Center for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Münster, Germany
Impaired sleep due to nocturnal pruritus is a common symptom in patients with chronic pruritus. How-ever, there is no standardized, simplified instrument for assessing sleep-related problems in patients with chronic pruritus. After a literature search, we conducted 50 interviews with patients with chronic pruritus and tested 12 items most frequently used in routine sleep questionnaires. Afterwards, 2 sleep assessment questionnaires (Pittsburgh Sleep Quality Index; Regensburg Insomnia Scale) were selected for use in 88 patients with chronic pruritus with sleep impairment due to pruritus. They were completed twice; once before optimizing their individual pruritus therapy and once again after 4 weeks. During the latter survey, 21 patients reported that pruritus no longer negatively affected their sleep. These patients also achieved a significant improvement in their sleeping behaviour in the Regensburg Insomnia Scale. Therefore, the Regensburg Insomnia Scale appears to be well-suited to assessing sleep impairment in patients with chronic pruritus.
Key words: itch; nocturnal pruritus; sleep assessment; prurigo; clinical trial.
Accepted Apr 24, 2018; Epub ahead of print Apr 24, 2018
Acta Derm Venereol 2018; XX: XX–XX.
Corr: Sonja Ständer, Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von-Esmarch-Str. 58, DE-48149 Münster, Germany. E-mail: email@example.com
Chronic pruritus (CP) is a common symptom in the general population. In some patients the itching occurs predominantly at night. Accordingly, sleep patterns can be partly negatively affected. In this study, pruritus-related sleep impairments (especially waking up in the middle of the night or too early in the morning because of pruritus) were identified. In addition, we found that one already existing, validated sleep assessment questionnaire, the Regensburg Insomnia Scale, captures the specific sleep restrictions of patients with CP and detect any positive therapy effects on patients’ sleep.
Chronic pruritus (CP), defined as pruritus persisting for more than 6 weeks (1), is a frequent subjective symptom in the general population, with an estimated lifetime prevalence between 22% and 25.5% (2, 3). Efforts are currently underway to standardize and validate instruments used to measure CP, especially due to its subjective nature (4). The documentation of the intensity of the pruritus and its influence on numerous aspects of quality of life (QoL) serve as the basis for an assessment of the efficacy of a treatment. One important aspect is the determination of sleep patterns, since CP often results in sleep disturbances. Up to 90% of patients with CP report impaired sleep due to nocturnal pruritus (5). Because sleep disturbances are only marginally addressed in current, standardized instruments for the QoL, assessments of sleep quality in patients with CP have thus far remained insufficient (6). A more detailed description of specific sleep-related problems could be useful for optimizing and adapting a therapy. The International Forum for the Study of Itch (IFSI) provides a general recommendation regarding which specific sleep instruments might be suitable (4). Several validated sleep assessment questionnaires described in the literature assess sleep impairment in a detailed manner; however, none of these instruments has been validated for use in patients with CP.
The aims of this study are to determine whether validated sleep questionnaires are able to detect specific sleep restrictions in patients with CP, and to attempt to define which questionnaire is most suitable to fulfil this task.
This study was conducted at the Center for Chronic Pruritus in the Department of Dermatology at the University Hospital Münster from November 2014 to December 2016.
To obtain an overview of current validated sleep questionnaires, literary research (step 1) was performed using databases such as PubMed (US National Institute of Health’s National Library of Medicine) on 19 December 2014.
For the next step, the informed consent of 50 patients (age ≥18 years) was obtained prior to conducting interviews regarding their sleep behaviour (step 2) and testing of 12 items most commonly used in routine sleep questionnaires (step 3). In this collective, all patients with CP were admitted, regardless of the existence of impaired sleep due to nocturnal pruritus, with the aim of gaining an overview of the prevalence of sleep impairment in patients with CP and to obtain a first impression of which sleep areas might be affected the most in this collective. Firstly, patients were prompted to describe, in their own words, their sleep patterns in the last 4 weeks, including any sleep problems. Post-interview, each patient was asked to complete an additional questionnaire comprised of the 12 items most frequently asked in examined sleep questionnaires, in order to increase the comparability of patients’ statements.
