Rare Presentation of Epstein Barr Virus

Address for correspondence: Dr. Abhijit Ari E-mail: abhijitari@gmail.com 1Dr. Abhijit Ari1, RMO CT, Department of Paediatric Medicine, Burdwan Medical College, 2Dr. Taraknath Ghosh2, Department of Paediatric Medicine, Burdwan Medical College, 3Dr. Sayan Bose3, Resident, Department of Pediatric Medicine, Burdwan Medical College, 4Dr. Prashant Kumar Shetty3, Department of Paediatric Medicine, Burdwan Medical College, 5Dr. Ruchi Chaudhary4, Senior Resident, Department of Paediatric Medicine, SMS Medical College. Abstract


Introduction
E pstein Barr virus (EBV) has a variety of clinical presenta ons that range from an asymptoma c carrier state to a fatal overwhelming infec on.In the majority of the popula on, EBV causes acute infec ous mononucleosis, a self-limi ng illness characterized by fever, lymphadenopathy, tonsillopharyngi s, and hepatosplenomegaly 1 .An infrequent complica on of EBV infec on is the development of Hemophagocy c Lymphohis ocytosis (HLH) and opsoclonus myoclonus syndrome (OMS).
Here we are repor ng two cases with these rare presenta ons of acute EBV which is serologically confi rmed in laboratory The Case (1) A nine year female child was admi ed in our hospital with the complaint of fever, jaundice, maculopapular rash, anasarca with decreased urine output.On examina on she was conscious but disoriented and had jaundice, edema, tachycardia, feeble pulse and hypotension and mild splenomegaly.A provisional diagnosis of sepsis with acute kidney injury was made and was ini ally treated with normal saline (NS) bolus to correct the shock along with intravenous an bio cs and other suppor ve management.Ini al inves ga on (Table 1) shows bicytopenia, altered renal func on, hyperbilirubinemia otherwise normal LFT, hypofi briginomia, hypertrigyceridemia and hyperferri nemia.On the basis of this inves ga on bone marrow aspira on has done which shows erythroid hyperplasia with RBC ingested macrophage without any features of malignancy.On the basis of the clinical features and laboratory inves ga on ini al diagnosis had changed to HLH.To know the cause diff erent viral an body ter was es mated which shows posi vity for EBV.Oral prednisolone has started at the dose of 2mg/kg/day from day 4 of admission along with intravenous an bio cs.Her general condi on and other clinical features has improved and all abnormal laboratory features became normal.She was discharged 13 days a er admission.

The Case (2)
An eight year old male child presented with high grade fever for one week and ac ve convulsion with altered sensorium for two days.On admission pa ent GCS was 9/15, febrile (101° F), having tachycardia but otherwise vitals stable.He had maculopapular skin rash present all over the body but predominant on trunk.His bilateral pupils were normal in size and normally reac ng to light, neck rigidity and Kerning's sign posi ve, refl exes are not exaggerated, plantar refl ex bilateral extensor but there was no neurological defi cit.There is mild splenomegaly without hepatomegaly.Inves ga ons revealed hemoglobin: 9.7 gm/dl; total leukocyte count: 16.0 × 10 9 /l; diff eren al leukocyte count: polymorphs 67%, lymphocytes 27%, monocytes 3%, and eosinophils 3%; and platelet count: 150 × 10 9 /l.Serum sodium was 139 mmol/l, serum potassium 4.5 mmol/l, blood urea 27 mg/dl, serum crea nine 0.5 mg/dl, random blood sugar 91 mg/dl, serum bilirubin 1.2 mg/dl, serum alkaline phosphatase 1095 IU/l, SGPT 103 IU/l, serum proteins 6.6 gm/dl, and serum albumin 3 gm/dl.Examina on of the cerebrospinal fl uid revealed proteins 49.4 mg/dl, and sugar 49.8 mg/dl (corresponding blood sugar was 127.4 mg/dl); total cell count was 15/mm 3 (polymorphs 30% and lymphocytes 70%).Gram's stain and AFB stain were nega ve.Ini al laboratory inves ga ons and lumber puncture report shows acute viral encephali s.An viral and an bio c has started along with the suppor ve management.
On 5 th day of admission he had involuntary, arrhythmic, high-amplitude, conjugate ocular movements in all direc ons.When asked to look at a target, his visual fi xa on was disrupted by bursts of high-frequency, conjugate ocular oscilla ons that had horizontal, ver cal, and torsional components, sugges ve of opsoclonus.He also had sudden brief involuntary jerky movements of his limbs, trunk, and head, sugges ve of myoclonus.The myoclonic movements increased on si ng or standing.Viral serology has sent which shows Epstein Barr virus VCA an gen IgG and IgM posi vity.Other viral serology was nega ve.Chest X-ray, USG abdomen and MRI brain of the child was normal.
Pa ent was diagnosed as a case of opsoclonus myoclonus syndrome with Epstein Barr virus infec on.Oral prednisolone at 2mg/kg/day all symptoms along opsoclonus myoclonus were subsided with 10days therapy.Then a er steroid was tapered from 10 th day onwards.At 1-month follow-up the pa ent was asymptoma c.

