Systemic associations of hidradenitis suppurativa

Systemic associations of hidradenitis suppurativa John J. Kohorst, MD,a Alexa B. Kimball, MD, MPH,b and Mark D. P. Davis, MDc Rochester, Minnesota, and Boston, Massachusetts Hidradenitis suppurativa (HS) is a progressive, inflammatory disease that affects mostly young women and appears to be caused by inflammation of hair follicles in areas of friction in the body (eg, the axillae, groin, perineum, and medial aspects of the thighs). Given this pathophysiology, one might expect comorbidities that contribute to inflammation and friction. Observed comorbidities fall into several categories: obesity and the metabolic syndrome, hormone-related disorders, deleterious health habits and mood, autoimmune disease, inflammatory disease and finally, the risk of skin cancer and sequelae of nonhealing wounds. The available literature on comorbid diseases of HS is limited but rapidly increasing. In this review, we summarize recent and major studies of HS disease association. ( J Am Acad Dermatol 2015;73:S27-35.) Key words: acne inversa; arthritis; depression; disease associations; hidradenitis suppurativa; inflammatory bowel disease; metabolic syndrome; smoking; spondyloarthropathy.

OBSERVATIONS

Obesity and the metabolic syndrome For decades, HS has shown a predilection for obese patients. Recent controlled studies have confirmed a strong association between obesity and HS. Obesity. Rates of obesity in HS range from 12% to 88%, depending on the population (Table I).1-5 Duration of HS disease has not been linked to obesity6; however, several studies suggest that HS disease severity is associated with an elevated body mass index (BMI).2,7-10 In addition, recent long-term follow-up data suggest that nonobese HS patients report more frequent HS remission.11 Independent of BMI, central obesity has also been linked to HS.3,4 Investigators have suggested that overlapping skin folds in overweight patients may lead to HS

development, but the proinflammatory state associated with obesity and concomitant hormonal problems may also play a role.12,13 Metabolic syndrome. MetS is defined as the presence of 3 of 5 physiologic alterations, including obesity, elevated fasting blood glucose level, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol (HDL-C) level, and hypertension. As a distinct entity, MetS has higher rates in HS than in control subjects, which is not surprising given the higher rate of obesity observed.3,4,14 Of note, onset of HS has been reported at younger ages in patients with comorbid MetS; however, neither HS disease duration nor HS disease severity has been linked to increased rates of MetS in HS.3,4,14 Diabetes mellitus. The association of diabetes mellitus and HS has been noted for [20 years,15-17 and recent studies support the finding.3,5,18 Reported rates of diabetes in HS have varied from 5% to 20%,3,5,18 whereas rates of hyperglycemia and glucose intolerance in HS have been reported at 26% and 39%, respectively.4,14 Diabetes in HS has not been significantly associated with increased HS disease severity, and the confounder of obesity is important to evaluate in assessing this risk.9 Lipid abnormalities. Recent studies have uniformly reported an association between

From the Mayo Clinic College of Medicine,a Rochester; Department of Dermatology,b Massachusetts General Hospital and Harvard Medical School, Boston; and the Department of Dermatology,c Mayo Clinic, Rochester. This publication was supported through funding provided by AbbVie Corporation. Conflicts of interest: None declared.

Accepted for publication July 16, 2015. Reprint requests: Mark D. P. Davis, MD, Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: [email protected]. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.07.055

The available literature on comorbid diseases of hidradenitis suppurativa (HS) is limited but rapidly increasing.1-53 Studies to date suggest that HS is most convincingly associated with the metabolic syndrome (MetS). Associations with many other conditions, including smoking, depression, autoimmune disease, and cutaneous oncology have been suggested, but the current evidence largely consists of retrospective reports and case series.

