ArticlePDF AvailableLiterature Review

Understanding the Relationship Between Smoking and Hidradenitis Suppurativa

Authors:
  • School of Medicine University of Zagreb, Zagreb, Croatia
  • University Hospital Center Zagreb, University of Zagreb School of Medicine

Abstract

Hidradenitis suppurativa (HS) is a chronic skin disease affecting hair follicles in intertriginous areas, characterized by deep, recurrent, painful nodules and abscesses, fistulae, sinus tracts, and scarring. With a prevalence of 1-4%, HS is not an uncommon disease. Several risk factors have been linked with the development of HS, such as genetic predisposition, smoking, and obesity, leading to the hypothesis that HS develops as a result of environmental triggers in a genetically susceptible individual. Smoking has been recognized as one of the environmental factors with the most impact on HS. This review aims to provide a comprehensive and holistic view on how smoking habits affect the incidence, severity, treatment, and pathophysiology of HS. A growing body of published literature has reported the association between smoking and HS, despite limitations in proving the causal relationship due to the retrospective design of the available studies. There is a consensus that patients with HS who are active smokers have a higher number of affected body areas than patients with HS who do not smoke or have stopped smoking. Similarly, it is recommended for patients with HS to discontinue tobacco use because of its association with weaker treatment response. Studies on the pathophysiological mechanism of smoking on the skin show that tobacco smoke with many of its chemicals as well as nicotine promote the proinflammatory cytokines found in HS lesions, activate the nicotinic acetylcholine (nAChRs) and aryl hydrocarbon receptors (AHRs), and further suppress Notch signaling pathway.
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ACTA DERMATOVENEROLOGICA CROATICA
Understanding the Relationship Between Smoking
and Hidradenitis Suppurativa
Zrinka Bukvić Mokos, Joško Miše, Anamaria Balić, Branka Marinović
Department of Dermatology and Venereology, University Hospital Centre Zagreb,
School of Medicine University of Zagreb, European Reference Network (ERN) – Skin
Reference Center, Zagreb, Croatia
Corresponding author:
Joško Miše, MD
Department of Dermatology and Venereology
University Hospital Center Zagreb
School of Medicine, University of Zagreb
Šalata 4
10000 Zagreb
Croatia
joskojerolim@gmail.com
Acta Dermatovenerol Croat 2020;28(1):9-13 REVIEW
ABSTRACT Hidradenitis suppurativa (HS) is a chronic skin disease
aecting hair follicles in intertriginous areas, characterized by deep,
recurrent, painful nodules and abscesses, stulae, sinus tracts, and
scarring. With a prevalence of 1-4%, HS is not an uncommon disease.
Several risk factors have been linked with the development of HS,
such as genetic predisposition, smoking, and obesity, leading to the
hypothesis that HS develops as a result of environmental triggers in
a genetically susceptible individual. Smoking has been recognized
as one of the environmental factors with the most impact on HS.
This review aims to provide a comprehensive and holistic view on
how smoking habits aect the incidence, severity, treatment, and
pathophysiology of HS. A growing body of published literature has
reported the association between smoking and HS, despite limita-
tions in proving the causal relationship due to the retrospective de-
sign of the available studies. There is a consensus that patients with
HS who are active smokers have a higher number of aected body
areas than patients with HS who do not smoke or have stopped
smoking. Similarly, it is recommended for patients with HS to discon-
tinue tobacco use because of its association with weaker treatment
response. Studies on the pathophysiological mechanism of smok-
ing on the skin show that tobacco smoke with many of its chemicals
as well as nicotine promote the proinammatory cytokines found
in HS lesions, activate the nicotinic acetylcholine (nAChRs) and aryl
hydrocarbon receptors (AHRs), and further suppress Notch signaling
pathway.
KEY WORDS: hidradenitis suppurativa, acne inversa, smoking, to-
bacco, cigarette
INTRODUCTION
Hidradenitis suppurativa (HS) is a chronic, relaps-
ing, inammatory skin disease that appears as a re-
sult of follicular occlusion and secondary rupture of
the sebofollicular junction of folliculopilosebaceous
units (FPSUs). Consequently, an inammatory cas-
cade occurs, presenting as recurrent, painful, and in-
amed nodules that often rupture and leak purulent
material (1). The chronic timeline of the disease leads
10 ACTA DERMATOVENEROLOGICA CROATICA
to the progression of nodules into abscesses, epithe-
lialized sinuses, stulae, and characteristic “rope-like”
scarring (2).
