The prevalence of metabolic syndrome in patients with hidradenitis suppurativa Daniel A. Gold,a Virginia J. Reeder, MD,a Meredith G. Mahan, MS,b and Iltefat H. Hamzavi, MDa Detroit, Michigan Background: Metabolic syndrome is a multifaceted disorder strongly associated with increased risk for development of cardiovascular disease. Chronic inflammatory diseases have been associated with metabolic syndrome. Hidradenitis suppurativa is a chronic inflammatory skin disease with significant physical and emotional sequelae. Objective: We sought to investigate a possible association between hidradenitis suppurativa and metabolic syndrome. Methods: A retrospective chart review of all dermatology clinic encounters over an 18-month period identified 366 patients with an appropriate diagnosis of hidradenitis suppurativa. A control population was created from patients seen in the same clinic during the same time period for the diagnoses of either keloids or verruca vulgaris using the matching criteria of age 65 years, race, and gender. All participants were examined for characteristics of the metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Program III guidelines. Results: The prevalence of metabolic syndrome in patients with hidradenitis suppurativa was 50.6%, which was significantly higher than the control group at 30.2% (P \ .001). Limitations: This was a retrospective review. Some participants could not be analyzed for metabolic syndrome presence as a result of missing data points. Conclusion: Our results indicate that patients with hidradenitis suppurativa may be at high risk for metabolic syndrome. ( J Am Acad Dermatol 2014;70:699-703.) Key words: acne inversa; dyslipidemia; glucose intolerance; hidradenitis suppurativa; hypertension; metabolic syndrome; obesity; Velpeau disease; Verneuil disease.
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etabolic syndrome is a multifaceted disorder associated with inflammation. It encompasses issues with obesity, dyslipidemia, hyperglycemia, and hypertension and is correlated with an increased risk for the development of cardiovascular disease.1 Individuals with National Cholesterol Education Programedefined metabolic syndrome are 2.9 times more likely to die
From the Departments of Dermatologya and Public Health Sciences,b Henry Ford Medical Center. The Henry Ford Medical Center Department of Dermatology receives support from and this study was funded by the Livingood Fund and Rodzik Fund, neither of which had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Disclosure: Dr Hamzavi has served and/or currently serves as an investigator in clinical trial activities for the following companies: Galderma, ViroXis, Abbvie, La RocheePosay, Dow, Centocor, Amgen, Clinuvel, and Pfizer. Dr Hamzavi also serves
Abbreviations used: CI: HDL: IL:
confidence interval high-density lipoprotein interleukin
from all causes. This includes heart disease.2 Studies have found that the prevalence of metabolic as a consultant for COMBE. Mr Gold, Dr Reeder, and Ms Mahan have no conflicts of interest to declare. Accepted for publication November 9, 2013. Reprint requests: Iltefat H. Hamzavi, MD, Department of Dermatology, Henry Ford Medical Center, 3031 W Grand Blvd, Suite 800, Detroit, MI 48202. E-mail: [email protected]. Published online January 16, 2014. 0190-9622/$36.00 Ó 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.11.014
699
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syndrome in the general population is 15% to 34%.3-5 determined by physician observation. A control Chronic inflammatory diseases, including psoriasis population was created using patients seen in the and rheumatoid arthritis, have been associated with dermatology clinic during the same time period for metabolic syndrome.6,7 Hidradenitis suppurativa is a the diagnoses of either keloids or verruca vulgaris chronic inflammatory skin disease with physical and using the matching criteria of age 65 years, race, and emotional sequelae. Inflammatory nodules and gender. Ethnicity for the control population was draining sinuses develop in intertriginous areas and based on patient and support staff report. Metabolic result in pain, chronic syndrome was defined using drainage, and scarring. The the National Cholesterol CAPSULE SUMMARY condition is more common in Education Program Adult women than in men and has Treatment Panel III criteria14 There is an association between chronic previously been found to be including: high-density lipoinflammatory processes