Prevalence, incidence and relative risk of cardiovascular disease risk factors in adults with atopic dermatitis: A systematic review

Abstract

Atopic dermatitis (AD) has been associated with cardiovascular disease (CVD). A better understanding of CVD risk factors in AD populations may help dermatologists better counsel their patients regarding potential risks and treatment choices. This systematic literature review evaluated the prevalence, absolute risk (i.e.,  incidence) and relative risk of CVD risk factors in adults with AD. MEDLINE, Embase and The Cochrane Library were searched for English‐language articles published between January 2005 and the search date (16–17 March 2021) using terms for AD, prevalence/risk and CVD risk factors. Observational studies that reported the prevalence, absolute risk and/or relative risk of CVD risk factors in adults with AD were eligible. Of the 1277 unique articles identified, 71 met the inclusion criteria. Most studies were cross‐sectional or retrospective cohort studies from Europe, North America or Asia; many used national databases. Studies were heterogeneous, with inconsistent definitions of AD and risk factors (especially smoking and obesity), different methodologies and different populations (e.g., ethnicity). Within most controlled studies, the prevalence of several risk factors, particularly obesity, hypertension and dyslipidemia, was higher for AD than for controls. Where assessed, the prevalence of most CVD risk factors increased with increasing AD severity. Relative risks varied across studies. Only nine studies reported the temporal relationship between AD and CVD risk factors. Six studies reported absolute or relative risk of developing CVD risk factors (diabetes, hypertension and smoking) in AD populations; only one of these reported an elevated risk (hypertension). Despite the high number of studies to date, conclusive data regarding the relationship between AD and many CVD risk factors are lacking, and additional, carefully designed, prospective studies are required.

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INTRODUCTION

Atopic dermatitis (AD) is an inflammatory skin disease primarily characterised by erythematous, pruritic, eczematous papules and plaques that are often painful. AD generally occurs in childhood and may persist into adulthood but can also first develop in adults. AD is associated with a range of comorbidities. Although not conclusively established, increasing evidence indicates that patients with AD, especially those with severe disease, have higher rates of cardiovascular disease (CVD) events, such as stroke and myocardial infarction, and metabolic disease compared with people without AD. These CVD and metabolic comorbidities may be linked to AD via common underlying inflammatory mechanisms. Indeed, the links between AD and CVD, as well as allergic diseases, psychiatric diseases and cancer, have led to AD increasingly being recognised as a multifactorial disorder. In addition, increased CVD in patients with AD may also relate to higher rates of modifiable risk factors, such as smoking, sedentary lifestyle and corticosteroid treatment. However, because of the prevalence of both CVD and risk factors for CVD in the general population, it is difficult to establish if patients with AD are more likely to have risk factors that contribute to CVD.

The relationship between AD and individual CVD risk factors was examined in several previous systematic reviews and meta-analyses. Significant associations with AD in adults have been reported for obesity (odds ratios [ORs] of 1.23 and 1.56), overweight (OR, 1.29), hypertension (ORs of 1.16 overall and 2.33 for moderate-to-severe AD), active smoking (ORs of 1.30 and 1.91) and exposure to passive smoke (OR, 3.62). However, no association was found for type 2 diabetes (T2D). These meta-analysis results are generally supported by systematic reviews without meta-analyses. However, most of these reviews focused on relative risk rather than prevalence or absolute risk (i.e., incidence) of CVD risk factors in AD populations. The objective of this systematic literature review was to evaluate the prevalence, absolute risk and relative risk (compared with a general [i.e., no specific known disease] non-AD population) of a range of CVD risk factors in patients with AD.

MATERIALS AND METHODS

Data sources and search terms

This systematic review followed a prepared protocol (not registered). The online databases MEDLINE (via OVID), Embase (via OVID) and The Cochrane Library were searched on 16 or 17 March 2021. Search strategies (Supporting Information: Table ) were adapted for each database and included terms for AD/atopic eczema; the CVD risk factors of interest; and risk, prevalence and incidence. The search was restricted to publications from January 2005 to the search date, with no geographic limitations.

Study selection

Titles and abstracts of retrieved studies were screened using predetermined criteria. Studies that included adult (typically aged ≥18 years) patients with AD, with or without non-AD control populations, were eligible. All study designs were included, except preclinical/animal studies, randomized controlled trials (RCTs; however, long-term follow-up studies of RCTs were eligible for inclusion), studies pooling AD populations with non-AD populations and post hoc subgroup analyses. Case reports, commentaries, editorials, letters (except those reporting original data), consensus reports, conference abstracts and non-English-language publications were excluded. Systematic reviews and meta-analyses were hand-searched to identify additional publications. There were no restrictions on therapy or intervention type.

