Otolaryngol Clin N Am

36 (2003) 595–605

Syphilis and otolaryngology

Steven D. Pletcher, MD, Steven W. Cheung, MD*
The Department of Otolaryngology–Head and Neck Surgery, University of California,
400 Parnassus Avenue, San Francisco, CA 94143, USA

Syphilis is a sexually transmitted disease caused by the spirochete

Treponema pallidum. Although there is some debate about its origin, the
symptom complex of syphilis and its sexual transmission were clearly
described in the fifteenth century. The disease draws its name from the
afflicted shepherd, Syphilis, whose symptoms were described in the early
1500s by the poet-pathologist Frascatorius.

Epidemiology
In the early twentieth century syphilis was a leading cause of neurologic
and cardiovascular disease in the United States and represented a major
public health risk. Before World War II an estimated 5% to 10% of first-
time admissions to United States mental health institutions suffered from
tertiary syphilis [1,2]. With organized public health efforts, syphilis rates in
the United States began to decline even before the advent of penicillin in the
1940s; however, the widespread availability of effective antibiotic treatment
led to an accelerated decline in the prevalence of the disease.
After the near elimination of syphilis in the United States in 1957, there
have been cyclic national epidemics every 7 to 12 years; the most recent was
in 1990. Since this time, reports of primary and secondary syphilis have
decreased 88%, to a rate of 2.5 cases per 100,000 people in the United States
in 1999. Most cases occur within the southeastern region. The number of
cases reported to the Centers for Disease Control (CDC) is believed to
represent 80% of all recently acquired cases [3]. The incidence of congenital
syphilis has followed the recent course of primary and secondary syphilis.
After peaking in 1991, the rate of congenital syphilis decreased 87%, to 14.3
cases per 100,000 live births in the United States in 1999 [4].

* Corresponding author.
E-mail address: scheung@ohns.ucsf.edu (S.W. Cheung).

0030-6665/03/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0030-6665(03)00025-2
596 S.D. Pletcher, S.W. Cheung / Otolaryngol Clin N Am 36 (2003) 595–605

Pathogenesis
Treponema pallidum is frequently transmitted when infectious lesions
come into contact with abraded skin or mucous membrane. Most commonly
this contact occurs during sexual contact, although materno-fetal trans-
mission in congenital syphilis represents a clear exception. Transmission by
blood transfusion or needle sharing is rare. Risk of infection after sexual
contact is higher when the infected partner is in the early stages of syphilis;
contact with partners with latent disease presents a low risk of transmission.
Risk of disease transmission after sexual contact with a partner with primary
or secondary syphilis is approximately 50% [5].
The clinical sequelae of T. pallidum infection are divided into stages.
Primary syphilis is defined by the presence of a chancre at the site of
treponemal inoculation. Secondary syphilis represents hematogenous spiro-
chete dissemination and is commonly followed by a latent or asymptomatic
phase. Following this latent phase patients may progress to develop
symptoms of tertiary syphilis.

Primary syphilis
Primary syphilis is defined by the presence of a lesion referred to as
a chancre, at the site of inoculation. These lesions tend to be indurated,
ulcerated, and painless. Chancres are seen between 10 and 90 days after
inoculation and most commonly occur on the external genitalia but may be
noted in the anal or oral mucosa. The chancre is often accompanied by firm
regional lymphadenopathy that is nontender. Primary lesions heal sponta-
neously within a few weeks. Pathologic examination of chancres reveals
central necrotic debris with chronic inflammation at the distal zones. Dark
field examination demonstrates plentiful spirochetes and is the criterion
standard for diagnosis in primary syphilis. A reactive rapid plasma reagin
(RPR) or cardiolipin test is seen in 80% of patients with primary syphilis and
can be followed as an indicator of active disease. The fluorescent treponemal
antibody absorption (FTA-ABS) test evaluates for the presence of
treponemal antibodies. The test is positive in 90% of patients who seek
therapy for primary syphilis and remains positive for life [5].

