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. 2021 Aug 20;67(3):139–145. doi: 10.4103/jpgm.JPGM_1270_20

Association of atopic dermatitis with an increased risk of systemic lupus erythematosus: A systematic review and meta-analysis

B Ponvilawan 1,✉, N Charoenngam 1, W Wongtrakul 2, P Ungprasert 3
PMCID: PMC8445124  PMID: 34427279

Abstract

Context:

Previous studies on the association between atopic dermatitis (AD) and systemic lupus erythematosus (SLE) have yielded inconsistent results.

Aims:

To investigate the relationship between atopic dermatitis and systemic lupus erythematosus.

Settings and Design:

Systematic review and meta-analysis.

Materials and Methods:

A systematic review was conducted on EMBASE and MEDLINE databases from inception to March 2020 using a search strategy that consisted of terms related to AD and SLE. Eligible study must be either cohort or case-control study. For cohort studies, they must include patients with AD and comparators without AD, then follow them for incident SLE. For case-control studies, they must include cases with SLE and controls without SLE and examine their prior history of AD.

Statistical Analysis Used:

Meta-analysis of the studies was performed using a random-effect, generic inverse variance method to combine effect estimate and standard error. Funnel plot was used to assess publication bias.

Results:

A total of 21,486 articles were retrieved. After two rounds of review by three investigators, six case-control studies were qualified for the meta-analysis. The case-control study meta-analysis found a significantly increased odds of SLE among patients with AD with the pooled odds ratio of 1.46 (95% CI, 1.05–2.04).

Conclusions:

A significant association between AD and increased odds of SLE was observed by this systematic review and meta-analysis.

KEY WORDS: Atopic dermatitis, eczema, meta-analysis, systemic lupus erythematosus

Introduction

Atopic dermatitis (AD), or atopic eczema, is the most common chronic inflammatory skin disease worldwide which typically develops during childhood. Patients with AD usually present with recurrent eczematous lesions in flexural areas that cause pruritus and can interfere with daily activities.[1,2] Several epidemiological studies have estimated that around 5–25% of the world population are affected by AD.[3,4,5] Family history of atopic diseases and several environmental factors, such as living in urban setting or regions with low ultraviolet light and smoking, are known risk factors for this disease.[1,6,7,8]

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous manifestations involving multiple organs such as joints, kidneys, nervous system, bone marrow, and skin.[9,10] The incidence rate varies considerably around the world, ranging from 0.3 to 23.2/100,000 person-years with a predilection for women of childbearing age and people of African, Hispanic, or Asian ancestry.[10,11] Known risk factors include family history, tobacco smoking, obesity, and vitamin D deficiency.[12,13,14]

Multiple studies have demonstrated that AD is associated with an increased risk of several chronic diseases such as cardiovascular, neuropsychiatric, and autoimmune disorders.[15,16,17,18] There are also studies to suggest the association between AD and SLE although the results are still conflicting.[19,20,21,22,23,24,25,26] This systematic review and meta-analysis was performed in order to comprehensively investigate the relationship between AD and SLE by identifying all relevant studies and summarizing their results together.

Method

Search strategy

Independent search for all relevant publications indexed in EMBASE and MEDLINE from inception to March 2020 was conducted by three investigators (B.P., N.C., and W.W.) using search terms related to AD and SLE. The detailed search strategy is exhibited in the Supplemental Material 1.

Inclusion criteria

Eligible study must be either cohort or case-control study. For cohort studies, they must include patients with AD and comparators without AD, then follow them for incident SLE. Relative risk (RR), incidence rate ratio (IRR), hazard risk ratio (HR), or standardized incidence ratio (SIR) with associated 95% confidence interval (95% CI) that compare the incidence of SLE between the two groups must be reported. For case-control studies, they must include cases with SLE and controls without SLE and examine their prior history of AD. Odds ratio (OR) with 95% CI of the association between AD and SLE must be reported.

Study eligibility was independently determined by three investigators (B.P., N.C., and W.W.). The senior investigator (P.U.) provided the final determination after discussions with all investigators if different conclusions were made by the three investigators. The Newcastle-Ottawa quality assessment scale for cohort study and case-control study was used for determination of the quality of each study.[27] This quality assessment was performed by two investigators (B.P. and P.U.).

Data extraction

Data extraction was performed using a standardized collection form which contains the following information: the first author's surname, country where the study was conducted, study design (case-control versus cohort study), year of publication, number of participants, recruitment of participants, diagnosis of SLE, diagnosis of AD, follow-up duration (for cohort studies only), average age of participants, percentage of female participants, comorbidities of participants, variables adjusted in multivariate analysis, and adjusted effect estimates along with their 95% CI.

