|Year : 2016 | Volume
| Issue : 1 | Page : 104-106
Unusual infectious mononucleosis complicated by vasculitis
Srimanta Kumar Sahu, Subhash Giri, Sarthak Malik, Nikhil Gupta
Department of Medicine, University College of Medical Sciences, Delhi, India
|Date of Web Publication||22-Dec-2015|
University College of Medical Sciences, C-158 Pushpanjali Enclave, Pitampura, Delhi - 110 095
Source of Support: None, Conflict of Interest: None
Infectious mononucleosis (IM) is a clinical syndrome caused by Epstein-Barr virus (EBV). It manifests as fever, pharyngitis, malaise, adenopathy, and atypical lymphocytosis. Cardiovascular complications are thought to be rare in IM. There are very few case reports of EBV-associated vasculitides, like Kawasaki disease and systemic polyarteritis nodosa, however, involvement of the large caliber arteries like the aorta and its branches have been reported only scarcely. Myocarditis also is rare as an early manifestation of EBV infection. We present here a rare case of IM, presented initially with acute myocarditis and later with large-vessels arteritis.
Keywords: Chronic active Epstein-Barr virus infection, infectious mononucleosis, medium and large-vessels arteritis
|How to cite this article:|
Sahu SK, Giri S, Malik S, Gupta N. Unusual infectious mononucleosis complicated by vasculitis. Med J DY Patil Univ 2016;9:104-6
| Introduction|| |
Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) is generally a mild self-limiting disease.  IM is of particular interest to the clinician because of the diversity of diseases simulated. Typical clinical features of IM are present in only 25-30% of patients. Atypical and severe presentations are rare. Cardiac complications of IM are rare. Vasculitides is one of them. There are very few case reports of EBV-associated vasculitides, like Kawasaki disease (KD) and systemic polyarteritis nodosa (PAN), however involvement of the large caliber arteries like the aorta and its branches have been reported only scarcely. Early myocarditis is also a rare manifestation of EBV infection. We present here a rare case of chronic active EBV infection, presented initially with acute myocarditis and later with large-vessels arteritis involving the abdominal aorta, superior mesenteric artery (SMA), and bilateral renal arteries with clinical manifestations of intestinal angina and renovascular hypertension.
| Case Report|| |
An 18-year-old girl presented with acute onset dyspnea with a preceding history of fever and sore throat for 10 days. There was no significant past medical history. On admission, she was febrile (38°C), other vital parameters were normal except for sinus tachycardia. General physical examination revealed mild anemia and bilateral discrete, nontender submandibular lymph nodes. Cardiovascular examination revealed elevated jugular venous pressure, a Grade II murmur of mitral regurgitation and a third heart sound in the mitral area. Bilateral basal crackles were present in the chest. There was mild hepatosplenomegaly. Her routine investigations showed hemoglobin of 10.6 g/dl, total leukocyte count 11.9 × 10 9 /L, and platelet count 190 × 10 9 /L, differential leukocyte count comprised of 46% polymorphs, 54% lymphocytes. Peripheral smear revealed atypical lymphocytes (20%). Chest X-ray revealed mild enlargement of the cardiac silhouette. Electrocardiogram showed T waves inversion in chest leads. Troponin T was positive, and CKMB was also raised (201 IU/L). Echocardiogram revealed a global reduction of left ventricular (LV) function with LV ejection fraction (LVEF) of 36% and mild mitral regurgitation. A provisional diagnosis of acute viral myocarditis was made. EBV viral capsid antigen (VCA) Immunoglobulin M (IgM) antibody was found to be high with a titer of 1:160. Serology for HIV 1 and 2, IgM hepatitis B virus, hepatitis B surface antigen, anti-hepatitis C virus, VDRL, anti-nuclear antibody, and anti-nuclear cytoplasmic antibodies was nonreactive. EBV DNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), with a viral load of 2 × 10 5 copies/mL. With a conservative management, her clinical condition improved gradually over 6-8 weeks. Echocardiogram was repeated during follow-up, which showed improved LV function with an LVEF of 48% and no evidence of MR. In the subsequent 4 months, she was complaining of fatigability, dull aching diffuse abdominal pain and low-grade fever; for which she was managed symptomatically, but her abdominal pain was worsening. She also found to have hypertension. Her blood pressures (BPs) in upper limbs were found to be higher than the corresponding lower limbs by 30 mmHg and 20 mmHg in systolic and diastolic BP, respectively. Peripheral pulses were symmetrical and of normal volume, and no bruit was audible. She did not give a history of limb claudication, angina or syncope. There was no pallor or icterus, and abdominal examination was also unremarkable. Fundus examination showed no abnormality. Her routine blood biochemistries such as creatinine, electrolytes, amylase, and lipase were normal. erythrocyte sedimentation rate was 40 mm/h, and serum C-reactive protein was <5 mg/L. X-ray abdomen in an erect position and USG abdomen were also normal. Contrast-enhanced computed tomography (CT) scan of the abdomen revealed circumferential thickening of the abdominal aorta. CT angiography revealed narrowing of the abdominal aorta from below the coeliac trunk up to the origin of the inferior mesenteric artery with stenoses and poststenotic dilatations of the proximal segments of both renal arteries.
