SYPHILIS

1. SYPHILIS GebreK.Tseggay, MD February 13, 2006

2. SYPHILISINTRODUCTION • Caused by Treponema pallidum. • Transmission: sexual; maternal-fetal, and rarely by other means. • Primary and secondary syphilis in the US dropped by ~ 90 %t from 1990 to 2000, the number of cases have gone up since then. • A dramatic increase in cases in men from 2000 to 2002 reflected syphilis in MSM. • Syphilis increases the risk of both transmitting and getting infected with HIV. • Do HIV testing in all patients with syphilis.

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

8. 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.

12. “Kissing chancres”

14. Oral chancres in primary syphilis

15. 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%)

16. 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

18. Condylomata lata

19. Alopecia areata

21. SECONDARY SYPHILISDifferential diagnosis • The rash may be confused with • Pityriasis rosea (usually has a herald patch and lesions seen along lines of skin cleavage) • Drug eruptions • Acute febrile exanthems • Psoriasis • Lichen planus • Scabies • The mucous patch may be confused with oral thrush. • Malaise, sore throat, generalized adenopathy, hepatitis, & rash may be confused with infectious mononucleosis. • Fortunately, the serologic tests for syphilis are positive in 99% of secondary syphilis pts.

22. RECURRENT SYPHILITIC SKIN LESIONS • Seen in 20-30% of pts, after resolution of primary or secondary syphilis. • Recurrent lesions are usually fewer & more firmly indurated than initial lesions • Are infectious (like those in primary & sec. syphilis)

23. Lesions of syphilis resolve without treatment although person remains infected

24. 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. • Diseases known to cause occasional false-positive nontreponemal test reactions for syphilis, such as systemic lupus erythematosus (SLE), and congenital syphilis must be excluded before the diagnosis of latent syphilis can be made. • Is divided into early and late latency.

25. 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.

26. World War II Poster: Both of These Men Had Syphilis • 1/3 of untreated pts will proceed to tertiarysyphilis

27. 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.

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

30. ASYMPTOMATIC NEUROSYPHILIS • Dx: CSF abnormalities, such as pleocytosis, protein elevation, or a reactive VDRL in the absence of signs and symptoms of neurologic disease. • Some untreated secondary syphilis pts have an abnormal CSF test result

31. SYPHILITIC MENINGITIS • ‘Aseptic meningitis’ • Usually within the first year of infection, but may occur at any time after the primary stage. • CSF shows: • Lymphocytic pleocytosis • Elevated protein and usually normal glucose concentrations • VDRL test is usually reactive. • It can mimic tuberculous or fungal meningitis or aseptic meningitis of various causes. • Often involves the base of the brain and may result in unilateral or bilateral cranial nerve palsies. • Without treatment, syphilitic meningitis usually resolves, like the other manifestations of early syphilis.

32. MENINGOVASCULAR SYPHILIS • Usually occurs 5 to 10 years after the initial infection. More common in men. • Caused by cerebrovascular thrombosis and infarction due to syphilitic endarteritis and perivascular inflammation. Often with associated aseptic meningitis. • Consider when young pt with a history of syphilis has a CVA without other causes for CVA. • But, most CVAs even in patients with a reactive serologic test for syphilis are not caused by this.

33. GENERAL PARESIS • Chronic meningoencephalitis resulting in gradually progressive loss of cortical function. • Occurs 10 to 20 years after the initial infection. • Pathologically, there is a perivascular and meningeal chronic inflammatory reaction with thickening of the meninges, granular ependymitis, degeneration of the cortical parenchyma, and abundant spirochetes in the tissues. • With effective penicillin therapy, this disease has become much less common; • In the US, first admissions to mental hospitals because of syphilitic psychosis declined from 7694 in 1940 to 154 in 1968, the last year for which definite figures are available. • Physical signs are primarily those of the altered mental status. Cranial nerve palsies are uncommon. Optic atrophy is rare. The complete Argyll Robertson pupil is also uncommon, but irregular or otherwise abnormal pupils are not infrequent. Peripheral reflexes are often somewhat increased. • CSF is almost always abnormal, with lymphocytic pleocytosis and increased protein. Serum & CSF VDRL is usually reactive. • Responds well to penicillin therapy if administered early. As many as 1/3 of treated patients may develop progressive neurologic decline in later years.

