Treponemas
Syphilis derives its name from a poem by a physician, Girolamo
Fracastoro (1478—1553), published in Venice in 1530. The poem tells of
the shepherd, Syphilus, who was struck down by the disease as a punishment for
insulting Apollo.
On
his return from Haiti in 1493, Christopher Columbus (1451—1506) brought
back syphilis, parrots and rare plants. The King and Queen of Spain received him
with highest honours.
For
a detailed description of venereal syphilis, reference should be made to a
textbook on sexually transmitted disease
(STD).
Acquired
syphilis
Acquired syphilis is an STD infection caused by Treponema pallidum, a
delicate spiral organism (spirochaete), 6—15 m in length. A dramatic
decline in incidence after the introduction of penicillin has been followed by a
gradual but significant increase throughout the world.
Transmission
is by direct contact with a surface lesion containing treponemes, which
penetrate the skin or mucosa at
Clinical
features
The disease is divided into four stages: primary, secondary, latent and
late.
Primary
syphilis. A primary sore or chancre (Fig 8.6 and Fig
8.7) develops at the site of
entry of the treponemes in about
3—4 weeks. It may resolve at any stage of its development and thus be
quite atypical. It may simulate other penile or vulval lesions, traumatic
lesions such as splits or tears chancroid, herpes genitalis, burns, furuncles and carcinoma, as well as
balanoposthitis and lymphogranuloma venereum (Chapter 67).
Starting
as an indurated papule, it becomes eroded and when fully developed will present
the following signs of a classic Hunterian chancre: a shallow, indurated,
painless, nonbleeding ulcer, usually single, oval or round, with a raised
hyperaemic margin, often extending into a dusky red oedema. A painless,
discrete and ‘shorty’ enlargement of the associated lymph nodes occurs
which has a rubbery consistency. The prepuce of the penis must always be
fully retracted as otherwise tiny sores in the coronal sulcus may be missed. As
there are no constitutional symptoms, a female patient will be unaware of the
presence of a cervical chancre, a lesion which accounts for about 45 per cent of
all sores in that sex. Extragenital chancres of the lip1, tongue,
nipple, etc., are now rare, but rectal and perianal primaries are common in
homosexuals and are usually atypical, frequently resembling painful anal
fissures which occasionally get excised in error. Spasm of the anal sphincter is
usually less with true sores and a typical (lateral) inguinal lymphadenitis may
be present.
Diagnosis
is by finding T pallidum in the clear exudate from the lesion by
dark-field microscopy. The serum tests do not become positive for 10—90 days
(usually 3—5 weeks) after the appearance of the chancre, hence initial
negative results must never be interpreted as excluding primary syphilis. This
is because the tests identify a gradually developing antibody response. The
tests should be repeated for up to 3 months where doubt persists.
Secondary
syphilis. Signs usually appear in 6—12 weeks, extremes being 3 weeks to 6
months. The commonest sign is a dull red or coppery rash, which is generalised,
symmetrical, indolent and nonirritant. Often inconspicuous, sometimes absent (in
25 per cent of cases), the rash is characteristically pleomorphic, being
roseolar or macular at first, with papular, papulosquamous or other elements
appearing later. Papules on contiguous moist sites, e.g. vulva and perineum, may
enlarge to form condylomata lata, fleshy, wart-like growths teeming with
treponemes. Small, round, superficial erosions may occur in the mouth where they
may coalesce to form the so-called snail-track ulcers. The rash can resemble
that of any known rash-producing condition in the whole of medicine. A
generalised, painless lymphadenopathy often occurs, and less common symptoms
include sore throat, hoarseness, ‘moth-eaten’ alopecia, hepatitis, inns, and
bone and joint pains. Bone pains may be severe and prolonged for several weeks
without any other supporting signs, and the diagnosis is often missed. Acute
meningitis or cranial nerve or spinal root palsies due to an irregular
pachymeningitis occur. Constitu
Full
spontaneous recovery always occurs.
Latent
syphilis. This follows the untreated secondary stage and lasts from 2 years to a
lifetime. There are no signs, but the serum tests are positive.
Late
syphilis (syn. tertiary syphilis). Syphilis in all its stages is essentially a
vascular disease. In each stage, treponemes cause inflammatory reactions in the
perivascular lymphatics with plasma cell cuffing of terminal vessels. In the
tertiary stage only there is subsequent obliterative endarteritis, tissue necrosis
and fibrosis. Since almost any structure may be involved, the signs can be
extraordinarily variable, and will be referable to the site or system involved.
