Sleep disturbance in patients with lichen simplex chronicus and its relationship to nocturnal scratching: a case control study.

Background: Lichen simplex chronicus (LSC) is a common pruritic disorder resulting from repeated rubbing and scratching. Nighttime pruritus is a common feature in LSC and may disrupt the sleep pattern. The aim of this study is to determine whether there are sleep abnormalities in patients with LSC.

Patients and Methods: Fifteen patients with LSC and 15 age-, sex- and body mass index-matched control subjects were enrolled in the study. No participant had any other medical or psychiatric illness. All subjects were evaluated by overnight polysomnography, scratch electrodes, Epworth sleepiness scale and a general questionnaire for demographic data and sleep problems.

Results: There were no significant differences in the groups for total sleep time, sleep efficiency, sleep latency, rapid eye movement (REM) latency, percentage of stage 1 non-REM sleep and REM sleep. The percentage of stage 2 non-REM sleep was higher (P < 0.05) and the percentage of slow wave sleep (stages 3 and 4) was lower in the study group (P < 0.05) than in the controls. The patient group had a mean of 15.9 [+ or -] 7.5 arousal index and 22.8 [+ or -] 14.1 awakenings compared with 9.5 [+ or -] 3.1 and 10.4 [+ or -] 3.9, respectively, in the controls (P < 0.05, P < 0.01, respectively). Arousals of patients were mainly observed in non-REM sleep. The number of scratching bouts ranged from 6 to 20 per night. Scratching episodes were observed frequently during stage 2 non-REM sleep.

Conclusion: Polysomnographic findings of patients with LSC demonstrated that sleep structure is disturbed by arousals and awakenings related to scratching bouts during sleep.

Key Words: lichen simplex chronicus, sleep, pruritus, scratching, polysomnography.

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Lichen simplex chronicus (LSC), also called circumscribed neurodermatitis, is a troublesome, common pruritic disorder resulting from repeated rubbing and scratching. Itch and lichenification are the hallmarks of the disease. (1,2) There is an itch-scratch-lichenification cycle that usually causes a prolonged course. The disease is most commonly seen in females and occurs predominantly after puberty; occurrence before adolescence is rare. The disease most commonly involves the nape of the neck, elbows, lower legs, ankles, wrists, extensor surface of the forearms, scalp, external auditory canal, vulva and pubis or scrotum. (3) The pruritus may be sporadic, paroxysmal or continuous and is often worse at night. Also sweat, warmth and xerosis may trigger the pruritus. (4)

Nighttime pruritus is a common feature of LSC and patients may be unaware of this behavior. (4) Scratching episodes during sleep may cause sleep abnormalities that may impair daytime functioning and lead to excessive daytime sleepiness. (5) This may result in emotional stress. Emotional disturbance may lead to itching, because reactions to stress may be relieved by ritualized behavior such as rubbing or scratching. There may be a relationship between emotional stress and bouts of scratching. (6) Therefore a scratch-sleeplessness-emotional stress-scratch cycle may occur in LSC.

It is not clear whether patients with LSC have an impaired sleep pattern. We considered that patients with LSC may develop sleep disturbance due to nighttime pruritus which may contribute to the perpetuation of the disease, and may affect quality of life. The aim of this study was to characterize sleep patterns in patients with LSC.