S27

S28 Kohorst, Kimball, and Davis

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NOVEMBER 2015

interestingly, a recent questionnaire reported hypertriglyceridemia and HS, which similarly lower rates of HS remission in smokers compared may be confounded by the presence of obesity with nonsmokers.11 and poor dietary habits.4,14 A study of HS patients Substance dependence. An association beat an outpatient clinic found an association in an tween HS and either drug or alcohol dependence HS population group with an odds ratio of 1.49 has not been shown in any controlled studies to date, (95% confidence interval [CI], 1.18-1.87).3 Major reports have also found associations between low although a phase II therapeutic study reported a HDL-C levels and HS,3,14 and higher use of opioids than a single study found no would be expected in the US CAPSULE SUMMARY relation.4 Rates of low population.5,18 Depression. A controHDL-C values in HS vary Recent studies have linked hidradenitis lled study involving 9619 from 33.1% to 54%, dependsuppurativa to several diseases. patients found a higher preving on the study population. This review summarizes systemic alence of depression (5.9%) Hypertension. The maassociations of hidradenitis suppurativa in HS patients relative to jority of reports have not reported to date. controls.21 In addition, refound a significant associaported mean Dermatology tion between HS and The data suggest that hidradenitis is Life Quality Index scores in comorbid or past history of most convincingly associated with HS are higher than in many hypertension, although it is a obesity and the metabolic syndrome, but other debilitating diseases, component of MetS.3,4,18 In continued investigation is needed. addition, hypertension has including atopic dermatitis not been shown to be assoand moderate psoriasis, and ciated with increased HS disease burden.8 range from a mean of 8.4 to 20.22-25 Reports to date are inconclusive with respect to the association between HS disease burden and the co-occurrence Hormone-related disorders of depression.2,7,8,12 Given the predilection of HS for women, hor11,45,46 monal pathogenesis has been long suggested. A recent case control study reported a strong Autoimmune disease association between HS and polycystic ovary The inflammatory nature of HS and the syndrome,5 which is also associated with obesity; observation of HS cases clustering with autoimmune however, the majority of information to date does diseases has motivated several case series. not confirm this association.11,31,37,45,46 Inflammatory bowel disease. A recent population-based incidence study found that paHealth habits and mood tients with inflammatory bowel disease are 9 times HS is a painful disease with severe psychological more likely to develop HS than the general morbidity. Recent studies have investigated an population, with an incidence rate ratio of 8.9 (95% association with smoking, substance dependence, CI, 3.6-17.5).26 The largest case series reported rates of HS in Crohn’s disease (CD) from 17% to 26%, and depression. whereas rates of HS in ulcerative colitis (UC) range Smoking. Reported rates of current smoking in from 14% to 18%.27,28 Of note, CD in the clinical HS patients range from 40% to 92%.2,5,9,11,18-20 An association between current smokers and HS setting of HS typically localizes to the large bowel prevalence has been found in 2 studies18,19 but and precedes HS onset by several years; HS in CD has been refuted in a third investigation.9 frequently arises in a perianal or perineal location.29 Similarly, reports conflict on the association beArthritis and spondyloarthropathy. Rates of tween ex-smokers and HS.9,18 Studies investispondyloarthropathy are reported to be significantly gating tobacco use in HS found that HS clinic higher in HS than controls.5,30 Comorbid arthritis has patients have increased cigarette consumption per been described predominantly in black men in day compared with controls,18 and increased HS peripheral rather than vertebral joints.31-33 Typically, HS precedes arthritis by a number of disease burden was associated with significantly years, but after it is present, the arthritis is chronic, more smoking pack-years, indicating smoking flares in conjunction with HS flares, and often may exacerbate disease.9 HS patients did not report starting to smoke at a significantly younger improves with effective HS treatment.31-34 Of note, 18 Cigarette smoking has arthritic disease occurring in association with HS is age than controls. been linked to more severe HS disease2,7 and, HLA-B27 negative.32,33 d

d

d

Metabolic syndrome Miller et al3

PubMed ID

Sample size

Gold et al4

25229996 15,209 (326 HS population; 32 HS hospital) 24433875 465

Sabat et al14

22359634

180

25440440

3460

Obesity Shlyankevich et al5

25229996 15,209 (326 HS population; 32 HS hospital)

Schrader et al9

24880664

846

Crowley et al8

24842009

154

Kromann et al11

24804604

127

Gold et al4

24433875

453

Vazquez et al2

22931916

255

Sabat et al14

22359634

180

Sartorius et al7

19438453

246

Canoui-Poitrine et al10

19406505

301

Measures of association

Prevalence of metabolic syndrome in population HS vs hospital HS vs control: 32.2% vs 53.1% vs 21.5%

Population: OR, 2.08 (95% CI, 1.61-2.69); hospital: OR, 3.89 (95% CI, 1.9-7.98)

Prevalence of metabolic syndrome in HS vs control: 50.6% vs 30.2% (P \ .001) Prevalence of metabolic syndrome in HS vs control: 40.0% vs 13.0% (P \ .001)

OR, 2.37 (95% CI, 1.62-3.47)