and metabolic strongly associated with protein (HDL) of less than or syndrome. obesity and smoking toequal to 40 mg/dL in males Hidradenitis suppurativa may also be bacco.8-10 In addition, there and less than or equal to 50 associated with the metabolic syndrome, mg/dL in females, hypertriwas an association between which may affect cardiovascular risk glyceridemia greater than or more severe hidradenitis profiles of these patients. equal to 150 mg/dL, blood suppurativa and obese pressure of greater than or women compared with In addition to treating the skin, health equal to 130/85 mm Hg or a women of normal weight.10 care practitioners should screen patients history of hypertension The highest prevalence of with hidradenitis suppurativa for noted by a physician in the hidradenitis suppurativa is metabolic syndrome. patient chart, and hyperglyin those aged 18 to 44 cemia of greater than or years.11 One small study has equal to 110 mg/dL fasting or a history of glucose previously looked for an association between intolerance noted by a physician in the patient chart. metabolic syndrome and hidradenitis suppurativa. Obesity was defined as body mass index 30 or higher This hospital-based study involved 80 patients with or a notation by a physician that the patient was hidradenitis suppurativa and showed an increased obese. Patients were classified as having metabolic prevalence of metabolic syndrome of 40% in patients syndrome if they had a minimum of 3 of the 5 above with hidradenitis suppurativa versus 13% in control criteria. subjects.12 This study focused on inpatients who tend to have more comorbidities and have increased disease severity. The aim of our study was to RESULTS further investigate the association of metabolic and The data consist of 366 cases and 366 controls physiologic alterations in patients with hidradenitis matched on age 65 years, sex, and race. If a patient suppurativa and to determine the prevalence of was missing data on 3 or more of these factors, metabolic syndrome in this population. they were excluded from the analysis. Among all 738 patients, 465 (243 patients with hidradenitis suppurativa and 222 control subjects) had enough METHODS data to determine the presence or absence of This study was approved by the Henry Ford metabolic syndrome, which was defined as having Hospital Institutional Review Board. A retrospective 3 or more of the following: obesity, hypertriglycerchart review of 39,055 total encounters in the idemia, low HDL, diabetes mellitus, and hypertendermatology clinic from January 1, 2011, to May 31, sion. All categorical data are described as count and 2012, was performed. Charts of patients with the column percentages, and continuous data as mean, International Classification of Diseases, Ninth SD, median, minimum, and maximum. Of the 243 Revision diagnostic code associated with hidradenipatients with hidradenitis suppurativa evaluated, tis suppurativa were included. In all, 366 patients 79.8% were female and 20.2% were male. The age with an appropriate diagnosis of hidradenitis supof patients with hidradenitis suppurativa ranged purativa were identified and included in this from 9 to 92 years. The mean age was 41.9 years review. Patients were given a diagnosis of hidradeand the median was 42 years. Of the study particinitis suppurativa by dermatologists based on pants, 65.0% were African American, 18.9% were clinical presentation, including a history of recurrent Caucasian, and the remaining 16.1% were classified inflammatory nodules, sterile abscesses, and drainas ‘‘other’’ (Table I). A significantly higher proportion ing sinuses. Severity of the disease was classified of the patients with hidradenitis suppurativa were using the Hurley staging system.13 Ethnicity was d
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Table I. Characteristics of patients with hidradenitis suppurativa and control subjects with enough nonmissing data for analysis Variable
Age
Race
Sex Metabolic syndrome
Response
Mean (SD) Median (minimum, maximum) Caucasian African American Other Female Male No Yes
Patients with HS (N = 243)
Control subjects (N = 222)
41.9 (16.1) 42 (9, 92)
44.6 (15.3) 44 (14, 90)
46 158 39 194 49 120 123
55 133 34 172 50 155 67
(18.9%) (65.0%) (16.1%) (79.8%) (20.2%) (49.4%) (50.6%)
(24.8%) (59.9%) (15.3%) (77.5%) (22.5%) (69.7%) (30.2%)
OR (95% CI) (patients with HS vs control subjects)
(reference) 2.37 (1.62-3.47)
P value
\.001
CI, Confidence interval; HS, hidradenitis suppurativa; OR, odds ratio.
