BJD

E P I DE M I O L O G Y A N D HE A L T H S E R V IC E S RE SE AR CH British Journal of Dermatology

Increased risk of lichen simplex chronicus in people with

anxiety disorder: a nationwide population-based
retrospective cohort study*
Y.-H. Liao,1,2 C.-C. Lin,3,4 P.-P. Tsai,1,2 W.-C. Shen,1,5 F.-C. Sung3,4 and C.-H. Kao2,6
1
Department of Radiology; 2Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine; 3Management Office for Health Data;
4
Department of Public Health; 5Department of Biomedical Imaging and Radiological Science, College of Health Care; and 6Department of Nuclear Medicine and
PET Center; China Medical University Hospital, No. 2 Yuh-Der Road, Taichung 404, Taiwan

Summary

Correspondence
Chia-Hung Kao.
E-mail: d10040@mail.cmuh.org.tw
Accepted for publication
20 December 2013
Funding sources
The study was supported in part by the Taiwan
Ministry of Health and Welfare Clinical Trial and
Research Center for Excellence (DOH102-TD-B-
111-004), Taiwan Ministry of Health and
Welfare Cancer Research Center for Excellence
(MOHW103-TD-B-111-03), Bureau of Health
Promotion, Department of Health, R.O.C.
(Taiwan) (DOH99-HP-1205) and International
Research-Intensive Centers of Excellence in Taiwan
(I-RiCE) (NSC101-2911-I-002–303).
Conflicts of interest
None declared.
*Plain language summary available online.
DOI 10.1111/bjd.12811
Background The cingulate cortex is the main area in the brain involved in pruritus
processing and is deactivated after scratching. Lichen simplex chronicus (LSC) is
a common pruritic skin disorder characterized by skin lichenification following
excessive scratching. Psychological factors may contribute to both the develop-
ment and persistence of LSC.
Objectives To estimate the hazard ratio (HR) of LSC in people with anxiety disor-
ders compared with the general population.
Methods In this nationwide population-based retrospective cohort study we iden-
tified a total of 69 386 people, who formed the anxiety cohort, by using the
Taiwan National Health Insurance Research Database from 2000 to 2009. The
comparison cohort was composed of randomly selected people frequency
matched for age (within 5-year intervals), sex and index date (the date of anx-
iety diagnosis) based on a 1 : 2 ratio. The risk of LSC was estimated as HRs
and 95% confidence intervals (CIs) using the Cox proportional hazards model.
Results After adjusting for age, sex and LSC-associated comorbidities, the people
with anxiety had a 1
41-fold greater risk of developing LSC compared with
the people in the comparison cohort (HR 1
41, 95% CI 1
30–1
52,
P < 0
0001). In particular, individuals with obsessive–compulsive disorder had
a significantly increased risk of developing LSC (HR 1
72, 95% CI 1
03–2
88,
P = 0
0395).
Conclusions This study demonstrates that having an anxiety disorder is associated
with an increased risk of LSC. Psychological factors were found to contribute to
LSC. We recommend combining the management of LSC and psychological dis-
orders to achieve favourable outcomes.

What’s already known about this topic?

• Lichen simplex chronicus (LSC) is a common skin disorder characterized by skin
lichenification following excessive scratching.
• LSC is not a life-threatening disease, but it can result in psychosocial problems and
impair quality of life through sleep disturbance and sexual dysfunction.

What does this study add?

• This study demonstrates that people with anxiety, especially those aged < 40 years,
are at an increased risk of having LSC. Psychological factors were found to contrib-
ute to LSC.
• We recommend combining the management of LSC and psychological disorders to
achieve favourable outcomes.

