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Risk for Appendicitis, Cholecystitis, Or Diverticulitis in Patients with Psoriasis

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Risk for Appendicitis, Cholecystitis, Or Diverticulitis in Patients with Psoriasis ORIGINAL RESEARCH Risk for Appendicitis, Cholecystitis, or Diverticulitis in Patients With Psoriasis Erica B. Lee, BS; Mina Amin, BS; Lewei Duan, MS; Alexander Egeberg, MD, PhD; Jashin J. Wu, MD soriasis is a chronic skin condition affecting approx- PRACTICE POINTS imately 2% to 3% of the population.1,2 Beyond • Patients with psoriasis may have elevated risk of P cutaneous manifestations, psoriasis is a systemic diverticulitis compared to healthy patients. However, copy inflammatory state that is associated with an increased psoriasis patients do not appear to have increased risk for cardiovascular disease, including obesity,3,4 type 2 risk of appendicitis or cholecystitis. diabetes mellitus,5,6 hypertension,5 dyslipidemia,3,7 meta- • Clinicians treating psoriasis patients should consider bolic syndrome,7 atherosclerosis,8 peripheral vascular assessing for other risk factors of diverticulitis at disease,9 coronary artery calcification,10 myocardial infarc- regular intervals. tion,11-13 stroke,9,14 and cardiac death.15,16 Psoriasis also has been associated with inflammatory bowel notdisease (IBD), possibly because of similar auto- Numerous comorbidities have been associated with psoriasis; immune mechanisms in the pathogenesis of both dis- however, no studies have considered the relationship between eases.17,18 However, there is no literature regarding the risk psoriasis and appendicitis, cholecystitis, or diverticulitis. To deter- for acute gastrointestinal pathologies such as appendicitis, mine the incidence rate and hazard risk (HR) ratio of appendicitis, cholecystitis, or diverticulitis in patients with psoriasis. cholecystitis, or diverticulitis in patients with psoriasis, we com- pared psoriasis patients with healthy controls from the Kaiser The primary objective of this study was to examine if Permanente Southern California (KPSC) health network.Do The Cox patients with psoriasis are at increased risk for appendici- proportional hazards regression model was used to examine the tis, cholecystitis, or diverticulitis compared to the general risk for appendicitis, cholecystitis, or diverticulitis. Patients with population. The secondary objective was to determine if psoriasis had a 1.16 times greater risk for developing diverticulitis patients with severe psoriasis (ie, patients treated with compared to controls (P<.01). There was no significant differ- phototherapy or systemic therapy) are at a higher risk for ence in risk for developing appendicitis or cholecystitis. Patients these conditions compared to patients with mild psoriasis. with psoriasis may have an elevated risk for diverticulitis compared to the general population and therefore might require additional monitoring by clinicians. Methods Cutis. 2019;103:175-179. Patients and Tools—A descriptive, population-based cohort study design with controls from a matched cohort Ms. Lee is from the John A. Burns School of Medicine, University of Hawaii, Honolulu. Ms. Amin is from the School of Medicine, University of California, Riverside. Ms. Duan is from the Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena. Dr. Egeberg isCUTIS from the Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Denmark. Dr. Wu is from the Dermatology Research and Education Foundation, Irvine, California. This research was supported by grant KP-RRC-20170505 from the Regional Research Committee of Kaiser Permanente Southern California. Ms. Lee, Ms. Amin, and Ms. Duan report no conflict of interest. Dr. Egeberg has received research funding from the Danish National Psoriasis Foundation, Eli Lilly and Company, Kongelig Hofbundtmager Aage Bang Foundation, and Pfizer Inc. He also is a consultant and/or speaker for Almirall; Eli Lilly and Company; Galderma Laboratories, LP; Janssen Pharmaceuticals; LEO Pharma; Novartis; Pfizer Inc; and Samsung Bioepis Co, Ltd. Dr. Wu is an investigator for AbbVie, Amgen Inc, Eli Lilly and Company, Janssen Pharmaceuticals, and Novartis. He also is a consultant for AbbVie; Almirall; Amgen Inc; Bristol-Myers Squibb; Celgene Corporation; Dermira Inc; Dr. Reddy’s Laboratories Ltd; Eli Lilly and Company; Janssen Pharmaceuticals; LEO Pharma; Novartis; Ortho Dermatologics; Promius Pharma; Regeneron Pharmaceuticals, Inc; Sun Pharmaceutical Industries, Ltd; and UCB. He also is a speaker for Celgene Corporation; Novartis; Sun Pharmaceutical Industries, Ltd; and UCB. The eTable is available in the Appendix online at www.mdedge.com/dermatology. Correspondence: Jashin J. Wu, MD ([email protected]). WWW.MDEDGE.COM/DERMATOLOGY VOL. 103 NO. 3 I MARCH 2019 175 Copyright Cutis 2019. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. GASTROINTESTINAL RISKS OF PSORIASIS was used to ascertain the effect of psoriasis status on Results were presented as crude (unadjusted) hazard patients’ risk for appendicitis, cholecystitis, or diverticulitis. ratios (HRs) and adjusted HRs, where confounding factors Our cohort was selected using administrative data (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, from Kaiser Permanente Southern California (KPSC) smoking status, income, education, and membership length) during the study period (January 1, 2004, through were adjusted. All tests were performed with SAS EG 5.1 December 31, 2016). and R software. P<.05 was considered statistically sig- Kaiser Permanente Southern California is a large nificant. Results are reported with the 95% confidence integrated health maintenance organization that includes interval (CI), when appropriate. approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. Results The geographic area served extends from Bakersfield in A total of 1,690,214 KPSC patients were eligible for the the lower California Central Valley to San Diego on the study; 10,307 (0.6%) met diagnostic and inclusion crite- border with Mexico. Membership demographics, socio- ria for the psoriasis cohort. Patients with psoriasis had a economic status, and ethnicity composition are represen- significantly higher mean BMI (29.9 vs 28.7; P<.0001) as tative of California. well as higher mean rates of alcohol use (56% vs 53%; Patients were included if they had a diagnosis of P<.0001) and smoking (47% vs 38%; P<.01) compared psoriasis (International Classification of Diseases, Ninth to controls. Psoriasis patients had a shorter average dura- Revision, Clinical Modification [ICD-9-CM] code 696.1; tion of membership within the Kaiser network (P=.0001) International Classification of Diseases, Tenth Revision, compared to controls. Clinical Modification [ICD-10-CM] codes L40.0, A total of 7416 patientscopy met criteria for mild pso- L40.4, L40.8, or L40.9) for at least 3 visits between riasis and 2891 patients met criteria for severe psoriasis January 1, 2004, and December 31, 2016. Patients were (eTable). Patients with severe psoriasis were significantly not excluded if they also had a diagnosis of psori- younger and had significantly higher mean BMI com- atic arthritis (ICD-9-CM code 696.0; ICD-10-CM code pared to patients with mild psoriasis (P<.0001 and L40.5x). Patients also must have been continuously P=.0001, respectively). No significant difference in rates of enrolled for at least 1 year before and 1 year after the alcohol or tobacco use was detected among patients with index date, which was defined as the date of the third mild and severe psoriasis. psoriasis diagnosis. Appendicitisnot—The prevalence of appendicitis was Each patient with psoriasis was assigned to 1 of not significantly different between patients with and with- 2 cohorts: (1) severe psoriasis: patients who received out psoriasis or between patients with mild and severe UVB phototherapy, psoralen plus UVA phototherapy, psoriasis, though the incidence rate was slightly higher methotrexate, acitretin, cyclosporine, apremilast, etaner- among patients with psoriasis (0.80 per 1000 patient-years cept, adalimumab, infliximab, ustekinumab, efalizumab, compared to 0.62 per 1000 patient-years among patients alefacept, secukinumab, or ixekizumab during theDo study without psoriasis)(Table 1). However, there was not a period; and (2) mild psoriasis: patients who had a diagno- significant difference in risk for appendicitis between sis of psoriasis who did not receive one of these therapies healthy patients, patients with severe psoriasis, and during the study period. patients with mild psoriasis after adjusting for potential Patients were excluded if they had a history of confounding factors (Table 2). Interestingly, patients with appendicitis, cholecystitis, or diverticulitis at any time severe psoriasis who had a diagnosis of appendicitis had before the index date. Only patients older than 18 years a significantly shorter time to diagnosis of appendicitis were included. compared to patients with mild psoriasis (7.4 years vs Patients with psoriasis were frequency matched (1:5) 8.1 years; P<.0001). with healthy patients, also from the KPSC network. Cholecystitis—Psoriasis patients also did not have Individuals were matched by age, sex, and ethnicity. an increased prevalence of cholecystitis compared Statistical Analysis—Baseline characteristics were to healthy patients. However, patients with severe described with means and SD for continuous variables as psoriasis had a significantly higher prevalence of cho- well as percentagesCUTIS for categorical variables. Chi-square lecystitis
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