Secondary syphilis
Secondary syphilis is characterized by widespread clinical manifestations
resulting from hematogenous spirochete dissemination. Epithelial surfaces
are frequently involved, resulting in a wide variety of cutaneous and mucus
membrane manifestations. A symmetric, papular rash involving the trunk
and the extremities is the most common cutaneous manifestation. In-
volvement of the palms of the hand and soles of the feet helps differentiate
the rash of syphilis from pityriasis rosea or psoriasis. Other cutaneous
manifestations include annular lesions, alterations of pigmentation, or
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‘‘moth-eaten’’ alopecia. Mucous patches, painless ulcers resembling

aphthous ulcers, may occur alone or in conjunction with the cutaneous
manifestations of secondary syphilis. These lesions may involve any mucosal
surface of the upper aerodigestive tract.
The condyloma lata is another lesion found in secondary syphilis. These
are large, raised, white or gray lesions found in warm, moist areas. These
lesions are found near the site of the original chancre (perineum or anus) and
are thought to result from direct rather than hematogenous treponemal
spread [5]. Constitutional symptoms such as fever, malaise, and generalized
lymphadenopathy often accompany the epithelial manifestations of second-
ary syphilis.
The arrival of secondary syphilis often coincides with the regression of
the primary lesion; symptoms last from 3 weeks to 3 months. Clinical
examination focused on potential sites of chancre formation in patients with
symptoms of secondary syphilis may reveal concurrent primary and
secondary symptoms. When untreated, approximately one fourth of patients
will develop a relapse of secondary symptoms. Ninety percent of such
relapses occur in the first year of infection and represent a rare contagious
period during the latent phase of syphilis [6]. The year following resolution of
secondary syphilis is often referred to as the early latent phase of syphilis to
distinguish the higher potential for disease transmission during this period
relative to the late latent phase of syphilis.
Plasma cells and lymphocytic infiltration are seen on pathologic exam-
ination of the epithelial lesions of secondary syphilis. Giant cells and endo-
thelial swelling with perivascular infiltrate are also noted. Spirochetes can
be visualized with dark field microscopy or silver staining of mucosal or cuta-
neous lesions.
Diagnosis of secondary syphilis is established with clinical evidence of
secondary syphilis combined with RPR titers above 1:32. A prozone
reaction in which the RPR test is falsely negative is seen in 1% to 2% of
patients with secondary syphilis [7]. The true positive test result may be
elucidated in these patients with serial dilutions. Thus, for patients with
a high index of suspicion of having secondary syphilis and a negative RPR,
dilutional testing should be requested. The FTA-ABS test is also positive in
patients with secondary syphilis. Because this test remains positive for life, it
is not a good indicator of active disease. A negative FTA-ABS test does rule
out secondary syphilis.

Late syphilis
Following secondary syphilis, patients enter a latent or asymptomatic
stage. The understanding of the untreated course of syphilis was derived
primarily from the prospective Oslo study in 1910. Data from nearly 2000
patients were collected by Boeck and a long-term follow up and analysis was
provided by Gjestland et al [6] who reported that approximately one third
598 S.D. Pletcher, S.W. Cheung / Otolaryngol Clin N Am 36 (2003) 595–605