890 British Journal of Dermatology (2014) 170, pp890–894 © 2013 British Association of Dermatologists
 Lichen simplex chronicus and anxiety disorder, Y.-H. Liao et al. 891
The brain and the skin originate from the same embryonic
neuroectoderm in the last differentiation of embryological
development. Pruritus is the major bridging symptom between
these two organs. The cingulate cortex is the area in the brain
mainly involved in pruritus processing and is deactivated after
scratching. Furthermore, the anterior cingulate cortex is
involved in emotional and cognitive activity modulation, such
as reward anticipation. Mood and motivation affect pruritus
perception and processing, and this can possibly be explained
by the physiology of the cingulate cortex.1,2 Lichen simplex
chronicus (LSC), or circumscribed neurodermatitis, is a com-
mon skin disorder characterized by skin lichenification follow-
ing excessive scratching.3 LSC affects up to 12% of the total
population, and affects the female and adult populations more
frequently than the male and young populations. LSC typically
involves the neck, elbow, ankles, vulva, face and eyelids. It is
not a life-threatening disease, but it can result in psychosocial
problems, and it can impair quality of life through sleep dis-
turbance and sexual dysfunction.4
Pruritus is a predominant symptom of LSC and causes a
strong desire to scratch. Long-term scratching results in skin
lesions that are thick, lichenified plaques, which further result
in pruritus. LSC is a chronic skin disease caused by the pruri-
tus scratching cycle. Psychological factors may contribute to
both the development of this neurodermatitis and its persis-
tence.5 A retrospective study of 30 participants indicated that
patients with LSC suffer disproportionately from depressive,
dissociative and anxiety disorders compared with the general
population.5 Another study of 60 participants showed that
patients suffering from LSC had a greater tendency to avoid
pain, and were more dependent on the desires of other peo-
ple, more conformist and more dutiful than the general popu-
lation.6 To estimate the impacts of psychological factors, such
as anxiety disorders, on the incidence of LSC in a large general
population, we conducted a nationwide population-based
cohort study.
Patients and methods
Data source
The National Health Insurance Research Database (NHIRD)
contains reimbursement claim data from the Taiwan National
Health Insurance programme, which was established as a
nationwide single-payer health insurance programme in 1996
and has covered > 99% of the residents of Taiwan since 1998.
The database is maintained and managed by the National
Health Research Institutes (NHRI).
This study was conducted using the Longitudinal Health
Insurance Database (LHID), which is a subset of the NHIRD.
The LHID consists of one million insured people who were
selected using random sampling between 1996 and 2000.
Before releasing the database to researchers, the NHRI created
a scrambled and anonymous identification number to identify
each insured person. Each record in the database includes sex,
© 2013 British Association of Dermatologists
birth date, occupation and medical services records. This study
was exempted by the Institutional Review Board of China
Medical University in central Taiwan (CMU-REC-101-012).
We recorded the disease history in inpatient and outpatient
files and defined the disease according to the International
Classification of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM).
Study population
This study was a population-based retrospective cohort study.
The anxiety cohort consisted of patients newly diagnosed with
anxiety (ICD-9-CM 300.0, 300.2, 300.3, 308.3 and 309.81)
between 2000 and 2009; the index date was set as the date
on which anxiety was diagnosed. The anxiety cohort was also
separated into two subcohorts: (i) individuals with general
anxiety (ICD-9-CM 300.0, 300.2, 308.3 and 309.81) and (ii)
individuals with obsessive–compulsive disorder (OCD; ICD-9-
CM 300.3). The comparison cohort contained people in the
LHID who had never been diagnosed with anxiety, and were
twofold frequency matched according to age (within 5-year
intervals) and sex. The index dates of the comparison cohort
were randomly assigned a day and month in the same index
year as the anxiety cohort. People who had received an LSC
diagnosis before the index date were excluded. An interesting
event in this study was the development of LSC (ICD-9-CM
698.3). Follow-up was terminated when a person withdrew
from the insurance plan, an event occurred, or on 31 Decem-
ber 2013.
Comorbidity history was considered a potential confound-
ing factor. The comorbidities included hypertension
(ICD-9-CM 401–405), diabetes (ICD-9-CM 250), depression
(ICD-9-CM 296.2, 296.3, 300.4 and 311) and schizophrenia
(ICD-9-CM 295).
Statistical analysis
We calculated the number and proportion of categorical vari-
ables, and the mean and SD of age to determine the distributions
of the comparison and anxiety cohorts. To assess the difference
between the two cohorts, we conducted a t-test for age and
v2-tests for sex and comorbidities. The incidence of LSC in the
two cohorts was calculated by dividing the total number of LSC
occurrences by the total sum of follow-up years in each cohort
by 10 000 person-years. The cumulative LSC incidence curves
were measured using the Kaplan–Meier method, and the differ-
ence between the two curves was tested using the log-rank test.
Hazard ratios (HRs) and 95% confidence intervals (CIs) were
estimated using the Cox proportional hazards model to deter-
mine the influence of anxiety on the risk of LSC.
All data management and statistical analyses were performed
using SAS 9.3 software (SAS Institute Inc., Cary, NC, U.S.A.).
The cumulative incidence curves were plotted using R soft-
ware (http://www.r-project.org/). The significance level was
defined using a two-sided P-value < 0
05.
British Journal of Dermatology (2014) 170, pp890–894
892 Lichen simplex chronicus and anxiety disorder, Y.-H. Liao et al.

