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By: Dr.Ahmad Shaheen

Tuberculosis Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and often deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs (as pulmonary TB(

Tuberculosis Commonly affects the lungs/pleura Extrapulmonary sites: • • • •

Lymph nodes – cervical most common-scrofula Bones/joints – spine most common – Pott’s GU system – sterile pyuria CNS – Elevated CSF WBC (lymphocytes predominant), low glucose, and high protein in TB meningitis (insidious onset) • Abdomen • Pericardium

Practically any organ can be involved

Pulmonary Tuberculosis Epidemiology Most common infectious cause of death worldwide Latent phase of TB enabled it to spread to one third of the world population 8,000,000 new cases each year 3,000,000 infected patients die

Pulmonary Tuberculosis Incidence 1985-1990 TB cases increased 55% in Hispanics and 27% in African Americans Populations at risk - Foreign-born individuals - Low socioeconomic status - Cancer pts - HIV - Cigarette smokers - TNF-a antagonists - Corticosteroids

Tuberculosis Epidemiology

Pulmonary Tuberculosis Transmission Transmitted by airborne particles 1-5 microns in size A single sneeze can release up to 40,000 droplets Ease of transmission depends on duration and proximity of contact as well as the number of bacteria excreted Infection can result from only 1-5 bacteria entering a terminal alveolus Only those with active pulmonary TB are infectious

Pulmonary Tuberculosis Transmission

Pulmonary Tuberculosis Pathogenesis Inhalation and deposition of the tubercle bacillus leads to four possible outcomes: (1) Immediate clearance of the organism (2) Chronic or latent infection (3) Rapidly progressive disease (or primary disease) (4) Active disease many years after infection (reactivation disease)

Pulmonary Tuberculosis Pathogenesis

Pulmonary Tuberculosis Primary Disease First exposure to MTB often a symptomatic Tubercle bacilli establish infection in the lung after they are carried in droplets (5 to 10 µm to reach the alveolar space Innate defense system unable to clear infection, bacilli proliferate in alveolar macrophages and kill the cells Infected macrophages produce cytokines and chemokines that attract other cells and form a tubercle Tubercle enlarges and bacilli enter lymph system

Pulmonary Tuberculosis Primary Disease Typically pul. Infiltrates: mid or lower lung fields with or without hilar adenopathy, these infiltrates non-specific in appearance and not cavitory In most cases pneumonitis clears without specific therapy and latent infections established In some cases, primary infection may progress, resembling reactivation disease

Pulmonary Tuberculosis latent infection following primary infection many persons remain asymptomatic with normal CXR • Exceptions: Nodules, pleural scarring Organisms remain latent within macrophages indefinitely Tuberculosis skin test (T-PPD) very important to discover these persons If no preventive therapy given, 1:10 persons with MTB infection will develop clinical disease at some time in their lives

Pulmonary Tuberculosis Reactivation of Disease Reactivation results when persistent bacteria suddenly proliferate (unclear as to what mechanism maintain the latent state or trigger reactivation) Reactivation occurs more likely in upper lobes and superior segment of lower Lobes Immunosuppressive conditions associated with reactivation of TB: - HIV/AIDS - Lymphoma - ESRD,DM -Corticosteroid use ** Diagnosis maybe difficult as pul sx mild or lacking.

Pulmonary Tuberculosis Diagnosis

“The first rule of TB diagnosis: is to think TB….”

Pulmonary Tuberculosis Diagnosis Diagnosis of tuberculosis in most cases clinical diagnosis based upon the clinical presentation (hx & PE)

Early diagnosis and initiation of effective therapy reducing morbidity and mortality from TB minimize the spread of infection

Pulmonary Tuberculosis Diagnosis Screening for prior infection Tuberculin skin test

Diagnosis of pulmonary TB Medical history Physical examination Chest radiograph Bacteriologic exam Other

Diagnosis Screening for prior infection Whom to screen High prevalence and high risk population

How to screen Mantoux tuberculin test (ie, purified protein derivative or PPD, tuberculin skin test)

How to interpret Determine maximum diameter of induration by palpation

Diagnosis Screening for prior infection Mantoux Test Inject intradermally 0.1 ml of 5TU PPD tuberculin Produce wheal 6 mm to 10 mm in diameter Represent DTH (delayed type hypersensitivity)

Diagnosis Screening for prior infection Read reaction 48-72 hours after injection Measure only induration Record reaction in mm

