Syphilis

Syphilis
by: Erik Austin, D.O., M.P.H.

Syphilis
* AKA lues
* Contagious, sexually transmitted disease caused by the
* Spirochete: Treponema pallidum
* Enters through skin or mucous membrane where primary manifestations are seen

Treponema pallidum
* Spiral spirochete that is mobile
* # of spirals varies from 4 to 14
* Length is 5 to 20 microns
* Can be seen on fresh primary or secondary lesions by darkfield microscopy or fluorescent antibody techniques

Syphilis epidemiology
* Major health problem throughout world
* 2.6 cases per 100,000 in 1999 in the US
* Lowest level ever recorded
* Concentrated in 28 counties in the SE U.S.
* Mainly gay men and crack cocaine users
* Enhances risk of transmission of HIV
* HIV testing recommended in all patients with syphilis
* Reportable disease

Serologic Tests
* Testing reveals patients immune status not whether they are currently infected
* Non-treponemal antigen test uses lipoidal antigens rather than T. pallidum or components of it
* RPR = rapid plasma reagin
* VDRL = Venereal Disease Research Laboratory
* Positive within 5 to 6 weeks after infection
* Strongly positive in secondary phase
* Strength of reaction is stated in dilutions
* May become negative with treatment or over decades
* MHA-TP: microhemagglutination assay for T. pallidum
* FTA-ABS: fluorescent treponemal antibody absorption test
* All positive nontreponemal test results should be confirmed with a specific treponemal test
* Treponemal tests become positive early, useful in confirming primary syphilis
* Remain positive for life, useful in diagnosing late disease
* Treatment results in loss of positivity in 13-24% of patients

Biologic False-Positive Test Results
* Positive test with no history or clinical evidence of syphilis
* Acute BFP: those that revert to negative in less than 6 months
* Chronic BFP: those that persist > 6 months

BFP Test Results in Syphilis
* Acute BFP
* Vaccinations
* Infections
* pregnancy
* Chronic BFP
* Connective tissue disease (SLE)
* Liver disease
* Blood transfusions
* IVDA

Cutaneous Syphilis
* Chancre is usually the first cutaneous lesion
* 18 to 21 days after infection
* Round indurated papule with an eroded surface that exudes a serous fluid
* Usually painless and heals without scarring

Chancre
* Inguinal adenopathy 1-2 weeks after chancre
* Generally occur singly, but may be multiple
* Diameter mm to cm

Chancres
* In women, the genital chancre is less often observed due to location within the vagina and cervix
* Edema of labia may occur
* Untreated, the chancre heals spontaneously in 1 to 4 months
* Constitutional symptoms begin just as chancres disappear
* Extragenital chancre: may be larger, frequently on lips, rarely tongue, tonsil, breast, finger, anus.

Chancre Histology
* Ulcer covered by neutrophils and fibrin
* Dense infiltrate of lymphocytes and and plasma cells
* Spirochetes seen with with silver stains; Warthin-Starry
* Direct fluorescent antibody tissue test (DFAT-TP) = serous exudate collected on a slide sent for exam

Serology
* Nontreponemal tests positive 50%
* Treponemal tests positive 90%
* Positivity depends upon duration of infection, if chancre has been present for several weeks, test is usually positive

Chancre vs. Chancroid
* Incubation 3 weeks
* Painless
* Hard
* Lymphadenopathy may be bilateral, nontender, nonsuppurative
* Incubation 4-7 days
* Painful
* Soft
* Lymphadenopathy unilateral, tender, suppurative

DDx in Syphilis
* Chancroid - multiple lesions, may coexist with chancre, must r/o syphilis
* Granuloma Inguinale - indurated nodule that erodes, soft red granulation tissue, Donovan bodies in macrophages with Wright or Giemsa stain
* Lymphogranuloma Venereum - small, painless, superficial non indurated ulcer, primary lesions followed in 7 to 30 days by adenopathy
* HSV - grouped vesicles, burning pain

Secondary Syphilis
* Skin manifestations in 80% called syphilids
* Symmetric, generalized, superficial, macular - later papular, pustular
* May affect face, shoulders, flanks, palms and soles, anal or genital areas

Secondary Syphilis Macular Eruptions
* Exanthematic erythema 6-8 weeks after chancre - may last hours to months
* Round, slightly scaly ham-colored macules
* Pain and pruritus may be present
* Generalized adenopathy