Table 1 Demographic status and comorbidity in the comparison and risk of developing LSC compared with people without anxiety.
anxiety cohorts Among other age groups (40–49, 50–59 and ≥ 60 years), the
risk of developing LSC was approximately 1
3-fold higher
Comparison cohort Anxiety cohort among people with anxiety compared with people without
(n = 138 772), (n = 69 386),
anxiety. Men with anxiety had a 1
47-fold increased risk of
Variable n (%) n (%) P-value
developing LSC compared with men without anxiety (HR
Age (years), 49
4  17
0 49
5  16
9 0
3581 1
47, 95% CI 1
30–1
66). In addition, women with anxiety
mean  SDa
had only a 1
36-fold increased risk of developing LSC com-
Sex
pared with women without anxiety (HR 1
36, 95% CI 1
22–
Female 86 490 (62
3) 43 245 (62
3) > 0
99
Male 52 282 (37
7) 26 141 (37
7) 1
50). However, the differences between men and women
Comorbidity were not significant (overlapping 95% CIs). In addition, peo-
Hypertension 32 802 (23
6) 26 149 (37
7) < 0
0001 ple with anxiety had a relatively higher risk of developing LSC
Diabetes 12 697 (9
1) 7691 (11
1) < 0
0001 than people without anxiety, especially in the population
mellitus without hypertension (HR 1
52, 95% CI 1
38–1
68), with
Depression 1888 (1
4) 8855 (12
8) < 0
0001
diabetes (HR 1
55, 95% CI 1
24–1
93), without depression
Schizophrenia 827 (0
6) 974 (1
4) < 0
0001
(HR 1
40, 95% CI 1
29–1
52) and without schizophrenia (HR
a
Calculated using the t-test. 1
38, 95% CI 1
27–1
49).

Results
This study included a cohort of 69 386 patients with anxiety
who were an average of 49
5 years old and predominantly
female (62
3%). The comparison cohort had the same mean
age and sex ratio (P > 0
05, Table 1). The proportion of LSC-
associated comorbidity in the anxiety cohort was much higher
than in the comparison cohort (P < 0
0001).
Table 2 shows an analysis of LSC risk stratified according to
the presence or absence of OCD in the general anxiety study
participants. The incidence of LSC in the anxiety cohort was
25
68 per 10 000 person-years, which was 1
45-fold greater
than in the comparison cohort (17
77 per 10 000 person-
years) (Fig. 1). After adjusting for age, sex and LSC-associated
comorbidities, people with anxiety were shown to have a
1
41-fold greater risk of developing LSC than people in the
comparison cohort (HR 1
41, 95% CI 1
30–1
52). When the
participants with general anxiety disorders were further
divided into the OCD and non-OCD subgroups, the OCD sub-
group had a 1
72-fold higher risk of developing LSC than the
comparison cohort, and the non-OCD subgroup had a 1
37-
fold higher risk of developing LSC.
Table 3 shows an analysis of LSC risk stratified according to
demographics and comorbidities. Among people younger than
40 years old, people with anxiety had a 1
54-fold increased
Discussion
This is the first nationwide population-based cohort study to
estimate the effects of anxiety disorder on LSC prevalence. Anx-
iety disorder, a major psychological disease, is both an aggra-
vating factor and a consequence of pruritus and scratching, the
major symptoms of LSC. The increased anxiety levels can
increase the severity of pruritic dermatitis, and one of the main
psychiatric sequelae secondary to chronic pruritus is anxiety.7
Anxiety and mood disorders are common in the general
population, and the difference in their prevalence is not sub-
stantial. The lifetime prevalence rate of anxiety disorder is 4–
7%.8 Patients with anxiety disorder often worry uncontrollably
and suffer from physiological symptoms such as sleep distur-
bance, muscle tension and difficulty concentrating. These peo-
ple may not be able to attain their social and occupational
potential. One study indicated that 38% of people with anxi-
ety exhibited an inability to work and loss of role functioning
for an average of 6
3 days per month because of the disor-
der.9 Some patients with anxiety disorder have an increased
risk of suicide.10 Anxiety disorders may go undiagnosed
because of the physical symptoms of anxiety and the stigma
of mental illness. The large sample size of our study, drawn
from a nationwide population-based dataset, strengthens the
statistical power of our study regarding the association
between anxiety disorder and LSC.

