10.5826/dpc.1204a208
Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the hair follicle characterized by intense discharge and pain. Recently, HS's intrinsic association with neuropsychiatric disorders has become a focus of attention, and bipolar disorder (BD) emerged as a relevant topic for such an association.  
Objective: This study aimed to evaluate BD's prevalence among HS patients and present the HS and BD overlap patients' demographics, detailed clinical characteristics with a discussion on aggravating factors. 
Patients-Method: A retrospective chart review of 247 HS outpatients (Group-1) identified eight patients with BD. The frequency of BD in HS patients is compared to psoriasis patients (Group-2) and controls (Group-3) in age- and gender-matched groups. The demographic and clinical features of the 8 patients revealing HS-BD co-existence were analysed.   
Results: BD (n=9) was the 7th most common co-morbidity in the HS cohort. The frequency of BD is detected as 3.6% in group 1, 0.7% (n=1) in group 2, and 0.6% (n=1) in group 3, respectively.  Group 1 demonstrated an increased prevalence of BD compared to other groups (p=0.001). Of the 8 patients revealing HS and BD co-existence, 75% were active smokers, 62.5% were obese and 50% had metabolic syndrome.
Conclusion: This study's results reveal that the prevalence of BD in HS patients is higher than psoriasis patients and controls. The pathogenetic mechanisms underlying BD and HS co-existence needs to be investigated further. 
text/xml
2160-9381
2081
en
Aysenur Maden
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
hidradenitis suppurativa; bipolar disorders psychiatric; co-morbidity; co-existence
 Increased Prevalence of Bipolar Disorders in Hidradenitis Suppurativa: More Than a Striking Coexistence?
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-10-31
2021-09-29
2022-10-31
2022-12-05
e2022208
Dermatol Pract Concept
Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the hair follicle characterized by intense discharge and pain. Recently, HS's intrinsic association with neuropsychiatric disorders has become a focus of attention, and bipolar disorder (BD) emerged as a relevant topic for such an association.  
Objective: This study aimed to evaluate BD's prevalence among HS patients and present the HS and BD overlap patients' demographics, detailed clinical characteristics with a discussion on aggravating factors. 
Patients-Method: A retrospective chart review of 247 HS outpatients (Group-1) identified eight patients with BD. The frequency of BD in HS patients is compared to psoriasis patients (Group-2) and controls (Group-3) in age- and gender-matched groups. The demographic and clinical features of the 8 patients revealing HS-BD co-existence were analysed.   
Results: BD (n=9) was the 7th most common co-morbidity in the HS cohort. The frequency of BD is detected as 3.6% in group 1, 0.7% (n=1) in group 2, and 0.6% (n=1) in group 3, respectively.  Group 1 demonstrated an increased prevalence of BD compared to other groups (p=0.001). Of the 8 patients revealing HS and BD co-existence, 75% were active smokers, 62.5% were obese and 50% had metabolic syndrome.
Conclusion: This study's results reveal that the prevalence of BD in HS patients is higher than psoriasis patients and controls. The pathogenetic mechanisms underlying BD and HS co-existence needs to be investigated further. 
Aysenur Maden
2022/10/31
10.5826/dpc.1204a208
e2022208
University of Health Sciences Gulhane Training and Research Hospital
2160-9381
hidradenitis suppurativa; bipolar disorders psychiatric; co-morbidity; co-existence
en
e2022208
 Increased Prevalence of Bipolar Disorders in Hidradenitis Suppurativa: More Than a Striking Coexistence?
https://dpcj.org/index.php/dpc/article/download/2081/1775
       Increased Prevalence of Bipolar Disorders in
      Hidradenitis Suppurativa: More Than a Striking
                      Co-existence?
                                                Pelin Esme1, Aysenur Botsali1


1 Department of Dermatology and Venereology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey



Key words: Hidradenitis suppurativa, bipolar disorders, psychiatric, co-morbidity, co-existence
Citation: Esme P, Botsali A. Increased Prevalence of Bipolar Disorders in Hidradenitis Suppurativa: More Than a Striking Co-existence?