found to have metabolic syndrome as compared with the control subjects (50.6% and 30.2%, respectively, P \ .001), odds ratio 2.37 (95% confidence intervals [CI] 1.62-3.47) (Table I). There was not, however, a significant association between hidradenitis suppurativa disease severity and the prevalence of metabolic syndrome (Table II). Of patients with hidradenitis suppurativa, 87.6% were found to be obese whereas only 66.4% of the control subjects met this criterion (P \.001). There was also a significantly higher percentage of patients with hidradenitis suppurativa at 43.8% versus control subjects at 28.4% who were noted to have hypertriglyceridemia (P \ .001). Of patients with hidradenitis suppurativa, 48.3%, as compared with 28.4% of control subjects, were noted to have glucose intolerance (P \ .001) (Table III). There was not a significant difference between patients with hidradenitis suppurativa and control subjects in the prevalence of hypertension or low HDL. The odds ratio indicate that the patients with hidradenitis suppurativa were 3.6 (95% CI 2.2-5.6) times more likely to be obese, 2.4 (95% CI 1.6-3.6) times more likely to have hypertriglyceridemia, and 2.0 (95% CI 1.3-2.9) times more likely to have glucose intolerance as the control subjects. There were no significant associations noted between prevalence of metabolic syndrome or disease severity with either race or gender. Obesity was not associated with more severe disease. The x2 tests are used to compare proportions. Wilcoxon 2-sample tests and KruskalWallis tests were used to compare age between severity groups and metabolic syndrome groups. When comparing the proportion of patients with metabolic syndrome by age quartiles, Hochberg method was used to adjust the P value as multiple pairwise comparisons were done. Univariate logistic regression models were used to obtain odds ratio
Table II. Metabolic syndrome and hidradenitis suppurativa disease severity as quantified by Hurley stage Severity, Hurley stage
I II III
No metabolic syndrome (N = 120)
43 (35.8%) 57 (47.5%) 20 (16.7%)
Metabolic syndrome (N = 124)
OR (95% CI)
44 (35.5%) (reference) 49 (39.5%) 0.84 (0.48-1.48) 31 (25.0%) 1.52 (0.75-3.06)
P value
.232
CI, Confidence interval; OR, odds ratio.
and 95% CI. Statistical significance was set at P less than .05. The data analysis for this article was generated using software (SAS/STAT, Version 9.2, SAS Institute Inc, Cary, NC).
DISCUSSION Associations between other disorders known to be associated with increased inflammation, such as psoriasis and rheumatoid arthritis, and metabolic syndrome have previously been investigated and are well documented.15-24 The link between psoriasis and metabolic syndrome has been particularly well established.15-17 This disease association appears to increase in a dose-responsive manner with the prevalence of metabolic syndrome increased in proportion to the severity of psoriasis.18,19 Studies looking for an increased prevalence of metabolic syndrome in patients with rheumatoid arthritis have been inconclusive.20-23 The presence of metabolic syndrome in patients with rheumatoid arthritis is, however, associated with poorer disease prognosis and increased disease activity.24 We found that our population of patients with hidradenitis suppurativa has a higher rate of metabolic syndrome when compared with age-, sex-, and race-matched control subjects. Specifically, patients
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Table III. Components of metabolic syndrome in hidradenitis suppurativa and control groups Variable
Response
Obesity (N = 453) Hypertriglyceridemia (N = 400) Low HDL (N = 401) Glucose Intolerance (N = 465) Hypertension (N = 465)
No Yes No Yes No Yes No Yes No Yes
N
103 350 246 154 196 205 317 148 243 222
Patients with HS
29 204 105 98 93 108 149 94 133 110
(12.5%) (87.6%) (51.7%) (48.3%) (46.3%) (53.7%) (61.3%) (38.7%) (54.7%) (45.3%)
Control subjects
74 146 141 56 103 97 168 54 110 112
(33.6%) (66.4%) (71.6%) (28.4%) (51.5%) (48.5%) (75.7%) (24.3%) (49.6%) (50.5%)
OR (95% CI)
P value
3.6 (2.2-5.6)
\.001
2.4 (1.6-3.6)
\.001
1.2 (0.8-1.8)
.295
2.0 (1.3-2.9)
\.001
0.8 (0.6-1.2)
.264
CI, Confidence interval; HDL, high-density lipoprotein; HS, hidradenitis suppurativa; OR, odds ratio.
