How to Tell the Difference Between Nummular Eczema and Ringworm
It’s often difficult to distinguish between nummular eczema and ringworm, so it’s always best to be evaluated by a dermatologist, say experts.
Published On: Oct 28, 2022
Last Updated On: Nov 1, 2022
While atopic dermatitis (AD) is primarily considered a disease of childhood, we know that for many, AD can persist into adulthood. For some patients, AD may even arise for the first time in adulthood.1
Population-based surveys looking at age of diagnosis of AD estimate that 50% of AD patients are diagnosed within the first year of life and about 85% by five years of age.2 However, many prior studies about AD diagnosis only followed children through the age of 20, which was considered adulthood, and did not take the study further into life or look at the possibility of adult-onset AD.1 Recent research has found that as many as 1 in 4 adults with AD report symptoms without having had AD in childhood.1 While there is ongoing scientific discourse about whether some or all of adult-onset AD is undiagnosed childhood AD (likely mild with few symptoms) that comes back later in life (considered a bimodal age distribution of AD),3 several publications support that true adult-onset AD does occur.4 Here we will discuss current research on the frequency, characteristics and underlying biology of AD appearing in adulthood, as well as the treatment of AD in adults and elderly populations no matter when their AD symptoms appeared.
One of the best ways to find out about when a disease first arises in a population is to follow people over the course of a lifetime. While a seemingly straightforward approach, these types of longitudinal research studies are very challenging to conduct for researchers as well as participants, especially when the study can potentially span many decades. For example, in one longitudinal study of children that enrolled 7,157 AD patients, 4,248 children were followed for 2 years and 2,416 children (only 1 in 3 originally enrolled) were able to be followed for 5 years.5 Owing to the difficulty of this longitudinal research approach, many of the studies investigating the prevalence of adult-onset AD or all adult incidence of AD have taken more of a single point in time “snapshot” within a population. A systematic review and meta-analysis (looking for all the studies published on a topic area and then analyzing the pooled data from those studies) arrived at the conclusion that on average worldwide 1 in 4 adults with AD report that their symptoms started later in life with no previous history of the disease.1 The highest proportion of adult-onset AD was found in the United States (53%) while Europe, Asia and other regions showed around 21% to 24% of adult AD cases to be adult-onset.1
Population studies conducted in various locations around the world have also looked at the incidence of AD in adults regardless of age of onset and found it varies widely from 1% to as much as 22%. A study from Finland using the Finnish Institute for Health and Welfare database that included over two million people seen in primary care for treatment of AD reported an overall incidence of patient consultations to be 1%.6 Of those patients treated for AD, nearly 50% were 0 to 14 years old, however 16.8% were over 50 years old and 9.3% were over 65. Another recent study out of Finland found that the lifetime prevalence of AD was 21.9% with the highest prevalence being in individuals 30-39 years old.7 The discrepancy between the two studies out of Finland may indicate that adult patients with AD may not always seek treatment for their symptoms. A comprehensive study in England followed patients throughout their lives from birth to age 42 or 50,8 each cohort with over 17,000 individuals (1958 British Cohort and 1970 British Cohort). The prevalence of AD in these two populations was between 5% and 15%. Between 40% and 43% of those with AD reported having experienced no childhood AD but having AD symptoms that arose in adulthood.8 Another British study of over 9 million individuals registered in the Health Improvement Network found AD in 18.3% of children, 7.7% of adults, and 11.3% of older adults (defined as >75 years old).9 This study seems to indicate a second peak of AD incidence in elderly individuals. A review of literature from patients in Poland and Japan found a 1.86% prevalence of AD in populations over 60 years in Poland and 2.6% in 60 and older populations in Japan.10 United States cohorts of adult AD patients have concluded that the prevalence of adult AD in US populations is around 7%, similar to the British cohort described above.11 Another United States population-based study found that in a population of 1,278 adults 7.3% of them had AD with nearly 40% of those with AD having moderate to severe symptoms.12 More studies are needed to understand the experience of adult individuals with AD around the world overall, and specifically for those with adult-onset disease.
