The relationship between atypical lymphocytosis and serological tests in infectious mononucleosis

The relationship between serological tests for infectious mononucleosis was compared with atypical lymphocytosis in one hundred cases with clinical features of the disease. All blood samples showed atypical lymphocytosis greater than 20 per cent of the total leucocyte count. Positive serological tests were obtained in 69 of these patients, whereas in patients with more than 40 per cent atypical lymphocytosis all had positive serology. Of the 31 patients with negative serological tests for infectious mononucleosis, significant antibody titres to Toxoplasma gondii were obtained in five and to cytomegalovirus in two. Twenty-four patients remained undiagnosed. The Paul-Bunnell-Davidsohn positive patients had a significantly higher white cell count, lymphocyte count and atypical lymphocyte count than the toxoplasmosis group or the undiagnosed group.     

Lymphopenic infectious mononucleosis.

Lymphopenic IM is a real phenomenon. It is likely to appear as a more severe clinical illness and, in contrast to the benign course to typical IM, may have a poorer prognosis. The clinical spectrum of IM should be extended to included to include lymphopenic patients if their diagnosis is supported by appropriate heterophil and EBV antibody titers.     

The pathology of infectious mononucleosis

This pathologic study is based on 9 autopsies and many biopsies in cases ofinfectious mononucleosis.

The gross changes were almost exclusively confined to enlargement of lymphoidtissues, especially the spleen. Nasopharyngeal lymphoid hyperplasia was constant,in one instance suggesting tumor. Other tissues presented no significant gross features related to the primary disease except for (1) rather consistent enlargement ofthe liver, (2) infrequent icterus, and (3) occasional cutaneous rash. Histologic observations revealed more or less generalized lesions resembling those of certainknown virus diseases, notably perivascular aggregates of normal and abnormallymphocytes. Reaction of this type inconstantly involved all tissues studied exceptthe bone marrow; here lymphocytes were virtually absent in sections, but werepresent in aspirated marrow because of dilution with peripheral blood.

More specific changes were invariably noted in lymphoid tissues. The abnormallymphocyte characteristic of the disease could be identified in thin, lightly stainedsections. Lymph node reactions varied from a predominantly follicular hyperplasiato a blurred pattern simulating a malignant lymphoma; the latter was due to alymphocytic and reticulo-endothelial proliferation in the medullary cords. Thespleen displayed a lymphocytic infiltration in the thinned capsule and trabeculae,frequently dissolving the latter and rendering the organ liable to rupture. The pattern was partially effaced in most instances and the follicles widely spaced. Bloodsinuses contained considerable numbers of normal and abnormal lymphocytes, andaccumulations of these cells constantly cuffed intratrabecular arteries and lay beneath the intima of veins. Tonsils displayed ulceration and necrosis in several cases,and the lymphocytic proliferation closely resembled malignant tumor in a tonsilthat enlarged rapidly.

A pneumonic exudate in 1 case was almost exclusively of round cell type, whilein another the pneumonia was of the usual lobular type with a neutrophilicexudate. Small myocardial infiltrates which we noted probably explain the electrocardiographic changes described in infectious mononucleosis. Other findings ofparticular interest were the periportal lymphoid collars in the liver which sometimes attained the proportions seen in leukemia, and the presence of meningo-encephalitis in 4 of the 6 brains examined.

We believe that the majority of cells in the lymphocytic "infiltrates" of connective tissues and the perivascular collars are metaplastic rather than inwandering,i.e., that they are formed in situ and stem from cells of the reticulo-endothelialsystem.

     

Karyotypes in infectious mononucleosis.

Using a trypsin-Giemsa banding procedure, chromosome analysis was performed on blood from 21 consecutive patients hospitalized for infectious mononucleosis. Mitoses were harvested after 2 and 24 h in vitro incubation without PHA and after 48 h with PHA. No abnormalities were seen.     