The full text of publications meeting the screening criteria, and those that could not be excluded at screening, were reviewed and included if they reported on the prevalence, absolute risk (i.e., incidence) or relative risk (usually compared with a non-AD population) of any of the following traditional CVD risk factors among patients with AD: obesity/overweight or reported body mass index (BMI) measurements; smoking (active or passive); hypertension; diabetes (T2D, type 1 diabetes [T1D], gestational or unspecified); or lipid disorders (e.g., dyslipidemia, hyperlipidemia, hypercholesterolemia). In addition, the less traditional risk factors of family history of CVD (prevalence only) and chronic kidney disease (CKD) were included as exploratory outcomes. Studies reporting actual BMI or lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and/or triglycerides) were also included. The search also included studies reporting on human immunodeficiency virus infection in patients with AD, but the results (one study) are not included in this report.

One independent researcher screened titles/abstracts and full texts; any discrepancies were resolved by consensus with the authors. Articles for inclusion were confirmed by the authors before data extraction began.

Data extraction

Data were extracted from full-text articles by one researcher into standardised, preapproved tables and were verified by a second researcher. Data extracted included study design and characteristics; patient demographics and disease characteristics; prevalence, absolute risk and/or relative risk of CVD risk factors; and BMI and/or lipid levels. All data reported in this systematic review are from the included studies, and no additional statistical analysis was conducted.

Study quality assessment

One researcher assessed study quality using study design–specific Critical Appraisals Skills Programme (CASP) checklists (); these assessments were verified by one author. Study quality grades were assigned based on the number of potential biases or limitations identified (A = 0–1, B = 2–3, C = 4–5 and D = >5) and agreed to by all authors.

RESULTS

Search results and study characteristics

A total of 1632 articles were identified through database searches, and an additional three were identified through hand-searching (Figure ). After removing duplicates, 1277 titles/abstracts were screened; of these, 192 full-text articles were assessed. Of the 71 included studies, 22 were retrospective cohort studies, 36 were cross-sectional studies, seven were prospective cohort studies and six were case-control studies (Supporting Information: Table ). Studies were conducted in a broad range of countries in Europe, North America and Asia, with the most numerous being from Denmark and the United States (n = 14 each). National databases or registries were the most common source of data, and many studies used the same databases (e.g., Danish national patient registries, the Korea National Health and Nutrition Examination Survey and the Taiwan National Health Insurance Research Database). Twenty-six studies matched patients with AD to non-AD patients, 35 studies included an unmatched control group and 10 studies had no control group.

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The overall quality of the included studies was generally considered high on the basis of CASP checklists for observational studies (Supporting Information: Table ). Most studies were graded A (n = 33) or B (n = 32); four studies were graded C and two studies were graded D. The main reason for downgrading studies from A to B was the potential for bias related to self-reporting of AD and/or CVD risk factors, although some studies were downgraded because of inadequate adjustment for confounders in the analyses.

Patient and AD characteristics

Overall, the studies involved more than 2.25 million adult patients with AD, although some patients were included in more than one study (Supporting Information: Table ). For example, two studies by Ivert et al. used the same Swedish patient sample but reported on different risk factors. Likewise, two studies by Shalom et al. used the same Israeli patient sample and mostly reported different risk factors, except mean BMI and prevalence of obesity, which were reported in both articles. The mean/median age of adult patients varied widely but was in the 40s for most studies. Mean or median age of AD onset or first diagnosis was reported in only six studies, although other studies indicated whether patients had childhood- or adult-onset AD; most patients had adult-onset AD. Only one study reported mean duration of AD (38.2 years).

There was wide variation between studies in how AD was defined (Supporting Information: Table ). Having AD, a diagnosis of AD and/or treatment for AD was self-reported in 27 studies; some studies provided specific questions that patients were asked, whereas other studies did not. International Classification of Diseases (ICD) codes were used in 24 studies (alone or in combination with other criteria), although the ICD version(s) depended on when the study was conducted or when medical records were made. ICD-8 code 691 was used by nine studies (all from Denmark or Sweden), ICD-9/ICD-9-CM code 691 (or subcodes) were used by 11 studies and ICD-10 code L20 was used by 15 studies. Hanifin and Rajka criteria were used in five studies, other specific criteria or medical records were used in 12 studies and four studies did not report how AD was defined.