In the 4th step, 2 of the investigated sleep questionnaires, containing the most relevant sleep items to patients with CP, were selected for testing in another collective (step 4).This selection was based on the results of the testing of the 12 most frequently asked items in routine sleep questionnaires (step 3).
A total of 88 patients (inclusion criteria: age ≥ 18 years with CP and thereby caused sleep disorders due to nocturnal pruritus) were included in this part of the study, for which their informed consent was obtained. The participating patients were asked to complete the 2 selected questionnaires twice, once during their visit (for the first time as well as repeatedly) at the Center for Chronic Pruritus and once more after 3–5 weeks (step 5). The aim was to prove whether one of the questionnaires is able to detect the specific sleep restrictions in patients with CP and associated sleep impairment. Moreover, we tried to verify whether one of them is able to determine any possible effects of changing or optimizing the individual anti-pruritic therapy on patients’ sleep behaviour after 3–5 weeks. The intensity of pruritus was also assessed at both points in time via the visual analogue scale (VAS, 0–10) and numerical rating scale (NRS, 0–10) (7). Clinical and sociodemographic data were also collected during their visits to the Center for Chronic Pruritus. In addition, the patients were asked about possible diseases or health-related conditions that might have a negative impact on the quality of their sleep. They were asked to complete the Hospital Anxiety and Depression Scale (HADS) (8, 9), Dermatology Life Quality Index (DLQI) (10) and ItchyQol (6) during the first session of data collection. The type of medical treatment was not analysed further, since each patient received a standard topical or routine systemic therapy in accordance with the guidelines, but still experienced pruritus (11).
Statistical analysis was performed with software IBM SPSS Statistics for Windows Release 23 (2015; Chicago, IL, USA). The results were presented using descriptive statistics. The level of significance was found at p < 0.05 and to be 2-sided. The differences between the non-normally distributed parameters were analysed between 2 independent groups using the Mann–Whitney U test. By means of a Wilcoxon test, the differences between the non-normalized parameters were able to be analysed between 2 dependent groups. The χ2 test and the Fisher’s exact test were used to compare the distribution of the categorical parameter between 2 independent groups.
The study was approved by the local ethics committee (2015-430-f-S) and registered in the DRKS (German Clinical Trials Register, DRKS-ID: DRKS00009767).
A brief description and comparison of the validated questionnaires selected for examination, with regard to year of publication and number of items, are illustrated in Table I (step 1).
Table I. Validated sleep questionnaires
A total of 50 patients with CP, irrespective of the presence of pruritus-caused sleep disturbances, were enrolled in this part of this study, including 25 women (mean ± standard deviation [SD] age 60 ± 14 years, range 36–83) and 25 men (mean age 57 ± 22 years, range 21–86). Asked about sleep-impacting comorbidities, 45 (90%) patients reported having no knowledge of having any pre-existing sleep disorder unrelated to their pruritus. Four patients (2 men, 2 women) described sleep apnoea to be the cause of their sleep disturbances and one patient reported having nightmares unrelated to pruritus. The results of the interviews (step 2) are presented in Table II.
Table II. Results of the interviews (n= 50 with chronic pruritus)
Testing the items most frequently used in the examined questionnaire (step 3) revealed the following results. In general, the 12 tested items were divided into 2 subgroups, 8 of which deal with qualitative aspects of sleep and the remaining 4 items concern quantitative statements.
The results of the qualitative items are described in Fig. 1. “Waking up in the middle of the night or too early in the morning” constitutes the single most relevant item of the questionnaire (74% of patients reported a strong or very strong burden). Thus, the detection of periods of awakening is a relevant component in the assessment of sleep behaviour in patients with CP due to its high prevalence in the examined collective, followed by “impaired sleep quality/sleepless nights” (46%) and “daytime sleepiness” (42%). The remaining 5 items “impaired quality of life” (36%), “impaired daytime” (22%), “thoughts of sleep” (14%), “use of sedatives” (10%) and “fear of insomnia” (8%) were less frequently mentioned and therefore less relevant to the assessment of sleep patterns in patients with CP. The last 4 items were utilized to assess the quantity of sleep and its impairment in order to provide an overview of their sleep behaviour. These could therefore be classified as being detrimental to the evaluation of patients’ sleep. It was found that the mean ± SD time of retirement to bed was 22.56 ± 1 h 18 min, while the mean ± SD time to get up was 07.04 h ± 1 h 2 min. Most patients required 38 ± 39 min to fall asleep, while 6 h and 10 min ± 1 h 42 min was the mean duration of sleep.