The liver in infectious mononucleosis

Summary 1. Twenty-two patients with infectious mononucleosis were studied by liver biopsy and paper electrophoresis of the serum proteins. The findings were compared with a similar group of 30 patients with infectious hepatitis.2. The essential histologic features of infectious mononucleosis were the presence in the hepatic sinusoids and portal tracts of chronic inflammatory cells resembling small lymphocytes, with essentially no parenchymal cell damage. Admixed with this lymphocytic infiltrate, but in relatively minimal numbers, were a few plasma cells and polymorphonuclear leukocytes. In addition, in infectious mononucleosis there were, with rare exceptions, no lipochrome-containing Kupffer cells. Thus, in the majority of cases, the histologic picture was distinct from that seen in infectious hepatitis. Only in comparing a few of the more severe infectious mononucleosis cases with subsiding infectious hepatitis cases was there any tendency for the two pictures to merge, and the distinction on histologic grounds between the two entities could be made in the great majority of cases.3. The most commonly seen abnormalities in the paper electrophoretic patterns of sera obtained from patients with infectious mononucleosis were decreased albumin, increased gamma globulin, not infrequent but variable changes in alpha₂ globulin, and the presence of abnormal proteins migrating with mobilities intermediate to alpha₂ and beta, and beta and gamma globulins. The abnormalities observed in infectious hepatitis were similar to those of infectious mononucleosis, except that in hepatitis alpha₂ globulin was decreased more consistently, gamma globulin increased less frequently, and beta globulin, which was normal in practically all the cases of infectious mononucleosis, was increased in a considerable number of cases.4. Treatment of patients with infectious mononucleosis need not include prolonged bed rest and restriction of activity in an effort to avoid the development of chronic liver disease.     

A rapid slide test for heterophile antibody in infectious mononucleosis

The sera of 473 individuals were examined for sheep cell agglutinins both by theslide test and the Paul-Bunnell method. In this group there were 46 patients withpositive slide tests and 35 of these individuals also had a diagnostic serum dilutiontest for heterophile antibody. In 11 cases the slide test was positive but the Paul-Bunnell test gave very low serum dilution values. However, when the slide testwas carried out at 37 C, it was negative in 9 of the 11 cases. In the remaining 2instances, one patient had a Forssman type of antibody which gave a 1:64 titer insaline and the slide test was positive at 37 C. In the other case no studies were madeon the effect of temperature and the nature of the agglutination reaction wasunfortunately not determined.

Using human and bovine albumen, sheep serum and human AB serum absorbedwith sheep cells as a diluent no evidence for blocking or hyperimmune antibodywas discovered in the cases of infectious mononucleosis studied in this series.Moreover, of the 6 patients with negative serology but with strong clinical andhematological evidence for the disease, no blocking or hyperimmune antibodywas disclosed by the slide test or by the use of absorbed human AB serum. Theconclusion seems justified that blocking, incomplete or hyperimmune heterophileantibody must be rather uncommon in infectious mononucleosis.

In the use of the rapid slide test it has been pointed out that cold agglutinins,(which may be abolished by warming to 37 C) and Forssman antibodies (whichmay be absorbed by guinea pig kidney) can give positive results. However, diseases in which cold agglutinins are strong enough to give a positive slide testare relatively rare and the occurrence of Forssman antibodies of a strength likely togive a positive slide test would be decidedly uncommon. In any event unless furtherexperience reveals more serious discrepancies, the rapid slide test as described inthis paper seems to offer a practical screening test to detect clinically significantamounts of heterophile antibody in cases of infectious mononucleosis.

     

The coexistence of hepatitis A and infectious mononucleosis.

Hepatitis A is an acute, self-limited disease that spreads predominantly by the fecal-oral route. Hepatitis A characteristically has an acute, sudden influenza-like onset with a prominence of myalgia, headache, fever and malaise. Infectious mononucleosis is an acute illness characterized clinically by sore throat, fever and lymphadenopathy. The virus usually spreads from person to person by close contact with nasopharyngeal secretions. In this case the coexistence of both diseases in the same patient is found interesting.     

Positive serological tests for infectious mononucleosis in a patient with mediterranean spotted fever

The Monospot test is an accurate and reliable test for infectious mononucleosis. False positive reactions have been seldom recorded. We report the conversion of the Monospot test from negative to positive during the course of Mediterranean spotted fever. Changes in the titre of the Paul-Bunnell test were observed also. The importance of measuring IgM antibodies as part of the routine investigation of infectious diseases is emphasised.     

Hodgkin's disease and infectious mononucleosis.

Sequential sero-positive infectious mononucleosis is described in 3 sibs, 2 of whom subsequently developed Hodgkin's disease. EB virus antibodies were present in the serum of both cases.