People with chronic itching conditions are at increased risk of stress – depression and suicidal

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Itch is a very common symptom in patients suffering from skin diseases.

In a new multicenter cross-sectional study on the psychological burden of itch in the Journal of Investigative Dermatology, published by Elsevier, investigators report that the presence of itch in dermatological patients was significantly associated with clinical depression, suicidal ideation and stress.

They recommend providing patients with access to a multidisciplinary team to prevent and manage problems associated with itch..

The burden of itch has already been described in conjunction with a number of specific skin diseases including hand eczema; psoriasis; nodular prurigo (a skin disease that causes hard, itchy lumps to form on the skin); hidradenitis suppurativa (a painful, long-term skin condition that causes abscesses and scarring on the skin) among hemodialysis patients; and in chronic itch patients in general.

“There are already studies showing evidence of a correlation between itch and mental health problems in general, and in specific skin disorders, but there is a lack of a cross-sectional study across chronic skin diseases,” explained lead investigator Florence J. Dalgard, MD, PhD, Department of Dermatology and Venereology, Skåne University Hospital, Lund University, Malmö, Sweden.

Part of a large European multicenter study conducted by the European Society for Dermatology and Psychiatry (ESDaP), the present study compared the psychological burden of disease and health-related quality of life between dermatological patients with itch and those without itch, as well as with healthy controls.

Investigators collected data from dermatological clinics in 13 European countries on 3,530 patients with skin diseases and compared the results with more than 1,000 healthy controls.

Patients completed questionnaires and were also examined clinically.

Outcome measures included the presence, chronicity and intensity of itch; the Hospital Anxiety and Depression Scale; sociodemographics; suicidal ideation, and stress, including negative life events; and economic difficulties.

The prevalence of itch in dermatological conditions was nearly 90 percent in prurigo and related conditions; 86 percent in atopic dermatitis; 82 percent in hand eczema; 78 percent in other eczema; 76 percent in urticarial; and 70 percent in psoriasis.

This shows a person with a rash scratching

Scratching that itch. Itchy patients were more likely to be seriously depressed and to have suicidal thoughts. The image is credited to Journal of Investigative Dermatology.

The prevalence of depression was 14 percent in patients with itch compared to 5.7 percent in patients without itch, six percent in controls with itch, and three percent in controls without itch.

The prevalence of suicidal thoughts was 15.7 percent in patients with itch, nine percent in patients without itch,18.6 percent in controls with itch and 8.6 percent in controls without itch.

The reported occurrence of stressful life events was higher in individuals with itch than in those without itch. Patients with itch were also likely to experience more economic problems.

“Our research shows that itch has a high impact on quality of life,” commented Dr. Dalgard. “This study illustrates the burden of the symptom of itch and its multidimensional aspect. The management of patients with itch should involve access to a multidisciplinary team when necessary, as is already the case in several European countries.”

The investigators also recommend preventive measures, such as psoriasis education programs or targeted web-based information.

In many chronic inflammatory skin disorders, early aggressive treatment tailored specifically for the patient might help to reduce itch at the earliest possible opportunity and prevent the development of mental health problems.

Existing anti-itch interventions should be implemented more frequently in the routine care of dermatological patients.


Eczema is a common skin disease associated with decreased quality of life comparable to many other chronic medical conditions.1 2

 Eczema affects approximately 1 in 9 children and 1 in 14 adults, most of whom have mild disease.2–4 

For patients with severe persistent eczema, however, the disease can be debilitating with severe itch, social embarrassment and impaired quality of life.5

 Patients with eczema can also experience financial hardships due to direct medical costs, missed days from employment and decreased work productivity.5 6 Sleep loss related to itch can be especially debilitating2 7 and nearly half of US adults who have eczema with fatigue rate their health as poor or fair.2

Past research has linked eczema to mental illness. In a claims-based study from Taiwan, patients had a sevenfold increased risk of a major depressive disorder and fourfold increased risk of an anxiety disorder.8 

In two American cross-sectional studies, eczema was associated with twice the risk of depression compared with the general population.9 One study from Denmark found no significant association between eczema and subsequent suicide.10 

Whereas a prior study found a suicide risk twice the population norm for patients with eczema.11 The risk of suicide associated with eczema has not been assessed in North America; moreover, most studies have excluded youth despite eczema being distinctly common and suicide being a leading cause of death in this age group.2 4 12

The objective of this case–control study was to assess the association of eczema with a patient’s subsequent risk of death from suicide.