Fig. 1. Result of analysis of qualitative items of sleep questionnaires: relevance to patients with chronic pruritus (n = 50). *In the middle of the night or too early in the morning.
The selection of the questionnaires (step 4) was based on the results of the testing of the most frequently asked items in routine sleep questionnaires (step 3). The Pittsburgh Sleep Quality Index (PSQI) (12, 13) and the Regensburg Insomnia Scale (RIS) (14) (Table SI) were then selected based on the importance of 7 and 6 of their items, respectively (Table SII). The Athens Insomnia Scale (15), a measuring tool recommended by the IFSI, also contains several important items (5 important items); however, there is currently no validated German language version available. Consequently, this questionnaire was not implemented into this study.
For the 5th step, 88 patients with CP and sleep disorders due to nocturnal pruritus completed the questionnaires on day 1 and after 4 weeks (3.94 weeks ± 0.7). Of these patients, 21 (23.86%) reported after 4 weeks (day 28) that pruritus no longer negatively influenced their sleep. The latter group was classified as “sleepers”, whereas 67 (76.14%) patients were found to have persistent nocturnal pruritus following the second assessment. This group was thus classified as “non-sleepers” (Tables III and IV). All patients were asked about comorbidities that might influence their sleep, in addition to pruritus (Table SIII). No significant differences between sleepers and non-sleepers were observed on day 1 (p = 0.874; χ2 test) and day 28 (p = 0.671; χ2 test). Furthermore, when comparing days 1 and 28, there was no noticeably significant difference between the groups due to comorbidities with a negative influence on sleep (Wilcoxon test, sleepers: p = 1.0, non-sleepers: p = 0.317).
Table III. Description of the collective which completed the two selected questionnaires (n=88 with chronic pruritus (CP))
Table IV. Comparison of sleepers (n = 21) and non-sleepers (n = 67) according to pruritus intensity
As shown in Table V, sleepers were found to achieve values on the total scale on day 1 in the pathological range (> 12) and values on day 28 that can be considered normal (≤ 12). In particular, the use of the items “early awakening”, “easy awakening” and “sleepless nights” point to a significant reduction in sleep impairment in sleepers between days 1 and 28. Non-sleepers obtained higher values for each item, as well as for the total scale days 1 and 28, with no significant differences between the 2 measuring points. There were no significant differences between days 1 and 28 in the group of sleepers and non-sleepers regarding their bedtime and the time to get out of bed (Table SIV).
Table V. Results of items from the Regensburg Insomnia Scale used by patients with chronic pruritus (n = 88)
According to the overall index sleepers and non-sleepers both improved between days 1 and 28, without a significant distinction between the 2 groups. They both stayed in the pathological range (overall index higher than 5 points). In detail, sleepers experienced a significant improvement in their sleeping behaviour within the 4 weeks with regard to the components “sleep latency” and “sleep disorders”, as well as to the items “sleep latency more than 30 min”, “impaired sleep maintenance”, “heat” and “pain”. In contrast, non-sleepers achieved significant differences in the components “impaired sleep quality” and “sleep duration” and in the item “impaired sleep quality”. Nevertheless, non-sleepers achieved higher values on days 1 and 28 for nearly each item, component and the overall index than the sleepers group (with 1 exception, “nightmares”) (Table VI). The results of the items regarding patients’ bedtime are shown in Table SV (“time to go to bed”, “time to fall asleep”, “time to get up”, “sleep duration”).