Materials and Methods

Patients and Controls

Seventeen patients with LSC (5 females and 12 males; median age 46.9 yr; range 37-67 yr) and 15 healthy control subjects (5 females and 10 males; median age 45.9 yr; range 34-66 yr) matched according to age, sex and BMI (body mass index) were originally included in the study. Two LSC patients were later excluded from the study due to the presence of obstructive sleep apnea syndrome. All of the subjects (patients and controls) were Caucasian. The controls were selected voluntarily from our hospital staff. They were healthy and had no known skin or systemic diseases. Patients who had other skin disorders, such atopic dermatitis, allergic-irritant contact dermatitis or nummular eczema, were not included. Since past studies had indicated that patients who had a psychological disorder may have impaired sleep patterns, (7) all patients and control subjects were examined by the same psychiatrist and subjects who had a psychological disorder were not included in the study. Systemic and local medications were discontinued 7 days before the sleep study. None of the patients or controls had alcohol abuse problems. All patients were evaluated for sleep-related disorders that may cause impairment in sleep and its quality such as narcolepsy, sleep apnea, or periodic limb movement syndrome. A questionnaire was filled out for each study subject to obtain the patient's history, demographic data and sleep problems. The Epworth questionnaire was applied to assess sleepiness and scores equal or greater than 10 were accepted as positive. (8)

This study was approved by the local ethics committee of the university hospital and each subject gave written informed consent to participate in the study.

Polysomnographic Evaluation

All patients underwent a full overnight polysomnography 1 hour before their usual bed time. They were admitted to the sleep laboratory at 9:00 PM and discharged at 8:30 AM the following morning. Sixteen parameters were recorded. Six electroencephalography (EEG) leads (bilateral frontal, central, and occipital), bilateral electro-oculographic leads, and submental electromyographic leads were applied. These surface leads were used to measure the stages of sleep, including time spent in rapid eye movement (REM) sleep. Respiratory parameters were measured to exclude sleep-related breathing disorders such as obstructive sleep apnea syndrome. For this, motion of the chest wall and abdomen were measured by respiratory inductance plethysmography. Airflow from the nose and mouth was measured with thermocouples. Oxyhemoglobin saturation was measured by pulse oximetry. Body motion was recorded with pretibial electromyographic leads. Scratching movements were evaluated by a mechanical strain gauge placed on both fingers and by an electromyography (EMG) measurement of the extensor digitorum muscle of the dominant hand. Cardiac rhythm was monitored with standard electrocardiography (ECG) leads.

Scoring

Data were collected by a digital sleep monitoring system (Compumedics, E series 44 channels). Signals were analyzed with computer software and all the results (sleep stages, arousals, respiratory parameters, etc) were evaluated by a sleep specialist who was blinded to the history. Nocturnal sleep/ wake cycles were scored in accordance with the Rechtschaffen and Kales criteria. (9)

Sleep latency was described as time from lights out to the first occurrence of three consecutive epochs (one epoch is 30 s). REM sleep latency was defined as the time from sleep onset to the first epoch of REM sleep. Sleep efficiency was calculated as the ratio of total sleep time to time in bed. The time spent in each sleep stage was expressed as the percentage of total sleep time. (10)

Arousals and awakenings were scored according to the American Sleep Disorders Task Force Recommendation. (11) Arousals were defined by a 3 second or longer abrupt shift in EEG frequency to alpha or theta or > 16 Hz, following at least 10 seconds of sleep, and if there is a rising in REM, there must be a rise in EMG tone. The arousal index was calculated as the number of arousals per hour of sleep. Awakenings were defined as the presence of a more than 15 second waking EEG following sleep onset with augmentation of the submental EMG and was calculated as total number of awakenings during the night. EMG results were also carefully examined to differentiate patients with periodic limb movement syndrome that may cause arousals and awakenings.

To rule out sleep-related breathing disorders, respiratory parameters were recorded. In the present study, obstructive apnea was defined as cessation of airflow for at least 10 seconds with paradoxical respiratory effort. (10) Hypopnea was defined as a reduction in airflow with synchronous chest wall and abdominal motion, resulting in either arousal or oxyhemoglobin desaturation of at least 4%. (10) Central apnea was defined as a 10 second period without airflow or respiratory effort. The type, number and duration of respiratory events were noted, as well as the median and minimum oxyhemoglobin saturation.

Statistical Analysis

All data were given as mean [+ or -] standard deviation (SD). Statistical package for the Social Sciences (SPSS) for Windows 11.0 was used for statistical analysis. Polysomnographic results of patients and controls were compared by the Mann Whitney U test. The differences were considered to be significant when the p value was less than 0.05.

