Latent Syphilis

By definition latent syphilis is that stage of syphilis where there are no clinical signs or symptoms of the disease; the spinal fluid has been examined and is negative; and serologic tests for syphilis are reactive. All syphilis is latent at some time during its course, and some cases may be virtually latent for the duration of the disease or the life of the patient. A clinical diagnosis of latency does not preclude the possibility of infectiousness, or of developing gummatous lesions, cardiovascular abnormalities, or of neurosyphilis, as yet not apparent. When any of the aforementioned conditions become apparent the diagnosis is no longer latent syphilis. ×Ö´®2

Syphilis should be diagnosed as latent only after careful history and physical examination have disclosed no abnormalities of syphilitic origin, and the spinal fluid has been shown to be normal.

×Ö´®5

The diagnosis of latent syphilis is made on the basis of repeated serologic tests in the absence of concurrent disease which may produce a false positive reaction. A treponemal test is often indicated to establish the syphilitic nature of the serologic test reactivity. ×Ö´®7

A history of exposure, of early lesions, of previous reactive serologic tests, or of antecedent treatment is helpful if elicited, and may help in classification as early or late.

After an infection with syphilis has persisted for more than 4 years, it is rarely communicable, except in the case of the pregnant woman, who if untreated, may transmit syphilis to the fetus, regardless of the duration of her disease. Also, if after 4 years of infection the spinal fluid is normal, in all probability it will remain so.

×Ö´®8

Late Syphilis ×Ö´®3

Syphilis is essentially a vascular disease from beginning to end, with the exception of the gumma, which is probably a hyperimmune phenomenon. Aside from gummas the lesions of late syphilis are produced by obliterative endarteritis of terminal arterioles and small arteries, and by the resulting inflammatory and necrotic changes. ×Ö´®5

As indicated in Table 1, there are practical differentiations in the lesions of early and late syphilis:

	TABLE 1 ×Ö´®8
Characteristic	Early Syphilis	Late Syphilis
Infectivity.	Yes.	No, except in pregnant female.
Darkfield.	Positive.	Negative.
Reinfection.	Can occur, after adequate treatment.	Rare, even after adequate treatment.
Destructive lesions.	No.	Yes.
Serologic tests.	Reactive, often with high titer, reverting to negative, or with marked fall to low titer, after treatment.	Usually reactive, often with low titer, with little or no change after treatment. High titers are frequently associated with gummas and paresis.

×Ö´®1

Untreated late syphilis may present a tremendous range of signs and symptoms, varying from none apparent to those indicating severe damage to one or more body systems. The most usual types of late syphilis, and the chances of their occurrence are: ×Ö´®2

Type of Late Syphilis	Frequency (percent)
Latent	60-70
Neurosyphilis (Symptomatic)	8
Late Benign Syphilis	17
Cardiovascular Syphilis	10

×Ö´®4

These divisions of late syphilis are not mutually exclusive. A patient may have more than one type of late involvement; for example:

• Of patients with late benign syphilis, about 13 percent will have cardiovascular involvement, and another 10 percent neurosyphilis.
• Of patients with cardiovascular syphilis, about 12 percent have associated neurosyphilis.
• Of patients with neurosyphilis, about 15 percent have associated cardiovascular syphilis.

Neurosyphilis

×Ö´®9

All neurosyphilis is asymptomatic at some time during its course, and it is rare for neurosyphilis to occur in "pure" forms. In all types of neurosyphilis the essential changes are the same: obliterative endarteritis, usually of terminal vessels, with associated parenchymatous degeneration which may or may not be sufficient to produce symptoms at the time of examination. ×Ö´®1

Neurosyphilis is somewhat arbitrarily divided into the following types of groups, which depend on the type and degree of central nervous system pathology present: Asymptomatic; meningovascular; and parenchymatous, consisting of paresis and tabes dorsalis.

×Ö´®9

Asymptomatic Neurosyphilis—The patient is usually seen because of a reactive serologic test for syphilis. There are no signs or symptoms indicative of central nervous system involvement. Examination of the cerebrospinal fluid is abnormal, with an increase in cells, total protein, and with a reactive VDRL, or Kolmer complement fixation test.