Statistical analysis

Review Manager 5.3 software (The Cochrane Collaboration, London, United Kingdom) was used for analysis of data. Point estimates along with their standard errors were extracted from each study and were combined together to calculate pooled effect estimates using the generic inverse variance method of DerSimonian and Laird which assigns weight for each study based on its variance.[28] Two meta-analyses of cohort studies and case-control studies were performed separately if there are enough number for each type of studies. IRR, HR, and SIR of cohort study was used as an approximation of RR to calculate pooled risk ratio for cohort studies. Random-effect model was used instead of fixed-effect model because of the difference in study design, protocols, and background populations of the included studies. Statistical heterogeneity was evaluated using Cochran's Q test along with I2statistic which quantifies the proportion of the total variation across studies that is from heterogeneity instead of coincidence. A value of I2of 0–25% implies insignificant heterogeneity, 26–50% low heterogeneity, 51–75% moderate heterogeneity, and >75% high heterogeneity.[29] The presence of publication bias was investigated by visualization of funnel plot to look for evidence of asymmetry.

Results

Search results

A comprehensive systematic review of EMBASE and MEDLINE database yielded 21,486 articles in which 2372 articles were duplication and were removed, resulting in 19,114 articles for title and abstract review. A total of 19,051 articles were then eliminated as they obviously did not meet the eligibility criteria based on study design, type of article, and participants, leaving 63 articles for full-length article review. A total of 55 articles were eliminated at this stage as they did not report the outcome of interest. Ultimately, two cohort studies[19,20] with 4,525,973 participants and six case-control studies[21,22,23,24,25,26] with 19,713 participants met all of the eligibility criteria. Due to the limited number of cohort studies, only case-control studies were included into the meta-analysis. Figure 1 illustrates the search methodology and selection process of this study. Tables 1 and 2 provide information on design and baseline characteristics of participants of the included cohort studies and case-control studies, respectively.

Figure 1.

Figure 1

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Study identification and literature review process

Table 1.

Main characteristics of the cohort studies included in the meta-analysis

Wei et al.[19] Krishna et al.[20]
Country Taiwan United Kingdom
Study design Retrospective cohort Retrospective cohort
Year of publication 2014 2019
Total number of participants Patients with atopic dermatitis: 192,357
Comparators: 769,428		 Patients with atopic dermatitis: 1,393,570
Comparators: 2,170,618
Recruitment of participants Patients with atopic dermatitis of age 1 to 18 years were identified from the National Health Insurance Research Database of Taiwan which consisted of half of all insured children in Taiwan from 2000 to 2008.
Comparators without atopic dermatitis were randomly identified from the same database. Each patient with atopic dermatitis was matched to four comparators by age, sex, urbanization of residential area, parental occupation, and index year.Participants who were previously diagnosed with SLE before the starting date were excluded.		 Patients with atopic dermatitis were identified from the Health Improvement Network database which contained coded data recorded by the patient’s general practitioner from January 1, 1990 to January 17, 2018. This database covered approximately 3 million patients across the United Kingdom.Comparators without atopic dermatitis were randomly identified from the same database. Each patient with atopic dermatitis was matched to up to two comparators by age, sex, and general practitioner.
Diagnosis of atopic dermatitis Presence of at least three consecutive diagnoses of atopic dermatitis from diagnostic code in the database (ICD-9-CM 691) Presence of diagnostic codes of atopic dermatitis in the Health Improvement Network database
Diagnosis of SLE Presence of diagnostic code of SLE (ICD-9-CM code 710.0) in the database with confirmation by the Registry for Catastrophic Illness Patient Database, which required medical record review by board-certified specialists Presence of diagnostic codes of SLE in the Health Improvement Network database
Follow-up period Until the development of SLE, death, withdrawal of insurance, or closing date (December 31, 2008) Until the development of SLE, death, emigration, or closing date (January 17, 2018)
Average duration of follow-up (years) Patients with atopic dermatitis: 5.1
Comparators: 2.1		 Patients with atopic dermatitis: 5.3 (median)
Comparators: 3.5 (median)
Average age of participants (years) Patients with atopic dermatitis: 3.2
Comparators: 3.3		 Patients with atopic dermatitis: 29.8
Comparators: 32.7
Percentage of female Patients with atopic dermatitis: 46.7%
Comparators: 46.7%		 Patients with atopic dermatitis: 54.1%
Comparators: 53.8%
Comorbidities N/A Patients with atopic dermatitis:
Obesity 9.4%
Smoking 13.0%
Comparators:
Obesity 9.3%
Smoking 14.0%
Variables adjusted in multivariate analysis Age, sex, urbanization of residential area, parental occupation, and index year Age, sex, body mass index, race, Townsend deprivation quintile, ethnicity, and smoking status
Newcastle-Ottawa score Selection: 4
Comparability: 2
Outcome: 3		 Selection: 4
Comparability: 2
Outcome: 3
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ICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification; N/A: Not Available; SLE: Systemic Lupus Erythematosus

Table 2.

