INFECTIOUS MONONUCLEOSIS

as indicated in false positives may eliminated how the heterophile agglutination test can be of great value in the diagnosis of infectious mononucleosis, the aid of the Davidsohn absorption tests.

of these diseases, and have stressed the vital importance to progress of pooling the skill of medical men, scientists, engineers, and managements. I have referred to the many variations from the classical types of these diseases and the consequential difficulties in diagnosis and prognosis and in assessment of the hazard of the causative work. I have indicated that the doctor's approach to problems in this field is three-pointed by way of occupational history, clinical findings, and radiographical appearances. Now, a few words on the third pointthe radiographical appearances. This is just as much a headache as the other two, but is vitally important and may be conclusive. The pathological basis of the disease, that is the fibrosis, is of course reflected in the x-ray picture, but the classical appearances are more often than not modified by coincident tuberculosis, or by other disease, or obscured by the highly diffracting effect of retained inert dust. Moreover, different radiographical techniques and different types of films can mislead completely. Pending internationally agreed techniques and type films which are long overdue, the only practical suggestion is to collect your own library of type films from cases whose complete occupational and clinical histories with autopsy findings are available. This can best be achieved by local medical societies.
In discussing this tremendous national problem of the control of pneumokoniosis, I may have given a pessimistic outlook in saying too much about the difficulties of the position, but history teaches us that always just prior to great advances in knowledge and its application, we have wallowed in just such confusion. Can we hope for a dramatic discovery to guide us, such as that of the bacillus of tuberculosis which ended one long period of confusion as to the nature of these diseases, or that of the roentgen rays which pointed so imperiously the route to better diagnosis? Is it too much to hope that lines of research at present being pursued will lead to a discovery of equal magnitude on the preventive side, such as a perfect inhibitor or an instantaneous continuously recording dust counter, or, dream of dreams, a dust arrester which could be worn on the chest or like a miner's head lamp or both, and prevent dust reaching the mouth and nose and yet leave the face completely free from encumbrance? I hope so. A\N analysis of the last 45 cases of mononiueleosis seen on the medical service of the Vancouver General Hospital has convinced us that it is timely to take stock of present knowledge of the condition.
Infectious mononueleosis is a self-limited disease occurring in young people and characterized by fever, sore throat, a swelling of the cervical lymph nodes and frequently of other lymph nodes, an increase in the mononuclear leukoeytes and a granulopeenia, and a positive Paul Bunnell test. Of these symptoms and findings three are of chief diagnostic importance: (1) Cervical lymphadenopathy.
(2) Increase in the mono- Unless a patient exhibits at least two of these three findings, it is difficult to see how the diagnosis can be more than pure speculation. All the eases in our series have at least two of three criteria, and most of them have all three. An analysis is as follows: Total cases, 45. Cases with cervical lymphadenopatliy, 36. Cases-with marked increase in mononuelear leucocytes, 44.
Cases with positive Paul Bunnell test, 36. Of the 9 cases in which cervical adenopathy was niot recorded, 5 had a marked tonsillitis.
The one case which did not have a marked increase in the mononuelear leukoeytes had 33% mononuelear forms in a total of 4,650, with 35% of polymorphonuelears and 28% staff cells. This patient had enlarged cervical glands, and the Paul Bunnell test was positive in dilution 1:320. He, therefore, showed the main features of the disease.
Before proceeding with an analysis of the cases it is appropriate to discuss the Paul Bunnell test or lheterophile agglutination. The serum of normal subjects coIntains an agglutinin (Forssman) for sheep 's red blood cells vhiell does not exceed a titre of 1:8. In most cases of infectious mononucleosis, after 7 to 10 days, the serum shows an increase in this slheep s red cell agglutinin and the titre may rise to very high figures (in this series to 1:10240). Several examinations at intervals of a few days may be necessary to determine whether the result is positive. It is generally agreed that a rise to 1:32 or more is definitely abnormal. A rise in titre has been observed in individuals who have recently received injections of horse serum, but it is rare in other conditions apart from infectious mononueleosis. It is * Resident, Department of Medicine, The Vancouver General Hospital, 1948 (1) The Forssman type, that commonly found in normal serum, is absorbed by guinea pig kidney, but not be autoclaved ox cells.
(2) The type occurring in infectious mononucleosis is obsorbed by ox cells but not by guinea pig kidney. (3) The type appearing after injections of horse serum is absorbed by both.
In questionable cases the dependability of the test is increased by demonstrating that the agglutinin is absorbed as indicated in (2).
This illustrates how false positives may be eliminated and how the heterophile agglutination test can be of great value in the diagnosis of infectious mononucleosis, particularly with the aid of the Davidsohn absorption tests.
These absorption tests were not used in the present series, but in none of our cases was there any history of recent injections of horse serum. The test was regarded as positive when there was agglutination at a dilution of 1:32 or more.
As in other series, we have noticed the large number of nurses and interns in our group of cases.
