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EB-virus negative infectious mononucleosis
Journal of Infection (1981) 3, 176-177
CASE REPORT
EB-virus negative infectious mononucleosis M. A. Mansell
Northwick Park Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ Summary A patient with infectious mononucleosis is reported in whom no increase in fluorescent antibodies to EB virus was detected. ~he literature concerning the specificity of a positive Paul Bunnell test is briefly reviewed.
Case Report A w o m a n of 32 years was admitted to hospital with an 11 day history of sore throat, headache, vomiting and generalised myalgia. Five days before admission she had noted pain in the left eye, with numbness of the left side of the face and diplopia on looking to the left. Her previous medical history was unremarkable and no other symptoms emerged on direct questioning. On examination she was toxic and unwell, with a pyrexia of 38.5°C. There was massive, bilateral tender cervical lymphadenopathy although no other nodes were enlarged and the spleen was not palpable. No abnormal signs were present in the cardiovascular, respiratory or alimentary systems, apart from the presence of one finger smooth hepatomegaly. In the central nervous system there was an obvious palsy of the left sixth cranial nerve, together with weakness and diminished sensation in the distribution of the left trigeminal nerve. There was no evidence of meningeal irritation and the remainder of the neurological examination was entirely normal. The haemoglobin was 12g/dl, with a white cell count of 17.8 x 109/1 (polymorphonuclear cells 22 per cent, lymphocytes 70 per cent, monocytes, 8 per cent, with many atypical lymphocytes), E S R 55 m m / h o u r and a normal platelet count. The Monospot test was positive. L u m b a r puncture revealed clear fluid at normal pressure, with 40 x 106 leucocytes/1 (100 per cent mononuclear cells), 24 x 106 erythrocytes/1, 0.71 g/1 protein and 2.7 mmol/1 glucose. No organisms were seen or grown on subsequent culture. The Paul Bunnell test was positive with an initial titre of 1:80, 1:40 after guinea pig absorption and zero after absorption with ox red cell antigen. The initial titre had fallen to 1:10 at three weeks and the test was negative after three months. The alkaline phosphatase and aspartate transaminase were 0163-4453/81/020176+02 $01.00/0
© 1981 The British Society for the Study of Infection
Infectious mononucleosis
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elevated on admission (44.8 kat units and 138 iu/1, respectively) although they had fallen to normal two weeks later. Fluorescent antibody titres to EB virus on admission in both serum and CSF were 1:32 (IgG) and < 8 (IgM), with no change in the serum titres five months later. C o m p l e m e n t fixing antibodies to adenovirus, enterovirus, RSV, varicella--zoster, M, pneumoniae, Coxiella burnetti (phase 1 and 2), Chlamydia/LGV and herpes simplex remained low throughout the course of the illness and the toxoplasma dye test was repeatedly negative. Soluble aspirin produced a good symptomatic response and the evidence of trigeminal involvement had disappeared by the time of her discharge from hospital one week after admission. The sixth nerve palsy was still present at this time, although she had made a complete recovery when reviewed three months after the onset of the illness. Comment
According to Evans (1972, 1978) EB virus is the only cause of heterophil antibody-positive infectious mononucleosis, with the antibody persisting at a titre of 1:40 or greater after guinea pig absorption. This is at variance with the negative antibody response to EB virus in this patient who, as judged by clinical, haematological and serological criteria, was suffering from infectious mononucleosis (Schumacher, Austin and Stass, 1979). Although heterophil antibody production may result from infection with cytomegalovirus or adenovirus (Wahren, 1969) and rubella (Phillips, 1972) they are usually of low titre and are removed by absorption with guinea pig antigen. The cause of the discrepancy between the clinical diagnosis and the E B V antibody titres in this patient remains unclear. (I thank Dr R. W. E. Watts for permission to report details of this patient and Professor H. Stern, Professor M. A. Epstein and Dr P. J. Sanderson for their helpful comments.) References
Evans, A. S. (1972). Infectious mononucleosis and other mono-like syndromes.New England Journal of Medicine, 286, 836. Evans, A. S. (1978). Infectious mononucleosis and related syndromes. American Journal of the Medical Sciences, 276, 325. Phillips, G. M. (1972). False-positive Monospot test result in rubella. Journal of the American Medical Association, 222, 585. Schumacher, H. R., Austin, R. M. and Stass, S. A. (1979). False-positive serology in infectious mononucleosis. Lancet, 1, 722. Wahren, B. (1969). Diagnosis of infectious mononucleosis by the Monospot test. American Journal of Clinical Pathology, 52, 303.
