Scientific Substantiation and Assessment of the Effectiveness of Pathogenetic Methods of Therapy for Congenital Ichthyosis in Children

This is an experimental non-randomized clinical study aimed at expanding the indications for the use of biological drugs with the aim of using them for the pathogenetic therapy of children with congenital ichthyosis.

The study will include 50 children aged 6 months to 18 years with a clinically and genetically confirmed diagnosis of congenital ichthyosis. Patients will be divided into 4 groups who will receive symptomatic therapy (using active external agents, emollients and / or systemic retinoids) or biologics targeting the cytokines IL-12 / IL-23, IL-4 / IL-13 and IL -17A. Immunophenotyping of all patients will be performed, the cytokine profile and spectrum of sensitization and the degree of NF-kB activation in lymphocytes will be determined. In experimental group №3, 10 patients with Netherton syndrome will receive dupilumab, in experimental group №2, 10 patients will receive ustekinumab, and in experimental group №1 10 patients will receive secukinumab. Efficiency will be assessed using the Ichthyosis Area Severity Index (IASI), determination of the level of TEWL, and the change in quality of life will also be assessed using the Children's Dermatological Life Quality Index (CDLQI) in comparison from baseline, than at 16 and 52 weeks. Throughout the study, the safety profile (registration of the development of infectious diseases) will be assessed.

• Secukinumab Injection (Drug): Pathogenetic therapy with biologic drugs
• Ustekinumab Injection (Drug): Pathogenetic therapy with biologic drugs
• Dupilumab Injection (Drug): Pathogenetic therapy with biologic drugs
• Symptomatic therapy (Other): Active external agents, Emollients, systemic retinoids if needed

Primary outcomes

• Change in Ichthyosis Area Severity Index (IASI) [From Baseline up to 16 weeks]: Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S)
• Change in Ichthyosis Area Severity Index (IASI) [52 weeks]: Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S)

Secondary outcomes

• Transepidermal water loss (TEWL) level change [From Baseline up to 16 weeks]: Change in transepidermal water loss (TEWL) while rebuilding the epidermal barrier of the skin (an indicator of the effectiveness of the therapy). Measured in g/hm2.
• Transepidermal water loss (TEWL) level change [52 weeks]: Change in transepidermal water loss (TEWL) while rebuilding the epidermal barrier of the skin (an indicator of the effectiveness of the therapy). Measured in g/hm2.
• Change in the Children's Dermatology Life Quality Index (CDLQI) [From Baseline up to 16 weeks]: increasing The Children's Dermatology Life Quality Index, as an indicator of the effectiveness of therapy. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The CDLQI can also be expressed as a percentage of the maximum possible score of 30.
• Change in the Children's Dermatology Life Quality Index (CDLQI) [52 weeks]: Change in the Children's Dermatology Life Quality Index (CDLQI), as an indicator of the effectiveness of therapy. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The CDLQI can also be expressed as a percentage of the maximum possible score of 30.

Sex: All, ages: 6 Months to 18 Years, accepts healthy volunteers

Inclusion Criteria:

* The subject has signed an informed consent; parental or legal representative consent for patients under 18 years of age, as well as additional consent for patients aged ≥ 15 and <18.

  * At the time of participation in the study, the age of the subject is not less than 6 months and not more than 18 years.
  * At the time of participation in the study, a clinical diagnosis was established: Congenital ichthyosis with various clinical forms, with the exception of vulgar and X - linked congenital ichthyosis (genetic research is not a prerequisite for participation in the study).
* Subjects should have at least moderate IASI erythema associated with his / her ichthyosis, and a decrease in the quality of life according to CDLQI ≥ 10
* Absence of signs of severe infectious diseases (pneumonia, tuberculosis, etc.)
* No previous history of the use of the following genetically engineered biological drugs: ustekinumab, secukinumab, dupilumab

Exclusion Criteria:

* Subjects who have an allergic reaction to ustekinumab, secukinumab or other components of the drugs.
* Subjects who have bacterial and/or fungal diseases.
* Subjects who have problems in dynamic observation.
* Subjects who will have a worsening of clinical symptoms