HS clinically presents at several predilection sites,
rich in apocrine glands, such as the axillae, perianal,
and perineal regions. However, other areas can often
be involved, such as the neck, retroauricular area,
back, inner thighs, scrotum or labia, and the inframa-
mmary and mammary region in women. In women,
inguinal and mammary regions are more commonly
aected, while the anogenital area is more often af-
fected in men (1). The early-stage diagnosis of hidrad-
enitis suppurativa is often missed due to patients rst
presenting to emergency wards or surgical depart-
ments and the general lack of awareness of the sever-
ity of the condition.
The prevalence of hidradenitis suppurativa has
been estimated at 1-4% in the general population (1).
It aects young adults in their early twenties with an
average disease onset at 21.8 years of age. HS is more
frequent among women, except in the age group
above 50 years, because in women the condition
tends to subside after menopause.
Several risk factors have been linked with the
development of HS, such as genetic predisposition,
smoking, and obesity, leading to the hypothesis that
HS develops as a result of environmental triggers in
a genetically susceptible individual. Among the en-
vironmental factors playing a role in HS, smoking
has been extensively researched as dermatologists
and scientists struggle to determine the relationship
between smoking and HS. This review article aims to
summarize the growing body of literature on smok-
ing and HS and to dene the role of smoking in the
development of HS.
METHODOLOGY
An extensive literature review was conducted of
the PubMed and Web of Science databases, as well as
a search on Google Scholar. Using the keywords (hi-
dradenitis suppurativa, acne inversa, smoking, tobac-
co, cigarette), we analysed original scientic articles,
review articles, and letters to the editors.
THE RELATIONSHIP BETWEEN SMOKING
AND HIDRADENITIS SUPPURATIVA: FROM
KARL MARX TO MODERN ERA
Little did Karl Marx know that his smoking habits
and skin condition would be in the center of derma-
tologists’ debate over the relationship between smok-
ing and HS. The debate over the causes of Karl Marx’s
skin condition started in 2007 when Sam Shuster
published that Marx’s incapacitating skin disease was
likely hidradenitis suppurativa (3). Since Marx was a
chronic heavy smoker, dermatologists were quick to
point out that smoking caused one of the most inu-
ential thinkers of the nineteenth century to develop
a debilitating skin disease, which aected his life and
work (4). Others were horried by the idea of using
Karl Marx, one of the symbols of scientic rationalism,
to causally link smoking and HS amidst the lack of
statistical evidence of a causal relationship (5). There
have been several studies assessing the relationship
between smoking and HS even before Sam Shuster’s
essay on Karl Marx. As early as 1997, the rst stud-
ies reported the observation of a high prevalence of
smokers among patients with HS. In 1997, Bassukas
and Hundeiker suggested that toxic tobacco smoke
might contribute to the pathogenesis of HS (6).
Konig et al. assessed the inuence of smoking
habits among 84 patients with HS and found out that
88.9% of their patients with HS were active smokers,
which was a signicantly higher rate than the rate of
active smokers in the matched-pair control group (7).
They further elaborate that it seems to be a rare event
that a never-smoker suers from HS. Happle and Ko-
nig’s later work from 2011 suggests the more specic
term “smoker’s boils” for HS lesions of patients who
are smokers, elaborating that the renaming would al-
low for a correct diagnosis at the initial stage of the
disease. Such a proposal came after several close
statistical relationships between HS and smoking
were reported in several studies (8,9). Newer research
methods, such as radioimmunoassay, have added to
the growing evidence showing that both active and
passive smokers excrete considerable amounts of
nicotine with their sweat (10).
A recent study that investigated HS incidence
among tobacco smokers in a large, diverse cohort of
50 million patients across the U.S. showed that the
odds of a new diagnosis of HS were increased by 90%
among those who smoked tobacco (11).
However, several articles have also been pub-
lished that downplay the importance of smoking as
a risk or triggering factor for HS (12,13). In a French
analysis of 302 medically assessed patients and 67
self-diagnosed patients with HS, current smokers had
12.5- and 4-times higher odds of having HS, respec-
tively (14). However, a history of previous smoking
was not associated with HS, suggesting that smoking
habits may have been a consequence of the disease.
Some authors have even gone further in questioning
the work of Garg et al., implying that their conclusions
about the relationship between smoking and HS go
well beyond what is permissible from the evidence
Bukvić Mokos et al. Acta Dermatovenerol Croat
Hidradenitis suppurativa and smoking 2020;28(1):9-13
11
ACTA DERMATOVENEROLOGICA CROATICA
(15). Shuster acknowledges the higher percentage
of active smokers among patients with HS but states
that this fact does not allow the presumption of cau-
sality, accusing some authors of misapplication of as-
sociative epidemiology to etiology (5). Several other
authors also questioned whether smoking increases
the risk of developing HS de novo or is instead a con-
sequence of the disease (high rates of depression and
anxiety among patients with HS; HS inuencing indi-
viduals to smoke tobacco to cope with the psycho-
logical impact of the disease) (16,17).