with hidradenitis suppurativa were significantly more likely to be obese, have hypertriglyceridemia, and have glucose intolerance when compared with control subjects but were not significantly more likely to be hypertensive or to have low HDL. These findings are consistent with a previous study involving 80 patients with hidradenitis suppurativa and 100 age- and gender-matched control subjects, which found an elevated incidence of metabolic syndrome in 40% of patients with hidradenitis suppurativa versus 13% of control subjects.12 This previous study found abnormalities in the same individual parameters of the metabolic syndrome in patients with hidradenitis suppurativa that we noted in our review, but that study also noted abnormalities in HDL levels. In addition, that study also noted no correlation between metabolic syndrome and hidradenitis suppurativa disease severity. Here we report similar associations in a much larger outpatient database. Hidradenitis suppurativa has been associated with abnormal expression of antimicrobial proteins, deficiency of interleukin (IL)-20 and IL-22, and elevated IL-10 levels.25-28 These immune abnormalities lead to bacterial persistence and sustained inflammation. A proinflammatory state has been thought to be the driving force for an increase in metabolic syndrome seen in patients with psoriasis. As in psoriasis, T helper-1- and -17-mediated inflammation with elevations of IL-12 and IL-23 is involved in the pathogenesis of hidradenitis suppurativa.29 This dysregulation is also involved in metabolic disturbances including insulin resistance, adipogenesis, and abnormal lipid metabolism.30,31 It is not known if the inflammatory disease triggers the metabolic syndrome or if the metabolic disorders predispose the individual to the development of the inflammatory disease. It is also not known if there are different biologic mechanisms that may explain the epidemiologic associations between metabolic
syndrome and various inflammatory diseases. In psoriasis, there seems to be a relationship between metabolic syndrome and severity of disease such that the association with metabolic syndrome increases with increasing severity of psoriasis. In addition, associations with obesity, hypertriglyceridemia, and hyperglycemia increase with increasing psoriasis disease severity independently of other metabolic syndrome components.18 In this study, the severity of hidradenitis suppurativa had no impact on the association with metabolic syndrome. This suggests that different inflammatory diseases could have different mechanisms of association with metabolic syndrome. Obesity may be the root of cause for both hidradenitis suppurativa and the comorbidities. Further studies are required to better elucidate whether adjusting for defined body mass index would still show an association of the individual factors of metabolic syndrome independent of obesity as was done by Langan et al.18 Metabolic syndrome is known to be associated with increased morbidity and mortality. Further analysis of this association is warranted as increased awareness of this may affect patient treatments and outcomes. It is unclear at this point whether successful treatment of hidradenitis suppurativa will reduce the comorbid disease. Clinicians should, however, be aware of these relationships while also helping patients manage and cope with this distressing disease. REFERENCES 1. Nikolopoulou A, Kadoglou NP. Obesity and metabolic syndrome as related to cardiovascular disease. Expert Rev Cardiovasc Ther 2012;10:933-9. 2. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16. 3. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356-9.
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4. Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med 2004;164:1066-76. 5. Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006. Natl Health Stat Report 2009:1-7. 6. Love TJ, Qureshi AA, Karlson EW, Gelfand JM, Choi HK. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol 2011;147:419-24. 7. Dessein PH, Norton GR, Joffe BI, Abdool-Carrim AT, Woodiwiss AJ, Solomon A. Metabolic cardiovascular risk burden and atherosclerosis in African black and Caucasian women with rheumatoid arthritis: a cross-sectional study. Clin Exp Rheumatol 2013;31:53-61. 8. Vazquez BG, Alikhan A, Weaver AL, Wetter DA, Davis MD. Incidence of hidradenitis suppurativa and associated factors: a population-based study of Olmsted County, Minnesota. J Invest Dermatol 2013;133:97-103. 9. Revuz JE, Canoui-Poitrine F, Wolkenstein P, Viallette C, Gabison G, Pouget F, et al. Prevalence and factors associated with hidradenitis suppurativa: results from two case-control studies. J Am Acad Dermatol 2008;59:596-601. 10. Sartorius K, Emtestam L, Jemec GB, Lapins J. Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity. Br J Dermatol 2009;161:831-9. 11. Cosmatos I, Matcho A, Weinstein R, Montgomery MO, Stang P. Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States. J Am Acad Dermatol 2013;68:412-9. 12. Sabat R, Chanwangpong A, Schneider-Burrus S, Metternich D, Kokolakis G, Kurek A, et al. Increased prevalence of metabolic syndrome in patients with acne inversa. PloS One 2012;7:e31810. 13. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach. In: Roenigk RK, Roenigk HH, editors. Dermatologic surgery: principles and practice. New York: Marcel Dekker Inc; 1989. pp. 729-39. 14. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421. 15. Al-Mutairi N, Al-Farag S, Al-Mutairi A, Al-Shiltawy M. Comorbidities associated with psoriasis: an experience from the Middle East. J Dermatol 2010;37:146-55. 16. Augustin M, Reich K, Glaeske G, Schaefer I, Radtke M. Co-morbidity and age-related prevalence of psoriasis: analysis of health insurance data in Germany. Acta Derm Venereol 2010;90:147-51.