Dermatol Pract Concept. 2022;12(4):e2022208. DOI: https://doi.org/10.5826/dpc.1204a208
Accepted: March 7, 2022; Published: October 2022
Copyright: ©2022 Esme et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Aysenur Botsali, Department of Dermatology and Venereology, University of Health Sciences, Gulhane Training and
Research Hospital, Ankara, General Dr. Tevfik Saglam Street, Kecioren/Ankara, zip code:06010, Turkey, E-mail: abotsali@hotmail.com




  ABSTRACT             Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the hair
                       ­follicle characterized by intense discharge and pain. Recently, HS intrinsic association with neuropsy-
                        chiatric disorders has become a focus of attention, and bipolar disorder (BD) emerged as a relevant
                        topic for such an association.
                       Objectives: This study aimed to evaluate BD prevalence among HS patients and present the HS and
                       BD overlap patients demographics, detailed clinical characteristics with a discussion on aggravating
                       factors.
                       Methods: A retrospective chart review of 247 HS outpatients (Group-1) identified nine patients with
                       BD. The frequency of BD in HS patients is compared to psoriasis patients (Group-2) and controls
                       (Group-3) in age- and gender-matched groups. The demographic and clinical features of the 9 patients
                       revealing HS-BD co-existence were analyzed.
                       Results: BD (N = 9) was the 7th most common co-morbidity in the HS cohort. The frequency of BD
                       is detected as 3.6% in group 1, 0.7% (N = 1) in group 2, and 0.6% (N = 1) in group 3, respectively.
                       Group 1 demonstrated an increased prevalence of BD compared to other groups (P = 0.001). Of the
                       9 patients revealing HS and BD co-existence, 66.6% were active smokers, 66.6% were obese and
                       44.4 % had metabolic syndrome.
                       Conclusions: This study results reveal that the prevalence of BD in HS patients is higher than psoriasis
                       patients and controls. The pathogenetic mechanisms underlying BD and HS co-existence needs to be
                       investigated further.




Original Article | Dermatol Pract Concept. 2022;12(4):e2022208                                                                           1
Introduction                                                       the University of Health Sciences between September 2018
                                                                   and November 2020 were included. The authors conducted
Hidradenitis suppurativa (HS) is a highly painful and ex-          a retrospective chart review to extract the variables of inter-
tremely destructive, inflammatory skin disease of the hair         est, including the patients demographic and clinical features
follicle with substantial negative psychosocial impacts on         (age, gender, age of onset, disease duration, Hurley stage,
patients. Many HS patients suffer from psychiatric condi-          ­International Hidradenitis Suppurativa Severity Score Sys-
tions, such as depression, anxiety, impaired self-esteem, and      tem (IHS4), accompanying medical co-morbidities, particu-
stigmatization. Therefore, a psychiatric evaluation of HS          larly psychiatric disorders, medications). The patients in this
­patients is strongly recommended [1]. Through the evalua-         manuscript have given informed consent to publication of
tion of neuro-psychiatric disorders in HS patients, bipolar        their case details.
disorders (BD) have just begun to attract attention [2,3].             Besides, two study groups, including age- and ­gender-
    HS and BD are relatively common conditions affecting           matched patients, were enrolled. These groups were com-
more than 1% of the population for each condition. The on-         posed of psoriasis patients (group-2) and patients admitted
set of these chronic, fluctuating diseases is typically in young   with a non-inflammatory skin disease (eg, xerosis, tinea
adulthood and both are considered as leading causes of dis-        ­pedis, and localized dermatitis) to the outpatient clinic of the
ability among young people [4-6].                                  same tertiary center (group-3).
