Haemophagocytic lymphohistiocytosis (HLH)
A rare but serious condition in which the immune system becomes severely overactive and can damage the body's own organs, needing urgent hospital assessment and treatment
Haemophagocytic lymphohistiocytosis, usually shortened to HLH, is a rare condition in which the immune system becomes severely overactive. Rather than settling once its work is done, the immune response keeps escalating and begins to damage the body's own tissues and organs. It can develop quickly and is potentially life-threatening, so it is treated as a medical emergency. In rheumatology, HLH can arise as a complication of certain autoimmune conditions, where it is often called macrophage activation syndrome (MAS). Because the early signs can resemble a severe infection, reaching the diagnosis quickly takes careful, urgent specialist assessment.
Urgent symptoms: a persistent high fever together with feeling very unwell, particularly in someone with an autoimmune condition, needs urgent hospital assessment. Do not wait for a routine appointment.
Written for patients and reviewed by Dr Liubov Borukhson, Consultant Rheumatologist (GMC 7021928). Last clinically reviewed: June 2026.
Common symptoms
HLH can affect the whole body, and the picture can build quickly. Features may include:
- A persistent high fever that does not settle
- Feeling very unwell, with marked tiredness or weakness
- An enlarged liver or spleen, or swollen glands
- A skin rash
- Easy bruising or bleeding
- Yellowing of the skin or eyes (jaundice)
- In more severe cases, confusion or other effects on the brain
Because HLH can progress rapidly, a persistent high fever together with feeling very unwell, particularly in someone known to have an autoimmune condition, should be assessed urgently in hospital.
How it is diagnosed
There is no single test that confirms HLH. The diagnosis is based on the overall pattern of symptoms together with urgent blood tests, which usually show signs of intense inflammation. A very high level of a protein called ferritin is an important clue, alongside low blood counts and changes in the liver tests. Sometimes a bone marrow sample is needed to complete the picture. Because HLH can closely resemble a severe infection, it can be easy to miss, so a high index of suspicion and prompt specialist assessment are important to reach the diagnosis quickly and start treatment without delay.
How it is treated
HLH is a medical emergency and is treated in hospital, often in intensive care. Treatment has two aims: to calm the overactive immune response, and to deal with whatever has triggered it. Calming the immune system usually involves steroids together with other medicines that dampen inflammation, chosen according to the cause and how severe the illness is. At the same time, any underlying trigger, such as an infection, a blood cancer or an active autoimmune condition, is looked for and treated. Care almost always involves several teams working closely together, and the plan is kept under continual review. Recognised and treated early, HLH can often be brought under control.
Coordinated, specialist-led care
HLH affects the whole body and can change quickly, so care almost always needs more than one specialty working together. Dr Borukhson practises within a world-renowned tertiary centre, with ready access to consultant colleagues across the other specialties that may be involved in caring for this condition. Where appropriate, she can involve those specialists directly, and bring particularly complex cases to a multidisciplinary team meeting (MDT) with minimal delay. This means that, when more than one area of expertise is needed, your care can be joined up and decisions reached promptly.
Why assessment matters
HLH is uncommon and can be life-threatening, and the outcome often depends on recognising it early and starting treatment quickly. This is particularly important for people with an autoimmune condition such as adult-onset Still's disease or lupus, in whom HLH can develop as macrophage activation syndrome. If you have one of these conditions and become acutely unwell with a persistent high fever, it is safer to seek urgent medical assessment than to wait. Prompt specialist input helps establish what is happening and get the right treatment started without delay.
Living with an autoimmune condition?
Regular specialist review helps keep conditions such as adult-onset Still's disease and lupus well controlled, and means warning signs are recognised and acted on early
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