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Risk for Appendicitis, Cholecystitis, or Diverticulitis in Patients With Psoriasis
Author(s)
Erica B. Lee, BS
Mina Amin, BS
Lewei Duan, MS
Alexander Egeberg, MD, PhD
Jashin J. Wu, MD

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,3,4 type 2 diabetes mellitus,5,6 hypertension,5 dyslipidemia,3,7 metabolic syndrome,7 atherosclerosis,8 peripheral vascular disease,9 coronary artery calcification,10 myocardial infarction,11-13 stroke,9,14 and cardiac death.15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.



The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.



Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

 

 

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.



Appendicitis
The prevalence of appendicitis was not significantly different between patients with and without psoriasis or between patients with mild and severe psoriasis, though the incidence rate was slightly higher among patients with psoriasis (0.80 per 1000 patient-years compared to 0.62 per 1000 patient-years among patients without psoriasis)(Table 1). However, there was not a significant difference in risk for appendicitis between healthy patients, patients with severe psoriasis, and patients with mild psoriasis after adjusting for potential confounding factors (Table 2). Interestingly, patients with severe psoriasis who had a diagnosis of appendicitis had a significantly shorter time to diagnosis of appendicitis compared to patients with mild psoriasis (7.4 years vs 8.1 years; P<.0001).



Cholecystitis
Psoriasis patients also did not have an increased prevalence of cholecystitis compared to healthy patients. However, patients with severe psoriasis had a significantly higher prevalence of cholecystitis compared to patients with mild psoriasis (P=.0038). Overall, patients with psoriasis had a slightly higher incidence rate (1.72 per 1000 patient-years) compared to healthy patients (1.46 per 1000 patient-years). Moreover, the time to diagnosis of cholecystitis was significantly shorter for patients with severe psoriasis than for patients with mild psoriasis (7.4 years vs 8.1 years; P<.0001). Mild psoriasis was associated with a significantly increased risk (HR, 1.33; 95% CI, 1.09-1.63; P<.01) for cholecystitis compared to individuals without psoriasis in both the crude and adjusted models (Table 2). There was no difference between mild psoriasis patients and severe psoriasis patients in risk for cholecystitis.



Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

 

 

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.19 Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,20 and psoriasis patients also might consume less whole-grain fiber.21 Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,18 which also has been supported by response to anti-inflammatory medications such as mesalazine.22 Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al23 found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.24 Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al25 hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (TH17) pathway,25 which also has been found to play a role in psoriasis pathogenesis.26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.



We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al28 found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.29 Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

