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A Nationwide Study of Prurigo Nodularis: Disease Burden and Healthcare Utilization in the United States

Open ArchivePublished:April 03, 2021DOI:https://doi.org/10.1016/j.jid.2021.02.756

      Abbreviations:

      AD (atopic dermatitis), ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification), PN (prurigo nodularis)
      To the Editor
      Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease characterized by symmetrically distributed hyperkeratotic nodules (
      • Kwatra S.G.
      Breaking the itch–scratch cycle in prurigo nodularis.
      ;
      • Kwon C.D.
      • Khanna R.
      • Williams K.A.
      • Kwatra M.M.
      • Kwatra S.G.
      Diagnostic workup and evaluation of patients with prurigo nodularis.
      ). The intense pruritus associated with PN often severely impacts QOL (
      • Huang A.H.
      • Williams K.A.
      • Kwatra S.G.
      Prurigo nodularis: epidemiology and clinical features.
      ;
      • Iking A.
      • Grundmann S.
      • Chatzigeorgakidis E.
      • Phan N.Q.
      • Klein D.
      • Ständer S.
      Prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 patients.
      ;
      • Pereira M.P.
      • Hoffmann V.
      • Weisshaar E.
      • Wallengren J.
      • Halvorsen J.A.
      • Garcovich S.
      • et al.
      Chronic nodular prurigo: clinical profile and burden. A European cross-sectional study.
      ). In our previous experience as well as in a European cohort, patients with PN had a greater severity of disease, greater itch intensity, and more dramatic reduction in QOL than other patients with chronic pruritus (
      • Whang K.A.
      • Khanna R.
      • Williams K.A.
      • Mahadevan V.
      • Semenov Y.
      • Kwatra S.G.
      Health-related QOL and economic burden of chronic pruritus.
      ;
      • Williams K.A.
      • Roh Y.S.
      • Brown I.
      • Sutaria N.
      • Bakhshi P.
      • Choi J.
      • et al.
      Pathophysiology, diagnosis, and pharmacological treatment of prurigo nodularis.
      ;
      • Zeidler C.
      • Pereira M.P.
      • Dugas M.
      • Augustin M.
      • Storck M.
      • Weyer-Elberich V.
      • et al.
      The burden in chronic prurigo: patients with chronic prurigo suffer more than patients with chronic pruritus on non-lesional skin: a comparative, retrospective, explorative statistical analysis of 4,484 patients in a real-world cohort.
      ). Thus, we hypothesized that patients with PN experience higher rates of disease comorbidities and healthcare utilization than patients who have other pruritic, inflammatory skin conditions. To address the current gaps in the understanding of PN, we employed national claims data to describe the epidemiology, comorbidities, and healthcare utilization of patients with PN.
      Using anonymized, nationally representative, private insurance claims data (October 2015‒December 2019), we defined patients with PN as individuals with ≥2 medical claims for PN using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. For comparison to patients with inflammatory skin diseases, ICD-10-CM codes were also used to identify patients with atopic dermatitis (AD) and psoriasis. Matched controls (age- and gender-matched to patients with PN) were selected from individuals without any ICD-10-CM codes for PN, AD, and psoriasis. Further details are provided in Supplementary Materials and Methods.
      In our analysis of nationwide claims data, we identified the number of cases of PN, AD, and psoriasis annually. In 2016, there were 2,658 patients with PN, 21,482 patients with AD, and 21,073 patients with psoriasis. In 2017, there were 4,823 patients with PN, 38,805 patients with AD, and 35,193 patients with psoriasis. In 2018, there were 6,992 patients with PN, 54,593 patients with AD, and 47,382 patients with psoriasis. In 2019, there were 9,426 patients with PN, 70,298 patients with AD, and 59,509 patients with psoriasis. The annual period prevalence estimates in the claims database are shown in Table 1. The prevalence estimates for PN in 2016 were 18 per 100,000 overall, 22 per 100,000 for adults, and 2 per 100,000 for children, and the estimates rose to 58 per 100,000 overall, 70 per 100,000 for adults, and 7 per 100,000 for children in 2019. The mean (SD) age of patients with PN was 57.5 (17.0) years in 2016 and increased to 59.8 (16.9) years in 2019. The gender breakdown ranged from 44.5% male in 2016 to 46.5% male in 2019. The demographics for the controls and for patients with AD and psoriasis are also shown in Table 2.
