In the clinical experience of Jonathan I. Silverberg, MD, PhD, MPH,
That’s because a disconnect often exists between clinician-reported and patient-reported outcome measures, Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University School of Medicine and Health Sciences, said during the Revolutionizing Atopic Dermatitis virtual symposium. For example, multiple studies showed only weak to moderate correlations between the patient-focused Worst Itch Numeric Rating Scale (NRS) and Average Pruritus NRS compared with clinician-reported outcomes such as the Eczema Area and Severity Index (EASI), the objective SCORAD, body surface area (BSA), and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), with only moderate correlation coefficients ranging from 0.3 to 0.6.
Dr. Jonathan I. Silverberg
“These findings suggest that clinician-reported outcome measures are poor indicators of the patient experience,” he said. “We need to do a better job capturing patient-reported outcomes to understand how patients are impacted. But there’s something more novel to this because the weak correlations may also suggest that itch and other symptoms follow a different course than the signs of the disease. Just because the lesions flare up doesn’t mean the itch does, and vice versa. Anecdotally, this came up at many patient encounters where the skin looked good, but the patient was miserable with itch.”
To understand how the combination of itch and lesion severity predicts the severity assessment, longitudinal course, burden, and treatment of AD, Dr. Silverberg and colleagues prospectively evaluated 592 adults with AD . They defined four different AD subsets using the verbal rating scale for NRS average itch combined with either the EASI, objective-SCORAD, or vIGA-AD as follows: mild-moderate itch and lesions (MI/ML), mild-moderate itch and severe lesions (MI/SL), severe itch and mild-moderate lesions (SI/ML; the itch dominant subset), and severe itch and lesions (SI/SL). They found that most patients had MI/ML (59.4%-62.3%), followed by SI/ML (21.3%-29.1%), SI/SL (6%-12.9%), and MI/SL (3.8%-6.4%). SI/ML was more common in female and Black patients.
In addition, patients with MI/SL or SI/ML described their AD as being more severe on patient global assessment and had poor quality of life (QOL) scores, while patients with SI/SL were most likely to describe their disease as severe and have poor QOL scores. Patients with SI/ML described their disease as being more severe overall, yet patients with MI/SL or SI/SL were far more likely to be assigned severe PGA scores by clinicians. “The patients who have severe itch and mild lesions consider their disease severe, but the clinician is missing it,” Dr. Silverberg said. “Occasionally they’re picking it up but they’re missing a lot of these severe itch cases when there are milder lesions.”
In other findings, patients who had baseline MI/SL, SI/ML, and SI/SL were associated with similar frequency of AD flares, periods of AD clearance/remission, more itch triggers, and longitudinal courses over time, “which is remarkable,” he said. “It means those that have severe itch, even when they have milder lesions, are going to have unstable, more persistent disease, and have a harder time keeping control of it, and are ultimately going to require systemic therapies.” In fact, most patients with SI/SL (57.8%-66.7%) and MI/SL (53.9%-57.7%) but fewer patients with MI/ML (36.7%-38.4%) and SI/ML (30.8%-32%) initiated systemic, biologic, or phototherapy for their AD during follow-up. “There is a real upshot here clinically, in that patients are just not getting stepped up appropriately to achieve better control of their disease when they have itch-dominant AD,” Dr. Silverberg said.
He described itch-dominant AD as a novel disease phenotype that requires further investigation. “Why is it that some patients are getting such severe itch and milder looking lesions?” he asked. “I don’t think it’s just a matter of poor outcome measures that we have. So, what is it? It’s not entirely clear. Clinically, itch-dominant AD is important as it relates to the issues of diversity and skin of color because in darker skin tones, we cannot easily appreciate erythema. We may totally miss the active lesions. I think that’s a big part of why we see this itch-dominant AD more commonly in Black patients. Therefore, it is so important to ask our patients about their symptoms and to assess the severity of itch. But, even if they have what we think are milder lesions and severe itch, we must recognize they may not be well controlled. They may not be happy. They may have poor quality of life, and they may need to be stepped up appropriately. We need a lot more information to guide the assessment and management of this important subset of patients.”
Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.