References
  1. Parisi R, Symmons DP, Griffiths CE, et al; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377-385.
  2. Channual J, Wu JJ, Dann FJ. Effects of tumor necrosis factor-α blockade on metabolic syndrome in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Dermatol Ther. 2009;22:61-73.
  3. Koebnick C, Black MH, Smith N, et al. The association of psoriasis and elevated blood lipids in overweight and obese children. J Pediatr. 2011;159:577-583.
  4. Herron MD, Hinckley M, Hoffman MS, et al. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol. 2005;141:1527-1534.
  5. Qureshi AA, Choi HK, Setty AR, et al. Psoriasis and the risk of diabetes and hypertension: a prospective study of US female nurses. Arch Dermatol. 2009;145:379-382.
  6. Shapiro J, Cohen AD, David M, et al. The association between psoriasis, diabetes mellitus, and atherosclerosis in Israel: a case-control study. J Am Acad Dermatol. 2007;56:629-634.
  7. Love TJ, Qureshi AA, Karlson EW, et al. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147:419-424.
  8. El-Mongy S, Fathy H, Abdelaziz A, et al. Subclinical atherosclerosis in patients with chronic psoriasis: a potential association. J Eur Acad Dermatol Venereol. 2010;24:661-666.
  9. Prodanovich S, Kirsner RS, Kravetz JD, et al. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol. 2009;145:700-703.
  10. Ludwig RJ, Herzog C, Rostock A, et al. Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol. 2007;156:271-276.
  11. Kaye JA, Li L, Jick SS. Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis. Br J Dermatol. 2008;159:895-902.
  12. Kimball AB, Robinson D Jr, Wu Y, et al. Cardiovascular disease and risk factors among psoriasis patients in two US healthcare databases, 2001-2002. Dermatology. 2008;217:27-37.
  13. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735-1741.
  14. Gelfand JM, Dommasch ED, Shin DB, et al. The risk of stroke in patients with psoriasis. J Invest Dermatol. 2009;129:2411-2418.
  15. Mehta NN, Azfar RS, Shin DB, et al. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2010;31:1000-1006.
  16. Abuabara K, Azfar RS, Shin DB, et al. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the United Kingdom. Br J Dermatol. 2010;163:586-592.
  17. Christophers E. Comorbidities in psoriasis. Clin Dermatol. 2007;25:529-534.
  18. Wu JJ, Nguyen TU, Poon KY, et al. The association of psoriasis with autoimmune diseases. J Am Acad Dermatol. 2012;67:924-930.
  19. Floch MH, Bina I. The natural history of diverticulitis: fact and theory. Clin Gastroenterol. 2004;38(5, suppl 1):S2-S7.
  20. Barrea L, Macchia PE, Tarantino G, et al. Nutrition: a key environmental dietary factor in clinical severity and cardio-metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire. J Transl Med. 2015;13:303.
  21. Afifi L, Danesh MJ, Lee KM, et al. Dietary behaviors in psoriasis: patient-reported outcomes from a U.S. National Survey. Dermatol Ther (Heidelb). 2017;7:227-242.
  22. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
  23. Brandl A, Kratzer T, Kafka-Ritsch R, et al. Diverticulitis in immunosuppressed patients: a fatal outcome requiring a new approach? Can J Surg. 2016;59:254-261.
  24. Buckius MT, McGrath B, Monk J, et al. Changing epidemiology of acute appendicitis in the United States: study period 1993-2008. J Surg Res. 2012;175:185-190.
  25. Cheluvappa R, Luo AS, Grimm MC. T helper type 17 pathway suppression by appendicitis and appendectomy protects against colitis. Clin Exp Immunol. 2014;175:316-322.
  26. Lynde CW, Poulin Y, Vender R, et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71:141-150.
  27. Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-α, IFN-γ, IL6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005:2005;273-279.
  28. Egeberg A, Anderson YMF, Gislason GH, et al. Gallstone risk in adult patients with atopic dermatitis and psoriasis: possible effect of overweight and obesity. Acta Derm Venereol. 2017;97:627-631.
  29. Smirnova SV, Barilo AA, Smolnikova MV. Hepatobiliary system diseases as the predictors of psoriasis progression [in Russian]. Vestn Ross Akad Med Nauk. 2016:102-108.
  30. Bagel J, Lynde C, Tyring S, et al. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. J Am Acad Dermatol. 2012;67:86-92.
  31. Foeldvari I, Krüger E, Schneider T. Acute, non-obstructive, sterile cholecystitis associated with etanercept and infliximab for the treatment of juvenile polyarticular rheumatoid arthritis. Ann Rheum Dis. 2003;62:908-909.
Article PDF
CT103003175.PDF
Author and Disclosure Information

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 is 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.

Correspondence: Jashin J. Wu, MD (jashinwu@gmail.com).

Issue
Cutis - 103(3)
Publications
MDedge Dermatology
Cutis
Journal of Clinical Outcomes Management
Topics
Mixed Topics
Dermatology
Gastroenterology
Emergency Medicine
Page Number
175-179, E1-E2
Sections
Original Research
Author(s)
Erica B. Lee, BS
Mina Amin, BS
Lewei Duan, MS
Alexander Egeberg, MD, PhD
Jashin J. Wu, MD
Author(s)
Erica B. Lee, BS
Mina Amin, BS
Lewei Duan, MS
Alexander Egeberg, MD, PhD
Jashin J. Wu, MD
Author and Disclosure Information

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 is 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.

Correspondence: Jashin J. Wu, MD (jashinwu@gmail.com).

Author and Disclosure Information

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 is 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.

Correspondence: Jashin J. Wu, MD (jashinwu@gmail.com).

Article PDF
CT103003175.PDF
Article PDF
CT103003175.PDF

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,3,4 type 2 diabetes mellitus,5,6 hypertension,5 dyslipidemia,3,7 metabolic syndrome,7 atherosclerosis,8 peripheral vascular disease,9 coronary artery calcification,10 myocardial infarction,11-13 stroke,9,14 and cardiac death.15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.



The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.



Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

 

 

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.



Appendicitis
The prevalence of appendicitis was not significantly different between patients with and without psoriasis or between patients with mild and severe psoriasis, though the incidence rate was slightly higher among patients with psoriasis (0.80 per 1000 patient-years compared to 0.62 per 1000 patient-years among patients without psoriasis)(Table 1). However, there was not a significant difference in risk for appendicitis between healthy patients, patients with severe psoriasis, and patients with mild psoriasis after adjusting for potential confounding factors (Table 2). Interestingly, patients with severe psoriasis who had a diagnosis of appendicitis had a significantly shorter time to diagnosis of appendicitis compared to patients with mild psoriasis (7.4 years vs 8.1 years; P<.0001).



