These are the top 5 skin conditions that are commonly mistaken for eczema (even by doctors!)
Published On: Sep 2, 2022
Last Updated On: Sep 28, 2022
Conventional teaching about atopic dermatitis (AD) has been that AD is a disease of childhood that typically resolves early in life. AD is often diagnosed in early childhood and often has cycles of flare and remission. Population-based surveys looking at diagnosis of AD estimate that 50% of AD patients are diagnosed within the first year of life and about 85% by 5 years old.1 While AD can and does often resolve in later in childhood, sometimes AD persists throughout life.2 Dr. David Margolis, MD, PhD, University of Pennsylvania said, “During my medical training and early career, I was taught that early onset childhood AD disappeared by the time a child was 10 years old, and that AD did not occur in adults. Neither of these statements are accurate. It is likely that a child with AD will have less severe AD or a period of remission in late childhood, but AD can and often does recur. When it recurs, it may not affect the same body sites and the severity might be different, but it is still AD. AD does occur in adulthood both as a return disease from childhood as well as new onset.”
Patients, caregivers and even clinicians often wonder whether AD will persist, or whether a child will ‘outgrow’ the disease. This is a complex question with currently only incomplete answers. In this article, we review the demographic, genetic, biological, clinical and environmental factors currently thought to underlie persistent AD, and the important research being done to develop predictive models for the course of AD. Studies on this topic remain in their infancy, largely due to the challenges of finding groups (cohorts) of AD patients to follow long-term. Dr. Margolis stated, “Having a cohort of individuals with AD and being able to follow that cohort for 10 or more years is essential to answering big picture questions about AD persistence. It is hard to establish such a cohort. Following an outcome like AD activity over time and then following biomarkers, gene variation, therapy, environmental exposures, would be necessary.” While a few patient cohorts have been studied over time, more long-term studies are still needed.
A few studies following AD patient cohorts have reported percentages of AD patients that experience symptoms that persist into their 20s. One study involved U.S. children (aged 2 to 17) enrolled in the Pediatric Eczema Elective Registry (PEER). Patients enrolled in the PEER cohort had mild to moderate AD at the time of enrollment that required the use of topical medications, and the average age of AD onset was 1.73 years. Of the 7,157 enrolled patients, 4,248 children were followed for two years and 2,416 children (only one in three originally enrolled) were able to be followed for five years, highlighting the difficulty in following a population for longer periods of time.2 At every age, more than 80% of the PEER cohort had symptoms of AD and/or were using medication to treat their AD, even into their 20s.2 For patients who began the study at age 17 and were studied until age 20, only 50% reported having had at least one six-month AD symptom and treatment-free period in their lives.2
A second study, involving a systematic review and meta-analysis (i.e., data from many studies are analyzed together), examined the results of 45 different studies including a total of 110,651 AD patients (age 4 months to 17 years) from 15 countries who had been followed for an average of four years (range of follow-up time was three months to 23 years). All patients had AD when they started their respective studies and 72.7% had persistent AD at various time points throughout their follow-up. However, when observed over time, the rates of AD persistence decreased such that only 20% of AD persisted by 8 years old and less than 5% of AD persisted by 20 years old.3 The 45 studies were conducted differently from one another and involved different patients in terms of disease severity and age of AD onset so they can be difficult to directly compare.4,5 Even so, the authors of the meta-analysis concluded that children with already persistent disease, later age of onset, and/or more severe disease seemed to have increased persistence.3 The longer AD already persisted, the more likely it was to continue to persist.3 In this study, children who developed AD in the first two years of life had significantly lower risk of persistent disease than those who developed AD later in childhood or adolescence.3 However, in a recent study of 8,015 AD patients from the PEER cohort mentioned above, early age of onset associated with persistent disease and older age of onset associated with better disease control and less persistent AD, highlighting the need for more confirmatory studies.6
A third study looked at children living in cities in the U.S. at the ages of 5, 9 and 15 years finding the prevalence of AD to be around 15% at all three ages with females and children of Black race having more persistent AD compared to male and white counterparts.7 Along these same lines, another study found that of patients with early childhood AD, non-Hispanic black children and Hispanic children were more likely to have persistent AD compared to non-Hispanic white children (aged 4 to 7 years).8 Together, all of these studies confirm that a sizeable proportion of individuals can ‘outgrow’ their AD, yet a notable number experience persistent AD into adulthood, with multiple factors such as demographics, environment, age of onset, and severity influencing whether AD persists.
