Syphilis Definition: Syphilis is a systemic infection caused by the spirochete Treponema pallidium, which is transmitted mainly by direct sexual intercourse (venereal syphilis) and less commonly via placenta (congenital syphilis) or by accidental inoculation from the infectious Materials T. Pallidum spirochetes cannot be cultured but are detected by silver stains, dark field examination and immunofluorescence technique

Pathogenesis: 􀂾 The organism is delicate and susceptible to drying and does not survive long outside the body. 􀂾 The organism invades mucosa directly possibly aided by surface abrasions following intercourse with an infected person, a primary lesion, an ulcer known as the chancre, develops at the site of infection usually on the external genetalia but also lips and anorectal region. Within hours, the T. pallidum pass to regional lymph nodes and gain access to systemic circulations. Thereafter, the disease is unpredictable. Its incubation period is about 3 weeks.

Whatever the stage of the disease and location of the lesions the histologic hallmarks of syphilis are A. Obliterative endarteritis B. Plasma cell rich mononuclear cell infiltrates. 􀂾 The endarteritis is secondary to the binding of spirochetes to endothelial cells mediated by fibronectin molecules bound to the surface of the spirochetes. The mononuclear infiltrates are immunologic response. 􀂾 Host humeral and cellular immune responses may prevent the formation of chancre on subsequent infections with T. pallidum but are insufficient to clear the spirochetes.

STAGES OF SYPHILIS Primary Secondary Latent Late or tertiary Early latent Late latent Late or tertiary May involve any organ, but main parts are: Neurosyphilis Cardiovascular syphilis Late benign (gumma)

PRIMARY SYPHILIS (The Chancre) Incubation period 9-90 days, usually ~21 days. Develops at site of contact/inoculation. Classically: single, painless, clean-based, indurated ulcer, with firm, raised borders. Atypical presentations may occur. Mostly anogenital, but may occur at any site (tongue, pharynx, lips, fingers, nipples, etc...) Non-tender regional adenopathy Very infectious. May be darkfield positive but serologically negative. Untreated, heals in several weeks, leaving a faint scar.

SECONDARY SYPHILIS Seen 6 wks to 6 mos after primary chancre Usually w diffuse non-pruritic, indurated rash, including palms & soles. May also cause: Fever, malaise, headache, sore throat, myalgia, arthralgia, generalized lymphadenopathy Hepatitis (10%) Renal: an immune complex type of nephropathy with transient nephrotic syndrome Iritis or an anterior uveitis Bone: periostitis CSF pleocytosis in 10 - 30% (but, symptomatic meningitis is seen in <1%)

SECONDARY SYPHILIS (Cont.) The skin rash: Diffuse, often with a superficial scale (papulosquamous). May leave residual pigmentation or depigmentation. Condylomata Lata: Formed by coalescence of large, pale, flat-topped papules. Occur in warm, moist areas such as the perineum. Highly infectious. Mucosal lesions: ~ 30% of secondary syphilis patients develop mucous patch (slightly raised, oval area covered by a grayish white membrane, with a pink base that does not bleed). Highly infectious

Lesions of syphilis resolve without treatment although person remains infected

LATENT SYPHILIS Positive syphilis serology without clinical signs of syphilis (& has normal CSF). It begins with the end of secondary syphilis and may last for a lifetime. Pt may or may not have a h/o primary or secondary syphilis. Is divided into early and late latency.

LATENT SYPHILIS (cont.) Early latent: The first year after the resolution of primary or secondary lesions, or A reactive serologic test for syphilis in an asymptomatic individual who has had a negative serologic test within the preceding year. Infectious. Late latent: Usually not infectious, except for the pregnant woman, who may transmit infection to her fetus.

LATE SYPHILIS ‘Tertiary Syphilis’ Is the destructive stage of the disease. Lesions develop in skin, bone, & visceral organs (any organ). The main types are: Late benign (gummatous) Cardiovascular & Neurosyphilis Can be crippling and life threatening Blindness, deafness, deformity, lack of coordination, paralysis, dementia may occur It is usually very slowly progressive, barring certain neurologic syndromes which may develop suddenly due to endarteritis and thrombosis in the CNS Late syphilis is noninfectious.

NEUROSYPHILIS Divided into 5 groups, which may overlap: Asymptomatic neurosyphilis Syphilitic meningitis Meningovascular syphilis General paresis Tabes dorsalis

TABES DORSALIS Occurs 20-30 years after the initial infection. It is uncommon. More common in whites and in men. It’s a slowly progressive, degenerative disease involving the posterior columns and posterior roots of the spinal cord. Results in progressive loss of peripheral reflexes, impairment of vibration and position sense, and progressive ataxia. Bladder incontinence & impotence are common. Chronic destructive changes of the large joints of the affected limbs may be seen in advanced cases (i.e., Charcot's joints).

CARDIOVASCULAR SYPHILIS May not manifest clinically until 20-30 years after infection, but usually begins within 5-10 years after initial infection. Primarily aortic insufficiency and aortic aneurysm of the ascending aorta. Other large arteries may sometimes be involved, and rarely the coronary ostia may be involved. Caused by obliterative endarteritis of the vasa vasorum with resultant damage to the intima & media of the great vessels, causing dilatation of the ascending aorta and eventually results in stretching of the ring of the aortic valve, producing aortic insufficiency. The valve cusps remain normal. Asymptomatic aortitis is best diagnosed by visualizing linear calcifications in the wall of the ascending aorta. More common in men than in women and possibly in blacks than in whites.

: Syphilitic gummas - there are grey white rubbery masses of variable sizes. They occur in most organs but in skin, subcutaneous tissue, bone, Joints and testis. In the liver, scarring as a result of gummas may cause a distinctive hepatic lesion known as hepar lobatum. - Collapse of the bridge of the nose and palate can occur with perforation - Osteitis and periosteitis may lead to thickening and deformity of long bones such as the sabre tibia - Histologically, gummas look like a central coagulative necrosis characterized by peripheral granumatous responses. TheTrepanosomas are scanty in these gummas and difficult to demonstrate

Late syphilis - ulcerating gumma

Congenital syphilis 􀂾 This infection is most severe when the mother's infection is recent. Treponemas do not invade the placental tissue or the fetus until the fifth month of gestation (since immunologic competence only commences then) syphilis causes late abortion, still birth or death soon after delivery or It may persist in latent forms to become apparent only during childhood or adult life. 􀂾 The out come of congenital syphilis depends on stage of maternal infection (i.e. the degree of maternal spirochataemia). In primary and secondary stages, the fetus is heavily infected and may die of hydrops in utero or shortly after birth. Liver and pancrease show diffuse fibrosis. The placenta is heavy, and pale with plasmacytic villitis. After maternal second stage, the effects of congenital syphilis are progressively less severe. 􀂾 Less dramatic visceral disease, papular lesions on skin and mucosae such as the nose snuffles, may be seen with Huchinson's teeth, and interstial keratitis. 􀂾 Children infected in utero who are sero -positive show no lesions until two or more years after birth are classified as having late congenital syphilis. The late congenital syphilis is distinctive for the triads: Interstial keratitis; Hutchinson teeth and Eight nerve deafness

TESTS FOR SYPHILIS Dark field Microscopy VDRL, RPR FTA-ABS, MHA-TP Direct Fluorescent Antibody (DFA)