GENTOFTE, Denmark, May 15 — Skin lesions on infants' arms and at their limb joints best predicted atopic dermatitis by age three, according Danish researchers.
"Although the predilection sites in the first years of life have been reported to be the head, trunk, and the extensor surfaces of the extremities, to our knowledge the early presentation and progression of eczema lesions have not been described prospectively in detail," said Hans Bisgaard, M.D., of Copenhagen University here, and colleagues, in the May 16 issue of the Archives of Dermatology.
For 356 high-risk children (208 female), in a prospective, longitudinal birth cohort, the cumulative incidence of atopic dermatitis by age three was 44% (155 children). The prevalence rate peaked at age two for boys and at age 2.5 for girls, although there were no other sex differences in the proportion of children who developed atopic dermatitis, the researchers reported.
The earliest sign of dermatitis leading to atopic dermatitis was recorded at one month, with the highest incidence occurring during the second half-year of life, according to the researchers. For those with complete follow-up, the cumulative incidence of atopic dermatitis was 31% (109) at one year, 41% (147) at age two, and 44% (155) at three years.
All children participated in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Of 411 children at the outset, 356 completed the study, and all were born to mothers with a history of asthma, while 48% of the mothers also had a history of atopic dermatitis.
A comparison of the skin lesions during the first year and a half of life between children who eventually were or were not diagnosed with atopic dermatitis found that eczema at the arms and around the arm and leg joints had the highest predictive value.
When the risk of atopic dermatitis at age three was estimated for 10 body regions, early lesions presenting on the arms and joints showed a strong correlation to later development of the skin disorder (OR, 7.5-11.8; maximum 95% CI 2.7-50.9), the researchers said.
By comparison, the odds ratio for the trunk was lower (OR 5.6 CI 2.9-10.6), while the diaper area showed no correlation (OR 1.9 CI 0.9-4.1).
The cheeks were affected in almost 80% of the children with atopic dermatitis, but cheek lesions were seen in more than 40% of children without atopic dermatitis, the investigators said.
Seborrheic dermatitis should not be mistakenly diagnosed as atopic dermatitis, the researchers cautioned, inasmuch as it was diagnosed equally in children with and without the inflammatory skin disease and also in those without other skin lesions, Dr. Bisgaard said.
Severity was scored using the Scoring Atopic Dermatitis (SCORAD) index, which included the extent, intensity, and subjective symptoms, such as pruritus and sleeplessness. According to the SCORAD index, mild symptoms were (<15>40 points).
Most infants presented with mild eczema, and the severity declined with age, with an increased fraction of mild cases, a reduced fraction of moderate to severe cases, and no obvious sex differences. Even if the present cohort is at high risk for atopic dermatitis, the severity of the symptoms should not necessarily be expected to increase compared with children from a non-risk population, Dr. Bisgaard noted.
In following the course, though not the significance, of the lesions, the researchers wrote that skin involvement for infants with atopic dermatitis began at the scalp, forehead, ear, and neck, and continued down to the trunk, finally affecting the flexor sides of the extremities. However, the eye area, palm of hand or foot sole, and nose regions were very rarely affected.
As for treatment, topical corticosteroids (mild, mid-strength, and potent) were prescribed in 7.6 courses per child during the first three years of life, with a mean ±SD of 15 ±14 days per treatment period. Seven children with respiratory symptoms received systemic corticosteroids on eight occasions, while children with other types of lesions also received topical corticosteroids.
The risk of misclassification in this study was low, the researchers wrote, because the diagnosis, detailed phenotyping, and management of skin lesions were controlled solely by the research unit's physicians. However, they added, results from high-risk children in this high-risk cohort cannot be generalized, and validation in unselected populations may be needed.
"This improved description of the progression of skin lesions facilitates early diagnosis of AD in infancy and allows studies examining early intervention and prevention strategies," Dr. Bisgaard concluded.
Although the children in Danish study were treated with topical corticosteroids, an editorial in the same issue of the Archives of Dermatology by Harvard's Abrar Qureshi, M.D., and Michael Fischer, M.D., warned about the use of topical calcineurin inhibitors, Protopic (tacrolimus) and Elidel (pimecrolimus), for atopic dermatitis for adults and children younger than two years.
The FDA is concerned, Drs. Qureshi and Fischer wrote, that the drugs are being inappropriately marketed to pediatricians and non-dermatologists who may be otherwise hesitant to use a topical steroid.
Data so far suggest that a significant number of prescriptions are being written for both Protopic and Elidel for children in this age group, despite this being an off-label use of both drugs, the researchers wrote.
A Black-Box warning issued by the FDA last January stated that reasons for this action include sporadic reports of lymphoma and skin cancer in some individuals using these topical calcineurin inhibitors; concerns about systemic absorption resulting in greater systemic exposure in a subpopulation of treated patients; unusually aggressive and inappropriate marketing of topical calcineurin inhibitors as first-line agents; and early carcinogenicity in animals treated with very high systemic doses.
The editorialists concluded: "When the next promising new agent is approved by the FDA, we hope that medical professionals will provide the guidance our patients so sorely need by choosing patients for new drugs carefully, monitoring them closely, and encouraging them to enroll in post-marketing research studies whenever possible."
Primary source: Archives of Dermatology
Source reference:
Liselotte Brydensholt Halkjaer, et al, "Development of Atopic Dermatitis During the First 3 Years of Life: The Copenhagen Prospective Study on Asthma in Childhood Cohort Study in High-Risk Children," Archives of Dermatology 2006; 142:561-566.
Additional source: Archives of Dermatology
Source reference:
Abrar A. Qureshi and Michael Fischer, "Topical Calcineurin Inhibitors for Atopic Dermatitis," 2006; 142: 633-637.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
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