Prevalence of obesity in HS vs control: 11.6% vs 0.75% (P \ .0001) General obesity—prevalence of general obesity in population HS vs hospital HS vs control: 32.8% vs 50.0% vs 18.8% Abdominal obesity—prevalence of abdominal obesity in population HS vs hospital HS vs control: 51.5% vs 62.5% vs 37.2% Mean BMI in HS Hurley stage I vs Hurley stage II vs Hurley stage III: 27.6 6 11.6 vs 28.5 6 5.9 vs 28.9 6 7.0 BMI [40 kg/m2 in high disease burden HS vs medium disease burden HS: 22/60 (36.7%) vs 21/94 (22.3%) Rate of HS disease remission in nonobese (BMI \30 kg/m2) vs obese: 45% vs 23% Prevalence of obesity in HS vs control: 87.6% vs 66.4% (P \ .001) Prevalence of Hurley stage II or III in obese vs nonobese: 42.1% vs 39.1% (P = .63) Prevalence of central obesity in HS vs control: 65.0% vs 24.0% (P \ .001) HS disease severity by median (IQR) Hidradenitis Suppurativa Score in obese BMI vs overweight BMI vs normal BMI: 50 (18-86) vs 44 (22-56) vs 32 (12-54) (P = .036) Median (IQR) Sartorius score in normal vs overweight vs obese: 15 (12), 20.5 (16.5), 25.5 (19) (P \ .001)

OR, 2.09 (95% CI, 1.03-4.22)

OR, 4.46 (95% CI, 2.02-9.96)

General obesity—population: OR, 2.58 (95% CI, 2.00-3.23); hospital: OR, 6.38 (95% CI, 2.99-13.62) Abdominal obesity—population: OR, 2.24 (95% CI, 1.78-2.82); hospital: OR, 3.62 (95% CI, 1.73-7.60)

OR, 1.03 (95% CI, 1.01-1.05)

OR, 2.01 (95% CI, 0.985-4.114) OR, 3.9 (95% CI, 1.4-11.0) OR, 3.6 (95% CI, 2.2-5.6) OR, 1.1 (95% CI, 0.7-1.9) OR, 5.88 (95% CI, 2.93-11.91) NA

OR, 0.85 (95% CI, 0.62-1.09)

Continued

Kohorst, Kimball, and Davis S29

Miller et al3

Outcome measure

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Table I. Recent and major studies of hidradenitis suppurativa disease associations

Study

Revuz et al

PubMed ID 18

Diabetes mellitus Shlyankevich et al5 Miller et al3

Sample size

Population: OR, 1.05 (95% CI, 0.99-1.10); hospital: OR, 1.12 (95% CI, 1.08-1.15)

25440440

Prevalence of diabetes in HS vs control: 20.4% vs 1.5% (P \ .0001) Prevalence of diabetes in population HS vs hospital HS vs control: 7.1% vs 12.5% vs 4.9%

OR, 16.8 (95% CI, 11.2-25.3)

Prevalence of history of diabetes in HS Hurley stage I vs Hurley stage II vs Hurley stage III: 5.2 vs 5.8 vs 16.1 Prevalence of glucose intolerance in HS vs control: 38.7% vs 24.3% (P \ .001) Prevalence of hyperglycemia in HS vs control: 26.3% vs 8.0% (P \ .001) Prevalence of diabetes in HS vs control: 4.5% vs 3.0% (P = .56)

OR, 1.43 (95% CI, 0.77-2.68)

Prevalence of dyslipidemia in HS vs control: 35.8% vs 1.6% (P \ .0001) Prevalence of hypertriglyceridemia in population HS vs hospital HS vs control: 48.8% vs 50.0% vs 43.3%

OR, 4.06 (95% CI, 2.54-6.48)

Prevalence of hypertriglyceridemia in HS vs control: 48.3% vs 28.4% (P \ .001) Prevalence of hypertriglyceridemia in HS vs control: 38.8% vs 22.0% (P = .014)

OR, 2.4 (95% CI, 1.6-3.6)

Prevalence of low HDL cholesterol in population HS vs hospital HS vs control: 33.1% vs 46.9% vs 18.1%

Population: OR, 1.94 (95% CI, 1.52-2.48); hospital: OR, 2.97 (95% CI, 1.45-6.08)

Prevalence of low 53.7% vs 48.5% Prevalence of low 50.0% vs 18.0%

OR, 1.2 (95% CI, 0.8-1.8)

3460

Schrader et al9 Gold et al4

24433875

465

Sabat et al14

22359634

180

Revuz et al18

18674845

267

25440440

3460

Miller et al3

Gold et al4

25229996 15,209 (326 HS population; 32 HS hospital) 24433875 400

Sabat et al14

22359634

Low HDL cholesterol Miller et al3

180

22359634

180

25440440

3460

Prevalence of hypertension in HS vs control: 34.3% vs 3.0% (P \ .0001)

OR, 2.0 (95% CI, 1.3-2.9) OR, 4.09 (95% CI, 1.59-10.84) OR, 1.53 (95% CI, 0.36-6.55)

Population: OR, 1.49 (95% CI, 1.18-1.87); hospital: OR, 1.67 (95% CI, 0.81-3.44)

OR, 2.24 (95% CI, 1.11-4.54)