AD severity was reported in 23 studies, most commonly by the SCORing Atopic Dermatitis index or based on the patient's previous/current systemic therapy. However, only 12 studies reported risk factors stratified by AD severity.

Risk factor: Obesity/overweight/BMI

The prevalence of obesity among patients with AD was reported in 25 studies (Supporting Information: Table ). Most studies defined obesity using a specific BMI cut-off, although the value varied (e.g., ≥25, ≥27.5 or ≥30 kg/m², often related to the ethnicity of the cohorts), whereas other studies did not define obesity. Obesity was qualitatively more prevalent in AD populations than non-AD populations, but the range of prevalences was very broad (AD: 0.70%–59.2% [weighted prevalence in patients with severe AD]; non-AD: 0.47%–36.1% [men with BMI ≥25 kg/m², not defined as obesity by the study]), likely because of the differing definitions and populations. Thirteen studies reported ORs or risk ratios (RRs) (95% confidence interval [CI]) from 0.62 (0.22–1.76) to 3.5 (1.4–8.7) (Supporting Information: Table  and Figure ). One study reported a crude hazard ratio (HR) for incident AD in obese patients (defined by ICD codes) of 0.82 (0.41–1.64). There was no clear relationship between AD severity and the prevalence or risk of obesity and no clear difference between geographic regions (Figure ).

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As with obesity, the definition of overweight varied, and some studies included obese patients within their ‘overweight’ category (Supporting Information: Table ). Twelve studies reported the prevalence of overweight (AD: 5.6% [women] to 52.3% [BMI, 23–27.4 kg/m², not defined as overweight by the study]; non-AD: 20.6%–45.9% [BMI, 23–27.4 kg/m², not defined as overweight by the study]). Nine studies reported ORs (Supporting Information: Table  and Figure ) ranging from 0.84 reported by two studies that defined overweight as BMI ≥25 to <30 kg/m² (OR, 0.84 [0.65–1.17]; OR, 0.84 [0.38–1.85] for men in a survey cohort) to 1.56 (0.64–3.76) for a lifetime AD cohort with a BMI of 23–27.4 kg/m².

Seventeen studies reported BMIs in patients with AD; mean/median baseline BMI ranged from 22.1 to 30.9 kg/m² (Supporting Information: Table ). One noncontrolled study reported mean BMI after 1 year of follow-up of 29.7 kg/m² in patients with severe AD and 26.9 kg/m² in those with mild AD. Mean/median BMI in non-AD populations in controlled studies ranged from 21.9 (subgroup of women) to 30.1 kg/m².

Risk factor: Diabetes

The prevalence of diabetes among patients with AD was reported in 35 studies and the absolute risk of diabetes was reported in two studies (Supporting Information: Table ). Five studies reported on T2D, four studies on T1D and one study on gestational diabetes; all other studies did not specify the type of diabetes. Among the controlled studies, the prevalence of diabetes was often, but not always, higher in AD populations and the range of prevalences was broad across different populations and diabetes types (AD: 0.19%–43.9% [severe AD]; non-AD: 0.28%–14.4%). One controlled study reported the absolute risk for incident T1D (AD: 0.08%; non-AD: 0.09%) and one study for incident T2D (AD vs. non-AD: 1.96 vs. 1.92 per 1000 person-years) in patients with AD. Where examined, the prevalence of diabetes increased with AD severity.

Relative risk for unspecified diabetes was reported in nine studies (Supporting Information: Table  and Figure ), with ORs ranging from 0.509 (0.366–0.709) to 5.38 (3.83–6.93) in severe AD; an additional study reported a decreased risk of incident AD developing in patients with diabetes (crude HR, 0.48 [0.28–0.81]). Four studies reported ORs for T2D from 0.74 (0.68–0.80) to 6.85 (3.00–15.7; moderate-to-severe AD relative to mild AD); one of these studies examined incident T2D. Geography did not appear to affect the risk of diabetes.