While there are inherent limitations in retrospec-
tive studies linking smoking and HS, including the
ability to establish a real temporal relationship, there
is a growing body of literature establishing the asso-
ciation between smoking and HS. As clinicians, how-
ever, it is our responsibility to inform every patient
with a dermatological condition about the harmful
eects of smoking on the skin.
TOBACCO SMOKING AND THE SEVERITY
OF HIDRADENITIS SUPPURATIVA
The role of lifestyle factors on HS, such as tobacco
smoking, deserves special consideration as they are
modiable by the patients themselves and could rep-
resent an opportunity for a successful self-mitigating
course for disease remission.
Available studies show conicting results on the
association of smoking with HS severity. Matusiak et
al., in an investigation of 54 Polish patients, found no
signicant correlation between smoking and clinical
severity based on the Hurley scale or with an earlier
onset of the disease. However, there was a signicant
dierence between the group of active smokers and
nonsmokers concerning the number of skin areas af-
fected by HS lesions (18).
Dessinioti et al., in their study of 133 patients, found
that the severity of HS according to Hurley staging
was not associated with current or former smoking
compared with non-smoking. However, similar to the
ndings of Matusiak et al., they reported that current
or former smoking was associated with the number
of aected body areas, i.e. with an increased risk for
active smokers to have more than two body areas af-
fected compared with non-smokers (19).
A study of 115 patients with HS conducted by Sar-
torius et al. reported higher severity HS (according to
the modied Hidradenitis Suppurativa Score (HSS)) in
smokers compared with nonsmokers (20). This nd-
ing might suggest that the recently developed, more
detailed HSS can capture more of the essential clini-
cal information on the patient’s habits than Hurley
staging.
Regarding the cessation of smoking and the re-
mission of HS, Matusiak et al. observed no signicant
alteration in the clinical manifestations of HS in pa-
tients who ceased to smoke (21). However, in study
on 212 patients by Kromann et al., no smoking was
2.8 times more likely to be associated with self-re-
ported remission compared to active smoking (21).
TOBACCO SMOKING AND TREATMENT
RESPONSE
While there are conicting studies on the link
between tobacco smoking and HS, both regarding
occurrence and disease severity, there is a growing
body of evidence suggesting that smoking status in-
uences response to treatment. Kroman et al. showed
that 66% of their patients who reported remission
were nonsmokers and that those who did not smoke
were two times more likely to self-report remission
compared with smokers (21).
A study by Denny et al. found that nonsmokers or
former smokers were almost three times more likely
to have an improvement in their disease compared
with current smokers by being more likely to positive-
ly respond to conventional medical therapies, includ-
ing antibacterial washes/creams/lotions, topical and
oral antibiotics, and intralesional corticosteroids (22).
There is a consensus suggesting physicians
strongly recommend their patients with HS to dis-
continue tobacco use because of its association with
weaker treatment response.
THE PATHOMECHANISM OF SMOKING
EFFECTS ON THE SKIN HELPS US UNDER-
STAND THE INTERESTING CLINICO-EPIDE-
MIOLOGICAL HYPOTHESIS ON THE LINK
BETWEEN SMOKING AND HS
In trying to determine the specic type of relation-
ship between smoking and HS (epidemiological or
causal), we need to delve into the pathomechanisms
of HS and how nicotine and chemicals from tobacco
smoke could induce the formation of HS lesions.
There is a growing body of literature on the patho-
physiology of HS suggesting multifactorial causes to
the emergence of HS phenotype. Cytokines involved
in HS pathogenesis include interleukin (IL)-1β, IL-17,
IL-10, IL-23, and, to a lesser extent TNF-α (23). Their
potent pro-inammatory capacity drives the inux
of immune cells and triggers the inammatory re-
sponse cascade. Studies of the genetic aberrations in
HS found that the loss of function mutations in the
gamma-secretase gene is associated with HS. Since
gamma-secretase cleaves intracellular Notch, the
Bukvić Mokos et al. Acta Dermatovenerol Croat
Hidradenitis suppurativa and smoking 2020;28(1):9-13
defect of the Notch signaling pathway leads to the
formation of follicular keratin-enriched epidermal
cysts and negative regulation of Toll-like receptors,
with a consequent excessive cornication in the pro-
inammatory environment.