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17. Gisondi P, Girolomoni G. Psoriasis and atherothrombotic diseases: disease-specific and non-disease-specific risk factors. Semin Thromb Hemost 2009;35:313-24. 18. Langan SM, Seminara NM, Shin DB, Troxel AB, Kimmel SE, Mehta NN, et al. Prevalence of metabolic syndrome in patients with psoriasis: a population-based study in the United Kingdom. J Invest Dermatol 2012;132:556-62. 19. Gelfand JM, Yeung H. Metabolic syndrome in patients with psoriatic disease. J Rheumatol Suppl 2012;89:24-8. 20. Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, et al. Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 2008;196:756-63. 21. Karvounaris SA, Sidiropoulos PI, Papadakis JA, Spanakis EK, Bertsias GK, Kritikos HD, et al. Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study. Ann Rheum Dis 2007;66:28-33. 22. La Montagna G, Cacciapuoti F, Buono R, Manzella D, Mennillo GA, Arciello A, et al. Insulin resistance is an independent risk factor for atherosclerosis in rheumatoid arthritis. Diab Vasc Dis Res 2007;4:130-5. 23. Toms TE, Panoulas VF, John H, Douglas KM, Kitas GD. Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60emore than just an anti-inflammatory effect? A cross-sectional study. Arthritis Res Ther 2009;11:R110. 24. da Cunha VR, Brenol CV, Brenol JC, Xavier RM. Rheumatoid arthritis and metabolic syndrome. Rev Bras Reumatol 2011;51: 260-8. 25. Wolk K, Warszawska K, Hoeflich C, Witte E, Schneider-Burrus S, Witte K, et al. Deficiency of IL-22 contributes to a chronic inflammatory disease: pathogenetic mechanisms in acne inversa. J Immunology 2011;186:1228-39. 26. Sabat R. IL-10 family of cytokines. Cytokine Growth Factor Rev 2010;21:315-24. 27. Wegenka UM. IL-20: biological functions mediated through two types of receptor complexes. Cytokine Growth Factor Rev 2010;21:353-63. 28. Witte E, Witte K, Warszawska K, Sabat R, Wolk K. Interleukin-22: a cytokine produced by T, NK and NKT cell subsets, with importance in the innate immune defense and tissue protection. Cytokine Growth Factor Rev 2010;21:365-79. 29. Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol 2011;65:790-8. 30. Davidovici BB, Sattar N, Prinz J, Puig L, Emery P, Barker JN, et al. Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol 2010;130:1785-96. 31. Azfar RS, Gelfand JM. Psoriasis and metabolic disease: epidemiology and pathophysiology. Curr Opin Rheumatol 2008;20:416-22.
