This content is for healthcare professionals outside of the UK only.

This activity is funded by an independent medical education grant from Sobi, Inc. This activity is jointly provided by USF Health and touchIME.

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touchMDT Recognizing and managing HLH in the critical care setting: Best practice for the multidisciplinary team

Multidisciplinary experts discuss the diagnosis and management of haemophagocytic lymphohistiocytosis (HLH)

 Overview & Learning Objectives
Patient with suspected HLH in critical care
  • Best practice in diagnosing HLH in the critical care setting
    HLH specialist and Paediatric intensivist
    Play Arrow Watch Video

    Watch an HLH specialist and a paediatric intensivist discuss the clinical presentation of HLH in patients presenting to the ED and when it is important to have a high index of suspicion of HLH. They also consider who should be involved in the multidisciplinary team when HLH is suspected.

    Time: 13:09
    Prof. Jordan, Dr Kernan
    Play Arrow Watch Video
  • The role of biomarkers and genetic testing in HLH
    HLH specialist and Pathologist
    Play Arrow Watch Video

    Watch an HLH specialist and a pathologist discuss the role of the pathologist in the diagnostic workup of patients suspected of having HLH, including the insights available from bone marrow biopsy in identifying triggers for HLH. They also consider how clinicians can communicate most effectively with their pathologists to support the diagnostic process.

    Time: 10:42
    Prof. Jordan, Dr Gars
    Play Arrow Watch Video
  • Treatment approaches for HLH
    HLH specialist, Paediatric intensivist and Critical care pharmacist
    Play Arrow Watch Video

    Watch an HLH specialist, paediatric intensivist and critical care pharmacist discuss the importance of an individualized approach to the treatment of HLH, particularly when considering the age of the patient. They highlight the importance of early and aggressive treatment, along with careful adaptation to the patient’s specific needs to improve outcomes.

    Time: 12:41
    Prof. Jordan, Dr Kernan, Prof. MacLaren
    Play Arrow Watch Video
  • Special considerations for primary HLH
    HLH specialist and Paediatric intensivist
    Play Arrow Watch Video

    Watch an HLH specialist and a paediatric intensivist discuss the standard of care for patients with primary HLH and highlight the introduction of novel agents for second-line therapy for patients who do not respond in the first line.

    Time: 11:11
    Prof. Jordan, Dr Kernan
    Play Arrow Watch Video

Expert Spotlight

Prof. Michael Jordan
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Dr Kate Kernan
UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
Get the Audio Version

Tutorial

These icons indicate there is something to be interacted with. Click it when you see it.

Poll

In which of these settings do you predominantly work?

Submit your answer to see the results

Critical care
   
Haematology
   
Infectious diseases
   
Other
   
HLH specialist and Paediatric intensivist
Get the Audio Version
Best practice in diagnosing HLH in the critical care setting
Time: 13:09
Prof. Jordan, Dr Kernan

Watch an HLH specialist and a paediatric intensivist discuss the clinical presentation of HLH in patients presenting to the ED and when it is important to have a high index of suspicion of HLH. They also consider who should be involved in the multidisciplinary team when HLH is suspected.

Watch Next
HLH specialist and Pathologist

The role of biomarkers and genetic testing in HLH

Watch Now

Expert Spotlight

Prof. Michael Jordan
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Dr Eric Gars
University of Florida Health, Gainesville, FL, USA
Get the Audio Version

Tutorial

These icons indicate there is something to be interacted with. Click it when you see it.

Poll

What is the main challenge in identifying patients with HLH?

Submit your answer to see the results

Overlap with other conditions
   
Variable presentation
   
Non-specific laboratory findings
   
Meeting HLH diagnostic criteria
   
HLH specialist and Pathologist
Get the Audio Version
The role of biomarkers and genetic testing in HLH
Time: 10:42
Prof. Jordan, Dr Gars

Watch an HLH specialist and a pathologist discuss the role of the pathologist in the diagnostic workup of patients suspected of having HLH, including the insights available from bone marrow biopsy in identifying triggers for HLH. They also consider how clinicians can communicate most effectively with their pathologists to support the diagnostic process.

Watch Next
HLH specialist, Paediatric intensivist and Critical care pharmacist

Treatment approaches for HLH

Watch Now

Expert Spotlight

Prof. Michael Jordan
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Dr Kate Kernan
UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
Prof. Rob MacLaren
University of Colorado, Denver, CO, USA
Get the Audio Version

Tutorial

These icons indicate there is something to be interacted with. Click it when you see it.

Poll

Which of these factors influences your treatment choice for HLH the most?