A secondary aim was to assess the recency of physician visits prior to suicide among patients with eczema. A randomised controlled trial was deemed impossible because patients cannot be assigned a diagnosis of eczema; therefore, we conducted a large-scale multiyear observational analysis of longitudinal individual patient data. We hypothesised that persistent eczema would increase a patient’s risk of death from suicide and that many deaths would be preceded by a recent physician visit.

If true, this would suggest that preventive efforts targeting vulnerable patients might save lives.

Patient and public involvement

There was no patient or public involvement in this study.

Selection of patients

We conducted a double matched case–control study of patients between the age of 15 and 55 years in Ontario. We included individuals 15 and older as eczema is a common diagnosis and suicide is a common cause of death in youth.2 4 12

 We excluded adults older than 55 to avoid misclassification of age-associated xerosis with itch as eczema. Cases of suicide were identified from the Ontario Vital Statistics Database from 1 January 1994 to 31 December 2014, representing all available data. We defined suicide using International Classification of Disease (ICD) codes (ICD-9 E950–E959, E980–E987; ICD-10×60–X84, Y10–Y32, Y34).13–15

 Inter-rater agreement from coroners on suicide diagnosis was high and showed 97% concordance with the vital statistics database.16 17 We also extracted data on the mechanism of suicide in five categories as asphyxiation, jumping, poisoning, violence and miscellaneous.

Controls were selected from the general population in Ontario using the Registered Persons Database that identified all patients insured under the Ontario Health Insurance Plan (OHIP).18 For each case of suicide, we selected two control patients from the general population matched on age (within 2 days), socioeconomic status (SES) quintile and sex using simple random selection when excess matches were available. All cases and controls were alive and eligible for OHIP coverage on the index date and 1 year prior.

SES at the index date was estimated from the Statistics Canada algorithm based on neighbourhood income19 20 and patients with missing SES were matched to controls who were also missing SES. As a result, we obtained exact triplets of one case matched to two controls with no missing matches. These datasets were linked using unique encoded identifiers and analysed at Institute for Clinical Evaluative Sciences.

Primary predictor

We used a 5-year look-back interval to assess each patient through a consistent ascertainment interval for cases and controls. The matching date in each triplet of patients was defined as the date of suicide death of the case.

Prior medical care for each patient was evaluated based on physician diagnoses documented as ICD-9 diagnostic codes.13 In Ontario, physicians document each encounter with a single ICD-9 code. Eczema was defined using diagnosis code 691.13 

In another population, ICD-9 codes for atopic dermatitis, a specific subtype of eczema, had a positive predictive value of 50% based on a requirement for two or more ICD-9 codes to identify cases of probable atopic dermatitis.21 

To increase the specificity and to define persistent eczema, we required five or more physician visits for the diagnosis, each separated by at least 1 week over the 5-year look-back interval. Given the uncertain validity of that definition, we refer to our predictor as ‘eczema’ rather than the more specific ‘atopic dermatitis’ throughout the manuscript.

Additional patient characteristics

Specific additional medical diagnoses (asthma, hay fever or rhinitis, alcoholism, drug dependence, tobacco abuse, sleep and other disorders, depression, anxiety disorders, psychoses, personality disorders, malignancy, benign skin tumours, psoriasis) were identified during the 5-year look-back interval using ICD-9 codes in the OHIP database. Measures of overall healthcare resource utilisation were obtained from the OHIP database, the National Ambulatory Care Reporting System and the Discharge Abstract Database (counts of clinic visits, emergency room visits, hospitalisations in the prior year). We collected data on patients’ most recent healthcare visit, the specialty of the physician and the associated diagnosis. We also collected data on the timing of suicide (proximity to the most recent visit with a dermatologist or psychiatrist and recency of a visit for eczema).

Statistical analysis

We used logistic regression to calculate ORs with 95% CIs for the association of persistent eczema with the risk of subsequent death from suicide. We examined the robustness of findings by additionally calculating associations using conditional logistic regression to fully account for matching.

