Chronic pruritus (CP), a symptom of many diseases, is often referenced as the most common skin complaint in dermatology, accounting for an average of 7 million office visits in the US each year, or ∼1% of total office visits1–3. Despite the relatively high prevalence of this condition, there is a scarcity of data on the characteristics of CP in the US, including the severity, duration, and frequency of pruritus experienced by patients who seek medical treatment3,4. CP is associated with a number of diverse conditions, and its underlying causes can be dermatologic, infectious, psychiatric, neuropathic, or systemic in nature5–7. Although there are several well-established factors associated with CP and guidelines for diagnosis exist, results from a large population-based study in Germany suggested that ∼50% of patients do not know the underlying cause of their pruritus5,8. No strong correlations have emerged between sex, age, geographic location, or socioeconomic status and frequency of CP8–10. However, men and women have been shown to differ regarding which symptoms of CP they consider most important11, and in specific aspects of their CP, such as the itch quality and location, as well as scratching behavior12. In addition, there is general agreement that CP occurs more frequently in certain ethnic groups such as blacks/African Americans or Asians/Pacific Islanders3,13–15.
The severity of CP is strongly associated with negative impact on patient quality of life, including sleep disturbances, impact on mood, and increased levels of depression16–19. CP is a prevalent component of several dermatologic conditions. Studies on psoriasis have consistently reported that >75% of patients experience CP and that it is one of the most distressing symptoms for these patients20. In addition, a German survey revealed that 74% of patients reported that pruritus interfered with their everyday life and 78% reported that they frequently/constantly experienced pruritus of moderate intensity21. Further, a study that evaluated pruritus in patients on hemodialysis found a 15% increased risk of mortality, likely due to sleep disturbances, versus patients on hemodialysis who did not experience pruritus22.
We surveyed practicing, community-based US dermatologists to better understand the characteristics of patients presenting specifically with CP, current treatment practices, and dermatologists’ perceptions of unmet needs for this patient population.
Dermatologists were selected to participate in an online survey based on the results of a 10-question, web-based screener. The screener was e-mailed in March 2015 to 9434 active US dermatologists from the American Medical Association Masterfile database (medical residents were excluded). The screener asked participants how many unique patients per year they manage for each of 9 different dermatologic conditions, including CP. Dermatologists who responded to the screener and reported managing ≥10 patients with CP per year were subsequently invited to participate in the survey.
The survey instrument was developed by Biomedical Insights Inc., and underwent 2 rounds of survey pilot testing a total of 23 dermatologists selected from the screener. For each round of pilot testing, 5 dermatologists were also interviewed via telephone to verify their answers and assess their interpretation of each question. Survey questions were iteratively refined based on this feedback. The final survey contained 55 questions, with 20 related specifically to CP, 7 related to the US community-based dermatologist sample, and the remaining questions related to prurigo nodularis or the use of an investigational neurokinin-1 receptor antagonist. Only the findings related to CP and the respondent sample are reported here. Respondents were informed that CP may be caused by one or more underlying conditions, or no identifiable underlying diagnosis or related condition, and were instructed not to consider patients with acute pruritus. From March 27 to April 10, 2015, screened dermatologists were invited to participate in the final web-based survey. Respondents were compensated for their participation. The survey was formatted so that respondents’ answers for multiple-answer percentage questions had to add up to 100%, and answers for each percentage answer box had to be a number between 0 and 100. Collected survey data were cleaned by excluding duplicates and unreliable responses according to uniformly applied rules. Open-ended textual data were categorized and coded thematically. Univariate descriptive statistics were generated using SPSS Statistics V22.0 (IBM, New York, NY) and Excel 2013 (Microsoft, Redmond, WA). Data are provided as frequencies, arithmetic means with SD, and 95% confidence intervals (CI), as relevant.
A total of 291 dermatologists responded to the screener, and 275 were subsequently invited to participate in the survey. After exclusion, the final number of surveys included for analysis was 212 (77.1% response rate after the screener).
Dermatologist and practice characteristics
The majority of the responders (88.7%) identified themselves as a general dermatologist with no subspecialization. Respondents primarily practice as part of a dermatology group practice (50.0%), a solo practice (29.2%), or a multispecialty group (14.6%); a small proportion identified as being part of an academic practice (5.2%). The distribution of respondents across the main regions of the US was largely comparable: Northeast (29.7%), South (25.5%), Midwest (23.6%), and West (21.2%).
CP patient characteristics
On average, respondents managed 185.7 (95% CI, 155.7–215.7) unique patients with CP (defined as pruritus of ≥6 wk in duration, per the International Forum for the Study of Itch classification23) over the previous year. These patients represent 4.8% of all unique patients managed over the previous year. Most respondents included “unspecified chronic itch” (97.2%) and “multifactorial chronic itch” (91.5%) in their estimate of CP; however, others included other conditions, such as “chronic itch in eczema” (56.6%), “chronic itch in atopic dermatitis” (55.2%), and “chronic itch in psoriasis” (32.1%; Table 1).
