Haemophagocytic Syndromes (HLH)
These questions specifically relate to Haemophagocytic Syndromes (HLH).
1. What causes HLH?
HLH can either be acquired (secondary HLH) or inherited (FHL). Both forms of the disease can be triggered by infections, although it is not known why this happens. Secondary HLH may be triggered by viral infections or other herpes viruses, or other underlying diseases such as autoimmunity or cancer. In FHL, defective genes are inherited from one or both parents. Some other rare inherited immunodeficiencies may also be associated with HLH. The underlying immune defect and/or triggering events result in an abnormal immune response with activation of certain types of white blood cells (lymphocytes and macrophages) and the release of inflammatory proteins which then cause disease.
2. Is there a cure for HLH?
HLH patients with an underlying genetic defect can only be cured when the defective immune system is replaced by a healthy one which is what happens with a hematopoietic stem cell transplant. Secondary HLH cases can usually be cured by treating the underlying disease and sometimes additional immunosuppressive/immunomodulatory therapy.
3. What are the different therapies/treatments commonly used to treat HLH?
Some cases of secondary HLH can resolve spontaneously or after treatment of the underlying disease. Other cases are treated with a combination of chemotherapy (VP-16, methotrexate), immunotherapy (ATG, cyclosporin), and steroids. Any triggering infection has to be treated with appropriate antimicrobial drugs. Patients with persistent or recurring HLH or those with FHL additionally require a hematopoietic stem-cell transplant for recovery.
4. Why is routine newborn screening not available?
Although HLH may occur more frequently than some of the diseases routinely tested for, genetic testing for this disease is very complicated and very expensive.
5. How do I know if my child has primary HLH (inherited/FHL) or secondary HLH?
The clinical symptoms and laboratory findings do not differ in genetic or acquired HLH. Specific immunologic testing can raise the suspicion of genetic disease. In families with more than one affected child or in cases with disease reactivations there is a high probability of genetic disease. However, the identification of a genetic defect is necessary to prove it. Genetic testing is therefore recommended, regardless of age. Depending on the ethnic background up to 30% of patients with FHL have no identified gene defect, so negative test results do not necessarily rule out FHL.
6. How can I find out if my child’s siblings have HLH?
In autosomal recessive forms of the disease, each sibling of a child with FHL has a 25% chance of being affected. In related genetic disorders, including X-linked lymphoproliferative disease, each male child has a 50% chance of being affected. If a genetic defect is known in your family, genetic testing (before or after onset of symptoms) is available to identify siblings who may also be affected.
7. How can I find out if future children are at risk for developing HLH?
If a genetic defect has been identified in your family, prenatal diagnosis is possible by performing either amniocentesis or chorionic villus sampling (CVS) to test if the fetus is affected.
8. What is MAS (macrophage activation syndrome)?
Macrophage activation syndrome is a severe, life-threatening illness caused by the excessive production of types of white blood cells called T cells and macrophages. MAS has strong similarities with familial Haemophagocytic Lymphohistiocytosis (FHL) and virus-associated Haemophagocytic Lymphohistiocytosis (HLH). The exact relationship between MAS and HLH is yet to be determined, although some researchers believe that MAS is a secondary HLH disorder. The term is typically used for the HLH-like syndrome that can occur in patients with systemic onset juvenile arthritis.
9. What is reduced-intensity conditioning (RIC)?
Reduced-intensity conditioning is a less toxic pre-transplant therapy with the goal of suppressing the patient’s immune system enough so that it will accept donor stem cells while reducing the side effects of high dose chemotherapy The RIC may be used in some HLH patients, as well as some LCH patients with severe, resistant disease.
The answers to the following questions may be found in the Support Information.
How is it diagnosed?
How is it treated?
What are the clinical trials?
How do I cope with the diagnosis?
How do I get the information I want?
How do I talk to my children about this?
How do we deal with the treatment?
What happens at the end of the treatment?
What resources are there for individuals or family support?
Where can I get financial support?
How do I find other patients?
Please be advised that all the information you read here is not a replacement for the advice you will get from your consultant and their team.
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