THE WASSERMANN REACTION IN INFECTIOUS
MONONUCLEOSIS*
WILLIAM SAPHIR
From the Medical Department of the Michael Reese Hospital, Chicago
If one is to judge from the literature, infectious mononucleosis
appears to be much more prevalent than in previous years. At
the Michael Reese Hospital in Chicago, there were diagnosed
three cases in 1934, four cases in 1935, seven cases in 1936,
eleven cases in 1937, and five cases during the first 3 months of
1938.
Whether this increase in cases, here and elsewhere, actually is
as great as it appears to be, or whether it is partly due to more
exact diagnostic procedures is an open question.
In Paul and Bunnell's 1 discovery in 1932 of the presence of antibodies against sheep red blood cells in the serum of patients
suffering from the disease we have a diagnostic criterion of great
accuracy. It is generally agreed that Paul and Bunnell's heterophilic antibody test is a specific test for infectious mononucleosis
provided that serum sickness is ruled out2.
In all the thirty cases of infectious mononucleosis reported at
the Michael Reese Hospital during the last four years, the test
was positive.
There seems to be no doubt that many cases formerly diagnosed as influenza, grippe, cervical lymphadenitis, aleukemic
myelosis, and lymphadenosis are recognized now as infectious
mononucleosis by means of this specific serologic test.
It is not intended to enter here into a review of the literature
on this subject, which may be found in recent publications3,
but to refer briefly to some communications pertinent to this
study, and to report a case of infectious mononucleosis not only
* Received for publication August 1st, 1938.
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WASSERMANN REACTION IN INFECTIOUS MONONUCLEOSIS 307
because of its serological aspects, but also because of its differential diagnostic difficulties. It is believed that this study maybe helpful in recognizing and evaluating similar clinical manifestations of infectious mononucleosis.
REPORT OF CASE
Mrs. L. K., aged 32 years, was admitted to Michael Reese Hospital 3-20-38
with a history of being ill for the past week with fever up to 101, sore throat,
backache, night sweats, lack of appetite and strength, as well as extreme fatique.
The past history was insignificant except that the patient had suffered a
fracture of the humerus in a recent automobile accident for which she still
was wearing a splint.
Significant physical findings were those of temperature (1022), a mild sore
throat with redness and follicular swelling, considerably enlarged painless
anterior and posterior cervical nodes, and slightly enlarged submaxillary,
axillary and inguinal lymph nodes. Heart and lungs were within normal
limits. There were no pathological auscultatory findings except a soft systolic
murmur over all the ostia of the heart. The spleen was moderately enlarged,
palpable, one finger breadth below the costal margin, soft and not painful.
Significant laboratory findings were a leukocyte count of 9,300, differential
count of polynuclear leukocytes—41, basophilic leukocytes—2, lymphocytes
and large mononuclear leukocytes—57. The heterophilic antibody test was
positive in a dilution of 1:32. There was a four plus Wassermann and a four
plus Kahn test. Blood chemistry, blood culture and agglutination tests for
typhoid, dysentery and bacillus of Bang were negative.
During the next week the patient's condition remained stationary, the temperature not exceeding 1016, the Wassermann and Kahn reactions remained
four plus positive on two subsequent examinations. The titre of the heterophilic
antibodies rose to 1:64. At the end of the week the patient developed a
generalized maculo-papular eruption with a rise in temperature to 103, the
eruption involving particularly the chest, abdomen, back and extensor surfaces
of the extremities. Another Wassermann test was four plus positive. The
white count was 12,500 with differential count similar to the above. With the
outbreak of the rash, the patient seemed to feel better.
The eruption gradually disappeared during the following week with a simultaneous decrease in temperature. The patient improved rapidly and regained
strength and appetite. Serological examination shortly before the patient's
discharge showed a negative Kahn test, a negative Wassermann test with
cholesterolized antigen and a four plus Wassermann with lipoid antigen. The
patient was discharged March 12th clinically recovered. A Wassermann and a
Kahn test performed one week after discharge were completely negative throughout as well as a test taken 5 weeks thereafter.
308
WILLIAM SAPHIR
COMMENT
From a clinical as well as from a serological viewpoint the
patient offered unusual features. Clinically, the case presented
a striking similarity to the pre-eruptive stage of primary syphilis.