Respondents had varied definitions of what constitutes “chronic” pruritus. An analysis of free-response answers demonstrated that 90.6% of respondents defined CP as a specific minimum duration of pruritus; 16.5% defined this minimum duration as 2 to <6 weeks, 46.7% as ≥6 weeks to <3 months, 25.5% ≥3 to <9 months, and 1.9% as ≥9 months.
Respondents’ patients with CP were reported to be predominantly middle-aged or elderly; 27.3% of patients were 45–64 years of age, 31.6% were 65–84 years of age, and 14.6% were ≥85 years of age (Table 2). Regarding CP severity, 22.3% of patients had CP characterized as mild, 37.7% as moderate, 27.2% as severe, and 12.7% as very severe (Table 3). The survey did not provide definitions for these severity categories, so respondents answered according to their own interpretation of each severity category.
CP was rated as having the highest perceived level of unmet need among the 9 dermatologic conditions included in the survey, as based on mean (SD) rating of 8.6 (1.3) on a 10-point scale, where 1 represented no unmet need and 10 represented a significant unmet need; the dermatologic conditions were randomized for each respondent (Fig. 1). Respondents were also asked to describe in their own words the level of unmet need for CP. A total of 84.9% of respondents’ free-response answers indicated that they believed that unmet needs for CP are related to a lack of safe, tolerable, and/or effective therapeutic options, 12.7% to disease etiology, and 11.8% to sedation.
Severe/very severe CP patient characteristics
Respondents were asked questions specifically about patients with severe or very severe CP (considered as 1 combined group). Respondents reported seeing an average of 61 patients per year with severe/very severe CP, constituting 32.7% of respondents’ total CP patients per year. Respondents reported that 44.9% of their patients with severe/very severe CP had a single dermatologic disease or condition that underlies their CP, and that 31.7% had ≥2 causes of pruritus (Table 4). Respondents were “confident” that the underlying cause(s) of pruritus was identified in 34.6% of their patients with severe/very severe CP, while 39.9% of patients with severe/very severe CP had no identified underlying cause(s) (Table 4).
The disease course of CP was highly varied among patients with severe/very severe disease. Respondents reported that 34.9% of their patients have had pruritus lasting 1–5 years and 18.8% have had pruritus for >5 years. In addition, approximately one-fourth (25.4%) of patients had pruritus episodes that lasted ≥6 months per year, and 44.4% of patients were affected by pruritus continuously throughout the year.
Nearly all respondents indicated prescribing antihistamines and corticosteroids for patients with severe/very severe CP (97.1% for each), typically as first-line therapy (77.5% and 76.1%, respectively; Table 5). Ultraviolet phototherapy was also commonly used (83.3% of respondents), with 42.1% using it as a second-line therapy. Antidepressants were prescribed by 75.6% of respondents, primarily as second-line and third-line treatments. Anticonvulsants and immunosuppressants were used by 56.0% and 54.5% of respondents, respectively, mainly as second-line treatment or later. Opioid antagonists and neurokinin-1 receptor antagonists were used by a minority of respondents (36.4% and 23.0%, respectively), mostly as fourth-line treatment or later.
Despite a range of therapeutic options available to dermatologists, respondents reported that more than one-third of their patients with severe/very severe CP did not adequately improve to mild or no itch after all treatment attempts [mean (SD), 36.3% (21.4); 95% CI, 33.4–39.2]. Respondents were asked to describe in their own words what they found to be the most challenging aspects of treating severe/very severe CP. The majority of free-response answers (73.6%) indicated that the most difficult aspect is related to the lack of effective, safe, and/or well-tolerated treatment options that are currently available. In another free-response question, respondents were asked to name specific populations of patients with severe/very severe CP who have a higher unmet need than the overall population of patients with severe/very severe CP. Of the 189 dermatologists who responded to the free-response question “name specific populations of patients with severe/very severe CP that have a higher unmet need than severe/very severe patients overall,” 157 (83.1%) indicated 1 or more specific population(s) or condition(s), with the most common answers being elderly patients (50.1%), patients with uremic or hepatic pruritus (19.0%), and patients with a psychiatric condition (9.3%).
The US dermatologists surveyed reported that among all their unique patients managed over the previous year, the prevalence of CP was 4.8%. The relatively low prevalence identified in this survey may be an underestimate driven by the large percentage of dermatologists who indicated that they excluded patients with chronic itch in psoriasis (67.9%) and chronic itch in atopic dermatitis (44.8%) from their estimates of CP prevalence in their practices. However, the dermatologists’ responses demonstrate that patients present with a broad range of CP syndromes, including chronic hepatic and uremic itch, along with dermatologic conditions (eg, prurigo nodularis) and cutaneous malignancies. This suggests that the medical care of patients with CP may be challenging in terms of the diagnosis and therapy of the underlying diseases. To minimize this challenge, dermatologists may need to employ an interdisciplinary approach with specific antipruritic therapy and the collaboration of an itch specialist or center24.
