Yin and Yang: A disrupted skin microbiome and an aberrant host immune response in hidradenitis suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic multifaceted, potentially scarring, inflammatory skin disease affecting the pilosebaceous units (PSU) of the axilla, inframammary folds, groin and buttocks. Clinical features include painful inflammatory nodules, abscesses and draining sinus tracts that produce a purulent, foul-smelling discharge. The estimated prevalence of HS is 0.2-0.6% globally, but the prevalence varies by geographic location: 0.5-1.3% in Europe, 0.7-1.2% in the United States and 0.01%-2.2% in the Asia-Pacific region. 1,2 Common comorbidities and behaviours associated with HS include diabetes, pulmonary disease, metabolic syndrome, obesity, polycystic ovary syndrome, inflammatory bowel disease, smoking and mechanical stress on skin. 1,3-5 HS negatively impacts patients' quality of life and causes significant economic burden on patients and the healthcare system. [6][7][8][9][10] The pathogenesis of HS is not fully understood. However, evidence supports the hypothesis that hair follicle occlusion leads to follicle rupture and an aberrant immune response to follicular and bacterial debris, triggering a cycle of damage and chronic inflammation. 7,[11][12][13][14] Factors involved in HS pathogenesis include genetics, hormones, local environmental factors (eg sweating, skin friction), abnormal host responses to skin bacteria and impaired wound healing. [15][16][17][18] Approximately 30% of patients have a family history of HS, and of these, about 10% of these familial cases have an inactivating mutation in the γ-secretase enzyme complex. 19,20 These γ-secretase mutations are relatively uncommon in sporadic cases of HS (~6%). 21 γ-secretase activity in the skin

The Core Human Microbiome: Does It Exist and How Can We Find It? A Critical Review of the Concept

“…This coexistence is fundamental for the fine-tuning of the immune system and requires an intimate relation with commensal microbes, especially during early childhood [ 152 , 153 ]. Therefore, it is not surprising that alterations in these close microbiome–immunity interactions are associated with increased susceptibility to pathogenic infections, overgrowth of commensals, and their potential spread throughout the body via impaired mucosal barriers [ 154 , 155 ]. These contribute to the onset and development of several disorders, including IBD [ 45 ], rheumatic arthritis [ 156 ], neurodegenerative diseases [ 157 ], and even tumors [ 158 ].…”

Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases

“…Although its pathogenesis is still unclear, many risk factors have been identified, including genetic predisposition, obesity, smoking habit, and hormonal disorders [ 97 ].…”

Insights into the Pathogenesis of HS and Therapeutical Approaches

“…Several findings suggested that HS is associated, as other inflammatory skin diseases (including atopic dermatitis and acne vulgaris), with dysbiosis, that is an imbalance (any change to the composition) of the skin "healthy" resident microbiome. Indeed, microbial dysbiosis in HS has been the subject of over 200 publications; nevertheless, its exact role in HS pathogenesis remains elusive and is yet to be fully clarified [53]. In their recent review (which includes 21 studies examining the cutaneous microbiome), Wark and Cains reported that (i) Staphylococcus aureus, coagulase-negative staphylococci, and Enterobacteriaceae species were commonly cultured from HS skin, and (ii) Porphyromonas and Prevotella (both anaerobic bacteria) were relatively increased in HS skin, as demonstrated by 16S rRNA sequencing studies [54].…”