K. Holmes rv—Jama 2003;290:1510

Cause: Treponema pallidum

Pathophys:

In 2°, marked bacteremia is present. Tertiary (3°) types probably represent hypersensitivity reactions since few organisms are present. Gummas, from endarteritis obliterans, which causes necrosis, eg, in aortic media. Three types of neurosyphilis:

• TABES DORSALIS
• Meningovascular
• GENERAL PARESIS OF THE INSANE(GPI), primary parenchymal involvement

All 3° complications are increased in AIDS (Nejm 1987;316:1600)

Incidence = 20+/100 000 in US, increasing since 1985; spread via direct contact (venereal) with primary (1°) or secondary (2°) lesion

Sx:

1°: Painless chancre

2°: Rash, round with pigmented center; fever; headache; alopecia; eye pain from iritis

Si:

1°: Chancre with edema (looks like squamous cell cancer), and nonsuppurative lymphadenitis

2°: Macular/papular/pustular rash with pustules, annular-appearing as ages, on palms and soles; split papules at mouth corners and other moist body areas (condyloma lata); diffuse lymphadenopathy; meningitis

3°:

• Neurosyphilis: Argyll Robertson pupils (small, unequal, reactive to accommodation not light); general paresis dementia; meningovascular, strokes, meningitis and cranial nerve palsies (Nejm 1994;331:1469, 1516) most commonly seen within 3-4 yr of primary infection, esp in AIDS pts; tabes dorsalis with motor long tract and sensory losses usually in lower extremities
• Vascular including aortitis with AI and aneurysms in 10%
• Gummas in 15%; 75% are cutaneous

Congenital: Onset at age 14+ weeks even if seronegative at birth; si: rash, fever, hepatosplenomegaly, rhinitis, lymphadenopathy, elevated LFTs, CSF cells, and protein (Nejm 1990;323:1299); notched permanent (Hutchinson's) teeth, in 25%; interstitial keratitis in 50%; saddle nose

1°: 9-90 d, 20-30% develop secondary syphilis

2°: Months if no rx

1°: r/o herpes and chancroid (both tender)

2°: Obstructive pattern hepatitis (Nejm 1971;284:1422); nephrosis from immune complex disease (Nejm 1975;292:449)

3°: Cirrhosis

Lab:

Bact:Dark field shows bacteria with 8-14 spirals, ~7 m long; false positives in mouth from normal treponema flora there

CSF:Do LP 1 yr post-rx of 1° or 2° types if VDRL or FTA still positive; in meningovascular syphilis elevated protein and cells are present; VDRL positive in 50% but can be negative even if bacteria present, getting FTA hence better. Probably best to just rx for 3-4 wk without LP if asx (Ann IM 1986;104:86)

Serol:(rv—Ann IM 1986;104:368)

• VDRL or RPR is positive in 76% of 1° cases (if negative, dark field positive still), 100% of 2° cases; and 75% of 3° cases; false pos (>1/16) in mononucleosis, malaria, collagen vascular diseases, sarcoid, leprosy, yaws, pinta
• TPI is positive in 50% of 1°, 98% 2°, and 90% of 3° cases
• FTA positive in 90% primaries, 99% secondaries, 98% tertiaries; false positives in only 30% VDRL false-positive patients, some with yaws, pinta, or in 10% lupus but is atypical (beaded—Nejm 1970;282:1287); remains positive all life
• TP hemagglutinin antibody now replacing FTA in common use

Xray:Congenital type has lytic areas (bites) in long bones, subperiosteal

Rx:

(Ann IM 2002;137:255; Med Let 1999;41:89) same even if HIV positive (Nejm 1997;337:307)

Prevent by partner notification, usefulness limited (Ann IM 1990;112:539)

of early disease (1°, 2°, or latent <1 yr): 1st, benzathine penicillin (Bicillin) 2.4 million U im × 1, or azithromycin 2 gm po × 1 (Nejm 2005;353:1236, 1291) but lots of drug resistance; 2nd, doxycycline 100 mg po bid × 14 d; or 3rd, erythromycin 500 mg po qid × 14 d

of late, short of neurosyphilis: 1st, benzathine penicillin 2.4 million U im weekly × 3 wk; or 2nd, doxycycline 100 mg po bid × 4 wk

of neurosyphilis: penicillin G 2-4 million U iv q 4 h × 10-14 d; or 24 million U iv over 10-14 d continuous; or procaine penicillin 2.4 million U im qd + probenecid (Benemid) 500 mg po qid × 10-14 d; or ceftriaxone 2 gm iv qd × 10-14 d

of congenital: penicillin G 50 000 U/kg im/iv q 8-12 h × 10-14 d, or procaine penicillin 50 000 U/kg im qd × 10-14 d

If penicillin allergy: ceftriaxone im qd × 10 d, or tetracycline 2 gm qd or doxycycline 100 mg po bid × 15 d (12% failure rate) or macrolide like erythromycin 2 gm qd × 10 d (30 d for tertiary) (12% failure rate) or azithromycin but drug resistance clearly had developed to it (Nejm 2004;351:154). Rx for 28 d if late latent disease

rx crs: <1% relapse; follow VDRL, goes negative in 3-6 mo; with CNS lues, follow CSF cells; Herxheimer reaction (endotoxin sx with fever) within hours after penicillin (Nejm 1976;295:21). Longer rx in AIDS where early neurosyphilis develops (Nejm 1994;331:1469, 1488, 1516; Ann IM 1991;114:872; 1988;109:855) and penicillin rx only transiently effective since long-term cure normally depends on immunity