THE SEROLOGICAL D I A G N O S I S OF SYPHILIS IN D E N T A L P A T I E N T S

MALCOLM HARRIS, M.B., F.D.S.R.C.S. Eastman Dental Hospital, London, I~.C.I.

THE incidence of venereal disease has risen sharply over the past decade. In 1964, according to a Home Office pamphlet, early infectious cases of syphilis (1738) attending special clinics were more than twice the number (704) seen in 1958.

As all stages of syphilis may present in the oro-facial region, the serological tests carried out on dental patients from 1949 to 1965 were reviewed in order to assess this problem.

During these 16 years, sera of 344 patients were subjected to Wassermann and allied investigations one or more times. The indications were varied and most commonly included white mucosal lesions of the tongue, suspicious ulcers, frank carcinoma, lymphadenopathy or an admitted history of luetic infection.

TESTS

Standard Tests. All the so called standard tests for syphilis are based on the fact that of the several antibodies produced by the treponema pallidum, one called 'reagin' combines with colloidal suspensions of lipids giving a visible flocculation. This combination also takes up complement. The result is established either by direct observation of the flocculation or the use of an indicator system which reveals complement fixation.

The flocculation tests most commonly used in this country are the Kahn test, the V.D.R.L. (Venereal Disease Reference Laboratory) slide test, and Price's precipitation reaction.

Two of the difficulties encountered with these are the assessment of partial flocculation, and also a paradoxical failure to flocculate at all where there is a high concentration of reagin. The latter, which is termed a prozone reaction, is over- come by serial dilutions of the serum so that the ratio of antibody and antigen concentrations optimum for precipitation is achieved (Annotation).

The classical complement fixation test, the Wassermann reaction, now employs a mixture of ox cardiolipin, lecithin and cholesterol as the antigen instead of crude extracts of beef heart.

Should the serum be contaminated with bacteria or the products of hae- molysis, the activity of the complement is destroyed and a fresh sample must be obtained. Rarely a patient's serum will prove to be persistently anti-complemen- tary despite repeated tests. In these instances only non-complement fixation tests can be employed.

False positives can arise through error in laboratory technique. There are also occasions when a non-infected individual may be shown to have an abnormally high concentration ofreagin. This, the so-called 'biological false positive', is as yet unexplained. Two groups of intercurrent disease and infection may also give misleading reactions.

The acute group consists of virus pneumonia, glandular fever, vaccinia, active 235

236 BRITISH JOURNAL OF ORAL SURGERY pulmonary tuberculosis, acute malaria and even rarer conditions such as typhus, Weil's disease and filariasis. The titres tend to be low and disappear within two to three months.

High titres may be found in the chronic collagen diseases, disseminated lupus erythematosus and rheumatoid arthritis, and also in leprosy, and often persists for years. Both groups give negative results with the more specific tests.

Unfortunately, other treponemal diseases such as yaws, pinta and bejal also give rise to antibodies which not only react to the standard tests for syphilis, but also to the following more refined tests.

Specific Tests T.P.I. The virulent Nichols strain of Treponema pallidum cultured in rabbits

is immobilised by infected sera, in the presence of complement. This Treponema pallidum immobilisation test (T.P.I.) is positive if 5o per cent. or more of the organisms are affected.

Whereas the standard tests become positive in the interval between the appearance of the chancre and the signs of secondary syphilis, they may become spontaneously negative in old cases of latent syphilis. However, the T.P.I. in such cases is invariably positive. Unfortunately, it also remains positive even with successful treatment if this has been carried out after the secondary stage. Both tests become negative if early syphilis has been adequately treated. Occasionally the T.P.I. is negative in late cases of congenital syphilis and tabes dorsalis.

R.P.C.F.T. By using a protein extract from the avirulent Reiter strain of treponema as the antigen in the conventional complement fixation test, another infective antibody may be detected. This, the Reiter protein complement fixation test, has the advantages of being simple and inexpensive. It becomes positive before the Wassermann reaction and will also confirm active late syphilis where the Wassermann reaction results are equivocal.

F.T.A. Recently fluorescent antibody techniques have been adapted to show antibodies from patients' sera adhering to a suspension of virulent T. pallidum. This is seen under ultra-violet light using a dark-field microscope, and like the R.P.C.F.T. become positive early.

The fluorescent treponemal antibody test will possibly prove as useful a specific test as the T.P.I.

R E S U L T S

TABLE I

r949-r965

Number of cases investigated . . Number of cases with positive serological tests

Diagnoses as: Syphilis. Yaws Biological False Positive .

Total .

I3 6 5

344 24

T H E S E R O L O G I C A L D I A G N O S I S OF S Y P H I L I S I N D E N T A L P A T I E N T S

TABLE II

SYPHILIS

237

Case

G.C.

D.H,

T.C.

R.C.

Age

34

36

58

69

59

54

63

66

22

45

26

6o

35

S." ~r.R.

+-

+

+

+

+

C.W.R.

+

+

+

+(8)

+

R.P.C.F.T.

+ (32)

+

+ (8)

+

+ (2)

+(8)

±

+

m

+ (4)

+

+

+

+

.T. V.D.R.L.

(8)

(2561

(z56)

+

(8)

+

+ (8)

T.P.I.

+

+

F.T.A.

+

Clinical Details

Chancre on tongue for 5 weeks.

Mucous patches--lip and gingiva.

Oral keratosis and his- tory of penile sore.

Leukoplalda of tongue.

Osteomyelitis of maxilla.

Gumma of hard palate.

Chronic buccal ulcer. (Inadequately treated?)

Depressed lingual scar. (Low but positive titre.

Aortic incompetence. Late active.

Known recently treatec syphilis.

