LETTERS TO THE EDITOR INDIAN PEDIATRICS 1253 VOLUME 42 __ DECEMBER 17, 2005 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 lympho-
cytosis; 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
improve-ment with supportive care including
intra-venous 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. HLH is a disorder of mononuclear phagocytic system characterized by proli-
feration 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 manage-
ment 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 cyclo-
sporine 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: sambakh@hotmail.com EBV-associated Hemophagocytic
Lymphohistiocytosis with
Spontaneous Regression LETTERS TO THE EDITOR INDIAN PEDIATRICS 1254 VOLUME 42 __ DECEMBER 17, 2005 TABLE IInvestigation Profile of the Patient A. Primary Investigations Hemoglobin 6.4 g/dL Platelet 41, 000/m 3 White Blood Cell 1900/m 3 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) REFERENCES 1. Imashuku S. Advances in the management of
Hemophagocytic Lymphohistiocytosis. Inter J
Hematol 2000; 72: 1-11. 2. Janka GE, Imashuku S, Elinder G, Schneider
M, Henter JI. Infection and malignancy associated hemophagocytic syndromes.
Secondary hemophagocytic lymphohistio-
cytosis. Hematol Oncol Clin North Am 1998;
12: 435-444. 3. Henter JI, Elinder G, Ost A. Diagnostic
guidelines for hemophagocytic lympho-
histiocytosis. Semin Onco1 1991; 18: 29 -33. LETTERS TO THE EDITOR INDIAN PEDIATRICS 1255 VOLUME 42 __ DECEMBER 17, 2005 4. Janka GE, Schneider EM. Modem manage-
ment of children with hemophagocytic
lymphohistio-cytosis. Br J Hematol 2004; 124:
4-14. Congenital cystic adenomatoid mal- formation (CCAM) of the lung represents an
abnormal hamartomatous proliferation of
bronchioles at the cost of alveoli(1). In the
developed world, CCAM is usually diagnosed
antenataly. The natural history of this
antenataly diagnosed condition may be very
varied. It may occasionally progress to non-
immune fetal hydrops, or it may decrease in
size or may even regress(2). The majority
would however present with respiratory
distress at birth. It may occasionally present as
recurrent chest infections in childhood or later
adulthood(3). We report our experience with a neonate, aged 3 weeks, referred to us for progressively
increasing respiratory distress since birth. No
antenatal workup was available. The clinical
and pre-operative radiological picture of the
patient mimicked congenital diaphragmatic
hernia (Fig. 1) for which he underwent
laparotomy, which revealed normal abdominal
anatomy with intact diaphragm. The follow-up
chest radiograph showed hyper-inflated lung
with mediastinal shift and was suggestive of
congenital lobar emphysema. Keeping in mind the significant respiratory distress, a left
thoracotomy was performed few hours later
that revealed multiple cysts in left lower lobe of
lung. Left lower lobectomy of lung was done.
The histopathology of resected specimen
however came as surprise; it was reported as
CCAM. The child had stormy post-operative
period. He required ventilatory and ionotropic
support and succumbed to persistent pulmo-
nary hypertension and sepsis on l0th post-
operative day. 5. Imashuku S, Hibi S, Ohara T, Iwai A, Sake M,
Kato M, et al. Effective control of Epstein-Barr
virus-related hemophagocytic lymphohistio-
cytosis with immunochemotherapy. Blood
1999; 93: 1869-1874. Fig. 1. Chest roentgenogram at first presentation that was suggestive of CDH. Unusual Congenital Cystic
Adenomatoid Malformation of the
Lung: A Diagnostic Dilemma