Only about 35 per cent of untreated syphilitics will develop tertiary syphilis.
About 5—15 years after infection, 10 per cent will develop
neurosyphilis, 10—12 per cent cardiovascular syphilis and after 6 months up to
many years later, 10—15 per cent will develop late benign syphilis involving
less vital structures. The three types are not mutually exclusive. The typical
lesion of late benign syphilis is the localised gumma (Fig.
8.8) or diffuse
gummatous infiltration. The gumma is a syphilitic hypersensitivity reaction
consisting of granulation tissue with central necrosis. Sloughing of a
subcutaneous gumma may produce the typical, painless, punched-out gummatous
ulcer with a ‘wash-leather’ base (Fig.
8.9 ). On healing, it
leaves a silvery ‘tissue-paper’ scar. Alternatively, the gummatous process may be nodular or infiltrative without
ulceration, and slow peripheral spread occurs with central healing. The
individual lesions are round and indurated, and grouped lesions are circinate
in outline with sharply defined, hyperpigmented margins.
Diagnosis.
Dark-field microscopy. This is performed on aspirates from skin or mucous
membrane lesions and is the quickest method of diagnosis in early acquired
syphilis.
Serological
tests for treponemal diseases are of
two types.
1. Nonspecific (syn. reagin,
nontreponemal, lipoidal antigen tests). Examples are the cardiolipin
Wasserman (WR), Kahn, Meinicke, and Venereal Disease Research Laboratory (VDRL)
slide test. The last is the best. These test the presence of any antibody reagin
in the serum of patients with treponemal infections, but biological false
positives (BFP) arise from reagin present in nontreponemal conditions, e.g.
malaria, vaccinia, glandular fever, and also after any kind of vaccination.
Stronger and persistent reactions may occur in leprosy, sarcoidosis, collagen
diseases and chronic liver disorders. A diagnosis of syphilis requires
confirmation from one or more of the specific tests.
2. Group-specific tests (treponemal
antigen tests). Examples are: Reiter’s protein complement fixation test (RPCF),
Treponema pallidum haemagglutination assay (TPHA), absorbed fluorescent
antibody test (FTA Abs) and Treponema pallidum immobilisation test (TPI).
The
first is obsolescent (in the UK) and the last rarely required. The routine
practice is to perform the VDRL and TPHA adding the FTA if either is positive or
the clinical findings justify it. In primary syphilis, the usual order of
conversion is ETA, VDRL with rising titre and TPHA, although this sequence is
not invariable. After treatment, the VDRL usually reverts to negative in up to 6
months, the FTA in 70 per cent, but the TPHA hardly ever, of which facts the
patients must be told — ‘a little scar in the blood’ is usually adequate.
Persistence of treponemal antibodies, if it is known that adequate treatment has
been given, is not a cause for concern but if there is any doubt, confirmed
reactions on repetition should be treated as for latent infection.
No local treatment except isotonic saline should be applied to a
suspected chancre until dark-field examinations have proved negative on 3 successive
days. No treponemicidal antibiotics should be prescribed until syphilis is
confirmed or excluded, but if there is secondary infection a course of
sulphonamides may help. Penicillin has supplanted all other forms of treatment.
A high cure rate is achieved in early syphilis with intramuscular procaine
penicillin G 1.2 g daily for 15 days. This dosage is prolonged to 21—30 days
for late syphilis. Clinical and serological observation should be continued for
2 years after treatment. In penicillin-allergic patients, tetracycline and
erythromycin are alternatives. The best treatment is doxycycline 100 mg twice
daily for the equivalent period.
Janisch—Herxheimer
reaction. About 6 hours after the first injection, 60 per cent of early
syphilitics will develop pyrexia, malaise and possible rigors lasting for a few
hours only. Patients must be warned about this. The reaction is
Prognosis
is excellent after standard treatment for early syphilis. In late syphilis,
particularly of the cardiovascular system, cure of the underlying disease may
not significantly improve the condition of the patient.
Congenital
syphilis
Transmission. Infection occurs when treponemes from an infected
expectant mother cross the placental barrier to the foetal circulation. The more
recent the mother’s infection, the more likely is this to occur and the more
serious the effects on the child. The results of foetal infection vary from
death in late foetal life or early infancy, or the birth and normal development
of an apparently healthy child who, nevertheless, has latent congenital
syphilis.