Tobacco smoke is composed of many chemicals,
some of which, along with nicotine, propagate the
pathophysiological pathway described in HS. Along
with nicotine, these chemicals activate keratino-
cytes via nicotinic acetylcholine (nAChRs) and aryl
hydrocarbon receptors (AHRs), leading to acantho-
sis, infundibular epithelial hyperplasia, and exces-
sive cornication (24). Nicotine also alters the host’s
defense by inducing the generation of pro-inam-
matory cytokines by keratinocytes, chemotaxis, and
Th17 cell induction (25). Moreover, nicotine elicits
the proliferation of Staphylococcus aureus (26), and
other tobacco smoke components enhance bacterial
virulence by increasing cellular adhesion and induc-
ing biolm production (27,28). A study by Melnik et
al. reported down-regulation of the Notch signaling
pathway in active smokers, suggesting that cigarette
smoke, which is prevalent in HS, may further suppress
already decient Notch signaling in HS (24).
Connecting the damaging eects of tobacco
chemicals and nicotine with the pathomechanism
that causes HS lesions seems to be one of the best
explanations of a causal relationship between smok-
ing and HS.
CONCLUSION
HS is a multifaceted skin disorder with a complex
etiology involving genetic and environmental fac-
tors. An investigation into the etiology and nature of
the disease presents an opportunity to identify and
address modiable risk factors that would potential-
ly alter the incidence and the course of the disease.
Smoking habits have been identied as one of the
risk factors, as it has been observed that many pa-
tients with HS smoke. To scientically prove the exact
causal relationship between smoking and HS, large
multicenter studies are needed instead of retrospec-
tive studies. Even though this relationship is likely to
remain debatable, we strongly encourage patients
with HS to quit smoking as evidence for damaging
pathomechanism eects of nicotine, tobacco smoke,
and its chemicals on skin and HS lesions is convinc-
ing. Thus, this review supports the hypothesis that
environmental triggers, such as cigarette smoking,
may result in the HS phenotype in a genetically sus-
ceptible individual.
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Bukvić Mokos et al. Acta Dermatovenerol Croat
Hidradenitis suppurativa and smoking 2020;28(1):9-13
... Some studies suggest that nicotine overstimulates sweat gland, leading to blockage of the glandular ducts 14 and a subsequent in ammatory reaction. Additionally, nicotine modi es sweat gland activity, producing proin ammatory cytokines, such as interleukin (IL)-8 and TNF-alpha, 15 which causes abnormal glandular secretion seen in HS. 14,15 Nicotine acetylcholine receptors suppress the NOTCH signaling pathway, a key cell pathway that is involved in cell-to-cell communication, gene regulation, cell regulation, and cell di erentiation. 15 Dysregulation of this pathway is associated with multiple disease states, including HS. 15 Moreover, nicotine is associated with Staphylococcus aureus growth, commonly found in severe HS lesions. ...
... Some studies suggest that nicotine overstimulates sweat gland, leading to blockage of the glandular ducts 14 and a subsequent in ammatory reaction. Additionally, nicotine modi es sweat gland activity, producing proin ammatory cytokines, such as interleukin (IL)-8 and TNF-alpha, 15 which causes abnormal glandular secretion seen in HS. 14,15 Nicotine acetylcholine receptors suppress the NOTCH signaling pathway, a key cell pathway that is involved in cell-to-cell communication, gene regulation, cell regulation, and cell di erentiation. 15 Dysregulation of this pathway is associated with multiple disease states, including HS. 15 Moreover, nicotine is associated with Staphylococcus aureus growth, commonly found in severe HS lesions. ...
... Additionally, nicotine modi es sweat gland activity, producing proin ammatory cytokines, such as interleukin (IL)-8 and TNF-alpha, 15 which causes abnormal glandular secretion seen in HS. 14,15 Nicotine acetylcholine receptors suppress the NOTCH signaling pathway, a key cell pathway that is involved in cell-to-cell communication, gene regulation, cell regulation, and cell di erentiation. 15 Dysregulation of this pathway is associated with multiple disease states, including HS. 15 Moreover, nicotine is associated with Staphylococcus aureus growth, commonly found in severe HS lesions. 16 A case-control study that reviewed demographic and anthropometric factors in relation to HS showed a 14-fold increase in the incidence of HS in smokers. ...
