10.5826/dpc.1301a53
Introduction: Atopic dermatitis (AD) is a global health problem. There are no data on the association of AD with obsessive-compulsive disorder (OCD).
Objectives: This study aimed to map a wide spectrum of different diseases among patients with atopic dermatitis compared to healthy controls in the Region of Jönköping County, Sweden with special focus on OCD.
Methods: We conducted a retrospective case control study from January 1st 2013 until December 31st 2021 using an electronic medical records database covering the entire population of the County of Jönköping. ICD-10 codes were used to identify patients with AD. Individuals without AD served as controls. A total number of 398,874 citizens under the age of 90 was included in this study and among these 2,946 individuals were diagnosed with AD. Regression analysis was performed to describe the risk for comorbidities in patients with AD compared to controls, adjusted for age and gender.
Results: We found an association between obsessive-compulsive disorder (OCD) in patients with AD (adjusted odd ratio 2.0, 95% confidence interval 1.5-2.7, p&lt;0.001). Other results are in the line with other studies.
Conclusion: Pointing to previous studies, the cause of AD and OCD share several gene-environmental mechanisms and this association should be further studied on larger populations. The results of the present study underline the need for dermatologists to be aware of OCD and to screen for this condition in AD patients because early diagnosis and treatment may improve outcome.
text/xml
2160-9381
2558
en
Sandra Gulin-Jerkovic
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
obsessive-compulsive disorder
Significant Association Between Obsessive-Compulsive Disorder And Atopic Dermatitis – A Retrospective Population-Based Case-Control Study
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-01-31
2022-04-26
2023-01-31
2023-02-27
e2023053
Dermatol Pract Concept
Introduction: Atopic dermatitis (AD) is a global health problem. There are no data on the association of AD with obsessive-compulsive disorder (OCD).
Objectives: This study aimed to map a wide spectrum of different diseases among patients with atopic dermatitis compared to healthy controls in the Region of Jönköping County, Sweden with special focus on OCD.
Methods: We conducted a retrospective case control study from January 1st 2013 until December 31st 2021 using an electronic medical records database covering the entire population of the County of Jönköping. ICD-10 codes were used to identify patients with AD. Individuals without AD served as controls. A total number of 398,874 citizens under the age of 90 was included in this study and among these 2,946 individuals were diagnosed with AD. Regression analysis was performed to describe the risk for comorbidities in patients with AD compared to controls, adjusted for age and gender.
Results: We found an association between obsessive-compulsive disorder (OCD) in patients with AD (adjusted odd ratio 2.0, 95% confidence interval 1.5-2.7, p&lt;0.001). Other results are in the line with other studies.
Conclusion: Pointing to previous studies, the cause of AD and OCD share several gene-environmental mechanisms and this association should be further studied on larger populations. The results of the present study underline the need for dermatologists to be aware of OCD and to screen for this condition in AD patients because early diagnosis and treatment may improve outcome.
Sandra Gulin-Jerkovic
2023/01/31
10.5826/dpc.1301a53
e2023053
Department of Dermatology and Venereology, General Hospital Sibenik, Croatia
2160-9381
obsessive-compulsive disorder
en
e2023053
Radtke MA, Schäfer I, Glaeske G, Jacobi A, Augustin M. Prevalence and comorbidities in adults with psoriasis compared to atopic eczema. J Eur Acad Dermatol Venereol. 2017;31(1):151-7.
Significant Association Between Obsessive-Compulsive Disorder And Atopic Dermatitis – A Retrospective Population-Based Case-Control Study
https://dpcj.org/index.php/dpc/article/download/2558/1978
             Significant Association between
        Obsessive-Compulsive Disorder and Atopic
       Dermatitis – a Retrospective Population-Based
                     Case-Control Study
            Sofia Åkerlund1, Oliver Seifert2,4, Johan Assarsson3, Sandra Gulin Jerkovic2,4


1 Department of Dermatology and Venereology, Höglandssjukhuset Nässjö, Region Jönköping County, Sweden
2 Division of Cell Biology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
3 Jönköping County Council, Sweden
4 Department of Dermatology and Venereology, Ryhov County Hospital, Jönköping, Sweden



Key words: atopic dermatitis, obsessive-compulsive disorder, comorbidities
Citation: Åkerlund S, Seifert O, Assarsson J, Gulin Jerkovic S. Significant association between obsessive-compulsive disorder and atopic
dermatitis – a retrospective population-based case-control study. Dermatol Pract Concept. 2023;13(1):e2023053. DOI: https://doi.
org/10.5826/dpc.1301a53
Accepted: June 27, 2022; Published: January 2023
Copyright: ©2023 Åkerlund et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Sandra Gulin Jerkovic, Department of Dermatology and Venereology, Ryhov County Hospital, Sjukhusgatan,
55305 Jonkoping, Sweden, Jonkoping, Sweden. E-mail: sandrajerkovicgulin@rjl.se; Sandra.jerkovic.gulin@liu.se




