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SYPHILIS Dr.Eman Mohammed MD/SMSB Dermatology and Venereology  INTRODUCTION Caused by Treponema pallidum. Transmission: sexual; maternal-fetal, and rarely by other means. Syphilis increases the risk of both transmitting a nd getting infected with HIV. Do...

SYPHILIS Dr.Eman Mohammed MD/SMSB Dermatology and Venereology  INTRODUCTION Caused by Treponema pallidum. Transmission: sexual; maternal-fetal, and rarely by other means. Syphilis increases the risk of both transmitting a nd getting infected with HIV. Do HIV testing in all patients with syphilis. Taxonomy  STAGES OF SYPHILIS 1. Primary 2. Secondary 3. Latent Early latent Late latent 4. 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 border s. Mostly anogenital, but may occur at any site (tongue, pharynx, lips, fingers, nipple s, etc...)  Non-tender regional adenopathy Very infectious. Darkfield positive but serologically negative. Untreated, heals in several weeks, leaving a fain t scar. Differentials ??? “Kissing chancres” Oral chancres in primary syphilis  SECONDARY SYPHILIS Seen 6 wks to 6 months after primary chancre Diffuse non-pruritic, indurated rash, including palms & so les. May also cause: – Fever, malaise, headache, sore throat, myalgia, arthr algia, generalized lymphadenopathy – Hepatitis (10%) – Renal: an immune complex type of nephropathy with t ransient nephrotic syndrome – Iritis or an anterior uveitis – Bone: periostitis  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 (slightl y raised, oval area covered by a grayish white membrane, with a pink base that does not bleed). – Highly infectious Condylomata lata Alopecia  SECONDARY SYPHILIS Differential 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 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.  RECURRENT SYPHILITIC SKIN LESIONS Seen in 20-30% of pts, after resolution of p rimary or secondary syphilis. Recurrent lesions are usually fewer & mor e firmly indurated than initial lesions Are infectious (like those in primary & sec. syphilis) Lesions of syphilis resolve without treatment although person remains infected  LATENT SYPHILIS Positive syphilis serology without clinical si gns of syphilis. – It begins with the end of secondary syp hilis 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. – Diseases known to cause occasional false-pos itive nontreponemal test reactions for syphilis , such as systemic lupus erythematosus (SLE), and congenital syphilis must be excluded befo re the diagnosis of latent syphilis can be mad e.  LATENT SYPHILIS (cont.) 1. Early latent: – The first year after the resolution of primary or seco ndary lesions, or – A reactive serologic test for syphilis in an asymptom atic individual who has had a negative serologic test within the preceding year. – Infectious. 2. Late latent: – Usually not infectious, except for the pregnant wom an, who may transmit infection to her fetus.  1/3 of untreated pts will proceed to tertiary syphilis World War II Poster: Both of These Men Had Syphilis  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 Late syphilis is noninfectious.  NEUROSYPHILIS Divided into 5 groups, which may overlap: – Asymptomatic neurosyphilis – Syphilitic meningitis – Meningovascular syphilis – General paresis – Tabes dorsalis  ASYMPTOMATIC NEUROSYPHILIS Dx: CSF abnormalities, such as lymphocy tosis, pleocytosis, protein elevation, or a re active VDRL  SYPHILITIC MENINGITIS ‘Aseptic meningitis’ CSF shows: – Lymphocytic pleocytosis – Elevated protein and usually normal glucose concentrations – VDRL test is usually reactive. Often involves the base of the brain and may result in uni lateral or bilateral cranial nerve palsies.  MENINGOVASCULAR SYPHILIS Caused by cerebrovascular thrombosis and infarction du e to syphilitic endarteritis and perivascular inflammation. Consider when young pt with a history of syphilis has a CVA without other causes for CVA.  GENERAL PARESIS Chronic meningoencephalitis resulting in gradually progress ive loss of cortical function Physical signs are primarily those of the altered mental stat us. Cranial nerve palsies are uncommon. Optic atrophy is r are. CSF is almost always abnormal, with lymphocytic pleocytos is and increased protein. Serum & CSF VDRL is usually rea ctive.  TABES DORSALIS It’s a slowly progressive, degenerative dise ase involving the posterior columns and p osterior roots of the spinal cord. Results in progressive loss of peripheral refl exes, impairment of vibration and position s ense, and progressive ataxia. Bladder incontinence & impotence are com mon. Chronic destructive changes of the large joi nts of the affected limbs may be seen in adv anced cases (i.e., Charcot's joints).  CARDIOVASCULAR SYPHILIS Primarily aortic insufficiency and aortic a neurysm of the ascending aorta. Caused by obliterative endarteritis of th e vasa vasorum.  LATE BENIGN SYPHILIS (THE GUMMA) The most common complication of late syph ilis. may involve any part of the body. Gummas may be single or multiple. Start as a superficial nodule or as a deepe r lesion that breaks down to form punched- out ulcers. Slowly progressive, May be destructive, but responds rapidly t o treatment, Penicillin, thus, is relatively be nign.  