Cholecystitis
Psoriasis patients also did not have an increased prevalence of cholecystitis compared to healthy patients. However, patients with severe psoriasis had a significantly higher prevalence of cholecystitis compared to patients with mild psoriasis (P=.0038). Overall, patients with psoriasis had a slightly higher incidence rate (1.72 per 1000 patient-years) compared to healthy patients (1.46 per 1000 patient-years). Moreover, the time to diagnosis of cholecystitis was significantly shorter for patients with severe psoriasis than for patients with mild psoriasis (7.4 years vs 8.1 years; P<.0001). Mild psoriasis was associated with a significantly increased risk (HR, 1.33; 95% CI, 1.09-1.63; P<.01) for cholecystitis compared to individuals without psoriasis in both the crude and adjusted models (Table 2). There was no difference between mild psoriasis patients and severe psoriasis patients in risk for cholecystitis.



Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

 

 

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.19 Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,20 and psoriasis patients also might consume less whole-grain fiber.21 Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,18 which also has been supported by response to anti-inflammatory medications such as mesalazine.22 Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al23 found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.24 Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al25 hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (TH17) pathway,25 which also has been found to play a role in psoriasis pathogenesis.26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.



We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al28 found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.29 Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,3,4 type 2 diabetes mellitus,5,6 hypertension,5 dyslipidemia,3,7 metabolic syndrome,7 atherosclerosis,8 peripheral vascular disease,9 coronary artery calcification,10 myocardial infarction,11-13 stroke,9,14 and cardiac death.15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.



The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.



Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

 

 

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.



Appendicitis
The prevalence of appendicitis was not significantly different between patients with and without psoriasis or between patients with mild and severe psoriasis, though the incidence rate was slightly higher among patients with psoriasis (0.80 per 1000 patient-years compared to 0.62 per 1000 patient-years among patients without psoriasis)(Table 1). However, there was not a significant difference in risk for appendicitis between healthy patients, patients with severe psoriasis, and patients with mild psoriasis after adjusting for potential confounding factors (Table 2). Interestingly, patients with severe psoriasis who had a diagnosis of appendicitis had a significantly shorter time to diagnosis of appendicitis compared to patients with mild psoriasis (7.4 years vs 8.1 years; P<.0001).



Cholecystitis
Psoriasis patients also did not have an increased prevalence of cholecystitis compared to healthy patients. However, patients with severe psoriasis had a significantly higher prevalence of cholecystitis compared to patients with mild psoriasis (P=.0038). Overall, patients with psoriasis had a slightly higher incidence rate (1.72 per 1000 patient-years) compared to healthy patients (1.46 per 1000 patient-years). Moreover, the time to diagnosis of cholecystitis was significantly shorter for patients with severe psoriasis than for patients with mild psoriasis (7.4 years vs 8.1 years; P<.0001). Mild psoriasis was associated with a significantly increased risk (HR, 1.33; 95% CI, 1.09-1.63; P<.01) for cholecystitis compared to individuals without psoriasis in both the crude and adjusted models (Table 2). There was no difference between mild psoriasis patients and severe psoriasis patients in risk for cholecystitis.



Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

 

 

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.19 Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,20 and psoriasis patients also might consume less whole-grain fiber.21 Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,18 which also has been supported by response to anti-inflammatory medications such as mesalazine.22 Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al23 found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.24 Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al25 hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (TH17) pathway,25 which also has been found to play a role in psoriasis pathogenesis.26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.



We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al28 found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.29 Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

