Re-emerging infections: Syphilis & Tuberculosis

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1 Re-emerging infections: Syphilis & Tuberculosis Nicholas Jones Manchester Royal Eye Hospital

2 Syphilis and TB - historical plagues?

3 Syphilis incidence over 40yrs

4 Manchester:

5 Manchester: The Syphilis Capital of Europe (BMJ 2004) Doris J et al. Ocular syphilis; the new epidemic. Eye 2006;20:703-5

6 Reasons for increasing diagnosis of syphilis-associated uveitis Huge increase in disease incidence because: HAART has changed AIDS from lethal to liveable Unsafe sex increasing again (Concurrent increases in other STDs) Better diagnostic methods ELISAs improving both sensitivity and specificity PCRs

7 Syphilis and uveitis Congenital Primary N N Secondary (early, active) Y (late, latent) (Y) Late (symptomatic) (Y)

8 Secondary syphilis - skin/mucosae

9 Secondary syphilis - skin/mucosae

10 When to suspect syphilis Any uveitis with: skin rash, especially involving palms/soles or with mucosal ulcer headache history of sexually transmitted disease(s) including known HIV Any retinitis or retinal vasculitis Any unresponsive uveitis

11 Ocular syphilis - manifestations Anterior uveitis/vitritis/panuveitis

12 Ocular syphilis - manifestations Retinitis/vasculitis

13 Ocular syphilis - manifestations Retinitis/vasculitis with multifocal periretinal satellite lesions

14 Ocular syphilis - manifestations Vitritis Papillitis optic neuropathy

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17 Ocular syphilis - manifestations Placoid chorioretinitis HIV risk

18 Syphilis - investigation Treponemal tests: ELISAs including ICE, DBE FTA-ABS, TPHA, TPPA Non-treponemal tests: Rapid Plasmin Reagent (RPR) Venereal Disease Research Laboratory (VDRL) quantitative (titre >1:4 shows current activity) confirms active infection monitors treatment progress T pallidum can t be cultured T p pertenue (Yaws) and others immunologically identical Infection gives lifelong +ve treponemal test, but NOT immunity you can catch it as many times as you wish!

19 Interpreting syphilis tests

20 T pallidum PCR on intraocular fluid Sensitivity and specificity not ratified for intraocular use TaqMan probe-enhanced real-time PCR enhances specificity Vitreous may be significantly more productive than aqueous Troutbeck R et al. PCR testing of vitreous in atypical ocular syphilis. Ocular immunology & inflammation 2013;21:227-30

21 Syphilis - treatment Regime as for presumed neurosyphilis: Procaine penicillin G 2.4MU/day I/M 17/7 Probenecid 500mg QID oral 17/7 Oral steroids to: treat sight-threatening uveitis (40-60mg/day) ameliorate Jarisch-Herxheimer reaction (20mg/day) Or: benzylpenicillin 18-24MU/day I/V 17/7 Or: doxycycline 200mg BD 4/52 Or: amoxycillin 2g TDS + probenecid 500QID 4/52 UK National Guideline 2002 for management of Late Syphilis (Assoc GUM)

22 Response to treatment May take weeks to settle, but often good VA Retinal atrophy more extensive than areas of active retinitis: Large visual field defects Nyctalopia

23 MUC experience: syphilis 95% male of these, 60% MSM 30% HIV+ Age at presentation % bilateral uveitis 80% retinitis 90% syphilis diagnosis made in MUC 100% standard UK management for neurosyphilis 100% had no uveitis 3 months after finishing treatment

24 Summary: syphilis Ocular syphilis is no longer rare: think of it! Take a sexual/std history Serology is diagnostic - always include it if syphilis is possible Always liaise with GUM physician Treatment curative, but visual recovery may be delayed

25 UK TB incidence over 100yrs

26 TB Prevalence 2012 UK incidence: Manchester: 42 London: 42 12/100,000/yr

27 TB uveitis incidence Manchester Uveitis Clinic 121 from 3503 referrals in 23 yrs (3.5%) Current diagnostic rate >1/month

28 Reasons for increasing diagnosis of presumed TB-associated uveitis Genuine increasing incidence immigration Better diagnostic methods Gamma-interferon tests PCRs New manifestations recognised serpiginous-like chorioretinitis Higher suspicion in low-risk cases More patients investigated Re-investigated old steroid-resistant uveitis

29 MUC experience: TB 80% with TB uveitis were born outside UK most common: India (esp Gujurat) 80% bilateral uveitis 50% history of contact with TB none of these received TB prophylaxis 20% old TB on chest X-ray 10% active TB elsewhere 100% standard 6 months TB treatment 75% also received oral steroids 70% had no uveitis 6 months after finishing TB treatment Sanghvi C et al. Presumed tuberculous uveitis: diagnosis, management and outcome. Eye 2011;25:475-80

30 When should TB uveitis be suspected? Granulomatous anterior uveitis Uveitis with focal episcleritis or scleritis) Single or multiple choroidal lesions Papillitis with chorioretinitis Retinal vasculitis, especially if occlusive Atypical outer retinal/inner choroidal inflammations Any uveitis if patient has active/latent TB

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32 Single choroidal nodule

33 Subretinal abscess

34 Multifocal choroiditis

35 Multifocal choroiditis with papillitis

36 Occlusive retinal vasculitis (Eales disease)

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39 Gan W-L, Jones NP. Serpiginous-like choroiditis: a marker for tuberculosis in a non-endemic area Br J Ophthalmol 2013;97:644-7

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42 Other ocular manifestations Meningo-encephalitis with neuroophthalmic signs or miliary choroiditis Orbital apex syndrome Nodular scleritis

43 Manchester Uveitis Clinic Diagnosis of TB-associated uveitis 100% Qualifying/suggestive clinical signs 50% History of TB exposure or risk 100% Evidence of previous exposure Mantoux +ve AND IGRA +ve 20% Supportive evidence of previous TB exposure Ghon focus, mediastinal lymphadenopathy on CXR/CT 10% Evidence of concurrent active pulmonary or extrapulmonary TB 0% PCR evidence from intraocular fluid (future?)

44 Manchester Uveitis Clinic Management of presumed TB-associated uveitis Standard UK 6-month regime for tuberculosis: 2 months: Rifampicin, isoniazid, ethambutol, pyrizinamide 4 months: Rifampicin, isoniazid Drug intolerance 9 months total Topical and oral steroid as required for intraocular inflammation Assess results

45 Management and diagnostic dilemmas 1. The patient with presumed TB uveitis who continues chronic anterior uveitis after TB treatment Probably a non-infective immune phenomenon (also ARN etc) Toxoplasmosis) 2. The patient who develops signs suggestive of recurrent TB uveitis, after treatment, and progressively deteriorates? treat again for 12 months,? treat with different antibiotics? immunosuppress 3. The patient with severe uveitis (usually with occlusive vasculitis) who worsens during TB treatment despite high-dose oral steroids? immunosuppress at same time how much?

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47 Summary: TB Suspect the diagnosis and investigate for it Be pragmatic microbiological proof of ocular TB is rare Find a physician who understands extrapulmonary TB and will supervise treatment Reconsider the diagnosis if uveitis unresponsive

48 In conclusion: Both syphilis and tuberculosis have become increasingly common over the last 15 years The syphilis epidemic is settling again, but: Tuberculosis is likely to continue to rise Multi-drug resistant TB is also rising in incidence PCRs for intraocular use may soon steer treatment Keep your eyes peeled!

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