Crohn's Disease, Dermatitis, Inflammatory Bowel Diseases, Skin Diseases
Conditions
Keywords
anti-TNFα therapies, Inflammatory Bowel Diseases, Staphylococcus aureus
Brief summary
The main objective of this study is to evaluate the change in the relative abundance of S. aureus within the lesion-site skin microbiota in SPIDER patients (change between inclusion and 6 months), and to assess whether this change in S. aureus abundance is associated with a favorable (or unfavorable) evolution of the wounds over the same period.
Detailed description
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affect around 2.5 million people worldwide, including 300,000 in France. These conditions mainly impact young adults and follow a relapsing-remitting course with significant morbidity. CD is a chronic, debilitating disease caused by complex interactions among genetic, environmental, and microbiota-related factors, leading to transmural inflammation of the digestive tract and both intestinal and extra-intestinal symptoms. UC affects the mucosa of the colon and rectum, with similar gastrointestinal symptoms and frequent cutaneous, ocular, and rheumatologic manifestations. Treatment aims for deep remission and relies largely on anti-TNFα therapies, complemented by other drugs or surgery; newer biologics like vedolizumab and ustekinumab are also used. However, anti-TNFα-treated patients often develop cutaneous comorbidities, such as psoriasis, granulomatous lesions, or neutrophilic dermatoses. A significant proportion also develop skin infections, commonly due to Staphylococcus aureus. One study reported inflammatory skin lesions in 40% of IBD patients on anti-TNFα, with S. aureus nasal or cutaneous carriage frequently associated. The precise relationship between S. aureus and these lesions, however, remains unclear. Description of the treatment/strategy/procedure: Swabbing of healthy areas and lesion sites will be performed in the same way in the SPIDER+ and SPIDER- groups at Day 0 (D0). Microbiota sequencing and cultures will be carried out under the same conditions in both groups. Description of follow-up: SPIDER+ patients will be recruited from the dermatology departments of the participating university hospitals (CHUs), notably in Montpellier, Millau, and Béziers. They will receive follow-up over a 12-month period, with an inclusion visit followed by two follow-up visits at 6 and 12 months. On the other hand, for SPIDER- patients a follow-up visit will take place at 12 months, in order to record adverse effects of the treatment (anti-TNF).
Interventions
None listed
Sponsors
Centre Hospitalier Universitaire de Nīmes
Study design
Observational model
CASE_CONTROL
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with IBD * Receiving anti-TNFα therapy * WITH skin lesions such as crusted rhinitis ± inflammatory alopecic scalp lesions ± intertrigo of the large skin folds ± folliculitis (Scalp and Periorificial Inflammatory DERmatis, SPIDER) * Parental consent for minor patients * Patient who has provided free and informed consent and has signed the consent form * Patient affiliated to or beneficiary of a health insurance system
Exclusion criteria
* Patients for whom a change in therapy is planned within 6 months (SPIDER+). * Patients receiving antibiotics (systemic or topical) at the time of enrollment, with a window of at least 1 month. * Patients who have participated in a clinical drug trial within the last three months * Patients currently in an exclusion period determined by a previous study * Patients under legal guardianship, conservatorship, or trusteeship * Patients who refuse to sign the informed consent form * Pregnant or breastfeeding patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative abundance of S. aureus in the SPIDER+ group | Month 0, baseline | Number of read sequences corresponding to S. aureus divided by the total number of read sequences (%) assessed after sequencing swabs from SPIDER lesions |
| Relative abundance of S. aureus in the control group | Month 0, baseline | Number of read sequences corresponding to S. aureus divided by the total number of read sequences (%) assessed after sequencing swabs from healthy areas |
| Relative abundance of S. aureus according to the Physician's Global Assessment score in the SPIDER+ group | Month 0, baseline | The Physician's Global Assessment score is a clinical scale widely used in dermatology to assess the overall severity of a skin condition. Since there is no specific score for these lesions, it is the only one that can be used. The Physician's Global Assessment score is a global visual assessment of the severity of skin lesions, performed by a healthcare professional (investigator). The Physician's Global Assessment score is an ordinal scale, typically ranging from 0 to 5. A common goal in studies is to achieve a Physician's Global Assessment score of 0 or 1 (resolved or minimal), often with an improvement of at least 2 points from the baseline score. The Physician's Global Assessment is often used as an endpoint in dermatological clinical trials. It is always combined with a quality-of-life score. |
