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Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis) Clinical Presentation

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
Updated: May 18, 2016


The diagnostic criteria set forth by the Histiocyte Society for inclusion in the International Registry for Hemophagocytic Lymphohistiocytosis (HLH) is as follows.[25] All 5 criteria must be met to establish a diagnosis of hemophagocytic lymphohistiocytosis:

  • Fever - Seven or more days of a temperature as high as 38.5°C (101.3°F)
  • Splenomegaly - A palpable spleen greater than 3 cm below the costal margin
  • Cytopenia - Counts below the specified range in at least 2 of the following cell lineages:
  • Hypofibrinogenemia or hypertriglyceridemia - (1) Fibrinogen less than 1.5 g/L or levels greater than 3 standard deviations below the age adjusted reference range value or (2) fasting triglycerides greater than 2 mmol/L or levels greater than 3 standard deviations above the age-adjusted reference range value
  • Hemophagocytosis - Must have tissue demonstration from lymph node, spleen, or bone marrow without evidence of malignancy
  • Rash - Skin findings in more than half of patients;[1] scaly and waxy lesions; rashes on the scalp and behind the ear
  • Other - Swollen or hemorrhagic gums that can result in tooth loss; feeding problems (especially prominent in infants); abdominal pain, vomiting, diarrhea, and weight loss
  • Hemophagocytic lymphohistiocytosis was noted in a boy with Chédiak-Higashi syndrome.[26]
    • In a sampling from Brazil, 90% of the those with hemophagocytic lymphohistiocytosis had fever and thrombocytopenia, although in adults, hepatomegaly, splenomegaly and jaundice were less common in children, and serous cavity effusion more frequent.[19]


See the list below:

  • Clinical findings, including evidence of infection due to decreased immunity and white cell killing defects, easy bruisability, and pallor, are related to pancytopenia secondary to bone marrow infiltration or splenic sequestration.
  • Evidence of a coagulopathy with an increased activated partial thromboplastin time (aPTT) is present.
  • Jaundice is often present due to hyperbilirubinemia.
  • As many as 65% of patients have a nonspecific rash that is often vaguely termed maculopapular although it has also been described as ranging from erythroderma to generalized purpuric macules and papules to morbilliform eruptions.[1]
  • One Swedish study described nearly 75% of patients having some form of CNS involvement, with half showing neurologic symptoms including seizures, ataxia, hemiplegia, mental status changes, or simply irritability.[27]
  • Because of the predilection of the disease for certain tissues, lymphadenopathy is commonly found on physical examination.
  • Other common constitutional findings such as malaise, anorexia with or without weight loss, and failure to thrive can occur.[25]
  • The skin can be involved in various ways; this is clinically best characterized as erythroderma, generalized purpuric macules and papules, or morbilliform eruptions.
  • Hemophagocytic lymphohistiocytosis may be complicated by central nervous system involvement.[28]


See the list below:

  • See Pathophysiology.
  • Epstein-Barr virus infection is most common one linked with hemophagocytic lymphohistiocytosis.[15]
  • Hemophagocytic lymphohistiocytosis may be a complication of dengue, although this association is unusual.[29, 30]
  • Scrub typhus may also be linked.[31]
Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

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: International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.


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.

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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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