34. TABES DORSALIS • Occurs 20-30 years after the initial infection. • It is uncommon. (The survey of newly diagnosed late syphilis cases in Denmark between 1961 and 1970 showed that ~ 11% of pts with late syphilis and 40% of those with clinical neurosyphilis had evidence of tabes dorsalis). 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. • Sudden and severe painful crises are a characteristic: • Usually involve the lower extremities but may occur at any site. • Severe, sharp abdominal pains may lead to exploratory surgery. • Attacks may be triggered by exposure to cold or other stresses or may arise with no obvious precipitating cause. • 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).

35. TABES DORSALIS(CONT.) • Optic atrophy is seen in 20% of cases. • Typical cases present with: lightning pains, ataxia, Argyll Robertson pupils, absent deep tendon reflexes, and loss of posterior column function. Atypical cases are difficult to diagnose. • Serum VDRL may be non-reactive in 30 - 40%, CSF-VDRL may be non-reactive in 10-20%, serum FTA-ABS is almost always reactive. • Penicillin may arrest progression but does not reverse the symptoms. Carbamazepine in doses of 400 to 800 mg/day may effectively treat the lightning pains.

36. 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.

37. LATE BENIGN SYPHILIS (THE GUMMA) • The gumma was the most common complication of late syphilis in the Oslo Study of untreated patients (1891 to 1951); rare in the penicillin era. • Usually develop 1-10 years after infection and may involve any part of the body. • Gummas may be single or multiple. Start as a superficial nodule or as a deeper lesion that breaks down to form punched-out ulcers. They are ordinarily indolent, slowly progressive, and indurated granulomata, with central healing with an atrophic scar surrounded by hyperpigmented borders. • Cutaneous gummas may be confused with skin lesions of TB, sarcoidosis, leprosy, and deep fungal infections (but, gumma is the only such lesion to heal dramatically with penicillin therapy). Gumma can also be papulosquamous type mimicking psoriasis. • T. pallidum is ordinarily not demonstrable by silver stain but can sometimes be recovered by inoculation of rabbits. • May be destructive, but responds rapidly to treatment, thus, is relatively benign.

38. LATE BENIGN SYPHILIS (Gumma) (Cont.) • May also involve deep visceral organs, particularly the respiratory tract, gastrointestinal tract, bones, larynx, lung, liver, • In earlier centuries, gummas of the nose and palate commonly resulted in septal perforations and disfiguring facial lesions. • Bone involvement may cause a characteristic symptom of nocturnal bone pain. • Radiologic abnormalities, when present, include periostitis, and lytic or sclerotic, destructive osteitis.

39. GUMMA

40. Late syphilis - serpiginous gummata of forearm

41. Late syphilis - ulcerating gumma

42. CLINICAL MANIFESTATION IN SUMMARY

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

47. NONTREPONEMAL SEROLOGIC TESTSIMPORTANT POINTS • VDRL and RPR: tests of choice for screening and monitoring response to tx. • Nonspecific; must be confirmed by treponemal test. False-positives usually have a titer of < 1:8. • VDRL and RPR titers are not interchangeable (RPR titer is often slightly higher than VDRL titer). • A nonreactive VDRL test does not exclude primary syphilis. • VDRL is positive for 99% of patients with secondary syphilis. • Consider the PROZONE PHENOMENON. Patients with very high titers of antibody may have a “negative’ VDRL; dilution of the serum results in conversion of a negative test to a positive test result. • VDRL reactivity tends to diminish in later stages of the disease • VDRL titers of treated patients may turn negative with time or may remain low-normal for long time, “serofast.”

48. TREPONEMAL TESTS FTA-ABS • Used as a confirmatory tests. • Sensitivity and specificity high. • 85% of patients with primary syphilis are reactive • 99% with secondary syphilis • > 95% with late syphilis (It may be the only test with a positive result for patients with cardiovascular or neurologic syphilis). • Remains reactive for lifein most, despite adequate therapy. Only 15-25 % of those treated for primay syphilis may turn negative by 2-3 yrs. • False positive in other treponemal diseases (pinta, yaws..) and other spirochete diseases (Lyme, leptospirosis…) MHA-TP test (microhemagglutination assay for T. pallidum; agglutination of RBCs to which T. pallidum antigens have been fixed is the basis).