M
etabolic syndrome is a multifaceted disorder associated with inflammation. It encompasses issues with obesity, dyslipidemia, hyperglycemia, and hypertension and is correlated with an increased risk for the development of cardiovascular disease.1 Individuals with National Cholesterol Education Programedefined metabolic syndrome are 2.9 times more likely to die
From the Departments of Dermatologya and Public Health Sciences,b Henry Ford Medical Center. The Henry Ford Medical Center Department of Dermatology receives support from and this study was funded by the Livingood Fund and Rodzik Fund, neither of which had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Disclosure: Dr Hamzavi has served and/or currently serves as an investigator in clinical trial activities for the following companies: Galderma, ViroXis, Abbvie, La RocheePosay, Dow, Centocor, Amgen, Clinuvel, and Pfizer. Dr Hamzavi also serves
Abbreviations used: CI: HDL: IL:
confidence interval high-density lipoprotein interleukin
from all causes. This includes heart disease.2 Studies have found that the prevalence of metabolic as a consultant for COMBE. Mr Gold, Dr Reeder, and Ms Mahan have no conflicts of interest to declare. Accepted for publication November 9, 2013. Reprint requests: Iltefat H. Hamzavi, MD, Department of Dermatology, Henry Ford Medical Center, 3031 W Grand Blvd, Suite 800, Detroit, MI 48202. E-mail: [email protected]. Published online January 16, 2014. 0190-9622/$36.00 Ó 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.11.014
699
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syndrome in the general population is 15% to 34%.3-5 determined by physician observation. A control Chronic inflammatory diseases, including psoriasis population was created using patients seen in the and rheumatoid arthritis, have been associated with dermatology clinic during the same time period for metabolic syndrome.6,7 Hidradenitis suppurativa is a the diagnoses of either keloids or verruca vulgaris chronic inflammatory skin disease with physical and using the matching criteria of age 65 years, race, and emotional sequelae. Inflammatory nodules and gender. Ethnicity for the control population was draining sinuses develop in intertriginous areas and based on patient and support staff report. Metabolic result in pain, chronic syndrome was defined using drainage, and scarring. The the National Cholesterol CAPSULE SUMMARY condition is more common in Education Program Adult women than in men and has Treatment Panel III criteria14 There is an association between chronic previously been found to be including: high-density lipoinflammatory processes and metabolic strongly associated with protein (HDL) of less than or syndrome. obesity and smoking toequal to 40 mg/dL in males Hidradenitis suppurativa may also be bacco.8-10 In addition, there and less than or equal to 50 associated with the metabolic syndrome, mg/dL in females, hypertriwas an association between which may affect cardiovascular risk glyceridemia greater than or more severe hidradenitis profiles of these patients. equal to 150 mg/dL, blood suppurativa and obese pressure of greater than or women compared with In addition to treating the skin, health equal to 130/85 mm Hg or a women of normal weight.10 care practitioners should screen patients history of hypertension The highest prevalence of with hidradenitis suppurativa for noted by a physician in the hidradenitis suppurativa is metabolic syndrome. patient chart, and hyperglyin those aged 18 to 44 cemia of greater than or years.11 One small study has equal to 110 mg/dL fasting or a history of glucose previously looked for an association between intolerance noted by a physician in the patient chart. metabolic syndrome and hidradenitis suppurativa. Obesity was defined as body mass index 30 or higher This hospital-based study involved 80 patients with or a notation by a physician that the patient was hidradenitis suppurativa and showed an increased obese. Patients were classified as having metabolic prevalence of metabolic syndrome of 40% in patients syndrome if they had a minimum of 3 of the 5 above with hidradenitis suppurativa versus 13% in control criteria. subjects.12 This study focused on inpatients who tend to have more comorbidities and have increased disease severity. The aim of our study was to RESULTS further investigate the association of metabolic and The data consist of 366 cases and 366 controls physiologic alterations in patients with hidradenitis matched on age 65 years, sex, and race. If a patient suppurativa and to determine the prevalence of was missing data on 3 or more of these factors, metabolic syndrome in this population. they were excluded from the analysis. Among all 738 patients, 465 (243 patients with hidradenitis suppurativa and 222 control subjects) had enough METHODS data to determine the presence or absence of This study was approved by the Henry Ford metabolic syndrome, which was defined as having Hospital Institutional Review Board. A retrospective 3 or more of the following: obesity, hypertriglycerchart review of 39,055 total encounters in the idemia, low HDL, diabetes mellitus, and hypertendermatology clinic from January 1, 2011, to May 31, sion. All categorical data are described as count and 2012, was performed. Charts of patients with the column percentages, and continuous data as mean, International Classification of Diseases, Ninth SD, median, minimum, and maximum. Of the 243 Revision diagnostic code associated with hidradenipatients with hidradenitis suppurativa evaluated, tis suppurativa were included. In all, 366 patients 79.8% were female and 20.2% were male. The age with an appropriate diagnosis of hidradenitis supof patients with hidradenitis suppurativa ranged purativa were identified and included in this from 9 to 92 years. The mean age was 41.9 years review. Patients were given a diagnosis of hidradeand the median was 42 years. Of the study particinitis suppurativa by dermatologists based on pants, 65.0% were African American, 18.9% were clinical presentation, including a history of recurrent Caucasian, and the remaining 16.1% were classified inflammatory nodules, sterile abscesses, and drainas ‘‘other’’ (Table I). A significantly higher proportion ing sinuses. Severity of the disease was classified of the patients with hidradenitis suppurativa were using the Hurley staging system.13 Ethnicity was d
d
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Table I. Characteristics of patients with hidradenitis suppurativa and control subjects with enough nonmissing data for analysis Variable
Age
Race
Sex Metabolic syndrome
Response
Mean (SD) Median (minimum, maximum) Caucasian African American Other Female Male No Yes
Patients with HS (N = 243)
Control subjects (N = 222)
41.9 (16.1) 42 (9, 92)
44.6 (15.3) 44 (14, 90)
46 158 39 194 49 120 123
55 133 34 172 50 155 67
(18.9%) (65.0%) (16.1%) (79.8%) (20.2%) (49.4%) (50.6%)
(24.8%) (59.9%) (15.3%) (77.5%) (22.5%) (69.7%) (30.2%)
OR (95% CI) (patients with HS vs control subjects)
(reference) 2.37 (1.62-3.47)
P value
\.001
CI, Confidence interval; HS, hidradenitis suppurativa; OR, odds ratio.