  ABSTRACT             Introduction: Atopic dermatitis (AD) is a global health problem. There are no data on the association
                       of AD with obsessive-compulsive disorder (OCD).
                       Objectives: This study aimed to map a wide spectrum of different diseases among patients with ­atopic
                       dermatitis compared to healthy controls in the Region of Jönköping County, Sweden with special
                       focus on OCD.
                       Methods: We conducted a retrospective case control study from January 1st 2013 until December 31st
                       2021 using an electronic medical records database covering the entire population of the County of
                       Jönköping. ICD-10 codes were used to identify patients with AD. Individuals without AD served as
                       controls. A total number of 398,874 citizens under the age of 90 was included in this study and among
                       these 2,946 individuals were diagnosed with AD. Regression analysis was performed to describe the
                       risk for comorbidities in patients with AD compared to controls, adjusted for age and gender.
                       Results: We found an association between obsessive-compulsive disorder (OCD) in patients with AD
                       (adjusted odd ratio 2.0, 95% confidence interval 1.5-2.7, p<0.001). Other results are in the line with
                       other studies.




Original Article | Dermatol Pract Concept. 2023;13(1):e2023053                                                                             1
                      Conclusion: Pointing to previous studies, the cause of AD and OCD share several gene-environmental
                      mechanisms and this association should be further studied on larger populations. The results of the
                      present study underline the need for dermatologists to be aware of OCD and to screen for this condi-
                      tion in AD patients because early diagnosis and treatment may improve outcome.




Introduction                                                       influence their mothers in terms of OCD and health-related
                                                                   quality of life [21, 22].
Atopic dermatitis (AD) is a chronic inflammatory disease
with a lifetime prevalence of up to 20% [1]. The disease is
                                                                   Objectives
associated with an impaired skin barrier, elevated levels of
total immunoglobulin E (IgE) and immune dysregulation.             Establishing comorbidity seen in AD can help to further
Genetic predisposition and environmental triggers are likely       understand the complex pathogenesis of AD, contribute to
involved in causing the disease [2]. Treatment strategies usu-     finding improved treatment strategies, and thus improve
ally involve moisturizing regimes, topical anti-inflammatory       quality of life in AD patients. Consequently, studies investi-
preparations, phototherapy and, in severe cases systemic           gating comorbidities related to AD are of great importance
therapy [3, 4]. AD usually develops in children as part of the     in order to screen for and treat them as early as possible. This
atopic march, thus frequently occurs together with asthma          study aimed to determine the association between AD and
and allergic rhinitis in the same individual [5). Different sub-   selected diagnoses, including OCD, in the population of the
types of hand eczema are additional conditions that have           Region Jönköping, Sweden.
well-established associations with AD [6]. Several studies
have indicated that the burden of comorbidity reaches well
                                                                   Methods
beyond the atopic march and hand dermatitis [7-9]. Previ-
ous studies have shown that patients with AD have an in-           In this retrospective population-based case-control study,
creased risk of bacterial, viral and fungal infections [9-12].     patients and controls were identified from Cosmic R8; the
Several studies have detected a positive association between       electronic medical record (EMR) used by the regional health-
AD and allergic and autoimmune diseases. Furthermore, al-          care provider. All registered citizens of the Region Jönköping
opecia areata has been shown to increase the risk of AD [8].       under the age of 90 were included from January 1, 2013, un-
Most recently, a large population-based study conducted in         til December 31, 2021, also including those who had never
Sweden has indicated significant autoimmune comorbidity            contacted a regional state facility. The case group included
of adults with AD, pointing to autoimmune dermatological,          all individuals with one of the following ICD-10 diagnoses;
gastrointestinal and rheumatological diseases [13].                L209 Atopic dermatitis, unspecified; L208A Atopic dermati-
    An association between overweight/obesity and AD has           tis in children without food allergy; L208B Atopic dermatitis
been significantly observed in North America and Asia, but         in children with food allergy; L208G Atopic dermatitis in
not in Europe [14]. Data has shown a greater risk for conges-      adult; registered in the Dermatology and Venereology Clinic
tive heart failure and coronary artery disease in adults with      or in the Pediatric Clinic. The control group included all cit-
AD, while results on increased risk in AD for myocardial           izens of the region who had never been diagnosed with one
infarction and stroke have varied [15].                            of the mentioned L20- diagnoses in one of the two clinics.
    The association between AD and cancer is the subject of        For each individual, data was collected about gender and
several previous studies but results are ambiguous. [8, 16].       age. In the case group, age was defined as the patients’ age
Depression, suicidality and anxiety are more frequently            the first time they acquired an AD diagnosis and for controls
occurring in patients with AD compared to the non-AD               as their age on December 31, 2021. Ethical approval for this
population [17, 18]. Several studies show that atopic dis-         study was obtained by Swedish Ethical Review Authority
ease and atopic eczema correlate to an increased risk of           (Dnr 2022-00212-01).
developing attention deficit/hyperactivity disorder (ADHD)            A literature search was performed in PubMed on articles
and autism spectrum disorder later in life [19-21]. Data is        exploring atopic dermatitis and comorbidities and resulted
limited when it comes to the association between AD and            in an arbitrary selection of 82 comorbidity diagnoses. Each
obsessive-compulsive disorder (OCD). Two studies exam-             individual, both cases and controls, was matched with each
ined the association of OCD in mothers of children with AD         comorbidity in Cosmic R8 and it was registered if they had
where results showed that having a child with AD does not          received one of the diagnoses during the test period. The data