      Table 1Period Prevalence Estimates (Per 100,000) for PN, AD, and Psoriasis
      PNADPsoriasis
      201620172018201920162017201820192016201720182019
      Overall18324558146255348432144232302366
      Children24674197421,0161,27515263340
      Adults2239547074127178227178286370445
      Abbreviations: AD, atopic dermatitis; PN, prurigo nodularis.
      Table 2Demographics for PN, Controls (Matched to Patients with PN), AD, and Psoriasis
      2016PNControlsADPsoriasis
      n2,65813,29021,48221,073
      Age, mean (SD)57.5 (17.0)57.5 (17.0)22.0 (24.2)52.1 (16.2)
      Gender, male (%)1,183 (44.5)5,915 (44.5)10,367 (48.3)10,284 (48.8)
      CCI1.53 (2.27)0.98 (1.82)0.53 (1.16)1.16 (1.88)
      2017PNControlsADPsoriasis
      n4,82324,11538,80535,193
      Age, mean (SD)57.7 (16.9)57.7 (16.9)21.9 (23.7)52.3 (16.3)
      Gender, male (%)2,197 (45.6)10,985 (45.6)18,610 (48.0)17,075 (48.5)
      CCI1.84 (2.52)1.21 (2.09)0.61 (1.31)1.38 (2.10)
      2018PNControlsADPsoriasis
      n6,99234,96054,59347,382
      Age, mean (SD)58.6 (17.0)58.6 (17.0)22.6 (23.8)53.0 (16.4)
      Gender, male (%)3,220 (46.1)16,100 (46.1)25,971 (47.8)22,684 (47.9)
      CCI2.04 (2.64)1.34 (2.26)0.68 (1.42)1.53 (2.26)
      2019PNControlsADPsoriasis
      n9,42647,13070,29859,509
      Age, mean (SD)59.8 (16.9)59.8 (16.9)23.7 (24.3)53.9 (16.5)
      Gender, male (%)4,383 (46.5)21,915 (46.5)33,216 (47.3)28,124 (47.3)
      CCI2.32 (2.84)1.57 (2.42)0.75 (1.52)1.71 (2.40)
      Abbreviations: AD, atopic dermatitis; CCI, Charlson Comorbidity Index; PN, prurigo nodularis.
      For a comprehensive analysis of the comorbidity burden, we quantified the overall comorbidity burden with the Charlson Comorbidity Index. We also examined the comorbidity profiles using the individual components of the Charlson Comorbidity Index (Figure 1). Patients with PN had the highest Charlson Comorbidity Index of these groups, with a mean (SD) of 1.53 (2.27) compared with 0.98 (1.82) for the controls (age- and gender-matched to patients with PN), 0.53 (1.16) for patients with AD, and 1.16 (1.88) for patients with psoriasis in 2016 and a mean (SD) of 2.32 (2.84) compared with 1.57 (2.42) for the controls, 0.75 (1.52) for patients with AD, and 1.71 (2.40) for patients with psoriasis in 2019 (Table 2).
      Figure thumbnail gr1
      Figure 1Comorbidity heatmap for PN, AD, and psoriasis. Comorbidity heatmap comparing the comorbidity prevalence (in percentages) for patients with PN, AD, and psoriasis; color scale where green indicates the lowest percentage of the comorbidity burden and red indicates the highest percentage of the comorbidity burden (prevalence corresponds to the annual period prevalence). AD, atopic dermatitis; AIDS, acquired immunodeficiency syndrome; CHF, congestive heart failure; DM, diabetes mellitus; MI, myocardial infraction; PN, prurigo nodularis.
      The top five specialties seen by patients with PN, by the estimated number of visits per year per patient, were internal medicine (2.01), dermatology (1.87), family practice (1.60), cardiology or cardiovascular disease (0.85), and orthopedics or orthopedic surgery (0.49). For comparison, the estimates of the most visited specialties for the controls and the patients with AD and psoriasis are provided in Table 3.
      Table 3Estimates of Healthcare Utilization Per Person for the Top Five Specialties Utilized by Patients with PN Compared with Controls (Matched to Patients with PN) and Patients with AD or Psoriasis
      PNControlsADPsoriasis
      SpecialtyVisits Per YSpecialtyVisits Per YSpecialtyVisits Per YSpecialtyVisits Per Y
      Internal medicine2.01Internal medicine1.41Pediatrics2.02Internal medicine1.60
      Dermatology1.87Family practice1.33Allergy and immunology0.93Family practice1.41
      Family practice1.60Cardiology or cardiovascular disease0.63Dermatology0.75Dermatology1.38
      Cardiology or cardiovascular disease0.85Orthopedics or orthopedic surgery0.34Family practice0.64Cardiology or cardiovascular disease0.55
      Orthopedics or orthopedic surgery0.49Dermatology0.31Internal medicine0.62Rheumatology0.51
      Abbreviations: AD, atopic dermatitis; PN, prurigo nodularis.
      Patients with PN had a higher burden of several cardiovascular, pulmonary, and other systemic diseases than those with AD and those with psoriasis (
      • Boozalis E.
