Lymphohistiocytosis hemophagocytic (LHH)

Hemophagocytic lymphohistiocytosis (HLH)

What is LHH?

Se pronuncia: Lymphohistiocytosis hemophagocítica.

Hemophagocytic lymphohistiocytosis, also called HLH, is an immunodeficiency disorder. In this type of disorder, there is a part of the immune system that is missing or malfunctioning. This means that the body cannot fight infection as well as it should. As a result, a person with HLH may have frequent infections that are usually more severe and last longer than usual.

When you have HLH, certain white blood cells (T lymphocytes and macrophages) cannot stop being active and accumulate in organs such as the skin, spleen, and liver. These cells then destroy other blood cells such as red blood cells, platelets, and neutrophils, causing damage to t

Types of HLH

There are two types of LHH. “Primary” or “familial” HLH is caused by an inherited problem with the immune system. “Secondary” HLH can occur when the immune system is compromised (for example, infections), but not necessarily because of an inherited condition. Both types of HLH can be life-threatening. LHH can cause liver failure, breathing problems, brain swelling, and the inability to fight infection.

HLH occurs most often in infants and young children. However, it can occur at any age, including adolescence and adulthood.

HLH is a rare disease (very rare). Statistics indicate that it occurs in approximately one in 50,000 children. As a result, many health care providers are unfamiliar with its symptoms, and it often goes undiagnosed for a long time.

What are the symptoms of HLH?

HLH can be difficult to diagnose because the initial symptoms can be similar to those of common infections. HLH symptoms that you may notice in your child include:

• persistent fever
• Rash
• Yellow appearance to the skin or eyes (jaundice)
• cough, shortness of breath
• Convulsion-like seizures
• altered mental state

Other problems your child’s doctor might find include:

• Hepatitis
• Liver failure
• Low blood component count
• enlarged liver
• enlarged spleen

How is HLH diagnosed?

Because it is so rare, many health care providers do not recognize the symptoms. HLH can “look like” certain types of cancer in the early stages of the disease. This is the reason why the disease is often misdiagnosed, or not diagnosed for too long.

HLH can only be diagnosed by proper blood tests in a proper clinical setting. Doctors may remove some fluid from the spinal canal to look for LHH in the brain. It is important to remember that some types of cancer (such as leukemia and lymphoma) can have symptoms similar to HLH, and so these conditions should be investigated appropriately during testing in a patient suspected of having HLH.

To diagnose HLH and develop a personalized treatment plan, doctors must do the following tests.

• Blood test. These include blood counts, liver function, infection studies, and markers of immune system activation, such as ferritin and soluble IL-2 receptor levels.
• Bone marrow aspiration and biopsy (taking samples of the patient’s bone marrow, the organ that makes blood)
• Lumbar puncture. Doctors do this to get spinal fluid to find out if LHH is affecting the brain.
• Imaging studies. These may include X-rays, CT scans, ultrasounds, and MRIs.
• Detailed genetic testing

What genetic conditions cause HLH?

“Primary” or “familial” HLH is caused by an inherited problem in the genes that control how the immune system kills virus-infected cells and other abnormal cells in a person’s body. These genes include PRF1, MUNC13-4, STXBP2, and STX11.

HLH also occurs in some closely inherited diseases. Some of them are:

• X-linked lymphoproliferative disease (XLP), which is due to mutations in the SH2D1A (XLP1) or XIAP (XLP2) genes
• Griscelli syndrome type II, which is due to mutations in the Rab27a gene
• Chediak-Higashi syndrome, which is due to mutations in the LYST gene.

“Secondary” HLH can occur when the immune system is compromised (for example, infections), but not necessarily because of an inherited condition.

Why does LHH result in these conditions?

In patients with primary HLH, T and NK cells cannot normally kill virus-infected cells or other abnormal cells. Typically, T and NK cells do this by excreting death signals into abnormal cells. When they can’t, they get “overexcited” and this creates unusual and severe inflammation.

The proteins that make the genes MUNC13-4, STXBP2, STX11, Rab27a, and LYST function like the machinery of a conveyor belt and are responsible for the secretion of death signals produced by T and NK cells. The PRF1 gene makes a protein called perforin. It works like a key, allowing excreted death signals to enter an abnormal cell, where the death signals can function.

SH2D1A is responsible for a more specialized mechanism for this killing and controls how the T cells themselves die. It is still not entirely clear why mutations in XIAP cause HLH.

How do doctors treat HLH?

Immediate treatment is very important for patients with HLH, as the disease is often fatal. The first treatments are usually used to stop inflammation in the body. These treatments suppress the immune system, which helps reduce the damage done to a patient’s body.

Treatments may include:

• Steroids plus chemotherapy, to calm hyperinflammation
• Antibody therapy, which blocks some inflammatory proteins or kills the T cells that make them
• Drugs that suppress the immune system
• Drugs that help treat any infection that is present and prevent new infections

With treatment, LHH may come under control after a few weeks. But it could come back and become more severe later on, especially as treatment is tapered off and a patient may need more treatment.

Often, patients with primary HLH need a bone marrow transplant. Patients who undergo a successful bone marrow transplant often live full and productive lives.

he affected organs.

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