Table 2 Incidence of lichen simplex chronicus and multivariate hazard ratios (HRs) for the study cohort, measured by Cox proportional hazards
regression analysis

Variable n Events PY Ratea Crude HR (95% CI) Adjusted HR (95% CI)b

Comparison cohort 138 772 1557 876 246 17
77 Reference Reference
Anxiety cohort 69 386 1144 445 546 25
68 1
45 (1
34–1
56) 1
41 (1
30–1
52)
General anxiety 68 536 1129 440 194 25
65 1
45 (1
34–1
56) 1
37 (1
26–1
48)
OCD 850 15 5353 28
02 1
57 (0
95–2
62) 1
72 (1
03–2
88)

PY, person-years; CI, confidence interval; OCD, obsessive–compulsive disorder. aIncidence rate per 10 000 PY. bAdjusted for age, sex, hyper-
tension, depression, schizophrenia and diabetes.

British Journal of Dermatology (2014) 170, pp890–894 © 2013 British Association of Dermatologists
 Lichen simplex chronicus and anxiety disorder, Y.-H. Liao et al. 893

Fig 1. Cumulative incidence of lichen simplex

chronicus in the comparison and anxiety
cohorts.

Table 3 Incidence of lichen simplex chronicus by demographic factors and comorbidities, and hazard ratios (HRs) measured by multivariate Cox
proportional hazards regression analysis

Comparison cohort Anxiety cohort

a
Variable Events PY Rate Events PY Rate Crude HR (95% CI) Adjusted HR (95% CI)b
Age group (years)
< 40 356 261 581 13
61 278 132 109 21
04 1
55 (1
32–1
81) 1
54 (1
31–1
80)
40–49 337 208 612 16
15 228 104 599 21
80 1
35 (1
14–1
60) 1
35 (1
13–1
60)
50–59 291 174 475 16
68 211 87 717 24
05 1
44 (1
21–1
72) 1
37 (1
14–1
64)
≥ 60 573 231 578 24
74 427 121 121 35
25 1
43 (1
26–1
62) 1
38 (1
22–1
57)
Sex
Female 921 559 641 16
46 643 284 970 22
56 1
37 (1
24–1
52) 1
36 (1
22–1
50)
Male 636 316 605 20
09 501 160 577 31
20 1
56 (1
38–1
75) 1
47 (1
30–1
66)
Hypertension
No 1076 683 677 15
74 650 279 706 23
24 1
48 (1
34–1
63) 1
52 (1
38–1
68)
Yes 481 192 569 24
98 494 165 840 29
79 1
21 (1
06–1
37) 1
25 (1
10–1
42)
Diabetes
No 1401 804 975 17
40 988 399 431 24
74 1
42 (1
31–1
54) 1
40 (1
29–1
52)
Yes 156 71 271 21
89 156 46 115 33
83 1
56 (1
25–1
95) 1
55 (1
24–1
93)
Depression
No 1518 866 355 17
52 991 391 534 25
31 1
45 (1
34–1
57) 1
40 (1
29–1
52)
Yes 39 9891 39
43 153 54 013 28
33 0
73 (0
51–1
03) 0
79 (0
55–1
13)
Schizophrenia
No 1549 871 362 17
78 1133 439 169 25
80 1
45 (1
35–1
57) 1
38 (1
27–1
49)
Yes 8 4884 16
38 11 6377 17
25 1
11 (0
45–2
75) 0
91 (0
32–2
57)

PY, person-years; CI, confidence interval. aIncidence rate per 10 000 PY. bAdjusted for age, sex, hypertension, depression, schizophrenia and
diabetes.

