Association between prurigo nodularis and malignancy in middle-aged adults

Abstract

To the Editor: Prurigo nodularis (PN) is an extremely pruritic, inflammatory skin disease associated with multiple underlying comorbidities.1Boozalis E. Tang O. Patel S. et al.Ethnic differences and comorbidities of 909 prurigo nodularis patients.J Am Acad Dermatol. 2018; (pii: S0190(18):30655-30658)Google Scholar Case reports have noted an association between PN and malignancies, including lymphoma2Schweda K. Hainz M. Loquai C. Grabbe S. Saloga J. Tuettenberg A. Prurigo nodularis as index symptom of (non-Hodgkin) lymphoma: ultrasound as a helpful diagnostic tool in dermatological disorders of unknown origin.Int J Dermatol. 2015; 54: 462-464Crossref PubMed Scopus (7) Google Scholar, 3Rubenstein M. Duvic M. Cutaneous manifestations of Hodgkin's disease.Int J Dermatol. 2006; 45: 251-256Crossref PubMed Scopus (82) Google Scholar and solid organ tumors.4Funaki M. Ohno T. Dekio S. et al.Prurigo nodularis associated with advanced gastric cancer: report of a case.J Dermatol. 1996; 23: 703-707Google Scholar The goal of this cross-sectional study was to evaluate an association between PN and a variety of malignancies in a diverse patient population. Institutional review board approval was waived for this study because only anonymous aggregate-level data were used. The study population consisted of 695 patients aged 40-69 years who presented to the Johns Hopkins Health System during 2013-2017 with a PN diagnosis. They were compared with 2,446,880 control patients also aged 40-69 years (Table I) because this age range is the peak for PN occurrence.1Boozalis E. Tang O. Patel S. et al.Ethnic differences and comorbidities of 909 prurigo nodularis patients.J Am Acad Dermatol. 2018; (pii: S0190(18):30655-30658)Google Scholar Patients with a diagnosed malignancy were identified within the PN and control groups, and odds ratios (ORs) were calculated. P values were calculated by using χ2 statistics with 1 degree of freedom. A Bonferroni correction was applied (alpha = 0.002). For malignancies of the genital tracts, only patients of the relevant sex were included.Table IDemographic characteristics of the PN group and comparison group without PNCharacteristicPN group, n = 695, %Control group, n = 2,454,685, %Sex Male48.3545.42 Female51.6554.58Race White, Caucasian41.4460.98 Black, African American51.3722.13 Asian2.593.81 American Indian or Alaskan native0.140.21 Native Hawaiian, other Pacific Islander0.140.05 Other4.326.31 Unknown1.158.13 Declined to answer0.140.21Age, y 40-4925.6132.85 50-5944.9336.34 60-6929.4630.80In total, 695 patients aged 40-69 years who presented to Johns Hopkins Health System during April 2013-December 2017 with a visit diagnosis, billing diagnosis, or active problem list entry of PN were identified. The comparison population was 2,446,880 patients aged 40-69 years without a diagnosis of PN.PN, Prurigo nodularis. Open table in a new tab In total, 695 patients aged 40-69 years who presented to Johns Hopkins Health System during April 2013-December 2017 with a visit diagnosis, billing diagnosis, or active problem list entry of PN were identified. The comparison population was 2,446,880 patients aged 40-69 years without a diagnosis of PN. PN, Prurigo nodularis. Of the 695 patients with PN, 124 had a concomitant diagnosis of malignancy during the study period (Fig 1, A). Patients with PN were >4 times more likely than controls to have a malignancy diagnosis (OR 4.54, 95% confidence interval [CI] 3.74-5.52). PN was significantly associated with cancers of the skin (OR 10.94, 95% CI 8.01-14.96), hematopoietic system (OR 5.41, 95% CI 3.39-8.64), and solid organs (OR 3.44, 95% CI 2.34-5.06) (Fig 1, B). Among the hematologic malignancies, PN was most strongly associated with primary cutaneous lymphoma (OR 24.82, 95% CI 7.96-77.46), multiple myeloma (OR 6.55, 95% CI 2.45-17.51), and non-Hodgkin lymphoma (OR 5.66, 95% CI 2.82-11.38). Among solid organ malignancies, PN was most strongly associated with cancers of the female genital organs (OR 11.00, 95% CI 4.90-24.68), gastrointestinal tract (OR 5.08, 95% CI 2.11-12.26), and lung (OR 4.63, 95% CI 1.92-11.16). There are several limitations to this study. There might be a selection bias for the detection of dermatologic malignancies because PN patients are more likely to be under the care of dermatologists. Also, we cannot draw conclusions about the causal relationship between PN and malignancy from these data. However, case reports have shown that PN can improve with cancer treatment,2Schweda K. Hainz M. Loquai C. Grabbe S. Saloga J. Tuettenberg A. Prurigo nodularis as index symptom of (non-Hodgkin) lymphoma: ultrasound as a helpful diagnostic tool in dermatological disorders of unknown origin.Int J Dermatol. 2015; 54: 462-464Crossref PubMed Scopus (7) Google Scholar, 3Rubenstein M. Duvic M. Cutaneous manifestations of Hodgkin's disease.Int J Dermatol. 2006; 45: 251-256Crossref PubMed Scopus (82) Google Scholar, 4Funaki M. Ohno T. Dekio S. et al.Prurigo nodularis associated with advanced gastric cancer: report of a case.J Dermatol. 1996; 23: 703-707Google Scholar suggesting that PN might be downstream. In the case of hematologic malignancies, PN might be the result of inflammatory infiltration of the skin, leading to pruritus and excoriation. The mechanisms by which other malignancies predispose patients to PN remain unclear but might be related to systemic inflammatory states. We conclude that PN might be associated with a wide variety of malignancies. The time course of the association and the risk-to-benefit ratio of cancer screening in this patient population requires further investigation, but cohort studies of generalized pruritus have suggested that the risk of cancer diagnosis is highest in the first 3 months after onset.5Johannesdottir S.A. Farkas D.K. Vinding G.R. et al.Cancer incidence among patients with a hospital diagnosis of pruritus: a nationwide Danish cohort study.Br J Dermatol. 2014; 171: 839-846Google Scholar At minimum, clinicians caring for PN patients should be vigilant for signs or symptoms suggestive of malignancy and ensure that these patients receive all recommended age-appropriate cancer screening.