A large international study suggests the association is independent of genetics and antibiotic exposure.
Children who catch frequent respiratory infections in their first three years of life are significantly more likely to develop atopic dermatitis, according to a large international study.
The research, published in JAMA Dermatology, analysed data from 663 children enrolled in Denmark’s Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) and validated the findings in a further 707 children from the US Vitamin D Antenatal Asthma Reduction Trial (VDAART).
The researchers say the analysis provided the strongest evidence to date linking early-life respiratory infection burden with childhood eczema.
“This study found that early respiratory infection burden is associated with AD diagnosis in a dose-dependent manner in two independent birth cohorts,” they wrote.
“These findings suggest a long-term relationship between early respiratory infections and AD that has previously been unclear due to inconsistent findings in previous studies.”
Although atopic dermatitis is one of the most common chronic diseases of childhood, affecting up to one in five children in some populations, its environmental triggers remained poorly understood, the researchers wrote.
Previous studies investigating infections have produced conflicting findings, with some supporting the hygiene hypothesis that early microbial exposure protects against allergic disease, while others have suggested infections may instead increase eczema risk.
To explore the question, investigators prospectively tracked infection episodes from birth to age three years using parent-completed daily symptom diaries, recording common colds, physician-diagnosed otitis media, tonsillitis, and pneumonia, as well as gastroenteritis and fever episodes.
Children then underwent regular clinical assessments for atopic dermatitis until age 10 years, with diagnoses based on the established Hanifin and Rajka criteria and disease severity measured using the SCORAD index.
The average child experienced 16 infection episodes and 138 infection days during the first three years of life, with the common cold accounting for the largest proportion of illnesses.
The researchers found no significant differences in baseline characteristics across infection groups, including sex, caesarean birth, maternal smoking, daycare attendance, pet ownership, prenatal antibiotic exposure, or socioeconomic factors, suggesting these variables were unlikely to explain the findings.
Children in the highest third for infection episodes were 63% more likely to receive an atopic dermatitis diagnosis than those in the lowest third, while children with the greatest number of infection days had an 80% higher risk.
Longitudinal analysis across the full 10-year follow-up produced similar findings, with adjusted odds ratios of 1.61 and 1.69 for infection episodes and infection days respectively.
Every additional infection episode was also associated with a modest but statistically significant increase in eczema risk, demonstrating a dose-response relationship rather than a simple threshold effect.
The association was driven almost entirely by respiratory illnesses, the researchers said.
Frequent common colds showed one of the strongest relationships with later eczema, with children in the highest tertile for cold episodes having a 71% increased risk of atopic dermatitis compared with those in the lowest tertile.
Acute otitis media nearly doubled the risk, while repeated tonsillitis and pneumonia were also associated with significantly higher odds of eczema. In contrast, gastroenteritis and fever episodes showed no significant relationship with disease development.
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Replication in the US cohort strengthened the findings. Children with the highest infection burden had 76% higher odds of developing atopic dermatitis by age six years, and each additional infection episode increased risk by approximately 3%, despite differences between the two study populations and methods of eczema ascertainment.
The researchers also examined whether the association could simply reflect greater antibiotic exposure among children experiencing frequent infections.
Earlier studies have linked early antibiotic use with increased eczema risk, raising the possibility that antibiotics rather than infections themselves drive the association.
However, adjusting for systemic antibiotic prescriptions throughout childhood had little effect on the results, and there was no evidence of interaction between infection burden and antibiotic exposure.
Likewise, the team investigated whether the well-established eczema risk gene FLG might explain the findings.
Children carrying loss-of-function filaggrin variants remained at higher overall risk of atopic dermatitis, but these variants neither increased infection susceptibility nor altered the relationship between infections and eczema, suggesting respiratory infection burden represents an independent risk factor rather than a marker of underlying genetic susceptibility.
The researchers noted that while children with frequent infections were more likely to develop atopic dermatitis, they did not experience more severe disease.
SCORAD scores, average disease severity, and age at first diagnosis were similar regardless of infection burden, indicating infections may influence whether eczema developed rather than how severe it became.
The researchers said their findings added weight to growing evidence that repeated respiratory infections early in life may influence immune development in ways that predispose children to atopic disease.
They noted that previous studies have reached inconsistent conclusions because of differences in study design, reliance on registry data or limited follow-up, whereas the current study combined prospective daily infection recording with detailed clinical phenotyping over 10 years and independent validation in a second international cohort.
However, they stressed that the observational study could not establish causality.
Because many children developed eczema during the same period that infections were being recorded, it remained unclear whether infections contribute directly to disease development, whether early immune dysfunction predisposes children to both infections and eczema, or whether another biological mechanism was underlying in both conditions.
The researchers said future studies should investigate whether preventing or reducing respiratory infections in infancy could ultimately lower the risk of childhood atopic dermatitis.
