Zinc deficiency in those with RDEB tied to worse skin damage, greater anemia
Tenfold higher wound risk seen with low zinc levels in new study
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Low levels of zinc — an essential mineral that supports wound healing — in people with recessive dystrophic epidermolysis bullosa (RDEB) are linked to worse disease, poorer nutritional status, and a higher risk of body-wide complications among those with the rare skin condition, a new study in Spain has found.
The researchers noted that zinc deficiency is tied to anemia, or too few red blood cells in the body, which is linked to chronic wounds like those seen in RDEB. Low zinc levels were also associated with more inflammation and a greater extent of skin involvement, the data showed.
Blood albumin, a protein that transports zinc, was the strongest determinant of zinc levels found in the study, the investigators noted, “partially mediating the effects of inflammation and skin involvement” among patients.
Overall, according to the team, the study’s findings highlight the key role that sufficient zinc levels play in reducing the effects of RDEB, a type of epidermolysis bullosa (EB).
“Zinc deficiency emerges as a clinically relevant and modifiable factor associated with complication burden, supporting the rationale for systematic monitoring and correction of deficiency as part of … supportive care and complication management in RDEB,” the researchers wrote.
The study, “Zinc as a Biomarker of Nutritional Status and Clinical Burden in Recessive Dystrophic Epidermolysis Bullosa: Implications for Preventive Monitoring,” was published in the journal Nutrients.
DEB is caused by mutations in the COL7A1 gene, which encodes for a portion of type VII collagen, a protein that connects the different layers of the skin. People with RDEB must inherit two copies of disease-causing mutations, one from each parent, to develop the disease.
Zinc is an essential trace element involved in tissue repair, immune function, and growth. In people, skin accounts for about 5% of the body’s total zinc.
Skin wounds can reduce zinc levels in people with RDEB
Skin wounds, systemic, or body-wide, inflammation, and difficulties with zinc intake from the diet may reduce zinc levels in people with RDEB.
To learn more, a research team based in Madrid investigated the factors associated with zinc deficiency in 84 people with RDEB registered at the Spanish Reference Unit for EB. About one-third of the patients had zinc deficiency, defined as levels lower than 670 micrograms (mcg)/L. That risk increased with age, as no preschool children (1 to 4 years) had zinc deficiency; in contrast, low levels were found in 32% of those aged 5 to 17 and 47% of adults.
Those with zinc deficiency exhibited higher EB Disease Activity and Scarring Index (EBDASI) total scores, as well as higher scores in disease activity and damage domains, indicating more severe disease.
“All patients with zinc deficiency fell within the severe EBDASI category,” the investigators noted.
Overall, according to the researchers, oral zinc supplements can fail to meet clinical needs, with many patients remaining zinc-deficient despite taking them. Other zinc-deficient patients were not taking supplements.
Further analysis demonstrated that zinc deficiency was associated with impaired growth in children and adolescents with RDEB, and with common disease complications. Among them were anemia, issues affecting the mouth, including premature tooth loss, extensive skin involvement, and chronic wounds.
Low zinc levels were also associated with levels of an inflammation biomarker called C-reactive protein (CRP), infections, and severe infections requiring hospitalization.
Researchers propose new cutoffs for measuring zinc levels
The most notable associations were with chronic wounds and anemia, marked by low levels of red blood cells or of hemoglobin, which carries oxygen in the bloodstream.
The data showed a 36 times higher risk of anemia among those with zinc deficiency, and a 10 times higher risk of chronic wounds.
“Zinc levels emerged as the strongest predictor of anemia risk in RDEB patients,” the team wrote.
However, team noted that the sensitivity of the current zinc deficiency cutoff of 670 mcg/L to detect most outcomes remains lower than 70%. That “[limits] its effectiveness as a clinically meaningful preventive supplementation threshold and [increases] the risk that vulnerable RDEB patients may go unrecognized,” the investigators wrote.
Zinc levels emerged as the strongest predictor of anemia risk in RDEB patients.
The research team proposed a revised cutoff of 780 mcg/L, which identified patients at risk of body-wide complications associated with zinc status with at least 80% sensitivity.
When accounting for other relevant variables, low blood zinc levels independently predicted anemia risk, as well as transferrin saturation and CRP levels. Transferrin saturation measures the percentage of transferrin, an iron-transport protein, that is actually bound to iron.
As an example, the researchers estimated that, for a 20-year-old woman with CRP at 15 mg/L and transferrin saturation not higher than 15%, the predicted probability of anemia would be approximately 69% when blood zinc was 670 mcg/L, but only 26% if zinc was at 780 mcg/L. This reflects a 43% risk reduction associated with higher zinc levels, “underscoring the proposed independent protective effect of zinc and supporting the clinical relevance of the 780 [mcg]/L threshold as a potential target for intervention,” the team wrote.
Further, blood albumin was identified as the strongest determinant of zinc levels, determining at least in part the effects of inflammation and skin involvement.
“These findings support a model in which skin damage and inflammation affect zinc levels primarily through their impact on [blood] albumin but may also exert a direct effect,” the researchers concluded.