Treated I2 years ago.

Perforation ofp~late and L. nerve deafness.

Aortic incompetence. (Treated.)

Osteomyelids. (Probably treated.)

Of the above I3 cases, 5 were considered to be adequately treated (P. P., E. F., C. M., G. L. F. and A. W.), although there were no investigations o f the cerebro- spinal fluid for latent neurosyphilis. The i r titres were low, with some tests giving negative reactions.

The remaining 8 showed titres of varying degrees of activity. I t seems feasible that inadequate treatment and the generous use of penicillin for other conditions masks the disease in those cases where the titres are low but consistently positive.

I t is of interest that only one primary and secondary lesion was found during this I6 year period, both in the same patient.

R

S.W.R.

B R I T I S H J O U R N A L OF O R A L S U R G E R Y

TABLE I I I

YAWS (6 cases)

Case

W . M .

J . L .

M L ,

L B .

C,B.

A.B.

Age

38

39

28

62

3I

25

238

C.W.R.R.P.~.E.T~ +

± I ÷

± ±

+ - +

- ±

P.P.R.

m

K . T - - ] V.D.R.L. I T.P.I.

+

F.T.A. Clinical Details

Discharging nodule on face adjacent to left nostril.

Presented with naso- pharyngeal tumor.

Serology discovered during investigation.

Submandibular lym- phadenopathy due to apical infection. Old Yaws.

Areas of patchy sclero- sis / . . . region.

Chronic osteomyelitis mandible.

History of yaws in childhood, but treated with penicillin.

Cervical and inguinal lymphadenopathy

] with lymphocytosis. Virus infection with

treated treponemal. infection.

All these patients were West Indians from rural areas, and gave a history of yaws. The low titres also tend to support this diagnosis (vide infra).

TABLE IV

BIOLOGICAL FALSE POSITIVES (5 Cases)

Case

I. G. S. 2. E. P.

3. E. B.

4. M. E.

5. S. L.

Ag S.W.R.

41 65

45

37 --

54

R.P.C.F.T.

+ ÷

P.P.R. K.T. V.D.R.L T.P.I . l F.T.A. Clinical Details

Oral keratosis. Sclerosing osteitis with

retained apices. Osteomyelitis and history

of malaria. Hyp. erplastic bleeding gin-

glva. Punched-out ulcer on pal-

ate following injection. Healed spontaneously.

Case I and 4 were cleared on the T.P.I. Cases 3 and 5 appear to have been doubtful positives even when one specimen was tested. However, there is no real evidence except the opinion of the laboratory that Case 2 was not syphilis

with a low titre. In fact, a T.P.I . should have been carried out.

S E R O L O G I C A L D I A G N O S I S OF S Y P H I L I S IN D E N T A L P A T I E N T S 239

DISCUSSION By using several tests quantitatively it is now possible to assess whether a

patient has active treponemal disease. In such cases there is a 9 ° per cent. cor- relation between the T.P.I. and R.P.C.F.T. (King and Nicol, 1964).

It is obvious from the above results that one of the greatest problems is differentiating syphilis from yaws. Bejal and pinta are less likely to be discovered since they occur in the underdeveloped parts of the Middle East, Central and South America respectively. Yaws is a non-venereal chronic infectious disease occurring in tropical rural areas. Surface contact especially in childhood and transmission by insects are the usual sources of infection. As with syphilis, the florid lesions are easily recognised, but one may have to rely on the history, the presence of atrophic cutaneous scars on the legs and radiographic evidence of old periostitis in making a diagnosis. Yaws does not affect the central nervous system, or the heart and aorta. Thus C.S.F. and chest examinations with positive signs confirm late syphilis, but the converse is of little value.

To illustrate the difficulties in coming to a final diagnosis one should consult Dunlop's (196o) investigations at the Whitechapel Clinic 1957-1958. He showed the incidence of untreated treponemal disease in 856 coloured immigrants was 6 per cent. in males and 33.1 per cent. in females. During the same period 2908 white patients proved to have 1. 3 per cent. disease in males and 2. 3 per cent. in females.

When one separates the cases of early syphilis in the immigrant group of treponemal disease the relative figures are very different. The incidence amongst coloured immigrants being less than twice as common than in white patients, and only 2 of the I I immigrants acquired the disease abroad. This suggested a good proportion of the total cases were yaws. On taking the group of 128 immigrants where treponemal disease was confirmed by serological tests, it was not possible in 45 cases to establish whether the condition was syphilis, yaws, or a combination of both (47 were actually diagnosed as yaws, 26 as syhpilis, and IO yaws with syphilis).

SUMMARY Three hundred and forty-four dental patients were subjected to serological

tests for syphilis over a period of 16 years. Only 24 gave positive results, of which half (12) were attributed to syphilis and the rest were to yaws or biological false positives.

Both the arbitrary manner of selection and the small numbers exclude the possibility of discerning any trend. However, the difficulty of differentiating syphilis from yaws is emphasised.

ACKNOWLEDGEMENTS I am grateful to Dr. E. M. C. Dunlop for his invaluable advice and the illustrations of yaws,

to Mr. Lawrence Cohen for the slides of his case with the early lesions, and to Professor H. C. Killey for his encouragement and helpful comments. I must also acknowledge Mr. G. G. Blake and Professor I. R. H. Kramer for kindly allowing me access to ~heir records.

REFERENCES British Medicalffournal (1965). Annotation. I, 76. DUNLOP, E. M. C. (196o). Brit. J. vener. Dis. 36, 40. H.M.S.O. Pamphlet (1964). On the State of the Public Health, p. 222. KING, A. & NICOL, C. (I964). Venereal Diseases, p. 99. London: Cassell.

R ~