    A substantial proportion of BD patients report a positive          Among the selection of the study population, all of the
family history for BD connoting the contribution of genetics;      psoriasis patients received at least one systemic agent, inclu-
however similar to HS, the multifactorial model including          ding conventional drugs or biologic agents. Only the cases
gene environment interactions is accepted as the best concept      with missing data were excluded from the overall study
to explain BD etiopathogenesis [7]. Furthermore, numerous          population, and no additional specific exclusion criteria
associations have been purported between bipolar disorder          were used.
and other medical co-morbidities including cardiovascular              The authors analyzed patients revealing BD and HS
disorders, diabetes and obesity [8-11]. The higher prevalence      co-existence, particularly for possible aggravating factors.
of these medical co-morbidities in BD is principally explained         The National Cholesterol Education Program (NCEP)
via three perspectives including the adverse effects of phar-      Adult Treatment Panel III (ATP III)-2001 Metabolic Syn-
macological treatments, genetic vulnerability, and lifestyle       drome Diagnosis Criteria was implemented to evaluate
(eg smoking, malnutrition, and sedentary life-style) [4,12].       metabolic syndrome as it is the most cited definition for
    Population-based studies were conducted to search for an       ­metabolic syndrome.
intrinsic relationship between HS and BD with conflicting re-
sults [2,3,13]. Some studies reported a remarkably increased       Statistical Analysis
prevalence of BD among HS patients; however, others did not        Statistical analyses were performed using the Statistics Pack-
confirm such an association. Lithium, one of the most effec-       age for the Social Sciences (SPSS) for Windows version 22.0
tive treatments for the prevention of both manic and depres-       (IBM, Armonk, NY, USA). Numerical variables were pre-
sive episodes is also acknowledged as an extrinsic factor to       sented as mean ± SD or median (min-max). Categorical vari-
exacerbate HS lesions [14]. Additionally, similar to BD, smok-     ables were shown by number and percentage. P < 0.05 was
ing and obesity are strongly linked to HS pathogenesis (4). BD     considered significant in all comparisons.
and HS are complex traits influenced by numerous common                This study must recruit 59 individuals for each group
genetic variants; however, the existence of a genetic associa-     to have 80% power with 5% type I error level to detect
tion between HS and BD has nott been investigated [15,16].         clinically significant difference of 1% prevalence when the
                                                                   ­expected value in the control group is 1%.
Objectives
                                                                   Results
This study aimed to evaluate BD prevalence among HS
­patients and present the HS and BD overlap patients’ demo-        A total of 247 HS patients (group 1), consisting of 105
graphics, detailed clinical characteristics with a discussion      ­females and 142 males, between 14-68 years of age (mean
on aggravating factors.                                            age: 33.48 ± 11.6 years), were eligible for inclusion in the
                                                                   study. The mean disease duration was 7.3 ± 6.9 years (range
                                                                   0-35). Of 247 patients, 186 (75,3%) and 14 (5,6%) were
Methods
                                                                   active and ex-smokers respectively with an average of 12,7 ±
The patients diagnosed and followed up in the HS outpa-            14,3 (range 1-90) pack-year smoking history. The mean body
tient clinic of Gülhane Training and Research Hospital of          mass index (BMI) was 28.6 ± 6,8 (min-max:14,8-85) and



2                                                                      Original Article | Dermatol Pract Concept. 2022;12(4):e2022208
                      Table 1. Demographic and clinical characteristics of 247 HS patients
                                 Demographic and clinical characteristics of 247 HS patients
 Gender (female/ male)                                                                            105 / 142
 Age, years (mean±SD) (min-max)                                                              33.48±11,6 (14-68)
 Mean disease duration, years (mean±SD) (min-max)                                               7.3±6,9 (0-35)
 Active smokers (%) / packet-year (mean±SD) (min-max)                                        75 /12.7±14.3 (1-90)
 Body mass index (mean±SD) (min-max)                                                          28.6±6.8 (14,8-85)
 Hurley stage (N/%)                                                                              82, 33.2%
 I                                                                                               81, 33.8%
 II                                                                                              84, 34.0%
 III
                                                         N (%)                                                      N( %)
 Diabetes mellitus                                      31 (12.5)              Psoriasis                            5 (2.0)
 Hypertension                                            16 (6.4)              Crohn disease                        4 (1.6)
 Spondyloarthropathy/ arthritis                          15 (6.0)              Pulmoner disease                     4 (1.6)
 Hyperlipidemia                                          12 (4.8)              Down syndrome                        2 (0.8)
 Familial Mediterranean Fever                            10 (4.0)              Pyoderma gangrenosum                 2 (0.8)
 Chronic cardiac disease                                 10 (4.0)              Vitiligo                             1 (0.4)
 Bipolar disorder                                         9 (3.6)              Multiple sclerosis                   1 (0.4)
 Thyroid disease                                          8 (3.2)

N = number of patients; SD = standard deviation; % percentage of patients.