There are currently no Food and Drug Administration (FDA)–approved therapies for CP, and neither the American Academy of Dermatology nor the National Institute of Arthritis and Musculoskeletal and Skin Diseases have current published guidelines for the treatment of CP. The treatments most commonly used by this survey’s respondents are as follows: a combination of antihistamines and corticosteroids are first-line treatment; depending on how patients respond, ultraviolet phototherapy is then given as second-line treatment; antidepressants are often used as third-line treatment; and, finally, if these therapies fail, immunosuppressive agents along with newer agents that target the pain and itch pathways may be tried. Indeed, preclinical research demonstrates a strong connection between itch and pain, and also argues for considering itch a condition with its own specific pathway25,26.
The community-based US dermatologists who participated in this survey—and who were unaware of the focus of the survey and were presented with a choice of 9 dermatologic conditions randomized for each respondent—ranked CP as having the highest level of unmet need. However, the respondents were not consistent in delineating which conditions they included in their estimates of patients with CP. This discrepancy may be due to differences in how physicians in the US conceptualize CP, which may be partially driven by a lack of safe, tolerable, and effective treatments and an accompanying lack of emphasis on pruritus during medical training. In addition, the dermatologists in this survey often indicated that the cause of their patients’ CP was unknown or that they lacked confidence in identifying the underlying cause. The dermatologists sampled described a CP patient population that was older, with multifactorial or unspecified diseases underlying CP. Approximately one third of patients seen by the community-based dermatologists in this survey were identified as having severe or very severe CP. These patients had frequent or persistent symptoms (itch episodes lasting ≥6 mo) or even continuous, year-round symptoms. Continuous symptoms may be quite detrimental to patients with CP because CP symptoms have been strongly associated with reductions in quality of life17.
A limitation of this survey is that it relied primarily on the ability of the dermatologists surveyed to recall information about the clinical course of patients with CP in their practice, which was reported to account for about 5% of their patients.
Treatment of CP, especially severe/very severe CP, can be challenging, and this could be driven in part by the complex and multifactorial nature of the disease, as well as by the age and comorbidities of affected patients1,23,27. Prior studies have indicated a high prevalence of CP in elderly patients, who often exhibit more severe disease28,29. Dermatologists in this study consider effective treatment of elderly patients an area of unmet need. Many of the current therapeutic options described in this report are used off label, and some have significant side effects, which further complicate the management of CP27,30. In addition, this survey’s finding of the low percentage of patients with CP who adequately improved with the currently available therapies argues that there exists a significant unmet need for a safe and effective therapy that can be utilized to treat CP.
Sources of funding
This study was funded by Menlo Therapeutics Inc.
Conflict of interest disclosures
S.S. is a former employee of Velocity Pharmaceutical Development and Menlo Therapeutics Inc. and has received compensation from and owns stock in Menlo Therapeutics Inc. G.Y. has received grant/research support for his role as an investigator from Menlo Therapeutics Inc., Vanda Pharmaceuticals, Kiniksa Pharmaceuticals, and Sun Pharmaceuticals Industries Ltd, and has received honoraria for participation in advisory boards for Menlo Therapeutics Inc., Trevi, Novartis, Pfizer, OPKO Health Inc., Sanofi, Galderma, and Sienna. M.B.K. has received personal fees from Velocity Pharmaceutical Development and is a shareholder of and consultant to Menlo Therapeutics Inc. and Velocity Pharmaceutical Development LLC. P.C.N. has received consulting fees, honoraria, travel support, and fees for participation in meetings, data monitoring, statistical analysis, and writing support, paid to him or his institution, from Menlo Therapeutics Inc.; through BioMedical Insights Inc., he has also consulted for many biotechnology, pharmaceutical, and medical device manufacturers, and his spouse has consulted for multiple biotechnology, pharmaceutical, and medical device manufacturers. S.S. has received grants/research support and honoraria for her role as an investigator and a consultant from Menlo Therapeutics Inc., Galderma, Kiniksa Pharmaceuticals, Pierre Fabre Dermo-Cosmetique, Trevi Therapeutics, and Vanda Pharmaceuticals; she has received honoraria for participation in advisory boards for Menlo Therapeutics Inc., Beiersdorf AG, Celgene GmbH, Galderma, Kneipp-Werke, NeRRe Therapeutics, and Sienna Biopharmaceuticals; and she has received patient fees from Menlo Therapeutics Inc., Dermasence, Trevi Therapeutics, and Vanda Pharmaceuticals.
The authors would like to thank BioMedical Insights Inc. for data collection and analysis. Medical writing and editorial assistance were provided by Nathan Hutcheson, PhD (ApotheCom, New York, NY), and funded by Menlo Therapeutics Inc.
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