2                                                                      Original Article | Dermatol Pract Concept. 2023;13(1):e2023053
was coded so that the person performing the analysis was                     CI = 1.6-2.0) (Table 2). Further, ADHD was significantly in-
blinded to personal information about the subjects.                          creased in AD.
    Data were processed into a Statistical Package for the                      Furthermore, our result indicated a positive association
Social Sciences (IBM SPSS version 27.0) data sheet for statis-               between AD and autoimmune disorders such as vitiligo
tical analysis. Continuous data were described as mean±SD.                   (OR =3.5; 95% CI = 2.2-5.4), alopecia areata (OR =3.9; 95%
To estimate the risk of comorbidity the odds ratio (OR) pre-                 CI = 2.8-5.5), Crohn’s disease (OR = 3.4; 95% CI = 2.4-4.9)
sented with a 95% confidence interval (CI) was calculated                    as well as ulcerative colitis (OR = 2.2; 95% CI = 1.5-3.2).
using a binominal logistic regression and ORs were adjusted                     Positive associations were seen among infections: other
for age and sex and presented as such unless stated otherwise.               bacterial intestinal infections (OR =2.4; 95% CI = 1.7-3.4),
                                                                             erysipelas (OR = 3.4; 95% CI =2.8-4.2), streptococcus and

Results                                                                      staphylococcal infection (OR =5.9; 95% CI = 4.6-7.4),
                                                                             herpes viral infections (OR = 3.3; 95% CI = 2.8-3.9), viral
The study included all 398,874 citizens of Jönköping County                  infections (OR = 1.6; 95% CI = 1.5-1.7), dermatophytosis
under the age of 90 that were registered in Cosmic R8 and                    (OR =2.5; 95% CI = 2.2-2.8), candidiasis (OR = 2.1; 95%
were alive on December 31, 2021. Among these, 2,946                          CI = 1.8-2.4), Lyme disease (OR = 1.7, 95% CI = 1.4-2.0)
(0.7%) were included in the case group and 395,928 (99.3 %)                  and impetigo (OR = 4.9; 95% CI = 4.5-5.4) and streptococ-
in the control group. There were 1,229 males and 1,717 fe-                   cal sepsis were significantly associated with AD (OR = 3.9;
males in the case group and 201,732 males and 194,196 fe-                    95% CI = 1.3-12.3).
males in the control group. The mean age in the case group                      Significantly increased risk of having cardiovascular
was 23.2 years and most patients (34.6 %) were seen in the                   disorders for patients with AD was found for hypertension
age groups 0-9. The control group had a more homogenous                      (OR = 2.2; 95% CI = 1.9-2.6), dyslipidaemia (OR = 1.8,
distribution between the age groups and a mean age of 40.5                   95% CI = 1.5-2.2), atherosclerosis (OR = 3.5; 95% CI =
years. (Table 1)                                                             1.9-6.2), cerebral infarction (OR = 3.0; 95% CI = 2.0-4.6),
    Our results showed that patients with atopic dermati-                    angina pectoris (OR =1.9; 95% CI = 1.3-2.8) and chronic
tis had an increased risk for several comorbidities includ-                  ischemic heart disease (OR = 2.0; 95% CI = 1.5-2.8). The
ing OCD (OR = 2.0; 95% CI =1.5-2.7), anxiety disorders                       diagnosis Z72 Problems related to lifestyle was significantly
(OR = 1.5; 95% CI = 1.4-1.7), depressive episodes and sleep                  increased in the AD group (OR = 1.5, 95% CI = 1.3-1.8).
disorders (OR = 1.4, 95% CI = 1.3-1.6; OR = 1.8, 95%                         The diagnoses include the sub-diagnoses Z72.0 Tobacco use,


       Table 1. Table showing patients demographics patients with atopic dermatitis and controls.
                                    Atopic Dermatitis                                                       Controls
                       n             %              M                F                  n             %                M           F
                     2946            0.7          1229             1717              395928          99.3         201732        194196
 Age
 Mean (±SD)        23.2 (20.6)                 19.9 (20.5)       25.6 (20.3)       40.5 (23.8)                   39.9 (23.5)   41.0 (24.1)
       0-9            989           34.6           535              454              45012           11.4          23106         21906
     10-19            531           18.0           217             314*              46627           11.8          23916         22711
     20-29            474           16.1           138             336**             54388           13.7          28376         26012
                                                                          #
     30-39            319           10.8            92              227              55676           14.1          29045         26631
                                                                         %
     40-49            228            7.7            98             130               45980           11.6          23725         22255
     50-59            189            6.4            78             111&              48409           12.2          24908         23501
                                                                         a
     60-69            123            4.2            41              82               41034           10.4          20813         20221
                                                                         b
     70-79             78            2.7            27              51               38717            9.8          19093         19624
     80-89             15            0.5              3              12              20085            5.1              8750      11335

n = number, M = male, F = female
* OR for females to develop eczema is 1.517 (95% CI 1.277-1.801)
** OR for females to develop eczema is 2.635 (95% CI 2.163-3.210)
#
  OR for females to develop eczema is 2.677 (95% CI 2.102-3.409)
%
  OR for females to develop eczema is 1.412 (95% CI 1.087-1.834)
&
  OR for females to develop eczema is 1.506 (95% CI 1.128-2.011)
a
  OR for females to develop eczema is 2.054 (95% CI 1.413-2.987)
b
  OR for females to develop eczema is 1.836 (95% CI 1.152-2.925)



Original Article | Dermatol Pract Concept. 2023;13(1):e2023053                                                                             3
4
                                                                                             Table 2. Number, frequency and odds ratio (OR) for comorbid conditions of patients with atopic dermatitis
                                                                                                                          between 2013 and 2021 compared to controls.
                                                                                                                                                Atopic dermatitis                       Adjusted OR #
                                                                                           Comorbidity                        ICD-10-code        (n=2946) n (%)      OR (95% CI)          (95% CI)       Significance level ##
                                                                 Predominantly allergic asthma                                   J45.0              177 (6.0)        8.6 (7.3-10.1)      6.4 (5.5-7.5)           ***
                                                                 Vasomotor and allergic rhinitis                                  J30              897 (30.4)        4.0 (3.7-4.4)       4.2 (3.8-4.5)           ***
                                                                 Acute atopic conjunctivitis                                     H10.1             530 (18.0)        6.4 (5.8-7.0)       5.6 (5.1-6.2)           ***
                                                                 Vitiligo                                                         L80                21 (0.7)        2.9 (1.8-4.4)       3.5 (2.2-5.4)           ***
                                                                 Alopecia areata                                                  L63                35 (1.2)        3.8 (2.7-5.4)       3.9 (2.8-5.5)           ***
                                                                 Crohn disease                                                    K50                29 (1.0)        2.5 (1.7-3.5)       3.4 (2.4-4.9)           ***
                                                                 Ulcerative colitis                                               K51                27 (0.9)        1.5 (1.0-2.3)       2.2 (1.5-3.2)           ***
                                                                 Essential hypertension                                           I10               280 (9.5)        0.5 (0.4-0.5)       2.2 (1.9-2.6)           ***
                                                                 Atherosclerosis                                                  I70                12 (0.4)        0.7 (0.4-1.2)       3.5 (1.9-6.2)           ***
                                                                 Cerebral infarction                                              I63                25 (0.8)        0.7 (0.5-1.1)       3.0 (2.0-4.6)           ***
                                                                 Angina pectoris                                                  I20                31 (1.1)        0.5 (0.3-0.7)       1.9 (1.3-2.8)           ***
                                                                 Disorders of lipoprotein metabolism and other lipidemias         E78               167 (5.7)        0.4 (0.4-0.5)       1.8 (1.5-2.2)           ***
                                                                 Obesity                                                          E66               253 (8.6)        1.1 (0.9-1.2)       1.6 (1.4-1.9)           ***
                                                                 Problems related to lifestyle                                    Z72               138 (4.7)        0.9 (0.8-1.1)       1.5 (1.3-1.8)           ***
                                                                 Depressive episode                                               F32              364 (12.4)        1.1 (0.9-1.2)       1.4 (1.3-1.6)           ***
                                                                 Other anxiety disorders                                          F41              502 (17.0)        1.3 (1.1-1.4)       1.5 (1.4-1.7)           ***
                                                                 Obsessive-compulsive disorder                                    F42                42 (1.4)        2.3 (1.7-3.1)       2.0 (1.5-2.7)           ***
                                                                 Non-organic sleep disorder                                       F51              296 (10.0)        0.9 (0.8-0.9)       1.5 (1.4-1.8)           ***
                                                                 Sleep-disorders                                                  G47               256 (8.7)        0.9 (0.9-1.1)       1.8 (1.6-2.0)           ***
                                                                 Other bacterial intestinal infections                            A04                31 (1.1)        1.7 (1.2-2.4)       2.4 (1.7-3.4)           ***
                                                                 Erysipelas                                                       A46                95 (3.2)        1.5 (1.2-1.8)       3.4 (2.8-4.2)           ***
                                                                 Lyme disease                                                    A69.2              140 (4.8)        1.1 (0.9-1.3)       1.7 (1.4-2.0)           ***
                                                                 Herpes simplex infections                                        B00               145 (4.9)        3.2 (2.7-3.8)       3.3 (2.8-3.9)           ***
                                                                 Viral infection of unspecified site                              B34              977 (33.2)        2.1 (2.0-2.3)       1.6 (1.5-1.7)           ***
                                                                 Dermatophytosis                                                  B35               236 (8.0)        1.8 (1.5-2.0)       2.5 (2.2-2.8)           ***
                                                                 Candidiasis                                                      B37               253 (8.6)        1.7 (1.5-1.9)       2.1 (1.8-2.4)           ***
                                                                 Streptococcus and staphylococcus as the cause of diseases        B95                75 (2.5)        2.6 (2.1-3.3)       5.9 (4.6-7.4)           ***
                                                                 classified to other chapters




Original Article | Dermatol Pract Concept. 2023;13(1):e2023053
                                                                                                                                           Atopic dermatitis                    Adjusted OR #
                                                                                            Comorbidity                      ICD-10-code    (n=2946) n (%)     OR (95% CI)        (95% CI)         Significance level ##
                                                                 Impetigo                                                       L01           585 (19.9)       8.0 (7.3-8.8)     4.9 (4.5-5.4)             ***
                                                                 Resistance to methicillin                                     U82.1            21 (0.7)       3.7 (2.4-5.7)     2.9 (1.9-4.5)             ***
                                                                 Tobacco use                                                   Z72.0            66 (2.2)       0.9 (0,7-1.1)     1.5 (1.2-2.0)             ***
                                                                 Cerebral atherosclerosis                                       I67.2             1 (0.0)      3.9 (0.5-28.9)   15.3 (2.1-114.1)            **
                                                                 Chronic ischemic heart disease                                  I25            48 (1.6)       0.4 (0.3-0.5)     2.0 (1.5-2.8)              **
                                                                 Scabies                                                        B86             37 (1.3)       2.2 (1.6-3.1)     1.6 (1.2-2.2)              **
                                                                 Other specified bacterial agents as the cause of diseases      B96             29 (1.0)       0.7 (0.5-0.9)     1.7 (1.2-2.5)              **
                                                                 classified to other chapters
                                                                 Arthritis                                                    M05-M09           32 (1.1)       1.0 (0.7-1.5)     2.0 (1.4-2.8)              **
                                                                 Coeliac disease                                               K90.0            34 (1.2)       1.7 (1.2-2.5)     1.7 (1.2-2.4)              **
                                                                 Lack of physical exercise                                     Z72.3            12 (0.4)       1.4 (0.8-2.4)     2.1 (1.2-3.8)              **
                                                                 Hyperkinetic disorder                                          F90            125 (4.2)       1.8 (1.5-2.2)     1.3 (1.1-1.5)              **
                                                                 Eating disorders                                               F50             36 (1.2)       2.5 (1.8-3.4)     1.6 (1.1-2.2)              **




Original Article | Dermatol Pract Concept. 2023;13(1):e2023053
                                                                 Streptococcal sepsis                                           A40               3 (0.1)      1.4 (0.4-4.3)     3.9 (1.3-12.3)              *
                                                                 Meningococcal infection                                        A39               1 (0.0)      9.0 (1.2-67.9)   12.9 (1.6-101.7)             *
                                                                 Pneumonia due to Streptococcus pneumonia                        J13              4 (0.2)      1.3 (0.5-3.6)     3.2 (1.2-8.5)               *
                                                                 Type 1 diabetes mellitus                                       E10             32 (1.1)       0.9 (0.6-1.3)     1.5 (1.1-2.2)               *
                                                                 Type 2 diabetes mellitus                                       E11             71 (2.4)       0.4 (0.3-0.5)     1.3 (1.0-1.7)               *
                                                                 Other sepsis                                                   A41               9 (0.3)      0.6 (0.3-1.2)     2.0 (1.0-3.9)               *
                                                                 Eosinophilic esophagitis                                      K209A              2 (0.1)      2.9 (0.7-12.0)    3.9 (0.9-15.9)             ns
                                                                 Autism                                                      F84.0/F84.1        40 (1.4)       1.9 (1.4-2.6)     1.2 (0.9-1.6)              ns
                                                                 Multiple sclerosis                                             G35               3 (0.1)      0.5 (0.2-1.5)     0.7 (0.2-2.2)              ns
                                                                 Systemic lupus erythematosus                                   M32               2 (0.1)      0.9 (0.2-3.5)     1.3 (0.3-5.1)              ns
                                                                 Acute myocardial infarction                                     I21            10 (0.3)       0.3 (0.2-0.5)     1.1 (0.6-2.1)              ns
                                                                 Subsequent myocardial infarction                                I22              0 (0.0)      0.0 (0.0-0.0)     0.0 (0.0-0.0)              ns
                                                                 Certain current complications following acute myocardial        I23              0 (0.0)      0.0 (0.0-0.0)     0.0 (0.0-0.0)              ns
                                                                 infarction
                                                                 Other acute ischaemic heart disease                             I24              0 (0.0)      0.0 (0.0-0.0)     0.0 (0.0-0.0)              ns
                                                                 Smoking                                                       Z72.0A           43 (1.5)       0.7 (0.5-0.9)     1.3 (0.9-1.7)              ns
                                                                 Alcohol use                                                   Z72.1              3 (0.1)      0.9 (0.3-3.0)     2.0 (0.6-6.3)              ns




5
                                                                                                                                                                                                          Table 2 continues
6
                                                                                                 Table 2. Number, frequency and odds ratio (OR) for comorbid conditions of patients with atopic dermatitis
                                                                                                                        between 2013 and 2021 compared to controls. (continued)
                                                                                                                                                                 Atopic dermatitis                   Adjusted OR #
                                                                                               Comorbidity                                       ICD-10-code      (n=2946) n (%)     OR (95% CI)       (95% CI)       Significance level ##
                                                                     Schizophrenia                                                                    F20               2 (0.1)      0.3 (0.1-1.1)    0.5 (0.1-2.0)            ns
                                                                     Other sexually transmitted chlamydial disease                                    A56             60 (2.0)       1.7 (1.4-2.3)    1.2 (0.9-1.5)            ns
                                                                     Tuberculosis of skin and subcutaneous tissue                                    A18.4              0 (0.0)      0.0 (0.0-0.0)    0.0 (0.0-0.0)            ns
                                                                     Human immunodeficiency virus (HIV) disease resulting in                          B20               0 (0.0)      0.0 (0.0-0.0)    0.0 (0.0-0.0)            ns
                                                                     infectious and parasitic disease
                                                                     Cytomegaloviral disease                                                          B25               3 (0.1)      2.5 (0.8-7.8)    2.8 (0.9-8.7)            ns
                                                                     Anogenital herpesviral (herpes simplex) infection                                A60             18 (0.6)       1.6 (1.0-2.5)    1.4 (0.9-2.2)            ns
                                                                     Other diseases caused by chlamydiae                                              A74             10 (0.4)       1.2 (0.6-2.1)    0.9 (0.5-1.8)            ns
                                                                     Gonococcal infection                                                             A54               2 (0.1)      1.6 (0.4-6.5)    1.5 (0.4-5.9)            ns
                                                                     Viral agents as the cause of diseases classified to other                        B97               5 (0.2)      1.3 (0.5-3.1)    1.4 (0.6-3.3)            ns
                                                                     chapters
                                                                     Tick-borne viral encephalitis                                                    A84               0 (0.0)      0.0 (0.0-0.0)    0.0 (0.0-0.0)            ns
                                                                     Hepatitis                                                                     B15-B18              5 (0.2)      0.4 (0.2-0.9)    0.5 (0.2-1.2)            ns
                                                                     Malignant melanoma of skin                                                       C43               8 (0.3)      0.6 (0.3-1.1)    1.5 (0.7-3.0)            ns
                                                                     Other malignant neoplasms of skin                                                C44             28 (1.0)       0.4 (0.2-0.5)    1.3 (0.9-1.9)            ns
                                                                     Lymphomas                                                                     C81-C86              4 (0.1)      0.7 (0.3-1.9)    1.9 (0.7-5.2)            ns
                                                                 #
                                                                     Odds ratio adjusted for age group and sex
                                                                 ##
                                                                      Significance level of adjusted odds ratio (* p<0.05; ** p<0.01; *** p<0.001; ns p>0.05).




Original Article | Dermatol Pract Concept. 2023;13(1):e2023053
Z72.1 Alcohol use, Z72.2 Drug use, Z72.3 Lack of physical        with AD. Furthermore, if microbes can trigger autoimmu-
exercise, Z72.4 Inappropriate diet and eating habits, Z72.5      nity that leads to OCD, it is not irrelevant to consider in-
High-risk sexual behaviour, Z72.6 Gambling and betting,          creased skin infection in AD as a possible risk factor for
Z72.8 Other problems related to lifestyle and Z72.9 Prob-        OCD. A ­total-population-based Swedish study found a sig-
lems related to lifestyle, unspecified.                          nificant association between OCD and several autoimmune
    None of the studied malignant diagnoses were signifi-        diseases including psoriasis vulgaris (32%). However, AD
cantly increased in the AD population (Table 2).                 was not included in the study. The authors evaluated the risk
    To our knowledge, this is the first large population-based   of 40 autoimmune diseases in people with OCD and their
study describing a significant association between OCD and       relatives and found an increased risk for autoimmune dis-
AD. There are only two previous studies analyzing the asso-      ease in first-degree relatives to patients with OCD compared
ciation between AD and OCD, but the authors studied symp-        to second- and third-degree relatives. Their results suggest a
toms of OCD in mothers of children with AD and found that        potential genetic link between OCD and autoimmune dis-
AD in the child did not influence their mothers in terms of      eases[34]. Similar studies could be performed with OCD and
OCD [22, 23]. However, our study only included 42 patients       AD to see if there are indications of genetic linkage between
diagnosed with OCD which makes studies on additional and         the two diseases.
preferably larger populations essential to further investigate      In conclusion, the two conditions likely share several
the association.                                                 common gene-environmental pathways. Optimized treat-
    OCD is characterized by recurrent thoughts, urges or im-     ment of AD to restore the skin barrier and prevent skin in-
ages that lead to repetitive behavior or mental acts, causing    fections might be of great importance in order to prevent
distress and anxiety. These are severely time-consuming and/     OCD. For future research, larger populations should be in-
or cause impairment in social, occupational or other import-     cluded and it should be investigated if those with both AD
ant situations [24]. The estimated one-year prevalence of        and OCD also have been diagnosed with PANDAS and if
OCD is 1.2% and the estimated lifetime prevalence is 2.3%,       they have other autoimmune diseases or infections in close
with an onset usually seen before the age of 30 [25]. During     temporal association with the onset of OCD. The connec-
our test period of nine years, 1.4% of the AD patients were      tion should be adjusted for comorbidity diagnoses shared
diagnosed with OCD, which correlates somewhat with the           between AD and OCD, such as anxiety disorder and depres-
global prevalence, but it was significantly less prevalent in    sion. Studies to see if OCD and AD share genetic material/
the control group (0.6%). The reason for the generally lower     activated gene sequences could also be interesting.
prevalence of OCD in the population of Jönköping com-               Depression and anxiety occurred more frequently in pa-
pared to the global population cannot easily be explained        tients with AD compared to the control population, which
and further studies are needed on large groups. The comor-       was in line with earlier findings. Sleep disturbance was in-
bidities most often seen with OCD are additional psychiatric     creased in AD patients in this study. Sleep disturbance, pru-
disorders [26].                                                  ritus, stigma, social isolation and poor quality of life are
    Previous studies and reviews investigated the role of the    associated with AD and might contribute to this correlation
immune system in the pathophysiology of OCD [27-29].             [9, 35, 36]. Pruritus and inflammation as part of AD can lead
There is some evidence that persistent low-grade inflamma-       to sleep disturbances which in turn may cause depression
tion is seen in OCD patients [28]. Specifically, the cytokines   and anxiety [9]. The systemic inflammation seen in AD is an-
IL-4 and IL-17 are elevated in both AD and OCD [30-32].          other possible explanation for the connection since inflam-
Autoantibodies against the basal ganglia are almost five         matory proteins are elevated in depressed patients in blood
times more likely to be detected in patients with OCD com-       and cerebrospinal fluid [37-39]. Cytokines can affect neu-
pared to controls. In some cases of OCD infectious agents,       rotransmission and behaviors and emotions associated with
such as streptococcus, other bacteria, viruses and parasites     both sickness and depression [40].
are seen as triggers of autoimmunity [28]. In some children,        This study found that ADHD was significantly in-
the onset or exacerbation of OCD is seen in association with     creased in the AD group which is in line with previous
Streptococcus A infection. The condition is named pediat-        studies [41, 42]. Most of these studies however include only
ric autoimmune neuropsychiatric disorder associated with         children or analyze children and adults separately [19-21].
group A streptococci (PANDAS). Hypothetically, Streptococ-       Buske-Kirschbaum et al propose three different explanations
cus A triggers an autoimmune reaction that interacts with        for the association between AD and ADHD: 1) Allergic in-
neurons in the basal ganglia and causes OCD [33].                flammation and psychologic stress due to chronic disease
    The above-mentioned studies suggest that a dysregulated      leads to the release of inflammatory cytokines that interfere
inflammatory response might contribute to the occurrence         with the maturation of prefrontal cortex regions and neuro-
of OCD and this could potentially explain the association        transmission involved in AHDH pathology; 2) elevated stress



Original Article | Dermatol Pract Concept. 2023;13(1):e2023053                                                               7
levels in ADHD trigger AD or 3) the conditions are separate          This study has several strengths. We used an electronic
but have shared risk factors (eg. genetics, prenatal stress)      medical record for the collection of all data. These records
that increase the risk of developing both disorders [43].         allowed easy access to data that was required for the anal-
    Similar to previous studies we saw increased risk for a       ysis. This furthermore enabled a large study population.
number of infections and autoimmune diseases in the AD            We chose to only include patients in the study group that
group. Somewhat surprisingly, we found an increase in Lyme        received their AD diagnosis in the Dermatology or Pediat-
disease in the AD group which logically cannot be explained       ric Clinic. At these clinics, physicians have more specialized
by a default skin barrier. Literature is scarce on the area and   competence to correctly recognize these conditions than in
future studies on the connection and potential co-factors,        other clinics. Understandably, this means that those with
such as neuroborreliosis, could be interesting.                   an AD diagnosis from another clinic were included in the
    The positive association between AD and Crohn’s dis-          control group rather than the study group, as were those
ease, ulcerative colitis, celiac disease, alopecia areata and     who received an AD diagnosis before and not during the
vitiligo detected in this study, correlates well with previous    test period. Most probably, the patients in our study group
study results [8, 13, 44]. Inflammatory bowel disease, psori-     have a moderate to severe degree of disease and most of
asis and alopecia areata share several genetic risk loci with     the AD diagnoses included in the control group have mild
AD [45-47]. A German cohort study showed an increased             symptoms. This can affect the results in different ways. It
risk of rheumatoid arthritis and inflammatory bowel disease       might make significant associations between AD and the
(and a decreased risk for type 1 diabetes) in combination         different comorbidity more difficult since those with one
with AD, independent of known risk alleles [48]. Elevated         of the examined comorbidities in the control group might
levels of Th1, Th2 and Th17 responses are present in the          have AD. If that is the case, then that would mean that their
pathogenesis of both inflammatory bowel disease and atopic        exclusion from the control group would make our results
dermatitis [10, 49].                                              even more significant. On the other hand, it could be specu-
    We found a significant association with several comor-        lated that comorbidity is mostly seen in moderate to severe
bidities that can be categorized as cardiovascular disease.       AD, which strengthens the choice of inclusion criteria. A
Four well-known risk factors for cardiovascular disease were      limitation of this study was that we did not specify the de-
also increased in the AD group, e.g. hyperlipidemia, obesity,     gree of AD symptoms, so we are not able to analyze disease
hypertension and diabetes. Poor health behavior is often          severity and how it correlates to comorbidity. Another lim-
seen in patients with AD. They have a higher incidence of         itation is that we initially only adjusted for age and gender.
smoking, drinking alcohol at a young age and have reduced         As discussed above, metabolic diseases share risk factors
physical activity. Children with AD participate less in sports    with some common comorbidity in AD. Unless we adjust
and play more videogames [50, 51]. This was to some extent        for those risk factors nothing can be said about a causal as-
reflected in our results. These combined increased cardio-        sociation between cardiovascular comorbidity and AD. The
vascular risk factors, as well as the aforementioned frequent     connection between AD and OCD should be adjusted for
sleep disturbance in patients with AD, likely play an import-     shared comorbidity. In agreement with the current litera-
ant role in the development of cardiovascular disease in the      ture, we found an increased risk for allergic rhinitis, allergic
AD population [7]. The systemic inflammation seen in AD           asthma and atopic conjunctivitis in AD patients. This is in
and to some extent in cardiovascular disease as well as in        line with previous knowledge and can be used as validation
some of the cardiovascular risk factors might be one reason       of the diagnostic code for AD [5]. We did not choose to
for the association, as well as genetic factors [52, 53]. Two     validate every comorbidity diagnosis since this study was
studies however found an increased risk for cardiovascular        intended as a screening for multiple comorbidities in order
disease and stroke in AD patients initially but not after ad-     to detect interesting correlations.
justing for cardiovascular risk factors, which suggests that
poor health behavior and cardiovascular risk factors are the
                                                                  Conclusions
major reason for increased cardiovascular disease in AD pa-
tients, rather than systemic inflammation [54, 55]. We did        Our results strengthen the knowledge that a wide spectrum
not choose to adjust for cardiovascular risk factors when an-     of comorbidity is seen in AD. We found an increased risk
alyzing the odds ratio for cardiovascular disease. Thus this      between AD and OCD. These findings are essential for clini-
study does not contribute to deeper insight into the mecha-       cians seeing patients with AD. Early detection and treatment
nism for the connection between such conditions and AD.           of OCD are crucial for optimal treatment of AD and the
Generally, cardiovascular risk factors are seen less often in     quality of life of AD patients. Future nationwide studies are
association with AD compared to psoriasis [56].                   needed to confirm our results.




8                                                                     Original Article | Dermatol Pract Concept. 2023;13(1):e2023053
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