What Are the Symptoms of HLH Disease?

Medically Reviewed on 1/11/2023
Symptoms of HLH Disease
The symptoms of HLH are so uncommon that many medical professionals are unaware of them.

The symptoms of hemophagocytic lymphohistiocytosis (HLH) commonly appear within the first few months or years of birth. The symptoms are similar to those of other childhood diseases, making diagnosis difficult.

What is hemophagocytic lymphohistiocytosis?

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and lethal immune condition. Your immune system protects you from diseases and maintains your health. In HLH, the immune system gets confused, and on rare occasions and it works too hard, causing severe tissue damage and inflammation. Sometimes, the immune system does not function properly and puts people at risk for life-threatening infections.

  • Histiocytes are the aberrant cells found in HLH. Histiocytes are a common form of white blood cell that can be found in the blood and organs, such as the liver, spleen, and lymph nodes. Normal histiocytes help manage infections and remove dead cells from the body.
  • HLH-affected histiocytes become hyperactive and begin attacking the body's tissues as if they were outside invaders. This may lead to injury of the brain, liver, and bone marrow.
  • HLH causes histiocytes to misidentify other cells as infections and make them discharge chemicals into the blood. This disoriented histiocyte population frequently congregates in inappropriate locations, which may lead to organ damage and multiple organ failure.

Most people with HLH are infants and young children. Seventy percent of HLH begin before the child is one year old. If left untreated, HLH can soon turn fatal. It is essential to recognize the problem and begin therapy as soon as possible because of the potential for rapid progression.

What are the types of HLH?

There are two types of hemophagocytic lymphohistiocytosis (HLH), which include:

  1. Primary (familial) HLH: Originates due to a genetic mutation. The symptoms of primary HLH often manifest in the first few years of life and are genetically predisposed to the child from birth. Rarely do the symptoms develop in adulthood.
  2. Secondary HLH: This might appear when you have an underlying medical condition that affects your immune system functions. Secondary HLH is frequently caused by cancers, infections (Epstein-Barr virus is the most common), and autoimmune illnesses. Secondary HLH is more common than primary HLH.


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What causes HLH?

Primary or familial hemophagocytic lymphohistiocytosis (HLH) is caused by inherited genetic abnormalities in the PRF1, MUNC13-4, STXBP2, STX11, and STXBP2 genes. Familial HLH accounts for 25 percent of HLH instances. If both parents are hereditary carriers, a child has a 25 percent chance of developing HLH, a 25 percent chance of not developing HLH, and a 50 percent chance of being a carrier.

Several factors can contribute to acquired or secondary HLH, such as:

How to diagnose hemophagocytic lymphohistiocytosis

The symptoms of hemophagocytic lymphohistiocytosis (HLH) are so uncommon that many medical professionals are unaware. Early in the illness, HLH may resemble a few different malignancies, such as leukemia and lymphoma.

Only accurate blood tests in a suitable clinical situation can diagnose HLH.

The following tests are necessary to diagnose HLH and plan a unique treatment strategy:

  • Blood tests: Include measurements of the number of blood cells, liver health, examinations of infections, and indicators of immune system arousal (such as ferritin and soluble IL-2 receptor levels).
  • Aspiration and biopsy: Bone marrow is examined.
  • Lumbar puncture: Cerebrospinal fluid is examined to determine whether HLH is impacting the brain.
  • Imaging analyses: X-rays, CT scans, ultrasounds, and MRIs are a few examples.
  • Comprehensive genetic testing.

What is the treatment for hemophagocytic lymphohistiocytosis?

Hemophagocytic lymphohistiocytosis could be lethal if left untreated. Early diagnosis and treatment are crucial.

The most prevalent therapies include:

  • A steroid medication, such as dexamethasone
  • Chemotherapy (etoposide) is administered directly into the spinal fluid (also called intrathecal therapy)
  • Antibiotics or antiviral medications to prevent or treat infections
  • Immunoglobulin, a substance made from human blood plasma that contains antibodies
  • Immunosuppressive medications, such as cyclosporine
  • Stem cell transplant
Medically Reviewed on 1/11/2023
Image Source: iStock image

Childhood Hemophagocytic Lymphohistiocytosis. https://www.dana-farber.org/childhood-hemophagocytic-lymphohistiocytosis/

What Is Hemophagocytic Lymphohistiocytosis (HLH)? https://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/hlh-syndromes

Hemophagocytic Lymphohistiocytosis. https://my.clevelandclinic.org/health/diseases/24292-hemophagocytic-lymphohistiocytosis#outlook--prognosis

Hemophagocytic Lymphohistiocytosis (HLH). https://www.cincinnatichildrens.org/health/h/hlh

Hemophagocytic Lymphohistiocytosis (HLH). https://www.rileychildrens.org/health-info/hlh