CASE REPORT
EB-virus negative infectious mononucleosis M. A. Mansell
Northwick Park Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ Summary A patient with infectious mononucleosis is reported in whom no increase in fluorescent antibodies to EB virus was detected. ~he literature concerning the specificity of a positive Paul Bunnell test is briefly reviewed.
Case Report A w o m a n of 32 years was admitted to hospital with an 11 day history of sore throat, headache, vomiting and generalised myalgia. Five days before admission she had noted pain in the left eye, with numbness of the left side of the face and diplopia on looking to the left. Her previous medical history was unremarkable and no other symptoms emerged on direct questioning. On examination she was toxic and unwell, with a pyrexia of 38.5°C. There was massive, bilateral tender cervical lymphadenopathy although no other nodes were enlarged and the spleen was not palpable. No abnormal signs were present in the cardiovascular, respiratory or alimentary systems, apart from the presence of one finger smooth hepatomegaly. In the central nervous system there was an obvious palsy of the left sixth cranial nerve, together with weakness and diminished sensation in the distribution of the left trigeminal nerve. There was no evidence of meningeal irritation and the remainder of the neurological examination was entirely normal. The haemoglobin was 12g/dl, with a white cell count of 17.8 x 109/1 (polymorphonuclear cells 22 per cent, lymphocytes 70 per cent, monocytes, 8 per cent, with many atypical lymphocytes), E S R 55 m m / h o u r and a normal platelet count. The Monospot test was positive. L u m b a r puncture revealed clear fluid at normal pressure, with 40 x 106 leucocytes/1 (100 per cent mononuclear cells), 24 x 106 erythrocytes/1, 0.71 g/1 protein and 2.7 mmol/1 glucose. No organisms were seen or grown on subsequent culture. The Paul Bunnell test was positive with an initial titre of 1:80, 1:40 after guinea pig absorption and zero after absorption with ox red cell antigen. The initial titre had fallen to 1:10 at three weeks and the test was negative after three months. The alkaline phosphatase and aspartate transaminase were 0163-4453/81/020176+02 $01.00/0
© 1981 The British Society for the Study of Infection
Infectious mononucleosis
177
elevated on admission (44.8 kat units and 138 iu/1, respectively) although they had fallen to normal two weeks later. Fluorescent antibody titres to EB virus on admission in both serum and CSF were 1:32 (IgG) and < 8 (IgM), with no change in the serum titres five months later. C o m p l e m e n t fixing antibodies to adenovirus, enterovirus, RSV, varicella--zoster, M, pneumoniae, Coxiella burnetti (phase 1 and 2), Chlamydia/LGV and herpes simplex remained low throughout the course of the illness and the toxoplasma dye test was repeatedly negative. Soluble aspirin produced a good symptomatic response and the evidence of trigeminal involvement had disappeared by the time of her discharge from hospital one week after admission. The sixth nerve palsy was still present at this time, although she had made a complete recovery when reviewed three months after the onset of the illness. Comment
According to Evans (1972, 1978) EB virus is the only cause of heterophil antibody-positive infectious mononucleosis, with the antibody persisting at a titre of 1:40 or greater after guinea pig absorption. This is at variance with the negative antibody response to EB virus in this patient who, as judged by clinical, haematological and serological criteria, was suffering from infectious mononucleosis (Schumacher, Austin and Stass, 1979). Although heterophil antibody production may result from infection with cytomegalovirus or adenovirus (Wahren, 1969) and rubella (Phillips, 1972) they are usually of low titre and are removed by absorption with guinea pig antigen. The cause of the discrepancy between the clinical diagnosis and the E B V antibody titres in this patient remains unclear. (I thank Dr R. W. E. Watts for permission to report details of this patient and Professor H. Stern, Professor M. A. Epstein and Dr P. J. Sanderson for their helpful comments.) References
Evans, A. S. (1972). Infectious mononucleosis and other mono-like syndromes.New England Journal of Medicine, 286, 836. Evans, A. S. (1978). Infectious mononucleosis and related syndromes. American Journal of the Medical Sciences, 276, 325. Phillips, G. M. (1972). False-positive Monospot test result in rubella. Journal of the American Medical Association, 222, 585. Schumacher, H. R., Austin, R. M. and Stass, S. A. (1979). False-positive serology in infectious mononucleosis. Lancet, 1, 722. Wahren, B. (1969). Diagnosis of infectious mononucleosis by the Monospot test. American Journal of Clinical Pathology, 52, 303.