Article
Full-text available
Objective: Hidradenitis suppurativa (HS) is a debilitating, chronic, dermatological inflammatory skin disease that affects apocrine gland bearing skin in the axillae, groin, and inframammary regions. It is underdiagnosed and its pathogenesis incompletely understood. This paper provides a comprehensive review of the existing literature on the surgical management of HS, focusing upon outcomes of definitive surgery. Methods: A literature search was conducted according to PRISMA guidelines. PubMed and EMBASE databases were searched for original studies pertaining to the surgical management of HS published from January 1970 to July 2020. A total of 33 papers were included for analysis. Results: Management options include risk factor modification, pharmacological agents, and surgical intervention. Many surgical management techniques exist, including incision and drainage, CO2 laser therapy, deroofing, wide local excision, and reconstructive surgery. Incision and drainage is commonly utilized for symptom relief of sepsis. While data on curative surgical management are lacking, studies on surgical approaches have shown favorable outcomes in highly selected cases.Wide excision with flap reconstruction results in high patient satisfaction rates, good cosmesis, and reduced disease recurrence. Limitations: A small number of suitable papers met our specific focus and inclusion and exclusion criteria. Novel techniques described in case studies were missed. Additionally, this study examined HS management as a whole, but region-specific management was not reviewed closely. Conclusion: The success of surgical management is dependent on multiple factors. Thus far, the precise role of surgery in elective treatment of refractory HS requires further analysis and reporting of outcomes.
... Hidradentitis Suppurativa (HS) is a primarily a chronic inflammatory skin disease that effects the folliculopilosebaceous unit [1]. Consequently, an inflammatory cascade occurs, presenting as recurrent, painful and inflamed nodules that often rupture and leak purulent materials [2]. The chronic timeline of the disease leads to the progression of nodules into accesses, epithelized sinuses, fistulae, and characteristic "rope-like scarring" [3]. ...
... HS is more in female than male (approximate ratio 3:1) [4]. Smoking is one of the risk factors [2]. Approximately 40% of the patients have family members affected by the disease [4]. ...
Article
Full-text available
Hidradentitis Suppurativa (HS) is a primarily a chronic inflammatory skin disease that effects the folliculopilosebaceous unit [1]. Consequently, an inflammatory cascade occurs, presenting as recurrent, painful and inflamed nodules that often rupture and leak purulent materials [2]. The chronic timeline of the disease leads to the progression of nodules into accesses, epithelized sinuses, fistulae, and characteristic "rope-like scarring" [3]. The HS prevalence is around 1% of the population, its onset is usually after puberty, and commonly developing early in the third decade of life, and frequently remains active during the third and fourth decades of life. The women experience often an improvement with the onset of menopause, while usually the men continue with the active disease after 50 years old [4]. HS is more in female than male (approximate ratio 3:1) [4]. Smoking is one of the risk factors [2]. Approximately 40% of the patients have family members affected by the disease [4].
... Konig and colleagues reported that the active cigarette smoker rate was 88.9% in the HS group [35]. Nevertheless, the role of cigarette smoking in HS pathogenesis (epidemiological or causal) has long been a subject of debate among researchers [36]; suffice it to say that even the philosopher of the 19th century Karl Marx (notorious smoker affected by HS) was involved in this debate [37,38]. A rather recent study evaluated the incidence of HS in a heterogeneous population-based sample of about 4 million smokers across the United States, estimating an overall 0.20% HS incidence (during the 3-year study period) among tobacco smokers (vs. ...
... Clinical efficacy of IFX-1, a C5a inhibitor, was demonstrated in a small open-label, single-arm trial in HS patients not eligible for adalimumab therapy: 800 mg of IFX-1 (as a 30 min intravenous infusion) was administered on days 1,4,8,15,22,29,36,43, and 50. The HiSCR was achieved by 75% of patients at the end of treatment and 83.3% at day 134, and therapy was well-tolerated [258]. ...
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Hidradenitis suppurativa (HS) is a debilitating, chronic, (auto)inflammatory disease primarily affecting apocrine gland-rich areas of the body. Although pathogenic mechanisms responsible for HS have not yet been fully elucidated, it is a multifactorial process whose main target is the terminal follicle. The role of the inflammatory process (and consequently of cytokine milieu) and of several other factors (genetics, lifestyle, hormonal status, microbiome, innate and adaptive immune systems) involved in HS pathogenesis has been investigated (and often defined) over the years with a view to transferring research results from bench to bedside and describing a unique and universally accepted pathogenetic model. This review will update readers on recent advances in our understanding of HS pathogenesis and novel (potential) medical therapies for patients with moderate-to-severe HS.
... Screening for comorbidities HSF recommends clinicians screen patients for comorbidities associated with HS (TABLE 2). 2 Overall, screening patients for active and past history of smoking is strongly recommended, as is screening for metabolic syndrome, hyperlipidemia, type 2 diabetes (1.5-to 3-fold greater risk of type 2 diabetes in HS patients), and PCOS (3-fold greater risk). 2,26,27,59 Screening patients for depression and anxiety is also routinely recommended. 2 However, the authors of this article strongly recommend screening all patients with HS for psychiatric comorbidities, as research has shown a 2-fold greater risk of depression and anxiety, social isolation, and low self-esteem that severely limits quality of life (QOL) in this patient population. ...
