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International Journal of TROPICAL DISEASE

& Health

29(2): 1-8, 2018; Article no.IJTDH.39649
ISSN: 2278–1005, NLM ID: 101632866

Multiorgan Failure Associated with Epstein-Barr
Viremia-An Elusive Diagnosis: A Case Series
Arun Agarwal1*, Mudit Agarwal2, Anudeep Saxena3 and Sheel Bhadra Jain4
1
Department of Internal Medicine, Narayana Multispeciality Hospital, Jaipur, Rajasthan, India.
2
All India Institute of Medical Sciences, New Delhi, India.
3
Department of Critical Care Medicine, Narayana Multispeciality Hospital, Jaipur, Rajasthan, India.
4
Department of Nephrology, Narayana Multispeciality Hospital, Jaipur, Rajasthan, India.

Authors’ contributions

This work was carried out in collaboration between all authors. Author AA designed the study and was
the primary consultant in first two cases. He contributed to the conception, draft, analysis, revision and
final approval of the work to be published. Author MA was involved with data acquisition, tabulation,
grammar and literature search for the study. Author AS contributed to data acquisition of images and
was actively involved in the critical care management of the cases reported. Author SBJ was primary
consultant in case 3. All authors read and approved the final manuscript.

Article Information

DOI: 10.9734/IJTDH/2018/39649
Editor(s):
(1) Arthur V. M. Kwena, Professor, Department of Medical Biochemistry, Moi University, Kenya.
Reviewers:
(1) Renshan Sun, Daping Hospital of Third Military Medical University, China.
(2) Oti Baba Victor, Nasarawa State University, Nigeria.
Complete Peer review History: http://www.sciencedomain.org/review-history/23269

th
Received 25 November 2017
Case Report Accepted 14th February 2018
Published 21st February 2018

ABSTRACT

Fulminant Epstein Barr Virus (EBV), also known as (herpes simplex virus-4(HSV-4) induced
multiple organ failure is rarely reported and should be considered a potential diagnosis in patients
with multiple organ failure. From a clinical perspective, it should be remembered that fulminant
herpes simplex Virus (HSV) infection may masquerade as “routine” bacterial severe sepsis/septic
shock. This potentially fatal condition should be diagnosed early and treated. Here we describe
three cases who were admitted with multi organ dysfunction and two of them finally deceasing in a
septic shock with multi organ failure. No bacterial or fungal infection could be detected in one of
these cases and were adequately treated in other two cases. The presence of EBV (HSV-4) was
detected in plasma confirming EBV viremia. The presentation, clinical course and management are
discussed.

_____________________________________________________________________________________________________

*Corresponding author: Email: mpicdrarun@gmail.com;