Diagnosis Screening for prior infection Mantoux test Interperation PPD >/= 5 mm: HIV patients Recent contacts of someone with TB Fibrotic changes on CXR c/w prior TB Organ transplant recipients Immunosuppressed (includes patients receiving the equivalent of 15 mg/day or more of prednisone for one month or more)

Diagnosis Screening for prior infection PPD >/= 10 mm: Recent arrivals from high-prevalence countries Injection drug users Residents and employees of high-risk settings Mycobacteriology laboratory personnel Persons with clinical conditions that place them at high risk Children <4 years, or children and adolescents exposed to adults in high-risk categories

Diagnosis Screening for prior infection PPD >/= 15 mm: Low risk people Routine tuberculin testing not recommended for low risk populations

Diagnosis Screening for prior infection Factors may affect TST Interperation: False negative Faulty application Acute TB (2-10 wks to convert) Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease

False positive BCG vaccination (usually <10mm by adulthood) Non-TB mycobacteria infection

Diagnosis Screening for prior infection BOOSTING Some people with LTBI may have negative skin test reaction when tested years after infection Initial skin test may stimulate (boost) ability to react to tuberculin Positive reactions to subsequent tests may be misinterpreted as a new infection

Diagnosis Screening for prior infection two-step testing Use two-step testing for initial skin testing of adults who will be retested within 1-3 weeks If first test (+), consider the person infected If first test (-), give second test 1-3 weeks later If second test (+), consider person infected If second test (-), consider person uninfected

Diagnosis Diagnosis of the disease Medical history Physical examination Chest radiograph Bacteriologic exam AFS Culture

other

Diagnosis Diagnosis of the disease Medical History and PE Symptoms of disease: -Productive, prolonged cough duration of ~3 weeks

-Chest pain -Hemoptysis -Fever/Chills -Night sweats -Appetite loss -Weight loss -Easily fatigued History of TB exposure, infection, or disease Past TB treatment Demographic risk factors for TB

Diagnosis Diagnosis of the disease

Diagnosis Diagnosis of the disease Chest Radiography Classical radiograph appearance Infiltration Cavitation Fibrosis with traction Enlargement of hilar and mediastinal LN In reactivaiton TB Classically fibrocavitary apical disease Primary TB Middle or lower lobe consolidation

Diagnosis Diagnosis of the disease Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower lobe May have unusual appearance in HIVpositive persons Cannot confirm diagnosis of TB!! cavity in patient‘s RUL classic" for adult-type, reactivation tuberculosis

Diagnosis Diagnosis of the disease No chest X-ray pattern is absolutely typical of TB 10-15% of culture-positive TB patients not diagnosed by X-ray 40% of patients diagnosed as having TB on the basis of x-ray alone do not have active TB

Diagnosis Diagnosis of the disease Bacteriologic Exam Specimen Collection: Obtain 3 sputum specimens for smear examination and culture Persons unable to cough up sputum induce sputum bronchoscopy gastric aspiration Follow infection control precautions during specimen collection

Diagnosis Diagnosis of the disease Three specimens optimal • Spot specimen on first visit; sputum container given to patient • Early morning collection by patient on next day • Spot specimen during second visit

Diagnosis Diagnosis of the disease Smear Examination Strongly consider TB in patients with smears containing acid-fast bacilli (AFB) Results should be available within 24 hours of specimen collection Presumptive diagnosis of TB Not specific for M. Tuberculosis

Diagnosis Diagnosis of the disease AFB Smear Sensitivity: 40-70% Specificity: 90%

Diagnosis Diagnosis of the disease Cultures Gold standard for TB diagnosis Use to confirm diagnosis of TB Culture all specimens, even if smear negative Results in 4 to 14 days when liquid medium systems used

Colonies of M. tuberculosis growing on media

Diagnosis Diagnosis of the disease Cultures Sensitivity: 80-85% Specificity: 98%

Times needed: Solid medium • 4-8 wks Liquid medium • 2 wks

Diagnosis Diagnosis of the disease Other Laboratory Tests for M.tb Direct/rapid tests for M.tb in sputum • Nucleic acid amplification\PCR • Results in 3-5 days • Limited experience, generally reliable • May help with decisions on isolation, contact investigations • Not useful for follow-up Genotyping • New technique; limited field experience • May be useful epi tool • No role in patient management

