Age and Ageing Advance Access originally published online on January 11, 2006
Age and Ageing 2006 35(2):196-198; doi:10.1093/ageing/afj021
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Acute Epstein–Barr virus infection in two elderly individuals
Second Department of Medicine, University of Athens Medical School, Hippokration General Hospital, 114 Vas. Sophias St, 11523 Athens, Greece
Address correspondence to: S. P. Dourakis. Tel: (+30) 210 7774 742. Fax: (+30) 210 7706 871. Email: spiros{at}ath.forthnet.gr
Abstract
Most individuals acquire Epstein–Barr virus (EBV) infection in young age. Because of uncommon presentation and misdiagnosis, clinical manifestations are less well described in older age. We present two cases of elderly patients with predominant symptoms attributed to cold agglutinin haemolytic anaemia due to acute EBV infection without fever, lymphadenopathy, pharyngitis or splenomegaly. We conclude that misleading clinical manifestations are frequent in older individuals and may lead to inappropriate diagnostic invasive procedures.
Keywords: acute EBV infection, elderly individuals, cold agglutinin haemolytic anaemia, elderly
Most people acquire Epstein–Barr virus (EBV) infection during childhood or teenage years. Only 3–10% of adults older than 40 years have never been infected [1]. Evans [2], in 1969, reported that among people with heterophile antibody-positive infectious mononucleosis, only 7.5% were older than 40 years. Older adults often exhibit atypical clinical manifestations, less lymphocytosis and less frequently heterophile antibody-positive test than younger individuals [3]. In this report, we present the case of two elderly patients 76 and 73 years old with acute EBV infection and cold agglutinin haemolytic anaemia.
Two female patients aged 76 and 73 years old were admitted 12 months apart with a history of falls and dizziness. On physical examination, lymphadenopathy, pharyngitis, splenomegaly and fever were absent. Autoimmune haemolytic anaemia was diagnosed because of anti-i cold agglutinins in a titre of 1/4,000 and 1/128, and the remaining tests were: haemoglobin (Hb) 5.1 and 8.4 g/dl; reticulocyte count 2 and 0.5%; total bilirubin 5.7 and 1.2 mg/dl; direct bilirubin 1.5 and 0.3 mg/dl; lactate dehydrogenase (LDH) 364 and 296 IU/l, for the former and the latter, respectively. Haptoglobulin was less than 30.5 mg/dl, white blood cell counts, liver function tests and protein electrophoresis were normal, and atypical lymphocytes were absent in both patients. The heterophil antibody test was repetitively negative in the former and positive in the latter. Bone marrow aspiration showed poor maturation of red blood cells and increased lymphocytes in both patients. Computerised tomography (CT) scan of the abdomen showed aortic lymphadenopathy in the former and was unremarkable in the latter.
Further serological examination revealed acute EBV infection with positive immunoglobulin M (IgM) antibodies against EBV capsid antigen >1/320 as well as positive IgG antibodies against EBV capsid antigen >1/320, negative anti-early antigen and absence of anti-EBV-associated nuclear antigen. Antibodies to cytomegalovirus, toxoplasma and mycoplasma indicated past infection (IgG positive/IgM negative) in both patients.
The patients were transfused with 8 and 7 units, respectively, of warmed packed red cells and treated with folate. Reticulocyte count progressively increased and peaked at 12 and 7% on the tenth and ninth day, respectively. Their condition progressively improved and they were discharged on the twentieth and fifteenth post-admission day, respectively, with Hb of 10 g/dl and normal values of LDH and bilirubin. Six months later, both patients were in good health with complete clinical and laboratory recovery.
Clinical course of acute EBV infection varies according to the age of presentation. Most acute EBV infections in children are subclinical. However, adolescents and young adults develop symptoms with a higher frequency ranging from 50 to 70% [1]. The frequency with which adults older than 40 years develop clinically overt disease is unknown because of low rates of susceptibility in this age group. However, case reports with acute EBV infection in older patients showed that clinical infection may be more severe in this age group [4]. It was apparent from the literature [3, 5] that once the infection was overt clinically, the clinical manifestations varied among older and young individuals. Patients over 40 years of age have been reported to develop, less commonly, peripheral lymphadenopathy, pharyngitis and splenomegaly and have more prolonged fever, liver involvement and jaundice when compared with young adults [1, 3–5]. The presenting symptoms were often misleading and delayed diagnosis. Our patients were older than 70 years and had neither the classical triad of acute EBV infection nor splenomegaly. The predominant signs and symptoms resulted from the cold agglutinin haemolytic anaemia. Initially, a hypoproliferative bone marrow response due to EBV infection contributed to the anaemia with impaired reticulocyte generation. Subsequently, the reticulocyte count increased, and when the haemolytic mechanism subsided, Hb started to increase gradually. Over this period of time, both patients needed multiple blood transfusions to stabilise Hb concentration.
Anti-i cold agglutinins have been detected in 31.8% of infectious mononucleosis cases [6]. However, clinically apparent presentations with a severe fall in Hb level and jaundice leading to multiple blood transfusions, as in our patients, are uncommon, occurring in less than 2% of patients with EBV infection [7]. There are several case reports in the literature of severe haemolytic anaemia complicating infectious mononucleosis [8–11]. Cold agglutinins were evident in the majority of primary EBV infections in a report of seven patients older than 40 years, but clinically overt haemolytic anaemia was not mentioned [4]. This finding demonstrated a rather severe and atypical clinical course of acute EBV infection in the elderly hosts.
Monocytosis and atypical lymphocytes were absent from both our patients, and heterophile antibody test was negative in the first case. Patients over 40 years usually lack monocytosis and atypical lymphocytosis. In addition, it has been reported that the prevalence of heterophil-negative acute EBV infection increases with age [1, 3, 4].
Atypical clinical presentation and laboratory findings resulted usually in misleading, initial diagnoses in the literature, including ‘leukaemia’, ‘lymphoma’, ‘cholecystitis’, ‘choledocholithiasis’, ‘bronchopneumonia’, ‘endocarditis’, ‘hepatitis’ and ‘Guillain–Barré syndrome’ [1, 3, 4]. In the literature, the patients were often hospitalised for a long period of time and underwent a number of non-invasive and invasive procedures such as CT scans, liver, lymph node and bone marrow aspirations or biopsies. Considerable diagnostic uncertainty was also encountered in both our patients because both had bone marrow aspirations and CT scans performed. Evidence of serological profiles of current, ongoing, acute EBV infection eventually led to the correct diagnosis in both our cases following long hospitalisation.
In conclusion, acute EBV infection does occur in the elderly. However, the clinical manifestations are different from those in young people. Clinical triad of pharyngitis, lymphadenopathy and fever may be absent. Clinicians should be aware of this misleading clinical picture and prevent such elderly patients from having inappropriate invasive diagnostic procedures.
- Acute EBV infection is uncommon in elderly individuals.
- Clinical manifestations of acute EBV infection may be atypical in elderly individuals.
- Misleading clinical manifestations in the elderly may lead to inappropriate invasive diagnostic procedures.
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