Indian J Pediatr DOI 10.1007/s12098-015-1720-8
SCIENTIFIC LETTER
Secondary Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus K. N. Vykuntaraju & T. Avinash & Jitender Saini & L. Appaji
Received: 27 July 2014 / Accepted: 2 February 2015 # Dr. K C Chaudhuri Foundation 2015
To the Editor: Epstein Barr virus (EBV) produces broad range of central nervous system (CNS) manifestations. We report a rare case of secondary hemophagocytic lymphohistiocytosis (HLH) associated with Epstein Barr virus (EBV) presenting as Acute disseminated encephalomyelitis (ADEM). A 5-y-old apparently asymptomatic girl presented with complaints of convulsions and ataxia of 7d duration in November 2012. On examination, her Glasgow Coma Scale was 13/15, with cerebellar signs. In July 2012 she was evaluated for fever, pallor, lymphadenopathy and hepatosplenomegaly. No etiology could be ascertained, however the child responded to symptomatic treatment. Investigations revealed normal complete blood counts,
K. N. Vykuntaraju Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India T. Avinash : L. Appaji Department of Pediatric Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India J. Saini Department of Neuroimaging and Intervention Radiology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India K. N. Vykuntaraju (*) Bangalore Child Neurology and Rehabilitation Center, #8/A, First Main, First Cross, Vijayanagar, Bangalore 560040, Karnataka, India e-mail: [email protected]
liver and renal function tests. Cerebrospinal fluid examination showed protein- 90 mg/dl, lymphocytes-7 and positive for oligoclonal bands. MRI of brain showed, multiple hyperintense lesions in cerebellar and cerebral white matter on T2W images (Fig. 1a and b). Posterior fossa lesions were hypointense on T1W images (Fig. 1d); increased signal intensity on FLAIR images (Fig. 1c) and there was heterogeneous enhancement in all the lesions (Fig. 1e and f). The child was diagnosed to have ADEM and was treated with steroids. While tapering steroids child had recurrence of cerebellar signs, hence steroids were restarted and continued further for 4 more weeks. While tapering the second course of steroids, her symptoms relapsed, hence re-evaluated. Repeat MRI of brain suggested change in the morphology and signal intensity of lesions on T2W images (Fig. 2a and b) and persistent contrast enhancement on post contrast T1W images (Fig. 2c). Few new lesions were also seen in bilateral parieto-occipital areas (Fig. 2a). One of the differential diagnoses considered was HLH. Child further developed pancytopenia and hepatosplenomegaly after stopping steroids. Serum ferritin (680 mcg/L), fasting triglycerides (350 mg/dl) and serum lactate dehydrogenase (650 U/L) were increased. Serum fibrinogen level (90 mg/dl) was low. Bone marrow examination showed histiocytes with hemophagocytes (Fig. 3). DNA PCR for EBV virus was positive in cerebrospinal fluid. Repeat MRI of brain after 8 mo of chemotherapy, shows partial resolution of lesions. Above features were consistent with HLH and have been well described with histiocytosis [1]. After 4 wk of stopping steroids, child developed other features confirming the diagnosis of HLH [2]. Hence a final diagnosis
Indian J Pediatr Fig. 1 a and b Axial T2W images showing hyperintense lesions in the bilateral cerebellar white matter. In addition, multiple lesions are seen in the cerebral white matter. c. Flair axial image shows increased signal intensity within lesions with absent perilesional edema. d. Posterior fossa lesions show hypointense signal on T1W image. e and f. Post contrast study shows strong heterogeneous enhancement in all the lesions
Fig. 2 Follow up imaging after 3 mo shows change in the morphology and signal intensity of lesions on T2W images (a and b) and persistent contrast enhancement on post contrast
T1W images (c). In addition few new lesions were also seen in bilateral parieto-occipital areas (a)
of EBV associated HLH presenting as ADEM was made. Child responded to HLH 2004 protocol chemotherapy. In steroid dependent demyelination, HLH should be considered and evaluated as the management protocol and prognosis would differ. EBV infection may be considered as a possible cause of HLH. Conflict of Interest None. Fig. 3 Normocellular marrow and histiocytes with hemophagocytes
Source of Funding None.
Indian J Pediatr
References 1. Prayer D, Grois N, Prosch H, Gadner H, Barkivich JA. MR imaging presentation of intracranial disease associated with langerhans cell histiocytosis. AJNR Am J Neuroradiol. 2004;25:880–91.
2. Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.
SCIENTIFIC LETTER
Secondary Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus K. N. Vykuntaraju & T. Avinash & Jitender Saini & L. Appaji
Received: 27 July 2014 / Accepted: 2 February 2015 # Dr. K C Chaudhuri Foundation 2015
To the Editor: Epstein Barr virus (EBV) produces broad range of central nervous system (CNS) manifestations. We report a rare case of secondary hemophagocytic lymphohistiocytosis (HLH) associated with Epstein Barr virus (EBV) presenting as Acute disseminated encephalomyelitis (ADEM). A 5-y-old apparently asymptomatic girl presented with complaints of convulsions and ataxia of 7d duration in November 2012. On examination, her Glasgow Coma Scale was 13/15, with cerebellar signs. In July 2012 she was evaluated for fever, pallor, lymphadenopathy and hepatosplenomegaly. No etiology could be ascertained, however the child responded to symptomatic treatment. Investigations revealed normal complete blood counts,
K. N. Vykuntaraju Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India T. Avinash : L. Appaji Department of Pediatric Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India J. Saini Department of Neuroimaging and Intervention Radiology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India K. N. Vykuntaraju (*) Bangalore Child Neurology and Rehabilitation Center, #8/A, First Main, First Cross, Vijayanagar, Bangalore 560040, Karnataka, India e-mail: [email protected]
liver and renal function tests. Cerebrospinal fluid examination showed protein- 90 mg/dl, lymphocytes-7 and positive for oligoclonal bands. MRI of brain showed, multiple hyperintense lesions in cerebellar and cerebral white matter on T2W images (Fig. 1a and b). Posterior fossa lesions were hypointense on T1W images (Fig. 1d); increased signal intensity on FLAIR images (Fig. 1c) and there was heterogeneous enhancement in all the lesions (Fig. 1e and f). The child was diagnosed to have ADEM and was treated with steroids. While tapering steroids child had recurrence of cerebellar signs, hence steroids were restarted and continued further for 4 more weeks. While tapering the second course of steroids, her symptoms relapsed, hence re-evaluated. Repeat MRI of brain suggested change in the morphology and signal intensity of lesions on T2W images (Fig. 2a and b) and persistent contrast enhancement on post contrast T1W images (Fig. 2c). Few new lesions were also seen in bilateral parieto-occipital areas (Fig. 2a). One of the differential diagnoses considered was HLH. Child further developed pancytopenia and hepatosplenomegaly after stopping steroids. Serum ferritin (680 mcg/L), fasting triglycerides (350 mg/dl) and serum lactate dehydrogenase (650 U/L) were increased. Serum fibrinogen level (90 mg/dl) was low. Bone marrow examination showed histiocytes with hemophagocytes (Fig. 3). DNA PCR for EBV virus was positive in cerebrospinal fluid. Repeat MRI of brain after 8 mo of chemotherapy, shows partial resolution of lesions. Above features were consistent with HLH and have been well described with histiocytosis [1]. After 4 wk of stopping steroids, child developed other features confirming the diagnosis of HLH [2]. Hence a final diagnosis
Indian J Pediatr Fig. 1 a and b Axial T2W images showing hyperintense lesions in the bilateral cerebellar white matter. In addition, multiple lesions are seen in the cerebral white matter. c. Flair axial image shows increased signal intensity within lesions with absent perilesional edema. d. Posterior fossa lesions show hypointense signal on T1W image. e and f. Post contrast study shows strong heterogeneous enhancement in all the lesions
Fig. 2 Follow up imaging after 3 mo shows change in the morphology and signal intensity of lesions on T2W images (a and b) and persistent contrast enhancement on post contrast
T1W images (c). In addition few new lesions were also seen in bilateral parieto-occipital areas (a)
of EBV associated HLH presenting as ADEM was made. Child responded to HLH 2004 protocol chemotherapy. In steroid dependent demyelination, HLH should be considered and evaluated as the management protocol and prognosis would differ. EBV infection may be considered as a possible cause of HLH. Conflict of Interest None. Fig. 3 Normocellular marrow and histiocytes with hemophagocytes
Source of Funding None.
Indian J Pediatr
References 1. Prayer D, Grois N, Prosch H, Gadner H, Barkivich JA. MR imaging presentation of intracranial disease associated with langerhans cell histiocytosis. AJNR Am J Neuroradiol. 2004;25:880–91.
2. Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.