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Risk factor: Hypertension

Prevalence of hypertension in patients with AD was reported in 34 studies (1.0%–68.0% [global severity reported as severe]) (Supporting Information: Table ). In controlled studies, prevalence was often higher in AD populations than in non-AD populations, especially if AD was severe. Thirteen studies reported relative risk of hypertension in patients with AD ranging from 0.730 (0.600–0.888) (crude OR) compared with unmatched controls to 2.67 (2.09–3.26) (crude RR) in patients with severe AD (according to self-reported global severity) compared with unmatched controls (Supporting Information: Table  and Figure ). Two studies reported conflicting results for the risk of developing hypertension in patients with AD. An additional study reported a crude HR for incident AD in patients with pre-existing hypertension of 0.63 (0.47–0.84). No clear pattern associated with geography was observed.

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Risk factor: Lipid disorders

Prevalence data on lipid disorders among patients with AD were reported in 17 studies (Supporting Information: Table ). Dyslipidemia or hyperlipidemia rates ranged from 0.33% to 53.7% (severe AD) in patients with AD and from 0.18%–30.3% in non-AD control groups. Three studies reported the prevalence of hypercholesterolemia; rates ranged from 1.3% (persistent AD in an uncontrolled study) to 53.0% in patients with AD and from 17.9% to 49.6% in controls. Two studies reported hypertriglyceridemia; rates were 4.1% and 8.3% in men and women with AD, respectively, compared with 4.8% in both sexes in non-AD in a controlled study, and 0% and 2.9% in persistent and adult-onset AD, respectively, in an uncontrolled study. Dyslipidemia/hyperlipidemia was often, but not always, more prevalent in AD than in controls, and, where studied, was more prevalent in severe AD than in mild or moderate AD.

Seven studies reported on the relative risk of lipid disorders (Supporting Information: Table  and Figure ) with ORs ranging from 0.73 (0.52–1.02) for cholesterol >6.5 mmol/L to 2.20 (1.29–4.03) for triglycerides ≥150 mg/dl in women. One additional study reported a crude HR for incident AD in patients with hyperlipidemia of 0.67 (0.49–0.91). Three controlled studies reported plasma levels of cholesterol, triglycerides, HDL-C and/or LDL-C; there were no major differences between AD and non-AD in any of the studies. No differences in the relative risk between geographies were apparent, although only one study was conducted in North America.

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Risk factor: Smoking

A broad range of smoking habits and exposure types were investigated, including current, former and second-hand smoking (Supporting Information: Table ). Prevalence of active smoking (current and/or former) among patients with AD was reported in 39 studies, with no clear pattern of higher or lower prevalence in AD compared with controls. Prevalence of passive smoking among adults was reported in five studies (AD vs. non-AD: 0.3% vs. 1.2% in men with ≥1 h of smoking exposure at home, up to 66.7% vs. 67.6% with any exposure at home).

Fifteen studies reported relative risks related to smoking (Supporting Information: Table  and Figure ); again, there was no clear pattern of increased association between smoking and AD. Two studies examined the risk of developing AD after exposure to active smoking, but only one of these reported that the risk was increased. About half of the studies on current or former smoking, and all the studies on passive smoking, were conducted in Asia; both the highest and the lowest relative risk estimates were reported by these studies, although with large 95% CIs, and there was no overall difference in risk between geographic regions.

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Other cardiovascular risk factors

Data on CKD and family history of CVD were very limited (Supporting Information: Table ).

DISCUSSION

This systematic review evaluated the prevalence, absolute risk and relative risk of diabetes, obesity, hypertension, dyslipidemia and other CVD risk factors in patients with AD and is the first systematic review to assess certain CVD risk factors. For most CVD risk factors, the reported prevalences varied widely and the range in AD and non-AD populations overlapped substantially. However, higher prevalences of some CVD risk factors, including diabetes, obesity, hypertension and dyslipidemia, among AD populations were noted in many studies, particularly among patients with severe AD. Correspondingly, although inconsistent across studies, relative risks were generally elevated in AD populations, especially in those with severe AD.

There were adequate data on the prevalence and relative risk of several important CVD risk factors, including obesity, smoking, hypertension, lipid disorders and unspecified diabetes (although many of these may be assumed to be T2D). However, data were lacking for specified T2D, as well as the less established CVD risk factors (T1D, CKD, family history of CVD). The range of prevalences reported varied widely, most likely because of differing study methods, definitions and populations. However, within most studies that included a control group, prevalences of almost all risk factors were higher for AD populations than for control populations. Overall, relative risks were often inconsistent, even when there were adequate data. The inconsistency of definitions (e.g., for obesity and smoking), as well as different methodologies used for matching controls to patients with AD and for adjusting for confounders, likely contributed to some of the variation in relative risk.