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Early diagnosis and treatment of hidradenitis suppurativa is key to avoiding severe disease and minimizing its negative psychological impact.
... Moreover, Sartorius et al. found lower disease severities, evaluated by the mSS, in non-smokers compared to active smokers [27]. At a molecular level, components of cigarette smoke have been demonstrated to further promote inflammation in HS via inhibition of the already compromised Notch signaling, induction of proinflammatory cytokine expression and causing infundibular epithelia hyperplasia and hypercornification [43,44]. Although clear evidence of tobacco as a trigger of HS has not been found yet, patients should be encouraged to quit smoking [20]. ...
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with recurrent inflammatory lesions in intertriginous body regions. HS has a pronounced impact on patients’ quality of life and is associated with a variety of comorbidities. Treatment of HS is often complex, requiring an individual approach with medical and surgical treatments available. However, especially in moderate-to-severe HS, there is an urgent need for new treatment approaches. In recent years, increased research has led to the identification of new potential therapeutic targets. This review aims to give a comprehensive and practical overview of current treatment options for HS. Furthermore, the clinically most advanced novel treatment approaches will be discussed.
... Tobacco smoking is one of the a major and well-known triggering factors in HS [41]. Many studies have demonstrated a significant association between HS and smoking. ...
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Hidradenitis suppurativa (HS) is a debilitating, chronic, inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. On the one hand, the presence of triggering factors—some identified, others only hypothesized—may initiate or perpetuate the pathogenic process of HS. In addition to cigarette smoking and diet, other trigger factors, including choice of clothing, are frequently observed in clinical practice. On the other hand, the presence of disease may influence habits of HS patients. Indeed, high incidences of sexual and sleep impairment have been reported in these patients. Consequently, alcohol and substance abuse may be a coping strategy for the emotional and psychological disease burden. Furthermore, a greater awareness of gender differences in HS may be important for dermatologists in their own clinical practice (i.e., pregnancy and breastfeeding). Consequently, in this loop interaction, comprehensive knowledge of all factors involved is crucial for the management of HS patients. Thus, the objective of this review is to (i) discuss the influence of gender on HS, (ii) summarize the most frequent triggering factors of HS and (iii) analyze the impact of HS on patient habits.
... (Table 1). Smoking and obesity have been recognized as environmental factors with a high impact on HS, 8 and 50% (5 of 10) of participants with HS in our study were obese (BMI > 30), although there was no significant difference between the HS group and the control group in relation to BMI (P = 0Á1). None of the participants with HS in our cohort were smokers (Table 1), which is in contrast to the prevalence studies from Australia and the UK. ...
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Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS.
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Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis with recurrent painful nodules and abscesses affecting the intertriginous areas. Patients often experience a significant negative impact on quality of life from associated pain, discharge, odor, scarring, and social stigma. Even with complex medical regimens, patients may report inadequate disease control. Lifestyle changes and complementary and alternative medicines (CAM) are used by a majority of HS patients. Conventional medicines and lifestyle and CAM modalities strategically incorporated together can increase treatment satisfaction and success. We aim to highlight lifestyle and CAM treatment modalities to use alongside conventional treatment plans for HS patients. Lifestyle modifications for HS patients include weight loss, reducing skin friction, smoking cessation, and stress reduction. Dietary modifications for HS patients include limiting foods containing dairy, Brewer's yeast, and simple carbohydrates, appropriate caloric reduction, and consuming foods in the Mediterranean diet. The CAM modalities studied in HS are vitamin D, niacinamide, vitamin B12, zinc, and magnesium. Potential CAM modalities for HS include probiotics, cannabinoids, turmeric, bathing regimens, and acupuncture. This review is a guide for clinicians to provide evidence‐based care for HS patients seeking non‐pharmacologic treatment modalities such as weight loss, clothing choices, dietary changes, and use of supplements and complementary medicine. Lifestyle and CAM modalities may be used in parallel with conventional medicines to synergistically improve patient disease outcomes.
