The Role of Host-microbiota Interplay in Hidradenitis Suppurativa Pathogenesis

Hidradenitis Suppurativa (HS) is a chronic disabling inflammatory skin disorder associated with the development of painful and purulent lesions of the folds (armpits, inguinal folds, sub-mammary glands). HS most often develops in adolescence or young adulthood and is characterized by inflammation of the pilo-sebaceous system, of progressive severity (folliculitis, nodule, abscess, fistula). The pathogenesis of HS is still poorly understood: the fact that patients respond to combinations of antibiotics and/or immunosuppressive treatments suggests that the disease could be due to a dysregulated immune response against microbial skin flora. Unconventional lymphocytes (UL), classically considered being at the interface of innate and adaptive immunity, play an important role in immune protection against microbial flora. But UL dysfunction has also been reported in many autoimmune diseases involving various tissues (joints, digestive tract, skin). The uncontrolled and chronic activation of these UL by skin microbiota could therefore play a role in the pathogenesis of HS.

Inclusion Criteria:Subject able to read, understand and give documented informed consentSubject willing and able to comply with the protocol requirements for the duration of the studySubject with health insurance coverage according to local regulationsFor woman with childbearing potential, negative pregnancy test at the inclusion visit Specific criteria for HS patientsSubject diagnosed with HS for at least 6 monthsSubject diagnosed with moderate-to-severe HS defined by HS PGA≥3Subject presenting an HS with inflammatory phenotype defined by the presence of folliculitis, nodules and/or abcessesSubject suffering from at least 4 flares/year and presenting 5 active inflammatory lesions (nodules and/or abcesses)Exclusion Criteria:Pregnancy or breast-feeding womenSubject treated by allergen immunotherapy within 4 weeks before inclusionSubject treated by Non-Steroidal Anti-Inflammatory Drugs (NSAID), antibiotics or proton-pump inhibitors within 4 weeks before inclusionSubject treated by live (attenuated) vaccine within 4 weeks before inclusionSubject treated by anti-viral treatment within 4 weeks before inclusionSubject treated by anti-diarrhea treatment including, but not limited to LoperamideSubject treated by immunosuppressive/immunomodulatory substances including oral corticosteroid or biological agents within 4 weeks before inclusionSubject presenting spondylo-arthritis or Inflammatory Bowel Disease (IBD)Subject with a Body Mass Index (BMI)<18.5 or BMI>35Subject consuming probiotics or using a specific diet (e.g. gluten free, vegetarian, vegan, intermittent fasting)Subject with any additional condition that, in the opinion of the investigator, may interfere with the assessment or put the subject at riskLinguistic or mentally incapacity to sign the consent formSubject protect by the law (adult under guardianship, or hospitalized in a public or private institution for a reason other than study, or incarcerated)Subject in an exclusion period from a previous study or who is participating in another clinical trial using a drug Specific criteria for HS patientsSubject currently experiencing or having a history of other concomitant skin conditions that would interfere with evaluation of HSHistory of allergic reaction to local anesthetic productHistory of wound healing disorders (e.g. hypertrophic scars, keloids)History of extensive armpit surgerySubject with known active infection to Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV)Subject treated for their HS by systemic therapy, investigational or commercial, approved or off label)Subject treated for their HS by immunosuppressants or intralesional corticosteroids within 4 weeks before the inclusionSubject treated for their HS by topical antibiotics within 4 weeks before the inclusionSubject previously treated with monoclonal antibodies