Diagnosis Summery High index of suspecion is essential Tuberculosis skin (PPD, mantoux) test important first step in identifying infected patients Lab. Techniques for MTB identification: * A.F.B. smear and cultures of resp. secretion (e.g. sputum) * A.F.B. smear and cultures of potentially infected body fluids or tissues: CSF, gastric fluid, urine, LN BX bone marrow BX, joint fluids, etc. * Rapid methods: PCR (polymerase chain reactions) and nucleic acid probes

Diagnosis of Pulmonary TB Cough 3 weeks If 1 positive, X-ray and evaluation

AFB X 3

If 2/3 positive: Anti-TB Rx

If negative: Broad-spectrum antibiotic 10-14 days

If symptoms persist, repeat AFB smears, X-ray

If consistent with TB Anti-TB Treatment

Pulmonary Tuberculosis Treatment The first rules of TB treatment are: Enough drugs (4 to start) The right drugs (antimicrobial sensitivities) Enough milligrams of each drug (patient weight) Enough doses (count doses) Enough attention to detail (monitoring of laboratory studies and clinical course)

Pulmonary Tuberculosis Treatment First-line Drugs Isoniazid Rifampin Rifapentine Rifabutin* Ethambutol Pyrazinamide

Second-line Drugs  Cycloserine  Ethionamide  Levofloxacin*  Moxifloxacin*  Gatifloxacin*  P-Aminosalicylic acid  Streptomycin  Amikacin/kanamycin*  Capreomycin  Linezolid

* Not approved by the U.S. Food and Drug Administration for use in the treatment of TB

Pulmonary Tuberculosis Treatment Active Disease Role of New Drugs Rifabutin: For patients receiving medications having unacceptable interactions with rifampin (e.g., persons with HIV/AIDS) Rifapentine: Used in once-weekly continuation phase for HIV-negative adults with drugsusceptible noncavitary TB and negative AFB smears at completion of initial phase of treatment

Pulmonary Tuberculosis Treatment Active Disease Role of New Drugs Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin): Used when -first-line drugs not tolerated; -strains resistant to RIF, INH, or EMB; or -evidence of other resistance patterns with fluoroquinolone susceptibility

Pulmonary Tuberculosis Treatment Active Disease Treatment Regimens Four drugs regimens recommended for treatment of culturepositive TB, with different options for dosing intervals in continuation phase Initial phase: Standard four drug regimen for first 2 months: • INH 300 mg • Rifampin 600 mg • PZA 15-30 mg/kg • Ethambutol 15-25 mg/kg or streptomycin 15 mg/kg Continuation phase: additional 4 months or (7 months for some patients) two drugs INH and rifampin

Pulmonary Tuberculosis Treatment Active Disease Why Extend Continuation-Phase Treatment for 3 Months? Cavitary disease and positive sputum culture at 2 months associated with increased relapse in clinical trials Extended continuation phase decreased relapses in silicotuberculosis (from 20% to 3%)

Pulmonary Tuberculosis Treatment Active Disease When to Extend Continuation-Phase Treatment for 3 Months? Cavitary pulmonary disease and positive sputum cultures at completion of initial phase Initial phase excluded PZA Once-weekly INH and rifapentine started in continuation phase and sputum specimen collected at the end of initial phase is culture positive HIV-infected with positive 2-month sputum culture

Pulmonary Tuberculosis Treatment Latent TB Infection Treatment of Latent TB Infection Need to exclude active disease before treatment (avoids single drug therapy of active TB) • CXR – if changes consistent with TB, send AFB sputum culture Single drug therapy appropriate for latent TB – bacterial load much lower compared with active TB

Pulmonary Tuberculosis Treatment Latent TB Infection Regimens: Isoniazid (INH) daily or twice weekly under directly observed therapy • 9 months of treatment is optimal • At least 6 months is needed • 12 months if treatment is interrupted

Rifampin daily • 4 months of treatment • Alternative regimen for those exposed to an INH resistant patient

Pulmonary Tuberculosis Treatment Latent TB Infection Rifampin/PZA for 2 months • Similar in safety and efficacy to 12 month regimen of INH • No longer recommended due to hepatic toxicity (including liver failure leading to death)

Pulmonary Tuberculosis Treatment Patients who require non-standard regimens Drug resistant TB Drug side effects/toxicity Other medical conditions • HIV • Renal failure • Liver disease • Conditions causing malabsorption Children (sometimes) Elderly (sometimes) Pregnant women

Pulmonary Tuberculosis Treatment Drug resistant TB MDR TB Multidrug-resistant TB (MDR TB) is TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampin XDR TB Extensively drug-resistant tuberculosis (XDR TB) is a relatively rare type of multidrug-resistant tuberculosis (MDR TB). It is resistant to almost all drugs used to treat TB, including the two best first-line drugs: isoniazid and rifampin. XDR TB is also resistant to the best second-line medications: fluoroquinolones and at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin).

