TB Intensive San Antonio, Texas November 11 14, 2014 Extrapulmonary TB Linda Dooley, MD November 13, 2014 Linda Dooley, MD has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity 1
Generalizations about Extrapulmonary TB Treated the same as pulmonary TB: same meds, DOT May be harder to diagnose; AFB culture often negative Can be (almost) anywhere Some patients have unsuspected pulmonary disease and may be infectious More generalizations Treat longer for 3 types: bone and joint, meningitis, miliary More common in immune suppressed patients (HIV, TNF blockers) More common in Asian patients 2
Pulmonary vs Extrapulmonary Pulmonary Extrapulmonary Distribution of Extrapulmonary TB Lymphatic Pleural Meningitis GI Bone and joint Miliary Genitourinary Other 3
DISTRIBUTION Patient with extrapulmonary TB may also have pulmonary involvement, even with a normal chest x ray ALWAYS GET SPUTUM FOR AFB EVEN IF THE CHEST X RAY IS NORMAL 4
Pleural Tuberculosis 2nd most common form of extra pulmonary TB (15 20%) In most of the world, TB is the most common cause of pleural effusions Higher incidence in HIV+ patients Commonly a manifestation of primary TB May progress from an exudative effusion to an empyema or bronchopleural fistula Pleural TB 5
TB Empyema Diagnosis Thoracentesis with pleural biopsy 30% yield for MTB from pleural fluid Exudative fluid with lymphocyte predominance, protein more than 4 g/l ; glucose varies Pleural biopsy and culture may double yield of + culture 6
Tuberculous pleural effusions often resolve without treatment but high risk for later pulmonary disease: treat as case anyway Treatment Same as pulmonary TB 6 months adequate if no drug resistance or immune problems Drop PZA at 2 months and leave EMB in regimen if cultures negative 7
Surgical/ Specialist Involvement For initial diagnosis: thoracentesis and pleural biopsy More rarely for repeat thoracentesis if pleural fluid re accumulates For chest tube placement and possible decortication if empyema develops Lymphatic TB 8
Most common form of extra-pulmonary TB (30-40%) Most common sites are cervical (scrofula) or mediastinal but can affect any node Diagnosis and Treatment Fine needle aspirate or open biopsy Culture for AFB Don t forget CXR and sputum More common in women, Asian population, immune suppression (HIV, TNF blockers) Treat like pulmonary TB Immune reconstitution may occur even with HIV negative patients 9
Surgical/Specialist Involvement ENT if cervical; site determines who does biopsy Initial diagnosis by fine needle aspirate or biopsy Repeat I&D if swelling worsens Site of disease determines need for surgical involvement: immune reconstitution can cause obstruction TB Meningitis 300 400 cases annually in US 1% of TB disease Even with effective treatment, case fatality high: 15 40% Early diagnosis both difficult and critical 10
Pathogenesis TB granuloma spills into subarachnoid space producing inflammation, proliferative arachnoiditis, vasculitis and communicating hydrocephalus Localized initially to base of brain Necrotizing granulomatous changes in arachnoid and blood vessels Basilar meningitis 11
Diagnosis Presentation may mimic bacterial meningitis: acute, rapidly progressive May be a slowly progressive dementia over months with personality change, social withdrawal or memory deficits Lumbar puncture: AFB stain and culture, PCR, NAAT, low CSF glucose, high protein, lymphocyte predominance Negative results do NOT exclude the diagnosis CSF examination Serial examination of the CSF by AFB stain and culture is the best diagnostic approach Use last fluid obtained; higher yield for larger volume CSF (10 15cc) Typically elevated protein, low glucose, and lymphocyte predominance Early CSF may be relatively acellular or PMN predominant Smears and cultures may yield positive results days to weeks after therapy has been initiated or may be negative 12
CT and MRI helpful in diagnosis Multiple tuberculomas along enhanced dural reflections Nov Basilar enhancement and hydrocephalus 13
Treatment Treat if meningitis suspected Early treatment essential Treatment 12 months for drug sensitive disease 18 months if no PZA Extend to 18 24 months for severe illness, slow clinical response, or immune suppression No guidelines for length of treatment for MDR or XDR TB: expert consult essential 14
CSF Penetration of TB Meds GOOD FAIR POOR Isoniazid * Rifampin * Streptomycin * Pyrazimamide Ethambutol Capreomycin * Ethionamide Quinolones * Amikacin * Cycloserine * Can Be Given IV Kanamycin * Linezolid * Steroids Adjunctive corticosteroids may be beneficial and are recommended for all children and adults being treated for TB meningitis Doses Children: 2 4 mg/kg prednisone tapered over 4 weeks Adults: 60 mg/d prednisone tapered over 6 weeks or.4 mg/kg/day dexamethasone IV tapered to.1 mg/kg/day May need longer slower taper 15
Surgery Hydrocephalus may require urgent shunting. Serial LP and steroid therapy may suffice for Stage I patients awaiting response to antibiotics. Shunting should not be delayed in patients with stupor, coma or progressive neurologic signs. Nov 2009 Surgical/Specialist Involvement ER doc, radiologist or hospital doc for initial LP for diagnosis Neurosurgeon for shunt placement if needed later: surgery need can be urgent 16