×Ö´®9

Meningovascular Neurosyphilis—There are definite signs and symptoms of central nervous system damage, which result from cerebral vascular occlusion, infarction, and encephalomalacia with focal neurologic signs varying according to the size and location of the lesion. The cerebrospinal fluid is always abnormal, with an increase in cells, in protein, and showing a reactive VDRL or complement fixation reaction.

Parenchymatous Neurosyphilis—Parenchymatous neurosyphilis presents as paresis or tabes dorsalis:

×Ö´®5

PARESIS: The signs and symptoms of paresis may be myriad, but are always indicative of widespread parenchymatous damage. Personality changes range from minor to frankly psychotic. Frequently there are focal neurologic signs. The cerebrospinal fluid is invariably abnormal. The VDRL or complement fixation test is reactive and cells and protein are increased. Serologic tests (blood) are reactive.

×Ö´®9

TABES DORSALIS: The prime signs and symptoms of tabes dorsalis are those of posterior column degeneration, with ataxia, areflexia, paraesthesias, bladder disturbances, impotency, and often, lancinating pain (lightning pains). The spinal fluid findings are abnormal in 90 percent of cases; the blood serology is reactive in 75 percent. Gastric or abdominal "crises" frequently begin with vomiting and severe abdominal pain. Persistent vomiting may cause serious electrolyte imbalance. Trophic joint changes (Char-cot's joints) result from the loss or impairment of the sensation of pain. The knee joint is most commonly involved and severe degeneration is common. Similar trophic joint changes may be found in conditions other than syphilis, i.e. syringomyelia, spinal cord injury, or diabetes. The loss of deep pain sensation may be associated with perforating ulcers on the soles or toes (mal perforans). ×Ö´®6

Syphilitic optic atrophy is a serious complication of neurosyphilis, and should be looked for in every patient. It is most frequently associated with tabes dorsalis and an examination of peripheral visual fields is imperative in every suspected neurosyphilitic. Pupillary changes may be seen in both forms of late neurosyphilis. The classic Argyll Robertson pupil is small, irregular, and fails to react to light, but reacts normally to convergence. Other pupillary variations from this typical pattern are common. ×Ö´®2

The signs and symptoms of paresis and tabes dorsalis frequently coexist (so-called taboparesis) in the same patient.

×Ö´®6

Examination of the Spinal Fluid in Neurosyphilis—The lumbar puncture can be performed with the subject in the sitting position or placed on his side. In the sitting position, the patient straddles a straight chair, facing the chair back, and arching the spine posteriorly. On his side, the patient arches his back by drawing up the knees and bending the head so that they almost touch. The lumbosacral area should be cleansed with iodine followed by alcohol. A sterile spinal needle is then inserted into the third, fourth, or fifth lumbar interspace and sufficient fluid is collected for study (6-8 ml.). The procedure may be safely performed in the clinic or in the physician's office.

There are three tests of spinal fluid essential for the diagnosis of neurosyphilis, and for its intelligent followup: ×Ö´®7

1. Cell count: Over 4 lymphocytes is abnormal.
2. Total protein: Protein is always elevated in active neurosyphilis. "Normal" values vary from laboratory to laboratory, depending on the test used. Know your laboratory, and its readings of normal limits. Individuals vary considerably in their normal total protein values, but a total protein of more than 40 mg% is usually abnormal.
3. Kolmer or VDRL spinal fluid tests: A reactive spinal fluid Kolmer or VDRL is practically always an indication of central nervous system syphilis, but not necessarily of its activity. False positive reactions in the spinal fluid are rare.

The presence of reagin in the spinal fluid is die only finding which is pathognomonic of neurosyphilis since any condition which causes meningeal irritation may result in an increase in the cell count and protein concentration of the spinal fluid. Consequently, reactive tests for syphilitic reagin in the spinal fluid are reliable evidence of past or present neurosyphilis. With the exception of late tabes dorsalis, the clinical syndrome is rarely so clear cut as to permit the diagnosis of neurosyphilis in the face of negative reagin serologic findings. Conversely, even in the absence of clinical signs or symptoms, a positive reagin test is indicative of asymptomatic neurosyphilis. Following successful treatment and arrest of late neurosyphilis, it may take many years for the spinal fluid reagin test to become nonreactive.