Submit your answer to see the results

Age
   
Primary or secondary HLH
   
Triggers of HLH
   
Pre-existing conditions
   
HLH specialist, Paediatric intensivist and Critical care pharmacist
Get the Audio Version
Treatment approaches for HLH
Time: 12:41
Prof. Jordan, Dr Kernan, Prof. MacLaren

Watch an HLH specialist, paediatric intensivist and critical care pharmacist discuss the importance of an individualized approach to the treatment of HLH, particularly when considering the age of the patient. They highlight the importance of early and aggressive treatment, along with careful adaptation to the patient’s specific needs to improve outcomes.

Watch Next
HLH specialist and Paediatric intensivist

Special considerations for primary HLH

Watch Now

Expert Spotlight

Prof. Michael Jordan
Cincinnati Children’s Hospital Medical Center
Dr Kate Kernan
UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
Get the Audio Version

Tutorial

These icons indicate there is something to be interacted with. Click it when you see it.

Poll

When do you consider emapalumab in patients with primary HLH?

Submit your answer to see the results

Second-line therapy after HLH-94
   
As a salvage therapy after all other options
   
In patients who are eligible for HSCT only
   
Do not have access to emapalumab
   
HLH specialist and Paediatric intensivist
Get the Audio Version
Special considerations for primary HLH
Time: 11:11
Prof. Jordan, Dr Kernan

Watch an HLH specialist and a paediatric intensivist discuss the standard of care for patients with primary HLH and highlight the introduction of novel agents for second-line therapy for patients who do not respond in the first line.

Watch Next
HLH specialist and Paediatric intensivist

Best practice in diagnosing HLH in the critical care setting

Watch Now
Back To Top
Overview & Learning Objectives
Overview

In this activity, US-based clinicians discuss multidisciplinary approaches to the diagnosis and treatment of haemophagocytic lymphohistiocytosis (HLH), drawing on their clinical expertise to highlight optimal approaches to management.

This activity is jointly provided by USF Health and touchIME.

Target Audience

This activity has been designed to meet the educational needs of a diverse range of US clinicians involved in the management of HLH, including haematologists, haemato-oncologists, emergency department physicians, critical care physicians, rheumatologists, immunologists, haematology nurses and nurse practitioners, and hospital pharmacists.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Prof. Michael Jordan discloses: Advisory board or panel fees from Sobi Inc. Consultancy fees from Vertex Pharmaceuticals (relationship terminated). Grants and research support from Bristol Myers Squibb and Sobi Inc.

Dr Kate Kernan has no interests/relationships or affiliations to disclose in relation to this activity.

Dr Eric Gars discloses: Grants and research support from Guided Therapeutics.

Prof. Rob MacLaren has no interests/relationships or affiliations to disclose in relation to this activity.

Content reviewer

Christy Thai, PharmD, BCPS and Alicia Canalejo, APRN have no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Contributors

Kathy Day has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu. 

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Pharmacists

USF Health is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This knowledge-based program has been approved for 1.0 contact hours (0.1 CEUs). Universal program number is as follows: 0230-9999-24-008-H01-P.

Nurses

USF Health is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation.

A maximum of 1.0 contact hour(s) may be earned by learners who successfully complete this  continuing professional development activity. USF Health, the accredited provider, acknowledges touchIME as the joint provider in the planning and execution of this CNE activity.

This activity is awarded 1.0 ANCC pharmacotherapeutic contact hour.

Date of original release: 18 July 2024. Date credits expire: 18 July 2025.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Describe the characteristic clinical and laboratory findings of HLH, and the confirmatory diagnostic tests
  • Explain the identification of predisposing conditions and acute triggers associated with HLH and how these affect treatment selection and monitoring
  • Implement effective multidisciplinary strategies for the diagnosis, monitoring and management of HLH in the critical care setting
Faculty & Disclosures
Prof. Michael Jordan

Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

Prof. Michael Jordan is a professor of paediatrics at Cincinnati Children’s Hospital Medical Center (CCHMC) and the University of Cincinnati School of Medicine, OH, USA. He is also the scientific director of the CCHMC HLH Center of Excellence. read more

Prof. Jordan provides clinical care and consultation for patients with HLH and other immune conditions. He conducts clinical and laboratory research to improve the diagnosis and treatment of HLH, and is internationally known for his scientific and medical expertise related to HLH and other inborn immunoregulatory disorders.

He is the past president of the Histiocyte Society, and his scientific work provides the foundation for modern understanding of how HLH develops. His discoveries over the last two decades led to the development of treatments for patients with HLH. Prof. Jordan also directs the INTO-HLH Registry, which aims to help improve the diagnosis, treatment and outcomes for children and adults with HLH.

