Therapeutic advances for atopic dermatitis (AD) were stagnant for decades. Ever since topical agents Pimecrolimus and Tacrolimus were given controversial black box cancer warnings, there was a pervasive chill on any new therapeutic development in AD. In fact, for moderate to severe AD, no new internal agents were FDA approved for more than four decades. This bleak situation suddenly changed with the recent introduction of Dupilumab, the first biologic agent for dermatologic use outside psoriasis. With the encouraging sign of repentance from the FDA which fast-tracked the approval of Dupilumab, there are now many new compounds in development for moderate to severe disease. This development is likely a sign of a new era of therapeutic advancement.
The past decades have seen remarkable development of medications for patients with moderate to severe psoriasis, and it appears reasonable today to assume that similar therapeutic ‘great leap forward’ may take place for AD in the coming decade. To optimize and generalize these therapeutic benefits of the coming new agents, a different conceptual change must be tackled and solved. This is because the two disorders, psoriasis and AD, have different characteristics even though they are both chronic and inflammatory. When a new medication is developed for psoriasis, the trials are done for the predominant subtype, plaque type. The same cannot be said for AD. When a new medication has been tested and approved for AD, only a small cohort is addressed: those who fit the diagnostic criteria for AD. In reality, AD is one member of the eczema family which includes many other phenotypic subtypes including nummular, xerotic, gestational, dyshidrotic, hand and foot, etc., all of which could potentially benefit from new medications in the pipeline. Moreover, because all these members of the eczema family prominently involve pruritus, there are millions of people who suffer from secondary manifestations of itching who may get labeled with other diagnosis such as lichen simplex chronicus or prurigo nodularis.
In regard to diagnosis and categorization, people are either ‘splitters or lumpers’. When splitters among clinicians, the FDA, and payers prevail, patients are put at risk of confining categorizations that may unfairly limit treatment access. On the other hand, if lumpers prevail, diversity and range of presentation are appreciated which benefit a large number of patients who may not fit narrow categorizations. This becomes illuminated when we realize that most, if not all, new agents will be developed for AD rather than any of the other member of the eczema family. The AD specifically has been highlighted as a high priority of the FDA and it is commonly recognized by payers. This begs us to ask: what about the other patient’s with disease in eczema family? Don’t they deserve that same priority and recognition? These are patients who do not fit the diagnostic criteria for AD but may respond beautifully to current and future therapies approved for AD. There are reports of patients with other disorders in the eczema family responding well to dupilumab, including at our UCSF center. The risk of narrow categorization is that these patients could be denied therapy. Similar situations are leading to clinical frustration around the world for a variety of patients including those with generalized lichen simplex chronicus, generalized nonspecific eczematous eruptions and other Th2 medicated dermatoses that do not meet the strict diagnostic criteria for AD.
One critical and bitter lesson our specialty learned through experience with the biologic agents for psoriasis is that new therapies, no matter how effective, are useless if the patients cannot access the medication. Moreover, access is most often determined by those who are neither clinicians nor scientists. It is often left in the hands of those who do not interact with diseases or patients directly but rather their entire exposure to healthcare is financial. These people do not have the knowledge base to understand the difference between psoriasis, where one subtype predominates, versus AD which is part of a more widely representative phenotypic group. If left to their own devices, these nonclinician, nonscientists, are more likely to drift toward narrow characterization since they have the financial incentive to deny treatment whenever possible.
One idea to solve this problem is to look at historical precedents such as in the field of psychiatry. A similar challenge was seen decades ago with the diagnosis of obsessive–compulsive disorder (OCD). Just like the variable presentations of eczema, there are many psychiatric diseases with OCD-like features. No matter how the specialty of psychiatry defined OCD (through five different revisions of the Diagnostic and Statistical Manual of Mental Disorders, DSM) there are always millions of patients who fell outside the diagnostic definitions. Compulsive gambling? Trichotillomania? Compulsive skin picking? Even though they did not fit the OCD diagnosis of DSM, and may even come with their own diagnostic terminology, they are still deserving of a trial of OCD-efficacious medications.
This dilemma was solved by the introduction and adoption of the concept and terminology ‘OCD-spectrum disorder’. In this, patients with OCD traits who do not meet the DSM criteria for OCD were legitimized. This simple term expanded an essential clinical concept and was effective in broadening the disease appreciation by insurance and government agencies. Subsequently, adoption of the term and concept ‘OCD spectrum disorder’ led to the expansion of the number of patients who could access new OCD medications. Similar broadening of categorization has also benefited those with autism spectrum disorder.
It is unlikely that medications are going to be developed for each subtype of eczema or secondary manifestation. In view of this, the authors of this editorial strongly recommend our specialty emulate this successful precedent of psychiatry. ‘Eczema’ is already a term that is devalued by payers. As you know, dermatologist cannot be reimbursed for a visit if the diagnosis is ‘eczema’ without further specification. Since eczema is a term no longer respected by payers, we advocate for replacement with a term that will aid in expanding the use of new AD therapeutics: ‘atopic dermatitis spectrum disorder’.
It is tragic to see patients suffering, unable to receive treatment, when we know there are possible therapeutic options. For the sake of our patients, now and in the future, the authors advocate the use of ‘atopic dermatitis spectrum disorder’. Ideally, this term will be adopted, utilized, and integrated into the framework of our conversations, practices, and research to help avoid the dangerous threat of narrow categorization – thus improving the lives of our current and future patients.
Disclosure statement
John Koo is Speaker for Regeneron and Sanofi.