Main characteristics of the case-control studies included in the meta-analysis

Goldman et al.[21] Morton et al.[22] Sekigawa et al.[23]
Country USA United Kingdom Japan
Year of publication 1976 1998 2002
Total number of participants Cases: 24
Controls: 27		 Cases: 49
Controls: 98		 Cases: 52
Controls: 52
Recruitment of participants Cases: Cases were consecutive patients with SLE who were recruited from wards and clinics of Grady Memorial Hospital, Emory University Clinic, and Emory University Hospital.
Controls: Controls without SLE were selected from patients who attended the Family Planning Clinic or werehospitalized in the Obstetric, Gynecology, and OrthopedicServices of Grady Memorial Hospital or in the OrthopedicService of Emory University Hospital. They were matched to cases by age, sex, and race.		 Cases: Cases were patients with SLE who were randomly selected from the cohort of 180 patients with SLE attending clinical immunology clinics at the Queens Medical Centre, Nottingham.
Controls: Controls without SLE were randomly selected from one rural and two urban general practices. They were 1:2 matched to cases by age and sex.		 Cases: Cases were patients with SLE who were randomly selected from the cohort of Japanese SLE patients attending Juntendo University Izu-Nagaoka Hospital.
Controls: Controls without SLE were randomly selected from the residents near Juntendo University Izu-Nagaoka Hospital. They were matched to cases by age and sex.
Diagnosis of SLE Physician diagnosis using preliminary criteria for the classification of SLE by the American Rheumatism Association or clinical arthritis with positive LE preparation Physician diagnosis using the 1982 American Rheumatism Association classification criteria of SLE Physician diagnosis using the 1982 American Rheumatism Association classification criteria of SLE
Diagnosis of atopic dermatitis Self-report from health questionnaire Self-report from health questionnaire Self-report from health questionnaire
Average age of participants (years) Total: 36.0 Cases: 45.6
Controls: 45.4		 Cases: 33.6
Controls: 33.7
Percentage of female Cases: 100.0%
Controls: 100.0%		 Cases: 98.0%
Controls: 98.0%		 Cases: 90.4%
Controls: 90.4%
Variables adjusted in multivariate analysis None None None
Newcastle-Ottawa score Selection: 3
Comparability: 1
Exposure: 2		 Selection: 4
Comparability: 1
Exposure: 2		 Selection: 4
Comparability: 1
Exposure: 2
Parks et al.[24] Hsiao et al.[25] Lin et al.[26]
Country USA Taiwan Taiwan
Year of publication 2010 2014 2018
Total number of participants Cases: 228
Controls: 293		 Cases: 1673
Controls: 6692		 Cases: 2105
Control: 8420
Recruitment of participants Cases: Cases were patients with SLE who were identified from the Carolina Lupus Study, comprising of SLE patients referred from 30 of the 40 community-based rheumatologists in eastern and central North Carolina and South Carolina.
Controls: Controls without SLE were randomly selected from driver’s license registries limited to the geographic region from which cases were identified. They were matched to cases by five-year age group, sex, and state.		 Cases: Cases were patients with SLE newly diagnosed between 2002 and 2010 who were identified from the Longitudinal Health Insurance Database 2000. This database collected health information from 1996 to 2010 of one million beneficiaries who were randomly selected from the original registry of beneficiaries in the Taiwan Health Insurance program.
Controls: Controls without SLE were randomly selected from the same Longitudinal Health Insurance Database. They were 1:4 matched to cases by age, sex, index-year, and index-month.		 Cases: Cases were patients with newly-diagnosed SLE who were identified from the Taiwan’s National Health Insurance Research Database from January 1, 2000 to December 31, 2011. This database contained outpatient and inpatient claims for all beneficiaries enrolled in Taiwan’s mandatory National Health Insurance program.
Controls: Controls without SLE were randomly selected from the same database of the National Health Insurance program. They were 1:4 matched to cases by age, sex, and first diagnosis date.
Diagnosis of SLE Physician diagnosis using the 1982 and 1997 American College of Rheumatology classification criteria of SLE. Presence of diagnostic codes of SLE in the database (ICD-9-CM code: 373.34, 695.4, 710.0). Presence of diagnostic codes of SLE in the database (ICD-9-CM code: 710.0).
Diagnosis of atopic dermatitis Self-report through direct interview Presence of diagnostic codes of atopic dermatitis in the database (ICD-9-CM code: 691.8) from at least one inpatient visit or two outpatient visits Presence of diagnostic codes of atopic dermatitis in the database (ICD-9-CM code: 691.8) from at least two outpatient claims six months before and after the index date
Average age of participants (years) Cases: N/A
Controls: N/A		 Cases: 40.1
Controls: 40.0		 Cases: N/A
Controls: N/A
Percentage of female Cases: 89.5%
Controls: 90.8%		 Cases: 82.5%
Controls: 82.5%		 Cases: 76.4%
Controls: 76.4%
Variables adjusted in multivariate analysis None None Number of hospital visits, infection/no infection and atopic diseases
Newcastle-Ottawa score Selection: 4
Comparability: 1
Exposure: 3		 Selection: 4
Comparability: 1
Exposure: 3		 Selection: 4
Comparability: 2
Exposure: 3
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ICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification; LE: Lupus Erythematosus; N/A: Not Available; SLE: Systemic Lupus Erythematosus; USA: United States of America

