Blood Test May Help Diagnose Anemia in RDEB Children
Anemia is common in recessive dystrophic epidermolysis bullosa patients
The level of soluble transferrin receptor (sTfR) in blood may help diagnose more children with anemia, a condition caused by having too few red blood cells that’s common in recessive dystrophic epidermolysis bullosa (RDEB), a study suggests.
The study, “Iron status and burden of anemia in children with recessive dystrophic epidermolysis bullosa,” was published by researchers in the U.S. in the journal Pediatric Dermatology.
Epidermolysis bullosa causes the skin to become very fragile and to blister easily. In one severe form, called RDEB, anemia is common. It occurs as a result of long-lasting inflammation or iron deficiency.
To find out the prevalence (how common) and how severe anemia is, researchers at Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine followed a group of 114 children with RDEB from 2010 to 2020.
More than half (51.8%) were girls, and 68 (59.6%) had generalized severe disease. When they entered the study, their mean age was 13.2 years; at their last visit, it was 17.4 years.
Anemia began in the first year of life and it was worse for children with generalized severe disease than for those with less-severe forms of the disease.
“In RDEB, anemia begins in the first year of life and becomes more frequent and severe with age,” the researchers wrote.
Without treatment, the median level of hemoglobin fell below the third percentile for age by 1 year for girls and 2 years for boys. Hemoglobin is the protein in red blood cells that carries oxygen to body tissues.
Transfusion of red blood cells resulted in only a slight increase in the median level of hemoglobin across all ages.
Ferritin, a protein that stores iron inside cells, was measured in blood shortly after entry to the study and then over time. At a mean of 13.5 years, the mean level of ferritin was 152 nanograms per milliliter (ng/mL), which increased to 259 ng/mL at a mean 4.2 years later.
About one-third (33.6%) of the children had ferritin less than 15 ng/mL, indicating anemia due to a deficiency in iron. However, this measure “likely underestimates the true prevalence because inflammation, which is common in RDEB, increases the ferritin despite low body iron stores,” the researchers wrote.
Indeed, almost all children (nine in 10 in the last measurement) had an abnormally high level of C-reactive protein (CRP), a marker of inflammation.
To differentiate between anemia without iron deficiency from anemic states with iron deficiency, the researchers turned to a test that looks at the level of sTfR. Transferrin receptor protein helps iron get into a cell. Sometimes, a part of it is cut up from the cell border. When this happens, a soluble protein (sTfR) circulates freely in blood.
When the first sTfR measurements were available, at a mean 1.6 years after entry to the study, 23 (29.6%) children had ferritin less than 15 ng/mL, indicating a deficiency in iron.
A ratio of sTfR divided by ferritin was on average 1.4, ranging from 0.2 to 7.2. In about half (50.6%) of the children, the ratio was greater than 1.1, indicating anemia due to a deficiency in iron (alone or taking inflammation into account).
This means that the true prevalence of iron deficiency anemia was about 1.5 times higher than that measured using ferritin.
Using sTfR “improves the detection of iron deficiency in the context of inflammation and guides therapy,” the researchers wrote.
Infusions and transfusions
More than half (53.5%) of the children received parenteral iron infusions, transfusions, or both. Parenteral means in a way other than via the mouth. The mean number of iron infusions per patient was 3.2, and that of iron transfusions was three.
During the course of the study, 19 (16.7%) of the children died. A higher level of ferritin was linked to earlier mortality.
“Ferritin could be considered a prognostic factor in RDEB because it reflects the degree of systemic [whole-body] inflammation,” the researchers concluded. However, used alone, ferritin may underestimate the prevalence of anemia in children with RDEB, they noted.