      • Tang O.
      • Patel S.
      • Semenov Y.R.
      • Pereira M.P.
      • Ständer S.
      • et al.
      Ethnic differences and comorbidities of 909 prurigo nodularis patients.
      ;
      • Huang A.H.
      • Canner J.K.
      • Khanna R.
      • Kang S.
      • Kwatra S.G.
      Real-world prevalence of prurigo nodularis and burden of associated diseases.
      ;
      • Whang K.A.
      • Kang S.
      • Kwatra S.G.
      Inpatient burden of prurigo nodularis in the United States.
      ). Patients with PN may experience a higher disease burden because the itch in PN is thought to be the most severe of chronic pruritic dermatoses (
      • Steinke S.
      • Zeidler C.
      • Riepe C.
      • Bruland P.
      • Soto-Rey I.
      • Storck M.
      • et al.
      Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: Results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of pruritus (PruNet) cross-sectional trial.
      ). PN is also associated with a broad range of diseases such as liver disease, renal disease, HIV, and malignancies, among others (
      • Dazzi C.
      • Erma D.
      • Piccinno R.
      • Veraldi S.
      • Caccialanza M.
      Psychological factors involved in prurigo nodularis: a pilot study.
      ;
      • Kwatra S.G.
      Breaking the itch–scratch cycle in prurigo nodularis.
      ).
      The higher disease burden of PN translates to higher healthcare utilization of specialty care by the patients. Patients with PN saw dermatologists more frequently than the controls as well as more frequently than those with AD and psoriasis. Consistent with our findings of the higher rates of comorbid cardiovascular disease in patients with PN, these patients also had the highest estimated utilization of cardiology or cardiovascular disease specialty visits in this study. Our results support previous findings indicating that patients with PN had a higher utilization of care from specialists (
      • Huang A.H.
      • Canner J.K.
      • Williams K.A.
      • Grossberg A.L.
      • Kwatra M.M.
      • Kwatra S.G.
      Healthcare resource utilization and payer cost analysis of patients with prurigo nodularis.
      ). In addition, patients with PN are more likely to be hospitalized, more likely to have longer inpatient stays, and more likely to have higher inpatient costs of care than the general population (
      • Whang K.
      • Gabriel S.
      • Chavda R.
      • Kwatra S.
      Emergency department utilization by patients with prurigo nodularis in the United States.
      ,
      • Whang K.A.
      • Kang S.
      • Kwatra S.G.
      Inpatient burden of prurigo nodularis in the United States.
      ).
      In summary, patients with PN had higher healthcare utilization of specialty care and comorbidity burden than age- and gender-matched controls as well as patients with AD and psoriasis. Patients with PN often remain recalcitrant to treatment and suffer from impaired QOL due to their chronic itch‒scratch cycle and associated comorbidity burden. Limitations of this study include the retrospective nature of the analysis and the identification of patients with PN using the ICD-10-CM code. To increase the validity of PN identification through ICD-10-CM codes for this study, we defined patients with PN as those who had at least two claims with the corresponding ICD-10-CM code on the basis of the methodology that has been previously published (
      • Huang A.H.
      • Canner J.K.
      • Khanna R.
      • Kang S.
      • Kwatra S.G.
      Real-world prevalence of prurigo nodularis and burden of associated diseases.
      ,
      • Huang A.H.
      • Canner J.K.
      • Williams K.A.
      • Grossberg A.L.
      • Kwatra M.M.
      • Kwatra S.G.
      Healthcare resource utilization and payer cost analysis of patients with prurigo nodularis.
      ). However, the ICD-10-CM code for PN requires further validation. Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in this study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession. Since the study is based on retrospective claims data, the findings presented in this study should be considered preliminary and the foundation for further research. Overall, this study provides a nationwide description of the epidemiology of PN and the comorbidities and healthcare utilization of patients with PN compared with those of control patients and patients with other similar pruritic, inflammatory skin diseases at the national level.

