A 9-year-old boy, previously healthy, was referred to our center with 10
days of fever, weakness, epistaxis and purpura. Examination revealed a
febrile child who had marked pallor; petechiae over limbs and trunk;
1-1.5 cm multiple sub-mental lymph nodes; 3 cm hepatomegaly and 5 cm
splenomegaly below costal margins respectively. Investigations (Table
I) showed pancytopenia with lymphocytosis; elevated ALT and AST;
repeated blood cultures were sterile. Bone marrow aspiration (BMA)
revealed dyserythropoiesis and several histiocytes, some of which were
exhibiting erythrophagocytosis suggestive of hemophagocytic
lymphohistiocytosis (HLH). Further investigations revealed corroborative
evidence of HLH in the form of elevated serum LDH, triglyceride and
ferritin levels. Hepatitis virus serology was suggestive of an old
infection with hepatitis B virus. Serology for Ebstein Barr Virus (EBV)
was suggestive of recent infection. Serum immunoglobulins revealed mild
reduction in IgA and IgM levels. Thus final diagnosis was EBV associated
HLH. Patient showed remarkable clinical improvement with supportive care
including intravenous antibiotics, platelet and blood trans-fusions.
Within a week, he was asymptomatic and follow-up showed gradual
improvement with normalization of bio-chemical abnormalities and BMA at
6 weeks. At 15 months of follow-up, he remains asymptomatic.
TABLE I
Investigation Profile of the Patient
A. Primary Investigations
|
Hemoglobin
|
6.4 g/dL
|
Platelet
|
41, 000/m3
|
White Blood Cell
|
1900/m3
|
Differential
|
N18, L81, M1; anisocytosis and macrocytic anemia,
nucleated RBC 1-2/100 WBC; no blasts.
|
Renal Function Tests
|
Normal
|
Aspartate aminotransferase
|
196 IU/L (N: <50 IU/L)
|
Alanine transferase
|
134 IU/L (N: <50IU/L)
|
Chest Radiograph
|
Normal
|
USG Abdomen
|
Hepatosplenomegaly with no focal lesions
|
B. Investigations for corroborative evidence of HLH
|
DIC
|
Profile Normal except thrombocytopenia
|
Fibrinogen
|
380 mg/dL (200-450 mg/dL)
|
Lactate dehydrogenase
|
973 U/L (N: 100-190 U/L)
|
Triglyceride
|
459 mg/dL (N: 50-150 mg/dL)
|
Ferritin
|
2450 ng/L (N: 15-400 ng/L)
|
C. Investigations for corroborative evidence of HLH
|
Hepatitis B Surface antigen
|
Positive
|
Hepatitis B core IgM antibody
|
Negative
|
Hepatitis C Serology
|
Negative
|
Parvovirus IgM
|
5.8 U/mL (N: <17 U/mL)
|
Cytomegalovirus IgM
|
0.35 A.I. (0-0.9)
|
Human immunodeficiency virus
|
Negative
|
EBV IgM
|
40.63 U/L (N: <12U/L)
|
EBV IgG
|
106.6 U/L (N: <12U/L)
|
IgG
|
2860 mg/dL (N: 960-1968 mg/dL)
|
IgA
|
90 mg/dL (N: 125-380 mg/dL)
|
IgM
|
65 mg/dL (N: 90-242 mg/dL)
|
HLH is a disorder of mononuclear phagocytic system
characterized by proliferation and activation of histiocytes and
macrophages. HLH comprises primary HLH (familial or hereditary HLH) and
secondary HLH(1). Secondary HLH could be due to infections(2) which is
termed as infection-associated hemophagocytic syndrome (IAHS); rheumatic
disease and malignancies. HLH is an uncommon manifestation of many
common tropical infections such as tuberculosis, leishmaniasis and
salmonella. IAHS has a fatality rate of more than 50% in children.
EBV-HLH is the most common reported IAHS resulting in severe disease.
Clinical features of EBV-HLH include high fever, hepato-slenomegaly,
cytopenia, liver dysfunction, coagulopathy, lipid changes because of
hypercytokinemia and organ infiltration by phagocytosing histiocytes(3).
Specific treatment includes using immuno-suppressants
such as steroids and cyclosporine A and cytotoxic agents such as
etoposide. For FHLH and relapsed/aggressive EBV-HLH, stem cell
transplantation is the only curative option. The main causes of early
death are hemorrhage and infection. The initial management of EBV-HLH is
aimed at reducing the likelihood of this early death, which includes
careful monitoring of hemostatic parameters, blood products
administration, treatment of infection and prompt introduction of
cyclosporine A. The decision whether to treat a child with presumed
secondary HLH with specific drugs should depend solely on the clinical
condition of the patient and associated laboratory changes(4). The
progression to lymphoma or leukemia also seems to be a special problem
in these cases(5); which is why the patient is, and will be on continued
follow-up and monitoring.
Sameer Bakhshi,
Jeremy L. Pautu,
Department of Medical Oncology,
Dr. B.R.A. Intstitute Rotary Cancer Hospital,
All India Institute of Medical Sciences,
New Delhi 110 029, India.
E-mail: [email protected]