As LSC is a type of neurodermatitis, treatment requires the
work of dermatologists, psychiatrists, psychologists and care-
givers who can educate patients to address the psychological
and physical aspects of the disease. To treat the dermatological
aspects of LSC, anti-inflammatory agents are useful. For wide-
spread skin lesions, phototherapy treatment may be consid-
ered. Moisturizers may help in repairing the skin. The
application of moisturizers distracts the patient from the sensa-
tion of pruritus and is an aspect of the behavioural replace-
ment for scratching. Covering local LSC lesions is crucial for
increasing the healing rate because it both enhances the effects
of the topical agent and provides protection from further
trauma. The most critical aspect of LSC treatment is breaking
the pruritus scratching cycle by making it difficult to scratch

© 2013 British Association of Dermatologists British Journal of Dermatology (2014) 170, pp890–894
894 Lichen simplex chronicus and anxiety disorder, Y.-H. Liao et al.
the lesions and reducing the euphoria derived from scratch-
ing.7,11 To treat the psychological aspects of LSC, education,
support and behavioural therapy can strengthen a person’s
psychological ability to control the scratch process.12 Patients
with neurosis or psychosis should be treated by a psychologist
or psychiatrist. Pharmacotherapeutic agents may be useful;
however, most LSC-affected patients prefer to see a dermatolo-
gist, and are unwilling to see a psychiatrist. In such cases a
multidisciplinary medical unit is necessary.13
It is our expectation that OCD could result in a significantly
higher risk of developing LSC. When the participants with
general anxiety disorders were further divided into OCD and
non-OCD subgroups (Table 2), individuals with OCD (HR
1
72, 95% CI 1
03–2
88) had a significantly higher risk of
developing LSC than patients without OCD (HR 1
37, 95% CI
1
26–1
48, P = 0
0395). Therefore, we think the level of anx-
iety could affect the outcome or prognosis of LSC. In addition,
LSC affects the female population predominantly. However, in
our study, male patients (1
47-fold) with anxiety disorder had
a higher (but not significantly) risk of developing LSC com-
pared with female patients (1
36-fold) (Table 3). A possible
explanation is that men who seek psychological help may have
a worse health status than women because of different person-
alities. Perhaps more follow-up or a different therapeutic strat-
egy should be given to male patients with anxiety disorders
with or without LSC. However, further studies are recom-
mended to ascertain the reasons scientifically.
A limitation of our study is the inconsistent diagnosis of
anxiety disorders. In general practice, not all anxiety disorders
are diagnosed strictly by psychiatrists in accordance with the
Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria.
Some patients may have been diagnosed with anxiety disor-
ders because of a transient anxious state. The anxiety cohort
used in this study therefore consisted partly of people without
anxiety disorder. Therefore, some of our study results could
be interpreted as the increased prevalence of LSC in people
with a personality tending to be anxious.
Another major limitation of our study is that the evidence
derived from a cohort study is generally of a lower methodo-
logical quality than that from randomized trials because a
cohort study design is subject to many biases related to adjust-
ments for confounding factors. Despite our meticulous study
design with adequate controls for confounding factors, a pri-
British Journal of Dermatology (2014) 170, pp890–894
mary limitation was that bias could still remain because of
possible unmeasured or unknown confounders.
In conclusion, our nationwide population-based retrospec-
tive cohort study provides evidence for the increased preva-
lence of LSC among people with anxiety disorders compared
with the general population without anxiety disorders. The
management of LSC should focus on its psychological aspects
to facilitate favourable outcomes.
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© 2013 British Association of Dermatologists