33.2% (N = 82) of the patient BMI were over 30. The dis-              was present in 4/9 (44.4%) of the patients with HS and
tribution of Hurley staging was as follows: stage I (N = 82,          BD. Totally (88.8%) 8 of the HS patients had moderate to
33,2%), stage II (N = 81, 33,8%), and stage III (N = 84,              severe HS according to the Hurley stage and IHS4 scores.
34%). Among 15 co-morbidities detected within the current             The median disease duration of HS and BD was as fol-
                            th
HS cohort, BD was the 7 most common, encountered in 9                 lows, 6 (min-max:4-20, interquartile range [IQR]: 11) and
(3.6 %) patients (Table 1).                                           7 (min-max:2-16, IQR: 10.5) Of the HS patients, 5 were
    The authors reviewed psoriasis patients (group 2,                 on adalimumab and 4 were on doxycycline. Of nine cases
N = 135) and patients without an inflammatory skin dis-               with HS and BD, 4 (44.4%) had concurrent metabolic syn-
order (group 3, N = 152) for the presence of BD. Only one             drome. Most frequently used current medications for BD in
patient had BD diagnosis per group 2 (0.7%, N:1/135) and              HS patients were lithium (N = 5/9) and sodium valproate
group 3 (0.6%, N:1/152).                                              (N = 4/9), respectively. Of 9 HS patients, 6had been pre-
    The patient in group 2 was a 40-year-old male. He had             scribed lithium previously, and 3/6 (50%) reported exacer-
been diagnosed with psoriasis 9 years ago and BP onset was            bations under lithium. Because of uncontrolled BD despite
noted within the following year. His BMI was 33.9 and he              multiple treatments, lithium had to be continued in two of
had never smoked before. He revealed chronic plaque psori-            these 3 patients who described exacerbations.
asis without psoriatic arthritis. His previous medical history
was unremarkable. The initial treatment choice for this pa-
                                                                      Conclusions
tient was methotrexate which was replaced by certolizumab
pegol injections due to inefficacy. Psoriasis Area Severity In-       In the current study, the prevalence of BD was 3,6 %.
dex [PASI] score reduced from the baseline value of 8 to 1.5          BD ­frequency was significantly higher in the HS cohort than
         th
on the 6 month of certolizumab pegol treatment.                       the psoriasis cohort and control patients. Physicians dealing
    The dermatological diagnosis of the BD case in the con-           with HS patients are familiar with psychiatric complaints,
trol group was basal cell carcinoma. The prevalence of BD in          occasionally leading to anxiety and depression [17-19].
the HS cohort (3.6%) was 4.5 and 6 times higher than in the           HS substantial burden on quality of life measures has been
psoriasis cohort (0.7%) and controls (0.6%) (P = 0.001 for            proposed as the principal causal factor for the association of
Group1-2 and Group 1-3).                                              HS and psychiatric co-morbidities [19,20].
    Table 2 exhibits the demographic and clinical character-                 Associations between several endocrinologic, meta-
istics of 11 patients with BD.The majority of the p
                                                  ­ atients           bolic and rheumatological disorders and HS reveal that
with BD were male (N=7/11). Similarly, 6/9 of the patients            HS is more than skin deep [21]. Deciphering the interdis-
with HS and BP were male. Family history of HS or BD                  ciplinary links is essential for HS optimal management and



Original Article | Dermatol Pract Concept. 2022;12(4):e2022208                                                                    3
    Table 2 Demographic and clinical characteristics of patients with bipolar disorders in Group 1 (HS patients), Group 2 (psoriasis patients) and Group 3
                                                                        (control group).
