tuberculous uveitis - cybersight · – ocular manifestations of tuberculosis are due to: •...
TRANSCRIPT
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Tuberculous UveitisRamana S. Moorthy, MD FACS
Associate Clinical Professor of Ophthalmology
Indiana University Medical Center: Eskenazi Hospital
Founding Partner
Associated Vitreoretinal and Uveitis Consultants
Indianapolis, Indiana
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Polling Question 1The global tuberculosis disease burden is greatest in which
part of the globe?
A. North America
B. South America
C. Sub-Saharan Africa
D. Southeast Asia
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Tuberculosis : Epidemiology• Global: WHO Global Tuberculosis Report 2015
– 9.6 Million new cases in 2014
– 1.5 million deaths in 2014 (0.4M with TB+HIV)
• Disease Burden – Incidence – total number of cases in 2014
– North and South America – 0.280M
– South East Asia – 4.0M
– Africa – 2.7M
– Middle East -0.740M
– Europe – 0.320M
– Western Pacific – 1.6M
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Tuberculosis – Global Incidence
WHO Global Tuberculosis Report 2015
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Tuberculosis – Global Distribution
WHO Global Tuberculosis Report 2015
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Tuberculosis • Latent TB infection (LTBI)
• TB Disease
– Pulmonary
– Extrapulmonary
• Uveitis
– Prevalence 0.7%-10%
• Renal Disease
– Prevalence
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Tuberculosis
• Concomitant HIV infection
– Increased risk of developing TB disease
• 7-10%/year risk if HIV + compared to 10% lifetime risk
for those with just LTBI without HIV
• 25% of HIV deaths are caused by TB disease
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Tuberculosis and HIV
WHO Global Tuberculosis Report 2015
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Tuberculosis• Drug resistant TB
– Multidrug resistant TB (MDR-TB)
• Resistant to rifampin and/or INH
– Extensively drug resistant TB (XDR-TB)
– Disease burden is highest in the poorest countries
• Treatment failures
– Lack of proper drug availability
– Non-compliance
– Increased prevalence of drug-resistance
– Higher HIV rates
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TB Disease• General symptoms
– Fevers
– Chills
– Night Sweats
– Weight Loss
– Appetite Loss
– Malaise
• Pulmonary TB Symptoms
– Cough lasting >3 weeks
• Sputum and/or hemoptysis
– Pleuritic pain with breathing and coughing
• Extrapulmonary TB
– Renal – Hematuria
– Spine – Back pain
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Tuberculous Uveitis• Etiology
– Intraocular inflammation resulting from Mycobacterium tuberculosis infection
– Transmitted by aerosolized respiratory droplets with the primary site of infection being
the lung
– High affinity for highly oxygenated tissues – Apex of lung and choroid
– Ocular manifestations of tuberculosis are due to:
• Active infection involving ocular tissue
– Primary inoculation of eye from adjacent sites – very rare
» May cause eyelid tubercle, conjunctivitis, dacryocystitis…
– Hematogenous dissemination
• Immunologic reaction to paucibacillary systemic or ocular disease
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Tuberculous Uveitis– Ocular Symptoms
• Waxing and waning course
• Progressive increase in floaters
• Worsening of vision due to progressive intraocular
inflammation, choroidal and retinal involvement or cystoid
macular edema
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Polling Question 2Tuberculosis can cause which of the following :
A. Scleritis
B. Anterior Uveitis
C. Intermediate Uveitis
D. Panuveitis
E. All of the Above
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Tuberculous Uveitis
– Ocular Signs
• Scleritis
– Nodular anterior scleritis
– Posterior scleritis with acute angle closure glaucoma
» Rare - TB should be considered in such cases
• Anterior uveitis: Mutton-fat keratic precipitates; Iris nodules; Posterior synechiae; Secondary
glaucoma; Rarely nongranulomatous
• Intermediate uveitis
– Vitreous cells and opacity
– Cystoid macular edema
» Retinal periphlebitis
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Tuberculous Uveitis– Posterior uveitis or panuveitis
» Vitreous opacities
» Disseminated choroiditis -most common presentation: Choroidal tubercles
» Deep, multiple, discrete, yellowish lesions
» Single, large elevated choroidal mass (tuberculoma)
» Serpiginous-like choroiditis
» Retinal periphlebitis-Eales disease
» Subretinal abscess in immunocompromised host
» Optic neuritis
» Acute panophthalmitis
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Tuberculous Uveitis• Testing
– Definitive diagnosis requires demonstration of mycobacteria from bodily fluids or affected
tissues
• Not accomplished in most cases of ocular TB, but...
