Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis

doi:10.1016/j.jaad.2018.03.017

Journal of the American Academy of Dermatology

Volume 79, Issue 3, September 2018, Pages 448-456.e30

https://doi.org/10.1016/j.jaad.2018.03.017 Get rights and content

Background

Atopic dermatitis (AD) has been associated with anxiety and depression, but the magnitude of the alleged association is unknown.

Objective

To perform a systematic review and meta-analysis of the association between AD in children and adults and, respectively, depression, anxiety, and suicidal behavior.

Methods

The medical databases PubMed, Embase, and PsychINFO were searched.

Results

There was a significant association between adult AD and, respectively, depression (pooled odds ratio [OR], 2.19; 95% confidence interval [CI], 1.87-2.57) and anxiety (pooled OR, 2.19; 95% CI, 1.75-2.73). AD was also associated with depression in children (pooled OR, 1.27; 95% CI, 1.12-1.45); few data were available for anxiety. A positive association was found between AD in adults and adolescents and suicidal ideation (pooled OR, 4.32; 95% CI, 1.93-9.66). Only a few studies examined the risk of completed suicide, but the majority showed a positive association between completed suicide and AD.

Limitations

Included studies used different definitions of depression and anxiety, and few studies examined the severity of AD.

Conclusion

Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD. Because AD disease improvement appears to reduce these risks, this should be a priority.

Section snippets

Literature search

Two of the authors (A.T.M.R. and A.H.) independently searched and extracted relevant literature from 3 medical databases, PubMed, Embase, and PsychINFO, by using the following search terms: (atopic dermatitis OR eczema) AND (depression OR suicide OR suicidal ideation OR antidepressant OR anxiety OR anxious OR panic attack OR worry OR anxiolytic). All studies in English that examined the relationship between patients with AD and either depression, anxiety, or suicidal ideation and/or attempt

Results

A total of 2107 nonduplicate articles were identified. After screening of the titles and abstracts, 1917 articles were excluded and the remaining 190 articles were obtained for full-text review. Of these articles, 130 were excluded for reasons listed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram (Supplemental Fig 1) (ie, irrelevant exposure or outcome). A total of 60 articles were included in the qualitative analysis,7, 9, 10, 13, 14, 15, 16, 17, 18, 19,

Main findings

In this systematic review and meta-analysis, a positive and significant association was found between AD in adulthood and, respectively, depression, anxiety, and suicidal ideation. For anxiety and depression, clinically meaningful increased risks were observed. Only a few studies examined the risk of completed suicide, but the majority showed a positive association. In children, a positive association was found between AD and depression, although the estimate was weaker than that for adults.

Interpretation

The

References (79)

A.B. Fishbein et al.
Nocturnal eczema: review of sleep and circadian rhythms in children with atopic dermatitis and future research directions
J Allergy Clin Immunol
(2015)
P. Yaghmaie et al.
Mental health comorbidity in patients with atopic dermatitis
J Allergy Clin Immunol
(2013)
S. Lee et al.
Association of atopic dermatitis with depressive symptoms and suicidal behaviors among adolescents in Korea: the 2013 Korean Youth Risk Behavior Survey
BMC Psychiatry
(2017)
F.J. Dalgard et al.
The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries
J Invest Dermatol
(2015)
S.H. Yu et al.
Association between atopic dermatitis and depression in US adults
J Invest Dermatol
(2015)
C.-M. Cheng et al.
Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study
J Affect Disord
(2015)
S. Bahreinian et al.
Depression is more common in girls with nonatopic asthma
Chest
(2011)
F. Catal et al.
Psychiatric disorders and symptoms severity in preschool children with atopic eczema
Allergol Immunopathol (Madr)
(2016)
M.E. Faulstich et al.
Psychophysiological analysis of atopic dermatitis
J Psychosom Res
(1985)
M. Hashiro et al.
The relationship between the psychological and immunological state in patients with atopic dermatitis
J Dermatol Sci
(1998)

R.M. King et al.