Pulmonary Tuberculosis Treatment Drug resistant TB Choice of drugs depends on resistance pattern May require second line drug(s) Requires DOT Requires >26 weeks of treatment Usually requires daily therapy Monitoring for culture conversion, clinical improvement, side effects/toxicity critical

Pulmonary Tuberculosis Treatment INH resistant TB: Rifampin, PZA, and ethambutol for 6 months

Rifampin resistant TB: INH, PZA, and streptomycin for 9 months or INH and ethambutol for 18 months

PZA resistance : INH and rifampin for 9 months

MDR/XDR TB: Based on susceptibility patterns

Pulmonary Tuberculosis Treatment Drug side effects/toxicity Some side effects (e.g., nausea) almost universal; do not require modifications in treatment Some adverse events uncommon but serious, reversible if identified early; require monitoring Hepatitis Hearing loss Visual acuity, color vision Selection of drugs and dosage based on weight, liver function and renal function can prevent toxicity Limit use of hepatotoxic drugs in patients with liver disease Change dosing frequency in patients with renal disease Some adverse effects cannot be accurately predicted Hepatitis in patients without known liver disease Bone marrow suppression or destruction of red blood cells, white blood cells, platelets

Pulmonary Tuberculosis Treatment Monitoring on Treatment INH: Side effects • • • • • • •

Abdominal pain, nausea, vomiting Dark urine Icterus , hepatitis Easy bruising/bleeding Arthralgias Rash Paresthesias/weakness – peripheral neuropathy is less likely with pyridoxine • Anorexia/fatigue

Pulmonary Tuberculosis Treatment INH Elevated transaminases in 10-20% of cases – especially with EtOH Should be withheld if transaminases increase more than 3x the upper limit of normal when associated with symptoms or 5x the upper limit of normal in asymptomatic patients

Pulmonary Tuberculosis Treatment Rifampin: Side effects GI upset Thrombocytopenia Hepatitis Flu-like syndrome – if taken irregularly Multiple drug interactions Orange bodily secretions due to excretion

Pulmonary Tuberculosis Treatment PZA: Side effects GI upset Hepatitis Arthralgias Hyperuricemia – acute gout uncommon

Ethambutol: Optic neuritis: reversible decreased red-green color perception and visual acuity Not hepatotoxic

Pulmonary Tuberculosis Treatment Special Conditions: Pregnancy: No evidence that PPD testing is harmful INH: not teratogenic; hepatotoxicity may be more likely Rifampin: generally considered safe – reports of hemorrhage in the newborn Ethambutol: okay Streptomycin: avoid (congenital deafness) PZA: no published safety data Breast-feeding is not contraindicated

Pulmonary Tuberculosis Treatment Special Conditions: Pregnancy: Active TB – treat Latent TB (immunocompetent host) – defer therapy until after delivery Latent TB (HIV or recent converter) – immediate therapy with INH

Pulmonary Tuberculosis Treatment Special Conditions: HIV: • Up to 20% of patients with CD4 counts < 200 can have a normal CXR with active TB – send sputum before treatment • Recent contact with someone with active TB: treat regardless of PPD result • Extrapulmonary TB more common • Immune reconstitution • Same treatment regimens (except rifabutin instead of rifampin for patients on PIs)

Pulmonary Tuberculosis Treatment Special Conditions: Children • • • • • • •

Same as adults Dosage based on weight Fewer problems with toxicity Harder to administer Harder to monitor Pills (crushed) vs. liquid preparations Some clinicians reluctant to use ethambutol

Pulmonary Tuberculosis Treatment Special Conditions: Elderly • Same as younger adults • Dosage based on weight • Can be difficult to monitor for side effects • May not tolerate 2 or 3 x per week dosing

Pulmonary Tuberculosis Treatment Current Surgical Intervention Patients with hemoptysis first received Bronchial Artery Embolization because of the recurrent hemoptysis. Current indication of Lung Resection for pulmonary tuberculosis includes MDR-TB with a poor response to medical therapy, hemoptysis due to bronchiectasis or Aspergillus superinfection, and destroyed lung as previously reported, which are consistent with our indications. Surgery remains a crucial adjunct to medical therapy for the treatment of MDR-TB and medical failure lesions.