of patients persist with latent disease, one third of patients spontaneously

clear the disease, and one third of patients progress to develop tertiary
syphilis.
The symptom complexes of tertiary syphilis are divided into neuro-
syphilis, cardiovascular syphilis, or benign (gummatous) syphilis. Antibiotic
treatment of the early stages of syphilis nearly eliminated the clinical entity
of neurosyphilis in the United States in the 1960s. During the following
2 decades, rates of neurosyphilis increased. Concurrent HIV infection has
been implicated in this resurgence of neurosyphilis [8,9].
Neurosyphilis has several potential symptom complexes, some of which
are not limited to the tertiary stage. Meningeal syphilis occurs within the first
year of infection and is characterized by classic meningeal symptoms: head-
ache, stiff neck, nausea, and vomiting. Cranial nerve involvement is seen in
40% of patients with syphilitic meningitis; hearing loss, facial paralysis,
and visual abnormalities are the most common associated symptoms [10].
Rarely, localized syphilitic meningitis may occur in which a gumma or
circumscribed mass of granulation tissue can lead to focal cranial nerve
symptoms.
Meningovascular syphilis may affect any site within the central nervous
system (CNS) and presents 4 to 7 years following infection [11]. Vascular
occlusion results in focal CNS ischemia and stroke. Meningovascular
syphilis can occur in patients who receive incomplete treatment for syphilitic
meningitis. Parenchymatous neurosyphilis (tabes dorsalis or generalized
paresis) is a late manifestation of syphilis, often occurring decades after
primary infection. Generalized paresis is a chronic, dementing illness that is
rarely seen today. This condition was previously a major cause of dementia.
Tabes dorsalis is characterized by sensory ataxia, lightening pains, and
autonomic dysfunction. Generalized paresis and tabes dorsalis can occur
concurrently.
Cardiovascular syphilis occurs with spirochete invasion of the aorta and
coronary vessels. Once a leading cause of death, cardiovascular syphilis in
the United States now exists only in sporadic case reports. Unlike other late
manifestations of syphilis, the incidence of cardiovascular syphilis has not
increased with the arrival of HIV infection. The inflammatory response to
spirochete invasion of the aortic vaso-vasorum and coronary arteries leads
to an obliterative endarteritis. Extensive damage to the aortic vaso-vasorum
leads to scarring and necrosis of the medial aortic wall resulting in aortic
aneurysms. These aneurysms occurs in the thoracic aorta and do not dissect
because of the extensive scarring. Rarely, these aneurysms present with
compression of surrounding structures such as the recurrent laryngeal nerve,
with resultant hoarseness. Other clinical manifestations of cardiovascular
syphilis include aortic insufficiency, congestive heart failure, myocardial
infarction, and sudden death.
Benign (gummatous) syphilis is characterized by destructive lesions
(gummata) that involve epithelial, skeletal, or visceral tissue but have been
 S.D. Pletcher, S.W. Cheung / Otolaryngol Clin N Am 36 (2003) 595–605 599

reported throughout the body. Unlike the chancre of primary syphilis,

spirochetes are rarely identified with silver staining of gummata. The gumma
is thought to represent a robust inflammatory response to a few spirochetes.
After extinction of this entity in the United States, multiple case reports have
been presented since 1990, primarily in HIV-infected patients [12–14].