Use of a diary technique to investigate psychosomatic relations in atopic dermatitis

J Psychosom Res

(1991)

M. Hashiro et al.

Anxiety, depression and psychosomatic symptoms in patients with atopic dermatitis: comparison with normal controls and among groups of different degrees of severity

J Dermatol Sci

(1997)

J. Seo et al.

Suicide idea and depressive symptom in Korean adolescent with allergic disease

Neuropsychiatrie de l'Enfance et de l'Adolescence

(2012)

A.C. Miers et al.

Developmental pathways of social avoidance across adolescence: the role of social anxiety and negative cognition

J Anxiety Disord

(2014)

K. Hawton et al.

Risk factors for suicide in individuals with depression: a systematic review

J Affect Disord

(2013)

S.H. Yu et al.

Burden of sleep and fatigue in US adults with atopic dermatitis

Dermatitis

(2016)

L.B. Norreslet et al.

The impact of atopic dermatitis on work life - a systematic review

J Eur Acad Dermatol Venereol

(2018)

N.G. Heede et al.

Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry-based study assessing risk of disability pension

Contact Dermatitis

(2017)

M.S. Senra et al.

Psychodermatological aspects of atopic dermatitis

Br J Dermatol

(2014)

A. Egeberg et al.

Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis

Allergy

(2016)

Y.W. Yang et al.

Cigarette smoking may modify the risk of depression in eczema among adults: a preliminary study using NHANES 2005-2006

J Eur Acad Dermatol Venereol

(2011)

C. Di Pietrantonj

Four-fold table cell frequencies imputation in meta analysis

Stat Med

(2006)

A. Stang

Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses

Eur J Epidemiol

(2010)

K. Shirata et al.

The importance of mental support to the patients with adult atopic dermatitis

Osaka City Med J

(1996)

R. Zachariae et al.

Psychological symptoms and quality of life of dermatology outpatients and hospitalized dermatology patients

Acta Derm Venereol

(2004)

R. Zachariae et al.

Itch severity and quality of life in patients with pruritus: preliminary validity of a Danish adaptation of the itch severity scale

Acta Derm Venereol

(2012)

A. Mizara et al.

Core beliefs and psychological distress in patients with psoriasis and atopic eczema attending secondary care: the role of schemas in chronic skin disease

Br J Dermatol

(2012)

N. Lind et al.

Psychological distress in asthma and allergy: the Västerbotten Environmental Health Study

Psychol Health Med

(2014)

A. Drucker et al.

Burden of atopic dermatitis: a claims-based analysis

J Am Acad Dermatol

(2016)

S.H. Kim et al.

Psychological distress in young adult males with atopic dermatitis: a cross-sectional study

Medicine (Baltimore)

(2015)

S. Kim et al.

The association between atopic dermatitis and depressive symptoms in Korean adults: the fifth Korea National Health and Nutrition Examination Survey, 2007-2012

Korean J Fam Med

(2015)

M.A. Radtke et al.

Prevalence and comorbidities in adults with psoriasis compared to atopic eczema

J Eur Acad Dermatol Venereol

(2017)

J. Whiteley et al.

The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey

Curr Med Res Opin

(2016)

J. Dieris-Hirche et al.

Suicidal ideation in adult patients with atopic dermatitis: a German cross-sectional study

Acta Derm Venereol

(2017)

J.P. Thyssen et al.

Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide

Allergy

(2018)

Y. Sato et al.

Asthma and atopic diseases in adolescence and antidepressant medication in middle age

J Health Psychol

(2016)

E.K. Johansson et al.

Association between preschool eczema and medication for attention-deficit/hyperactivity disorder in school age

Pediatr Allergy Immunol

(2017)

M. Augustin et al.

Epidemiology and comorbidity in children with psoriasis and atopic eczema

Dermatology

(2015)

H. Kimata

Prevalence of suicidal ideation in patients with atopic dermatitis

Suicide Life Threat Behav

(2006)

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: Ms Rønnstad and Ms Halling-Overgaard contributed equally to this project.

: Funding sources: Dr Thyssen is supported by an unrestricted grant from the Lundbeck Foundation. Ms Anne-Sofie Halling-Overgaard is supported by a scholarship from Herlev and Gentofte Hospital.