Discussion
HLH was fi rst described in 1939 and has since been broken down into primary and secondary HLH 2  EBV-related secondary HLH may occur at any age.A secondary form of HLH may also occur in pa ents with normal immune systems.However, it may also be seen in pa ents with immune system defects 2,3 .
Precise mechanism of EBV-induced HLH is that EBV-infected B cells s mulate cytotoxic T lymphocytes leading to hypercytokinemia and s mula on of histoly c cells.On the other hand, EBV causes s mula on, genera on and uncontrolled secre on of T-and NK-cells, as well as genera on of IL2, INFa and IL6.These materials are said t o be responsible for Hemophagocy c Lymphohis ocytosis.There is another mechanism by which EBV s mulates membrane protein (LMP-1) in cells.The cells exceedingly secrete INFa, leading to macrophages ac va on 4,5 .
As the signs and symptoms of EBV-induced HLH imply, the diff eren al diagnosis is extremely broad, par cularly in a cri cally ill pa ent.The hematologic and clinical abnormali es o en suggest sepsis, leukaemia, lymphoma, or systemic autoimmune vasculi s as the underlying cause.
In our second pa ent was diagnosed as having OMS caused by EBV and the diagnosis was based on demonstra on of an body ters in the serum.
The term 'opsoclonus' is defi ned as chao c, conjugate, mul factor, back-to-back, saccadic eye movements without intersaccadic latency.Although the exact pathophysiology of opsoclonus remains unclear, fi ndings of recent pathological and func onal MRI studies suggest that disinhibi on of the fas gial nucleus of the cerebellum is involved.The classic concept of damage to the omnipause cells in the pon ne raphe is not supported by autopsy studies 6 .Opsoclonus is o en precipitated or exacerbated by blinking or eyelid closure, both of which may suppress omnipause neurons.OMS is encountered in pa ents with encephali s, in associa on with certain neoplasms (notably, neuroblastoma in children and gynecological cancers in adults), and certain toxins.The onconeuronal an bodies associated with OMS are an -Ri an bodies (gynecologic cancers) and, less frequently, an -Hu, an -Yo, and an -Ma-2 an bodies 6 .Epstein-Barr virus, coxsackie virus, and enterovirus have been incriminated in OMS.Epstein-Barr virus, coxsackie virus, and enterovirus have been incriminated in OMS 7,8 .Our pa ent was treated with cor costeroids which is also cost-eff ec ve, easily available, and free of serious side eff ects when used for a short dura on.

Conclusion
Though EBV infec ons in most cases are asymptoma c or very few manifesta ons but it also presents with this rare presenta on which should be kept in mind to prevent mortality.Rarely, lifethreatening complica ons develop that require immediate recogni on and treatment.In the presence of severe hemodynamic collapse with pancytopenia, coagulopathy, and hepatosplenomegaly, EBV-induced HLH should be suspected and warrant determina on of ferri n levels, EBV studies, and a bone marrow aspira on to expedite diagnosis and direct life-saving therapy.EBV is also associated with OMS and it is easily treated with cor costeroids with favourable prognosis.

Table 1 :
. Primary Laboratory Values on Admission