OR, 4.56 (95% CI, 2.21-9.46)

OR, 1.84 (95% CI, 1.22-2.79)

NOVEMBER 2015

Sabat et al14

HDL cholesterol in HS vs control: (P = .295) HDL cholesterol in HS vs control: (P \ .001)

Population: OR, 2.44 (95% CI, 1.55-3.83); hospital: OR, 5.74 (95% CI, 1.91-17.24)

J AM ACAD DERMATOL

Gold et al4

25229996 15,209 (326 HS population; 32 HS hospital) 24433875 401

Hypertension Shlyankevich et al5

Measures of association

18674845 1475 (67 HS Mean BMI in population HS vs control: 25.6 vs 24.3; population; mean BMI in hospital HS vs control: 25.6 vs 23.2 302 HS hospital) (P \ .0001)

25229996 15,209 (326 HS population; 32 HS hospital) 24880664 846

Hypertriglyceridemia Shlyankevich et al5

Outcome measure

S30 Kohorst, Kimball, and Davis

Table I. Cont’d

Gold et al4

24433875

465

Revuz et al18

18674845

267

25440440

3460

Smoking Shlyankevich et al5 Schrader et al9

24880664

Kromann et al11

24804604

Vazquez et al2

22931916

Sartorius et al7

19438453

Revuz et al18

18674845

10393449

Population: OR, 1.08 (95% CI, 0.85-1.38); hospital: OR, 2.14 (95% CI, 1.01-4.53)

Hypertension in high disease burden HS vs medium disease burden HS: 11 of 60 (18.3%) vs 23 of 94 (24.5%) Prevalence of hypertension in HS vs control: 45.3% vs 50.5% (P = .264) Prevalence of treated hypertension in HS vs control: 20.9% vs 17.0% (P = .47)

OR, 0.69 (95% CI, 0.31-1.551)

Prevalence of current OR, former smokers in HS vs control: 29.5% vs 0.92% (P \ .0001) 846 Current smoker—prevalence of current smoker in HS Hurley stage I vs Hurley stage II vs Hurley stage III: 67.9 vs 74.7 vs 68.2; exsmoker—prevalence of exsmoker in HS Hurley stage I vs Hurley stage II vs Hurley stage III: 13.3 vs 13.2 vs 20.0; smoking pack-years—mean smoking pack-years in HS Hurley stage I vs Hurley stage II vs Hurley stage III: 15.5 6 12.7 vs 19.3 6 13.2 vs 27.9 6 24.5 127 Rate of HS disease remission in nonsmokers vs active smokers: 40% vs 29% (P = .012) 265 Prevalence of Hurley stage II or III in past/current smoker vs never smoker: 45.2% vs 29.1% (P = .016) 246 HS disease severity by median (IQR) Hidradenitis Suppurativa Score in smokers vs nonsmokers: 41 (22-75.5) vs 22 (10-57) (P = .032) 1475 (67 HS Current smoker—prevalence of current smokers in population; population HS vs control: 40.3% vs 19.2% (P = .01); 302 HS hospital) prevalence of current smokers in hospital HS vs control: 75.6% vs 24.7% (P \ .001) Exsmoker—prevalence of exsmokers in population HS vs control: 28.4% vs 28.8%; prevalence of exsmokers in hospital HS vs control: 9.3% vs 21.6% Cigarettes per day—cigarettes per day in population HS vs control: 13.9 vs 11.2 (P = .25); cigarettes per day in hospital HS vs control: 16.1 vs 13.0 (P = .0001) Age of smoking start—age of starting smoking in population HS vs control: 18.9 vs 19.6 (P = .77); age of starting smoking in hospital HS vs control: 17.4 vs 17.6 (P = .49) 126 Prevalence of active smokers in HS vs control: 88.9% vs 46% (P \ .001)

OR, 0.8 (95% CI, 0.6-1.2) OR, 1.39 (95% CI, 0.61-3.19)

OR, 5.34 (95% CI, 2.09-9.83) Current smoker: OR, 0.94 (95% CI, 0.60-1.47); exsmoker: OR, 1.14 (95% CI, 0.64-2.02); pack-years: OR, 1.02 (95% CI, 1.01-1.03)

OR, 2.8 (95% CI, 1.3-6.3) OR, 2.0 (95% CI, 1.1-3.5) NA

Current smoker—population: OR, 3.79 (95% CI, 1.86-7.74); hospital: OR, 12.55 (95% CI, 8.58-18.38) Exsmoker—population: OR, 1.55 (95% CI, 0.74-3.32); hospital: OR, 1.46 (95% CI, 0.86-2.46) Cigarettes per day—population: OR, 1.04 (95% CI, 0.98-1.10); hospital: OR, 1.05 (95% CI, 1.02-1.08) Age of smoking start—population: OR, 0.98 (95% CI, 0.91-1.06); hospital: OR, 0.98 (95% CI, 0.93-1.03) OR, 9.4 (95% CI, 3.7-23.7) Continued