Association between atopic dermatitis and systemic lupus erythematosus

The meta-analysis of case-control studies also showed a significantly elevated odds of SLE among patients with AD compared with individuals without AD with the pooled odds ratio of 1.46 (95% CI, 1.05–2.04). Statistical heterogeneity of this meta-analysis was moderate with I2of 63% [Figure 2].

Figure 2.

Figure 2

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Forest plot of the meta-analysis of case-control studies of atopic dermatitis and risk of SLE

Evaluation for publication bias

Presence of publication bias was assessed by visualization of funnel plot. The plot for case-control studies was asymmetrical, which was suggestive of the presence of publication bias [Figure 3].

Figure 3.

Figure 3

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Funnel plot of the meta-analysis of case-control studies of atopic dermatitis and risk of SLE

To assess the effect of this publication bias on the pooled result, trim-and-fill sensitivity analysis as described by Duval et al.[30] was performed using Comprehensive Meta-analysis Program (Biostat, Englewood, New Jersey, USA). Using this technique, one hypothetical missing study was identified [Figure 4]. Inclusion of this hypothetical missing study into the meta-analysis did not significantly alter the pooled result with the new pooled OR of 1.56 (95% CI, 1.09–2.23).

Figure 4.

Figure 4

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Trim-and-fill sensitivity analysis of the meta-analysis of case-control studies of atopic dermatitis and risk of SLE

Discussion

This systematic review and meta-analysis included data from 19,713 participants and found that patients with AD had 1.46-fold increased odds of developing SLE compared with individuals without AD. The results of two cohort studies further supported the result of our meta-analysis as they also reported the significantly increased risk of developing SLE in patients with AD.[19,20] The exact mechanisms responsible for this association are still not known with certainty. Some possible explanations are discussed below.

First, immunologic pathways involving Th1, Th2, and Th17 cells might be responsible for both AD and SLE. A considerable amount of evidence shows that both patients with AD and SLE have an upregulation of Th2 cytokines, such as IL-5 and IL-13, and Th17 cytokines, such as IL-17 and IL-22. On the other hand, they had a downregulation of IL-2, one of the major cytokines of Th1 cells.[31,32,33,34,35,36,37,38] Moreover, recent studies have demonstrated an increased level of IgE among patients with SLE, particularly among those with active disease, similar to patients with AD.[39,40,41] Thus, it is possible that dysregulation of Th1, Th2, and Th17 activities in AD could give rise to evolution of SLE in the same patients later in life.

Second, genetic factor might also play a role in the association between AD and SLE as family history is a known predisposing factor for both diseases.[7,12] In fact, individuals with certain human leukocyte antigen (HLA) genotypes, such as HLA-B and HLA-DRB1, are found to have an increased tendency to develop both diseases.[42,43,44,45] Nonetheless, common susceptibility locus and single nucleotide polymorphisms (SNPs) in HLA genes are yet to be found.

Apart from genetic risk factor, AD and SLE also share some environmental risk factors. Tobacco smoking and obesity are reported to be associated with an increased risk of both AD and SLE.[6,13,14] Tobacco smoking could promote elevation of serum IgE level and inflammatory response which, in turn, generate dysregulation of T and NK cells, DNA damage, and epigenetic changes. Obesity could create proinflammatory effect via adipokines secreted from dysfunctional adipocytes.[46,47,48,49,50,51,52,53,54]

Last, surveillance bias could also partially be responsible for an increased risk of SLE as patients with AD tend to have a more frequent exposure to healthcare providers due to the chronic nature of AD. However, SLE is a disease which would generally cause noticeable symptoms that patients usually seek for medical attention. Therefore, surveillance bias is probably not the only reason for the observed relationship.

