Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis) Clinical Presentation

Updated: Jun 09, 2020
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Presentation

History

The diagnostic criteria set forth by the Histiocyte Society for inclusion in the International Registry for Hemophagocytic Lymphohistiocytosis (HLH) is as follows. [1] 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

Skin findings are noted in more than half of patients, such as scaly and waxy lesions and rashes on the scalp and behind the ear. [3]  Other findings include swollen or hemorrhagic gums that can result in tooth loss; feeding problems (especially prominent in infants); and abdominal pain, vomiting, diarrhea, and weight loss.

Hemophagocytic lymphohistiocytosis was noted in a boy with Chédiak-Higashi syndrome. [38]  In a sampling from Brazil, 90% of patients with hemophagocytic lymphohistiocytosis had fever and thrombocytopenia, although in adults, hepatomegaly, splenomegaly, and jaundice were less common than in children, and serous cavity effusion was more frequent. [25]

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Physical Examination

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.

The skin can be involved in various ways. 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. [3]

Hemophagocytic lymphohistiocytosis may be complicated by central nervous system (CNS) involvement.  [39]  One Swedish study described nearly 75% of patients as having some form of CNS involvement, with half showing neurologic symptoms including seizures, ataxia, hemiplegia, mental status changes, or simply irritability. [40]

Because of the predilection of the disease for certain tissues, lymphadenopathy is frequently found on physical examination. Common constitutional findings are malaise, anorexia with or without weight loss, and failure to thrive. [1]

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