Congenital syphilis
Syphilis is the oldest recognized congenital infection. Materno-fetal
transmission rates are highly dependent on the stage of maternal syphilis.
Children born to parents with primary or secondary syphilis are virtually
always afflicted with disease; half are born prematurely or die in the peri-
natal period, whereas the other half develop congenital syphilis [15]. Children
born to mothers without active early disease are rarely affected by disease.
Only 2% of children born to mothers with a remote (>4-year) history
of infection develop congenital syphilis [15].
Similar to those of acquired syphilis, the symptoms of congenital syphilis
are divided into early and late stages. Although congenital syphilis has been
linked to prematurity and low birth weight [16], most patients are
asymptomatic at birth [17]. Nearly all patients with congenital syphilis
demonstrate early symptoms on physical examination or radiographic
or laboratory findings by 3 months [18,19]. The severity of the clinical
manifestations in early congenital syphilis varies from life-threatening multi-
organ involvement to asymptomatic laboratory or radiographic abnormal-
ities. Clinical findings may include mucocutaneous lesions, rhinorrhea,
hepatosplenomegaly, ocular abnormalities, skeletal involvement, and CNS
involvement. Currently in the United States, it is exceedingly rare to see late
congenital syphilis. Many of the clinical findings of late congenital syphilis
are similar to those of late acquired syphilis. Small notched teeth, congenital
deafness, and interstitial keratitis make up Hutchinson’s clinical triad of
congenital syphilis. Palatal deformities, saddle nose deformity, neuro-
syphilis, and skeletal abnormalities may also be seen with late congenital
syphilis.
The diagnosis of congenital syphilis is complicated by the ability of
maternal antibodies to cross the placenta and confound immunologic
testing of the infant. Identification of spirochetes on dark field microscopy,
silver stain, or by immunofluorescence represents the only true confirmation
of congenital syphilis. The high concentration of spirochetes in pathologic
nasal discharge, mucous patches, vessiculobullous lesions, and condylomata
allows easy confirmation of the diagnosis in patients with these lesions. In
the absence of such lesions a confident diagnosis my be established if the
mother has reactive RPR serologies and the infant has classic signs of
congenital syphilis, or if the infant has treponemal titers more than four
times greater than those of the mother [16].
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Diagnostic tests
Diagnostic tests for syphilis [20] can be divided into four categories: dark
field examination, serologic tests, spinal fluid examination, and histopatho-
logic studies. Dark field examination is most useful when moist lesions with
abundant spirochetes are available. Lesions of primary syphilis (chancres),
of secondary syphilis (mucous patches, condyloma lata), and of early
congenital syphilis are excellent candidates for direct dark field examina-
tions. Fluid from enlarged regional lymph nodes may also be used. The
collected specimens must be evaluated immediately. The patient must be
tested in a facility where both dark field examination and skilled technicians
are available. The sensitivity of dark field examination approaches 80%.
Dark field examination using fluorescent antibodies is also available and
confers a higher sensitivity [21].
Serologic tests for T. pallidum fall into two categories, nontreponemal and
treponemal. Four nontreponemal tests are currently used: venereal disease
research laboratory (VDRL) slide test, unheated serum regain (USR), RPR,
and toluidine red untreated serum test (TRUST). These tests measure
antibody response to cellular particles released as a result of treponemal
infection. Because other disease processes may cause release of similar
antigens, these tests are relatively nonspecific. Systemic lupus erythematosus,
diseases with immunoglobulin abnormalities, leprosy, intravenous drug
abuse, and malignancy may all cause chronic elevation of nontreponemal
titers. Hepatitis, malaria, pregnancy, mononucleosis, and other viral in-
fections have been noted to cause an acute elevation in nontreponemal
titers. Despite these confounding factors, nontreponemal tests may be used
either as qualitative screening examinations or as quantitative tests to follow
treatment. Because of its nonspecific nature, a positive nontreponemal test
does not confirm T. pallidum infection in the absence of other evidence for the
diagnosis of syphilis. After successful treatment or eradication of the disease,
nontreponemal tests are no longer positive.
Treponemal tests (FTA-ABS and microhaemagglutination-Treponema
pallidum [MHA-TP] use T. pallidum as the antigen and are based on the
detection of antibodies against treponemal components. These tests are used
primarily to verify the accuracy of nontreponemal tests. For nearly all
syphilis patients, the treponemal tests remain positive for life even if the
disease is eradicated [22]. These tests are not quantified and may not be used
to monitor disease progression.
Examination of the spinal fluid is useful in determining the presence of
neurosyphilis. The VDRL test is most frequently used for examination
of cerebrospinal fluid. The FTA-ABS test should not be used with
cerebrospinal fluid because trace amounts of blood in the cerebrospinal
fluid may lead to a false-positive result in patients with seropositive syphilis
[23]. Pathologic examination using silver staining is of use only in autopsy
material.
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Manifestations of syphilis in the head and neck