and Kaposi's investigations are shown in Table 1. Later her SES panel report received on 12. severe metabolic acidosis and succumbed to her illness 2. erosive gastritis. On examination she was febrile. there are more than sepsis. Her blood and other body fluid There are 9 herpes virus types known to infect cultures done outside were persistently sterile in humans: herpes simplex viruses 1 and 2. with variable leukocyte counts. of shortness of breath (orthopnea).1 Case 1 on 12. 29(2): 1-8. diuretics. 42 year. The pathogenesis of these infections was managed with antibiotics (initially is not completely understood.IJTDH.08. B.2017. Her serology de novo infection or reactivation of the latent for anti nuclear antibody (ANA).09. Thus.08. attended triage on 19. azotemia. However. and leucocytosis.2017 through triage in blood sample. but certainly cefoperazone+sulbactum. In immunocompromised patients such and E. pulmonary edema. human with respiratory rate 24/minute. human herpes virus-4 (HHV-4). and HSV-2. leptospira and human autoimmune disease. However she progressively immunocompetent patients.She also had moderate pulmonary hypertension immunocompromised individuals as a result of with features of right heart failure. nasopharyngeal swab for Influenza A (H1N1- reactivation of these viruses may have serious 2009) and all cultures were also negative. sore off and on and was diagnosed to have right lung throat. polyserositis. 1. coagulopathy. immunocompetent.08. saturation 90-91% on room air. Article no. known case of hypertension. She had metabolic acidosis with high 130 herpes viruses [1]. she 2. antihypertensives.also known as HHV. crepitations and non tender hepatomegaly. pulse 98/minute. prompt treatment with anti viral drugs of 6 gram positive bacteria. She outcomes. pneumonitis herpes viruses the feature of initial infection of (Fig. aztreonem. In total. high “reactivation” later in life. IJTDH. Epstein–Barr virus (EBV or HHV-4).08. establishment of latency. Aspergillus and Cryptococcus neoformans). Her human herpes virus 7 (HHV-7). hepatitis A.2 Case 2 loose stools and vomiting of 4-5 days duration. was considered in all patients presenting with liver & intubated and mechanically ventilated on respiratory failure of unknown cause or persistent 11. moxifloxacin. 2018. raised inflammatory markers. 3 fungi (Candida. pneumonitis. Her human immunodeficiency virus infection. it generally affects . oxygen varicella-zoster virus (VZV. pneumonitis and Multiorgan failure in management.2017 was positive for human herpes Ms SG.Syndromic evaluation system (SES) panel was management of associated co-pathogens. BP 108/62 mm Hg. 1) with hypoxemia. malnutrition.. mild bilateral pleural last 4-5 days. also diagnosed to have multi-organ dysfunction with known as HHV-8). 8 viruses and 1 parasite (Toxoplasma gondii). and sepsis with multi organ dysfunction. occasional 2. mild tachypnea 3). later multifaceted [2]. bibasal fine herpes virus 6A and 6B (HHV6A and HHV-6B). swelling in left thigh. Agarwal et al. CASE REPORT developed resistant hypotension. INTRODUCTION effusion.2017 which detects DNA suspected.17 years. Autopsy was declined by the medical intensive care unit (MICU) with a history family. (ANCA). He had primary dengue fever 2 .SK. EBV must be deteriorated. blood Here. meropenem. pain abdomen in right upper quadrant.39649 Keywords: Epstein barr virus.17. we report three cases of EBV associated and blood products and other supportive hepatitis. young hosts. and later raised procalcitonin consequences. C infection. methylprednisolone. EBV share with other lactate.08. She had pan cytomegalovirus (HCMV or HHV-5). transaminitis. cancer chemotherapy. multi organ failure. anti neutrophil cytoplasmic antibody as post transplant.2017 past two months for similar symptoms with fever with the complaints of diffuse body-aches. 11 gram negative should be initiated. Hemodialysis was also done multi organ dysfunction despite adequate . and colisitn). burns or immunodeficiency virus were negative. HSV-1 last two months. virus-6(HHV-6) and epstein barr virus (EBV) in was admitted on 06. developed hypotension. If done on blood on 11. moderate occasional loose stools and fever off and on for pulmonary hypertension. bacteria. She had three admissions at tertiary centers in Mr. (also known as HHV1 and HHV2). She was sarcoma-associated herpes virus (KSHV. sepsis. human systolic grade 3/6 murmur. breathlessness.