To assess for potential mediation, we conducted stratified analyses by major suicide risk factors (depression, psychoses, personality disorders, sleep and other disorders, drug dependence and alcoholism) within triads of cases and controls.

Further, we used logistic regression with suicide as the outcome and major suicide risk factors as covariates to derive an overall suicide predilection score. We then conducted logistic regression stratified by low (at or below the median) or high (above the median) overall suicide predilection score. To assess for potential mediation or confounding by a major atopic comorbidity, we conducted analyses further stratified by history of asthma.

We plotted Kaplan-Meier curves for patients who died from suicide with and without persistent eczema to assess the time interval between the most recent physician visit and ultimate suicide. We compared the two curves using the logrank test.

To assess potential differences in the mechanism of suicide between patients with and without persistent eczema, we calculated descriptive ORs with 95% CIs for the different categories of suicide with no prespecified hypotheses.

We conducted several sensitivity analyses as tests of robustness. We replicated separate analyses to check results using alternative definitions of eczema:

(1) spanning between 1 and 10 claims associated with the diagnosis;

(2) requiring a comorbid atopic condition (asthma or rhinitis) and

(3) excluding patients who had a history of stasis ulcers, varicose veins, lymphoedema, contact dermatitis, seborrheic dermatitis or psoriasis. These latter two analyses were based on the rationale that comorbid asthma and rhinitis can improve the positive predictive value of ICD codes for atopic dermatitis21 and because excluding commonly confused conditions can also decrease false positive cases.

As a test for residual confounding, we conducted tracer analyses with two additional control predictors: benign skin tumours and psoriasis (another chronic skin disease with effective treatment options). We anticipated benign skin tumours and psoriasis might not be associated with an increased risk for suicide and thereby validate the distinctive association with eczema.

Results

We identified 18 441 cases of suicide matched to 36 882 alive controls over the 21-year accrual period. The median patient age was 38 years, 74% were male and the average SES was below the population median. Mental health disorders were more common among patients who had died from suicide than among controls, as were malignant neoplasms and asthma (table 1). Patients who died from suicide had more clinic visits, emergency department visits and inpatient admissions in the year prior to the index date than controls.

Table 1

Patient characteristics

Suicide cases
n=18 441, (%)
Matched controls
n=36 882, (%)
Age (years)
 15–242825 (15)5650 (15)
 25–343746 (20)7492 (20)
 35–445595 (30)11 190 (30)
 45–556275 (34)12 550 (34)
Sex (male)13 680 (74)27 360 (74)
Income quintile
 Q5 (highest)2839 (15)5678 (15)
 Q43162 (17)6324 (17)
 Q33426 (19)6852 (19)
 Q23814 (21)7628 (21)
 Q1 (lowest)4969 (27)9938 (27)
 Unknown/suppressed231 (1)462 (1)
Home location
 Urban15 532 (84)32 158 (87)
 Rural*2893 (15)4462 (12)
 Missing16 (<1)262 (1)
Comorbidities†
 Alcoholism3109 (17)750 (2)
 Drug dependence/addiction3645 (20)1164 (3)
 Psychoses5373 (29)979 (3)
 Depression5753 (31)1788 (5)
 Anxiety disorder12 807 (69)10 690 (29)
 Personality disorder2391 (13)469 (1)
 Sleep disorders2844 (15)2536 (7)
 Malignancy1024 (6)1331 (4)
 Asthma2291 (12)3247 (9)
 Rhinitis1956 (11)4204 (11)
Health services use in the preceding year
 Six or more clinic visits11 946 (65)12 365 (34)
 One or more emergency room visits4053 (22)3173 (9)
 One or more inpatient admissions1379 (8)511 (1)
OHIP eligible for entire 5-year look-back period17 701 (96)34 447 (93)

*Rural includes unknown/suppressed home location.

†Comorbidities defined by truncated ICD-9 codes: alcoholism (303), drug dependence/addiction (304), psychoses (291, 292, 295, 296, 298, 299), depression (311), anxiety disorder (300), personality disorder (301), sleep and other disorders (307), malignancy (140–165, 170–175, 179–208), asthma (493), rhinitis (477).

ICD-9, International Classification of Disease, Ninth Revision; OHIP, Ontario Health Insurance Plan.

