G. Yosipovitch, E. Simpson, A. Bushmakin, J. Cappelleri, T. Luger, S. Ständer, W. Tom, K. Benjamin, W. Ports, A. Tallman, H. Tan, R. Gerber
{"title":"Assessment of pruritus in atopic dermatitis: validation of the Severity of Pruritus Scale (SPS)","authors":"G. Yosipovitch, E. Simpson, A. Bushmakin, J. Cappelleri, T. Luger, S. Ständer, W. Tom, K. Benjamin, W. Ports, A. Tallman, H. Tan, R. Gerber","doi":"10.1097/itx.0000000000000013","DOIUrl":"https://doi.org/10.1097/itx.0000000000000013","url":null,"abstract":"Introduction: Pruritus, or itch, is a central feature of atopic dermatitis (AD) and is often cited as the most bothersome symptom. The Severity of Pruritus Scale (SPS) is a 4-point rating scale adapted from the Atopic Dermatitis Severity Index to provide a measure of pruritus severity within a 24-hour recall period. The objective of this analysis was to assess the qualitative and quantitative validity of the SPS in AD. Methods: Content validity of the SPS was evaluated qualitatively in US patients with AD. Psychometric properties of the SPS were evaluated using data from 2 phase 3 trials conducted to investigate crisaborole in mild to moderate AD (study AD-301: NCT02118766; study AD-302: NCT02118792). Results: Fourteen patients were included in the qualitative analysis, considered adequate because of the single-item, single-concept nature of the SPS. Itch was the most prevalent symptom, and the SPS was easily understood and completed in US English (n=9) and US Spanish (n=5). The psychometric analysis used data from 1344 patients. Test-retest reliability analysis identified an intraclass correlation coefficient of 0.54 for a single SPS observation, and at least 0.70 when at least 2 SPS observations were averaged. SPS scores correlated with Investigator’s Static Global Assessment (ISGA) scores, measures of quality of life, and 4 of 5 signs of AD (Pearson correlations, ≥0.40 at day 29). The difference in score between the no disease group/clear (ISGA 0) and the severe disease group (ISGA 4) was 0.80. The clinically important difference was estimated to be 0.20 and the clinically important response was estimated to be at least a 0.19-point reduction from baseline. Discussion: The SPS is an appropriate tool to assess itch in patients with AD and is a valid and reliable measure of pruritus severity.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"3 1","pages":"e13"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/itx.0000000000000013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42266332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Yosipovitch, E. Simpson, H. Tan, R. Gerber, T. Luger, S. Ständer, W. Tom, J. Cappelleri, A. Bushmakin, W. Ports, A. Tallman
{"title":"Effect of crisaborole topical ointment, 2%, on atopic dermatitis–associated pruritus: an extended analysis of 2 phase 3 clinical trials","authors":"G. Yosipovitch, E. Simpson, H. Tan, R. Gerber, T. Luger, S. Ständer, W. Tom, J. Cappelleri, A. Bushmakin, W. Ports, A. Tallman","doi":"10.1097/itx.0000000000000012","DOIUrl":"https://doi.org/10.1097/itx.0000000000000012","url":null,"abstract":"Introduction: Pruritus is an essential feature of atopic dermatitis (AD) and is widely considered the most distressing symptom. Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate AD. The efficacy of crisaborole for AD-associated pruritus was assessed in 2 phase 3 trials using the Severity of Pruritus Scale (SPS). Post hoc validation of the SPS identified that 1 SPS observation provided inadequate test-retest reliability. Therefore, extended analyses were conducted using at least 2 SPS observations for robust assessment of pruritus in the phase 3 crisaborole trials. Methods: Data were analyzed from 2 identically designed, vehicle-controlled, double-blind, phase 3 trials designed to investigate the efficacy and safety of crisaborole in AD patients aged 2 years and above (AD-301: NCT02118766; AD-302: NCT02118792). At least 2 SPS observations were averaged for acceptable test-retest reliability. Results: At least 2 baseline observations were available for 569 patients in AD-301 and 561 patients in AD-302. Median time to pruritus improvement (SPS score ⩽1 with at least 1-point improvement from baseline) was shorter with crisaborole than with vehicle (AD-301: 5.0 vs. 10.0 d, P=0.0003; AD-302: 6.0 vs. 9.0 d, P=0.0087). At week 4, more crisaborole-treated patients than vehicle-treated patients experienced pruritus improvement (AD-301: 37% vs. 21%, P<0.0001; AD-302: 34% vs. 21%, P=0.0006), mean pruritus scores were lower with crisaborole than with vehicle (AD-301: 0.97 vs. 1.28, P<0.0001; AD-302: 1.08 vs. 1.35, P<0.0001), and more crisaborole-treated patients than vehicle-treated patients experienced a clinically important pruritus response (AD-301: 75% vs. 57%, P<0.0001; AD-302: 72% vs. 64%, P=0.0828). Conclusions: These extended analyses show that patients treated with crisaborole experienced rapid and clinically relevant improvement in AD-associated pruritus.