                                         P1              P2            P3               P4               P5              P6              P7              P8            P9            P10           P11
    Age (years)                          45              52            33               43               59              30              40              33            33             40            37
    Gender                               M               M             M                 F                F              M               M               M              F             M                 F
    Family history HS/psoriasis          -                -             -                +                -               -               +               +             +              -                -
    Family history BD                    -                +             -                -                -               +               +               _             +              -                -
    BMI                                25,7             36,1          29,2             29,4              30             30.7            37.0            35,4          43,6           23.5          22.3
                        a
    NCEP-ATPIII MS                       -                -             +                +                +               -               +               -             -              -                -
    a
        Waist circumference (cm)         87              94            115              98               84             115             135             122            110             -                -
    a
        Trigliceryde (mg/dL)            225             179            430             320               175            235             391             259            194             -                -
    a
        HDL-c (mg/dL)                    30              35            34               32               35              40              40              43            59              -                -
    a
     Blood pressure                      -                -             -                +                +               -               +               -             -              -                -
    >130/85 mmHg
    a
        Fasting glucose (mg/dL)          89              91            188             103               95              81             121              99            73              -                -
    Active smoker                        +                +             +                +                -               +               +               -             -              -                +
    Hurley stage                         1                3             3                2                3               2               3               3             2          Current              -
    IHS4 score                           6               15            18               11               14               4               9              12             3          PASI:1.5             -
                                                                                                                                                                                      -
    Duration of HS/                      10               4             6               20               20               6               5              0,5           12              9                -
    psoriasis (years)
    Duration of BD (years)              12                7             2                2               10               6              16               4            15              6            12
    Current treatment-HS               Doxy        ADA, 2 years       ADA,        Doxy, surgery         ADA,           Doxy            ADA,            ADA,           Doxy      Certolizumab            -
                                                                     2 years                           4 years                       6 months        6 months                       pegol
    Current treatment-BD             Lithium,        Lithium,        Lithium,    Trifluoperazine       Lithium,       Sodium         Lithium,          Sodium        Sodium        Sodium        Lithium
                                     sodium         Ziprasidone     quetiapine   hydrochloride,      lamotrigine     valproate,     Risperidone      valproate,     valproate     valproate
                                    valproate,     hydrochloride                  Venlafaxine                       aripiprazole                     fluoxetine
                                    quetiapine,
                                    bupropion
    Co-morbidities                       -            DM, HL            -           HT, DM,            HL, HT             -              HT         Hypertrigly­­       -              -                -
                                                                                 spondylarthritis,    glaucoma                                       ceridemia
                                                                                      FMF
Ada = adalimumab; BD = bipolar disorders; BMI = body mass index; doxy = doxycycline; F = female; M = male; P = patient; P1-P9 = hidradenitis suppurativa; P10 = psoriasis; P11 = basal cell carcinoma
a
    NCEP-ATPIII MS: Presence of at least 3 of the 5 items marked.
determining novel treatment strategies. In this study, the HS     lesions in 25% and 75% of the patients [2]. In the current
patients with BD were analyzed in detail for the presence of      study, six of nine BD patients with a history of lithium use
common predisposing factors. Of these 9 patients, 4 (44.4%)       experienced HS exacerbations. Accordingly, a key question
had metabolic syndrome (Table 2). Three (33.3%) patients          for the physicians encountering HS and BD co-existence is as
were overweight, and 6 (66.6%) patients BMI were over 30.         follows: should lithium be avoided in these cases even in the
Furthermore, 6 (66.6%) of them were active smokers. These         earliest stages of HS to prevent HS progression? The correct
findings suggest the contribution of extrinsic factors to the     response relies on each patient’s individual features and the
HS-BD co-existence. Among psychiatric research, genome            interdisciplinary interactions. Considering other treatment
wide association studies (GWAS) have introduced interest-         options may be more appropriate, if not, indeed required for
ing perspectives on the intricate relationship of psychiatric     BD management. However, in the current cohort, three cases
disorders with concurrent co-morbidities, especially obesity      never used lithium. Additionally, six cases defined HS onset
and metabolic syndrome [22].                                      before or concurrent with BD diagnosis, highlighting addi-
    On the other hand, more recently, HS and neuropsychi-         tional factors’ contribution.