Stenosis was also noted in the SMA near its origin from the aorta [Figure 1]. There was no involvement of the thoracic aorta, pulmonary artery, and their branches. We were not able to make tissue diagnosis due to involvement of major arteries thus increasing the chances of life-threatening complications, patient reluctance for the same and previous reports also being histological proven on autopsy only. EBV DNA was repeated which was found to be high (1.5 × 10 5 copies/mL), EBV VCA IgM antibody was also detected at a titer of 1:80, which suggest an active EBV infection. Patient was started on oral prednisolone (1 mg/kg) and following 6 months of treatment her CT angiography was repeated which showed significant improvement of SMA and minimal improvement in the thickening of abdominal aorta, however, no improvement was observed in renal arteries [Figure 2]. EBV DNA was also repeated by RT-PCR, which was undetectable this time. Patient is now planned for bilateral renal artery stenting.
|Figure 1: Computed tomography angiography showing narrowing of the abdominal aorta from below the coeliac trunk up to the origin of the inferior mesenteric artery with stenoses and poststenotic dilatations of the proximal segments of both renal arteries. Stenosis is also noted in the superior mesenteric artery near its origin from the aorta|
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|Figure 2: Repeat computed tomography angiography showing significant improvement of superior mesenteric artery and minimal improvement in the thickening of the abdominal aorta, however, no improvement was observed in renal arteries|
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| Discussion|| |
Infectious mononucleosis is an under-diagnosed entity caused by EBV, a member of the family of herpes family.  IM is also called kissing disease as the virus can be transmitted by saliva. IM may present as fever, pharyngitis, malaise, adenopathy, and atypical lymphocytosis. Hoagland's criteria  can be used for diagnosis of IM according to which: At least 50% lymphocytes and at least 10% atypical lymphocytes in the presence of fever, pharyngitis, and adenopathy, and confirmed by a positive serologic test are required for its diagnosis. Our patient had recurrent febrile illness with lymphocytes being 54%, atypical lymphocytes 20%, persistent EBV IgM anti-VCA antibodies and EBV viral DNA in peripheral blood thus fulfills the criteria for the diagnosis of IM. Cardiovascular complications are thought to be uncommon in IM. Myocarditis due to acute EBV infection has been rarely reported, however, it is unusual that heart failure appears as the initial presentation. EBV infections could lead to myocarditis in immunocompromised patients particularly with chronic EBV replication. Viral studies in acute myocarditis showed about 1% EBV prevalence.  Intramyocardial viral genome quantification in idiopathic dilated cardiomyopathy (n = 246) has shown a high prevalence of viral genomes, like parvovirus B19 (51.4%) or HHV-6 (21.6%) but EBV genome was found only in 2% of patients. Endomyocardial biopsy demonstrated intense mononuclear cell infiltrates mainly T lymphocytes and necrosis of cardiac myocytes in similar earlier case reports. EBV genome also have been demonstrated in the infiltrating T lymphocytes and thought to have played an important role in the pathogenesis of myocarditis due to EBV. Various mechanisms have been postulated for EBV induced myocardial injury. There may be direct cytopathic effects of EB virus. Complement activation and immune mechanisms may also lead to a direct or indirect damage to cardiomyocytes.
There have been very few case reports of EBV-associated vasculitides such as KD and systemic PAN. Systemic PAN has been reported in an 8-year-old boy with acute EBV infection, demonstrating fibrinoid necrosis of medium size arteries on renal biopsy.  Several reports have shown an association between EBV and KD. BS Choi et al., reported a case of adolescent KD in a patient with acute EBV infection, where a causal relationship was attributed to an elevated EBV DNA in peripheral blood. A case of large-vessel arteritis similar to our case has been reported in a 10-year-old girl with involvement of the abdominal aorta and bilateral common carotid and subclavian arteries.  EBV DNA genome was detected on autopsy of diseased aortic tissue by PCR analysis and in the infiltrating lymphocytes by in situ hybridization. They suggested that EBV-infected lymphocytes, possibly T lymphocytes might have participated in the pathogenesis of the arteritis. EBV genome has also been detected in coronary and aortic tissues and in CD4 positive lymphocytes in patients with EBV complicated by coronary aneurysm.  Causal relationship between EBV and large-vessel arteritis has been controversial. Most of the earlier attempts to find a causal relation of EBV with vasculitides were based on autopsy. The possible mechanisms leading to the involvement of large arteries in our patient could be due to infiltration of EBV-infected lymphocytes as described in an earlier case reports. Whether there is any possibility of direct damage caused by EBV to the vessels needs to be evaluated. Tissue biopsy to ascertain the role of EBV in causing the arteritis was difficult in our case. Findings supporting the causal relation of EBV and the arteritis in our case were a persistent EBV DNA with a high viral load in peripheral blood and elevated serum titers of EBV VCA IgM antibody. Chronic inflammation with eventual fibrosis and later stenoses of the arteries explain the clinical and radiological scenario of the present case. Common differential diagnoses such as tuberculosis and Takayasu arteritis were considered early during evaluation. However, there was no granuloma or acid-fast bacillus detected on FNAC of submandibular lymph nodes, her chest X-ray was normal and tuberculin test was also negative. Moreover, her clinical profile did not meet the ACR 1990 criteria for the classification of Takayasu arteritis. The patient was managed with antihypertensive agents and prednisolone (1 mg/kg). Response to the steroid in our case was remarkable and after 20 weeks of steroid therapy her symptoms improved significantly. However, in view of repeat CT angiography findings which showed no improvement in stenosis of renal arteries, the patient is now planned for bilateral renal artery stenting.
The present case highlights the potential virulence and pathogenicity of EBV infection. EBV infection though runs a self-limited course, could lead to vascular complications like medium and large-vessel arteritis and renovascular hypertension. This reflects the need for a long-term follo p after an acute EBV infection.
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[Figure 1], [Figure 2]