Nonetheless, this systematic review and meta-analysis carries some limitations and the pooled results should be interpreted with caution. First, statistical heterogeneity of the meta-analysis was not low. We believe that difference in study design, protocols, and characteristics of the participants across the studies was responsible for the inter-study variation. Second, the accuracy of case identification of AD and SLE could be limited as about half of the included studies used diagnostic codes from administrative databases[19,20,25,26] to identify and confirm the diagnosis. Finally, publication bias may have been present as evident by the asymmetrical funnel plot.

Conclusion

This systematic review and meta-analysis observed an elevated odds of incident SLE among patients with AD compared with individuals without AD. Limitations included between-study heterogeneity, limited accuracy of case identification in the primary studies, and publication bias. Clinicians who take care of patients with AD should be aware of the higher risk and further evaluation is warranted when they develop new systemic symptoms.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Supplemental Material 1 – Searching Strategy

EMBASE Database

  1. 'asthma'/exp OR 'asthma'

  2. 'reactive airway disease'/exp OR 'reactive airway disease'

  3. 'bronchus hyperreactivity'/exp OR 'bronchus hyperreactivity'

  4. 'bronchial hyperresponsiveness'/exp OR 'bronchial hyperresponsiveness'

  5. 'atopic dermatitis'/exp OR 'atopic dermatitis'

  6. 'eczema'/exp OR 'eczema'

  7. 'allergic rhinitis'/exp OR 'allergic rhinitis'

  8. 'atopy'/exp OR 'atopy'

  9. atopic

  10. 'autoimmune disease'/exp OR 'autoimmune disease'

  11. 'rheumatic disease'/exp OR 'rheumatic disease'

  12. 'lupus'/exp OR 'lupus'

  13. 'systemic lupus erythematosus'/exp OR 'systemic lupus erythematosus'

  14. 'lupus erythematosus'/exp OR 'lupus erythematosus'

  15. 'sle'/exp OR 'sle'

  16. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9

  17. #10 OR #11 OR #12 OR #13 OR #14 OR #15

  18. #16 AND #17

Ovid MEDLINE Database

  1. asthma.mp. or exp asthma/

  2. exp bronchial hyperreactivity/or reactive airway disease.mp.

  3. reactive airway disease.mp

  4. atopic dermatitis.mp. or exp dermatitis, atopic/

  5. eczema.mp. or exp eczema/

  6. allergic rhinitis.mp. or exp rhinitis, allergic/

  7. atopic.mp.

  8. atopy.mp.