| Relative abundance of S. aureus according to the Dermatology Quality of Life Index in the SPIDER+ group | Month 0, baseline | The Dermatology Quality of Life Index is a standardized, validated, and widely used questionnaire designed to assess the impact of a dermatological condition on a patient's quality of life. It consists of 10 questions, each scored from 0 to 3 points, for a total score ranging from 0 to 30. Topics covered include: symptoms and feelings, discomfort, daily activities, and personal relationships.The optimal goal is a maximum score of 5 points or a reduction of at least 4 points compared to baseline (M0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative abundance of S. aureus within the lesion microbiota in the experimental group according to the Physician's Global Assessment score | Month 0, baseline | The Physician's Global Assessment score is a clinical scale widely used in dermatology to assess the overall severity of a skin condition. Since there is no specific score for these lesions, it is the only one that can be used. The Physician's Global Assessment score is a global visual assessment of the severity of skin lesions, performed by a healthcare professional (investigator). The Physician's Global Assessment score is an ordinal scale, typically ranging from 0 to 5. A common goal in studies is to achieve a Physician's Global Assessment score of 0 or 1 (resolved or minimal), often with an improvement of at least 2 points from the baseline score. The Physician's Global Assessment is often used as an endpoint in dermatological clinical trials. It is always combined with a quality-of-life score. |
| Relative abundance of S. aureus within the lesion microbiota in the experimental group according to the Dermatology Quality of Life Index | Month 0, baseline | The Dermatology Quality of Life Index is a standardized, validated, and widely used questionnaire designed to assess the impact of a dermatological condition on a patient's quality of life. It consists of 10 questions, each scored from 0 to 3 points, for a total score ranging from 0 to 30. Topics covered include: symptoms and feelings, discomfort, daily activities, and personal relationships.The optimal goal is a maximum score of 5 points or a reduction of at least 4 points compared to baseline (M0). |
| Relative abundance of species found in the experimental group (SPIDER+ patients) | Month 0, baseline | Relative abundances (in %) of each bacterial species, calculation of alpha diversity (Shannon index) and beta diversity (Bray-Curtis index) following sequencing of swabs taken from lesions at M0, M6, and M12 in SPIDER+ patients. |
| Presence of S. aureus in the experimental group (SPIDER+ patients) at different colonization sites: axillary folds | Month 0, baseline | Yes/No |
| Presence of S. aureus in the experimental group (SPIDER+ patients) at different colonization sites: nostrils | Month 0, baseline | Yes/No |
| Presence of S. aureus in the experimental group (SPIDER+ patients) at different colonization sites: navel | Month 0, baseline | Yes/No |
| Relative abundance of S. aureus in the experimental group (SPIDER+ patients) at different colonization sites: navel | Month 6 | Yes/No |
| Presence of S. aureus in the experimental group (SPIDER+ patients) at different colonization sites: ears | Month 0, baseline | Yes/No |
| Presence of S. aureus in the experimental group (SPIDER+ patients) at different colonization sites: cheek | Month 0, baseline | Yes/No |
| Evolution of lesions according to the Physician's Global Assessment score in SPIDER+ patients | Month 6 | A "favorable" change in the lesion at Month12 will be defined as: a decrease of at least 2 points in the Physician's Global Assessment score (0-5, wherein 0 indicates improvement and 5 indicates worsening) compared to M0, or a Physician's Global Assessment score of 1 or less. |
| Evolution of lesions according to the Dermatology Live Quality Index in SPIDER+ patients | Month 6 | A "favorable" change in the lesion at Month12 will be defined as: an optimal target of up to 5 points or a reduction of at least 4 points compared to Month 0. |
| Staphylococcus aureus carriage in relation to the relative abundance of S. aureus in SPIDER+ lesion sites: axillary folds | Month 0, baseline | Score/5: 1 point for each staphylococcal colonization site (axillary folds, nostrils, navel, ears) and 1 point for the healthy skin area (cheek) if S. aureus is isolated after culture at M0, M6, and M12 in SPIDER+ patients. |
| Staphylococcus aureus carriage in relation to the relative abundance of S. aureus in SPIDER+ lesion sites: nostrils | Month 0, baseline | Score/5: 1 point for each staphylococcal colonization site (axillary folds, nostrils, navel, ears) and 1 point for the healthy skin area (cheek) if S. aureus is isolated after culture at M0, M6, and M12 in SPIDER+ patients. |
| Staphylococcus aureus carriage in relation to the relative abundance of S. aureus in SPIDER+ lesion sites: navel | Month 0, baseline | Score/5: 1 point for each staphylococcal colonization site (axillary folds, nostrils, navel, ears) and 1 point for the healthy skin area (cheek) if S. aureus is isolated after culture at M0, M6, and M12 in SPIDER+ patients. |