found to have metabolic syndrome as compared with the control subjects (50.6% and 30.2%, respectively, P \ .001), odds ratio 2.37 (95% confidence intervals [CI] 1.62-3.47) (Table I). There was not, however, a significant association between hidradenitis suppurativa disease severity and the prevalence of metabolic syndrome (Table II). Of patients with hidradenitis suppurativa, 87.6% were found to be obese whereas only 66.4% of the control subjects met this criterion (P \.001). There was also a significantly higher percentage of patients with hidradenitis suppurativa at 43.8% versus control subjects at 28.4% who were noted to have hypertriglyceridemia (P \ .001). Of patients with hidradenitis suppurativa, 48.3%, as compared with 28.4% of control subjects, were noted to have glucose intolerance (P \ .001) (Table III). There was not a significant difference between patients with hidradenitis suppurativa and control subjects in the prevalence of hypertension or low HDL. The odds ratio indicate that the patients with hidradenitis suppurativa were 3.6 (95% CI 2.2-5.6) times more likely to be obese, 2.4 (95% CI 1.6-3.6) times more likely to have hypertriglyceridemia, and 2.0 (95% CI 1.3-2.9) times more likely to have glucose intolerance as the control subjects. There were no significant associations noted between prevalence of metabolic syndrome or disease severity with either race or gender. Obesity was not associated with more severe disease. The x2 tests are used to compare proportions. Wilcoxon 2-sample tests and KruskalWallis tests were used to compare age between severity groups and metabolic syndrome groups. When comparing the proportion of patients with metabolic syndrome by age quartiles, Hochberg method was used to adjust the P value as multiple pairwise comparisons were done. Univariate logistic regression models were used to obtain odds ratio
Table II. Metabolic syndrome and hidradenitis suppurativa disease severity as quantified by Hurley stage Severity, Hurley stage
I II III
No metabolic syndrome (N = 120)
43 (35.8%) 57 (47.5%) 20 (16.7%)
Metabolic syndrome (N = 124)
OR (95% CI)
44 (35.5%) (reference) 49 (39.5%) 0.84 (0.48-1.48) 31 (25.0%) 1.52 (0.75-3.06)
P value
.232
CI, Confidence interval; OR, odds ratio.
and 95% CI. Statistical significance was set at P less than .05. The data analysis for this article was generated using software (SAS/STAT, Version 9.2, SAS Institute Inc, Cary, NC).
