor gastrointestinal absorption and lack of bone marrow response may also contribute to poor results. Adequate vitamin C levels can improve iron absorption, she said.

Blood transfusions are reserved for patients with low hemoglobin (less than 7 g/dL). Use of transfusions tends to be restricted because of adverse events, said Dr. Murrell. These adverse events include the potential risk of infection (for example, from hepatitis). In addition, transfusions may require time off from work for family members, and may result in psychological costs as well.

Iron transfusions had fallen out of favor because of reactions to intravenous iron-dextran and intramuscular iron-sorbitol-citric acid. However, ferric hydroxide–sucrose mixtures are safer to use. "We're now using these iron infusions many times as an alternative to blood transfusions," she said.

Iron deficiencies need to be corrected for erythropoietin to increase erythropoiesis and raise hemoglobin levels. Studies of erythropoietin that was given to improve chronic anemia in children with inflammatory arthritis have shown improvements in quality of life, energy levels, appetite, and mental functioning. However, the drug did not work without adequate iron levels.

At the EB clinic in Sydney, patients have blood work done 3 weeks prior to a visit. Physicians look at patient levels of hemoglobin, mean corpuscular volume, reticulocyte count, and soluble transferring receptor levels. If iron levels are low, they will start the patient on oral iron and vitamin C supplements, along with nutritional support.

However, if a patient fails to respond, erythropoietin levels are checked. Iron infusions are then given every 3 months. If iron levels increase, the patient is started on erythropoietin every 2 weeks. Blood parameters are monitored every 3 months.

Squamous Cell Carcinoma in EB

SCC in patients with EB is more aggressive than other cutaneous SCCs and occurs at a much younger age, Dr. Murrell noted. "These tumors behave in a highly anaplastic way, despite looking well differentiated on pathology." SCC is the No. 1 cause of death in patients with recessive dystrophic EB, she said.

Most SCCs arise on the hands and feet. "However, [these SCCs] are often multifocal, so you can't just examine the hands and feet of these patients. SCCs arise in wound margins at the sites of chronic blistering and scarring," Dr. Murrell said. The appearance of these lesions can be highly variable. "They may look hyperkeratotic and exophytic, but sometimes they just look like ulcers that haven't been healing," she said. Typically, several biopsies are necessary to exclude SCC.

SCCs in patients with EB appear to be associated with chronic wounds. "One of the theories is that there are mutations arising during wound repair [that] are not being recognized and being fixed," said Dr. Murrell.

"The early recognition of SCC is really important. In my mind, it's like early recognition of melanoma," she said.

Dr. Murrell and her colleagues have been following 16 RDEB patients since 1999. They perform biopsies on any nodules or ulcers that persist for more than 3 months, or any nodules that become enlarged or are painful. Photographic monitoring provides documentation of erosion size and location. This is very helpful in identifying and performing biopsies on lesions that persist.

One of the keys to this approach is patient participation. Dr. Murrell told of a 20-year-old patient who did not regularly attend these sessions, and ultimately had to have her hand amputated. In contrast, a 60-year-old patient has had more than 50 early SCC excisions and is still doing well. "She jumps at getting the biopsies done as soon as she realizes there is anything unusual or untoward about any of her wounds," said Dr. Murrell.

Patients with EB need vigilant monitoring for SCCs. Treating physicians should have a low threshold for biopsy. If an SCC is identified, a wide excision should be performed, said Dr. Murrell.

In terms of treatment, Mohs surgery has been used for SCCs in patients with RDEB. However, "I'd be hesitant to use that because the margins are not very big," she said.