Kohorst, Kimball, and Davis S31

Konig et al19

Prevalence of hypertension in population HS vs hospital HS vs control: 48.2% vs 56.3% vs 60.6%

J AM ACAD DERMATOL

Crowley et al8

25229996 15,209 (326 HS population; 32 HS hospital) 24842009 154

VOLUME 73, NUMBER 5

Miller et al3

Study

PubMed ID

Sample size

Outcome measure

Depression Shavit et al21

24909646

9619

Crowley et al8

24842009

154

Vazquez et al2

22931916

268

Onderdijk et al25

22339940

444

Sartorius et al7

19438453

246

11298541

160

Prevalence of depression in HS vs control: 5.9% vs 3.5% (P \ .001) Depression (PHQ-9 scores $10) in high disease burden HS vs medium disease burden HS: 31 of 60 (51.7%) vs 33 of 94 (35.1%) Prevalence of Hurley stage II or III in previous depression diagnosis vs no previous depression diagnosis: 39.1% vs 41.2% (P = .74) DLQI scores in HS vs control: 8.4 6 7.5 vs 4.3 6 5.6 (P \ .0001) Mean DLQI score in HS was 10.3 6 7.5; HS disease severity by Hidradenitis Suppurativa Score correlated with DLQI according to Spearman R = 0.342 (P = .0003) Mean DLQI score in HS was 8.9 6 8.3

25440440

3460

Von Der Worth et al53 Substance dependence Shlyankevich et al5

Revuz et al18 Crohn’s disease Yadav et al26 Van der Zee et al27 Van der Zee et al28

18674845

267

25952308 24673289 19681876

679 255 102 61

24673289

255

Van der Zee et al28

19681876

56

Spondyloarthropathy Shlyankevich et al5

25440440

3460

24429166

640

Richette et al30

OR, 1.94 (95% CI, 1.004-3.764)

OR, 0.9 (95% CI, 0.6-1.5)

NA NA

NA Alcohol—OR, 0.25 (95% CI, 0.087-0.73) Drugs—OR, 1.20 (95% CI, 0.41-3.52) OR, 1.09 (95% CI, 0.59-2.01)

Incidence rate ratio of HS in IBD was 8.9 (95% CI, 3.6-17.5) Prevalence of HS in Crohn’s disease: 181 of 688 (26.3%) Prevalence of painful boils in groin or axilla in Crohn’s disease: 17 of 102 (17%) Prevalence of Crohn’s disease in HS: 38%

NA NA NA

Prevalence of HS in ulcerative colitis disease: 74 of 405 (18.2%) Prevalence of painful boils in groin or axilla in ulcerative colitis: 8 of 56 (14%)

NA

Prevalence of arthropathies in HS vs control: 52.5% vs 3.0% (P \ .0001) Prevalence of spondyloarthritis by ESSG criteria in HS vs French population estimate: 3.7% vs 0.3%

OR, 9.41 (95% CI, 6.81-12.9)

NA

NA

NA

NOVEMBER 2015

8245664

OR, 1.7 (95% CI, 1.4-2.1)

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Church et al29 Ulcerative colitis Van der Zee et al27

Alcohol dependence—prevalence of alcohol dependence in HS vs control: 4.2% vs 0.52% (P \ .0001) Drug dependence—prevalence of drug dependence in HS vs control: 6.5% vs 0.40% (P \ .0001) Prevalence of [1 alcoholic drink per day in HS vs control: 16.7% vs 15.1%

Measures of association

S32 Kohorst, Kimball, and Davis

Table I. Cont’d

44

Nonmelanoma skin cancer Lavogiez et al51 20029163 11405761 Lapins et al50

13 2119

Pilonidal disease Vazquez et al2

22931916

268

19406505

298

Acne vulgaris Schrader et al9

24880664

846

Vazquez et al2

22931916

266

Canoui-Poitrine et al10

19406505

300

25440440

3460

Canoui-Poitrine et al10

Hyperandrogenism Shlyankevich et al5

Prevalence of peripheral arthropathy vs axial arthropathy vs both peripheral and axial arthropathy in HS: 29% vs 14% vs 57%

NA

Largest case series to date Standardized prevalence ratio of nonmelanoma skin cancer in HS: 4.6 (95% CI, 1.5-10.7)