References
  1. Parisi R, Symmons DP, Griffiths CE, et al; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377-385.
  2. Channual J, Wu JJ, Dann FJ. Effects of tumor necrosis factor-α blockade on metabolic syndrome in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Dermatol Ther. 2009;22:61-73.
  3. Koebnick C, Black MH, Smith N, et al. The association of psoriasis and elevated blood lipids in overweight and obese children. J Pediatr. 2011;159:577-583.
  4. Herron MD, Hinckley M, Hoffman MS, et al. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol. 2005;141:1527-1534.
  5. Qureshi AA, Choi HK, Setty AR, et al. Psoriasis and the risk of diabetes and hypertension: a prospective study of US female nurses. Arch Dermatol. 2009;145:379-382.
  6. Shapiro J, Cohen AD, David M, et al. The association between psoriasis, diabetes mellitus, and atherosclerosis in Israel: a case-control study. J Am Acad Dermatol. 2007;56:629-634.
  7. Love TJ, Qureshi AA, Karlson EW, et al. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147:419-424.
  8. El-Mongy S, Fathy H, Abdelaziz A, et al. Subclinical atherosclerosis in patients with chronic psoriasis: a potential association. J Eur Acad Dermatol Venereol. 2010;24:661-666.
  9. Prodanovich S, Kirsner RS, Kravetz JD, et al. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol. 2009;145:700-703.
  10. Ludwig RJ, Herzog C, Rostock A, et al. Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol. 2007;156:271-276.
  11. Kaye JA, Li L, Jick SS. Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis. Br J Dermatol. 2008;159:895-902.
  12. Kimball AB, Robinson D Jr, Wu Y, et al. Cardiovascular disease and risk factors among psoriasis patients in two US healthcare databases, 2001-2002. Dermatology. 2008;217:27-37.
  13. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735-1741.
  14. Gelfand JM, Dommasch ED, Shin DB, et al. The risk of stroke in patients with psoriasis. J Invest Dermatol. 2009;129:2411-2418.
  15. Mehta NN, Azfar RS, Shin DB, et al. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2010;31:1000-1006.
  16. Abuabara K, Azfar RS, Shin DB, et al. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the United Kingdom. Br J Dermatol. 2010;163:586-592.
  17. Christophers E. Comorbidities in psoriasis. Clin Dermatol. 2007;25:529-534.
  18. Wu JJ, Nguyen TU, Poon KY, et al. The association of psoriasis with autoimmune diseases. J Am Acad Dermatol. 2012;67:924-930.
  19. Floch MH, Bina I. The natural history of diverticulitis: fact and theory. Clin Gastroenterol. 2004;38(5, suppl 1):S2-S7.
  20. Barrea L, Macchia PE, Tarantino G, et al. Nutrition: a key environmental dietary factor in clinical severity and cardio-metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire. J Transl Med. 2015;13:303.
  21. Afifi L, Danesh MJ, Lee KM, et al. Dietary behaviors in psoriasis: patient-reported outcomes from a U.S. National Survey. Dermatol Ther (Heidelb). 2017;7:227-242.
  22. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
  23. Brandl A, Kratzer T, Kafka-Ritsch R, et al. Diverticulitis in immunosuppressed patients: a fatal outcome requiring a new approach? Can J Surg. 2016;59:254-261.
  24. Buckius MT, McGrath B, Monk J, et al. Changing epidemiology of acute appendicitis in the United States: study period 1993-2008. J Surg Res. 2012;175:185-190.
  25. Cheluvappa R, Luo AS, Grimm MC. T helper type 17 pathway suppression by appendicitis and appendectomy protects against colitis. Clin Exp Immunol. 2014;175:316-322.
  26. Lynde CW, Poulin Y, Vender R, et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71:141-150.
  27. Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-α, IFN-γ, IL6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005:2005;273-279.
  28. Egeberg A, Anderson YMF, Gislason GH, et al. Gallstone risk in adult patients with atopic dermatitis and psoriasis: possible effect of overweight and obesity. Acta Derm Venereol. 2017;97:627-631.
  29. Smirnova SV, Barilo AA, Smolnikova MV. Hepatobiliary system diseases as the predictors of psoriasis progression [in Russian]. Vestn Ross Akad Med Nauk. 2016:102-108.
  30. Bagel J, Lynde C, Tyring S, et al. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. J Am Acad Dermatol. 2012;67:86-92.
  31. Foeldvari I, Krüger E, Schneider T. Acute, non-obstructive, sterile cholecystitis associated with etanercept and infliximab for the treatment of juvenile polyarticular rheumatoid arthritis. Ann Rheum Dis. 2003;62:908-909.
References
  1. Parisi R, Symmons DP, Griffiths CE, et al; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377-385.
  2. Channual J, Wu JJ, Dann FJ. Effects of tumor necrosis factor-α blockade on metabolic syndrome in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Dermatol Ther. 2009;22:61-73.
  3. Koebnick C, Black MH, Smith N, et al. The association of psoriasis and elevated blood lipids in overweight and obese children. J Pediatr. 2011;159:577-583.