Otosyphilis
The diagnosis of otosyphilis remains controversial. Otosyphilis has been
defined as the presence of a positive RPR in the setting of unexplained
sensorineural hearing loss [24]. This definition, however, lacks a clear, causal
relationship between the presence of disease and the clinical symptoms and
is confounded by multiple disease processes that may result in a positive
RPR test. Otosyphilis can occur in both congenital and acquired syphilis
and is a late manifestation of the disease. Classic symptoms include
unexplained hearing loss and Meniere’s syndrome with fluctuating tinnitus
and episodic vertigo. Several pathogenic mechanisms, including direct
spirochete perilymphatic invasion, temporal bone osteotitis, and microvas-
cular inflammation and infarction, have been proposed. Patients with acute
meningeal syphilis have a 20% incidence of significant sensorineural hearing
loss, which is frequently associated with other cranial neuropathies [10].
Laboratory test confirmation should include FTA-ABS as well as
a lumbar puncture with cerebrospinal fluid VDRL or RPR analysis.
Treatment of otosyphilis has involved penicillin and steroids. Several
authors have demonstrated that intramuscular penicillin does not achieve
treponemocidal levels in the cerebrospinal fluid or perilymph; thus in-
travenous penicillin is recommended for patients with otosyphilis [25–28]. In
multiple studies the combination of intravenous penicillin and steroid
treatment shows efficacy in 15% to 35% of treated patients. In an attempt to
identify patients who would benefit from such therapy, Gleich et al [29]
studied the clinical course of 18 patients with unexplained sensorineural
hearing loss and positive VDRL and FTA-ABS serologies following
treatment with penicillin and steroids. They found an overall treatment
response rate of 23%. In their study group patients with symptoms of
fluctuating hearing loss, CSF abnormalities on lumbar puncture, and
unilateral hearing loss were more likely to benefit. They also found high rates
of subjective improvement of tinnitus (85%) and vertigo (86%). They
recommended treatment with intravenous penicillin and steroids in patients
with positive blood serologies combined with CSF abnormalities, severe
vertigo or tinnitus, or in patients younger than 60 years with a recent history
of fluctuating hearing loss.
The hearing loss of otosyphilis typically begins at high frequency and
often progresses to a complete loss of bilateral cochlear and vestibular
function. Congenital syphilis has been described as having a more rapid
course, symmetric loss pattern, and less tinnitus/vertigo than seen in adults
[30]. In patients with concurrent HIV infection, the time course of
otosyphilis is accelerated: patients frequently develop symptoms within
the first 5 years of infection rather than after the classic 6- to 15-year in-
cubation period [31,32].
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The low incidence of otosyphilis as a causative factor for idiopathic

sensorineural hearing loss in patients without a known history of syphilis
has led some to question the necessity of RPR screening. Gagnebix et al [33]
found a single case of latent syphilis after screening 182 patients with idio-
pathic sensorineural hearing loss in Switzerland. Syphilis is a rare treatable
cause of sensorineural hearing loss, so screening for syphilis in patients
with unexplained sensorineural loss may be prudent despite a relatively
low yield.
Manifestations of otosyphilis are not limited to the inner ear. Middle ear
involvement with fibrosis between the incus and malleus has been reported;
thus a conductive component to hearing loss does not exclude a treponemal
cause. Fibrosis between the stapes footplate and membranous labyrinth can
result in a positive fistula test of Hennebert’s sign (a fistula sign without
a fistula) [34,35].

The oral cavity

The oral cavity may be affected in primary syphilis. Other than the
genitalia, the lips are the most common site of initial spirochete inoculation
and chancre formation [36]. Chancres of the tongue and tonsil have also
been reported [37]. The mucous patches of secondary syphilis may present
throughout the upper aerodigestive tract. Secondary syphilis may present as
pharyngitis or tonsillitis. The gummata of tertiary syphilis may involve any
site within the oral cavity including the tongue or palate [37]. These painless
lesions may be accompanied by regional lymphadenopathy and mimic
neoplastic disease.
The oral cavity is commonly affected by congenital syphilis. Mucous
patches on tongue, palate, and lips may become fissured and hemorrhagic
resulting in radial scars or rhagades [38]. Children who progress to develop
symptoms of late congenital syphilis may have teeth that are notched,
hypoplastic, and lack enamel. These teeth are referred to as ‘‘Hutchinson’s
teeth.’’ These children are also at risk for gummata, which may be present
anywhere in the upper aerodigestive tract.