NA NA

Prevalence of Hurley stage II or III in pilonidal disease vs no pilonidal disease: 43.8% vs 40.1% (P = .77) Prevalence of pilonidal disease in 90 of 302 (30.2%); median (IQR) Sartorius score with vs without pilonidal disease: 19.5 (27) vs 16.8 (15) (P = .13)

OR, 1.2 (95% CI, 0.4-3.2)

Prevalence of history of severe acne vulgaris in HS Hurley stage I vs Hurley stage II vs Hurley stage III: 23.1 vs 26.3 vs 24.4 Prevalence of Hurley stage II or III in previous acne diagnosis vs no previous acne diagnosis: 44.3% vs 38.5% (P = .35) Prevalence of current acne in HS: 39 of 302 (13.0%); median (IQR) Sartorius score in history of severe acne vs no history: 18 (18) vs 17 (14) (P = .03)

OR, 1.09 (95% CI, 0.74-1.59)

Prevalence of polycystic ovary syndrome in HS vs control: 4.0% vs 0.17% (P \ .0001)

OR, 13.7 (95% CI, 4.00-47.3)

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Rosner et al33

NA

OR, 1.3 (95% CI, 0.8-2.1)

OR 3.61 (95% CI, 0.32-6.90)

BMI, Body mass index; CI, confidence interval; ESSG, European Spondyloarthropathy Study Group; HDL, high-density lipoprotein; HS, hidradenitis suppurativa; IQR, interquartile range; OR, odds ratio.

Kohorst, Kimball, and Davis S33

S34 Kohorst, Kimball, and Davis

Inflammatory disease and associated syndromes Pathological investigation has shown HS to be an inflammatory disease of the hair follicle. Diseases with a similar etiology have been noted in limited reports. Follicular occlusion tetrad. Limited studies have described disease associations of the follicular occlusion tetrad (ie, HS, pilonidal cyst, acne conglobata, and dissecting cellulitis of the scalp) with HS. Pilonidal cysts, often gluteal in location, comprise the most common manifestation of the tetrad, and the most reliable observations to date report a 6% prevalence.2 No association between pilonidal disease and HS disease severity has been reported.2,10 Acne conglobata has been linked to HS and arthritis in 2 case series.35,36 Because dissecting cellulitis is rare, comorbidity with HS is difficult to establish; however, a few cases have been reported, predominantly in black men.36-38 Acne vulgaris. Evidence for an association between acne vulgaris and HS is weak.34 Major studies have reported the rates of previous acne vulgaris in HS from 23% to 44% and current acne in HS from 13% to 36%.2,9,10 In addition, a current or past history of acne vulgaris has not been shown to significantly affect HS severity.2,9,10 Pyoderma gangrenosum. Pyoderma gangrenosum has been linked to HS independently in case reports and series.39-43 Pyoderma gangreosum has also been described with HS in case reports of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH), pyogenic arthritis, pyoderma gangrenosum, acne, and suppurative hidradenitis (PAPASH), and psoriatic arthritis, pyoderma gangrenosum, acne, and suppurative hidradenitis (PsAPASH) syndromes.44-49 Cutaneous oncology It is uncertain whether nonmelanoma skin cancer (NMSC) has a true association with HS or is a complication of the chronic inflammation of HS. A large retrospective study found a 4.6-fold increased risk of NMSC among patients with HS.50 Studies have reported a 0.5% to 4.6% prevalence of cutaneous squamous cell carcinoma in HS.5,51 Characteristics of comorbid NMSC in HS suggest that patients have NMSC in perineal or gluteal locations and have HS for 25 years on average before cancer development.52 In conclusion, although the HS comorbidity literature is in early stages, it is clear that patients may have additional medical issues and risk factors that would benefit from intervention and management. Future research will likely refine these