Ideally, it would be desirable for a healthcare provider to be able assess the unique characteristics of a person with AD, their environment and biology and predict the risk or probability of AD persisting or the severity of disease. Dr. Joy Wan, MD, MSCE of Johns Hopkins University agreed and stated, “If we could predict the natural history of AD for any given patient, I believe it would have a huge impact on treatment, especially as we get closer to being able to tailor treatment to a specific patient’s AD. How we manage treatments over the long-term will be influenced by the likelihood of persistence versus remission of their AD. Strategies may also be developed for prevention of AD.” While this ideal is not currently possible, several researchers are working to understand what factors might underlie AD persistence and whether any of them could be used to build this type of predictive model.
Dr. Wan said, “AD is driven by a complex interplay of genetic and environmental factors. Understanding how molecular mechanisms of AD vary across individuals and how they interact with extrinsic (e.g. environmental) influences will be key. There is no one single factor that will perfectly predict persistence or remission of AD.” Only a few studies have looked at the role of inheritance (a trait passed from one generation to the next) and genetics in persistence of AD. In a European cohort of 1,038 children, children born to two parents who both had allergies were found to be five times more likely to develop early onset, persistent AD compared to children with parents that had no allergy history.9 A study following 411 Danish children until age 13 found that a family history of paternal asthma or paternal AD associated with greater risk of persistent AD in children.10 Another study with a cohort of 260 Chinese individuals with AD onset before the age of 2 also found that family history of asthma associated with persistent AD.11
Since the filaggrin gene (Filaggrin is an important part of the skin barrier) is frequently mutated in AD and its mutation has been previously associated with more severe disease, mostly in European populations, the filaggrin gene of the 260 Chinese patients with AD was sequenced. However, there was not found to be any association between filaggrin mutations and persistent AD in this particular population.11 One study found an association between variations in the filaggrin-2 gene and persistent AD in African American patients.12
Moving beyond filaggrin, researchers have looked at variations in other genes, such as those involved in the immune system and believed to potentially contribute to AD, including thymic stromal lymphopoietin (TSLP) and its receptor IL-7R.13,14 A subset (741 children) of the PEER cohort of over 8000 children had their TSLP gene sequenced. One variant of TSLP (called rs1898671) associated more highly with children who experienced remission of AD (i.e. subsiding of their AD symptoms) compared to those without the variant.14 Other TSLP variants were found to associate with more persistent AD; rs61423440 and rs60340825 associated with a 4-fold increase in AD persistence, and rs10073816 associated with a 1.4-fold increase in AD persistence, possibly through these variants impacting the qualities of the TSLP protein.13. In addition, one variant in a component of the TSLP receptor IL-7R associated with more persistent AD.13 More studies are needed in larger cohorts of patients, particularly non-white patients, in order to better understand the genetic differences that may underlie more persistent AD.
The main clinical feature that appears to associate with more persistent AD is more severe disease at onset.10,11,15 Biologically, more persistent AD associated with signs of an allergic inflammatory profile when patient blood was analyzed for chemical messengers of the immune system, such as cytokines and growth factors.15 Environmental factors like increased stress and pollen exposure associated with more persistent AD and the authors of this study worked to put together a predictive model of AD persistence, perhaps the first of its kind. More work would be needed to confirm these findings and validate the predictive model.15
Information is also emerging on how social determinants of health can impact persistence disparities seen between individuals of different races with AD, but far more studies are needed. Stress, exposure to allergens, chemicals and other pollutants and lack of access to health care may all be reasons for increased severity and persistence in specific patients.16 Dr. Wan said, “Research indicates that individuals of Black race and other racial/ethnic minority backgrounds have greater AD prevalence, severity and persistence compared to white individuals. Our understanding of what drives these differences is very limited. While most research has focused on genetics to explain variations across racial/ethnic groups, it is very likely that social determinants of health — e.g., socioeconomic factors, environmental factors and health care access and quality — underlie the observed differences. Research on these factors is critically needed.” Being able to follow patient cohorts long-term to examine diet, environmental exposures, changes in inflammation markers in the blood and clinical features would help provide more information on real-world factors leading to persistent AD.
A previous article published by the National Eczema Association covered the association between AD and other atopic diseases such as environmental allergy, food allergy and asthma. Researchers are also investigating the connectivity of AD persistence to the development of future allergy and asthma. A study of a birth cohort of children in Japan, called the Japan Environment and Children’s Study (JECS) found that persistent AD resulted in enhanced development of food allergy, which correlated with impaired growth.17 Another study of 1,038 children in rural Europe (The Protection Against Allergy Study in Rural Environments [PASTURE]) found that children who had developed AD prior to 2 years old where symptoms persisted were more likely to develop food allergy and asthma compared to children with later onset AD symptoms or symptoms that did not persist.9
While researchers have much yet to explore regarding the natural history of AD, it is clear that a deeper understanding of the variable onset, remission and persistence characteristics of AD will help not only answer the common question of ‘will my child outgrow AD’, but ideally, eventually provide a framework for patients and their healthcare providers to better tailor management of their condition.