Secondary Syphilis Papular Eruptions
* Occurs on face and flexures of arms, legs, and trunk
* Yellowish-red spots may appear on palmar and plantar surfaces
* Ollendorf’s sign = tender papule
* May produce a psoriasiform eruption
* May appear as minute scale-capped papules
* Tend to be disseminated, but may be localized, asymmetrical, configurate, hypertrophic or confluent.
* Annular syphilid - mimics sarcoidosis and is more common in blacks
* Pustular syphilid – rare - face, trunk, extremities red small crust-covered ulceration
* Rupial syphilid - superficial ulceration is covered with a pile of terraced crusts resembling an oyster shell.
* Lues Maligna - rare, severe ulcerations, pustules, or rupioid lesions, accompanied by severe constitutional symptoms.
* Condylomata lata - papular mass, weeping, gray 1-3cm, groin, anus (not vegetative like condylomata acuminata)
* Syphilitic alopecia - irregular, scalp has a moth-eaten appearance 5% of pts

Secondary Syphilis Mucous Membrane
* Present in 1/3 of secondary syphilis
* Most common is “syphilitic sore throat”
* Diffuse pharyngitis, hoarseness
* Tongue may show patches of desquamation of papillae
* Ulcerations of tongue and lips in late stages
* Mucous patches are the most characteristic mucous membrane lesions; macerated, flat. Grayish, rounded erosions covered by a delicate, soggy membrane.

Secondary Syphilis Systemic Involvement
* Lymphadenopathy common.
* Acute glomerulonephritis, gastritis, proctitis, hepatitis, meningitis, iritis, uveitis, optic neuritis, Bell’s palsy, pulmonary nodular infiltrates, osteomyelitis, polyarthritis.

Secondary Syphilis Diagnosis
* Nontreponemal serologic tests for syphilis are strongly reactive (seronegativity rarely in AIDS)
* Spirochetes on darkfield exam

Secondary Syphilis DDx “Great Imitator”
* Pityriasis rosea
* Drug eruptions (pruritic)
* Lichen planus; Wickham’s striae, Koebner’s, pruritic
* Psoriasis; no adenopathy
* Sarcoidosis; need serology and silver staining of biopsy
* Infectious mononucleosis, false pos RPR
* Geographic tongue
* Aphthous stomatitis

Latent Syphilis
* After the lesions of secondary syphilis have involuted, a latent period occurs where the patient has no clinical signs, but positive serological tests
* May last a few months or a lifetime
* 60-70% of pts that are untreated remain asymptomatic for life
* Women may infect unborn child for 2 years
Late Syphilis
* Defined by CDC as infection of greater than 1 years duration
* Tertiary Cutaneous Syphilis
* Late Osseous Syphilis
* Neurosyphilis
* Late Cardiovascular Syphilis

Tertiary Cutaneous Syphilis
* Tertiary syphilids usually occur 3-5 years after infection
* 16% of untreated pts will develop lesions of skin, mucous membrane, bone or joints
* Skin lesions are localized, destructive, heal with scarring

Tertiary Syphilids
* Two main types; Nodular syphilid and the Gumma
* Nodular - reddish brown firm papules or nodules 2mm or larger, scales.
* Gumma - larger

Nodular Tertiary Syphilid
* Lesions tend to form rings and undergo involution as new lesions develop
* Characteristic circular or serpiginous pattern
* “kidney-shaped” lesion occurs on the extensor surfaces of the arms and on back
* Patches have scars and fresh ulcerated lesions
* Process may last for years, slowly marching across large areas of skin

Gumma
* May occur as unilateral, isolated, single or disseminated lesions, or serpiginous
* May be restricted to the skin, or originate in deeper tissues, and break down the skin
* Lesions begin as small nodules, enlarge to several centimeters
* Central necrosis, deep ulcer with a gummy base, most frequent site is lower legs

Diagnosis of Tertiary Syphilis
* Histopathology - tuberculoid granules with multinucleated giant cells
* Nontreponemal tests (VDRL, RPR) positive in 75%
* Treponemal tests (FTA-ABS, MHA-TP, TPI) positive in nearly 100%
* Darkfield negative, PCR may be positive

DDx Tertiary Syphilis
* R/O tumors; SCCA tongue, leukemic infiltrates, sarcoidosis
* Ulcerated syphilids resemble scrofula, atypical mycobacterium, sporotrichosis, blastomycosis
* Mycosis fungoides (CTCL) has eczema and pruritus
* Perforation of hard palate and septum