Importantly, there were only nine studies in which the temporal relationship between AD and CVD risk factors was clear, and of these, only four used matched controls. Moreover, only four studies reported the absolute risk of developing or acquiring a CVD risk factor within a known time frame in patients with AD—one each for T2D, T1D, gestational diabetes and smoking in patients with childhood-onset AD. In these studies, AD was excluded as an independent causal factor for the development of diabetes or taking up smoking and was associated with a lower risk of gestational diabetes. An additional study also reported that neither incident hypertension nor incident T2D were elevated in patients with AD, but the study design did not allow the time frame to be determined. Standl et al. reported a slightly elevated relative risk of incident hypertension, resulting in about 15 excess cases per 10,000 person-years. Conversely, three studies examined whether pre-existing CVD risk factors were associated with incident AD; two of these reported conflicting results as to whether smoking exposure is a causal factor for AD, whereas the third study found no association between hypertension, obesity, diabetes or hyperlipidemia and subsequent development of AD.

Only 12 studies examined the relationship between AD severity and the association with CVD risk factors. In most of these studies, patients with severe or moderate-to-severe AD had higher prevalence or relative risk of CVD risk factors compared with milder AD. This was especially apparent for diabetes and hypertension, both of which increased with AD severity in six studies, with one additional study also reporting higher relative risk of diabetes and another study reporting higher prevalence of hypertension in patients with severe AD than in patients with mild AD. Severe AD was also associated with higher prevalence and/or risk of lipid disorders in three studies and risk of CKD in one study. Although less consistent results were seen for obesity and smoking, the evidence as a whole suggests that CVD risk factors are of particular concern among patients with severe AD. Whether the increased prevalence of risk factors in severe AD is related to underlying immune mechanisms, modifiable behaviours, systemic treatments or other confounding factors remains to be established.

Obesity and overweight were generally more prevalent in AD populations than in non-AD populations, and many relative risk studies reported an elevated risk of obesity in patients with AD. These results are consistent with previous systematic reviews. However, unlike the meta-analysis of Zhang and Silverberg, which reported an increased risk of obesity in patients with AD from Asian and North American, but not European, populations, we did not observe any clear differences across geographies. Hypertension was also often more common in AD than in non-AD populations, especially among patients with moderate-to-severe AD, which is consistent with the recent meta-analysis by Yousaf et al. However, only some of the relative risk studies included in our review reported that the risk was significantly elevated. Likewise, lipid disorders tended to be more prevalent among patients with AD, although not all relative risk studies reported an elevated risk. The evidence regarding diabetes was less consistent, with only some studies reporting higher risks in AD compared with non-AD populations. Similarly, previous systematic reviews have reported that there was no significant association between AD and T2D (or presumed T2D). Notably, because patients in most studies in the current review were relatively young, comorbidities such as hypertension, dyslipidemia and diabetes (particularly T2D) may not have developed yet, and studies of older adults are needed. Finally, there was no consistent relationship between active or passive smoking and AD among the studies in our review, although the diversity of definitions may have contributed to the variation in results. A previous meta-analysis by Kantor et al. was more conclusive, reporting that both active and passive smoking were significantly associated with AD in adults, as well as in children.

This systematic literature search investigated the prevalence, absolute risk and relative risk of a broad range of CVD risk factors, including dyslipidemia and renal disease, which have not been reviewed previously. Moreover, our review included more than 30 studies published since 2018, which are too recent to have been included in previous reviews. In addition, the directionality of the relationship between AD and risk factors was assessed, although this was limited to a small number of studies. Our review included various study designs, and although all studies were observational, most were of high quality based on CASP checklists.