Prof. Michael Jordan discloses: Advisory board or panel fees from Sobi Inc. Consultancy fees from Vertex Pharmaceuticals (relationship terminated). Grants and research support from Bristol Myers Squibb and Sobi Inc.
Dr Kate Kernan

UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA

Dr Kate Kernan is an assistant professor of critical care medicine at the Children’s Hospital of Pittsburgh of UPMC, PA, USA, and is a National Institute of Child Health and Human Development Pediatric Critical Care and Trauma Scientist Development Program Scholar. read more

Dr Kernan completed her paediatric residency at Washington University in St. Louis followed by fellowship training at the Children’s Hospital of Pittsburgh. She has been a scientist at the Safar Center for Resuscitation Research since 2021. In 2023, she was awarded a K23 through the National Institute of General Medical Sciences to facilitate development of her research portfolio. Dr Kernan’s research is focused on understanding how individual genetic variation contributes to critical illness susceptibility and outcomes. Dr Kernan’s work has shown that children with genetic variation related to primary immunodeficiencies are at high risk for bacterial infections, extreme inflammation and often require extracorporeal therapy. Additional studies of children with innate immune variants, particularly those related to complement disorders, show that these children share unique illness characteristics typical of disorders of complement activation such as atypical haemolytic uremic syndrome.

Dr Kate Kernan has no interests/relationships or affiliations to disclose in relation to this activity.
Dr Eric Gars

University of Florida Health, Gainesville, FL, USA

Dr Eric Gars is a clinical assistant professor in the Department of Pathology, Immunology and Laboratory Medicine at the University of Florida in Gainesville, FL, USA. read more

Dr Gars is board certified in anatomic pathology and haematopathology. His clinical interests include lymphoma, leukaemia and gynaecological cancer. He has published on diagnostic approaches for HLH.

Dr Eric Gars discloses: Grants and research support from Guided Therapeutics.
Prof. Rob MacLaren

University of Colorado, Denver, CO, USA

Prof. Rob MacLaren is a professor in the Department of Clinical Pharmacy at the University of Colorado and clinical pharmacist in the medical intensive care unit (ICU) at the University of Colorado Hospital, Denver, CO, USA. read more

Prof. MacLaren completed his undergraduate degree in pharmacy at the University of British Columbia. He earned his D Pharm at the University of Utah and completed a critical care specialty residency at the University of Tennessee/Baptist Memorial Hospital in Memphis, TN.

Prof. MacLaren has over 150 peer-reviewed publications relating to the pharmacologic and nutritional therapies of critically ill patients and has secured over $800,000 in grant funding to support various research initiatives. His primary research areas include gastrointestinal disturbances of the critically ill, optimizing patient comfort in the ICU, and demonstrating the value of clinical pharmacy services. He has been an invited speaker at national and international meetings. He is also a fellow of the American College of Clinical Pharmacy and master of the Society of Critical Care Medicine.

Prof. Rob MacLaren has no interests/relationships or affiliations to disclose in relation to this activity.
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This activity is funded by:

An independent medical education grant from Sobi, Inc.
This activity is jointly provided by USF Health and touchIME.

The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgement of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

This content is intended for healthcare professionals.

Date of original release: 18 July 2024. Date credits expire: 18 July 2025. 

This content is intended for healthcare professionals outside of the UK only. Please confirm that you are a healthcare professional.

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Question 1/5
A 12-month-old infant presents in the ED with a persistent fever and splenomegaly. Which of the following clinical features would provoke a suspicion of HLH and urgent diagnostic work up?

ED, emergency department; HLH, haemophagocytic lymphohistiocytosis.
Correct

HLH should be considered in the differential diagnosis when there is unexpected and rapid deterioration with evolving organ failure that does not respond to appropriate supportive care.1 Bicytopenia may be a temporary symptom caused by a range of things including viral infections.2 A generalized rash is a non-specific symptom reflective of many different conditions.3 While HLH can be accompanied by DIC,4 it is more commonly associated with bleeding diathesis than hypercoagulation.5  

Abbreviations

DIC, disseminated intravascular coagulation; HLH, haemophagocytic lymphohistiocytosis. 

References

  1. Hines MR, et al. Crit Care Med. 2022;50:860–72.
  2. Yalaki Z, et al. J Pediatr Inf. 2014;8:23–7.
  3. Ely JW, Seabury Stone M. Am Fam Physician. 2010;81:726–34.
  4. Valade S, et al. Medicine (Baltimore). 2015;94:e1692.
  5. Valade S, et al. PLoS One. 2021;16:e0251216.
Question 2/5
For a 16-year-old patient, who has been admitted to the ED with a persistent fever, splenomegaly, persistent bicytopenia and elevated ferritin where HLH is part of the differential diagnosis, which of the following tests would be particularly informative?