To date, adult-onset AD is known to be similar to childhood-onset AD in that it is a chronic, relapsing disease with times of improvement and times of more severe symptoms. Dr. Katrina Abuabara, MD, MSCE of the University of California San Francisco said, “There seem to be some differences in both the clinical presentation and immunological profile of AD in older adults as compared to younger adults and kids. Although there is a lot of variation in how AD can present at any age, early childhood AD often includes weepy lesions around the mouth, whereas childhood AD classically involves skin feet, and AD among older adults may impact the outsides of the arms and have a drier, more thickened appearance.”
To tease apart symptom differences and similarities between childhood and adult-onset AD, Silverberg and colleagues studied 356 adults with AD (> age 18).13 A total of 42% of these adults reported adult-onset AD with about 1 in 4 reporting AD symptoms starting after 50 years old.1,13 Although the physical symptoms and signs of AD were reported on multiple body sites, individuals in one study predominantly reported AD symptoms on the hands and neck13 while another study reported higher incidence of foot lesions.1 Several studies showed less severe symptoms on the face, hands, and feet in adult AD compared to childhood AD.4 The most common locations for AD lesions specifically in adult-onset AD were the hands, eyelids, neck, and flexural surfaces of the upper limbs.14
Very few studies have compared adult-onset AD with AD that initiated in childhood and persisted. One Italian, multicenter study of 253 patients indicated that AD severity was worse in persistent AD, but that itch intensity was higher in adult-onset AD.15 A US-based survey reported no differences in disease severity between adults who had childhood-onset AD compared to adult-onset AD.13 Adult-onset AD also did not seem to associate with a family or personal history of AD, and other atopic conditions (i.e. asthma, hay fever, food allergy), suggesting other factors besides genetics (such as environment) playing a role.13
At present, the same general criteria are used as are used for diagnosing adult-onset AD as childhood AD.4,16 Yet despite the similarities in diagnostic criteria the differences in morphology and distribution can make the diagnosis of adult-onset AD “very challenging even for expert clinicians.” 4 In addition, the differential diagnosis (i.e. assessment of patient history and/or test results to arrive at the correct diagnosis among several conditions that may share signs and symptoms), is more broad in adults than children. For example, AD and the skin disease psoriasis can be difficult to tell apart in certain adult patients.17,18 AD can also be confused with allergic contact dermatitis, certain skin infections, and other diseases. In order to rule out these other diseases physicians may use skin biopsies, skin scrapings, patch testing, and testing for levels of the allergic immune marker IgE to complement the physical exam and patient history.4 Researchers are currently exploring new diagnostic testing options, such as the use of skin tape strips that could aid diagnostic accuracy and timeliness.19 Accuracy and timeliness are both important as a 2019 survey of AD patients from the More Than Skin Deep meeting indicated that individuals with adult-onset AD were more likely to experience delays in diagnosis with over 20% of adults reporting diagnosis taking more than 2 years.
We asked AD researchers, “Are there differences in the underlying genetics or molecular pathways of patients with childhood-onset versus adult-onset AD?” Dr. Jonathan Silverberg, MD, PhD, of George Washington University said, “Studies showed that specific genetic factors may contribute to more severe and persistent disease, such as Filaggrin (a gene that codes for a protein that helps form the skin barrier) loss of function mutations in adults that had childhood-onset AD. Some adult-onset patients have a high number of triggers of itch and flare ups. Additional factors include exposure to contact allergens and, less commonly, airborne or food allergens that can worsen the underlying AD.” This is probably true of both childhood-onset, persistent AD and adult-onset AD”. Dr. John Hanifin, MD, professor emeritus of Oregon Health and Science University followed up by saying factors that made AD worse for adults, whether child-onset or adult-onset included, “Genetics, surroundings (dry climate/home heating/irritating job exposures), psychological stresses, allergies and infections.”
