Haemophagocytic Lymphohistiocytosis (HLH) or Macrophage Activation Syndrome (MAS)

Key Points

• Haemophagocytic Lymphohistiocytosis (HLH) is a rare condition in which histiocytes and lymphocytes become overactive and attack other blood cells which can lead to fever, organ damage and failure - a presentation which can resemble sepsis.
• HLH can be difficult to diagnose and requires thorough clinical evaluation as well as comprehensive imaging and laboratory investigations.
• There is currently no consensus on the diagnosis and treatment of HLH in pregnant women.

Surveillance period

1st October 2024 - 30th September 2029

Background

HLH is the coexistence of immune dysregulation and unchecked inflammation and is a rare and often life threatening condition. Primary HLH is genetic in origin and often diagnosed in infancy. Secondary HLH is the form typically seen in adults, and arises secondary to a trigger condition such as an infection, malignancy or rheumatic disease. Historically, HLH associated with an underlying rheumatic disease has been termed Macrophage Activation Syndrome (MAS) but modern guidelines advocate that all forms of this disease are now referred to as HLH, regardless of the underlying driver.¹ HLH is clinically associated with fever, cytopaenia, liver dysfunction, hepatosplenomegaly, hypertriglyceridaemia and hyperferritinaemia and treatment involves the use of immunosuppressive agents. MBRRACE-UK maternal mortality reports 2013-2021^2,3,4 documented 8 maternal deaths secondary to HLH, however the incidence of the women who survived is unknown. By adding HLH to the UKOSS programme of work will be able to determine the incidence of the condition in the pregnant population, describe the main aetiologies of HLH in pregnancy, document the outcomes for both mother and fetus/neonate and describe the treatments used.

Objective

To use the UK Obstetric Surveillance System (UKOSS) to describe the incidence of HLH or MAS in the UK and analyse subsequent management and outcomes.

Research Questions

• What is the incidence of HLH or MAS in pregnancy?
• What are the causes of HLH or MAS in pregnancy?
• What are the outcomes of HLH or MAS in pregnancy for mothers and their babies?
• What treatments are being used during pregnancy and the puerperium?

Case definition

Any pregnant or recently pregnant woman (<6 weeks since the end of pregnancy) with a diagnosis or suspected diagnosis of haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS).

Funding

This study is funded by Elizabeth Garrett Anderson Hospital Charity.

Ethics committee approval

This study has been approved by the London Brent REC (Ref. Number: 10/H0717/20).

Investigators

Bethan Goulden, Jessica Manson, Ian Giles, University College London; Charlotte Frise, Queen Charlotte's and Chelsea; Nick Barkham, David Churchill, New Cross Hospital Wolverhampton; Simon Stanworth, John Radcliffe Hospital.

References

1. Cox MF, Mackenzie S, Low R, et al. Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline. Lancet Rheum 2023. Online first: DOI 10.1016.

2. Knight M, Nair M, Tuffnell D, Shakespeare J, Kenyon S, Kurinczuk JJ (Eds) on behalf of MBRRACE-UK Saving Lives, Improving Mothers' Care - Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2013-2015. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2017.

3. Knight M, Bunch K, Tuffnell D, Shakespeare J, Kotnis R, Kenyon S, Kurinczuk JJ (Eds) on behalf of MBRRACE-UK. Saving Lives, Improving Mothers' Care - Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2016-2018. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2020.

4. Knight M, Bunch K, Felker A, Patel R, Kotnis R, Kenyon S, Kurinczuk JJ (Eds) on behalf of MBRRACE-UK. Saving Lives, Improving Mothers' Care Core Report - Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Death and Morbidity 2019-2021. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2023.

5. Fardet L, Galicier L, Lambotte O et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014;9:e94024.