Definition

What is Hemophagocytic lymphohistiocytosis (HLH)?

Hemophagocytic lymphohistiocytosis (HLH) is a condition in which the body makes too many activated immune cells (macrophages and lymphocytes). People with HLH usually develop symptoms within the first months or years of life. Symptoms may include fever, enlarged liver or spleen, cytopenia (decreased number of blood cells), and neurological abnormalities.

How common is Hemophagocytic lymphohistiocytosis (HLH)?

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of the immune system primarily affecting young infants and children, although it can develop for the first time at any age.  According to a large, population-based study published in Sweden, it was estimated to occur in 1.2 cases per million children, which corresponds to 1 in 50,000 births.  However, this number must be considered minimal, as there are probably many patients today who are not diagnosed.  For the autosomal-recessive forms of HLH (FHL), there is believed to be an equal number of males and females diagnosed with this disease.  In addition, there are two known X-linked forms of FHL, affecting only males. Please discuss with your doctor for further information.

Symptoms

What are the symptoms of Hemophagocytic lymphohistiocytosis (HLH)?

The signs and symptoms of hemophagocytic lymphohistiocytosis typically develop during the first months or years of life. However, in rare cases, affected people may not show symptoms until later in childhood or even into adulthood. The features of this condition may include:

  • Fever
  • Enlarged liver and/or spleen
  • Skin rash
  • Lymph node enlargement
  • Breathing problems
  • Easy bruising and/or abnormal bleeding
  • Kidney abnormalities
  • Heart problems
  • Increased risk for certain cancers (leukemia, lymphoma)

Many people with this condition also develop neurologic abnormalities. The neurological symptoms vary but may include irritability, fatigue, abnormal muscle tone, seizures, neck stiffness, mental status changes, ataxia, blindness, paralysis, and/or coma.

There may be some symptoms not listed above. If you have any concerns about a symptom, please consult your doctor.

When should I see my doctor?

If you or your loved one has any signs or symptoms listed above or you have any questions, please consult with your doctor. Everyone’s body acts differently. It is always best to discuss with your doctor what is best for your situation.

Causes

What causes Hemophagocytic lymphohistiocytosis (HLH)?

There are inherited and non-inherited (acquired) causes of hemophagocytic lymphohistiocytosis (HLH).

There are five subtypes of inherited (or familial) HLH which are designated familial HLH, types 1-5. Each subtype is caused by a change (mutation) in a different gene that helps regulate the immune system. Type 1 is due to a gene defect on chromosome 9. Familial HLH, type 2 is caused by mutations in the PRF1 gene. Familial HLH, type 3 is caused by mutations in the UNC13D gene. Familial HLH, type 4 is caused by mutations in the STX11 gene. Familial HLH, type 5 is caused by mutations in the STXBP2 gene.

All of the genes involved with HLH normally provide instructions for proteins that help destroy or turn off activated immune cells when they are no longer needed. Changes in these genes lead to an overproduction of immune cells which results in an excessive immune response and the many signs and symptoms of familial HLH.

The acquired causes of HLH include: infection, medications that suppress the immune system, autoimmune diseases, immunodeficiencies, certain types of cancer and/or metabolic diseases.

When HLH results from an inappropriate immune response to Epstein-Barr virus or another viral illness, it may be due to a separate genetic condition called X-linked lymphoproliferative disease (XLP). XLP is caused by a mutation in the SH2D1A or XIAP gene and is inherited in an X-linked manner.

Risk factors

What increases my risk for Hemophagocytic lymphohistiocytosis (HLH)?

Hemophagocytic lymphohistiocytosis (HLH) may be inherited or acquired (due to non-genetic factors).

Familial HLH is inherited in an autosomal recessive manner. This means that to be affected, a person must have a change (mutation) in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Acquired HLH is not inherited. The non-genetic causes of HLH include: infection, medications that suppress the immune system, autoimmune diseases, immunodeficiencies, certain types of cancer and/or metabolic diseases.

When HLH results from an inappropriate immune response to Epstein-Barr virus or another viral illness, it may be due to a separate genetic condition called X-linked lymphoproliferative disease (XLP). XLP is caused by a mutation in the SH2D1A or XIAP gene and is inherited in an X-linked manner.

Please consult with your doctor for further information.

Diagnosis & treatment

The information provided is not a substitute for any medical advice. ALWAYS consult with your doctor for more information.

How is Hemophagocytic lymphohistiocytosis (HLH) diagnosed?

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) can be established if 1 and/or 2 below is fullfilled:

  1. A genetic test identifying a mutation in one of the genes involved with this condition
  2. At least five out of the following 8 signs or symptoms:
  • Fever
  • Enlarged spleen
  • Cytopenia (lower-than-normal number of blood cells)
  • Elevated levels of triglycerides or low levels of fibrinogen in the blood
  • Hemophagocytosis (the destruction of certain types of blood cells by histiocytes) on bone marrow, spleen or lymph node biopsy
  • Decreased or absent NK cell activity
  • High levels of ferritin in the blood
  • Elevated blood levels of CD25 (a measure of prolonged immune cell activation)

Clinical genetic testing is available for the four genes known to cause familial hemophagocytic lymphohistiocytosis, types 2-5. The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetic professional.

How is Hemophagocytic lymphohistiocytosis (HLH) treated?

The best treatment options for hemophagocytic lymphohistiocytosis (HLH) are determined by a number of factors, including the severity of symptoms, the age of onset, and the underlying cause of the condition.

In acquired HLH, it is often necessary to treat the underlying condition. For example, antiobiotics or antiviral medications can be used to treat or prevent infections that may have triggered the exaggerated immune response.

Allogeneic hematopoietic cell transplantation is considered a cure for familial HLH. It is often recommended that people with confirmed or suspected familial HLH undergo this treatment as early in life as possible. Prior to hematopoietic cell transplanation, people with HLH are usually treated with chemotherapy and/or immunotherapy to destroy excess immune cells which can lead to life-threatening inflammation.

Lifestyle changes & home remedies

What are some lifestyle changes or home remedies that can help me manage Hemophagocytic lymphohistiocytosis (HLH)?

If you have any questions, please consult with your doctor to better understand the best solution for you.

Hello Health Group does not provide medical advice, diagnosis or treatment.

Sources

Review Date: March 30, 2018 | Last Modified: March 30, 2018

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