Prevalence of Diagnosed/Highly Symptomatic Pachyonychia Congenita (PC) Patients Managed Annually by US Dermatologists-National Real World Occurrence (RWO) Physician Study
Received Date: Jun 05, 2019 / Accepted Date: Jul 19, 2019 / Published Date: Jul 26, 2019
Background: Pachyonychia Congenita (PC) is a chronically debilitating and lifelong genetic disease that typically causes constant, disabling pain. PC appears to be rare, but its prevalence is unsubstantiated by large-scale epidemiologic studies. We conducted the first national prevalence study of a cohort of PC patients, those managed annually by US dermatologists.
Methods: Potential study participants were randomly selected from a national panel of patient-care dermatologists and invited to participate in a brief study of a patient condition that would be disclosed at the study website.
Results: Of the 423 dermatologists contacted, 400 participated, of whom 53% reported managing at least one PC patient during the past 12 months, an annual prevalence of 6.4/10,000 patients (extrapolated to 8,900 to 9,800 nationally), according to the study model.
Conclusions: Study findings indicate PC is likely to be far more prevalent than previous estimates in the literature and that the frequency and level of disability caused by pain-related symptoms may be under-recognized by the treating dermatologist. Additional research is needed to determine the extent to which PC diagnosis has been or could be genetically confirmed.
Keywords: Pachyonychia Congenita (PC); Prevalence; Real World; Epidemiologic survey
Pachyonychia congenita (PC) is a rare, chronically debilitating, and lifelong genetic disease in which severe plantar pain is the most debilitating feature and which causes many PC patients to rely on canes, crutches, wheelchairs or other ambulatory aids to reduce plantar pain from walking [1-3]. PC is thought to be rare, but its prevalence is unsubstantiated by large-scale epidemiologic studies. The prevalence of PC has been estimated at 5,000 to 10,000 cases worldwide (Figure 1). This value, however, is based on an order-of-magnitude estimate supplied in a personal communication more than a decade ago. No epidemiologic study was performed to generate this value .
In the absence of previous population-based studies, it is useful to note that a registry has been created by the Pachyonychia Congenita (PC) Project, a non-profit organization initially founded in 2003 that is dedicated to finding treatments and a cure for PC and connects patients, researchers, and physicians in nearly 60 countries to help those with PC . The PC Project registry had accrued more than 2,000 patients globally as of April 2019 . Though PC Project has made significant strides in advancing scientific research, the registry is -neither designed-nor resourced to achieve complete ascertainment of the prevalent population.
Given the limitations of existing published data, the prevalence of PC remains an open question. This is the first study designed to estimate the national prevalence of a pachyonychia congenita cohort, specifically, the number of diagnosed PC patients managed annually by dermatologists in the United States.
Materials and Methods
We conducted a national, retrospective, observational survey of patient-care dermatologists in the United States to collect data on the extent to which patients diagnosed with PC are being managed for the condition. The basic approach was to:
• Obtain a representative sample of patient-care dermatologists (a key specialty that manages the target condition),
• Determine the proportion of dermatologists who manage PC,
• Determine the volume of PC patients each of these dermatologists, on average, manages annually and
• Extrapolate these findings to the national universe of dermatologists and the corresponding prevalence of their PC-managed patients.
This physician-based methodology and its variants have been successfully used to estimate the size of various patient cohorts on national and multi-national levels [7-9]. The study was conducted between August 10 and September 5, 2018.
Selection and description of participants
Potential study participants were randomly selected from a national master file of patient-care dermatologists developed and constantly updated by Medefield, a global physician research company. Selected dermatologists were sent an invitation electronically to participate in “a brief national study of a patient condition that would be disclosed at the study website.” This procedure was used to minimize the loss of quantifiable responses from physicians who manage no PC patients and might self-select out of the study before being study qualified or disqualified, which could bias the resulting national prevalence estimates of our PC patient cohort. A total of 400 dermatologists accessed the study website. A study-eligible dermatologist was required to be actively managing the care of patients but not required to have ever managed a patient’s PC. Of the 423 patient-care dermatologists invited to the study site, 400 participated in the study (94.6%).