The larynx and hypopharynx

Laryngeal chancres have been reported as a manifestation of primary
syphilis. The mucous membrane manifestations of secondary syphilis may
also involve the larynx and hypopharynx with resultant laryngitis and
hoarseness. Hoarseness may also occur in tertiary syphilis as a result of either
laryngeal injury or damage to the recurrent laryngeal nerve. Gummata of the
larynx may directly cause hoarseness, or they may scar and result in
infraglottic stenosis, adhesion between the vocal folds, or arytenoid fixation
[37]. Dysfunction of the recurrent laryngeal nerve may be seen with
neurosyphilis or with cardiovascular syphilis–induced aortic aneurysms that
compress the recurrent laryngeal nerve.
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The nose and nasopharynx

Primary syphilis of the nose is rare but has been reported to occur at the
mucocutaneous junction in the nasal vestibule [37]. Secondary syphilis may
present as acute rhinitis with a scant thick discharge and irritation of the
anterior nares. Patients with benign tertiary syphilis may develop gummata
of the nose. The septum is commonly involved and eventually destroyed,
resulting in a saddle nose deformity. The differential diagnosis of tertiary
syphilis of the nose includes tuberculosis, malignancy, leprosy, sarcoidosis,
Wegener’s granulomatosis, cocaine abuse, and midline lethal granuloma.
Nasal discharge is often the earliest sign of congenital syphilis, occurring
1 to 2 weeks before the rash. This watery discharge contains high concen-
trations of spirochetes. Over time the discharge becomes thick and purulent,
then bloody. The resulting nasal obstruction may interfere with feeding.
Erosion of the septal cartilage may occur, thus compromising nasal dorsum
integrity. The incidence of the symptoms ranges from 10% to 75% in
various series [39–41].
Tertiary syphilis rarely affects the nasopharynx. A case of an extensive
lesion resulting in ophthalmoplegia and blindness has been reported [42],
along with stenosis of the nasopharynx from extensive scarring [43].

Human immunodeficiency virus and syphilis

The relationship between HIV and syphilis is more than concomitant
transmission of sexually transmitted disease [44]. Syphilis produces genital
lesions and evokes a systemic inflammatory response; both actions may lead
to increased transmission of HIV [45,46]. Concomitant infection of HIV is
believed to increase the incidence of neurosyphilis and benign tertiary
syphilis [12–14,47]. Patients diagnosed with syphilis should be tested for HIV.

Treatment
Penicillin G, given parenterally, is the treatment of choice for syphilis.
The preparation of penicillin used, dosing, and duration of treatment
depend on the clinical scenario. The CDC guidelines for the treatment of
syphilis [48] are periodically updated and should guide therapeutic regimens.
Treatment may result in the Jarish-Herxheimer reaction, an acute febrile
illness which may occur in the first 24 hours following treatment. Myalgias,
headache, and other constitutional symptoms may be manifest. Fetal
distress in pregnant patients has been reported. All patients being treated
with syphilis should be warned of these symptoms and may be treated with
antipyretics. The potential consequences in pregnant patients should not
preclude treatment [48].
In conclusion, although the incidence of syphilitic infections has
dramatically decreased in the last 40 years, small epidemics of these
604 S.D. Pletcher, S.W. Cheung / Otolaryngol Clin N Am 36 (2003) 595–605

infections continue to occur. These infections continue to be easy to control

once the diagnosis has been made. It is prudent for the otolaryngologist to
continue to be aware of the many clinical manifestations of syphilis and be
suspicious of these infections in the patients that they encounter.