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Background: The pathogenesis of hidradenitis suppurativa (HS) remains unclear. In order to develop effective treatment strategies, a deeper understanding of pathophysiology is needed. This is impaired by multiple small studies with inconsistent methodologies and the impact of co-occurring pro-inflammatory conditions such as smoking and obesity. Methods: This systematic review aimed to collate all published reports of cytokine studies in tissue, blood, serum and exudate. It was registered with PROSPERO (Registration number CRD42018104664) performed in line with the PRISMA checklist. Results: 19 studies were identified comprising 564 individual HS patients and 198 control patients examining 81 discrete cytokines. Methodology was highly varied and the quality of studies was generally low. There was a large degree of variance between the measured levels of cytokines. 78.2% of cytokines demonstrated heterogeneity by the chi-squared test for homogeneity and hence meta-analysis was not deemed appropriate. However, a strong and significant IL-17 signalling component was identified. Conclusions: Cytokines consistently elevated in lesional, peri-lesional and unaffected tissue are identified and discussed. Areas for further investigation include the role of dendritic cells in HS; the contribution of obesity, smoking, diabetes and the microbiome to cytokine profiles in HS; and examining the natural history of this disease through longitudinal measurements of cytokines over time.
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. HS has been associated with obesity, adipokine imbalance, dyslipidemia, pro-inflammation, and metabolic syndrome (MS). The aim of this study was to determine the association between HS, and serum visfatin levels (SVLs), small-dense low-density lipoprotein cholesterol (sdLDL-C), and ischemia-modified albumin (IMA), as well as the association between HS, and smoking, alcohol consumption, anthropometric measurements, blood pressures (BPs), fasting blood glucose (FBG) and lipids, inflammatory markers, homocysteine, uric acid (UA), serum insulin levels (SILs), insulin resistance (IR) and MS, so as to identify relevant risk factors for HS. This case–control study included 40 patients (M/F: 23/17) and 40 age- and gender-matched controls (M/F: 23/17). Demographic data, smoking status and alcohol consumption, personal and family medical history, previous and current treatments were noted. Anthropometric data, BPs, FBG and lipids, homocysteine, UA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), hemoglobin A1c (HbA1c), SILs, SVLs, IMA and sdLDL-C were measured. Homeostasis model assessment for IR (HOMA-IR) was calculated. The associations were made by univariate and multivariate analyses. Univariate analysis showed that there was a significant association between HS and smoking, pack-years of smoking, weight, body mass index (BMI), waist circumference (WC), triglycerides (TGs), high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, SILs, CRP, hs-CRP, homocysteine, UA, ESR, HOMA-IR, SVLs, and MS. After adjusting for BMI and smoking status, the SVLs, SILs, and hs-CRP levels remained higher in the patients than in the controls (P = 0.02, P = 0.01, and P = 0.02, respectively). Multivariate analysis showed that there was a significant association between HS, and the SVLs and SILs, and smoking. Each unit increase in the SVL (P = 0.003, 95% CI 1.16–2.11) and SIL (P = 0.03, 95% CI 1.01–1.17) increased the risk of HS 1.56- and 1.09-fold, respectively. Furthermore, smoking was associated with a 14.87-fold increase in the risk of HS (P = 0.001, 95% CI 2.82–78.56). This study indicates that HS patients have higher SVLs, SILs, and hs-CRP levels than healthy controls—independent of BMI and smoking status. The SVL and SILs and smoking were independent risk factors for HS.
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Hidradenitis suppurativa (HS), a relatively common and chronic inflammatory skin disorder. HS can have debilitating consequences if not diagnosed and treated appropriately. Clinically defined by recurrent, inflamed nodules in intertriginous regions (i.e., axillary, inguinal, and perianal areas), HS can cause intense pain and, in severe disease stages, lead to the formation of fistulas, sinus tracts, and extensive scarring. Postpubertal onset and female preponderance further characterize HS. Numerous pathogenic mechanisms have been proposed in HS, including immune dysregulation, genetics, smoking, and obesity; however, the exact etiology remains to be elucidated. The association of HS with inflammatory bowel disease, cardiovascular disease risk factors, and psychiatric disorders suggests HS is a systemic disease. HS significantly impairs quality of life in patients in excess versus other skin diseases. Unfortunately, experiences indicate long diagnostic delays, which in many cases might be due to disease unawareness among physicians. Increased knowledge of HS is therefore important in order to optimize disease management and ultimately improve the quality of life of patients.
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Hidradenitis suppurativa (HS) is a chronic, recurrent, and painful disease in which there is inflammation in areas of the apocrine sweat glands. These glands are found mainly in the armpits and groins. Within HS there may be a blockage of the hair follicles. This causes a mixture of boil‐like lumps, areas leaking pus, and scarring. Despite a common belief that tobacco smoking increases the risk of developing the disease, the evidence linking the two is controversial. This study is important because it includes a very large sample of people to compare rates of HS in smokers and non‐smokers. Using healthcare data, the researchers identified 3 924 310 tobacco smokers and 8 027 790 non‐smokers in the USA and found that the overall incidence of HS was 0.20% among smokers and 0.11% among non‐smokers. Incidence of HS was greatest among smokers who were aged 30–39 years (0.35%), women (0.28%), African Americans (0.46%), and those with BMI ≥ 30. In conclusion, incidence of HS appears to be doubled among tobacco smokers. These findings may support evidence‐based counselling to help people at risk of HS to quit smoking.