bibasal coarse crepitations.09.09. HBsAg. Mr. teicoplanin chronic kidney disease-renal failure. enlarged right iliac and inguinal lymph nodes. and mild pleural effusion myositis with marked aches his blood was sent for SES panel which detected DNA for 2. Agarwal et al. With persistence of showing bibasal pneumonitis with bilateral fever. Salmonella typhii IgM. which were later changed to colistin. 1.3 Case 3 staphylococcus aureus and EBV. and mild pedal edema.2017 (case 1) Table 1. respiratory rate 39/minute. portal hypertension. was admitted on antibiotics were changed to intravenous 18. tender swelling over left thigh and gluteal area. Ultrasound of left thigh showed edema in subcutaneous tissue and myofascial planes. He was diagnosed to have expanded showing bilateral pneumonitis with? pleural dengue fever with myocarditis.08. on and meropenem.2017 and was admitted outside where he received antibiotics and symptomatic treatment. leptospira antibody. effusion panniculitis. 29(2): 1-8. ANCA(c and p) and extractable nuclear antigens Fig. lymphadenopathy. he was given 250 mg of methylprednisolone for 3 days. urine.2017 (case 2) (ENA) were not detected. virus reactivation secondary to underlying free fluid in abdomen. respiratory rate 37/minute. and multiorgan dysfunction. He had persistent fever and raised inflammatory markers. X ray chest dated 20. On examination he 0 was febrile 101 F. clindamycin. myositis. Article no. Presence of EBV DNA in blood and 94% on room air. Hepatitis C virus. 48 years. Rest of the systemic examination was 3 .2017 with the complaints of fever. 2). 2. SJ. X-ray chest 11. chikungunya virus IgM antibody. serology for HIV. bilateral pneumonitis (Fig. piperacillin+tazobactum. He was treated with supportive treatment. All his cultures (blood. He had mild transaminitis. mild splenomegaly. On treatment he became afebrile and was examination he was febrile 99. BP 90/60 mm Hg.4°F. BP 114/60 mm Hg . known case of alcoholism. mild (just palpable) hepatosplenomegaly. panniculitis.39649 (Dengue NS1 detected) on 07. His abdomen ultrasound showed mild hepato- splenomegaly. With plasma leakage and persistent symptoms he was evaluated to rule out associated other tropical diseases. few oropharyngeal ulcers.2017. 3). nasopharyngeal swab for influenza A(H1N1-2009). and azithromycin.++ grade) with homogeneous pattern. oxygen saturation healed. Scrub typhus IgM antibody. developed ulcers on gluteal and leg areas (Fig.. However.09. cough vancomycin and acyclovir. He was admitted in MICU and further evaluated. positive EBV IgG serology suggests that he had bilateral coarse crepitations. and few ulcers on both lateral upper third of thighs. His cutaneous ulcers 114/minute.oxygen saturation 93% on room air.10.IJTDH. His investigations are tabulated in Fig. His venous doppler for lower limbs. 2018. chronic liver disease. mediastinal and peripheral lymphadenopathy. IJTDH. After SES panel report maintenance hemodialysis. and malaria parasite antigen were negative. ANA by IFA was moderately positive (1:320. pulse discharged on 02. With antiviral and weakness of four days duration. bilateral mild pleural effusion and minimal ascites (evidence of plasma leakage). With a possibility of vasculitic ulcer. and swab from ulcer bed) were sterile. pulse 130/minute. infection leading to EBV viremia.