Pulmonary Tuberculosis Chemoprophylaxis of TB Household members and other close contacts of a patient with active TB. A positive skin test in persons less than 35 years. A positive skin test reactive in the immunosuppressed, persons with leukemia, and Hodgkin's Disease, HIV + patients with a positive TB test, The drug of choice for chemoprophylaxis is isoniazid. Prophylaxis uses only one drug. In patients who are HIV+ and TB+ and have the disease; they are treated for a minimum of 9 months, The first 2 months using isoniazid and rifampin and for the next 7 months or longer, use only 2 or 3 of the 2nd line drugs and Isoniazid/Rifampin.

Pulmonary Tuberculosis Vaccination Many countries use Bacillus Calmette-Guérin (BCG) vaccine as part of their TB control programs, especially for infants. According to the W.H.O., this is the most often used vaccine worldwide, with 85% of infants in 172 countries immunized in1993 BCG provides some protection against severe forms of pediatric TB unreliable against adult pulmonary TB, Currently, there are more cases of TB on the planet than at any other time in history urgent need for a newer, more effective vaccine that would prevent all forms of TB—including drug resistant strains —in all age groups and among people with HIV.

Pulmonary Tuberculosis Infection Prevention If active pulmonary TB is suspected: AFB isolation Negative pressure Particulate respirator masks

Isolation not required for: Latent TB Extrapulmonary TB

Pulmonary Tuberculosis Infection Prevention Isolation can be discontinued: If AFB smears x 3 are negative An alternative diagnosis is made

If patient has active TB, then: After 2 weeks of effective therapy Resolution of cough, fever Negative or “less positive” AFB smears

Extrapulmonary Tuberculosis Proportion in all TB in USA : 7% (1963) to 18% (1987) to 20% (now) Increase maybe due to HIV infection More in minorities and foreign-borns Lymphatic TB (30%) > Pleural TB (24%) > Bone and joint TB (10%) > Genitourinary TB (9%) > Miliary TB (8%) > Meningeal TB (6%) (New York, 1995)

Extrapulmonary Tuberculosis Lymphadenitis TB Most common form of EPTB Peak age: children shift to 20-40 y/o High risk: Asians, female (2x to male), HIV Hilar, paratracheal and neck lymphnodes Self-limited (>90%), a little with pulmonary calcification

Extrapulmonary Tuberculosis Lymphadenitis TB Differential Diagnosis: Non-TB mycobacteria (young age, unilateral and normal CXR) Virus or fungus infection Neoplasm

Diagnosis: Tuberculin skin test, history and CXR Total excision biopsy and culture

Extrapulmonary Tuberculosis Lymphadenitis TB Treatment Anti-tuberculous chemotherapy for 6 months course (1st line: pyrazinamide, isoniazid, rifampin, streptomycin) Surgical intervention (drainage and incision aren’t suggested)

Extrapulmonary Tuberculosis Bone and joint TB Pott’s disease Increasing since 1980s 13-25%: HIV positive in several trials Location: lumbar spine (29.5%) > thoracic spine (20.5%) > knee (13.2%) > hip (8.2%) > soft tissue or muscle (4.5%) (Los Angeles, 1990-1995) Hematogenous dissemination

Extrapulmonary Tuberculosis Bone and joint TB Pathophysiology Invasion of joint space: direct or indirect Cartilage preservation Cold abscess and sinus tract formation Fibrosis and ankylosis, calcification

Extrapulmonary Tuberculosis Bone and joint TB Clinical Presentation Tuberculous spondylitis Tuberculous osteomyelitis Tuberculous arthritis Tuberculous tensynovitis Tuberculous myositis

Extrapulmonary Tuberculosis Bone and joint TB Tuberculous spondylitis Most commonly, especially in developing countries Back pain and rigidity Vertebral body involvement and diskitis Kyphosis and paraplegia

Extrapulmonary Tuberculosis Bone and joint TB Tuberculous osteomyelitis Initial: painful mass attached to bone with soft tissue swelling Predilection to metaphysis of long bones May extend to a joint or tenosynovium Single in adults; multiple in children, elders, immunosuppressive and HIV infection

periositis

Extrapulmonary Tuberculosis Bone and joint TB Tuberculous arthritis Large weight-bearing joint like hip, knee Painful, ankylosed or swollen mono-arthropathy, limitation of motion Phemister's triad radiographic findings that is typical of tuberculous arthritis. The triad consists of: narrowing of the interosseous space , juxta-articular osteoporosis, and juxtaarticular bone erosions located peripherally.