To determine how well our sample of patient-care dermatologists matched the corresponding universe of dermatologists nationally, we compared the respective distributions by US Census Bureau regions. Table 1 reveals that our sample of dermatologists closely mirrors the corresponding geographic distribution of the national universe of dermatologists (Table 1).
|Region||National (%)||Study (%)|
National n = 11,627 dermatologists Study n = 400 dermatologists
Table 1: Distributions of patient-care dermatologists in the US and study by US Census Bureau region.
After qualification for the study, dermatologists were informed that the purpose of our study was to understand the number of patients managed who are diagnosed or symptomatic with plantar keratodermas and thickened nails and were shown the patient examples pictured in Figures 1 and 2. Physicians were then asked to indicate the number of patients managed in the past 12 months “with plantar keratodermas and/or thickened nails ” and the number “diagnosed with Pachyonychia Congenita (PC)” (Figures 2 and 3).
Statistical Analysis and Prevalence Model
We used descriptive statistics to examine physician demographic and patient- volume characteristics. Significant differences (p < 0.05) were evaluated using independent samples t-tests for comparison of the means of two independent groups on a continuous dependent variable and Chi-square test for homogeneity to determine if a difference exists between the binomial proportions of two independent groups on a dichotomous dependent variable. We also developed an analytical model that provides an estimate of the total number of dermatologist-treated PC patients nationally. A step-by-step description of this model and resulting outputs are presented in the next section. Data were analyzed using IBM SPSS Statistics 23.
Table 2 describes the practice characteristics of the study population, composed of 400 patient-care dermatologists. The mean self-estimated total number of unique patients reportedly managed by study physicians in past 12 months was 1,835 (SD 159.2) of whom the mean number reportedly diagnosed with plantar keratodermas and/or thickened nails was 46.8 (SD 44.5) and 70.1 (SD 75.4) for patients diagnosed with palmar keratodermas, follicular hyperkeratosis, or leukokeratosis that are unrelated to another known disease. About half of study physicians (53%) reported managing at least one PC-diagnosed patient in the past 12 months; two-thirds of these physicians (68%) reported managing only one or two PC patients (mean 1.18 SD 1.48). In addition to these currently managed PC patients, almost half of study physicians (45.8%) reported managing PC for an additional 1 to 8 PC patients in the past five years (Mean 1.8 SD 2.3).
|Variables (physician self-estimates)|
|Number of total unique patients managed in past 12 months|
|1,001 - 1,500||32.40%|
|1,501 - 1,700||31.50%|
|1,701 - 2,000||10.80%|
|Number of unique patients managed in past 12 months who are diagnosed with plantar keratodermas and/or thickened nails|
|26 - 49||15.30%|
|50 - 99||25.40%|
|Number of unique patients managed in past 12 months managed for palmar keratodermas, follicular hyperkeratosis, or leukokeratosis which are unrelated to another known disease|
|26 - 50||20.00%|
|51 - 150||24.70%|
|Number of unique patients managed in past 12 months who are diagnosed with Pachyonychia Congenita (PC)|
|Number of unique patients seen for PC in past 5 years in addition to those PC patients managed in past 12 months|
Table 2: Practice characteristics of the study population.
Table 3 provides the distribution of physician-estimated symptoms observed in patients diagnosed with PC. The most frequently reported PC symptoms were thickened toenails (92%), thickened fingernails (90%), and calluses and blisters (76%).
|Variables (physician self-estimates)|
|Presence of calluses and blisters||75.90%|
|Difficulty performing activities on feet, including standing||62.30%|
|Ambulation impairment, including difficulty with walking||51.90%|
|Reliance upon ambulatory aids or alternative forms of mobility||24.50%|
|Neurovascular structures or cutaneous thromboses on feet||12.70%|
Table 3: Symptoms observed in patients diagnosed with PC.
Figure 4 describes and presents the results of the 11-step dermatologist PC-managed prevalence model for the study cohort. According to model-derived estimates, US dermatologists manage PC for 9,330 PC patients annually (CI ±4.8%) or about 8,900 to 9,800 patients. The estimated prevalence of the dermatologist PC-managed cohort in the US is 6.4 PC patients per 10,000 patients managed.
Study physicians were asked, “Are you familiar with PC Project, a public US charity dedicated to patients with PC and providing free genetic testing?” Only 15.2% indicated awareness of PC Project, and only 40.8% of these physicians (9.0% of all physicians) expressed awareness that the organization offers free genetic testing to diagnose PC.