moderate to gross ascites. none without causing symptoms of illness. corticosteroids and anti staphylococcal antibiotics. He was treated with anti pseudomonas Fig. 3. 4.IJTDH. presented with Multiorgan dysfunction and had EBV viremia along with staphylococcal aureus infection.39649 unremarkable. clarithromycin. Case 3 had co-infection with Pseudomonas aeruginosa along with EBV viremia. or due to nonspecific symptoms [3]. His serology for IgM and IgG EBV antibodies was Fig. Though rare. Case 1 had multi organ dysfunction related to EBV viremia along with HHV6 virus infection. predominantly be seen in immunocompromised Most persons are infected during infancy and individuals like patients with hemato-oncologic early childhood and are asymptomatic or have malignancies. 4 . Article no. vasopressors.09. Case 2 had recent dengue infection.Later SES panel test reported on 27.2017 on blood detected DNA of pseudomonas aeruginosa and EBV. they could be the cause for sepsis and should be thought of. 4). It is a ubiquitous to viscera in adults are rare and can virus that infects at least 95% of the population. His investigations are mentioned in Table 1. However. portal hypertension. 3. of these three adult cases were but reactivation has potential to create chaos in immunocompromised.09. Punched out superficial ulcers on right drugs but antiviral were not given in view of gluteal and upper lateral thigh in case 2 deteriorating renal status.. transplant recipients. Achong. bilateral bright small kidneys with loss of corticomedullary differentiation. Agarwal et al. Acyclovir.2017 (case 3) negative confirming it to be a acute primary showing cardiomegaly with bibasal (newly acquired) EBV viremia.2017.09. and Barr [1]. supportive treatment and maintenance hemodialysis. He was managed as suspected infective endocarditis with sepsis and multi organ dysfunction syndrome with meropenem. It can be reactivated immunosuppressive medication. We have presented three immune competent cases with EBV viremia who presented as severe sepsis along with underlying other co-infection in two of them.2017. He also succumbed to his illness. 2018. Viremia and dissemination Epstein. He responded to acyclovir.09. She succumbed to her illness. DISCUSSION EBV DNA was detected in EDTA The Epstein–Barr virus (EBV) was discovered 51 (ethylenediaminetetraacetic acid) plasma years ago by electron microscopy of cells samples in all these three cases indicating florid cultured from Burkitt's lymphoma tissue by systemic infection. however was not added in view of deteriorating renal status. his fever persisted and he had to be intubated and mechanically ventilated on 29. He was successfully discharged. However. USG showed evidence of chronic liver disease. splenomegaly. He succumbed to his illness on In developed countries the incidence of viral 29. the immune system. Autopsy was refused by his family. and right renal calculus with few concretions-ray chest showed bilateral pneumonitis (Fig. IJTDH. X ray chest dated 18. nevertheless. sepsis is believed to be less than 1% of septic episodes of patients admitted to intensive care [2]. Colisitin was pneumonitis added in modified renal doses. 29(2): 1-8.

0 6.68 IgG:7.28 9.7%.99 Serum 0.76 1. Multi organ failure associated with EBV among the cases investigated Test Normal value Case 1 Case 2 Case 3 Lowest 12-15 gm/dl 7.03 Creatine Kinase < 235 U/L 1226 Weil felix Test OX2 1:80 OX19 NR OXK NR Cultures Sterile Blood/urine/ET: Blood/urine/pus Blood/urine/ascitic sterile swabs: sterile fluid/ET: sterile SES Panel Not detected HHV 6 DNA Staphylococcus Pseudomonas detected Aureus DNA Aeruginosa DNA EBV DNA detected detected detected EBV DNA EBV DNA detected detected EBV serology IgM <8 U/ml Not done IgM:2.4 mm Hg.47 IgG <8 U/ml IgG:59.27 31. mild Suspicion of mobile mm small pulmonary vegetation on perimembranous Hypertension thickened aortic VSD. BE(ecf) (-) Lactate 11.2 gm/dl 5.39649 Table 1. 2018.3 pO2 61.09.6 S.38 (-) 8.2 S.8 8.9-1.1 ALT 30-65 U/L 4164 40.1.3 mg/dl 3.3 mg/dl 5.4 28. HCO3 7.9 pH7. IJTDH.0 gm/dl 2.62 1.1 mm Hg.57 5.5 ng/ml < 0.IJTDH.50 IgM:3.HCO3 19.02 0. 29(2): 1-8.3 mm mmol/L.408.6 PT-INR 0.74 2.65 29.2 30.07 3 Lowest platelet 150-400x10 /ul 50 36 31 counts st ESR 0-10 mm 1 hour 25 110 CRP <=3 mg/L 116 31.5-5. 5 .ALP 50-136U/L 95.Direct 0-0.95 S.3 27.Total Proteins 6. mmol/L.69 2.08.09 6.370.50 bilirubin S. pO2 96. sO2 1. sO2 92. Procalcitonin < 0. mild to RVSP 44 mm valve.7 7.17 S.sO2 96.01 <0.5 ug/ml 10. mm Hg.73 creatinine S.5 18.pCO2 38. Albumin 3.424. Article no.1 4. mm Hg.08.Ferritin 10-232 ng/ml 446 1190 BUN 7-18 mg/dl 89.09.17 >10.2 25. 5 Mild TR. BE(ecf) mmol/L.3 ng/ml <1.2 134 100.8%.6 hemoglobin 3 Highest TLC 4-10x10 /cmm 24.HCO3 23..01 BNP TNI ECHO RA.7 mm pO2 64.2. Lactate 3. mmol/L 92.4-8. BE(ecf) (-) Hg.pCO2 pH7. mild MR.3 mmol/L Cardiac 0-4.6-1 mg/dl 4.2 Hg.17 22.84 1.03 ABG pH7.0 on 11.6%.pCO2 12.09 D-Dimer 0-0.8 markers 0-100 pg/ml 910 1560 CK-MB 0-0.49 S.25 69. RV dilated.76 2. Total 0-1.38 1.02ng/ml <0.5 on 06.87 1.72 bilirubin AST 15-37 U/L 4750 113.17 >2<10 on >2<10 on 25. Agarwal et al.

