Summary Haemophagocytic,

Haemophagocytic
Lymphohistiocytosis (HLH)
Guidance on the diagnosis, treatment,
management and governance.


July 2024




GIRFT is part of an aligned set of programmes within NHS England

,Contents
1. Introduction .......................................................................................................................................3

1.1 HLH – Key Information: ...................................................................................................................3

Paediatric HLH......................................................................................................................................4

2. HLH pathway ....................................................................................................................................5

2.1 Pathway overview .....................................................................................................................5

2.1.1 Presentation .............................................................................................................................6

2.1.2 Aetiopathogenesis of HLH ........................................................................................................6

2.1.3 Clinical Feature and Diagnosis of HLH .....................................................................................7

2.1.4 HScore .....................................................................................................................................7

2.1.5 Hyperinflammatory biomarkers and scores ...............................................................................8

2.1.6 Treatment .................................................................................................................................9

2.1.7 Support with treatment/management decisions ......................................................................12

2.1.8 Investigating HLH ...................................................................................................................13

3. Case studies ...................................................................................................................................17

3.1 Case Study 1 – Sheffield Teaching Hospitals NHS Foundation Trust (STH) ...........................18

3.2 Case Study 2 – University College London Hospitals NHS Foundation Trust (UCLH) .............19

3.3 Case study 3 – Kent & Medway HLH MDT....................................................................................20

3.4 Case Study 5 – HLH at Croydon ..................................................................................................21

4. Further information ..........................................................................................................................22

5. Authors & Contributors ....................................................................................................................24

5.1 Lead Authors ................................................................................................................................24

5.2 Contributors ..................................................................................................................................24

5.3 Contributing Organisations ............................................................................................................26




We are proud to say this guide has been co-badged with:

British Society for Rheumatology

Histio UK



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, 1. Introduction
Haemophagocytic Lymphohistiocytosis (HLH) is a devastating syndrome with uncontrolled activation of
the immune system leading to hyperinflammation, tissue damage and multi-organ failure. HLH can be
triggered by infection (including COVID-19), malignancy, autoimmune/autoinflammatory disease,
pregnancy, therapeutic interventions including some drugs, CAR-T cell therapy and bone marrow
transplant.


1.1 HLH – Key Information:
• Symptoms are non-specific (often mimicking sepsis) and can present to any medical or surgical
speciality.
• If untreated, HLH leads to multi-organ failure and death.
• HLH affects people of all ages and from a broad demographic background.
• HLH is considered to be a rare disease, although incidence is increasing, and it is likely under-
diagnosed.
• Even with treatment, recent UK data has shown a crude mortality rate of 50%: a nationwide study all
cases of HLH diagnosed between 2003 and 2018 reported a crude one-year survival rate of 50%.
This varied considerably by age, gender and associated comorbidity, highlighting the need for
greater recognition and identification of underlying drivers of the condition.
• HLH requires cross-specialty management: the possible triggers of HLH span a range of
specialities. Management can be nuanced and complex and patients often require critical care.
Diagnosis is a challenge because there is no single test for HLH although there is increasing
evidence that a combination of easily available biomarkers can be readily used in people at risk
(those with fever and falling blood counts and uncertain precipitating illness or in at-risk groups e.g.
with rheumatic disease) and a multi-disciplinary approach to management is advocated.


In 2018 Dr Rachel Tattersall (Sheffield) and Dr Jessica Manson (London), both rheumatologists, came
together with the aim of trying to improve outcomes for patients with HLH, to standardise
approaches to investigation and treatment as well as characterise HLH to improve research. The
resulting network HiHASC (Hyperinflammation and HLH Across Specialty Collaboration) Across
Speciality Collaboration www.hihasc.org) has 200 members across the UK from paediatric and adult
medicine and disciplines including; rheumatology, haematology, neurology, critical care, infectious
diseases, immunology, virology and acute/general medicine. London and North of England now have
weekly national MDT provision, and have evidence to confirm that since formation, death rates have
significantly reduced. A video showcasing patient experience can be found here:
https://vimeo.com/906468560/5cf551d605?share=copy with the kind permission of the patients involved.
The national framework has fostered new local/regional services but there remains inequity of access to
care for people with HLH.

GIRFT is proud to release this best practice guidance in collaboration with Dr Rachel Tattersall
and Dr Jessica Manson and would like to thank them for sharing their experience, expertise and clinical
outcomes with fellow acute providers, via this guidance and the associated pathway.


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