Haemophagocytic lymphohistiocytosis (HLH) and MAS

HLH happens when the immune system loses its normal "off switch". Certain immune cells, including a type called macrophages, keep activating and release a flood of inflammatory signals. Instead of clearing a threat and settling, this self-sustaining storm starts to harm healthy tissues and organs.

It usually arises in response to a trigger. Common ones include a viral or other infection, a blood cancer such as lymphoma, and an active autoimmune condition, where the same process is often called macrophage activation syndrome. A rarer inherited form, driven by faulty immune genes, mainly affects young children.

In adults, those most often affected have an underlying autoimmune condition, typically adult-onset Still's disease or lupus, a serious infection, or a blood cancer.

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.

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.

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.

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.

Recovery from HLH is led by your hospital team, not something managed alone, and getting better can take time. Be patient with yourself: tiredness often lingers for weeks or months as your body and blood counts recover.

While treatment is dampening your immune system, you are more prone to infection. Keep up with recommended vaccinations, raise any fever or new symptom promptly, and take medicines exactly as prescribed. If you are on steroids, never stop them suddenly.

• Attend every follow-up appointment and blood test, as these track recovery and catch any return early
• Rest and build activity back gradually
• Eat well and stay hydrated to support healing
• Lean on family, friends or a counsellor; a serious illness takes an emotional toll too

If an underlying condition triggered your HLH, keeping it well controlled lowers the risk of it happening again.

HLH can move quickly, so trust your instinct: if you feel seriously unwell, seek help the same day rather than waiting.

Call 999 or go to A&E if you develop:

• A persistent high fever with feeling very unwell, especially if you have an autoimmune condition
• New confusion, drowsiness, a severe headache or a seizure
• Easy bruising, unusual bleeding, or blood in your urine or stools
• Yellowing of the skin or eyes, or breathlessness

Contact your specialist team or GP urgently, within a day or two, for a fever that keeps returning, new or worsening swollen glands, marked tiredness, or any symptom that feels like a previous flare coming back.

For milder, settled questions about your recovery or medicines, a routine appointment is fine. When in doubt, it is always safer to be checked.

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.

How is HLH diagnosed?

There is no single test, so the diagnosis rests on the overall picture together with urgent blood tests. These often show intense inflammation, a markedly raised ferritin, low blood counts and abnormal liver tests. Sometimes a bone marrow sample helps complete the picture. Because HLH can mimic a severe infection, prompt specialist assessment and a high index of suspicion matter, so the diagnosis is reached quickly and treatment begins without delay.

What does treatment for HLH involve?

HLH is a medical emergency treated in hospital, sometimes in intensive care. The aims are to calm the overactive immune response, usually with steroids and other medicines that dampen inflammation, and to find and treat whatever triggered it, such as an infection, a blood cancer or an active autoimmune condition. Several teams typically work together and the plan is reviewed continually. Recognised and treated early, HLH can often be brought under control.

How is HLH linked to autoimmune conditions, and what is macrophage activation syndrome?

In rheumatology, HLH can develop as a complication of certain autoimmune conditions, where it is often called macrophage activation syndrome, or MAS. The immune system, already active, escalates further and starts to damage the body's own tissues. It arises most often in conditions such as adult-onset Still's disease or lupus, which is one reason regular specialist review and quick action when acutely unwell are so important.

When should I seek urgent help if I have an autoimmune condition?

If you have a condition such as adult-onset Still's disease or lupus and become acutely unwell with a persistent high fever that does not settle, seek urgent hospital assessment rather than waiting for a routine appointment. Other warning signs include feeling very unwell with marked tiredness, easy bruising or bleeding, yellowing of the skin or eyes, or confusion. With HLH, early recognition genuinely changes the outcome, so it is always safer to be checked.

Why does HLH need 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 specialties that may be involved. Where appropriate she can involve them directly and bring complex cases to a multidisciplinary team meeting with minimal delay, so decisions are joined up and reached promptly when more than one area of expertise is needed.