DISCUSSION Associations between other disorders known to be associated with increased inflammation, such as psoriasis and rheumatoid arthritis, and metabolic syndrome have previously been investigated and are well documented.15-24 The link between psoriasis and metabolic syndrome has been particularly well established.15-17 This disease association appears to increase in a dose-responsive manner with the prevalence of metabolic syndrome increased in proportion to the severity of psoriasis.18,19 Studies looking for an increased prevalence of metabolic syndrome in patients with rheumatoid arthritis have been inconclusive.20-23 The presence of metabolic syndrome in patients with rheumatoid arthritis is, however, associated with poorer disease prognosis and increased disease activity.24 We found that our population of patients with hidradenitis suppurativa has a higher rate of metabolic syndrome when compared with age-, sex-, and race-matched control subjects. Specifically, patients
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Table III. Components of metabolic syndrome in hidradenitis suppurativa and control groups Variable
Response
Obesity (N = 453) Hypertriglyceridemia (N = 400) Low HDL (N = 401) Glucose Intolerance (N = 465) Hypertension (N = 465)
No Yes No Yes No Yes No Yes No Yes
N
103 350 246 154 196 205 317 148 243 222
Patients with HS
29 204 105 98 93 108 149 94 133 110
(12.5%) (87.6%) (51.7%) (48.3%) (46.3%) (53.7%) (61.3%) (38.7%) (54.7%) (45.3%)
Control subjects
74 146 141 56 103 97 168 54 110 112
(33.6%) (66.4%) (71.6%) (28.4%) (51.5%) (48.5%) (75.7%) (24.3%) (49.6%) (50.5%)
OR (95% CI)
P value
3.6 (2.2-5.6)
\.001
2.4 (1.6-3.6)
\.001
1.2 (0.8-1.8)
.295
2.0 (1.3-2.9)
\.001
0.8 (0.6-1.2)
.264
CI, Confidence interval; HDL, high-density lipoprotein; HS, hidradenitis suppurativa; OR, odds ratio.
with hidradenitis suppurativa were significantly more likely to be obese, have hypertriglyceridemia, and have glucose intolerance when compared with control subjects but were not significantly more likely to be hypertensive or to have low HDL. These findings are consistent with a previous study involving 80 patients with hidradenitis suppurativa and 100 age- and gender-matched control subjects, which found an elevated incidence of metabolic syndrome in 40% of patients with hidradenitis suppurativa versus 13% of control subjects.12 This previous study found abnormalities in the same individual parameters of the metabolic syndrome in patients with hidradenitis suppurativa that we noted in our review, but that study also noted abnormalities in HDL levels. In addition, that study also noted no correlation between metabolic syndrome and hidradenitis suppurativa disease severity. Here we report similar associations in a much larger outpatient database. Hidradenitis suppurativa has been associated with abnormal expression of antimicrobial proteins, deficiency of interleukin (IL)-20 and IL-22, and elevated IL-10 levels.25-28 These immune abnormalities lead to bacterial persistence and sustained inflammation. A proinflammatory state has been thought to be the driving force for an increase in metabolic syndrome seen in patients with psoriasis. As in psoriasis, T helper-1- and -17-mediated inflammation with elevations of IL-12 and IL-23 is involved in the pathogenesis of hidradenitis suppurativa.29 This dysregulation is also involved in metabolic disturbances including insulin resistance, adipogenesis, and abnormal lipid metabolism.30,31 It is not known if the inflammatory disease triggers the metabolic syndrome or if the metabolic disorders predispose the individual to the development of the inflammatory disease. It is also not known if there are different biologic mechanisms that may explain the epidemiologic associations between metabolic
syndrome and various inflammatory diseases. In psoriasis, there seems to be a relationship between metabolic syndrome and severity of disease such that the association with metabolic syndrome increases with increasing severity of psoriasis. In addition, associations with obesity, hypertriglyceridemia, and hyperglycemia increase with increasing psoriasis disease severity independently of other metabolic syndrome components.18 In this study, the severity of hidradenitis suppurativa had no impact on the association with metabolic syndrome. This suggests that different inflammatory diseases could have different mechanisms of association with metabolic syndrome. Obesity may be the root of cause for both hidradenitis suppurativa and the comorbidities. Further studies are required to better elucidate whether adjusting for defined body mass index would still show an association of the individual factors of metabolic syndrome independent of obesity as was done by Langan et al.18 Metabolic syndrome is known to be associated with increased morbidity and mortality. Further analysis of this association is warranted as increased awareness of this may affect patient treatments and outcomes. It is unclear at this point whether successful treatment of hidradenitis suppurativa will reduce the comorbid disease. Clinicians should, however, be aware of these relationships while also helping patients manage and cope with this distressing disease. REFERENCES 1. Nikolopoulou A, Kadoglou NP. Obesity and metabolic syndrome as related to cardiovascular disease. Expert Rev Cardiovasc Ther 2012;10:933-9. 2. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16. 3. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356-9.
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