References
[1] Catterall RD. Neurosyphilis. Br J Hosp Med 1977;17:585.
[2] Moore M, Merritt HH. Role of syphilis of the nervous system in the production of mental
disease. JAMA 1936;107:1292.
[3] Cates W, Rothenberg RB, Blount JH. Syphilis control. The historic context and
epidemiologic basis for interrupting sexual transmission of Treponema pallidum. Sex
Transm Dis 1996;23(1):68–75.
[4] Division of STD Prevention. Sexually transmitted disease surveillance, 1999. Atlanta,
Centers for disease control and preventions (CDC), US Dept of Health and Human
Services, 2000.
[5] Holmes, Mardtt PA, Sparling PF, et al. Sexually transmitted diseases. 3rd edition. New
York: McGraw-Hill; 1999. p. 467–507.
[6] Gjestland T. The Oslo study of untreated syphilis: an epidemiologic investigation of the
natural course of syphilitic infection based on a restudy of the Boeck-Bruusgaard material.
Acta Derm Venereol (Stockh) 1955;35(Suppl 34):I.
[7] Jurado RL, Campbell J, Martin PD. Prozone phenomenon in secondary syphilis: has its
time arrived? Arch Intern Med 1993;153:2496–8.
[8] Musher DM, Hamill RJ, Baughn RE. Effect of human immunodeficiency virus infection
on the course of syphilis and the response to treatment. Ann Intern Med 1990;113:872.
[9] Musher DM. Syphilis, neurosyphilis, penicillin, and AIDS. J Infect Dis 1991;163:1201.
[10] Wilcox RR, Goodwin PG. Nerve deafness in early syphilis. Br J Vener Dis 1971;47:401.
[11] Holmes MD, Brant-Zawadzki MM, Simon RF. Clinical features of meningovascular
syphilis. Neurology 1984;34:553.
[12] Kearns G, Pogrel MA, Honda G. Intraoral tertiary syphilis (gumma) in a human immu-
nodeficiency virus-positive man: a case report. J Oral Maxillofac Surg 1993;51:85.
[13] Sule RR, Deshpande SG, Dharmadhikari NJ, et al. Late cutaneous syphilis. Cutis
1997;59:135.
[14] Kasmin F, Reddy S, Mathor-Wagh V, et al. Syphilitic gastritis in an HIV infected
individual. Am J Gastroenterol 1992;87:1820.
[15] Ingraham NR. The value of penicillin alone in the prevention and treatment of congenital
syphilis. Acta Derm Venereol (Stockh) 1951;31(Suppl 24):60.
[16] Stoll BJ, Lee FK, Larsen S, et al. Clinical and serologic evaluation of neonates for con-
genital syphilis: a continuing diagnostic dilemma. J Infect Dis 1993;167:1093.
[17] Reyes MP, Hunt N, Ostrea EMJ, et al. Maternal/congenital syphilis in a large tertiary-care
urban hospital. Clin Infect Dis 1993;17:104.
[18] Stokes JH, Beerman H, Ingraham NR Jr. Modern clinical syphilology. Philadelphia: W.B.
Saunders; 1934.
[19] Findlay L. Syphilis in childhood. Oxford: Oxford Medical Publications; 1919.
[20] Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for
syphilis. Clin Microbiol Rev 1995;8(1):1–21.
[21] Daniels KC, Ferneyhough HS. Specific direct fluorescent antibody detection of Treponema
pallidum. Health Lab Sci 1977;14:164–71.
[22] Schroeter AL, Lucas JB, Price EV, et al. Treatment of early syphilis and reactivity of
serologic tests. JAMA 1972;221:471–6.
[23] Davis LE, Sperry S. The CSF-FTA test and significance of blood contamination. Ann
Neurol 1979;6:68–9.
 S.D. Pletcher, S.W. Cheung / Otolaryngol Clin N Am 36 (2003) 595–605 605