  9. rheumatic disease.mp. or exp rheumatic diseases/

  10. autoimmune disease.mp. or exp autoimmune diseases/

  11. systemic lupus erythematosus.mp or exp lupus erythematosus, systemic/

  12. sle.mp

  13. 1 or 2 or 3 or 4 or 5 or 6 or 7

  14. 8 or 9 or 10 or 11 or 12

  15. 13 and 14

References

  • 1.Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4:1. doi: 10.1038/s41572-018-0001-z. [DOI] [PubMed] [Google Scholar]
  • 2.Dharmage SC, Lowe AJ, Matheson MC, Burgess JA, Allen KJ, Abramson MJ. Atopic dermatitis and the atopic march revisited. Allergy. 2014;69:17–27. doi: 10.1111/all.12268. [DOI] [PubMed] [Google Scholar]
  • 3.Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: A US population-based study. J Allergy Clin Immunol. 2013;132:1132–8. doi: 10.1016/j.jaci.2013.08.031. [DOI] [PubMed] [Google Scholar]
  • 4.Flohr C, Mann J. New insights into the epidemiology of childhood atopic dermatitis. Allergy. 2014;69:3–16. doi: 10.1111/all.12270. [DOI] [PubMed] [Google Scholar]
  • 5.Abuabara K, Yu AM, Okhovat JP, Allen IE, Langan SM. The prevalence of atopic dermatitis beyond childhood: A systematic review and meta-analysis of longitudinal studies. Allergy. 2018;73:696–704. doi: 10.1111/all.13320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Bonamonte D, Filoni A, Vestita M, Romita P, Foti C, Angelini G. The role of the environmental risk factors in the pathogenesis and clinical outcome of atopic dermatitis. BioMed Res Int. 2019;2019:2450605. doi: 10.1155/2019/2450605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Pyun BY. Natural history and risk factors of atopic dermatitis in children. Allergy Asthma Immunol Res. 2015;7:101–5. doi: 10.4168/aair.2015.7.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Wadonda-Kabondo N, Sterne JA, Golding J, Kennedy CT, Archer CB, Dunnill MG, et al. Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: Birth cohort study. Arch Dis Child. 2004;89:917–21. doi: 10.1136/adc.2003.034033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Tamirou F, Arnaud L, Talarico R, Scirè CA, Alexander T, Amoura Z, et al. Systemic lupus erythematosus: State of the art on clinical practice guidelines. RMD Open. 2018;4:e000793. doi: 10.1136/rmdopen-2018-000793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365:2110–21. doi: 10.1056/NEJMra1100359. [DOI] [PubMed] [Google Scholar]
  • 11.Rees F, Doherty M, Grainge MJ, Lanyon P, Zhang W. The worldwide incidence and prevalence of systemic lupus erythematosus: A systematic review of epidemiological studies. Rheumatology (Oxford) 2017;56:1945–61. doi: 10.1093/rheumatology/kex260. [DOI] [PubMed] [Google Scholar]
  • 12.Bengtsson AA, Rylander L, Hagmar L, Nived O, Sturfelt G. Risk factors for developing systemic lupus erythematosus: A case–control study in southern Sweden. Rheumatology. 2002;41:563–71. doi: 10.1093/rheumatology/41.5.563. [DOI] [PubMed] [Google Scholar]
  • 13.Cozier YC, Barbhaiya M, Castro-Webb N, Conte C, Tedeschi S, Leatherwood C. A prospective study of obesity and risk of systemic lupus erythematosus (SLE) among Black women. Semin Arthritis Rheum. 2019;48:1030–4. doi: 10.1016/j.semarthrit.2018.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kamen DL. Environmental influences on systemic lupus erythematosus expression. Rheum Dis Clin North Am. 2014;40:401–12,vii. doi: 10.1016/j.rdc.2014.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Ascott A, Mulick A, Yu AM, Prieto-Merino D, Schmidt M, Abuabara K, et al. Atopic eczema and major cardiovascular outcomes: A systematic review and meta-analysis of population-based studies. J Allergy Clin Immunol. 2019;143:1821–9. doi: 10.1016/j.jaci.2018.11.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Kokkonen J, Niinimäki A. Increased incidence of autoimmune disorders as a late complication in children with early onset dermatitis and/or milk allergy. J Autoimmun. 2004;22:341–4. doi: 10.1016/j.jaut.2004.03.006. [DOI] [PubMed] [Google Scholar]
  • 17.Magyari A, Lam V, Wehner MR, Margolis D, Langan S, Abuabara K. Atopic eczema in adulthood and the risk of dementia: A population-based cohort study. J Invest Dermatol. 2019;139:S33. [Google Scholar]
  • 18.Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, et al. Atopic eczema in adulthood and risk of depression and anxiety: A population-based cohort study. J Allergy Clin Immunol. 2020;8:248–57.e16. doi: 10.1016/j.jaip.2019.08.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Wei CC, Lin CL, Tsai JD, Shen TC, Sung FC. Increased incidence of juvenile onset systemic lupus erythematosus in children with atopic dermatitis. Lupus. 2014;23:1494–9. doi: 10.1177/0961203314543920. [DOI] [PubMed] [Google Scholar]
  • 20.Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K. Allergic diseases and long-term risk of autoimmune disorders: Longitudinal cohort study and cluster analysis. Eur Respir J. 14(54):1900476. doi: 10.1183/13993003.00476-2019. [DOI] [PubMed] [Google Scholar]
  • 21.Goldman JA, Klimek GA, Ali R. Allergy in systemic lupus erythematosus. IgE levels and reaginic phenomenon. Arthritis Rheum. 1976;19:669–76. doi: 10.1002/1529-0131(197607/08)19:4<669::aid-art1780190403>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  • 22.Morton S, Palmer B, Muir K, Powell RJ. IgE and non-IgE mediated allergic disorders in systemic lupus erythematosus. Ann Rheum Dis. 1998;57:660–3. doi: 10.1136/ard.57.11.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Sekigawa I, Yoshiike T, Iida N, Hashimoto H, Ogawa H. Allergic disorders in systemic lupus erythematosus: Prevalence and family history. Lupus. 2002;11:426–9. doi: 10.1191/0961203302lu221oa. [DOI] [PubMed] [Google Scholar]
  • 24.Parks CG, Biagini RE, Cooper GS, Gilkeson GS, Dooley MA. Total serum IgE levels in systemic lupus erythematosus and associations with childhood onset allergies. Lupus. 2010;19:1614–22. doi: 10.1177/0961203310379870. [DOI] [PubMed] [Google Scholar]
