AMSTERDAM – Living in a locale with hard water – defined as a calcium carbonate concentration of 258 mg/L or more in the domestic water supply – was associated with significantly increased risk of eczema at 3 months of age in a large study conducted across England and Wales.
The study findings have potentially far-reaching implications for the prevention of childhood eczema, as well as halting what is often called the “atopic march” from eczema to food allergies to asthma. A national follow-up study is now being prepared in which families will be given an effective water softener machine when a child is born, with randomization to the machine being switched on or off.
“We want to see whether we might be able to prevent eczema by removing calcium carbonate from domestic water,” Dr. Carsten Flohr explained at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.
He reported on 1,303 infants who at 3 months of age underwent a structured skin examination with SCORAD (SCORing Atopic Dermatitis) measurement. Twenty-four percent were diagnosed as having eczema, which was typically mild.
Calcium carbonate concentrations in the local water supply vary enormously across England and Wales because rich limestone beds are found in some areas, notably the south and east, Dr. Flohr noted.
Babies living in areas with a calcium carbonate water concentration above the median level had a 45% increase in eczema risk. This risk was mediated by filaggrin loss-of-function (FLG) mutations. All study participants underwent testing for the six most common such mutations. In children without an FLG mutation, water hardness made little difference in eczema risk.
But FLG carriers living in the third quartile for water hardness – defined as a calcium carbonate concentration of 258-285 mg/L – had a 4.9-fold greater risk of eczema than did the general study population. Those in the highest quartile were at 2.67-fold increased risk, which just missed achieving statistical significance.
Looking at calcium carbonate concentration as a continuous variable, FLG carriers had an impressive 1% increase in the risk of eczema for each 1 mg/L rise in domestic water hardness, added Dr. Flohr, a pediatric dermatologist at St. Thomas’ Hospital, London.
The investigators also measured transepidermal water loss (TEWL) as an indicator of skin barrier function. FLG carriers without eczema living in hard-water areas had a high rate of excessive TEWL, defined as at least 15 g/m2 per hour. Those in the third quartile for calcium carbonate were at a 4.63-fold greater risk of abnormal TEWL, compared with FLG carriers living in areas in the two lowest quartiles of water hardness. The risk of excessive TEWL among FLG carriers without eczema rose by 1% for every 1 mg/L increase in calcium carbonate concentration.
“This suggests that the interaction between filaggrin mutation, water hardness, and eczema is related to a direct skin barrier effect,” Dr. Flohr said.
He and his coinvestigators have found supporting evidence in an adult population for their findings of a link between water hardness and infant eczema and TEWL. In a large national United Kingdom cohort of individuals born in 1958, who are part of an ongoing epidemiologic study, data show that those living in areas of high water hardness have increased rates of atopic disease.
As to the possible mechanism involved, Dr. Flohr said it’s known that as calcium carbonate concentration increases, it alters the skin surface pH. This could potentially have a detrimental effect on skin barrier function, although such an effect remains speculative. The attenuated risks of eczema and TEWL seen in FLG-carrying infants in the fourth water hardness quartile as compared to the third water hardness quartile warrants further study, but it might be the result of a calcium-scavenging effect, perhaps because of magnesium in the water, he added.
“I really think that the skin pH is involved in this,” Dr. Flohr emphasized.
Session cochair Dr. Ulf Darsow of Technical University, Munich, noted that Dr. Flohr’s countrymen at the University of Nottingham, England, have already performed an interventional study involving the use of water-softening devices. In the Softened Water Eczema Trial (SWET), the Nottingham group found no beneficial effect on pediatric eczema (PLoS Med. 2011; doi: 10.1371/journal.pmed.1000395).
“That is true, but it was a 12-week trial in children with established moderate to severe eczema,” Dr. Flohr replied. “What I’m suggesting is that potentially calcium carbonate concentration could be involved in the initiation of the skin inflammation, even if fitting a water softener once you’ve got established skin inflammation doesn’t seem to make much of a difference.”