atric disorders’ possible intrinsic relationship has become a        Some immunological studies have highlighted the in-
focus of attention. Genetic studies point out shared patho-       creased level of tumor necrosis factor-alpha (TNF)-α, soluble
genesis for HS and Alzheimer disease (AD), both revealing         interleukin (IL)-2 receptor, soluble TNF receptor 1 (TNFR1),
mutations within the adjacent parts of the gamma-­secretase       IL-26 and IL-6 levels in BD, just as HS [2,8,29]. HS is dis-
gene [23]. However, population-based studies do not d
                                                    ­ etect       tinguished among other inflammatory skin diseases related
an increased risk of AD in HS patients [[24,25]. This is          to the substantially increased cytokine burden [30]. Thus,
not surprising considering the relatively younger age of          the CNS effects of the altered cytokine pattern may be more
HS patients.                                                      pronounced compared to other inflammatory skin diseases.
    BD increased prevalence among HS patients emerged as          Upon study design, to search for the confounding role of
another relevant topic to search for an intrinsic relationship.   chronic inflammation on BD, the authors selected the age-
For the 9 patients revealing HS-BD co-existence, 4 (44.4%)        and gender-matched controls from psoriasis patients, the
had a positive family history for HS and 4 (44.4%) had a          prototypic chronic inflammatory skin disease which is also
positive family history for BD. Only two (22.2%) patients         linked to metabolic syndrome and obesity [31]. Moreover,
reported a positive family history for both BD and HS.            another control group was assigned among outpatients with-
    Scarce data exist on the co-existence of HS and BD.           out a chronic inflammatory skin and/or systemic disease.
Initially, Tzur Bitan et al. reported a sevenfold increase        The results of the study pointed out an increased prevalence
in the prevalence of BD among HS patients (0.7%, 29 of            of BD in only HS patients but not psoriasis patients com-
4,191) compared with controls (0.1%) in a nationwide              pared to that of the control group.
population-based study [2]. In another large cohort, BD              The association between the inflammatory cytokines
prevalence in HS was 0.6% (9 of 1,411 HS patients) [3].           and BD warrants further investigation related to both di-
BD frequency in HS is relatively lower in these two studies       agnostic and also possible therapeutic insights. Due to the
compared to the current research [2,3]. On the contrary, a        shared immunologic pathways, a single immunomodulatory
Finnish nationwide registry study indicated a higher figure       drug has the potential to relieve both HS and BD symptoms.
of 3.1% in HS patients, similar to the current study results      While the anhedonia symptoms of the patients with bipolar
[4]. The apparent differences between these studies reveal the    I/II depression improved significantly under infliximab [32],
requirement of an additional evaluation for the study region      no clinical improvement was evident in resistant depression
baseline characteristics. Studies related to BD in Turkey have    with infliximab in two other placebo-controlled clinical tri-
exhibited a similar prevalence to those in other countries        als [33,34]. Even if there is no clinical benefit, a considerable
[26,27]. Turkey is considered one of the countries with the       reduction in highly sensitive C-reactive, TNFR1, and nuclear
lowest prevalence of mental disorders [28]. Geographic loca-      factor-kappa B (NF-κB) proteins were remarkable for bipo-
tion cannot explain BD increased prevalence in the current        lar depression [34,35].
study. Instead, it may be related to our department character-       Currently, the only FDA-approved treatment for HS is
istics as a referral center with higher awareness and clinical    adalimumab [1]. Although the direct efficacy of adalim-
experience for HS patients.                                       umab on BD has not been reported, the available data from
    Lithium effect on HS is possibly patho-physiologically        Crohn disease, rheumatoid arthritis, and ankylosing spon-
related to acneiform eruption induction [2]. Benhadou et          dylitis cohorts receiving adalimumab report lower depres-
al detected exacerbations in eight of nine HS patients who        sion scores, improvement in somatic symptoms, and mental
were prescribed lithium for BD. Lithium was suggested as          scores amelioration [36]. In the current study, 5/9 patients
the potential cause for the initiation and worsening of HS        with BD and HS have been taking adalimumab for 6 months



Original Article | Dermatol Pract Concept. 2022;12(4):e2022208                                                                   5
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Original Article | Dermatol Pract Concept. 2022;12(4):e2022208                                                                                     7
