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Background: Prurigo nodularis (PN) is a poorly understood, understudied pruritic dermatosis that reduces quality of life., Objective: To characterize the demographics and comorbidities associated with PN., Methods: Cross-sectional study of patients 18 years and older who were seen at the Johns Hopkins Health System between December 6, 2012, and December 6, 2017., Results: Over the past 5 years, 909 patients with PN were seen at Johns Hopkins Health System. African American patients were 3.4 times more likely to have PN than white patients were (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.9-3.9; P < .001). A comparison of the study patients and race-matched controls revealed that PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities, including chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis. Black patients with PN were 10.5 times more likely (OR, 10.5; 95% CI, 7.9-13.9; P < .001) to have HIV than were race-matched controls with atopic dermatitis, and 8 times more likely (OR, 8.0; 95% CI, 5.7-11.1; P < .001) to have HIV than were African American patients with psoriasis., Limitations: Our data describe patients seen by 1 hospital system. Our data identify associated conditions and comorbidities but are unable to support a causal relationship., Conclusion: PN disproportionately affects African Americans and is associated with several systemic conditions, including HIV, chronic kidney disease, and diabetes., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)