: Disclosure: Dr Thyssen has attended an advisory board for Roche and Sanofi-Genzyme and been a speaker on atopic dermatitis for LEO Pharma and Sanofi-Genzyme. Dr Skov has received research funding from Sanofi, LEO Pharma, Pfizer, Novatis, and Janssen, as well as honoraria as a consultant and/or speaker from Pfizer, AbbVie, Eli Lilly, Novartis, LEO Pharma, Janssen-Cilag, and Sanofi; Dr Skov has also served as an investigator for Pfizer, AbbVie, Eli Lilly, Novartis, Amgen, Regeneron, Boehringer Ingelheim, and LEO Pharma. Dr Egeberg has received research funding from Pfizer and Eli Lilly and honoraria as a consultant and/or speaker from LEO Pharma, Samsung Bioepis, Pfizer, Eli Lilly, Novartis, Galderma, and Janssen Pharmaceuticals. Ms Halling-Overgaard, Ms Rønnstad, and Dr Hamann have no conflicts of interest to disclose.

: Dr Thyssen, Dr Egeberg, Ms Halling-Overgaard, and Ms Rønnstad had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis, as well as for the study concept and design. All the authors take responsibility for acquisition, analysis, and interpretation of the data; critical revision of the manuscript for important intellectual content; administrative, technical, or material support; and study supervision. Dr Thyssen, Dr Hamann, Ms Halling-Overgaard, and Ms Rønnstad take responsibility for drafting of the manuscript. Dr Egeberg takes responsibility for statistical analysis.

: Reprints not available from the authors.

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Original articleAssociation of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Literature search

Results

Main findings

Interpretation

J Allergy Clin Immunol

J Allergy Clin Immunol

BMC Psychiatry

J Invest Dermatol

J Invest Dermatol

J Affect Disord

Chest

Allergol Immunopathol (Madr)

J Psychosom Res

J Dermatol Sci

J Psychosom Res

J Dermatol Sci

Neuropsychiatrie de l'Enfance et de l'Adolescence

J Anxiety Disord

J Affect Disord

Burden of sleep and fatigue in US adults with atopic dermatitis

Dermatitis

The impact of atopic dermatitis on work life - a systematic review

J Eur Acad Dermatol Venereol

Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry-based study assessing risk of disability pension

Contact Dermatitis

Psychodermatological aspects of atopic dermatitis

Br J Dermatol

Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis

Allergy

Cigarette smoking may modify the risk of depression in eczema among adults: a preliminary study using NHANES 2005-2006

J Eur Acad Dermatol Venereol

Four-fold table cell frequencies imputation in meta analysis

Stat Med

Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses

Eur J Epidemiol

The importance of mental support to the patients with adult atopic dermatitis

Osaka City Med J

Psychological symptoms and quality of life of dermatology outpatients and hospitalized dermatology patients

Acta Derm Venereol

Itch severity and quality of life in patients with pruritus: preliminary validity of a Danish adaptation of the itch severity scale

Acta Derm Venereol

Core beliefs and psychological distress in patients with psoriasis and atopic eczema attending secondary care: the role of schemas in chronic skin disease

Br J Dermatol

Psychological distress in asthma and allergy: the Västerbotten Environmental Health Study

Psychol Health Med

Burden of atopic dermatitis: a claims-based analysis

J Am Acad Dermatol

Psychological distress in young adult males with atopic dermatitis: a cross-sectional study

Medicine (Baltimore)

The association between atopic dermatitis and depressive symptoms in Korean adults: the fifth Korea National Health and Nutrition Examination Survey, 2007-2012

Korean J Fam Med

Prevalence and comorbidities in adults with psoriasis compared to atopic eczema

J Eur Acad Dermatol Venereol

The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey

Curr Med Res Opin

Suicidal ideation in adult patients with atopic dermatitis: a German cross-sectional study

Acta Derm Venereol

Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide

Allergy

Asthma and atopic diseases in adolescence and antidepressant medication in middle age

J Health Psychol

Association between preschool eczema and medication for attention-deficit/hyperactivity disorder in school age

Pediatr Allergy Immunol

Epidemiology and comorbidity in children with psoriasis and atopic eczema

Dermatology

Prevalence of suicidal ideation in patients with atopic dermatitis

Suicide Life Threat Behav

Original article
Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis