Anxiety and depression in patients with hand eczema: A population‐based study among 853 middle‐aged subjects

Hand eczema (HE) is a common dermatological disorder with considerable effect on the health‐related quality of life (HRQoL). The data on mental comorbidities of HE is sparse and mostly studied among selected patient groups.

The severity of HE varies from mild to severe and it often has a relapsing and long-term course. 5,7ronic HE affects daily life in many ways and has a similar impact on the health-related quality of life (HRQoL) as psoriasis and asthma. 8,9The association between HE and HRQoL has been widely studied, 8,[10][11][12] but less attention has been paid to the risk for mental comorbidities of HE.4][15] A Greek casecontrol study (n = 71) found a positive association between chronic HE and symptoms of anxiety, but no association between HE and symptoms of depression. 14A cross-sectional study from 13 European countries found a positive association between HE (n = 143) and anxiety and depression symptoms in women. 15Similarly, high prevalence of psychiatric symptoms was found in a German study of occupational HE (n = 122). 13nce HE is mostly affecting working-aged people, we aimed to investigate in this cross-sectional study the association between HE and depression and anxiety symptoms by using validated questionnaires in middle-aged general population by using the Northern Finland Birth Cohort 1966 Study (NFBC1966).

| MATERIALS AND METHODS
The Northern Finland Birth Cohort 1966 (NFBC1966) is a longitudinal study from general population in the two northern Finland provinces, Oulu and Lapland. 16,17The NFBC1966 study sample comprised 12 058 live-born children from 12 055 pregnant women whose expected delivery date was between 1 January and 31 December 1966.The study subjects were followed via medical check-ups and health questionnaires from prenatal time up to the age of 46 years with four main follow-up surveys at the age of one, 14, 31, and 46 years. 16,17The study subjects have the possibility to update their permission constantly and the number of study subjects can thus vary depending on the time of the study.

| Questionnaire
In the 46-year follow-up survey, the study subjects answered an extensive questionnaire including questions about health, lifestyle as well as environmental and socioeconomic factors.HE was determined by asking 'Do you have or have you ever had hand eczema diagnosed by a doctor or hand eczema treated by a doctor?' 2 Depression and anxiety symptoms were screened by using Hopkins Symptom Checklist-25 (HSCL-25), which was included in the questionnaire. 18,19HSCL-25 consists of 13 items concerning depression and 10 items concerning anxiety symptoms in the past week.The intensity of psychosocial symptoms was estimated on a four-point scale from 'not at all', 'some', 'considerably' to 'very much'.Based on the responses, a depression and anxiety mean score was generated ranging from 1.0 to 4.0.A value <1.55 referred to 'no or almost no symptoms', a value ranging from 1.55 to 1.75 to 'mild symptoms', and a value >1.75 to 'moderate/severe symptoms'.In this study, the mean value 1.75 was used as a cut-off to categorize the severity of depression and anxiety symptoms. 18,19

| Previous atopic dermatitis
Records of AD diagnosis were obtained from the Finnish Institute of Health and Welfare's statutory Care Register of Health Care (CRHC) and selected by the International Classification of Diseases (ICD) 10 code of AD (L20.0).The CRHC includes inpatient data from all state-administered Finnish hospitals and the largest private hospitals since 1987.Each record consists of the identification numbers of the patient and hospital, primary and subsidiary diagnoses, and duration of hospital stay.The Care Register also includes outpatient visits from 1998 onwards.In Finland, ICD-10 has been used since 1996.Mildto-moderate AD is treated in primary health care and thus not registered in CRHC.Those with more severe AD are commonly sent for hospital consultation.Since AD is known to be associated with depression and anxiety and the risk increases according to the severity of the disease, [20][21][22] we excluded from the analysis those (n = 51) with at least one note of diagnosis of AD in CRHC (indirectly defined as 'severe AD').

| Statistical analysis and confounding factors
Smoking, 23 alcohol consumption, 24 body mass index (BMI), 25 physical activity 26 and socioeconomic status (SES) 27 are known to be associated with psychiatric symptoms and were consequently noted as possible confounding factors.The definitions of confounding factors are described in our previous study 2 with the exception of weight, which was categorized by BMI (kg/m 2 ) and classified in accordance with the Word Health Organization (WHO) guideline into obesity (>30 kg/m 2 ) and overweight (25.0 to <30 kg/m 2 ). 28Normal weight (18.5 to <25 kg/m 2 ) and underweight (<18.5 kg/m 2 ) were combined into one subgroup (<25 kg/m 2 ).
Categorical variables were expressed as numbers and percentage of proportions and tested by using χ 2 test.A logistic regression analysis was used to examine associations between HE and symptoms of depression and anxiety with crude (OR) and adjusted odds ratios (aOR) and 95% confidence intervals (CIs).The following potential confounding factors were adjusted for SES, physical activity, alcohol consumption, smoking, and BMI.The data was analysed using the R software package version 4.1.0.A P-value <0.05 was considered statistically significant.

| ETHICS STATEMENT
The Ethical Committee of the Northern Ostrobothnia Hospital District approved Cohort 1966 and the study which were performed according to the principles of the 1983 Helsinki Declaration.Written informed consent for scientific purposes was obtained from all participants.

| RESULTS
The health questionnaires were sent to 10 331 living study subjects aged 45-46 whose address was known.The questionnaires were answered by 6772 (65.6%) study subjects; of those, 6695 (98.9%) also replied to the question regarding HE.After excluding those with severe AD, the study population consisted of 6644 (64.3%) study subjects.Having ever suffered from HE was reported by 853 (12.8%) subjects.The characteristics of the study subjects are presented in Table 1.Questions about mental health (measured by HSCL-25) were answered by 6582 (99.1%) of study population; of those, 846 (12.9%) ever had HE (Figure 1).Symptoms of depression appeared in 1056 (16.0%) subjects in total population.Frequency of depression symptoms was significantly higher among (n = 172, 20.3%) HE subjects compared with (n = 884, 15.4%) subjects without HE (P < 0.001).Correspondingly, symptoms of anxiety affected (n = 538, 8.2%) study subjects.Anxiety symptoms were also more common among (n = 90, 10.6%) HE subjects than among (n = 448, 7.8%) subjects without HE (P = 0.007).
The odds for symptoms of depression and anxiety in patients who self-reportedly ever had HE was 1.4-fold compared with subjects without HE (OR 1.40 for both, 95% CI: 1.17-1.68for depression and 95% CI: 1.10-1.78for anxiety, respectively).In an adjusted model, after adjusting with sex, BMI, SES, alcohol consumption, smoking and physical activity in multivariate logistic regression analysis, statistically significant associations remained between HE and symptoms of depression (aOR 1.3, 95% CI: 1.08-1.57,P = 0.007) and symptoms of anxiety (aOR 1.34, 95% CI: 1.04-1.71,P = 0.021), Table 2. Note: The definitions of socioeconomic status, smoking, alcohol consumption and physical activity are described in our previous study.There are some missing data because not all study subjects answered every question.Chi-square test was used to examine the associations between hand eczema and confounding factors.Abbreviation: HE, hand eczema. a The definition of body mass index is described in Section 2. The possible two-way interaction between gender and HE with depression and anxiety was examined and no statistically significant interactions were detected (P = 0.627 and 0.501, respectively; Figure 2).

| DISCUSSION
In the present study, we found a positive and statistically significant association between self-reportedly ever having HE and both depression and anxiety symptoms.Our results are consistent with the previous finding of a smaller European study (n = 143) including HE patients of outpatient clinics in which depression and anxiety symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS). 15However, in that study, higher anxiety and depression scores were only found in females with HE but not in males with HE compared with controls, differing from our results. 15 a German study (n = 122), correlation between depressive symptoms and occupational HE was found, with 14% of the study population having positive depression score (screened by HADS) with no significant sex differences. 13Moreover, positive anxiety score was reached by 20% of the study population and was higher in women with occupational HE compared with men. 13 This study population included occupational HE patients with at least 6 months history of resistant outpatient treatment and approximately one-quarter of the patients were on sick leave at the time of the study.The predominance of anxiety symptoms could be caused by the study population of selected dermatological patients with quite severe disease, which differs from our study of general population.However, a Greek study  F I G U R E 2 Association of hand eczema on symptoms of anxiety and depression, stratified by gender.Error bar represents crude odds ratio and 95% CI by gender.Horizontal line and shaded area show adjusted odds ratio and 95% CI of association between hand eczema and having symptoms of anxiety (A) or depression (B), adjusted for sex, socio-economical status, body mass index, smoking, alcohol consumption and physical activity.CI, confidence interval; OR, odds ratio.

T A B L E 2
The association between hand eczema and psychiatric symptoms.
Subjects with severe atopic dermatitis have been excluded from the analysis.Abbreviations: CI, confidence interval; HE, hand eczema; OR, odds ratio.a Adjusted for sex, body mass index, socio-economical status, smoking, alcohol consumption and physical activity.b By Hopkins Symptom Checklist-25, cut-off value 1.75.

1
Characteristics of study subjects.