Our study represents the first attempt using a nationally representative sample to estimate the prevalence of any pachyonychia congenita (PC) cohort in any country in the world. The prevalent population examined in this study is the cohort of PC-diagnosed patients managed annually by dermatologists in the United States.
We found that management of PC by dermatologists is more common than one might expect based on previously published PC prevalence estimates, none of which used a nationally representative epidemiology study. About half the dermatologists in our study (53%) reported managing PC for one or more patients during the past 12 months, representing 8,900 to 9,800 patients, according to the study analytical model (Figure 4).
Our study also raises the possibility that the level of disability caused by pain-related symptoms may be under-recognized by the treating dermatologist. Study physicians mentioned pain as a symptom for only 69% of their PC patients. By contrast, pain was almost universal among 101 livestream respondents who participated in an in-person or online PC survey conducted during a 2018 Food and Drug Administration (FDA) externally led patient-focused drug development (EL-PFDD) meeting: 91% indicated that they typically feel some level of pain with every step that they walk .
We also found that study dermatologists were about 58 times more likely to report managing a patient for palmar keratodermas, follicular hyperkeratosis, or leukokeratosis that are unrelated to another known disease (mean 70.1 SD 75.4) than for PC (mean 1.2 SD 1.5). Thus, dermatologists appear to manage many non PC-diagnosed patients who have prominent symptoms of PC.
It is important to note that the current study was not designed to estimate the total national prevalence of PC, but rather the prevalence of a particular, though important, subset. Using the model’s best PC patient estimate (9,330) and the estimated number of total patients managed annually by dermatologists (14,500,000), the estimated prevalence is 6.4 PC patients per 10,000 total dermatologist-managed patients.
These estimates must be viewed in light of several potentially serious study limitations. Among the most important limitations is a possible “study-participation” effect. This is a positive-response bias that could be caused if a physician unfamiliar with PC until viewing the patient-symptom pictures and descriptions presented in the electronic survey instrument realized that some of his/her previously undiagnosed PC patients should have been diagnosed with this condition. PC-diagnosed prevalence over estimation would occur if any these newly PC-diagnosed patients were added by the physician to the number of study-reported PC-patients that he/she manages. Other potentially serious biases include:
• Surveys are subject to sampling error and other possible surveyrelated biases;
• Recall errors, which may be minimized because most physicians had only two or fewer PC patients to recall;
• Possible duplication of patients if the patients have seen more than one dermatologist for management of PC in the last 12 months; and
• Possible lack of genetic confirmation of PC. It is important that dermatologists be aware that the PC Project provides free genetic testing .
Unfortunately, only 15.2% of study dermatologists were aware of the PC Project and 40.2% of those physicians (9% of total physicians) were not aware that the organization offers free genetic testing. These findings indicate that efforts are needed by various dermatology-supporting organizations to raise awareness of PC Project ’ s free genetic testing and other contributions to PC-related scientific research, including its support of the first large-scale, randomized, placebo-controlled study of an experimental therapy for PC. At present there is no FDA-approved treatment for PC. The FDA recently has acknowledged pachyonychia congenita as a serious condition and has granted fast-track designation for the advancement of PTX-022 (QTORIN rapamycin) for the treatment of PC . Additional information on PC Project and its services to physicians, patients, scientists, and others is contained in the Supplemental section of this article.
In conclusion, this research underscores the need for future research to determine the proportion of patients diagnosed with PC whose diagnoses are recorded in the patients’ medical records, the proportion whose diagnosis is genetically confirmed, and the proportion of non- PC-diagnosed patients with PC-like symptoms and who would likely be diagnosed with PC if they received genetic testing. Research also is needed to determine the total national prevalence of PC patients, which requires including physician specialties other than dermatology and deduplication of patients who see multiple physicians for management of PC.
