Conference Coverage
Standardization lacking in pediatric trials of atopic dermatitis
CHICAGO – Severity assessments may not hold up in pediatric AD studies.
CHICAGO – A streamlined set of diagnostic criteria from the American Academy of Dermatology’s most recent consensus criteria for diagnosing atopic dermatitis (AD) produced a specificity of more than 95%, and was also highly sensitive, a prospective analysis found.
“Atopic dermatitis typically presents in childhood and is associated with a worsened quality of life, with severe itch and lack of sleep, and substantial health care costs due to therapeutic management and increased hospitalizations,” study author Jeremy Udkoff said at the World Congress of Pediatric Dermatology. “We also know that in order to treat the disease and to learn more about it, we have to have a good tool for diagnosing it. When it comes to clinical studies and research, we require a systematic and refined set of criteria.”
Jeremy Udkoff
The next set of commonly used criteria to appear were created by the U.K. working party, for which researchers used logistic regression to systematically create a minimum set of effective criteria for AD (Br J Dermatol. 1994;131[3]:383-96). For these guidelines, meeting a diagnosis of AD requires an itchy skin condition, followed by three or more of the following: a history of flexural involvement; a personal history of asthma or hay fever; a history of general dry skin in the last year; visible flexural eczema, and onset under the age of 2 years. “A subsequent validation trial found [the U.K. working party criteria] to have a low sensitivity, which as you can imagine, could be a very large problem,” he said (Arch Dermatol. 1999;135[5]:514-6).
In 2001, the AAD consensus conference created revised hierarchical criteria known as the AAD consensus criteria (J Am Acad Dermatol. 2003;49[6]:1088-95). “These were initially created for more of a gestalt-type picture of AD in the clinic, but because it flows so well, it’s currently being used in about one-third of clinical trials,” Mr. Udkoff said. “However, [the AAD criteria] have not been validated, so we didn’t know its sensitivity or specificity. In addition, we didn’t have a ‘checkbox’ form that tells us how many of each of the criteria are required to make the diagnosis. We didn’t know how many ‘essential,’ ‘important,’ or ‘associated’ features we need to make this diagnosis.”
For the current study, he and his associates set out to determine how many “essential,” “important,” and “associated” criteria are necessary to make the AAD consensus criteria work. They also set out to create a usable checkbox form, validate the criteria, and compare it to the Hanifin-Rajka (HR) and U.K. criteria. To accomplish this, they created a questionnaire comprised of HR, U.K., and AAD criteria, examined the criteria on 60 subjects with and without AD, and compared the diagnostic features of each of those criteria against a gold standard dermatology diagnosis from one of seven pediatric dermatologists. Next, they ranked all 56 possible AAD criterion combinations based on their overall sensitivity and specificity, and chose the most predictive combination. “Once we had the optimal set of criteria, we validated it on a new cohort to determine its sensitivity and specificity, and compared it with the classic HR and U.K. criteria,” Mr. Udkoff explained.
Overall, the researchers evaluated findings from 100 subjects: 58 with AD, and 42 controls. Those with AD were about 3 years younger, compared with controls (a mean age of 5 years vs. about 8 years, respectively). About 40% of patients were Hispanic and about 30% were white. Mr. Udkoff and his associates confirmed the hierarchical structure of the AAD criteria and found that individual “essential” AAD criteria of pruritus, typical AD pattern, and chronic/relapsing course each had a sensitivity that exceeded 96%. This was followed by the “important” criteria of early age of onset, atopy, and xerosis, which had a sensitivity that ranged between 88% and 95%, while the associated criteria had a sensitivity that ranged between 50% and 85%.
Next, the researchers systematically tested all combinations of the AAD criteria and found that three “essential” AAD criteria, two or more of the “important” criteria, and one or more of the “associated” criteria were optimal in diagnosing AD. Mr. Udkoff noted that the findings can be translated into a simple “3-2-1 rule” that “is both practical and pragmatic,” he said. Using this rule, sensitivity was 91.4% and specificity was 95.2%.
Currently, the researchers are working to validate this criteria in different subgroups of patients. To date, they have found that children younger than 1.5 years get one bonus “essential” criteria for being an infant, so for that population a 2-2-1 rule would apply.
Mr. Udkoff reported that the research was supported by a training grant from the National Institutes of Health. He reported having no financial disclosures.