ED, emergency department; HLH, haemophagocytic lymphohistiocytosis; VCA IgM, viral capsid antigen immunoglobulin M.
 Correct

The HLH-2004 diagnostic criteria, which remain the standard for the diagnosis of HLH in paediatric patients, include bone marrow aspirate/biopsy in the initial set of diagnostic tests.1 Together with lymph node or other biopsy, it may provide evidence for potential HLH, underlying haematological malignancy or other contributing condition or trigger.1–3 Genetic testing is used to confirm primary HLH.1 Lumbar puncture can help diagnose HLH where the CNS is affected, or identify acute infectious triggers affecting the CNS.4,5 VCA IgM supports the detection of EBV-specific antibodies in immunocompetent individuals.6

Abbreviations

CNS, central nervous system; EBV, Epstein-Barr virus; HLH, haemophagocytic lymphohistiocytosis; VCA IgM, viral capsid antigen immunoglobulin M.

References

  1. Hines MR, et al. Crit Care Med. 2022;50:860–72.
  2. Kikuchi A, et al. Histopathology. 2022;80:616–26.
  3. De Gottardi J, et al. PLoS One. 2019;14:e0226899.
  4. Shyu S, et al. Am J Clin Pathol. 2021;156:381–90.
  5. Song Y, et al. Chin Med J. 2018;131:776–83.
  6. Hess RD. J Clin Microbiol. 2004;42:3381–7.
Question 3/5
You have a 3-month-old infant who was diagnosed with primary HLH following a recent infection. You initiated treatment with the HLH-94 regimen, but the infant has not responded. Which of the following therapies do you consider next to stabilize them prior to curative HSCT?

HLH, haemophagocytic lymphohistiocytosis; HSCT, haematopoietic stem-cell transplantation
Correct

Emapalumab is indicated for the treatment of adult and paediatric (newborn and older) patients with refractory, recurrent or progressive primary HLH or intolerance to conventional HLH therapy.1 The HLH-2004 regimen, also for primary HLH, involves an intensification of the HLH-94 regimen; it failed to improve patient outcomes significantly.2 Dexamethasone ± anakinra is used to treat secondary HLH, while ruxolitinib is a potential salvage therapy that has been investigated in the context of secondary HLH.3 

Abbreviation

HLH, haemophagocytic lymphohistiocytosis.

References

  1. FDA. Emapalumab. PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2018/761107lbl.pdf (accessed 24 June 2024).
  2. Bergstein E, et al. Blood. 2017;130:2728–38.
  3. Hines MR, et al. Crit Care Med. 2022;50:860–72.
Question 4/5
When a patient presents with signs and symptoms consistent with HLH, a pathologist might be particularly valuable for supporting the clinical team in establishing a diagnosis when the patient has which of the following?

CNS, central nervous system; EBV, Epstein-Barr virus; HLH, haemophagocytic lymphohistiocytosis.
 Correct

A pathologist would be particularly helpful in diagnosing HLH if the trigger for the disease was due to a disseminated fungal disease like histoplasmosis. In addition to providing information about bone marrow involvement of a fungal organism, presence of leuco-phagocytosis and erythrophagocytosis can provide evidence for HLH. 

Abbreviation

HLH, haemophagocytic lymphohistiocytosis.

Reference

Zhong Q, et al. IDCases. 2022;29:e01603.

Question 5/5
Your 42-year-old patient has a persistent fever, generalized rash, persistent bicytopenia and hyperferritinaemia (762–4,338 ng/mL). HLH is in the differential diagnosis. To support you in confirming the diagnosis, identifying the likely trigger and initiating therapy, which of the following specialists would you seek to involve in the diagnosis and management of this patient?

HLH, haemophagocytic lymphohistiocytosis.
 Correct

Secondary HLH is most commonly associated with haematological malignancy, in particular lymphomas,1 or infections.2 Diagnosis and treatment of patients where HLH is in the differential diagnosis are ideally managed through a HLH multidisciplinary team that includes representatives from haematology, infectious diseases, rheumatology and critical care, with additional specialties as clinically indicated.1

Abbreviation

HLH, haemophagocytic lymphohistiocytosis.

References

  1. Bauchmuller K, et al. J Intensive Care Soc. 2020;21:256–68.
  2. Hines MR, et al. Crit Care Med. 2022;50:860–72.
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