IPEX syndrome

Most individuals with IPEX have had at least some degree of nutritional compromise due to chronic diarrhea and malabsorption, often leading to significant weight loss and poor growth, so nutritional support is very important. Some individuals can improve by receiving supplemental oral feeding using elemental formulas made up of basic nutrients. Often, these need to be given by nasogastric tube (NG-tube) or gastrostomy tube (G-tube) so they can be delivered at a slow, steady rate throughout the day. 

In some individuals, even this slow, gentle approach of delivering nutrients to the bowel leads to worsening of the diarrhea. In these individuals, a central venous catheter is placed, and nutrition is delivered intravenously in the form of total parenteral nutrition (TPN). Little or no food is given into the bowel. This allows the individual to receive much-needed nutrition without making the diarrhea worse.

The severity of skin disease in IPEX varies widely, with some individuals having only mild eczema and other individuals having severe psoriasis-like rashes that are associated with skin fissuring and ulceration. Aggressive treatment of the skin using a combination of moisturizers, steroid ointments, ointments containing other immunosuppressants, like tacrolimus, and wet wraps can help to control skin disease. Often, referral to dermatology and, in severe cases, consultation with wound care specialists is very helpful.

All individuals with IPEX need to be screened for diabetes and thyroid disease. Individuals diagnosed with diabetes or hypothyroidism should be evaluated by an endocrinologist and treated with appropriate insulin and/or thyroid hormone. Individuals with autoimmune diseases causing anemia or low platelet counts may require transfusions with red blood cells or platelets. Supportive treatments to counteract the effects of autoimmunity on other organs should also be provided as needed.

As described above, previous research in the animal model of IPEX has determined that T cells play a major role in driving the immune attack that is characteristic of the disease. Initial immunosuppressive treatments therefore focus on decreasing the activity of T cells with drugs like tacrolimus, cyclosporine, or rapamycin. Steroids like prednisone are often used initially when individuals have very active disease, but as they improve, the steroids can often be discontinued, and individuals can be maintained on tacrolimus, cyclosporine, or rapamycin alone. 

In individuals with autoantibodies that target specific organs and make the autoimmunity worse, treatment with rituximab or similar drugs that deplete the B cells can be helpful. Since anything that activates the immune system, like vaccination or severe infection, may cause disease symptoms and autoimmunity to worsen, individuals who have not been vaccinated may be started on intravenous or subcutaneous immunoglobulin replacement to prevent infections and avoid further vaccination. Often, individuals require progressively increasing immune suppression over time, which leads to a need for other treatments, such as hematopoietic stem cell transplantation (HSCT). 

The only transformative treatment for IPEX at the present time is HSCT, also referred to as bone marrow transplantation. There are a variety of approaches used to perform the transplants in individuals with IPEX, and the approach used often varies by transplant center. Often, HSCT in IPEX is complicated because individuals are ill, and pre-existing organ damage caused by autoimmunity or side effects of medications can increase the risk of transplant. Aggressive supportive care to stabilize individuals and improve their clinical status prior to initiating a transplant is critical. Overall survival after transplant has been reported to be 60-85% in most studies. Gene therapy and gene editing approaches to treat IPEX are under development and may be available in the future, but neither is clinically available at the present time.