  4. Herron MD, Hinckley M, Hoffman MS, et al. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol. 2005;141:1527-1534.
  5. Qureshi AA, Choi HK, Setty AR, et al. Psoriasis and the risk of diabetes and hypertension: a prospective study of US female nurses. Arch Dermatol. 2009;145:379-382.
  6. Shapiro J, Cohen AD, David M, et al. The association between psoriasis, diabetes mellitus, and atherosclerosis in Israel: a case-control study. J Am Acad Dermatol. 2007;56:629-634.
  7. Love TJ, Qureshi AA, Karlson EW, et al. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147:419-424.
  8. El-Mongy S, Fathy H, Abdelaziz A, et al. Subclinical atherosclerosis in patients with chronic psoriasis: a potential association. J Eur Acad Dermatol Venereol. 2010;24:661-666.
  9. Prodanovich S, Kirsner RS, Kravetz JD, et al. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol. 2009;145:700-703.
  10. Ludwig RJ, Herzog C, Rostock A, et al. Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol. 2007;156:271-276.
  11. Kaye JA, Li L, Jick SS. Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis. Br J Dermatol. 2008;159:895-902.
  12. Kimball AB, Robinson D Jr, Wu Y, et al. Cardiovascular disease and risk factors among psoriasis patients in two US healthcare databases, 2001-2002. Dermatology. 2008;217:27-37.
  13. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735-1741.
  14. Gelfand JM, Dommasch ED, Shin DB, et al. The risk of stroke in patients with psoriasis. J Invest Dermatol. 2009;129:2411-2418.
  15. Mehta NN, Azfar RS, Shin DB, et al. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2010;31:1000-1006.
  16. Abuabara K, Azfar RS, Shin DB, et al. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the United Kingdom. Br J Dermatol. 2010;163:586-592.
  17. Christophers E. Comorbidities in psoriasis. Clin Dermatol. 2007;25:529-534.
  18. Wu JJ, Nguyen TU, Poon KY, et al. The association of psoriasis with autoimmune diseases. J Am Acad Dermatol. 2012;67:924-930.
  19. Floch MH, Bina I. The natural history of diverticulitis: fact and theory. Clin Gastroenterol. 2004;38(5, suppl 1):S2-S7.
  20. Barrea L, Macchia PE, Tarantino G, et al. Nutrition: a key environmental dietary factor in clinical severity and cardio-metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire. J Transl Med. 2015;13:303.
  21. Afifi L, Danesh MJ, Lee KM, et al. Dietary behaviors in psoriasis: patient-reported outcomes from a U.S. National Survey. Dermatol Ther (Heidelb). 2017;7:227-242.
  22. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
  23. Brandl A, Kratzer T, Kafka-Ritsch R, et al. Diverticulitis in immunosuppressed patients: a fatal outcome requiring a new approach? Can J Surg. 2016;59:254-261.
  24. Buckius MT, McGrath B, Monk J, et al. Changing epidemiology of acute appendicitis in the United States: study period 1993-2008. J Surg Res. 2012;175:185-190.
  25. Cheluvappa R, Luo AS, Grimm MC. T helper type 17 pathway suppression by appendicitis and appendectomy protects against colitis. Clin Exp Immunol. 2014;175:316-322.
  26. Lynde CW, Poulin Y, Vender R, et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71:141-150.
  27. Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-α, IFN-γ, IL6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005:2005;273-279.
  28. Egeberg A, Anderson YMF, Gislason GH, et al. Gallstone risk in adult patients with atopic dermatitis and psoriasis: possible effect of overweight and obesity. Acta Derm Venereol. 2017;97:627-631.
  29. Smirnova SV, Barilo AA, Smolnikova MV. Hepatobiliary system diseases as the predictors of psoriasis progression [in Russian]. Vestn Ross Akad Med Nauk. 2016:102-108.
  30. Bagel J, Lynde C, Tyring S, et al. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. J Am Acad Dermatol. 2012;67:86-92.
  31. Foeldvari I, Krüger E, Schneider T. Acute, non-obstructive, sterile cholecystitis associated with etanercept and infliximab for the treatment of juvenile polyarticular rheumatoid arthritis. Ann Rheum Dis. 2003;62:908-909.
Issue
Cutis - 103(3)
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Cutis - 103(3)
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175-179, E1-E2
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175-179, E1-E2
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MDedge Dermatology
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Journal of Clinical Outcomes Management
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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
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Practice Points

  • Patients with psoriasis may have elevated risk of diverticulitis compared to healthy patients. However, psoriasis patients do not appear to have increased risk of appendicitis or cholecystitis.
  • Clinicians treating psoriasis patients should consider assessing for other risk factors of diverticulitis at regular intervals.
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