The presence of cervical, axillary and inguinal adenopathy,
followed by a generalized maculo-papular eruption associated
with four plus Wassermann and Kahn tests seemed almost conclusive evidence of a syphilitic infection. The prevalence of
cervical adenopathy, a slightly enlarged spleen, and a low grade
fever did not seem to contradict this assumption. However,
the characteristic mononucleosis as well as the positive heterophils antibody test left doubt as to whether we were dealing with
infectious mononucleosis in a patient suffering from syphilis, or
whether the positive Wassermann reaction was due to the presence of infectious mononucleosis.
The subsequent course, namely, the disappearance of the positive Wassermann reaction, made it clear that the patient was
suffering from infectious mononucleosis accompanied by a
positive Wassermann reaction.
The pitfalls the case presented are clear: had we failed to conduct the heterophilic antibody test, and had we failed to consider
the characteristic blood findings, the patient doubtless would
have been diagnosed as a case of pre-eruptive syphilis and thus
would have been treated anti-luetically. The disappearance of
the positive Wassermann reaction would then have been attributed to the result of the antiluetic treatment which raises the
question whether cases of infectious mononucleosis clinically
and serologically resembling pre-eruptive syphilis, may have
been so diagnosed and treated erroneously in the past. If so,
such cases seem extremely rare for none of the thirty cases in
the series of infectious mononucleosis mentioned above, had a
four plus Wassermann and Kahn reaction, and only two had a
temporary one plus Wassermann reaction. None of the cases of
this series presented any clinical resemblance to pre-eruptive
syphilis.
What is the mechanism of the Wassermann reaction in infectious mononucleosis?
WASSERMANN REACTION IN INFECTIOUS MONONUCLEOSIS
309
In a recent publication Hatz 4 expresses the opinion that the
presence of Forrsman antibodies in the blood of patients with
infectious mononucleosis could be the cause of a positive Wassermann reaction, provided that the antigen used for the Wassermann reaction was prepared from the tissue of an animal in the
Forrsman group, such as guinea pig or horse. This assumption
cannot be accepted for this case since our Wassermann antigens
were beef heart extracts. In addition, it seems doubtful as to
whether the sheep cells antibodies in infectious mononucleosis
are identical with the Forrsman antibodies. Results 5 of inhibitory and adsorption experiments agree in showing that sheep
cell antibodies in infectious mononucleosis are not Forrsman
antibodies for they reacted differently in their immunologic
behavior.
What, then, may be the cause of the positive Wassermann
reaction in infectious mononucleosis? No satisfactory explanation can be given at present for this phenomenon. In analogy
with similar serological conditions the author believes that infectious mononucleosis creates a disturbance in the protein
fractions of the serum, which renders the serum "labil" and may
be responsible for a non-specific protein reaction such as is seen
in pneumonia, malaria, and pregnancy. While this explanation
of necessity is of a hypothetical nature, it may be well to include
infectious mononucleosis in the number of those diseases which
at times may be associated with a positive Wassermann reaction.
SUMMARY AND CONCLUSION
1. A patient suffering from infectious mononucleosis presented
a clinical picture similar to that of pre-eruptive and later secondary syphilis.
2. A four plus Wassermann and Kahn reaction and a maculopapular rash increased the differential diagnostic difficulties.
3. The underlying serological mechanism is discussed and the
opinion is expressed that a proper evaluation of clinical and
serological findings may be helpful in recognizing similar clinical
manifestations.
310
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(2)
(3)
(4)
WILLIAM SAPHIR
REFERENCES
PAUL, I. R., AND BUNNELL, W. W.: Presence of heterophile antibodies in
infectious mononucleosis. Am. J. Med. Sc, 183, 90, 1932.
DAVIDSOHN, I.: Serologic diagnosis of infectious mononucleosis. J. A.
M. A., 108, 289, 1937.
ISAACS, H. J.: Infectious mononucleosis. 111. Med. J., 71, 161, 1937.
MCKINLAY, C. A.: Infectious mononucleosis. J. A. M. A., 105, 761, 1935.
TIDY, H. L.: Glandular fever and infectious mononucleosis. Lancet, 2,
180 and 236, 1934.
HATZ, B.: The Wassennann test in infectious mononucleosis. Am. J.
Clin. Path., 8, 39, 1938.
(5) STUART, C. A., GBIFFIN, A. M., FULTON, M., AND ANDERSON, E. G.
E.:
Nature of antibodies for sheep-cells in infectious mononucleosis.
Proc. Soc. Exp. Bio., 34, 209, 1936.