LATE BENIGN SYPHILIS (Gumma) (Cont.) May involve visceral organs, particularly the res piratory tract, gastrointestinal tract, bones, larynx , lung, liver, Gummas of the nose and palate result in septal perforations and disfiguring facial lesions. Bone involvement may cause a characteristic no cturnal bone pain. – Radiologic abnormalities, when present, inclu de periostitis, and lytic or sclerotic, destructive osteitis. GUMMA Late syphilis - ulcerating gumma CLINICAL MANIFESTATION IN SUMMARY  TESTS FOR SYPHILIS Dark field Microscopy VDRL, RPR FTA-ABS, TPHA Direct Fluorescent Antibody (DFA)  Dark feild examination For primary syphilis  Non TREPONEMAL TESTS Rapid, Sensitive but Non specific(false-positive results) : 1.VDRL (Venereal disease research laboratory) 2.RPR (rapid plasma reagin)  TREPONEMAL TESTS FTA-ABS The fluorescent treponemal antibody absorption test Used as a confirmatory tests. Sensitivity and specificity high Remains reactive for life in most, despite adequate therapy. False positive in other treponemal diseases (pinta, yaws..) and other spirochete diseases (Lyme, leptospirosis…) MHA-TP test (microhemagglutination assay for T. pallidum; agglutinatio n of RBCs to which T. pallidum antigens have been fixed is the basis).  Treatment Primary, Secondary, Early Latent Syphilis Recommended regimen -Benzathine Penicillin G, 2.4 million units IM Penicillin Allergy* -Doxycycline 100 mg twice daily x 14 days or -Ceftriaxone 1 gm IM/IV daily x 8-10 days (limited studies) or -Azithromycin 2 gm single oral dose (preliminary data)  Latent Syphilis Recommended regimen Benzathine penicillin G 2.4 million units IM a t one week intervals x 3 doses Penicillin allergy* Doxycycline 100 mg orally twice daily x 28 days or Tetracycline 500 mg orally four times daily x 28d  Neurosyphilis Recommended regimen Aqueous crystalline penicillin G, 18-24 million units administered 3-4 million units IV ever y4 hours for 10-14 days Alternative regimen Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg orally four times daily for 10- 14 days  Neurosyphilis Penicillin Allergy Ceftriaxone 2 gm daily IM/IV for 10-14 days Consideration of cross-reactivity Pregnant patients should undergo penicillin d esensitization Other regimens have not been evaluated  Congenital Syphilis In utero transmission Divided into early and late types. Early Congenital similar to secondary syphilis, 2-8 weeks after birth, f ailure to thrive, muco-cutaneous lesions (condyloma ta lata), generalized lymphadenopathy, nasal snuffle s and skin rash. Late Congenital The onset at or near puberty. Well-known stigmata i nclude nerve deafness, interstitial keratitis, Hutchiso n's teeth (Hutchison's triad), rhagades around mouth , clutton's joint, osteitis & chondritis (saddle nose, fro ntal bossing, sabre tibia) and perforated palate.  Congenital Syphilis Proven/highly probable disease Aqueous crystalline penicillin G 100,000-150,000 u nits/kg/day, administered as 50,000 units/kg/dos e IV q 12 hours during the first 7 days and there after q 8 hours for 10 days or Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days  Syphilis-HIV Interactions Syphilis, like other genital ulcer disea ses, is associated with a three-fold to five-fold increased risk for HIV acquisi tion. Neurosyphilis may be more common i n patients with HIV infection;. Failure of treatment is more common i n patients with coexistent HIV infectio n.  Differential diagnosis of a genital ulcer Genital herpes: usually multiple, painful, superficial, and if seen early, vesicular. Chancroid: usually painful, often multiple, frequently exu dative, non-indurated that bleeds easily. Lymphogranuloma venereum: a small, papular lesion associated with a regional adenopathy. Other conditions: granuloma inguinale, drug eruptions, carcinoma, superficial fungal infections, traumatic lesions , lichen planus.  Chancroid Chancroid or soft chancre, most commoncause of genital ulcer in Africa, is caused by Haemophilus Ducreyi, a small,G-ve streptobacilli, rod like, with rounded ends, with tendency to group to form parallel short chains (school of fish) Incubation period: 3--5 days  Clinically Multiple, shallow, extremely painfull, genital ulcers with ragged undermined edges and soft base,thats bleed easily and ooze foul smelling seropus. Ulcers multiply rabidly by autoinculation. Lymphadenopathy usually unilateral,painfull, tender, matted and may suppurate (buboes) to give sinuses No systemic manifestations Chancroid  Investigations Direct smear :Gram stain, from border of the ulcer or LN aspirate - - - > school of fish appearance Culture : of LNs aspirateon enriched media PCR  Complications Phimosis and paraphimosis Urethral fistula Inguinal abscess Associated Vincent organism (fusiform bacilli) -----> more distructive---->phagedenic ulcer Spread of HIV infection  Treatment General treatment Azithromycin 1gm single oral dose Ceftrixone 250mg IM single dose Ciprofloxacin 500mg twice daily x 3 days Erythromycin 500mg 4 times daily for 7 days Chancre VS Chancroid Lymphogranuloma venereum LGV A chronic ulcerative infection of the lymphatic system caused by different serovars/serotypes of Chlamidia Trachomatis particularly L1, L2 & L3 Sexuallytransmited IP: 3--12 days  Clinically Tree clinical stages: 1ry stage: start at site of inoculation as painless transient papule or ulcer that commonly unnoticed 2ndry stage 2-6wks unilateral inflamatory enlarged tender lymphadenopathy(bubo) in the Inguinal and some times Femoral Femoral region  cont When both Inguinal and Femoral LNs are swollen, they are separated by the Inguinal Ligament giving rise to the appearance of groove sign. Buboes may lead to abscesses --- > rupture ---->sinuses  Tertiary stage Chronic (months to year) Inflamatory response with hyperplasia, ulceration, tissue distruction with lymphatic obstruction - - - - - > genital elephantiasis and fibrosis  Investigations Culture from ulcer base or bubo aspirate Serology: complement fixation test Micro-imuno-fluresent (more specific Biopsy  Treatment General treatment Doxycycline 100 mg orally twice daily for 3 wks Erythromycin 500mg 4 times daily for 3 wks