What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Erythrophagocytic Lymphohistiocytosis
• fHLH (Familial Hemophagocytic Lymphohistiocytosis)
• Primary Hemophagocytic Lymphohistiocytosis

What is Familial Hemophagocytic Lymphohistiocytosis? (Definition/Background Information)

• Familial Hemophagocytic Lymphohistiocytosis (fHLH) is a rare and severe autosomal recessive disorder characterized by recurrent fever, skin rash, and anemia, as well as increased activity of certain cells (histiocytes and lymphocytes) of the immune system
• The disorder normally affects children. Familial Hemophagocytic Lymphohistiocytosis is caused by mutations in the genes that code for certain proteins that regulate the activity of histiocytes and lymphocytes. These mutations lead to excessive and uncontrolled activation of these cells leading to tissue damage
• Familial Hemophagocytic Lymphohistiocytosis is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated gene, one from each parent, to develop fHLH. Therefore, the primary risk factor includes a positive family history of the disorder
• Other signs and symptoms of Familial Hemophagocytic Lymphohistiocytosis include enlargement of the lymph nodes and spleen, and inflammation of various organs, including the liver, lungs, and bones. A diagnosis is based on a combination of clinical examination, laboratory tests, and genetic testing
• Treatment typically includes immunosuppressive and immunomodulatory medications. In some cases, additional treatments such as blood transfusions, splenectomy (surgical removal of the spleen) may be required. Presently, it is not possible for prevent the development of Familial Hemophagocytic Lymphohistiocytosis
• The prognosis of Familial Hemophagocytic Lymphohistiocytosis is evaluated on a case-by-case basis, depending on its severity and treatment effectiveness. With appropriate treatment, the majority of patients with Familial Erythrophagocytic Lymphohistiocytosis can have a good quality of life. The disorder can be life-threatening if left untreated

Who gets Familial Hemophagocytic Lymphohistiocytosis? (Age and Sex Distribution)

• Familial Hemophagocytic Lymphohistiocytosis is a rare genetic disorder that affects individuals of all ages but is most commonly diagnosed in childhood.
• Both male and females are affected
• Worldwide, no racial/ethnic group predilection is noted

What are the Risk Factors for Familial Hemophagocytic Lymphohistiocytosis? (Predisposing Factors)

The risk factors for Familial Hemophagocytic Lymphohistiocytosis include:

• Having a family history of the disorder 
• Inheriting two copies of the mutated gene from each parent

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others. 

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Hemophagocytic Lymphohistiocytosis? (Etiology)

Familial Hemophagocytic Lymphohistiocytosis (fHLH) is caused by mutations in the genes that code for the proteins that regulate the activity of histiocytes and lymphocytes.

• These mutations lead to excessive and uncontrolled activation of these cells leading to tissue damage
• fHLH is inherited in an autosomal recessive manner

There are five subtypes of Familial Hemophagocytic Lymphohistiocytosis. The genetic cause of Type 1 is not known. The other subtypes with their affected genes are Type 2-PRF1, Type 3-UNC13D, Type 4-STX11, and Type 5-STXB2.

Autosomal recessive mode of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Familial Erythrophagocytic Lymphohistiocytosis?

The common signs and symptoms of Familial Hemophagocytic Lymphohistiocytosis include:

• Recurrent episodes of fever
• Skin rash
• Anemia
• Lymphadenopathy (swelling of the lymph nodes)

How is Familial Hemophagocytic Lymphohistiocytosis Diagnosed?

Familial Hemophagocytic Lymphohistiocytosis is typically diagnosed based on a combination of the following:

• Clinical examination and medical history evaluation
• Assessment of one’s signs and symptoms
• Laboratory tests
• Imaging studies
• Genetic testing

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Hemophagocytic Lymphohistiocytosis?

Complications of Familial Hemophagocytic Lymphohistiocytosis may include:

• Splenomegaly (enlargement of the spleen)
• Inflammation of various organs, including the bone marrow, liver, lungs, and brain, leading to organ damage
• Life-threatening infections or bleeding in severe cases

How is Familial Hemophagocytic Lymphohistiocytosis Treated?

• Treatment for Familial Hemophagocytic Lymphohistiocytosis typically includes immunosuppressive and immunomodulatory medications
• In some cases, additional treatments may be required such as: 
  • Blood transfusions
  • Splenectomy (surgical removal of the spleen)
• Allogeneic hematopoietic stem cell transplantation

How can Familial Hemophagocytic Lymphohistiocytosis be Prevented?

• Presently, there are no known measures available to prevent Familial Erythrophagocytic Hemophagocytic as the cause is a genetic mutation
• Genetic counselling and testing may be recommended for individuals with a family history of the disorder and for couples planning to have children

What is the Prognosis of Familial Hemophagocytic Lymphohistiocytosis? (Outcomes/Resolutions)

The prognosis for Familial Hemophagocytic Lymphohistiocytosis varies depending on the severity of the disorder and the effectiveness of the treatment.

• With timely adequate treatment, most of the affected individuals can have an improved quality of life
• In severe cases, fHLH can be life-threatening, especially when left untreated

Additional and Relevant Useful Information for Familial Hemophagocytic Lymphohistiocytosis:

The following link is a useful resource for information on hemophagocytic lymphohistiocytosis (HLH):

https://www.dovemed.com/diseases-conditions/hemophagocytic-lymphohistiocytosis-hlh/