Extrapulmonary Tuberculosis Bone and joint TB Tuberculous myositis More in immunosuppressive and AIDS Most in psoas muscle involvement Swelling, less pain; a solitary nodule with cold abscess, limitation of muscle function; iliac fossa pain or tenderness in some case

Extrapulmonary Tuberculosis Bone and joint TB Diagnosis and DDx DDx: sarcoid arthritis and pyogenic arthritis; fungus infection; neoplasm Monoarthritis, chronic pain, minimal sign Tuberculin skin test Plain radiography, open biopsy CT, MRI, CT-guided fine-needle aspiration biopsy

Extrapulmonary Tuberculosis Bone and joint TB Treatment Early diagnosis Anti-tuberculosis drugs with minimal operative intervention for abscess drainage (86% complete recovery) Operative decompression (laminectomy should be avoided) Arthroplasty

Extrapulmonary Tuberculosis Genitourinary TB Developing >> developed countries (400:13) Male/female=2:1, most 20-40y/o (45-55y/o) Vague urinary tract symptoms: painless frequent micturition is common microscopic hematuria: 50% Recurrent E. coli infection Urine pus cell, suprapubic pain, hemospermia, painful testicular swelling: all rare

Extrapulmonary Tuberculosis Genitourinary TB Diagnosis Tuberculin skin test Urine examination and culture Elevated ESR Plain film, high-dose IV urography, percutaneous antegrade pyelography Limited value: endoscopy, biopsy, ultrasonography and CT

Extrapulmonary Tuberculosis Genitourinary TB Pathology Kidney: chronic parenchymal abscess, large renal calcification; may spread to ureter, bladder, seminal visicle Bladder: bullous granulation from ureteric orifice, obstruction; fistula to rectum Epididymis: bloodstream spread, present with discharging sinus; may spread to testis

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In this intravenous urogram the right kidney and ureter appear normal, but the left pelvicalyceal system is dilated with clubbed calyces. The lower pole calyces appear to be calcified. These calcifications continue along the line of the left ureter. the ureter is irregularly narrowed. Retention of contrast in left ureter and pelvicalyceal system, but not on the right side, implies a degree of obstruction.

Extrapulmonary Tuberculosis Genitourinary TB Treatment Anti-tuberculous chemotherapy (effective) Surgery (>80%): nephrectomy, nephroureterectomy, epididymectomy and reconstructive surgery

Extrapulmonary Tuberculosis Cutaneous TB Uncommon (<1% in the west) but increase very rapidly in recent years May contagious spread Exogenous source: Tuberculous chancre and prosector’s wart Endogenous source: scrofuloderma Hematogenous source: Lupus vulgaris (apple jelly nodules) and multiple soft tissue cold abscess (most in AIDS) Tuberculous masitis: most in 20-50 y/o female

Extrapulmonary Tuberculosis Cutaneous TB Diagnosis and Treatment Excisional biopsy for AFB stain and culture ELISA and PCR Tx: chemotherapy (isoniazid is first) and surgery (excisional biopsy and debridement)

Extrapulmonary Tuberculosis CNS TB Pathogenesis and clinical presentation Tuberculous meningitis (TBM) May produce damage to vessels, infarction of brain, edema, fibrosis Predilection: base of brain In AIDS: cerebral abscess or tuberculomas Space-occupying sign: headache, seizure, paralysis, personality change, CN defects, neck stiffness, papilledema

Extrapulmonary Tuberculosis CNS TB Diagnosis and Treatment CSF: clear or slightly opalescent; elevated protein and low glucose (virus: high) AFB and culture: limited Meningeal biopsy: may contaminating CT and MRI: helpful Tx: chemotherapy, surgery and steroids

Extrapulmonary Tuberculosis Miliary TB Lympho-Hematogenous dissemination of TB Commonly affects the lungs, liver, spleen, bone marrow, kidneys, and adrenals Can occur at the time of primary infection or reactivation CXR – diffuse nodules <2 mm PPD and sputum for AFB can be negative bone marrow or liver biopsy may be helpful Chemotherapy for 9-12 months (HIV at least 12 months) or steroids (controversial, prevent reactivation and infection)

Extrapulmonary Tuberculosis Other Otologic Tuberculosis Ocular Tuberculosis Cardiovascular Tuberculosis Tuberculous Peritonitis Tuberculous Enteritis Tuberculosis of the liver and biliary tract