Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach

Abstract

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. <b><i>Objectives:</i></b> To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. <b><i>Methods:</i></b> Lesional skin specimens deriving from two groups of HS patients (BMI >30 and smokers, <i>n</i> = 12 vs. BMI <30 and non-smokers, <i>n</i> = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. <b><i>Results:</i></b> Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. <b><i>Conclusions:</i></b> The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.

Hidradenitis Suppurativa and Comorbid Disorder Biomarkers, Druggable Genes, New Drugs and Drug Repurposing—A Molecular Meta-Analysis

“…A chronic low-grade subclinical inflammatory response is strongly implicated in the pathogenesis of insulin resistance and metabolic syndrome. The clinically relevant peroxisome proliferator-activated receptor (PPAR) pathway was down-regulated in adipocytes of HS lesions [4]. In agreement with these data, reduced serum levels of adiponectin were currently found in non-diabetic patients with HS [28].…”

“…Among them, 61 records were removed as duplicates, leaving 104 titles and abstracts to be screened. After careful screening and manual search, six records were excluded based on title and abstract and 49 records due to inappropriate design and two records due to overlapping data sets with another record, resulting in 47 studies that were included in the quantitative synthesis [3,4,11, (Figure 1).…”

“…Although HS has well-documented associations with the metabolic syndrome, which is characterized by systemic inflammation identified at a molecular level [77], the role of adipose tissue in HS has barely been investigated. Obesity is currently shown to represent the primary risk factor in HS at the molecular level [4,28]. A chronic low-grade subclinical inflammatory response is strongly implicated in the pathogenesis of insulin resistance and metabolic syndrome.…”

Identification of clinical features affecting diagnostic delay in paediatric hidradenitis suppurativa: results from a multicentre observational study

“…The majority of cases of NAM are caused by an accumulation of ultraviolet radiation-induced mutations, but most AMs lack these mutations, suggesting a different biological basis. 2,3 Given the unique biology of AM, 4 we sought to investigate the risk of developing NAM in patients previously treated for AM.…”

Similar Levels of Efficacy of Two Different Maintenance Doses of Adalimumab on Clinical Severity and Quality of Life of Patients with Hidradenitis Suppurativa

“…Regarding the incidence, it has been estimated around 11.4 cases per 100000 person-years in the United States, with a much higher risk for women than men (16.1 vs. 6.8) [ 7 ]. HS is typically a multifactorial disease, although currently, it is considered an auto-inflammatory disease [ 8 , 9 ]. Several cytokines such as TNF- α, IL-1, IL-17 and IL-23 are involved in HS pathogenesis, and their blockade could be a rational therapeutic approach.…”