      Data availability statement

      Under law and regulations, the database used in this study cannot be made available. Owing to data use agreements, the claims data must remain private; inquiries regarding the data can be directed to the corresponding author (SGK).

      Conflict of Interest

      SGK is an advisory board member and/or consultant for AbbVie, Galderma, Incyte Corporation, Pfizer, Regeneron Pharmaceuticals, and Kiniksa Pharmaceuticals and has received grant funding from Galderma, Pfizer, and Kiniksa Pharmaceuticals. The remaining authors state no conflict of interest.

      Acknowledgments

      SW is funded by the National Institutes of Health (NIH) F30HL142131 and 5T32GM007309 grants. SGK is a recipient of a Dermatology Foundation Medical Dermatology Career Development Award and has received a research grant from the Skin of Color Society. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, Dermatology Foundation, or Skin of Color Society. We thank Susanne Churchill, Erica Meyer, and Nathan Palmer of the Department of Biomedical Informatics at Harvard Medical School (Boston, MD) for providing assistance with the claims data access.

      Author Contributions

      Conceptualization: SGK, YRS, SW; Data Curation: SW; Formal Analysis: SW; Investigation: SGK, YRS, SW; Methodology: SGK, YRS, SW; Project Administration: SGK, YRS, SW; Resources: SGK, YRS, SW; Supervision: SGK, YRS; Validation: SGK, YRS, SW; Visualization: SGK, YRS, SW; Writing – Original Draft Preparation: SW, NS, YSR, JC, DK; Writing – Review and Editing: SW, NS, KAW, AHH, JC, YSR, MH, DK, VP, WM, MPA, PB, AW, YRS, SGK

      Disclaimer

      The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

      Supplementary Materials and Methods

      Study cohort

      Unidentifiable claims data from a nationwide United States health insurance plan between October 2015 and December 2019 were analyzed. The data include deidentified medical claims, pharmacy claims, and enrollment, and demographic information.
      We defined patients with prurigo nodularis (PN) as individuals with ≥2 medical claims (on different dates) for PN using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code L28.1. For further comparison, patients with atopic dermatitis (AD) and patients with psoriasis were also identified. Patients with AD were defined as those with ≥2 medical claims (on different dates) for AD using the ICD-10-CM code L20.9. Patients with psoriasis were defined as those with ≥2 medical claims (on different dates) for psoriasis using the ICD-10-CM code L40.9. Control patients were selected as PN age- and gender-matched individuals without any ICD-10-CM codes for PN, AD, and psoriasis.
      Due to the deidentified nature of the database, the study was exempt from Institutional Review Board approval. Funding sources for this project had no role in the design and/or conduct of the study; data collection, management, and analysis; manuscript preparation, or in the decisions about submitting the manuscript for publication.

      Statistical analysis

      Period prevalence of PN, AD, and psoriasis

      The period prevalence of PN, AD, and psoriasis overall and by age groups (age <18 years and ≥18 years) was estimated annually from the claims data using the ICD-10-CM definitions for PN, AD, and psoriasis as described earlier. Demographic information, including age and gender, was determined from the enrollment ata.

      Charlson Comorbidity Index and period prevalence of comorbidities

      Comorbidity burden and the Charlson Comorbidity Index were estimated annually using ICD-9-CM and ICD-10-CM codes on the basis of previously published methodology (
      • Charlson M.
      • Szatrowski T.P.
      • Peterson J.
      • Gold J.
      Validation of a combined comorbidity index.
      ;
      • Quan H.
      • Sundararajan V.
      • Halfon P.
      • Fong A.
      • Burnand B.
      • Luthi J.C.
      • et al.
      Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.
      ). The period prevalence for the comorbidities in each group was estimated annually and is expressed as percentages.

      Utilization rates for the top specialties visited

      The claims data regarding provider specialty were used to estimate the utilization rates of the top five specialties visited for controls over the entire study period and starting at the time corresponding to the second ICD-10-CM diagnosis of patients with PN, AD, and psoriasis. The rates were calculated in units of visits per year per patient.

      Selection of controls

      Control patients without PN, AD, and psoriasis were selected with 1:5 exact matching by age and gender with patients with PN.

      Analysis software

      Analyses were conducted in R, version 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria).

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