| Staphylococcus aureus carriage in relation to the relative abundance of S. aureus in SPIDER+ lesion sites: ears | Month 0, baseline | Score/5: 1 point for each staphylococcal colonization site (axillary folds, nostrils, navel, ears) and 1 point for the healthy skin area (cheek) if S. aureus is isolated after culture at M0, M6, and M12 in SPIDER+ patients. |
| Staphylococcus aureus carriage in relation to the relative abundance of S. aureus in SPIDER+ lesion sites: cheek | Month 0, baseline | Score/5: 1 point for each staphylococcal colonization site (axillary folds, nostrils, navel, ears) and 1 point for the healthy skin area (cheek) if S. aureus is isolated after culture at M0, M6, and M12 in SPIDER+ patients. |
| Abundance of Staphylococcus aureus and the microbiota (composition, alpha and beta diversity) of a healthy skin area in SPIDER + patients | Month 0, baseline | Relative abundances (in %) of each bacterial species, including S. aureus following sequencing of swabs taken from a healthy skin area in SPIDER+ subjects and from a site at the same location in SPIDER- subjects at time point M0. |
| Abundance of Staphylococcus aureus and the microbiota (composition, alpha and beta diversity) of a healthy skin area in SPIDER + patients: Alpha diversity | Month 0, baseline | Calculation of alpha diversity (Shannon index) following sequencing of swabs taken from a healthy skin area in SPIDER+ subjects and from a site at the same location in SPIDER- subjects at time point M0. |
| Abundance of Staphylococcus aureus and the microbiota (composition, alpha and beta diversity) of a healthy skin area in SPIDER + patients: Beta diversity | Month 0, baseline | Calculation of beta diversity (Bray-Curtis index) following sequencing of swabs taken from a healthy skin area in SPIDER+ subjects and from a site at the same location in SPIDER- subjects at time point M0. |
| Abundance of Staphylococcus aureus and the microbiota (composition, alpha and beta diversity) of a healthy skin area in SPIDER - patients | Month 0, baseline | Relative abundances (in %) of each bacterial species, including S. aureus following sequencing of swabs taken from a healthy skin area in SPIDER+ subjects and from a site at the same location in SPIDER- subjects at time point M0. |
| Abundance of Staphylococcus aureus and the microbiota (composition, alpha and beta diversity) of a healthy skin area in SPIDER - patients: Alpha diversity | Month 0, baseline | Calculation of alpha diversity (Shannon index) following sequencing of swabs taken from a healthy skin area in SPIDER+ subjects and from a site at the same location in SPIDER- subjects at time point M0. |
| Abundance of Staphylococcus aureus and the microbiota (composition, alpha and beta diversity) of a healthy skin area in SPIDER - patients: beta diversity | Month 0, baseline | Calculation of beta diversity (Bray-Curtis index) following sequencing of swabs taken from a healthy skin area in SPIDER+ subjects and from a site at the same location in SPIDER- subjects at time point M0. |
| Genomes and phenotypic characteristics of S. aureus strains isolated from SPIDER+ lesion sites, healthy areas, and staphylococcal reservoirs via bacterial culture: length | Month 0, baseline | Measured in Mb |
| Genomes and phenotypic characteristics of S. aureus strains isolated from SPIDER+ lesion sites, healthy areas, and staphylococcal reservoirs via bacterial culture: guanine-cytosine content | Month 0, baseline | Measured in % |
| Genomes and phenotypic characteristics of S. aureus strains isolated from SPIDER+ lesion sites, healthy areas, and staphylococcal reservoirs via bacterial culture: presence of plasmids | Month 0, baseline | YES / NO |
| Genomes and phenotypic characteristics of S. aureus strains isolated from SPIDER+ lesion sites, healthy areas, and staphylococcal reservoirs via bacterial culture: genome alignment | Month 0, baseline | Measured in % |
| Quantification of messenger RNA from S. aureus virulence genes isolated from SPIDER+ lesion sites | Month 0, baseline | Measured via long-read sequencing (MinION, Oxford Nanopore) in µg |
| Quantification of messenger RNA from S. aureus virulence genes isolated from healthy areas in SPIDER+ patients | Month 0, baseline | Measured via long-read sequencing (MinION, Oxford Nanopore) in µg |
| Quantification of messenger RNA from S. aureus virulence genes isolated from staphylococcal reservoirs | Month 0, baseline | Measured via long-read sequencing (MinION, Oxford Nanopore) in µg |
| Real-time monitoring of the growth of S. aureus strains isolated from SPIDER+ lesion sites | Month 0 to Month 12 | Real-time monitoring using the Quantum automat, in % |
| Real-time monitoring of the growth of S. aureus strains isolated from apparently healthy areas in SPIDER+ patients | Month 0 to Month 12 | Real-time monitoring using the Quantum automat, in % |
| Biofilm formation of S. aureus strains isolated from SPIDER+ lesion sites | Month 0 to Month 12 | Growth curves using the Bioflux automat |
| Biofilm formation of S. aureus strains isolated from apparently healthy areas in SPIDER+ patients | Month 0 to Month 12 | Growth curves using the Bioflux automat |
| Constitution of a biobank of samples taken by swabbing of lesion sites in SPIDER+ patients | Month 0, baseline | Number of samples |
Countries
France
Contacts
CONTACTCatherine DUNYACH-REMY, Dr.
CONTACTAnissa MEGZARI
Outcome results
None listed