×Ö´®2

The degree of activity of neurosyphilis is indicated by increased numbers of lymphocytes and increased protein in the spinal fluid. A cell count of more than 4 per cu. mm. is usually abnormal and indicative of an active central nervous system infection. Every effort should be made to perform cell counts as soon as possible and to avoid contamination of the fluid with red cells since leukocytic cells disintegrate quite rapidly at room temperature and erythrocytes inevitably interfere with accurate counting. ×Ö´®8

In the diagnosis of central nervous system syphilis, beware of the bloody tap. Small quantities of reactive blood serum in spinal fluid can produce a positive Kolmer or VDRL reaction, and red cells may be mistakenly interpreted as white cells. ×Ö´®7

Increased total protein in association with pleocytosis and reactive spinal fluid reagin is also indicative of active neurosyphilis. Following successful treatment, high total protein values decline slowly, and they may not become normal for a year, or even several years. In general, the cell count may be expected to return first to normal followed by the protein and finally the serologic test. Examples are given in Table 2. ×Ö´®4

Colloidal tests of spinal fluid such as the colloidal gold test, once widely utilized, are of no diagnostic significance and are not a reliable guide to the activity of neurosyphilis. These tests have no value in the management of neurosyphilis.

TABLE 2. ?Typical Serologic and Cerebrospinal Fluid Responses Following Therapy for Neurosyphilis
		Cerebrospinal Fluid ×Ö´®2
Days after Therapy	(Serum) Quantitative VDRL	Lymphocytes (per mm3)	Protein (mg %)	VDRL Slide
I. Asymptomatic Neurosyphilis ×Ö´®3
0	8 dils	143	92	4 dils
93	8 dils	27	83	4 dils
178	4 dils	9	89	4 dils
271	8 dils	?/TD>	?/TD>	?/TD>
347	4 dils	3	54	2 dils
526	4 dils	?/TD>	?/TD>	?/TD>
727	2 dils	4	47	WR 0 dils
929	N	?/TD>	?/TD>	?/TD>
1344	N	0	44	N
II. Symptomatic Neurosyphilis ×Ö´®4
4	16 dils	35	64	4 dils
188	8 dils	8	52	4 dils
374	8 dils	4	50	4 dils
505	4 dils	?/TD>	?/TD>	?/TD>
735	8 dils	5	43	4 dils
984	4 dils	?/TD>	?/TD>	?/TD>
1288	4 dils	4	45	2 dils

×Ö´®3

Cardiovascular Syphilis

×Ö´®1

Cardiovascular syphilis is usually caused by medial necrosis of the aorta, with aortic dilatation which may extend into the valve commissures.

×Ö´®1

The essential signs of cardiovascular syphilis are those of aortic insufficiency or saccular aneurysm of the thoracic aorta. When fully developed, these conditions are not difficult to detect. Careful. clinical evaluation of hypertension, arteriosclerosis, and previous rheumatic heart disease is essential. ×Ö´®4

Saccular aneurysm of the thoracic aorta is prima facie evidence of cardiovascular syphilis; aortic insufficiency with no other valvular lesions in a person of middle age, with a reactive serologic test, should be considered cardiovascular syphilis until proven otherwise.

Serologic tests for syphilis are usually reactive in cardiovascular syphilis.

Late Benign Syphilis

The term "benign" is used because the lesions of late benign syphilis seldom result in total physical incapacity or death, although when such gummas occur in the brain or other vital organs the word "benign" is misleading. The essential lesion of late benign syphilis is the gumma. ×Ö´®4

Gummas are probably the result of hypersensitivity reactions of treponemal infection. The most common sites are skin, bone and liver, but nearly any organ may be involved. ×Ö´®7

Skin lesions may be solitary or multiple, tend to form circles or segments of circles, are destructive and chronic, and tend to heal centrally and extend peripherally.

Bone lesions are usually marked by periostitis with associated new bone formation, or by gummatous osteitis, with bone destruction. The cardinal signs are those of pain, swelling, and bony tumor. The most common sites are the cranial bones, the tibia, and the clavicle.

In late benign syphilis, the serologic tests are almost always reactive and usually of high titer.

×Ö´®5