Background:
Autosomal dominant hyper-IgE syndrome (HIES), also called Job syndrome, is a genetic disorder that affects the immune system. It can cause skin and lung infections and problems with blood vessels, connective tissues, and bones. People with HIES often have lupus-like disease or atopic dermatitis (skin rash). Researchers want to know if a drug approved to treat other immune system diseases (baricitinib) can help people with HIES.
Objective:
To test baricitinib in people with HIES with lupus-like disease or skin rash.
Eligibility:
People aged 12 years and older with HIES with lupus-like disease or skin rash.
Design:
Participants will have 5 clinic visits, 4 remote visits, and 2 phone visits in 9 months.
Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of the speed and pressure of blood flow through their body: Blood pressure cuffs will be placed on each arm and leg; electrodes will be placed on the wrists and a microphone on the chest.
The study has a 3-month lead-in period. Participants will not take the study drug during this time. They will continue with their usual medical care. They will have 2 phone calls with the study team.
Baricitinib is a tablet taken by mouth. Participants will take 1 or 2 tablets by mouth every day for 6 months. They will start with a low dose and may increase to a higher dose.
Blood and urine tests will be repeated during each study visit. Other tests may also be repeated during some visits. A skin sample may also be taken....
Must be able to understand and provide informed consent or assent.
Aged >=12 years.
Documented STAT3 variant causing hyper-IgE syndrome.
Enrollment in NIH protocol 00-I-0159, Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES).
Known history of hypersensitivity to baricitinib or other JAK inhibitors.
Current or recent use of any investigational drug/intervention (within 6 months or 5 half-lives, whichever is longer, prior to Day 0) except for COVID-19 vaccines or therapies that have been granted an FDA emergency authorization.
Scheduled to participate in another clinical study involving an investigational drug during the course of this study.
Use of systemic immunosuppressive or immune-modulating agents within 90 days prior to Day 0, except systemic steroids <=10 mg of prednisone equivalent per day.