Study of the Immunomodulation in the Hidradenitis Suppurativa and Evaluation of a New Therapeutic Strategy

Study of the Immunomodulation of the Immune Response in Hidradenitis Suppurativa and in Vitro and ex Vivo Evaluation of a New Therapeutic Strategy (IMOHS)

Hidradenitis suppurativa (HS), also known as Verneuil's disease, is a chronic inflammatory dermatosis of the hair follicule located mainly in the skin folds (axillae, inguinal, submammary, etc.).

Currently, treatments are mainly limited to the use of broad-spectrum antibiotics in order to control outbreaks of hidradenitis suppurativa. Surgical treatment is the only curative treatment, but requires disfiguring removals with major scarring consequences.

Pathophysiologically, HS appears to be a primary abnormality of the pilosebaceous-apocrine unit, causing follicular occlusion, followed by the development of perifollicular cysts with commensal bacterial overgrowth, and finally rupture into the dermis causing an exaggerated inflammatory response. At present, few studies have examined the role of the regulatory immune system and its involvement in this disease.

We are also interested in analyzing the impact of new therapeutic strategies on hidradenitis suppurativa, and more particularly the impact of photodynamic therapy (PDT) which is a technique that has been used for a long time in dermatology, notably for the treatment of precancerous and cancerous lesions.

This technique has shown interesting results on inflammatory dermatoses such as acne.

This research consists in studying the immunomodulation of the immune response in HS and in evaluating a new therapeutic strategy based on PDT alone or in combination with antimicrobial peptides (PAMs).

Hidradenitis suppurativa (HS), also known as Verneuil's disease, is a chronic inflammatory dermatosis of the hair follicule located mainly in the skin folds (axillae, inguinal, submammary, etc.). The disease is characterized by pain, inflammatory nodules, abscesses, fistulas and hypertrophic " rope " scars that considerably alter the quality of life of patients.

Currently, the treatment is mainly limited to the use of broad-spectrum antibiotics in order to control the outbreaks of HS. This medical treatment is currently controversial because of the risk of inducing bacterial resistance. Surgical treatment is the only curative treatment, but requires disfiguring removals with major scarring consequences.

Pathophysiologically, HS appears to be a primary abnormality of the pilosebaceous-apocrine unit, which causes follicular occlusion, followed by the development of perifollicular cysts with commensal bacterial proliferation, and finally rupture into the dermis causing an exaggerated inflammatory response. At present, few studies have examined the role of the regulatory immune system and its involvement in this disease.

In the context of HS, it has recently been shown from patient samples that there is an abnormality concerning the stem cells present in the follicular bulb. It can be asked whether the abnormalities observed in hair follicle stem cells of HS patients could be the source of pro-inflammatory exosomes playing a role in HS flares.

The impact of new therapeutic strategies on hidradenitis suppurativa, and more particularly the impact of photodynamic therapy (PDT) which is a technique used for a long time in dermatology, notably for the treatment of precancerous and cancerous lesions will be also evaluated.

This technique has shown interesting results on inflammatory dermatoses such as acne with an " antibiotic " effect.

Thus, this research consists in studying the immunomodulation of the immune response in HS and in evaluating a new therapeutic strategy based on PDT alone or in combination with antimicrobial peptides (PAMs). This is a prospective observational multicenter study of type 3. This study is composed of two steps : first an in vitro part, secondly an ex vivo part allowing to validate the results obtained in vitro on human samples.

Inclusion criteria for HS patients :

• Adult patients (≥18 years)
• Carrier of moderate to severe (Hurley grade ≥2) hidradenitis suppurativa of classical or gluteal phenotype
• Having an indication for surgical treatment (indication for excision)
• Not receiving immunomodulatory treatments (corticotherapy, biotherapy, apremilast, retinoids) or immunosuppressive treatments (methotrexate, ciclosporin) in the 6 months before inclusion, excluding antibiotics
• Agreement to participate
• Affiliated to social security

Inclusion criteria for control receiving abdominoplasty :

• Adult patients (≥18 years)
• With no history of hidradenitis suppurativa or lesions suggestive of hidradenitis suppurativa (recurrent fold abscesses, recurrent fold suppuration, repeated draining in fold areas)
• With an indication for abdominoplasty surgery
• Not receiving immunomodulatory treatments (corticotherapy, biotherapy, apremilast, retinoids) or immunosuppressive treatments (methotrexate, ciclosporin) in the 6 months preceding inclusion, excluding antibiotics
• Agreement to participate
• Affiliated to social security

Criteria for non-inclusion of patients with HS :

• Immunosuppression, autoimmune disease(s), cancerous disease, or acute or chronic infectious disease
• Difficulty understanding or reading French
• Patients already included in a therapeutic interventional trial
• Patients under guardianship or curatorship
• Pregnant or breast feeding women
• Syndromic hidradenitis suppurativa, hidradenitis suppurativa of follicular phenotype

Criteria for non-inclusion of controls receiving abdominoplasty :

• Immunosuppression, autoimmune disease(s), cancerous disease, or acute or chronic infectious disease
• Difficulty understanding or reading french
• Patients already included in a therapeutic interventional trial
• Patients under guardianship or curatorship
• Pregnant or breastfeeding women