Hemophagocytic Lymphohistiocytosis (HLH)
What is Hemophagocytic Lymphohistiocytosis (HLH)?
Hemophagocytic lymphohistiocytosis, or HLH, is a rare and serious immune disorder. In HLH, your immune system becomes overactive and starts attacking your own healthy cells. White blood cells called macrophages begin destroying other blood cells throughout your body.
This condition causes dangerous inflammation and can damage organs like your liver, spleen, and bone marrow. HLH can be inherited, meaning you are born with genetic changes that cause it. It can also be acquired later in life, triggered by infections, cancers, or autoimmune diseases. Either form requires urgent medical care.
HLH is life-threatening without treatment. Early detection through blood testing is critical because symptoms can look like many other conditions. The condition affects both children and adults, though inherited forms usually appear in infancy.
Symptoms
- Persistent high fever that does not respond to antibiotics
- Enlarged spleen or liver
- Severe fatigue and weakness
- Easy bruising or unusual bleeding
- Yellowing of the skin or eyes, called jaundice
- Skin rashes
- Neurological symptoms like confusion, seizures, or difficulty walking
- Swollen lymph nodes
- Difficulty breathing
- Rapid heartbeat
Some people may have only a few of these symptoms at first. The condition can progress quickly, so any combination of persistent fever with other symptoms needs medical evaluation.
Concerned about Hemophagocytic Lymphohistiocytosis (HLH)? Check your levels.
Screen for 1,200+ health conditions
Causes and risk factors
Primary HLH is caused by genetic mutations that affect how immune cells function. These inherited forms usually appear before age 1, though some genetic types emerge later in childhood. More than 10 different genes can cause primary HLH when they contain mutations.
Secondary HLH develops when something triggers your immune system to overreact. Viral infections like Epstein-Barr virus are common triggers. Cancer, especially lymphomas and leukemias, can also cause HLH. Autoimmune diseases like lupus or rheumatoid arthritis sometimes lead to secondary HLH. People with weakened immune systems from HIV or organ transplants face higher risk. In some cases, doctors cannot identify a specific trigger.
How it's diagnosed
Doctors diagnose HLH using specific criteria that include clinical findings and lab tests. Blood tests are essential for diagnosis. Ferritin levels are typically extremely high in HLH, often above 10,000 ng/mL and sometimes exceeding 50,000 ng/mL. White blood cell count usually drops progressively as the condition worsens. Other important blood tests check for low blood cell counts, high triglycerides, and liver function problems.
Rite Aid offers testing for key HLH markers including ferritin and white blood cell count. These tests can help identify warning signs early. If your results show concerning patterns, your doctor may order additional specialized tests. These can include bone marrow biopsy, genetic testing, and tests that measure immune cell activity. Early detection saves lives with HLH.
Treatment options
- Chemotherapy drugs to suppress the overactive immune system
- Steroids like dexamethasone to reduce inflammation
- Immunosuppressive medications such as cyclosporine or etoposide
- Treatment of underlying triggers like infections or cancer
- Antibiotics or antiviral medications when infections are present
- Blood transfusions for severe anemia or low platelet counts
- Stem cell transplant for inherited forms or severe cases
- Intensive care monitoring for organ support
- Regular blood testing to monitor treatment response
HLH requires immediate treatment in a hospital setting. The condition is medical emergency that needs specialist care. Most patients work with hematologists and immunologists. Treatment plans depend on whether HLH is primary or secondary and what triggered it. Long-term follow-up with regular blood work is necessary even after initial treatment succeeds.
Concerned about Hemophagocytic Lymphohistiocytosis (HLH)? Get tested at Rite Aid.
- Simple blood draw at your nearest lab
- Results in days, not weeks
- Share results with your doctor
Frequently asked questions
Primary HLH is caused by inherited genetic mutations and usually appears in infants or young children. Secondary HLH develops later in life when infections, cancers, or autoimmune diseases trigger the immune system to overreact. Both types cause the same dangerous immune response and require urgent treatment. Genetic testing can help identify which type you have.
Primary HLH affects about 1 in 50,000 to 1 in 100,000 births. Secondary HLH is more common but still rare in the general population. However, secondary HLH may be underdiagnosed because its symptoms look like many other conditions. Adults with certain cancers or severe infections face higher risk of developing secondary HLH.
Blood tests are essential but usually not sufficient alone for HLH diagnosis. Doctors look for a combination of findings including very high ferritin, low blood cell counts, high triglycerides, and other markers. Clinical symptoms like persistent fever and enlarged organs are also part of the diagnostic criteria. Most cases need additional testing like bone marrow biopsy to confirm the diagnosis.
Extremely high ferritin levels suggest massive immune system activation. While many conditions raise ferritin modestly, levels above 10,000 ng/mL are uncommon and concerning. In HLH, ferritin often exceeds 50,000 ng/mL due to overactive macrophages releasing large amounts of this protein. Higher ferritin levels often indicate more severe disease and worse prognosis.
Treatment can control HLH and even achieve remission, but outcomes depend on the type and severity. Secondary HLH may resolve if the underlying trigger is treated successfully. Primary HLH often requires stem cell transplant for long-term cure. Without treatment, HLH is usually fatal within weeks to months. Early diagnosis and aggressive treatment greatly improve survival rates.
Anyone with persistent high fever plus enlarged liver or spleen should be evaluated. People with unexplained low blood cell counts and very high ferritin need testing. Children with family history of HLH or unexplained infant deaths should be screened. Cancer patients or those with severe infections who develop new fevers and organ enlargement may need HLH evaluation.
HLH can progress very rapidly, sometimes within days to weeks. The speed varies based on the underlying cause and whether it is primary or secondary. Some cases develop more slowly over several weeks. Regardless of speed, HLH always requires urgent medical attention because delayed treatment increases the risk of organ damage and death.
Yes, HLH can recur, especially in people with genetic forms who have not had stem cell transplant. Secondary HLH may return if the original trigger reappears or if new triggers emerge. Regular monitoring with blood tests helps catch recurrence early. People who have had HLH need ongoing medical follow-up even after successful treatment.
HLH is a medical emergency that requires hospital treatment, not lifestyle changes alone. Once in remission, maintaining general health supports your immune system. This includes eating nutritious foods, getting adequate rest, and avoiding infections when possible. Regular medical monitoring and blood testing are the most important factors for managing HLH long-term.
White blood cell counts typically drop in HLH as the condition progresses. Overactive macrophages destroy other blood cells, including white blood cells. This creates pancytopenia, which means low counts of all blood cell types. Monitoring WBC counts helps doctors track disease severity and treatment response. Falling WBC is one of the diagnostic criteria for HLH.