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associations and lead to more targeted recommendations that will benefit these patients and improve their overall health status. REFERENCES 1. Rompel R, Petres J. Long-term results of wide surgical excision in 106 patients with hidradenitis suppurativa. Dermatol Surg. 2000;26:638-643. 2. 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. 3. Miller IM, Ellervik C, Vinding GR, et al. Association of metabolic syndrome and hidradenitis suppurativa. JAMA Dermatol. 2014;150:1273-1280. 4. Gold DA, Reeder VJ, Mahan MG, Hamzavi IH. The prevalence of metabolic syndrome in patients with hidradenitis suppurativa. J Am Acad Dermatol. 2014;70:699-703. 5. Shlyankevich J, Chen AJ, Kim GE, Kimball AB. Hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chart-verified case-control analysis. J Am Acad Dermatol. 2014;71:1144-1150. 6. Barth JH, Layton AM, Cunliffe WJ. Endocrine factors in preand postmenopausal women with hidradenitis suppurativa. Br J Dermatol. 1996;134:1057-1059. 7. 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: 831-839. 8. Crowley JJ, Mekkes JR, Zouboulis CC, et al. Association of hidradenitis suppurativa disease severity with increased risk for systemic comorbidities. Br J Dermatol. 2014;171: 1561-1565. 9. Schrader AM, Deckers IE, van der Zee HH, Boer J, Prens EP. Hidradenitis suppurativa: a retrospective study of 846 Dutch patients to identify factors associated with disease severity. J Am Acad Dermatol. 2014;71:460-467. 10. Canoui-Poitrine F, Revuz JE, Wolkenstein P, et al. Clinical characteristics of a series of 302 French patients with hidradenitis suppurativa, with an analysis of factors associated with disease severity. J Am Acad Dermatol. 2009; 61:51-57. 11. Kromann CB, Deckers IE, Esmann S, et al. Risk factors, clinical course and long-term prognosis in hidradenitis suppurativa: a cross-sectional study. Br J Dermatol. 2014;171:819-824. 12. Edlich RF, Silloway KA, Rodeheaver GT, Cooper PH. Epidemiology, pathology, and treatment of axillary hidradenitis suppurativa. J Emerg Med. 1986;4:369-378. 13. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60:539-561. 14. Sabat R, Chanwangpong A, Schneider-Burrus S, et al. Increased prevalence of metabolic syndrome in patients with acne inversa. PLoS One. 2012;7:e31810. 15. O’Loughlin S, Woods R, Kirke PN, et al. Hidradenitis suppurativa. Glucose tolerance, clinical, microbiologic, and immunologic features and HLA frequencies in 27 patients. Arch Dermatol. 1988;124:1043-1046. 16. Barth JH, Ng LL, Wojnarowska F, Dawber RP. Acanthosis nigricans, insulin resistance and cutaneous virilism. Br J Dermatol. 1988;118:613-619. 17. Wiltz O, Schoetz DJ Jr, Murray JJ, et al. Perianal hidradenitis suppurativa. The Lahey Clinic experience. Dis Colon Rectum. 1990;33:731-734. 18. Revuz JE, Canoui-Poitrine F, Wolkenstein P, et al. Prevalence and factors associated with hidradenitis suppurativa: results

J AM ACAD DERMATOL VOLUME 73, NUMBER 5

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32. 33.

34. 35.

36.

from two case-control studies. J Am Acad Dermatol. 2008;59: 596-601. Konig A, Lehmann C, Rompel R, Happle R. Cigarette smoking as a triggering factor of hidradenitis suppurativa. Dermatology. 1999;198:261-264. Kohorst JJ, Hagen C, Baum CL, Davis MD. Treatment experience in a local population with hidradenitis suppurativa. J Drugs Dermatol. 2014;13:827-831. Shavit E, Dreiher J, Freud T, et al. Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2015;29:371-376. Alavi A, Anooshirvani N, Kim WB, Coutts P, Sibbald RG. Quality-of-life impairment in patients with hidradenitis suppurativa: a Canadian study. Am J Clin Dermatol. 2015;16:61-65. Lesage C, Adnot-Desanlis L, Perceau G, et al. Efficacy and tolerance of prolonged infliximab treatment of moderate-to-severe forms of hidradenitis suppurativa. Eur J Dermatol. 2012;22:640-644. Verdolini R, Clayton N, Smith A, Alwash N, Mannello B. Metformin for the treatment of hidradenitis suppurativa: a little help along the way. J Eur Acad Dermatol Venereol. 2013; 27:1101-1108. Onderdijk AJ, van der Zee HH, Esmann S, et al. Depression in patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2013;27:473-478. Yadav S, Singh S, Edakkanambeth Varayil J, et al. Hidradenitis Suppurativa in Patients with Inflammatory Bowel Disease: A Population-Based Cohort Study in Olmsted County, Minnesota. Clin Gastroenterol Hepatol. doi: http://dx.doi.org/ 10.1016/j.cgh.2015.04.173. Published online May 5, 2015. van der Zee HH, de Winter K, van der Woude CJ, Prens EP. The prevalence of hidradenitis suppurativa in 1093 patients with inflammatory bowel disease. Br J Dermatol. 2014;171: 673-675. van der Zee HH, van der Woude CJ, Florencia EF, Prens EP. Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study. Br J Dermatol. 2010;162:195-197. Church JM, Fazio VW, Lavery IC, Oakley JR, Milsom JW. The differential diagnosis and comorbidity of hidradenitis suppurativa and perianal Crohn’s disease. Int J Colorectal Dis. 1993;8:117-119. Richette P, Molto A, Viguier M, et al. Hidradenitis suppurativa associated with spondyloarthritis—results from a multicenter national prospective study. J Rheumatol. 2014;41:490-494. Leybishkis B, Fasseas P, Ryan KF, Roy R. Hidradenitis suppurativa and acne conglobata associated with spondyloarthropathy. Am J Med Sci. 2001;321:195-197. Bhalla R, Sequeira W. Arthritis associated with hidradenitis suppurativa. Ann Rheum Dis. 1994;53:64-66. Rosner IA, Burg CG, Wisnieski JJ, Schacter BZ, Richter DE. The clinical spectrum of the arthropathy associated with hidradenitis suppurativa and acne conglobata. J Rheumatol. 1993;20:684-687. Fimmel S, Zouboulis CC. Comorbidities of hidradenitis suppurativa (acne inversa). Dermatoendocrinol. 2010;2:9-16. Thein M, Hogarth MB, Acland K. Seronegative arthritis associated with the follicular occlusion triad. Clin Exp Dermatol. 2004;29:550-552. Lim DT, James NM, Hassan S, Khan MA. Spondyloarthritis associated with acne conglobata, hidradenitis suppurativa and dissecting cellulitis of the scalp: a review with illustrative cases. Curr Rheumatol Rep. 2013;15:346.