Results

Two patients (one female, one male) were excluded from the study due to the presence of obstructive sleep apnea syndrome. The demographic data of both groups are shown in Table 1. The groups were comparable for age, sex and BMI.

The sleep characteristics are summarized in Table 2. Although sleep latency and REM latency were longer in the patient group, the results of the polysomnographic tests revealed no significant differences in the groups for total sleep time (TST), sleep efficiency, sleep latency, rapid eye movement (REM) latency, percentage of stage 1 non-REM sleep and REM sleep. There were significant differences in the percentage of stage 2 non-REM sleep and slow wave sleep (SWS, stages 3-4) between groups. In the patient group, the percentage of stage 2 non-REM sleep was higher and the SWS stage was lower than in the control group (P < 0.05). The patient group had a mean of 15.9 [+ or -] 7.5 arousal index and 22.8 [+ or -] 14.1 number of awakenings compared with 9.5 [+ or -] 3.1 and 10.4 [+ or -] 3.9, respectively, in the control group (P < 0.05, P < 0.01, respectively). Arousals were observed more frequently in non-REM sleep than in REM sleep (17.4 [+ or -] 7.9 versus 5.7 [+ or -] 6.9). To assess sleepiness, the Epworth questionnaire was applied and the results were statistically not different from the controls (4.9 [+ or -] 2.7 versus 3.0 [+ or -] 2.3, P > 0.05). Only two subjects in the patient group were found to be sleepy (Epworth scores were 11 and 13 respectively). The two patients having high Epworth scales also had a high arousal index, awakenings and scratching numbers (25, 15, 17 and 22, 17, 20, respectively).

Scratching episodes were observed in all stages of non-REM and REM sleep, but mainly in the non-REM period. Total numbers of scratching for stage 1, stage 2, SWS stage and REM stage were 30, 55, 44 and 13, respectively. Mean scratching index was found to be 1.9 [+ or -] 1.0 bouts per hour. Scratching range was from 6 to 20.

Discussion

The underlying pruritogenic stimuli in many LSC cases often remain undetermined. These patients may have a personal or family history of atopic diathesis. Some patients have another underlying dermatologic disorder such as contact dermatitis or frictional irritation, which may precipitate the disease. It is believed that a psychogenic factor may play an important contributory role in the development or perpetuation of lesions. (3,12) It is believed that the disease may occur as a direct response to stress, although this has not been confirmed. (12) However, the patients and controls that have enrolled in our study have not had any psychological disturbance.

Sleep is divided into non-REM and REM sleep. Non-REM sleep consists of 4 stages. Stages 1 and 2 are named as "light non-REM" and stages 3 and 4 as "deep non-REM" (slow wave sleep [SWS]) sleep. In deep non-REM sleep, a strong stimulus is necessary to awaken the patient. An adequate deep non-REM sleep is necessary for health. (10)

Aoki et al investigated the relationship between nocturnal scratching and sleep in severely itchy patients, and demonstrated that patients spent little time in deep non-REM sleep (stages 3 and 4). They found that scratching bouts occurred in all stages, but the frequency was higher in stage 1 non-REM sleep. (13) In our study, scratching bouts were observed both in non-REM and REM sleep. In particular, the average frequency of scratching episodes was greatest in stage 2, followed by stage 1 SWS, and REM sleep. In the patient group, the percentage of SWS (deep non-REM sleep) was lower, and light non-REM sleep (particularly stage 2) was higher than the controls. These results indicated that patients with LSC have a disturbed light and deep non-REM sleep patterns. Although sleep latency and REM latency were longer in the patient group, there were no significant differences between patients and controls. This may be due to the inadequate number of patients. Itching may prevent patients from falling asleep, or may induce REM sleep earlier.