It seems most likely that this high incidence amongst hospital staff is due to the more accurate diagnosis these people.
One cannot stress too of the condition in much the fact that infectious mononucleosis has an important place in the differential diagnosis of tonsillitis and pharyngitis: 41 out of 45 cases (or 91%o) had a sore throat. Actual ulceration of the pharynx was found in 4 patients and membrane formation on the tonsils in 11 more. The presence of the membrane naturally can lead to confusion with diphtheria, while the ulceration with marked granulopenia is suggestive of agranulocytic angina or leuksemia. Of the 45 cases in the present series, 33 followed what we would describe as the typical pattern of the disease, while the remaining 12 were atypical. The 33 typical cases (Table I) all showed marked enlargement of the cervical lymph nodes, pharyngitis, or both, had a marked increase in mononuclear white cells of the blood, and in 76%o of cases had a positive heterophile agglutination test. They all suffered from fever and malaise: 5 (or 15%) of the group had a palpable spleen: none of them had any physical or laboratory findings which would be considered unusual in this disease.
The remaining 12 patients (Table II) all showed a deviation from this pattern in some important respect. Cases 34 and 35 presented with symptoms suggesting disease of the central nervous system. Case 34 was drowsy and had an abnormal degree of blurring of the medial margins of the optic discs, as well as tonsillitis with exudates. She complained also of a severe frontal headache.
Case 35 presented with fever, stiffness of the neck, drowsiness, photophobia and epistaxis. It was felt that she most likely had a meningitis. A lumbar puncture was done with normal findings. Her meningeal signs gradually faded and both liver and spleen became palpable.
Cases 37 and 38 both had marked tenderness in the right lower quadrant of the abdomen, together with fever. Case 38 presented with abdominal pain as well and a diagnosis of appendicitis was made. However, operation was withheld, as the patient appeared to be improving. In case 37 the abdominal findings were less definite, but appendicitis was again considered. Both of these cases had enlargement of the cervical glands and one of them had enlargement of the axillary and inguinal glands as well. Both had a positive Paul Bunnell test and a white cell count in keeping with infectious mononucleosis.
Cases 36 and 39 presented with fever, malaise and signs of pneumonia at the base of the left lung. In both cases there were increased markings in the hilar regions of the lungs by x-ray, suggestive of a bronchopneumonia. Both cases showed a white cell count typical of infectious mononucleosis and a positive heterophile agglutination test. Neither of them showed enlargement of the cervical or other superficial lymph nodes.
Case 44, a woman of 34, presented with a history of pain in the right loin on and off for 6 weeks, fever and anorexia for 4 days, and a temperature of 101.8 degrees. At no stage did she show any abnormality of the superficial lymph nodes, but there was marked tenderness in the right upper quadrant of the abdomen and in the right costo-vertebral angle. She had a positive heterophile agglutination test 1:160 and a white blood count typical of infectious mononueleosis. The remaining 5 cases were chiefly remarkable for the skin lesions which they showed. Case 42 was a case of acne conglobata of very severe grade, who was under treatment for this condition for several months, and who had a normal white cell count when first seen anid for the first two miionths of treatment. He later developed a generialized enlargemiient of lvmph nodes, a palpable spleen and the typical blood picture of infectious mononueleosis, together with a positive heterophile agglutination test (1 :320). The other 4 displayed either a macular or papular rash on the trunk and limbs. In addition they had a sore throat with associated enlargement of the cervical lyvnpli nodes, as well as fever, a typical blood picture and a positive heterophile agglutination test.
The disease as already stated is self-limiiited and treatment therefore need be only palliative or symptomatic. There is no place for the sulfonamides in this condition, and the antibioties are unnecessary. In spite of the fact that these patients appear acutelv ill and may, run an alarming fever masterful inactivity is the proper therapeutic piroecdure.
It is apparent then that there is a typical pattern in infectious nmononueleosis which is as follows. The patient, usually a young adult, has fever and malaise followed by a sore throat with pharyngitis which may go on to uleeration, enlargement of the cervical lYmph nodes and frequently of other ly-mph nodes, a significant increase in the mononuelear leukoeytes and a positive heterophile agglutination test.
Our main point in this presentation is in respect to those cases which showed the atypical picture. The nature of the condition known as infectious mononucleosis is still imperfectly understood. The suggestion is hlere mlade that it may represent a tissue reaction to some unknown factor. This possibility is particularly suggested by case 42, where infectious mononueleosis developed under observation in hospital in a patient with acne conglobata. In this respect it may be comparable to the tissue reaction which is shown in the group of so-called collagen diseases. SUMMARY 1. We have discussed 45 cases of infectious mononueleosis, of which 33 have followed the typical pattern and 12 were atypical.
2. The mode of presentation and the subsequent course in the 12 atypical cases have been outlined.
3. The heterophile agglutination test has been discussed. 4. The suggestion has been put forward that infectious mononueleosis may represent a tissue reaction to some unknown factor.