– Acid fast staining should be performed in all cases of chorioretinal biopsy performed for uveitis unresponsive to
therapy
– Diagnosis - presumptive in most cases
• Indirect evidence
– Positive PPD or IGRAs
– Therapeutic response to anti-TB agents
– A positive PPD is indicative of prior exposure to TB but not necessarily of active systemic infection
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Tuberculous Uveitis : Testing– Positive Tuberculin Skin Test (TST)
• Interpretation depends on the size of induration and the
person’s risk factors for TB (5mm, 10mm, >15mm)
• Booster effect – Two step testing can help differentiate
or IGRA
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Tuberculous Uveitis : Testing– In the United States, PPD is considered positive requiring
intervention if:• Induration of > 5 mm in
– HIV– contact with active TB– Radiographs consistent with healed tuberculous lesions
• Induration of > 10 mm in– Diabetes– Renal failure– Immunosuppressive agents– Health care workers– Recent immigrants from high prevalence countries
• Induration is > 15 mm with no known risk factors
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Tuberculous Uveitis : Testing– False-negative skin testing occurs at a rate of 25%
• Profound acute illness
• Immunosuppression
• Corticosteroid use
• Advanced age
• Poor nutrition
• Sarcoidosis
– False positives skin tests
• Individuals infected with atypical mycobacteria
• Immunized with BCG (Bacillus Calmette-Guerin)
• Treated with intra-luminal BCG injections for bladder carcinoma
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Tuberculosis : Testing – IGRA
• Used in place of TST
• Cannot reliably differentiate LTBI from TB disease
• QuantiFERON® TB-Gold In Tube – measures concentration of interferon γ produced – against ESAT-
6, CFP-10, TB7.7 antigens
• T-SPOT®-TB - measures number of interferon γ producing cells (spots) against ESAT-6 and CFP-10
antigens
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Tuberculous Uveitis : Testing– Definitive diagnosis may require intraocular fluid analysis or tissue biopsy
• Nucleic acid amplification techniques
– PCR
– X-Pert MTB/RIF assay - Multiplex PCR – can determine if TB present in sputum and if Rifampin
resistant in 2 hours
» Not evaluated for ocular fluids yet
• Biopsy of affected ocular tissue
• Culture and Sensitivity testing - Important in sputum evaluation
– Slow growth
– Mycobacteriology laboratory required
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Tuberculous Iris Ganuloma
Photographs Courtesy of Prof. S. Rathinam
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Tuberculous Choroiditis
Photographs Courtesy of Prof. S. Rathinam
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Multifocal Tuberculous SerpiginoidChoroiditis
Photographs Courtesy of Dr. Narsing A. Rao
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Tuberculous ScleritisTuberculousScleritis
Photographs courtesy of Debra A. Goldstein, MD
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Tuberculous Sclerokeratitis
Photographs Courtesy of Prof. S. Rathinam
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Tuberculous Scleritis and Choroiditis
Photographs Courtesy of Prof. S. Rathinam
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Tuberculous Choroiditis
Photographs Courtesy of Prof. S. Rathinam
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Tuberculous Multifocal Choroiditis
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Tuberculous Retinal Vasculitis with NVD
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Pediatric Tuberculous Anterior Uveitis
Photographs Courtesy of Prof. S. Rathinam
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Pediatric Tuberculous Anterior Uveitis
Photographs Courtesy of Prof. S. Rathinam
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Pediatric Tuberculous Anterior Uveitis
Photographs Courtesy of Prof. S. Rathinam
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Anterior Chamber Tuberculous Granuloma
Photograph Courtesy of Prof. S. Rathinam
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Anterior Chamber Tuberculous Granuloma
Photographs Courtesy of Prof. S. Rathinam
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Tuberculous Scleritis in HIV
Photographs Courtesy of Prof. S. Rathinam
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Tuberculous Scleritis in HIV After Immune Reconsttitution
SR Rathinam and P Lalitha. Eye (2007) 21, 667–668.