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"226 24","pages":"e12"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/itx.0000000000000012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41258805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the symptom of itch ambulatory office-based care in the United States","authors":"A. Fleischer","doi":"10.1097/itx.0000000000000015","DOIUrl":"https://doi.org/10.1097/itx.0000000000000015","url":null,"abstract":"Introduction: This study was designed to assess the characteristics of visits for itch from a cross-sectional study of office-based ambulatory care in the United States. Methods: To characterize itch as a symptom, ambulatory visits from the 1993 to 2015 National Ambulatory Medical Care Survey were analyzed when they included “itching” as a symptom or itch as a diagnosis code (ICD-9-CM 692.X). Results: This study finds 129 million itch visits occurred, averaging 5.6 million visits per year. There is seasonality to itch visits, with the largest numbers occurring in summer and fewest in winter. Vulvovaginal conditions including candidiasis and vaginitis and vulvovaginitis are commonly associated with itching, yet under-represented in the dermatology literature. Discussion: These data provide insights for further investigation into the burden of itch-related diseases.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"3 1","pages":"e15"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/itx.0000000000000015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43556773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"9th World Congress on Itch report","authors":"K. M. Sanders, L. Nattkemper","doi":"10.1097/ITX.0000000000000014","DOIUrl":"https://doi.org/10.1097/ITX.0000000000000014","url":null,"abstract":"","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/ITX.0000000000000014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44483384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mrgprs activation is required for chronic itch conditions in mice.","authors":"Yuyan Zhu, Claire E Hanson, Qin Liu, Liang Han","doi":"10.1097/itx.0000000000000009","DOIUrl":"https://doi.org/10.1097/itx.0000000000000009","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic itch has been drawing much attention due to its clinical significance and the complexity of its mechanisms. To facilitate the development of anti-itch strategies, it is necessary to investigate the key players in itch sensation under chronic itch conditions. Several members of the Mrgpr family were identified as itch receptors that detect cutaneous pruritogens in primary sensory neurons. However, the role of Mrgprs in chronic itch conditions has not been well described.</p><p><strong>Methods: </strong>Scratching behaviors of WT and <i>Mrgpr-clusterΔ<sup>-/-</sup></i> mice were examined in dry skin model and contact dermatitis model to examine the role of <i>Mrgpr</i> genes in mediating chronic itch sensation. Scratching behaviors of the mice were also examined in allergic itch model. Real-time PCR were performed to examine the expression level of MrgprA3 and MrgprC11 under naïve and dry skin conditions. The MrgprA3<sup>+</sup> itch-sensing fibers were labeled by tdTomato fluorescence in <i>Mrgpra3<sup>GFP-Cre</sup>; ROSA26<sup>tdTomato</sup></i> mice, and the morphology and density of those fibers in the epidermis were analyzed under dry skin condition.</p><p><strong>Results: </strong>We showed that deleting a cluster of <i>Mrgpr</i> genes in mice reduced scratching behavior severely under two chronic itch conditions, namely dry skin and contact dermatitis, and the allergic itch condition. Moreover, the gene expressions of itch receptors MrgprA3 and MrgprC11 in dorsal root ganglia (DRG) were upregulated significantly under dry skin condition. Consistently, the percentage of MrgprA3<sup>+</sup> itch-sensing neurons was increased as well. We also observed hyperinnervation of MrgprA3<sup>+</sup> itch-sensing fibers in the epidermis of the skin under dry skin condition.</p><p><strong>Discussion: </strong>We demonstrate that Mrgprs play important roles in mediating chronic itch and allergic itch. These findings enrich our knowledge of itch mechanism and may lead to the development of novel therapeutic approach to combat itch.</p>","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/itx.0000000000000009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35945858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. H. Andersen, L. Arendt-Nielsen, G. Yosipovitch, J. Elberling
