Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies

Abstract:

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults.

Source:Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985 Jan;102(1):1-7. doi: 10.7326/0003-4819-102-1-. PMID: 2578266. https://pubmed.ncbi.nlm.nih.gov/2578266/

Clinical and pathogenetic observations on children with chronic mononucleosis

Abstract:

Epstein-Barr virus is seldom the causative agent of a prolonged atypical illness, known as chronic mononucleosis syndrome, characterized by a persistent pattern of clinical manifestations and by a defective immune response to specific viral antigens. This paper refers about 6 children for whom clinical and serological findings suggest the chronic Epstein-Barr virus infection. The authors believe that this chronic state might be explained by the unusual antibody pattern to EBV virus, with the persistent presence of anti-EA and the absence of anti-EBNA titers, expression of a reduced EBV-specific cytotoxic T cell activity.

 

Source: Cataldo F, Ammatuna P, Bellia L, Sammartano F, Violante M, Albeggiani A. Clinical and pathogenetic observations on children with chronic mononucleosis. Pediatr Med Chir. 1991 Sep-Oct;13(5):489-94. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/1664943

 

Neurasthenia in the 1980s: chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders

Abstract:

In the 1980s, patients suffering from unexplained fatigue and what seemed like a prolonged attack of acute mononucleosis were given the diagnosis of chronic mononucleosis or chronic infection with the Epstein-Barr virus.

Although the diagnosis has great appeal, the Epstein-Barr virus does not cause the syndrome (CFS) of chronic fatigue, which has been renamed and redefined chronic fatigue syndrome to remove the inference that the virus is its cause.

From a historical perspective, both syndromes represent the 1980s equivalent of neurasthenia, a disease of fatigue that influenced the development of psychiatric nosology. Because patients with depression and anxiety also have chronic fatigue and because most patients with CFS have an affective disorder, the assessment of organic causes of this syndrome requires careful psychiatric diagnosis and treatment.

Defining chronic fatigue syndrome as a medical disorder may deprive patients of competent treatment of their affective disorder.

 

Source: Greenberg DB. Neurasthenia in the 1980s: chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders. Psychosomatics. 1990 Spring;31(2):129-37. http://www.ncbi.nlm.nih.gov/pubmed/2184452

 

Chronic mononucleosis syndrome

Abstract:

We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome.

Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied.

Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission.

Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms.

 

Source: DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S, Bechtold TA, Pearson G, Purtilo DT. Chronic mononucleosis syndrome. South Med J. 1984 Nov;77(11):1376-82.  http://www.ncbi.nlm.nih.gov/pubmed/6093268

 

A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?

Abstract:

A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada.

Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control-persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor.

As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology.

 

Source: Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987 May 1;257(17):2297-302. http://www.ncbi.nlm.nih.gov/pubmed/3033337