Kohorst, Kimball, and Davis S35

37. Koshelev MV, Garrison PA, Wright TS. Concurrent hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of the scalp, and pyoderma gangrenosum in a 16-year-old boy. Pediatr Dermatol. 2014;31:e20-e21. 38. Maintz L, Betz RC, Allam JP, et al. Keratitis-ichthyosis-deafness syndrome in association with follicular occlusion triad. Eur J Dermatol. 2005;15:347-352. 39. Shenefelt PD. Pyoderma gangrenosum associated with cystic acne and hidradenitis suppurativa controlled by adding minocycline and sulfasalazine to the treatment regimen. Cutis. 1996;57:315-319. 40. Garcia-Rabasco AE, Esteve-Martinez A, Zaragoza-Ninet V, Sanchez-Carazo JL, Alegre-de-Miquel V. Pyoderma gangrenosum associated with hidradenitis suppurativa: a case report and review of the literature. Actas Dermosifiliogr. 2010;101:717-721. 41. Reddick CL, Singh MN, Chalmers RJ. Successful treatment of superficial pyoderma gangrenosum associated with hidradenitis suppurativa with adalimumab. Dermatol Online J. 2010;16:15. 42. Ah-Weng A, Langtry JA, Velangi S, Evans CD, Douglas WS. Pyoderma gangrenosum associated with hidradenitis suppurativa. Clin Exp Dermatol. 2005;30:669-671. 43. Hsiao JL, Antaya RJ, Berger T, et al. Hidradenitis suppurativa and concomitant pyoderma gangrenosum: a case series and literature review. Arch Dermatol. 2010;146:1265-1270. 44. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)—a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol. 2012;66:409-415. 45. Staub J, Pfannschmidt N, Strohal R, et al. Successful treatment of PASH syndrome with infliximab, cyclosporine and dapsone. J Eur Acad Dermatol Venereol. doi: http://dx.doi. org/10.1111/jdv.12765. Published online October 28, 2014. 46. Duchatelet S, Miskinyte S, Join-Lambert O, et al. First nicastrin mutation in PASH syndrome. Br J Dermatol. doi: http://dx.doi. org/10.1111/bjd.13668. Published online January 20, 2015. 47. Marzano AV, Ishak RS, Colombo A, Caroli F, Crosti C. Pyoderma gangrenosum, acne and suppurative hidradenitis syndrome following bowel bypass surgery. Dermatology. 2012;225:215-219. 48. Marzano AV, Trevisan V, Gattorno M, et al. Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene. JAMA Dermatol. 2013;149:762-764. 49. Saraceno R, Babino G, Chiricozzi A, Zangrilli A, Chimenti S. PsAPASH: a new syndrome associated with hidradenitis suppurativa with response to tumor necrosis factor inhibition. J Am Acad Dermatol. 2015;72:e42-e44. 50. Lapins J, Ye W, Nyren O, Emtestam L. Incidence of cancer among patients with hidradenitis suppurativa. Arch Dermatol. 2001;137:730-734. 51. Lavogiez C, Delaporte E, Darras-Vercambre S, et al. Clinicopathological study of 13 cases of squamous cell carcinoma complicating hidradenitis suppurativa. Dermatology. 2010;220:147-153. 52. Talmant JC, Bruant-Rodier C, Nunziata AC, Rodier JF, Wilk A. Squamous cell carcinoma arising in Verneuil’s disease: two cases and literature review. Ann Chir Plast Esthet. 2006;51: 82-86. 53. von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppurativa. Br J Dermatol. 2001;144:809-813.