Arousal is defined as brief awakening from sleep. (10) After an arousal, sleep structure changes from deep to light sleep or the patient may awaken and be unable to fall into REM sleep. The average arousal index and awakening number was also higher in the patient group compared with controls, and arousals were observed mainly in non-REM sleep. Increased arousal index and awakening numbers are nonspecific findings, as many factors or diseases may cause this. However, we were careful to differentiate and exclude other factors which may cause arousal and awakening, such as periodic limb movement and sleep apnea.

Nighttime pruritus that may change sleep structure and quality is an important symptom in some dermatitis syndromes. It is reported that scratching episodes are more common during light non-REM sleep than deep non-REM sleep. (14) Although studies have been done in children with atopic dermatitis, (5,15,16) we were unable to find an article regarding the sleep patterns of LSC patients in the literature. Monti et al (16) demonstrated that scratching episodes occurred mainly during light non-REM sleep (stages 1 and 2). Also they found an increased number of nocturnal awakenings and decreased total sleep time related to smaller amounts of non-REM sleep. They suggested that altered sleep continuity in atopic dermatitis is likely to be a consequence of nighttime pruritus. Parallel to our results, that study found that nighttime pruritus adversely affected both non-REM and REM sleep structure. However, another study found that sleep abnormalities in patients with atopic dermatitis are not associated with scratching. (5)

Patients who have inadequate deep non-REM sleep may complain of daytime sleepiness and impaired daytime cognitive functioning. (8,17) In our study, the Epworth sleepiness scale results in the patient group were not different from the control group. However, two of the patients had high Epworth sleepiness scale scores with high arousal, awakening and scratching scores. Sleepiness in these two patients may be caused not only by scratching, but also by an upper airway resistance syndrome. Unfortunately, we could not rule out the upper airway resistance syndrome as we could not measure intrathoracic pressure.

In conclusion, although the number of patients are small in this study, polysomnographic findings show that the sleep structure in patients with lichen simplex chronicus is adversely influenced by arousals and awakening which may be caused by nocturnal scratching episodes. We concluded that patients with LSC have sleep disturbance due to nighttime pruritus, but these findings need to be investigated by further studies.

References

1. Yosipovitch G, Sugeng MW, Chan YH, et al. The effect of topically applied aspirin on localized circumscribed neurodermatitis. J Am Acad Dermatol 2001;45:910-913.

2. Braun-Falco O, Plewing G, Wolff HH, et al. Erythemato-Papulo-Squamous Diseases. Dermatology. Berlin, Springer-Verlag, 2nd Ed, 2000, pp 571-647.

3. Novick NL. Unilateral, circumscribed, chronic dermatitis of the papillary-areolar complex: case report and review of the literature. Mt Sinai J Med 2001;68:321-325.

4. Weichert GE. An approach to the treatment of anogenital pruritus. Dermatol Ther 2004;17:129-133.

5. Reuveni H, Chapnick G, Tal A, et al. Sleep fragmentation in children with atopic dermatitis. Arch Pediatr Adolesc Med 1999;153:249-253.

6. Holden CA, Berth-Jones J. Eczema, Lichenification, Prurigo and Erythroderma. In: Rook's Textbook of Dermatology. Burns T, Breathnach S, Cox N, Griffiths C (eds). Turin, Blackwell Publishing, 7th Ed, 2005, pp 17.1-17.55.

7. Gupta MA, Gupta AK, Kirkby S, et al. Pruritus associated with nocturnal wakenings: organic or psychogenic? J Am Acad Dermatol 1989;21: 479-484.

8. Johns MW. A new method for measuring daytime sleepiness: the Ep-worth sleepiness scale. Sleep 1991;14:540-545.

9. Rechtschaffen A, Kales A. A manual of standardized terminology: techniques and scoring system for sleep stage of human subjects. Washington, DC, US Public Health Service, 1968.