Late Osseous Syphilis
* Gummatous lesions can involve the periosteum and bone
* Head, face, tibia
* Periostitis, osteomyelitis, osteitis, gummatous osteoarthritis
* “Osteocope” - bone pain often at night
* Charcot joint - loss of contours of joint, hypermobility, painless
* Associated with tabes dorsalis

Neurosyphilis
* CNS involvement with syphilis can occur at any stage
* Most are asymptomatic; CSF shows pleocytosis
* 4-10% of untreated pts will develop neurosyphilis

Early Neurosyphilis
* First year of infection - meningeal
* Headache, stiff neck, cranial nerve disorders, seizures, delirium, increased ICP

Meningovascular Neurosyphilis
* 4-7 years after infection
* Thrombosis of vessels in the CNS
* Hemiplegia, aphasia, hemianopsia, transverse myelitis, progressive muscular atrophy
* CN palsies; CN IIX, III, IV, VI
* “Argyll Robertson Pupil” accommodates, but doesn’t react

Late Neurosyphilis
* Parenchymatous neurosyphilis occurs more than 10 years after infection
* Two classical patterns; Tabes Dorsalis, and General Paresis

Tabes Dorsalis
* Degeneration of the dorsal roots of the spinal nerves and posterior columns of the the spinal cord
* Gastric crisis with severe pain and vomiting is most common
* Pain, urination problems, paresthesias, ataxia, diplopia, vertigo, deafness
* Signs: Argyll Robertson pupil, reduced lower cord reflexes, Romberg sign, sensory loss, atonic bladder, Charcot’s joints, optic atrophy
* Personality changes, memory loss, apathy, megalomania, delusions, dementia

Late Cardiovascular Syphilis
* Occurs in 10% of untreated pts
* Aortitis, aortic insufficiency, coronary disease, aortic aneurysm

Congenital Syphilis
* Prenatal syphilis acquired in utero
* Infection through the placenta usually does not occur before the fourth month, so treatment of the mother before this time will almost always prevent infection in the fetus.
* If infection occurs after the fourth month 40% risk of fetal death

* 40% of pregnancies in women with untreated early syphilis will result in a syphilitic infant.
* Most neonates with congenital syphilis are normal at birth.
* Early congenital syphilis - lesions occurring within first two years of life
* Late congenital syphilis - lesion occur after two years

Early Congenital Syphilis
* Cutaneous manifestations appear most commonly during 3rd week
* Snuffles (a form of Rhinitis) is most frequent, bloody drainage, ulcers may develop, later septal perfs
* 30-60% of infants develop cutaneous lesions similar to secondary syphilis
* Red to copper maculopapular, become large, scaling, pustules, crusting
* Face, arms, buttocks, legs, palms and soles

Early Congenital Syphilis
* Face, perineum, and intertriginous areas, usually fissured lesions resembling mucous patches. Radial scarring results leading to Rhagades
* Bone lesions occur in 70-80% , epiphysitis is common and causes pain on motion, leading to infant refusing to move; Parrot’s pseudoparalysis.
* Radiologic features of the bone lesions in congenital syphilis during the first 6 months are characteristic.
* Bone lesions occur at the epiphyseal ends of long bones.
* Lymphadenopathy, hepatomegaly, nephrotic syndrome, meningitis, nerve palsies may all occur

Late Congenital Syphilis
* Lesions are two types - malformations of tissue affected at critical growth periods (Stigmata) and persistent inflammatory foci
* Inflammatory - lesions of the cornea, bones, and central nervous system, i.e., interstitial keratitis in 20-50%, perisynovitis of knees (Clutton’s joints), tabes dorsalis, seizures, and paresis

Late Congenital Syphilis
* Malformations (Stigmata) - destructive effects leave scars or developmental defects
* Hutchinson’s Triad - Changes in incisors, corneal scars, and eighth nerve deafness
* Also, saber shins, rhagades of the lips, saddle nose, mulberry molars

Hutchinson’s Teeth
* Malformation of the central upper incisors that appears in the second or permanent teeth. Teeth are cylindrical rather than flattened, cutting edge narrower than base, notch may develop
* Mulberry molar - first molar hyperplastic, flat occlusal surface covered with knobs representing abortive cusps

Treatment of Syphilis
* PCN is drug of choice for treatment of all stages of syphilis.
* HIV testing is recommended in all patients
* If less than one year; 2.4M U of Benzathine PCN G
* PCN-allergic; Tetracycline 500mg QID for 14 days