In the English study of two cohorts followed from birth to age 42 or 50 years, women, smokers in adulthood and adults of lower socioeconomic status in childhood were more likely to have adult-onset AD while childhood-onset AD had more closely associated molecular changes like Filaggrin mutations and high levels of allergen-specific IgE.8 While a few other studies have indicated that being male was more highly associated with adult AD or that the sex of the individual did not matter,4,10 the consensus in the United States literature appears to be that being female is most often associated with higher levels of adolescent and adult AD.11 Environmental factors associated with adult AD in the United States have been listed as being born in another country and migrating to the United States, exposure to airborne pollution, such as in urban cities, smoking, stress and alcohol consumption.11
Adult-onset AD may also arise due to contributions from physical factors that can change as individuals age. For example, as we get older, our immune system generally becomes less able to fight off infections (a process called immunosenescence).10 The immune system can also switch to activating components more associated with AD (Th2 skewed immune system). At the same time, IgE levels, which indicate an allergy component to adult AD, can increase later in life, which may be associated with a second peak in AD incidence in elderly adults.10 In addition, the integrity of the physical skin barrier can also worsen with age, becoming more physically fragile and exhibiting increased transepidermal water loss, increasing susceptibility to changes in the microbiome and environmental irritants.10
One study looked at features including the appearance of AD lesions under a microscope (histology), changes in gene expression, and immune system changes with age in a cohort of 246 patients with AD (in age groups 18-40, 41-60, and more than 60 years old) and 71 healthy controls.20 Immune cells decreased with age in the skin lesions and blood of AD patients but increased in the controls, and IgE levels increased with age in AD patients. However, in this study, some of the typically abnormal features associated with disrupted barrier in AD were normal in aged patients with AD.20 Clinical and biomarker research studies such as these are important to continue to identify the similarities and differences of AD at various times of onset to facilitate use of the best treatment approaches.
The current framework for the step-wise treatment of adult-onset AD is comparable to adults with AD who have persistent disease from earlier in life, although this is not a group of individuals that has been specifically studied in clinical trials or other observational studies. Reports providing real-world data about the treatment of adult-onset AD patients are beginning to emerge with one recent report demonstrating the efficacy of dupilumab in the treatment of a small group of 16 adult-onset AD patients (median age 41 years).21
Significant treatment challenges arise in treating AD in older adults, as older individuals in general have not traditionally been well represented in clinical trials, making it difficult to apply what is known about successful treatments in children and young adults to elderly patients.22 For example, dupilumab was found to be the most commonly prescribed systemic treatment for AD in elderly patients,23 while less than 5% of patients who received dupilumab in clinical trials were older than 65 years old.24 Importantly, there are specific concerns in the treatment of elderly individuals with AD, regardless of age of onset. Elderly patients may have one or more comorbidities (co-occurring diseases), including liver or kidney disease, cancer, or infection with hepatitis B or C or with HIV, that make it difficult to use certain drugs for AD treatment.23
There is hope for more personalized medicine in the future. Dr. Abuabara, said, “AD, even among children and certainly in adults, is very heterogeneous (meaning can vary widely from one person to another). I anticipate that one day soon, we will have better diagnostic tools to understand different types of AD among all age groups and identify the treatments that are most likely to help specific patients.” Further study is needed to understand the underlying factors and contributors to adult-onset AD that can guide timely diagnosis and treatment selection.
References:
1. Lee HH, Patel KR, Singam V, Rastogi S, Silverberg JI. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532 e1527.
2. Fishbein AB, Silverberg JI, Wilson EJ, Ong PY. Update on Atopic Dermatitis: Diagnosis, Severity Assessment, and Treatment Selection. J Allergy Clin Immunol Pract. 2020;8(1):91-101.