Early
congenital syphilis. Signs in the newborn, which may be delayed for a few weeks,
include a generalised rash, mucous erosions as in secondary syphilis and the
‘souffles’, a syphilitic rhinitis with nasal discharge which interferes with
suckling causing loss of weight, epiphysitis, periostitis, osteochondritis,
hepatosplenomegaly and basal meningitis. Signs may be so slight as to escape
notice or so severe as to cause death in early infancy, usually due to
syphilitic ‘pneumonia alba’.
Late
congenital syphilis. The extraordinary variety of clinical manifestations which
can occur in acquired tertiary syphilis can also occur in childhood or puberty
in late congenital syphilis, e.g. congenital neurosyphilis, cutaneous, visceral
or skeletal gummata, but congenital cardiovascular syphilis is practically
unknown. In addition, some manifestations, the stigmata, occur in congenital,
but never in acquired, syphilis.
The
stigmata of late congenital syphilis (Hutchinson’s classic triad) consist of
the following:
1. interstitial keratitis: the most
frequent of the stigmata is a syphilitic hypersensitivity reaction with onset
between 5 and 15 years. The cornea becomes inflamed causing pain,
lacrimation and photophobia. It tends to be bilateral and recurrent. Prolonged
severe recurrent attacks result in a hazy ‘ground glass’ appearance of the
cornea, with yellowish-red corneal patches in severe cases (salmon patches, not
to be confused with the salmon-patch birthmark). It is uninfluenced by
antisyphilitic treatment but can be controlled by local cortisone treatment;
2. eighth nerve deafness: a
progressive, bilateral, perceptive deafness, onset about puberty, but
occasionally delayed until later and uninfluenced by treatment;
3. Hutchinson’s teeth: a peg or
band-shaped deformity of the upper central incisors, second dentition. Moon’s
molars (mulberry molars):
the 6-year molars erupt with dwarfed cusps. Other classic signs include nasal deformities, e.g. saddle nose (Fig. 8.10), collapsed nasal septum (Fig. 8.11), perforation of the palate (Fig. 8.12), sabre tibia, Glutton’s joints (painless effusions, commonly in the knee joint) and parietal bossing
prevention
and treatment. A dosage of 1.2 million units of procaine penicillin G given to
the mother for 15 days as early as possible in pregnancy not only will
protect her from the ravages of late syphilis, but will prevent infection of the
foetus, or may even cure it in utero, if already infected. An infected
neonate, whose mother received no treatment during pregnancy, should be treated
as for late acquired syphilis with the dosage adjusted to weight.
Neonatal
serology. An expectant mother who has received no treatment during pregnancy, or
who is an untreated latent syphilitic, may produce a child free from syphilis
but seropositive owing to passive transfer of maternal antibodies. This
serological problem can be solved by performing tests on the immunoglobulin G (IgG)
and 1gM fractions of the infant’s serum but not on the cord blood. In the case
of passive transfer, the IgG tests will be positive and the 1gM tests negative.
Positive 1gM tests indicate active disease in the child since the 1gM fraction
of the maternal serum proteins does not cross the barrier of the normal
placenta. Exceptions occur if the placenta has been damaged from other causes.
In all cases, careful clinical and serological follow-up of mother and child is
essential. The virtual disappearance of congenital syphilis from the UK and
similar countries is one of the great triumphs of modern medicine.
Syphilis
contacts. At all stages of the disease, the known contacts must be followed up.
This applies to late and congenital cases when other members of the patient’s
family are often found to have untreated latent syphilis.
Yaws2
(framboesia3)
Yaws is an endemic disease of rural areas in tropical countries of high
humidity. The causative organism, Treponema pertenue, appears
indistinguishable from T pallidum and produces identical serological
reactions. Direct contact with an early lesion is the usual mode of
transmission. It is not sexually transmitted. The primary lesion is most
frequently seen on the legs of children. About a month after infection, a papule
appears at the site of entry of the treponeme; this ulcerates giving the lesion
a pink, raised, raspberry-like (framboesia2) appearance. Secondary
lesions, usually papillomatous, appear some weeks later. After 5 or more
years of latency, a minority of patients develops late gummatous-like lesions of
soft tissue or bone similar to those of tertiary syphilis. The cardiovascular
and nervous systems are not involved and congenital yaws does not occur. Treat
as for syphilis.