Medical Care

Rapid diagnosis and early therapy can be pivotal.^[48] A pediatric hematology-oncology specialist is best equipped to manage hemophagocytic lymphohistiocytosis (HLH), which is a rare and potentially life-threatening disease.

Emapalumab, a monoclonal antibody that binds and neutralizes INF-gamma, was approved by the FDA in 2018. It is indicated for primary HLH in adults and children with refractory, recurrent, or progressive disease or who are intolerant to conventional HLH therapy. Approval was based on a phase 2/3 trial of 27 patients with refractory, recurrent, or progressive HLH. Result showed 63% achieved either a complete response, a partial response, or HLH improvement of emapalumab plus dexamethasone. Additionally, 70% of trial participants were able to continue on to hematopoietic stem cell transplant (HSCT).^[49] Emapalumab was found beneficial for primary hemophagocytic lymphohistiocytosis.^[2]

Protocol HLH-2004, opened on January 1, 2004, is based on the Histiocyte Society's original HLH-94 protocol, which had previously opened on January 1, 1995, with some minor modifications. The full HLH-2004 protocol is available by contacting the Histiocytosis Association of America. It represents a consolidation of the various approaches to treatment, with the goals being to first achieve clinical stability and then to cure with bone marrow transplantation (BMT).

Antimycotic prophylaxis is used during the initial doses of dexamethasone. Sulfamethoxazole and trimethoprim (ie, cotrimoxazole) is continuously administered as prophylaxis for Pneumocystis carinii because of immune suppression.^[50]

One group found that intravenous immunoglobulin (IVIG) was effective in suppressing symptoms when administered within hours of disease onset. Serum ferritin was used as a marker for macrophage activation, and treatment was administered accordingly.^[51]Patients may be classified into high-risk and low-risk groups, with only the high-risk groups receiving the etoposide (ie, VP-16) regimens. Patients who are at low risk may be treated as effectively with only cyclosporine, corticosteroids, or IVIG.^[42]More studies, including randomized controlled trials, are needed.

Persons with hemophagocytic lymphohistiocytosis may be at increased risk for developing posterior reversible encephalopathy syndrome.^[52] Central nervous system (CNS) involvement of hemophagocytic lymphohistiocytosis may trigger this syndrome and other neurotoxic side effects experienced during therapy.

Surgical Care

Bone marrow transplantation is performed when a suitable donor can be found and the patient is stable.

A study has found favorable long-term disease control in patients who received a reduced-intensity conditioned regimen instead of the conventional stem cell transplant.^[53]

If the patient is experiencing life-threatening respiratory difficulty or uncontrolled hypersplenism, splenectomy is an option.

Consultations

Consultation with a gastroenterologist may be helpful, especially if a transcutaneous liver biopsy is necessary.

If the primary form of hemophagocytic lymphohistiocytosis is suspected, a genetic counselor may be helpful. In addition to analyzing inheritance patterns and determining risk, they can provide supportive counseling to the patient and family.

Medication

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Media Gallery

A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Kathleen M Sakamoto, MD, PhD Shelagh Galligan Professor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, Society for Pediatric Research, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Nicole L Lacz, MD, and Franklin Desposito, MD, to the original writing and development of this article.

Sections Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis)
Overview
Presentation
DDx
Workup
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Medication
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Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis) Treatment & Management

Medical Care

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