{"title":"A prospective case of postherpetic itch monitored by quantitative sensory testing for 1 year while undergoing 8% topical capsaicin treatments","authors":"H. H. Andersen, L. Arendt-Nielsen, G. Yosipovitch, J. Elberling","doi":"10.1097/itx.0000000000000008","DOIUrl":"https://doi.org/10.1097/itx.0000000000000008","url":null,"abstract":"Following reactivation of a latent ganglionic varicella zoster virus and skin eruption in the corresponding dermatome(s) ∼20% of patients develop chronic postherpetic neuralgia. A subset of these patients develop severe and often intractable chronic postherpetic itch in the affected area. However, this is rarely studied and little is known about its epidemiology, pathogenesis, and management. In this case study we followed a patient with moderate to severe chronic postherpetic itch characterized by pure itch sensation, using standardized quantitative sensory testing and observed a profound loss-of-function for C-fibers, A&dgr;-fibers, and A&bgr;-fibers within the affected area. The testing was conducted before, during, and after 8% topical capsaicin treatments applied in 4 cycles (3 months apart) over the course of ∼1 year. During this period the hypoesthesia gradually normalized, but heat hypoalgesia remained unchanged. The 8% topical capsaicin had a good and long lasting antipruritic effect eventually resulting in complete resolution of the itch in parallel with partial recovery of initial hypoesthesia, particularly for warmth and cold detection, likely unrelated to the treatments.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"2 1","pages":"e8"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/itx.0000000000000008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44237469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Lloyd, R. Dodd, C. Higgins, M. Burke, F. McGlone
{"title":"Are sex and history of pruritic skin conditions factors which affect the phenomenon of visually evoked itch? An exploratory study","authors":"D. Lloyd, R. Dodd, C. Higgins, M. Burke, F. McGlone","doi":"10.1097/itx.0000000000000010","DOIUrl":"https://doi.org/10.1097/itx.0000000000000010","url":null,"abstract":"Introduction: We have previously shown that sensations of itch and the scratch response can be evoked using itch-related images. However, we did not determine whether individual differences in a person’s experience of itch could moderate this effect. This exploratory study aimed to determine whether sex or a history of pruritic skin conditions (PSCs) could influence the effects of visually evoked itch and scratch. Methods: Forty-one participants (19 males; 16 with a history of PSCs) viewed static images that could either be itch or nonitch related. These were further separated by picture type: “skin contact” (ants crawling on the hand vs. a butterfly on the finger); “skin response” (scratching an insect bite vs. washing the hands); “skin condition” (psoriasis vs. freckles) or “context only” (insects vs. birds). Images were rated using a 10-point scale by answering: “How itchy do you feel?” (Self-rating) and “How itchy do you think the person in the picture feels?” (Other-rating). Frequency and location of scratching was also recorded. Results: The highest itch scores were to itch-related skin contact pictures. Females gave higher itch ratings than males, and people with a history of PSCs gave higher itch ratings when viewing images of people scratching. There was no correlation between itch ratings and scratch response, and no relationship between body site viewed and location of scratching. Discussion: There is a heightened response to itch-related cues in females and those with PSCs, indicating a more centrally mediated pathway bringing subconscious itch sensations into conscious awareness in these populations. These findings could influence personalized treatment interventions aimed at reducing awareness of itch sensations in susceptible individuals.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"2 1","pages":"e10"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45326324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Itch (Philadelphia, Pa.)Pub Date : 2017-09-01Epub Date: 2017-10-02DOI: 10.1097/itx.0000000000000007
Hideki Mochizuki, Alina Shevchenko, Leigh A Nattkemper, Rodrigo Valdes-Rodriguez, Gil Yosipovitch