The authors thank the 400 physicians who took time to participate in this study. We are also most grateful to Janice Schwartz, Executive Director of PC Project, and Holly Evans, International Patient Support Officer for PC Project, for their guidance and substantive contributions to research of pachyonychia congenita. Sponsorship of this study and the article processing charges were funded by Palvella Therapeutics. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. All authors had full access to all of the data in this study and take responsibility for the integrity of the data and accuracy of the data analysis. Jack Gallagher (JRG), Kylee Heap (KH) and Susan Carroll (SC) contributed to study planning and design. JRG, KH and SC contributed to the acquisition of the study-physician provided data. JRG, KH and SC conducted the analysis of the data. All authors contributed to the interpretation of the data. All authors contributed to the drafting and critical review of the manuscript.
The study and publication development were supported by Palvella Therapeutics, Inc, Wayne, PA, USA.
Conflict of Interest
Jack R. Gallagher is an employee of Clarity Pharma Research, LLC, Spartanburg, SC, a scientific research organization that conducted the study, and declares that he has no conflicts of interest. David Lapidus is an employee of LapidusData, Inc., and declares that he has no conflicts of interest. Kylee Heap is an employee of Clarity Pharma Research, LLC, Spartanburg, SC, and declares that she has no conflicts of interest. Susan Carroll is an employee of Clarity Pharma Research, LLC, Spartanburg, SC, and declares that she has no conflicts of interest.
Ethics Approval and Consent to Participate
This article is based on previously existing observational data, and the research did not involve any new interventional studies of human or animal subjects performed by any of the authors. This retrospective study used deidentified data, and no personally identifiable health information was collected. Such studies are exempt according to 45CFR46.101(b)(4): Existing Data & Specimens - No Identifiers.
Availability of Data and Materials
The dataset generated during and/or analyzed during the current study is available from the corresponding author on reasonable request.
- McLean WHI, Hansen CD, Eliason MJ, Smith FJD (2011) The phenotypic and molecular genetic features of Pachyonychia Congenita. J Investig Dermatol 131: 1015-1017.
- Pachonychia Congenita (PC) Project (2018) Voice of the Patient: Report from the Pachyonychia Congenita (PC) Externally-led Patient-Focused Drug Development (EL-PFDD) Meeting pp: 1-70.
- Leachman S, Kaspa RL, Fleckman P, Florell SR, Smith F, et al. (2005) Clinical and pathological features of Pachyonychia Congenita. J Investig Dermatol Symp Proc 10: 3-17.
- Kaspar RL (2005) Challenges in developing therapies for rare diseases including pachyonychia congenita. J Investig Dermatol Symp Proc 10: 62-66.
- Pachonychia Congenita (PC) Project. History of PC Project (2019) Holladay, Utah: Pachyonchia Congenita Project.
- Pachonychia Congenita (PC) Project (2019) IPCRR Growth Report. Holliday, Utah: PC Project.
- Goring S, Wilson J, Risebrough N, Gallagher J, Carroll S, et. al. (2018) The cost of Mycobacterium avium complexlung disease in Canada, France, Germany and the United Kingdom: A nationallyrepresentative observational study. BMC Health Serv Res 18: 700.
- Van Ingen J, Wagner D, Gallagher J, Morimoto K, Lange C, et. al. (2017) Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases. Eur Respir J 49: 1601855.
- Adjemian J, Prevots R, Gallagher J, Heap K, Gupta R, et al. (2014) Lack of Adherence to Evidence-based Treatment Guidelines for Nontuberculous Mycobacterial Lung Disease. Ann Am Thorac Soc 11: 9-16.
- Pachonychia Congenita (PC) Project (2019) International PC Research Registry (IPCRR) [Internet]. Pachyonychia Congenita Project Website. Holladay, Utah: Pachyonchia Congenita Project.
- Pachonychia Congenita (PC) Project (2018) FDA grants Fast Track Designation for PC Treatment. Holladay, Utah: Pachyonchia Congenita Project.
Citation: Gallagher JR, Lapidus D, Heap K, Carroll S (2019) Prevalence of Diagnosed/Highly Symptomatic Pachyonychia Congenita (Pc) Patients Managed Annually by US Dermatologists-National Real World Occurrence (RWO) Physician Study . J Dermatol Dis 6: 280.
Copyright: © 2019 Gallagher JR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Select your language of interest to view the total content in your interested language
Share This Article
- Total views: 294
- [From(publication date): 0-0 - Oct 22, 2019]
- Breakdown by view type
- HTML page views: 266
- PDF downloads: 28