Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder that can cause chronic swelling of the lymph nodes, spleen, and liver.

In addition to causing swelling, ALPS can result in low levels of red blood cells, neutrophils (white blood cells that fight infections), and platelets (cell fragments that help with blood clotting).

ALPS often begins in childhood but can develop at any age. Let’s look deeper at the causes, symptoms, and treatment of ALPS.

ALPS primarily occurs due to gene mutations that control cell death (apoptosis) in the immune system. Mutations disrupt the body’s process of removing old or damaged cells, leading to the disease.

There are several subtypes of ALPS, including ALPS-FAS (the most common), ALPS-FAS/CASP10, ALPS-FASL, and others. Each subtype is associated with specific genetic mutations that interfere with the cell removal process, contributing to the development of ALPS.

Mutations in the FAS gene or other genes involved in apoptosis prevent cells from dying when they should, causing an accumulation of excess immune cells characteristic of ALPS.

Studies suggest that FAS mutations may also play a role in autoimmune diseases and cancer, indicating a broader impact on health beyond ALPS.

How common is autoimmune lymphoproliferative syndrome?

ALPS is a rare disorder, and there are no exact numbers for how many people have it. ALPS can be challenging to diagnose because its symptoms can look like other conditions, such as Evans syndrome or other lymphoproliferative disorders.

Lymphoproliferative diseases can have many signs and symptoms, depending on the specific condition and its severity.

ALPS can result in low levels of red blood cells (anemia), low levels of neutrophils (neutropenia), and low levels of platelets (thrombocytopenia), which are all essential for fighting infections and maintaining healthy blood clotting.

Common signs and symptoms may include:

ALPS is treated based on its symptoms and severity. Treatment aims to reduce lymphocyte (a type of white blood cell) accumulation, manage autoimmune symptoms, and prevent complications.

Common treatments include:

  • Sirolimus: Also known as rapamycin (Rapamune), this medication inhibits a pathway that promotes cell growth and may help reduce lymphocyte accumulation.
  • Corticosteroids: Corticosteroids, such as prednisone, can reduce inflammation and suppress the immune system.
  • Immunosuppressive therapy: Drugs like mycophenolate mofetil (CellCept) or azathioprine (Imuran) may be used to suppress the immune system and reduce lymphocyte proliferation.
  • Splenectomy: In some cases, surgical removal of the spleen may be necessary to reduce lymphocyte accumulation and improve symptoms.
  • Hematopoietic stem cell transplant (HSCT): In severe or treatment-resistant cases, HSCT, a type of bone marrow transplant, may be an option. Stem cells from a donor are infused into the recipient’s bloodstream, where they can travel to the bone marrow and start producing new blood cells, including immune cells.
  • Supportive care: This includes treatment for anemia, neutropenia, and thrombocytopenia, such as blood transfusions or medications to stimulate blood cell production.
  • Monitoring and surveillance: Regular monitoring of blood cell counts, lymphocyte levels, and organ function is essential to manage ALPS and detect complications early.

While most cases of ALPS are due to mutations in genes like FAS, FASL, and CASP10 (about 70%), some cases have unknown genetic causes (ALPS-U). People with ALPS-U often have more severe and complex symptoms, including multi-organ involvement and more autoimmune markers.

Treatments can be more challenging, often requiring multiple therapies and targeted treatments.

Many people with ALPS live a typical lifespan. The estimated survival rate for people with ALPS-FAS by age 50 is approximately 85%, while people without ALPS have an expected survival rate of 93–95% by the same age.

Even though ALPS can increase the risk of cancer and severe blood disorders, most people, especially those with FAS mutations, see their swollen lymph nodes improve over time.

Resources for support and information on ALPS

Autoimmune lymphoproliferative syndrome (ALPS) causes the production of too many lymphocytes, which is a type of white blood cell. The condition can lead to enlarged lymph nodes, spleen, and liver and result in autoimmune issues. Mutations in the FAS gene cause ALPS, but other genes can also be involved.

With proper management and treatment, many of the symptoms, such as swollen lymph nodes and autoimmune issues, can be controlled. Ongoing research is uncovering new insights into the condition, which may lead to even more effective treatments.