Autoimmune lymphoproliferative syndrome (ALPS): symptoms, causes and treatment

ALPS stands for autoimmune lymphoproliferative syndrome in this guide. It is a rare genetic disorder. Great Ormond Street Hospital (GOSH), in a leaflet produced with PID UK and paediatric immunodeficiency centres, describes it as associated with an excessive number of lymphocytes (lymphoproliferation), leading to enlargement of the lymph nodes (lymphadenopathy) and the spleen (splenomegaly).

These lymphocytes can attack other parts of the body, particularly other blood cells, leading to autoimmune disease, which often shows up as anaemia or bruising. Immunodeficiency UK lists ALPS among the diseases of immune dysregulation, a group of primary immunodeficiencies in which the immune system cannot control specific viruses or cannot switch off activated cells. It says over 450 different primary immunodeficiencies have been identified.

GOSH says ALPS shows up in various ways at different stages of life. Lymphoproliferation affecting the spleen and lymph nodes generally appears during childhood. Parents may notice persistently enlarged glands in the child's neck, armpits and groin, often with no other symptoms at this stage.

A classic form of ALPS-related autoimmunity occurs when antibodies attack red blood cells (haemolytic anaemia) and platelets (thrombocytopenia), leading to tiredness and pallor, easy bruising and bleeding. This combination is called Evans syndrome. Other autoimmune diseases are much less common.

The NHS explains that an enlarged spleen does not always cause symptoms, but otherwise you might feel full very quickly after eating, have discomfort or pain behind the left ribs, anaemia and fatigue, frequent infections and easy bleeding.

The NHS says that swollen glands are usually a sign the body is fighting an infection and that swollen glands caused by an infection will usually get better by themselves within 1 to 2 weeks. It advises seeing a GP if swollen glands are getting bigger, have not gone down within 1 week, feel hard, or come with night sweats or a very high temperature.

In ALPS, GOSH describes glands that are persistently enlarged from childhood. If you have long-lasting swollen glands without an obvious cause, a GP can arrange tests, and Cancer Research UK explains that for people aged 24 or younger in England and Wales, unexplained swollen lymph nodes or an enlarged spleen should lead to an urgent referral to a haematologist within 48 hours.

GOSH says ALPS results from mistakes (mutations) in one of a number of genes controlling how lymphocytes work. The most common gene affected is called FAS. These mutations cause the immune system to remain active even when no infection is present.

In most people with ALPS, a single copy of the faulty gene is passed on from one parent and a normal copy from the other, called autosomal dominant inheritance. Sometimes new gene changes happen out of the blue in people with no family history. Rarely, ALPS is inherited in an autosomal recessive pattern.

GOSH says the diagnosis depends on recognising suggestive clinical features, along with blood tests looking at the different types of lymphocytes, particularly double-negative T lymphocytes. Many conditions can cause similar symptoms, so careful evaluation is needed to exclude them. Special tests, including genetic tests, are available if ALPS is strongly suspected.

Complications may need to be evaluated in their own right, for example with scans or further blood tests. If lymphoma needs to be ruled out, a small biopsy of one of the lymph glands might be performed, GOSH says.

GOSH says most patients do not require any treatment, but just need to have the size of their glands and the number of blood cells in a blood sample monitored regularly. Some patients might require medication to control the overgrowth of lymphocytes or autoimmune complications. This immunosuppressive treatment is individualised for each patient.

For very severe disease, replacement of the abnormal lymphocytes by haematopoietic stem cell transplantation might be considered, but this is rare. GOSH says that an enlarged spleen should generally be treated with medicines rather than splenectomy (surgical removal of the spleen), because the spleen does an important job in protecting us from serious infection.

The NHS says spleen removal weakens the immune system and can make you more likely to get an infection, and that if there is time you will be advised to have certain vaccinations before the operation. It also says the spleen is not usually removed if it is just enlarged, and that you will be treated for any underlying condition and monitored.

GOSH says most people with ALPS have a good outlook and that symptoms often improve after puberty. The increased risk of lymphoma means patients should be followed up by a specialist. It also says genetic counselling, both for affected people and for family members, is important if the genetic cause is known.

GOSH says lymphoma causes symptoms such as fever, fatigue, loss of appetite, weight loss or more marked enlargement of one or more lymph nodes, and that doctors and patients will look out for these features so that appropriate tests and treatment can be arranged.

See a GP if swollen glands persist, keep getting bigger or feel hard, or if you notice unusual bruising or bleeding, tiredness and pallor. If you already have a diagnosis, contact your specialist team if you develop fever, marked fatigue, weight loss, loss of appetite or a lymph node that is clearly bigger.

The NHS says to ask for an urgent GP appointment or get help from NHS 111 if you have swollen glands and are finding it very difficult to swallow or have difficulty breathing. For heavy bleeding or collapse, call 999.

ALPS is managed by clinical immunology and haematology teams, with paediatric immunodeficiency centres looking after children. A GP is the usual route to NHS referral. Immunodeficiency UK is a charity that provides information and support for people with immunodeficiency.

Some people choose a private immunology or haematology opinion. If you do, make sure results and treatment plans are shared with your NHS team, because monitoring of blood counts, spleen size and lymphoma risk needs to be coordinated.