a sepsis-like hemophagocytic syndrome. have been described for less than proliferating B cells [4]. hypertension. Grade 1 LV DRA. Article no. Usually. they can be an but point to the diversity of clinical manifestations important cause of morbidity and mortality. cardiomegaly Minimal Right pleural with mildly dilated effusion. RVSP: Right ventricular systolic pressure. In young adults. Agarwal et al.9.bilateral atelactatic minimal pleural Changes in effusion. mild pericardial effusion. HHV: Human herpes virus. pneumonitis. cause a hemophagocytic syndrome. subhepatic. and myocarditis..7. and syndrome caused by EBV triggering widespread interstitial nephritis. Acute EBV can also 1% of patients: conjunctivitis. Multiple middle lobe. but by damage.8] these complications are uncommon. pericarditis. None of the three cases fulfilled psychological disorders. Primary EBV infection is often asymptomatic. hemolytic anemia. right paracolic gutter and pelvis. Focal consolidation and Ground glass ground glass attenuation changes attenuation in Right upper and changes. The following complications. [4. EBV is Mononucleosis (IM). to a cytokine storm with multiple organ failure pancreatitis. listed causing immune suppression of these alphabetically. recovery are transformed and tend to proliferate is complete within a few weeks. DRA: Diastolic relaxation abnormality Whether primary or reactivation.5.LVEF 50% moderate TR. of parenchyma No e/o PTE. Symmetric Chest with Prominent multifocal areas CTPA Pulmonary arteries. although cases spontaneously and if uncontrolled it can result in lasting several months have been reported in serious and fatal disease. Mild hepatomegaly. pulmonary RVSP 60 mm Hg.6. This infection does not literature. Small b/l renal concretions. NCCT Mild free fluid seen abdomen in perihepatic. lymphohistiocytosis syndrome (sHLHS). especially in children. involving an activated and prominent cervical lymphadenopathy and distorted immune system.10]. 2018. 29(2): 1-8. criteria for secondary hemophagocytic [4. hepatitis. SES: Syndrome evaluation system. neurologic macrophage activation and histiocytosis leading diseases other than meningoencephalitis. LVEF: Left ventricular ejection fraction. mild b/l lower lobes. parotitis.5.IJTDH. Hg. cause illness by causing lyses of tissues as seen invasive viral disease or to immune-mediated in cytomegalovirus (CMV) infection. TNI: Troponin I. IJTDH. Pleural mediastinal Thickening. of acute EBV infection. reticular lymph nodes < opacities. RVSP 51 mm Hg. BNP: B type natriuretic peptide. moderate pulmonary moderate hypertension. EBV can 6 . EBV infected B cells significant fatigue and malaise. the The pathogenesis of these infections is not infection causes EBV associated Infectious completely understood. a febrile pharyngitis with immunopathogenic. 12mm. NCCT/CECT Mild cardiomegaly.39649 moderate TR. Complications may be due to tissue. and splenic rupture. pulmonary arteries.

