Study of Skin and Gut Microbiome in a Skin Condition Involving Skin Barrier Impairment and Allergic Symptoms: Netherton Syndrome

Netherton syndrome (NS) is a genodermatosis characterized by the combination of (i) pruritic erythematous-squamous skin lesions, often erythrodermic, with inflammatory skin flare-ups, (ii) frequent hypernatremic dehydration in the neonatal period, (iii) food allergies with increased IgE levels, and (iv) growth retardation. Autosomal recessive in transmission, it is linked to mutations in the SPINK5 gene encoding the LEKTI protein, leading to abnormalities in epithelial barriers, particularly in the skin and esophagus. Digestive disorders such as abdominal pain, chronic diarrhea, or eosinophilic digestive disorders are common, as described by the dermatology team at Necker-Enfants Malades Hospital, MAGEC center. Thus, NS is a model of a rare disease combining skin inflammation and impaired epithelial barriers. It is essential to define all therapeutic strategies that can relieve patients of what is currently a chronic, severe, and orphan disease. Currently, there is no specific treatment available. The permeability of the skin barrier means that treatment with topical corticosteroids should be avoided as much as possible. Their use therefore remains very limited.

Recent data concerning the study of the skin microbiome of patients with SN have confirmed the presence of dysbiosis and shown the over-representation of Staphylococcus aureus and epidermidis strains, as well as the harmful role of certain proteases produced or stimulated by these strains. However, these studies involved a limited number of patients (a maximum of 10 NS patients), all adults, and did not include skin sampling sites of particular interest, such as skin folds in patients with chronic vegetative cellulitis, which is rarely described but observed in some NS patients. Furthermore, although these patients frequently present with digestive disorders, the digestive microbiome has never been studied in NS. A comparison between studies of the skin and digestive microbiome in systemic inflammatory diseases such as NS throughout life remains unprecedented.

Inclusion criteria

Group A:

• Children aged 10 years and older and adults with confirmed Netherton syndrome diagnosed at age 10 years or older (clinical and histological and/or molecular)
• Patients and legal guardians informed about the study and not opposed to participation in the study

Group B:

• Children aged 10 years and older and adults with no skin barrier impairment, dermatosis, inflammatory disease, or autoimmune disease.
• Subjects and legal guardians informed about the study and who do not object to participation in the study.

Exclusion criteria

• Refusal by parents/guardians, children, adolescents, or adults.
• General or local antibiotic therapy within the month preceding the consultation.