Table VI. Results of the Pittsburgh Sleep Quality Index (items, components, index) used by patients with chronic pruritus (n = 88)
Patients with CP frequently have nocturnal pruritus and associated sleep disturbances (5, 16). There is no validated sleep questionnaire specifically designed for these patients. The current study demonstrates that some of the already existing validated sleep questionnaires, available in multiple languages, are appropriate for use in patients with CP.
In the open interviews, we gained an overview of the high degree of impaired sleeping behaviour in patients with CP due to scratching in the night (72%) and nocturnal awakening caused by pruritus (44%).
Based on comparison of the existing sleep questionnaires, we were able to identify the 12 most often asked items, which include 4 quantitative (hours of night sleep) and 8 qualitative (e.g. “waking up in the middle of the night or too early in the morning”) aspects. Using these 12 items in patients with CP, we were able to demonstrate that several of them are relevant to this population. The most important aspects of an impaired sleep concern periods of waking up in the night or too early in the morning, reduced sleep quality or the experience of sleepless nights as well as daytime sleepiness.
An evaluation of the quantitative parameters is also essential. The mean ± SD sleep duration per night was 6 h 10 min ± 1 h 42 min, whereas the recommended (e.g. by the National Sleep Foundation) sleep duration for young adults/adults is 7–9 h and for elderly people 7–8 h (17).
In sum, patients with CP experience sleep interruption and disturbances during the night, resulting in reduced sleep quality and shortened sleeping time. The RIS and the PSQI were found to contain most of the relevant items and were therefore selected for testing.
Testing the RIS yielded the most interesting results. Patients classified as sleepers (no sleep-related disturbances due to pruritus at the second visit) achieved a significant reduction in their total RIS value, which was in the normal range by re-assessment after 4 weeks (total value ≤ 12) (14), whereas non-sleepers remained in the pathological range. The results of the PSQI are more ambiguous than the results of the RIS. Based on this data, we can conclude that the RIS is a useful instrument for assessing nocturnal pruritus in patients with CP.
In this study, a comparison of the general comorbidities with a negative influence on patients’ sleep between both groups did not exhibit relevant differences. Previous studies have established a significant connection between sleep quality and psychiatric diseases, such as anxiety and depression (18, 19). Our data support this as non-sleepers have significant higher values for anxiety, depression and an impaired QoL. These factors might prevent improvements in quality of sleep and a positive response to a treatment and should be considered in the evaluation of the results. Anxiety and depression are also known to increase the intensity of pruritus (20). Interestingly, a significant difference in the pruritus intensity between sleepers and non-sleepers was not observed on day 1, whereas on day 28 a significant difference in pruritus intensity could be detected between these groups. Therefore, it could be assumed that an effective pruritus therapy with a significant reduction in pruritus intensity is the basis for sleep improvement in patients with CP. However, as shown in Table IV, the non-sleepers also achieved a significant reduction in VAS average in the last 24 h and in VAS worst in the last 24 h between both measuring points. This overall reduction in intensity is too slight to show a clinical improvement in sleep. However, future studies should determine the influence and cut-off of the pruritus intensity leading to sleep disturbances.
Despite confirming the usability of sleep questionnaires for patients with CP, various issues associated with nocturnal pruritus, such as the influence of warmth in bed as mentioned in the interviews, are not assessed by current sleep questionnaires, which instead focus on the general aspects of sleep. The use of sleep questionnaires for patients with CP, such as the RIS, is unable to capture all dimensions of a disturbed sleep, but it is a feasible approach to assess many sleep problems in this population. Unless larger analyses focus on specific sleep-related problems due to pruritus, the development of a sleep questionnaire specific to CP is not pragmatic.
Although nocturnal pruritus is well-known in the context of limiting the QoL of patients with CP, its underlying pathophysiological mechanisms require more investigation in order to produce an effective therapy (16, 21, 22), which, without a more detailed measurement and evaluation is unfeasible. In this regard, a more comprehensive insight into the obstacles faced by patients with CP with nocturnal pruritus may be useful for further investigation into its pathophysiological mechanism and corresponding therapies.
The authors have no conflicts of interest to declare.