His ulcers healed and succumbed to her disease. and may adversely Though we did not do any biopsy of the lesion affect the course of the disease. Hodgkin’s lymphoma. Acute HHV-6 further clinical research. post supportive care. Nevertheless. coagulopathy. He case 3 it appeared to be a de-novo acquired was not considered for acyclovir due to chronic infection. these cutaneous lesions could be causative agent in 1% of sepsis and multi attributed to herpes virus infection. Primary infection with two different herpes mucosal and even genital ulcerations have been viruses may occur simultaneously or in described in infectious mononucleosis [12. A blood stream represent viral reactivation in an and B and HHV-6A and HHV-6B are officially individual whose immune system is impaired by considered distinct species rather than a variant ongoing sepsis syndrome by another causative of 1 species . Serology We could not treat case 1 with these therapies as could not be done in case 1 as we did not diagnosis was made posthoumously. Case 2 was suspected it to be the underlying cause and the managed with acyclovir and corticosteroids and report of DNA PCR was received after the patient responded to treatment. lymphadenopathy.. EBV and HHV6 clinician should take into consideration of viral PCR assay were positive in her blood and she sepsis as a possibility and do every effort to had no evidence of any other co-infection. primary CNS suggest that these agents induce a modest lymphoma. nasopharyngeal carcinomas of improvement with diminishment of lymphoid and Southeast Asia. A variety of cutaneous. 4. and since tests for vasculitis were negative 2. Article no. though reported to be the (ANA. This patient had sepsis with no evidence of any other co-infection thrombocytopenia. viral antigens. CONCLUSION Case 2 had oral and cutaneous ulcers as described earlier. IJTDH. it has treatment for patients with EBV associated been adequately treated. 29(2): 1-8. We would also emphasize much symptoms were contributed by either of the that in addition to supportive intensive care in two viruses cannot be commented but it does these patients. the mainstay of agent in cultures or even if present.IJTDH. 2018. liver failure) or other severe complications or other therapies can be affected promptly. One of the mimics of EBV is HHV6 disease [11].39649 also result in a broad spectrum of neoplasm’s infectious mononucleosis and other and lymphoproliferative states including Burkitt’s manifestations of primary EBV disease is lymphoma. fulminant hepatitis. X-linked therapy alone have been imperfect but do lymphoproliferative disorder. or does detectable EBV in the blood of case 1. Acyclovir is a demonstration of the appropriate serologic nucleoside analogue that inhibits permissive EBV findings. In all three cases detection of EBV polymerase but has no effect on latent infection. kidney disease stage 5 with severe azotemia. unexplained fever.. or even if present and adequately treated. azotemia. close succession. All these three cases infection is rare in immunocompetent adults but were immunocompetent. ANCA). Viral infections. Studies focusing on steroid transplant lymphoproliferative disorder. HHV-6 comprises 2 forms. DNA in blood confirmed acute viremia. T cell and NK cell lymphomas. and DNA confirm the infection through inhibition of EBV DNA diagnosis. and hepatitis or encephalitis. and pneumonitis. multi organ dysfunction. should be considered if there is no usual causative As regards management. 1. Is EBV virus the primary cause of sepsis and HHV6 and EBV DNA were isolated from the multi-organ failure. warranted in individuals with impending airway and should be considered in those suffering from These viral infections need to be recognized severe overwhelming life-threatening infection early in their course so that antiviral intervention (e. clinical outcome. our case may manifest as a mononucleosis like illness series highlights that in a patient with characterized by fever. A trial of corticosteroids is and leiomyosarcomas [4]. organ dysfunction cases. In case 2 serology lymphadenopathy subsided. adversely affecting the course evidence of sHLHS) could contribute to the poor of the disease. The such as aplastic anemia. How salvage the patient. mucosal swelling [14]. Case 3 expired suggested it to be a reactivation viremia and in within 48 hours of diagnosis of EBV viremia. Agarwal et al.g. a delay in diagnosis and show that primary infection with two different initiation of specific antiviral therapy and herpes viruses may occur simultaneously or in immunosuppressive treatment (if there is close succession.Sub typing was not done in this organism or other underlying disease needs case as it wasn’t available. 7 .13].

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