HLH is an abbreviation for hemophagocytic lymphohistiocytosis. It is a potentially fatal condition that can be classified as either primary or secondary HLH. Primary HLH, also known as “familial” HLH, occurs when the condition is inherited. Secondary HLH is used when your doctor believes the condition occurred due to a variety of other non-inherited causes.
Patients with primary HLH have immune system cells called T and NK cells that do not function properly. These cells become overactive, resulting in excessive inflammation. Normally, these cells should destroy infected or damaged body cells. The immune system begins to damage the patient’s own tissues and organs in HLH, including the liver, brain, and bone marrow, which produces blood.
When doctors use a microscope to examine a patient’s bone marrow, they can sometimes see these angry immune cells “eating” other cells. This is known as hemophagocytosis.
What Are the Signs and Symptoms of HLH?
Because the initial symptoms of HLH can mimic other problems, such as common infections, it can be difficult to diagnose. HLH signs and symptoms may include:
Fever that persists
Rash
Spleen and liver enlargement
Lymph node enlargement
Anemia
Platelets are low.
Low white blood cell count
Jaundice
Hepatitis
Failure of the liver
Respiratory problems (coughing, respiratory distress)
Seizures
Changes in mental functions
How Is HLH Detected?
Only with the proper tests can HLH be diagnosed. Blood tests include cell counts, liver function, infection tests, and immune system activation markers like ferritin and soluble IL-2 receptor levels. To look for microscopic evidence of hemophagocytosis, a bone marrow aspirate and biopsy may be performed. A lumbar puncture may be performed to collect cerebrospinal fluid and ensure that the HLH is not affecting the brain. These two procedures are carried out while the patient is asleep.
X-rays, CT scans, ultrasounds, and MRIs may be taken.
Specialized blood tests can also be used to quickly screen patients for the genetic causes of HLH. In-depth genetic testing should also be carried out.
What Genetic Disorders Cause HLH?
Problems in genes that control how the immune system kills virus-infected or other abnormal cells in a person’s body cause primary HLH. PRF1, MUNC 13-4, STXBP2 and STX11 are among the genes involved.
Some closely related inherited diseases also have primary HLH. These include X-linked lymphoproliferative disease (XLP), which is caused by mutations in the SH2D1A gene (XLP1) or the XIAP / BIRC4 gene (XLP2), Griscelli syndrome type II, which is caused by Rab27a gene mutations, and Chediak-Higashi syndrome, which is caused by LYST gene mutations.
Why Do These Conditions Cause HLH?
T and NK cells in patients with primary, or familial, HLH cannot normally kill virus-infected or other abnormal cells in the patient’s body. T and NK cells normally accomplish this by secreting death signals into specific abnormal cells.
The proteins produced by the MUNC 13-4, STXBP2, STX11, Rab27a, and LYST genes function similarly to conveyor belt machinery, and are responsible for the secretion of death signals produced by T and NK cells. The PRF1 gene produces a protein known as perforin. It functions as a key, allowing the secreted death signals to enter a targeted abnormal cell where they can work.
How Is HLH Handled?
Treatment is critical for HLH patients because the condition is life-threatening. Doctors use treatments that suppress the immune system. Steroids, chemotherapy (etoposide), and/or antibody therapies that target and destroy T cells (anti-thymocyte globulin / ATG, as well as alemtuzumab) are typically used to treat patients. Other immune-suppressing medications may be administered to patients. In addition, your doctor may prescribe medications to help prevent and/or treat infections.
To be cured of HLH, many patients must also have their immune systems replaced by receiving a hematopoetic (blood or bone marrow) stem cell transplant. If this is the case for you or your child, consult your doctor.
Conditions Handled
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammation syndrome. Cincinnati Children’s Hospital offers specialised care for both primary and secondary HLH.
- Primary HLH, also known as “familial” HLH, occurs when the condition is inherited. This means that the disease was caused by a genetic mutation (change).
- Secondary HLH occurs when the condition develops as a result of another medical condition, such as rheumatologic disorders or cancer.
- In HLH, the body’s immune defence system becomes overly active and is unable to “switch off.” Without treatment, inflammation escalates, causing organ damage. Because children with HLH have complex medical needs, our care team includes specialists from many fields of medicine, including cancer and blood diseases, bone marrow transplantation, rheumatology (immune diseases), pathology (the study of disease), genetics, neurology, and radiology.
Advanced Therapies and Diagnostic Tests
Diagnosis of HLH can be difficult because the symptoms can be confused with those of other conditions. Through specialised lab tests, radiology studies, and genetic tests, Cincinnati Children’s provides rapid, accurate diagnosis and treatment. Our HLH team of physicians, genetics specialists, and laboratory personnel are well-versed in the disease and can provide expert test interpretation as well as personalised treatment recommendations.
Once the team has determined that the patient has HLH, treatment should begin immediately. It usually includes the following treatments.
Corticosteroids and Chemotherapy
These medications are used to reduce the abnormal inflammation caused by HLH.
Antibody Treatments
Antibody therapies that target specific inflammatory proteins or the cells that produce them may be administered to patients.
- Hematopoietic Stem Cell Transplantation (HSCT) is a procedure used to treat HLH by replacing the body’s immune system. Cincinnati Children’s Bone Marrow Transplantation Program has extensive experience performing HSCTs for children with HLH. They were the first to use reduced-intensity conditioning for HLH, which uses less chemotherapy than the standard regimen and thus reduces the risk of transplant-related complications.