Article
Background Disintegration of the infundibula of terminal hair follicles (HF) in intertriginous skin areas exhibits the histological hallmark of hidradenitis suppurativa (HS)/acne inversa, featuring a dissecting terminal hair folliculitis. Elevated serum levels of interleukin 17 and local increase in the ratio of proinflammatory Th17 cells and antiinflammatory regulatory T cells (Tregs) have been reported. Perifollicular Tregs play a key role for HF stem cell homeostasis and infundibular integrity. Objectives In this review, we evaluate the Th17/Treg ratio in HS, its aggravating conditions and associated comorbidities. Furthermore, we intended to clarify whether drugs with reported beneficial effects in HS readjust the deviated Th17/Treg axis. Methods PubMed‐listed, peer‐reviewed original research articles characterizing Th17/Treg regulation in hidradentitis suppurativa/acne inversa and associated comorbidities have been selected. Results This review presents HS as a disease exhibiting an increased Th17/Treg ratio. Perifollicular deficiencies in Treg numbers or function may disturb HF stem cell homeostasis initiating infundibular dissection of terminal HFs and perifollicular inflammation. The Th17/Treg imbalance is aggravated by obesity, smoking as well as decreased Notch signalling. In addition, HS‐associated autoimmune diseases exhibit a disturbed Th17/Treg axis resulting in a Th17‐dominant state. All drugs that have beneficial effects in the treatment of HS normalise the Th17/Treg ratio. Conclusions HS immunopathogenesis is closely related to deviations of the Th17/ Treg balance, which may negatively affect Treg‐controlled HF stem cell homeostasis and infundibular integrity. Pharmacological intervention should not only attenuate Th17/IL‐17 signalling but should improve Treg function to stabilize HF stem cell homeostasis and infundibular integrity This article is protected by copyright. All rights reserved.
Article
We thank Saleem et al., for providing commentary on a relevant aspect of statistical analysis and interpretation as it relates to our study, the primary objective for which was to assess the directionality and strength of relationship between tobacco smoking (TS) and hidradenitis suppurativa (HS).1 To our knowledge, no previous population-based study has evaluated the effect of TS on actual incidence of disease. While we were able to establish that smokers had twice the adjusted likelihood of incident disease compared to non-smokers, we agree that relative measures of risk may overestimate the effect of an exposure, particularly when the outcome of interest is rare. This article is protected by copyright. All rights reserved.
Article
Smoking is common in patients with hidradenitis suppurativa and may be a risk factor for the disease.1 Garg et al reported in a large, population-based, retrospective cohort study that apparently new hidradenitis was seen in 0.20% (7,860/3,924,310) of smokers versus 0.11% (8,430/8,027,790) of non-smokers over a 3 year period.2 They concluded that hidradenitis is twice as common among smokers, a finding that lay media have covered3, and suggest that populations at risk for hidradenitis be counselled for smoking cessation.2 This article is protected by copyright. All rights reserved.
Article
Background: Treatment for hidradenitis suppurativa is often empiric and inadequate, and determining which patients will respond is difficult. Objective: We sought to determine which patient factors are associated with a positive response to first-line medical therapy. Methods: A single-center retrospective cohort study of all patients with hidradenitis suppurativa seen between January 1, 1992, and October 1, 2014, was conducted. Response to first-line medical therapy (oral/topical antibiotics, intralesional corticosteroids, and topical washes) was examined at follow-up within 6 months of initiating therapy. A multivariate binary logistic regression model was built examining response to treatment and the interplay of patient factors and treatment initiated. Results: In all, 198 patients were included in the final model. Nonsmokers (odds ratio 2.634, 95% confidence interval 1.301-5.332, P = .007) and older individuals (odds ratio 1.046 for each additional year, 95% confidence interval 1.020-1.072, P < .001) were more likely to have improvement at follow-up. In addition, current smokers differed significantly from nonsmokers in several regards. Limitations: The retrospective nature of this study is a limitation, as is relying on classification of disease severity from physical examination findings in some patients. Conclusions: The results of this study suggest that clinicians may be able to more accurately predict which patients with hidradenitis suppurativa will respond to first-line medical therapy, and which patients may require therapy escalation.