10. Douglas NJ. Clinicans' Guide to Sleep Medicine. London, Oxford University Press, 2002.

11. EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep 1992;15:173-184.

12. Ferry AP, Kaltreider SA. Lichen simplex chronicus of the eyelid. Arch Ophthalmol 1999; 117:829-831.

13. Aoki T, Kushimoto H, Hishikawa Y, et al. Nocturnal scratching and its relationship to the disturbed sleep of itchy subjects. Clin Exp Dermatol 1991;16:268-272.

14. Savin JA, Paterson WD, Oswald I, et al. Further studies of scratching during sleep. Br J Dermatol 1975;93:297-302.

15. Bartlet LB, Westbroek R, White JE. Sleep patterns in children with atopic eczema. Acta Derm Venereol 1997;77:446-448.

16. Monti JM, Vignale R, Monti D. Sleep and nighttime pruritus in children with atopic dermatitis. Sleep 1989;12:309-314.

17. Johns MW. Daytime sleepiness, snoring, and obstructive sleep apnea: the Epworth Sleepiness Scale. Chest 1993;103:30-36.

Rafet Koca, MD, Remzi Altin, MD, Numan Konuk, MD, H. Cevdet Altinyazar, MD, and Levent Kart, MD

From the Departments of Dermatology, Pulmonology, and Psychiatry, Zonguldak Karaelmas University Faculty of Medicine, Zonguldak, Turkey.

Reprint requests to Dr. Rafet Koca, Zonguldak Karaelmas Universitesi, Tip Fakultesi, Dermatoloji Anabilim Dali, Kozlu 67600, Zonguldak, Turkey. Email: [e-mail]

Accepted January 23, 2006.

RELATED ARTICLE: Key Points

* Repeated rubbing and scratching episodes are characteristic features of lichen simplex chronicus (LSC).

* It is important to determine whether scratching bouts during sleep in patients with LSC cause an abnormal sleep pattern.

Table 1. Demographic data of both groups

                              Patients (n=15) (a)  Controls (n=15)

Age (mean years [+ or -] SD)  46.1 [+ or -] 9.0    45.9 [+ or -] 9.6
Gender (n, %)
  Male                        11 (72.3)            10 (66.7)
  Female                       4 (26.7)             5 (33.3)
BMI                           27.7 [+ or -] 4.2    27.4 [+ or -] 2.6

(a) Two patients were excluded from the study.
BMI, body mass index.

Table 2. Sleep characteristics (a)

                     Patients (n=15)      Controls (n=15)      P value

TST, min             342.2 [+ or -] 71.4  362.3 [+ or -] 46.2  >0.05
Sleep efficiency, %   83.8 [+ or -] 12.7   90.1 [+ or -] 5.2   >0.05
Sleep latency, min    16.6 [+ or -] 11.2   11.8 [+ or -] 4.2   >0.05
REM latency, min     130.6 [+ or -] 89.2  109.4 [+ or -] 71.9  >0.05
AR, no                15.9 [+ or -] 7.5     6.5 [+ or -] 3.1   <0.05 (b)
AR REM                 5.7 [+ or -] 6.9     5.0 [+ or -] 3.0   >0.05
AR non-REM            17.4 [+ or -] 7.9     8.2 [+ or -] 3.2   <0.05 (b)
Awakening, no         22.8 [+ or -] 14.1    7.4 [+ or -] 3.9   <0.05 (b)
Stage 1, %             3.0 [+ or -] 1.9     2.0 [+ or -] 1.2   >0.05
Stage 2, %            61.9 [+ or -] 8.5    52.7 [+ or -] 7.7   <0.05 (b)
SWS, %                17.8 [+ or -] 6.9    25.3 [+ or -] 6.9   <0.05 (b)
REM, %                17.9 [+ or -] 7.9    20.3 [+ or -] 3.6   >0.05
Epworth scores         4.9 [+ or -] 2.7     3.0 [+ or -] 2.3   >0.05

(a) Data are presented as mean [+ or -] SD.
(b) Statistically significant.
TST, total sleep time, REM, rapid eye movement. AR. arousal, SWS.
slow-wave sleep.