Jarisch- Herxheimer Reaction
* Febrile reaction occurs after the initial dose of antisyphilitic tx, 60-90% of pts
* 6-8 hours after dose - chills, fever, myalgia, increase in inflammation (neurosyphilis)

Treatment of Sex Partners
* Persons exposed to a patient with early syphilis within the previous 3 months should be treated, even if seronegative
* Single dose azithromycin effective in treating incubating syphilis

Serologic Testing after Tx
* VDRL or RPR repeated every 3 months in first year, every 6 months in second year, than annually
* A fourfold decrease in titer should be seen at 6 months, if not then 3 weekly PCN IM injections
* Response for latent syphilis is slower, 12-24 months
* If not responding; HIV and CSF testing repeated
* Pts with late syphilis may be “serofast”, and titers may not improve
* Neurosyphilis pts should have CSF every 6 months

Syphilis and HIV
* Most HIV pts exhibit the classic clinical manifestations and course, and respond similarly to tx
* More likely to present with secondary syphilis and have a persistent chancre

Yaws
* Treponema pallidum subsp. Pertenue
* Endemic in some tropical, rural regions
* Overcrowding, poor hygiene, transmitted by contact with infected lesions
* Children, disabling course, affects skin, bones, and joints

Early Yaws
* Primary papule or group of papules appear at site of inoculation after 3 week incubation period, initial lesion becomes larger and crusted (Mother Yaw, maman pian )
* Feet, legs, buttocks, face, not genitals
* Mother yaw disappears after a few months
* Secondary Yaws – appears weeks or months after mother yaw appears. May be smaller and appear around primary lesion; may be annular (ringworm yaws)
* Condylomata may develop around body orifices and creases
* Palms and soles may form hyperkeratotic plaques leading to a painful crab-like gait (crab yaws)

Late Yaws
* 10% progress to late stage where gummas occur
* Ulcer with clean edges that tend to fuse to form con figurate and serpiginous patterns similar to tertiary syphilis
* Bone, joint, saddle nose, saber shin, Gangosa (destruction of palate and nose)
* Diagnosis = Darkfield, VDRL or RPR

Endemic Syphilis (Bejel)
* Bejel is a Bedouin term for nonvenereal treponematosis, nomadic tribes of North Africa, Southwest Asia, Eastern Mediterranean
* T. pallidum subsp. Endemicum
* Usually occurs in childhood through skin contact
* May affect the skin, oral mucosa, and skeletal system

Bejel
* Primary lesions rare, probably go undetected in the oral mucosa
* Secondary oral lesions - shallow, painless ulcers, laryngitis
* Condyloma of axillae and groin, lymphadenopathy, osteoperiostitis causes night leg pain
* Untreated secondary bejel heals in 6-9 months
* Tertiary stage - gummatous ulcerations of the skin, nasopharynx, and bone.
* Neuro - uveitis, choritis, optic atrophy

Pinta
* T. carateum; nonvenereal, endemic
* Only skin lesions occur
* All ages, Brazilian rain forest
* Primary Stage - 7 to 60 days after inoculation. Lesion begins as a tiny red papules and become an elevated erythematous infiltrated plaque 10cm in diameter over 2-3 months. Legs -satellite lesions, no erosion or ulceration as in chancres.
* Secondary Stage - 5 months to 1 year
* Small, scaling papules that enlarge and coalesce – affects extremities and face
* Red to blue, black with postinflammatory hyperpigmentation
* Nontreponemal tests reactive in 60%
* Late Dyschromic Stage - young adults – may appear as hyperpigmented and depigmented macules resembling vitiligo
* Face, waist, wrist, trochanteric areas
* Histo - acanthosis, lichenoid, spirochetes in epidermis

Treatment of Yaws, Bejel, and Pinta
* Benzathine PCN G 1.2 to 2.4 M units IM
* Tetracycline 500mg QID for adults
* EES 10mg/kg children QID for 14 days
Nonvenereal Treponematoses
* Yaws
* Endemic Syphilis
* Pinta

Treatment
* Syphilis >1year; 2.4M PCN G weekly for 3 weeks Pcn-allergic; Tetra 500mg QID for 30 days
* Neurosyphilis; IV
* Infant 100,000 to 150,000 units/kg/day Procaine PCN BID for first seven days of life

Syphilis.ppt