[24] Becker BD. Late syphilitic hearing loss: a diagnostic and therapeutic dilemma.
Laryngoscope 1979;89:1273–88.
[25] Wiet RJ, Milko DM. Isolation of spirochetes in the perilymph despite prior antisyphilitic
therapy. Arch Otolaryngol 1975;101:104–6.
[26] Yoder FW. Penicillin treatment of neurosyphilis: are recommended dosages sufficient?
JAMA 1975;232:270–1.
[27] Mohr JA, Groffiths W, Jackson R, et al. Neurosyphilis and penicillin levels in cerebrospinal
fluid. JAMA 1976;236:2208–9.
[28] Dunlop EM, Al-Egaily SS, Houang ET. Penicillin levels in blood and CSF achieved by
treatment of syphilis. JAMA 1979;241:2538–40.
[29] Gleich LL, Linstrom CJ, Kimmelman CP. Otosyphilis: a diagnostic and therapeutic
dilemma. Laryngoscope 1992;102:1255–9.
[30] Karmody CS, Schuknecht DF. Deafness in congenital syphilis. Arch Otolaryngol 1966;
83:18.
[31] Johns DR, Tierney M, Felsenstein D. Alteration in the natural history of neurosyphilis by
concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;216:
1569–72.
[32] Berry CD, Hooton TM, Collier AC, et al. Neurologic relapse after benzathine penicillin
therapy for syphilis in a patient with HIV infection. N Engl J Med 1987;316:1587–9.
[33] Gagnebix J, Maire R. Infection screening in sudden and progressive idiopathic sensori-
neural hearing loss: a retrospective study of 182 cases. Otol Neurotol 2002;23:160–2.
[34] Belal A, Stewart TJ. Pathological changes in the middle ear joints. Ann Otol Rhinol
Laryngol 1974;83(5):158–67.
[35] Nadol JB. Positive ‘‘fistula sign’’ with an intact tympanic membrane. Arch Otolaryngol
1974;100:273–8.
[36] Fiumara NJ. Venereal diseases of the oral cavity. J Oral Med 1976;31:36–40.
[37] McNulty JS, Fassett RL. Syphilis: an otolaryngologic perspective. Laryngoscope 1981;91:
889–905.
[38] Nabarro D. Congenital syphilis. London: E. Arnold; 1954.
[39] Platou RV. Treatment of congenital syphilis with penicillin. Adv Pediatr 1949;4:39.
[40] Saxoni F, Lapaanis P, Pantekalis SN. Congenital syphilis: a description of 18 cases and
reexamination of an old but ever-present disease. Clin Pediatr 1967;6:687.
[41] Wile U, Mundt LK. Congenital syphilis: a statistical study with special regard to sex
incidence. American Journal of Syphilis, Gonorrhea, and Venereal Diseases 1942;26:70.
[42] Gager WE, Smith JL, Israel CW. Nasopharyngeal syphilis with blindness. Arch
Otolaryngol 1969;90(11):125–30.
[43] Ramstadt T, Traaholt L. Destruction of the soft palate by tertiary ‘‘benign’’ syphilis: a case
report. J Oral Rehab 1980;7:111–5.
[44] Schofer H, Imhof M, Thoma-Gerber E, et al. Active syphilis in HIV infection: a multicentre
retrospective survey. Genitourin Med 1996;72:176.
[45] Quinn TC, Cannon RO, Glasser D, et al. The association of syphilis with risk of human
immunodeficiency virus infection in patients attending sexually transmitted disease clinics.
Arch Intern Med 1990;150:1297.
[46] Hutchinson CM, Pompalo AM, Reichart CA, et al. Characteristics of patients with syphilis
attending Baltimore STD clinics: multiple high-risk subgroups and interactions with
human immunodeficiency virus infections. Arch Intern Med 1991;141:511.
[47] Smith ME, Canalis RF. Otologic manifestations of AIDS: the otosyphilis connection.
Laryngoscope 1989;99:365–72.
[48] Workowski KA, Levine WL. Sexually transmitted diseases treatment guilines 2002.
MMWR Morb Mortal Wkly Rept 2002;51(RR-6):18–29.