{"title":"Suppression of scratching-induced pleasurable sensation by compression nerve blocking and its association with itch relief.","authors":"Hideki Mochizuki, Alina Shevchenko, Leigh A Nattkemper, Rodrigo Valdes-Rodriguez, Gil Yosipovitch","doi":"10.1097/itx.0000000000000007","DOIUrl":"https://doi.org/10.1097/itx.0000000000000007","url":null,"abstract":"<p><p>Itch can be suppressed by scratching. At the same time, scratching evokes a pleasurable sensation. In the present study, we investigated the peripheral mechanism of scratching-induced pleasurability and its association with itch relief using compression nerve block. We found that myelinated nerve fibers (Aβ-fibers and possibly Aδ-fibers), are involved in transmission of scratching-induced pleasurability. We observed that itch relief effect was the same regardless of whether the pleasurable sensation was evoked by scratching an itch, indicating that pleasure is not a necessary component to induce itch relief. This is the first study to investigate the peripheral mechanism of scratching-induced pleasurability and itch relief.</p>","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"2 2","pages":"e7"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/itx.0000000000000007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37018875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Itch (Philadelphia, Pa.)Pub Date : 2017-09-01Epub Date: 2017-10-02DOI: 10.1097/itx.0000000000000006
Manuel P Pereira, Sabine Steinke, Philipp Bruland, Hartmut F Ständer, Martin Dugas, Matthias Augustin, Sonja Ständer
{"title":"Management of chronic pruritus: from the dermatological office to the specialized itch center: a review.","authors":"Manuel P Pereira, Sabine Steinke, Philipp Bruland, Hartmut F Ständer, Martin Dugas, Matthias Augustin, Sonja Ständer","doi":"10.1097/itx.0000000000000006","DOIUrl":"10.1097/itx.0000000000000006","url":null,"abstract":"<p><p>Patient care for those affected by chronic pruritus is remarkably complex due to its high prevalence and multifactorial nature. It requires a comprehensive assessment of the patient's medical history, extensive diagnostic procedures, and long treatment duration, including management of possible accompanying disorders such as sleep disturbances and mental distress. It is important to prioritize patient's needs when developing a therapeutic treatment plan. Standardized questionnaires and scales should be used to better analyze the patient history, quality of life, symptom intensity, and course of treatment. These can be distributed via digital platforms, allowing for more effective communication between the treating agents and gathering of large volumes of data in central databases. In today's health care system, it is essential for physicians with itch-related specializations and specialized itch centers to cooperate. It is thus crucial to focus efforts on the further development of specialized treatment centers and training courses for medical practitioners. There are, however, various regulatory and economic barriers to overcome in the modern health care system before patients with chronic pruritus can be offered the best possible care. Accordingly, health care authorities should be made aware of the difficulties associated with the management of chronic pruritus and of the high individual and societal burden it represents.</p>","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"2 2","pages":"e6"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/53/itx-2-e6.PMC6372054.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37018874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brief communication: MRGPRX2, atopic dermatitis and red man syndrome.","authors":"Ehsan Azimi, Vemuri B Reddy, Ethan A Lerner","doi":"10.1097/itx.0000000000000005","DOIUrl":"10.1097/itx.0000000000000005","url":null,"abstract":"<p><p>Vancoymycin causes red man syndrome, an itchy erythematous eruption involving the face, neck and upper torso. Atopic dermatitis also manifests itch and erythema, and staphylococcus δ-toxin contributes to this process. The antibiotic and toxin each provoke mast cell degranulation but the mechanism had not been understood. We have determined that these compounds evoke degranulation via interaction with the same receptor, MRGPRX2, on mast cells. A receptor antagonist inhibits this process. Antagonists of this receptor may have therapeutic potential.</p>","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/f6/itx-2-e5.PMC5375112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34877110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}