  • 25.Hsiao YP, Tsai JD, Muo CH, Tsai CH, Sung FC, Liao YT, et al. Atopic diseases and systemic lupus erythematosus: An epidemiological study of the risks and correlations. Int J Environ Res Public Health. 2014;11:8112–22. doi: 10.3390/ijerph110808112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Lin CH, Hung PH, Hu HY, Chung CJ, Chen TH, Hung KY. Clinically diagnosed urticaria and risk of systemic lupus erythematosus in children: A nationwide population-based case-control study. Pediatr Allergy Immunol. 2018;29:732–9. doi: 10.1111/pai.12962. [DOI] [PubMed] [Google Scholar]
  • 27.Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analysis 2000. [accessed on 2020 Jul 1]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp .
  • 28.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  • 29.Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. doi: 10.1136/bmj.327.7414.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455–63. doi: 10.1111/j.0006-341x.2000.00455.x. [DOI] [PubMed] [Google Scholar]
  • 31.Talaat RM, Mohamed SF, Bassyouni IH, Raouf AA. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine. 2015;72:146–53. doi: 10.1016/j.cyto.2014.12.027. [DOI] [PubMed] [Google Scholar]
  • 32.Morimoto S, Tokano Y, Kaneko H, Nozawa K, Amano H, Hashimoto H, et al. The increased interleukin-13 in patients with systemic lupus erythematosus: Relations to other Th1-, Th2-related cytokines and clinical findings. Autoimmunity. 2001;34:19–25. doi: 10.3109/08916930108994122. [DOI] [PubMed] [Google Scholar]
  • 33.El-Gazzar II, Bahgat DMR, El Khateeb EM. IL22 in Egyptian SLE patients, could it reflect disease activity, skin or renal involvement or is it only an expensive ESR? Egypt Rheumatologist. 2017;39:13–8. [Google Scholar]
  • 34.Comte D, Karampetsou MP, Kis-Toth K, Yoshida N, Bradley SJ, Kyttaris VC, et al. Brief Report: CD4+T cells from patients with systemic lupus erythematosus respond poorly to exogenous interleukin-2. Arthritis Rheumatol. 2017;69:808–13. doi: 10.1002/art.40014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139:S65–76. doi: 10.1016/j.jaci.2017.01.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol. 2008;128:2625–30. doi: 10.1038/jid.2008.111. [DOI] [PubMed] [Google Scholar]
  • 37.Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009;123:1244–52.e2. doi: 10.1016/j.jaci.2009.03.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Yoshizawa Y, Nomaguchi H, Izaki S, Kitamura K. Serum cytokine levels in atopic dermatitis. Clin Exp Dermatol. 2002;27:225–9. doi: 10.1046/j.1365-2230.2002.00987.x. [DOI] [PubMed] [Google Scholar]
  • 39.Sanjuan MA, Sagar D, Kolbeck R. Role of IgE in autoimmunity. J Allergy Clin Immunol. 2016;137:1651–61. doi: 10.1016/j.jaci.2016.04.007. [DOI] [PubMed] [Google Scholar]
  • 40.Laske N, Niggemann B. Does the severity of atopic dermatitis correlate with serum IgE levels? Pediatr Allergy Immunol. 2004;15:86–8. doi: 10.1046/j.0905-6157.2003.00106.x. [DOI] [PubMed] [Google Scholar]
  • 41.Rasheed Z, Zedan K, Saif GB, Salama RH, Salem T, Ahmed AA, et al. Markers of atopic dermatitis, allergic rhinitis and bronchial asthma in pediatric patients: Correlation with filaggrin, eosinophil major basic protein and immunoglobulin E. Clin Mol Allergy. 2018;16:23. doi: 10.1186/s12948-018-0102-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Kreiner E, Waage J, Standl M, Brix S, Pers TH, Couto Alves A, et al. Shared genetic variants suggest common pathways in allergy and autoimmune diseases. J Allergy Clin Immunol. 2017;140:771–81. doi: 10.1016/j.jaci.2016.10.055. [DOI] [PubMed] [Google Scholar]
  • 43.Park H, Ahn K, Park MH, Lee SI. The HLA-DRB1 polymorphism is associated with atopic dermatitis, but not egg allergy in Korean children. Allergy Asthma Immunol Res. 2012;4:143–9. doi: 10.4168/aair.2012.4.3.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Margolis DJ, Mitra N, Kim B, Gupta J, Hoffstad OJ, Papadopoulos M, et al. Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis. Hum Immunol. 2015;76:571–7. doi: 10.1016/j.humimm.2015.08.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.de Holanda MI, Klumb E, Imada A, Lima LA, Alcântara I, Gregório F, et al. The prevalence of HLA alleles in a lupus nephritis population. Transpl Immunol. 2018;47:37–43. doi: 10.1016/j.trim.2018.02.001. [DOI] [PubMed] [Google Scholar]
  • 46.Speyer CB, Costenbader KH. Cigarette smoking and the pathogenesis of systemic lupus erythematosus. Expert Rev Clin Immunol. 2018;14:481–7. doi: 10.1080/1744666X.2018.1473035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Yi O, Kwon HJ, Kim H, Ha M, Hong SJ, Hong YC, et al. Effect of environmental tobacco smoke on atopic dermatitis among children in Korea. Environ Res. 2012;113:40–5. doi: 10.1016/j.envres.2011.12.012. [DOI] [PubMed] [Google Scholar]
  • 48.Qiu F, Liang CL, Liu H, Zeng YQ, Hou S, Huang S, et al. Impacts of cigarette smoking on immune responsiveness: Up and down or upside down? Oncotarget. 2017;8:268–84. doi: 10.18632/oncotarget.13613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Santos-Alvarez J, Goberna R, Sánchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol. 1999;194:6–11. doi: 10.1006/cimm.1999.1490. [DOI] [PubMed] [Google Scholar]
  • 50.Lord GM, Matarese G, Howard JK, Bloom SR, Lechler RI, et al. Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines. J Leukoc Biol. 2002;72:330–8. [PubMed] [Google Scholar]
  • 51.Tian Z, Sun R, Wei H, Gao B. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: Leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun. 2002;298:297–302. doi: 10.1016/s0006-291x(02)02462-2. [DOI] [PubMed] [Google Scholar]
  • 52.Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115:911–9. doi: 10.1016/j.jaci.2005.02.023. [DOI] [PubMed] [Google Scholar]
  • 53.Winer S, Paltser G, Chan Y, Tsui H, Engleman E, Winer D, et al. Obesity predisposes to Th17 bias. Eur J Immunol. 2009;39:2629–35. doi: 10.1002/eji.200838893. [DOI] [PubMed] [Google Scholar]
  • 54.Chung CP, Long AG, Solus JF, Rho YH, Oeser A, Raggi P, et al. Adipocytokines in systemic lupus erythematosus: Relationship to inflammation, insulin resistance and coronary atherosclerosis. Lupus. 2009;18:799–806. doi: 10.1177/0961203309103582. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