LIMITATIONS

The results of this review are subject to a number of limitations. The heterogeneity of the studies, including wide variation in the definitions of risk factors and AD, precluded any meta-analysis of results. Variation in reported prevalence and relative risk results may also be partly related to regional or ethnic differences (e.g., Asia vs. Europe or North America; African American vs. White vs. Asian ethnicity) in physiology, social habits, environment and/or underlying AD mechanisms; however, the role of ethnicity in the risk of CVD in patients with AD has not been studied, and we did not discern a clear effect of geography on any of the risk factors. Despite the large number of studies in our review, many of them defined AD and/or CVD risk factors based solely on questionnaires, with no independent or consistent verification. In addition, many studies used registries or other databases, which limited the extent of information available and the ability to adjust for such variables in the statistical analysis. Registry-based studies are also subject to potential detection bias caused by misclassification of AD and/or CVD risk factors. Moreover, because the same databases were used in several studies, some patients will be included in more than one study. Although most studies reporting relative risk adjusted for patient characteristics, many did not adjust for other CVD risk factors, such as BMI or smoking, or for other factors that may affect the association of AD with CVD risk factors, such as socioeconomic status; hence, confounding may make it difficult to determine the independent relationship between each risk factor and AD, particularly when using population-wide databases where detailed information on possible confounders is not always available. There were very limited data on certain risk factors, such as CKD and family history of CVD; other less commonly studied risk factors for CVD (e.g., sleep apnoea, atrial fibrillation, oral contraceptive use) that were not included in this review may be worth examining in the future. Although our search strategy aimed to identify the most relevant studies reporting prevalence, absolute risk or relative risk, it is possible that not all publications were identified (e.g., publications reporting only baseline CVD risk factor data). Finally, we did not examine the possible relationship between treatment and CVD risk factors; for example, systemic corticosteroids, cyclosporine and antimetabolites, which may be used to treat moderate-to-severe AD or comorbid disease, such as asthma, are linked to increased risk of hypertension, diabetes, glucose intolerance, weight gain and dyslipidemia.

CONCLUSION

In conclusion, although numerous studies have reported on the prevalence or relative risk of a range of CVD risk factors in patients with AD, the diversity of study designs, geographies, populations, definitions and methodologies prevents any definitive conclusions regarding the tendencies and associations between most of these risk factors and AD (Table ). Moreover, inconsistencies in relative risk may mean that the association between AD and some CVD risk factors is weak or even nonexistent. Additional studies specifically designed to address the link between AD and CVD risk factors are required. Nevertheless, dermatologists and other physicians should be aware of the potential relationship between AD and CVD and counsel their patients with AD accordingly, particularly with respect to lifestyle modifications that could reduce their risk.

Table 1 Cardiovascular disease (CVD) risk factors in atopic dermatitis (AD): key points

CVD risk factor	Association with AD
Obesity	↑↑
Overweight	↑
Diabetes
Type 1	↓
Type 2	-
Not specified	↑
Hypertension	↑
Lipid disorders	↑
Smoking
Active	-
Passive	↑
Chronic kidney disease	-
Family history of CVD	-
Inconsistencies in study designs, populations and reported results make it difficult to draw firm conclusions about the relationship between CVD risk factors and AD in adults.
Limited evidence suggests that CVD risk factors are a particular concern for patients with severe AD.
For patients with severe AD and multiple CVD risk factors, particularly obesity, hypertension, diabetes and/or smoking, dermatologists should discuss the potential for CVD and advise patients accordingly (e.g., lifestyle modifications to reduce risk, consultations with CVD specialists).
Additional carefully designed studies are required to better delineate the relationship between CVD risk factors and AD.

ACKNOWLEDGEMENTS

This systematic review was sponsored by Eli Lilly and Company, manufacturer/licensee of baricitinib. Literature search support and medical writing assistance was provided by Rebecca Lew, PhD, CMPP, and Luke Carey, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Eli Lilly and Company. ProScribe's services complied with international guidelines for Good Publication Practice (GPP3). Eli Lilly and Company was involved in the study design, data collection, data analysis and preparation of the manuscript.

AUTHOR CONTRIBUTIONS

All authors participated in the development of the literature search strategy; interpretation of literature search results; and the drafting, critical revision and approval of the final version of the manuscript.

CONFLICTS OF INTEREST

JPT is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Coloplast, Eli Lilly and Company, LEO Pharma, OM Pharma, Pfizer, Regeneron, Sanofi Genzyme and UNION Therapeutics; a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi Genzyme. JART is a former employee of Eli Lilly and Company. EJP and MAF are employees and minor shareholders of Eli Lilly and Company. MAF is also a clinical instructor in the Department of Dermatology at Mount Sinai Hospital, New York, NY. JIS has received honoraria as a consultant and/or advisory board member from AbbVie, AFYX Therapeutics, AOBiome, Arena Pharmaceuticals, Asana BioSciences, BiomX, Bluefin, Bodewell, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte Corporation, Kiniksa, LEO Pharma, Luna Pharma, Menlo Therapeutics, Novartis, Pfizer, RAPT Therapeutics, Regeneron and Sanofi Genzyme; is a speaker for Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; and his institution has received grants from Galderma.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

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