Original Research, Human Studies, Itch, Psychology

Three patient-reported outcome (PRO) questionnaires-Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)-were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation.

Sleep, which is crucial for restoring of physiological functions and health, is reportedly impaired in psoriasis. The role of different potential sleep confounding factors, including detailed pruritus characteristics, and the complex interplay between psychological variables (anxiety and depression), pruritus and sleep disturbance in psoriasis remain insufficiently investigated.

Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD).

Evidence from pain research shows that the effectiveness of active pharmacological treatments can be enhanced by placebo effects. The "open drug administration" is superior to hidden drug administration. In a RCT we aimed to show that the targeted use of placebo effects increases the efficacy of an antihistamine (dimetindene) infusion in participants with atopic dermatitis. We openly infused dimetindene (drug) in full sight with information (intervention group 1: OPEN-DRUG+INST), openly infused drug with an additional classical conditioning learning experience (intervention group 2: OPEN-DRUG+INST+COND) or infused drug without any information or sight, i.e., hidden administration (control group 1: HIDDEN-DRUG). Control group 2 received a placebo infusion (saline) declared as dimetindene and also experienced the conditioning experience (PLAC+INST+COND). Itch was experimentally induced with histamine via a skin prick test. Outcome was assessed at the subjective (primary endpoint: experimental itch intensity, numeric rating scale), and objective level (secondary endpoint: wheal size, mm ). Experimental-induced itch intensity decreased in all groups but at different rates (p<0.001). The groups with the open administration, whether it was dimetindene or placebo, had significantly stronger reductions in itch compared to the HIDDEN-DRUG group (OPEN-DRUG+INST+COND: p<0.001; OPEN-DRUG+INST: p=0.009; PLAC+INST+COND: p<0.001). Additional drug conditioning mediated via expectation led to a stronger reduction of itching (p=0.001). Results on wheal size were similar (p=0.048), however, no significant difference between the HIDDEN-DRUG group and the PLAC+INST+COND group (p=0.967) was found. We conclude that specifically generated targeted placebo effects can significantly increase the action of a drug (dimetindene) and should be used in clinical practice.

Patients with atopic dermatitis experience increased nocturnal pruritus which leads to scratching and sleep disturbances that significantly contribute to poor quality of life. Objective measurements of nighttime scratching and sleep quantity can help assess the efficacy of an intervention. Wearable sensors can provide novel, objective measures of nighttime scratching and sleep; however, many current approaches were not designed for passive, unsupervised monitoring during daily life. In this work, we present the development and analytical validation of a method that sequentially processes epochs of sample-level accelerometer data from a wrist-worn device to provide continuous digital measures of nighttime scratching and sleep quantity. This approach uses heuristic and machine learning algorithms in a hierarchical paradigm by first determining when the patient intends to sleep, then detecting sleep-wake states along with scratching episodes, and lastly deriving objective measures of both sleep and scratch. Leveraging reference data collected in a sleep laboratory (NCT ID: NCT03490877), results show that sensor-derived measures of total sleep opportunity (TSO; time when patient intends to sleep) and total sleep time (TST) correlate well with reference polysomnography data (TSO: r = 0.72, p < 0.001; TST: r = 0.76, p < 0.001; N = 32). Log transformed sensor derived measures of total scratching duration achieve strong agreement with reference annotated video recordings (r = 0.82, p < 0.001; N = 25). These results support the use of wearable sensors for objective, continuous measurement of nighttime scratching and sleep during daily life.

Itch draws our attention to allow imposing action against bodily harm (e.g., remove insects). At the same time, itch is found to interfere with ongoing tasks and daily life goals. Despite the key role of attention in itch processing, interventions that train individuals to automatically disengage attention from itch cues are lacking. The present proof-of-principle attention bias modification (ABM) training study was aimed at investigating whether attention to itch as well as sensitivity to mild itch can be changed. Healthy volunteers were randomized over three ABM-training conditions. Training was done via a modified pictorial dot-probe task. In particular, participants were trained to look away from itch stimuli ( = 38), toward itch stimuli ( = 40) or not trained toward or away from itch at all (sham training, = 38). The effects of the ABM-training were tested primarily on attention to itch pictures. Secondarily, it was investigated whether training effects generalized to alterations in attention to itch words and mechanical itch sensitivity. The ABM-training did not alter attention toward the itch pictures, and there was no moderation by baseline levels of attention bias for itch. Also, attention bias to the itch words and itch sensitivity were not affected by the ABM-training. This study was a first step toward trainings to change attention toward itch. Further research is warranted to optimize ABM-training methodology, for example increasing motivation of participants. Eventually, an optimized training could be used in patient populations who suffer most from distraction by their symptoms of itch. Identifier: NL6134 (NTR6273). The website URL is: https://www.trialregister.nl/.

To investigate learning processes underlying nocebo effects on itch, this study measured the efficacy of classical conditioning and observational learning for inducing nocebo effects on cowhage-evoked itch and scratching behaviour. A total of 58 healthy female participants were assigned to classical conditioning, observational learning, or sham conditioning groups. In the classical conditioning group, experimenters associated the application of an inert gel with increased itch intensity first-hand. In the observational learning group, a video of the conditioning paradigm was shown. Nocebo effects were measured as the difference in itch or scratching between control and nocebo test phase trials, compared between learning and control groups. Compared with sham conditioning, classical conditioning induced a significant nocebo effect on itch, while observational learning did not. No nocebo effect on scratching was detected. These results highlight the role that learning through direct experiences plays in pruritic symptoms. Future research should investigate how a patient's history of unsuccessful treatments shapes treatment outcomes.

Psoriasis (PS) is a chronic inflammatory skin disease accompanied by reduced quality of life. Mindfulness is the ability to focus on the present moment without evaluation. Findings on the effects of 8-week mindfulness trainings in patients with PS reveal positive effects on the severity of the disease and quality of life. However, it remained unclear what distinguishes patients with PS interested in psychological interventions from those without interest and whether also a shorter, namely 2-week mindfulness-based intervention is beneficial in this patient group. This will be investigated with this study.