A history of persistent eczema occurred in 174 (0.94%) suicide cases and 285 (0.77%) controls. In univariate analysis, persistent eczema was associated with a 22% increased risk of suicide. Results were identical for ordinary and conditional logistic regression (OR 1.22, 95% CI 1.01 to 1.48, p=0.037). The net increase was equal to 31 excess cases of suicide associated with eczema (more than one patient per year).

Stratified analyses showed the association of eczema with suicide was accentuated among older men with a history of addiction (figure 1). There was no significant differential association of eczema with suicide between strata of patients with and without asthma, malignancy or other individual suicide risk factors such as depression.

Patients with eczema had significantly higher suicide predilection scores compared with patients without eczema (median 0.32 vs 0.15, p<0.0001; online supplementary figure 1). Comparisons based on mean scores showed similar imbalance (0.42 vs 0.33, p<0.0001). The highest decile of suicide predilection score was nearly twice as common among patients with eczema as controls (17% vs 10%, p<0.0001). Stratified analysis by high or low predilection scores showed no significant further association of eczema with suicide between patients with high predilection scores (OR 0.97, 95% CI 0.78 to 1.22, p=0.81) and low predilection scores (OR 0.59, 95% CI 0.34 to 1.03, p=0.06), suggesting that eczema was not an independent contributor to suicide risk beyond its influence on mental health risk overall.

Supplementary data

bmjopen-2018-023776supp001.pdf

Nearly all patients with persistent eczema who died from suicide had visited a physician in the year prior to their death, 67% within a month and 37% within a week. Among patients who died from suicide, those diagnosed with persistent eczema visited a physician more recently than patients without persistent eczema (p<0.0001, figure 2). For both patients with and without persistent eczema who died from suicide, the most recent physician visit was most frequently with a family physician (table 2).

Among patients with persistent eczema, 1 in 25 had visited a dermatologist last. For 1 in 16 patients with persistent eczema who died from suicide, their last visit was for eczema. We found no meaningful differences in season or in day of the week of death distinguishing patients who did and did not have persistent eczema (table 3).

Analyses of suicide cases showed diverse mechanisms, of which about 8% were unclassified due to uncertain, multifactorial or missing details. Asphyxiation was the most common single cause of suicide and was less frequent among individuals who had persistent eczema than controls (OR 0.55, 95% CI 0.38 to 0.78, p=0.0008). In contrast, jumping from a vertical height had the largest relative increased risk among patients who had persistent eczema (OR 1.87, 95% CI 1.21 to 2.89, p=0.0047).

Poisoning was the second largest relative increased risk among patients who had persistent eczema (OR 1.41, 95% CI 1.04 to 1.91, p=0.03). Violent forms of suicide were infrequent and generally balanced between the two groups (OR 1.04, 95% CI 0.71 to 1.54, p=0.83).

In sensitivity analyses requiring fewer than five visits for eczema to define the predictor, the association with suicide was somewhat attenuated (online supplementary figure 2). When 10 or more visits for eczema were required, the CIs widened substantially and the association was ambiguous.

When a diagnosis of asthma or rhinitis was required to identify cases of eczema, the estimated association for the risk of suicide was similar to the primary analysis but not statistically significant (OR 1.26, 95% CI 0.94 to 1.69, p=0.12). When patients who had a diagnosis of stasis ulcers, varicose veins, lymphoedema, contact dermatitis, seborrheic dermatitis and psoriasis were excluded, the results were similar to the primary analysis (OR 1.26, 95% CI 0.99 to 1.61, p=0.06), although not statistically significant. Benign skin tumours were associated with no increase in suicide risk (OR 0.90, 95% CI 0.84 to 0.97, p=0.008). Psoriasis was associated with an equivocal increase in suicide risk (OR 1.14, 95% CI 0.99 to 1.31, p=0.06).


Source:
Elsevier
Media Contacts:
Theresa Monturano – Elsevier
Image Source:
The image is credited to Journal of Investigative Dermatology.

Original Research: Open access
“Itch and mental health in dermatological patients across Europe: a cross sectional study in 13 countries”. Florence J. Dalgard et al.
Journal of Investigative Dermatology doi:10.1016/j.jid.2019.05.034 .

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