EMBASE Database

  1. 'asthma'/exp OR 'asthma'

  2. 'reactive airway disease'/exp OR 'reactive airway disease'

  3. 'bronchus hyperreactivity'/exp OR 'bronchus hyperreactivity'

  4. 'bronchial hyperresponsiveness'/exp OR 'bronchial hyperresponsiveness'

  5. 'atopic dermatitis'/exp OR 'atopic dermatitis'

  6. 'eczema'/exp OR 'eczema'

  7. 'allergic rhinitis'/exp OR 'allergic rhinitis'

  8. 'atopy'/exp OR 'atopy'

  9. atopic

  10. 'autoimmune disease'/exp OR 'autoimmune disease'

  11. 'rheumatic disease'/exp OR 'rheumatic disease'

  12. 'lupus'/exp OR 'lupus'

  13. 'systemic lupus erythematosus'/exp OR 'systemic lupus erythematosus'

  14. 'lupus erythematosus'/exp OR 'lupus erythematosus'

  15. 'sle'/exp OR 'sle'

  16. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9

  17. #10 OR #11 OR #12 OR #13 OR #14 OR #15

  18. #16 AND #17

Ovid MEDLINE Database

  1. asthma.mp. or exp asthma/

  2. exp bronchial hyperreactivity/or reactive airway disease.mp.

  3. reactive airway disease.mp

  4. atopic dermatitis.mp. or exp dermatitis, atopic/

  5. eczema.mp. or exp eczema/

  6. allergic rhinitis.mp. or exp rhinitis, allergic/

  7. atopic.mp.

  8. atopy.mp.

  9. rheumatic disease.mp. or exp rheumatic diseases/

  10. autoimmune disease.mp. or exp autoimmune diseases/

  11. systemic lupus erythematosus.mp or exp lupus erythematosus, systemic/

  12. sle.mp

  13. 1 or 2 or 3 or 4 or 5 or 6 or 7

  14. 8 or 9 or 10 or 11 or 12

  15. 13 and 14

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