3. Hanifin JM. Adult-Onset Atopic Dermatitis: Fact or Fancy? Dermatol Clin. 2017;35(3):299-302.
4. Silverberg JI. Adult-Onset Atopic Dermatitis. J Allergy Clin Immunol Pract. 2019;7(1):28-33.
5. Margolis JS, Abuabara K, Bilker W, Hoffstad O, Margolis DJ. Persistence of mild to moderate atopic dermatitis. JAMA Dermatol. 2014;150(6):593-600.
6. Salava A, Rieppo R, Lauerma A, Salo V. Age-dependent Distribution of Atopic Dermatitis in Primary Care: A Nationwide Population-based Study from Finland. Acta Derm Venereol. 2022;102:adv00738.
7. Kiiski V, Salava A, Susitaival P, Barnhill S, Remitz A, Heliovaara M. Atopic dermatitis in adults: a population-based study in Finland. Int J Dermatol. 2022;61(3):324-330.
8. Abuabara K, Ye M, McCulloch CE, et al. Clinical onset of atopic eczema: Results from 2 nationally representative British birth cohorts followed through midlife. J Allergy Clin Immunol. 2019;144(3):710-719.
9. Chan LN, Magyari A, Ye M, et al. The epidemiology of atopic dermatitis in older adults: A population-based study in the United Kingdom. PLoS One. 2021;16(10):e0258219.
10. Tanei R, Hasegawa Y. Atopic dermatitis in older adults: A viewpoint from geriatric dermatology. Geriatr Gerontol Int. 2016;16 Suppl 1:75-86.
11. Sacotte R, Silverberg JI. Epidemiology of adult atopic dermatitis. Clin Dermatol. 2018;36(5):595-605.
12. Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and Disease Burden of Atopic Dermatitis in the US Adult Population. J Invest Dermatol. 2019;139(3):583-590.
13. Silverberg JI, Vakharia PP, Chopra R, et al. Phenotypical Differences of Childhood- and Adult-Onset Atopic Dermatitis. J Allergy Clin Immunol Pract. 2018;6(4):1306-1312.
14. Chan AR, Sandhu VK, Drucker AM, Fleming P, Lynde CW. Adult-Onset Atopic Dermatitis: Presentations and Progress. J Cutan Med Surg. 2020;24(3):267-272.
15. Megna M, Patruno C, Balato A, et al. An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease. Arch Dermatol Res. 2017;309(6):443-452.
16. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.
17. Guttman-Yassky E, Krueger JG. Atopic dermatitis and psoriasis: two different immune diseases or one spectrum? Curr Opin Immunol. 2017;48:68-73.
18. Noda S, Suarez-Farinas M, Ungar B, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015;136(5):1254-1264.
19. He H, Bissonnette R, Wu J, et al. Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis. J Allergy Clin Immunol. 2021;147(1):199-212.
20. Zhou L, Leonard A, Pavel AB, et al. Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2019;144(1):144-156.
21. Erbagci E, Demirel Ogut N, Koc Yildirim S, Hapa FA. Is dupilumab effective in adult-onset atopic dermatitis: Real-life experience of 16 patients. J Cosmet Dermatol. 2022.
22. Sreekantaswamy SA, Tully J, Edelman LS, Supiano MA, Butler D. The underrepresentation of older adults in clinical trials of Janus kinase inhibitors in the treatment of atopic dermatitis. J Am Acad Dermatol. 2022.
23. Drucker AM, Lam M, Flohr C, et al. Systemic Therapy for Atopic Dermatitis in Older Adults and Adults With Comorbidities: A Scoping Review and International Eczema Council Survey. Dermatitis. 2022.
24. Lam M, Zhu JW, Maqbool T, et al. Inclusion of Older Adults in Randomized Clinical Trials for Systemic Medications for Atopic Dermatitis: A Systematic Review. JAMA Dermatol. 2020;156(11):1240-1245.
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