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Tuberculous Uveitis • Differential Diagnosis
– Sarcoid uveitis
– Syphilitic uveitis
– Retinal Vasculitis
– Vogt-Koyanagi-Harada disease
– Sympathetic ophthalmia
– Serpiginous choroiditis,
– Herpes simplex or varicella zoster infection,
– Lepromatous uevitis
– choroidal granulomas from Toxoplasmosis, Toxocariasis, and Cryptococcus.
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Tuberculosis Therapy• Therapy for LTBI
– 9 months INH – definitive
• 6 months is acceptable
– Alternative – 12 dose (Weekly ) DOT of INH+Rifapentine
– Alternative – 4 months Rifampin (if INH resistance)
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Tuberculosis Therapy
– Prophylactic treatment: single agent
• Positive PPD or abnormal chest film
– If systemic treatment with corticosteroids is being considered or
– If received corticosteroids for longer than 2 weeks at doses greater than 15 mg per day
– Prophylactic treatment with INH for 6 months to a year
• If anti-TNF therapy is being considered in patients with latent TB (positive
PPD or IGRA)
– INH prophylaxis beginning at least 3 weeks prior to the first infusion
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Tuberculosis Therapy
Isoniazid Rifampin Pyrazinamide Ethambutol
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Tuberculosis Therapy• Therapy for TB disease
– Multi-drug regimen for 6 months – to ensure death of bacilli and reduce drug resistance
• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB)
– 6+ Months of therapy
• 2 months with all 4 drugs
• 4-6 months with 2 or more drugs tailored to susceptibility test results (if available)
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Tuberculosis Therapy• Complications
– Side effects of therapeutic agents
• INH
– Hepatotoxicity
– Neurotoxicity – due to pyridoxine deficiency
» Peripheral neuropathies, seizures, agitation, insomnia
» Treated with pyridoxine
• Pyrazinamide
– Hepatotoxicity
• Rifampin
– Thrombocytopenia
– Nephritis
– Hepatotoxicity
• Ethambutol
– Optic neuropathy
» Can improve with drug cessation
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Tuberculosis Therapy
• Multi-drug-resistant tuberculosis (MDRTB)
– Risk Factors for MDRTB development
» Noncompliant patients on single-agent therapy
» Migrant or indigent populations
» Immunocompromised patients – e.g. HIV
» Recent immigrants from countries where INH and rifampin are
available over the counter
• Direct observed therapy (DOT) ideal
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Tuberculosis Therapy : MDR and XDR-TB
(GROUP 2) Fluoroquinolones
1
Always use in MDR andor
XDR tuberculosis
(GROUP 3) Injectable drugs
2
Always use in MDR and d
XDR tuberculosis
(GROUP 4)
Nearly always use:
Ethionamide/prothionamide
(GROUP 5)
Used in MDR and XDR-TB
but - clinical data are sparse3
Ofloxacin
Streptomycin Ethionamide/Prothionamide Clofazimine
Levofloxacin Kanamycin Cycloserine/Terizidone
Amoxicillin with clavulanate
Moxifl oxacin Amikacin
P-aminosalicylic acid (acid salt) Linezolid
Capreomycin Imipenem
Clarithromycin
Thioacetazone
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Tuberculous Uveitis
– Corticosteroids
• Topical and systemic corticosteroids
– Should be used only with appropriate anti-tuberculosis coverage
– Intensive steroid treatment administered without appropriate
anti-tuberculosis cover leads to progressive worsening of ocular
disease
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TB – Future Directions
• New Anti-tuberculosis
drugs under
investigation
• TB vaccine