Case: HIV+ man with abnormal MRI MRI done after fall Extensive work-up all negative except +QFT Empiric Rx for TB meningitis tried without reporting and drug induced hepatitis DOT begun: pt. able to tolerate TB Rx without PZA 17
Case: 20 yo Pakistani woman with severe headache and swollen neck nodes Fine needle aspirate: granulomatous tissue Normal CXR Consultant recommended LN biopsy for better chance MTB and sensitivities Pt declined: did not have $8000 required down payment Abnormal CT head; no LP done Observed induced sputum collection done by NCM had positive NAAT Drug sensitive MTB from sputum One month later also grew TB from neck aspirate Headache resolved on TB therapy 18
Pericardial TB Pericardial TB 19
Pericardial TB Uncommon and difficult diagnosis Presents with acute or insidious onset; nonspecific symptoms Ultrasound helpful; acid fast studies may not be positive Surgery for progressive tamponnade or recurrent effusions on TB Rx Steroids reduce mortality and need for surgery or repeat pericardiocentesis: start at 60 mg/d 1st month and reduce over 11 weeks Surgical/Specialist Involvement Cardiothoracic surgeon essential for initial diagnosis as well as for management of recurrent effusion or tamponnade May require urgent management Pericardial stripping may be needed 20
Bone and Joint TB Skeletal TB Spinal TB (Pott s disease) most common location: 40% Next most common: hip (40%) and knee (10%) Can be anywhere Frequently delayed diagnosis X ray not helpful in distinguishing other infectious destructive etiology 21
Diagnosis Joint aspiration: WBC may be granulocytes or lymphocytes WBC count varies widely Protein 4 6 g/dl; glucose may be low Acid fast culture yield high (up to 80%) Presence of positive smear much lower (20%) Treatment Standard TB therapy with extended treatment 12 months minimum but extend for slow or uncertain response 22
Surgical/Specialist Involvement Orthopedist, primary care, or rheumatologist may do initial arthrocentesis for diagnosis Surgery may be needed if bone/joint stabilization required or if prosthesis needs to be removed With spinal TB, neurosurgery or spine surgeon involvement essential for spine stabilization (external or surgical) Effective treatment may preclude need for surgery Soft Tissue TB 23
Soft Tissue TB Often adjacent to bony and may be direct spread from bony structure or may erode into bone: can be difficult to know if bone involved If not sure if bone involved, treat like skeletal TB (longer duration) I&D of abscess will only be diagnostic if acid fast cultures done Surgical involvement for diagnosis and management of large abscesses Gastrointestinal and Peritoneal TB Peritoneal TB 10% extra pulmonary GI tract: any site possible but more common terminal ileum and cecum then rest of colon Often delayed diagnosis TB bacilli may be ingested rather than inspired: consider early if patient drank or ate unpasteurized milk products Acid fast cultures frequently negative: pathology caseating necrotizing granulomas 24
Peritoneal TB Laparoscopic view of peritoneal granulomas Peritoneal TB: laparoscopic view of spiderweb adhesions 25
Treatment If cultures negative or pending, assume PZA resistance Esophageal TB Duodenal TB Consider the age of your patient and possible childhood exposure to M. bovis 84 yo man with normal CXR 26
Surgical/Specialist Involvement Gastroenterologist or general surgery may make initial diagnosis Patient may need paracentesis for initial diagnosis or management of recalcitrant ascites Urogenital TB 27
Genitourinary TB 10 15% extrapulmonary TB Often insidious onset, subtle nonspecific symptoms, delay in diagnosis Hematogenous spread from primary site, often years after infection Any part of GU tract may be affected Ureteral abnormalities (multiple beading strictures); may be virtually diagnostic of renal TB 28
Renal TB May have pyuria or hematuria or both Acid fast cultures of urine for sterile pyuria May need more than 3 specimens of first morning urine collection Urine AFB studies not always positive NAAT testing may be helpful but negative result does not preclude diagnosis Surgery or stenting for obstruction Prostatic TB 29
Testicular TB Uterine TB 30
Female Genital TB With Fallopian tube involvement, unlikely that preservation of fertility possible since usual scarring Often diagnosed by pathology after hysterectomy: treat even if involved organ removed Surgical/Specialist Involvement Urology or gynecology involved in initial diagnosis Urologist essential if renal obstruction develops for ureteral stent placement and removal Obstruction may develop after therapy underway: immune reconstitution 31
Other TB Laryngeal TB Tuberculous Otitis Media 32
TB Mastoiditis XXXXXXXXXX Adrenal TB 33
Adrenal insufficiency and TB May have unsuspected adrenal involvement alone or with disseminated TB Assessment of adrenal function if slow response or hypokalemia, hyponatremia, hypotension Don t forget adrenal insufficiency possiblity if steroids were stopped after long use Ocular TB 34
Ocular TB Diagnosis made by ophthalmologist Diagnosis of exclusion: patient should be followed by ophthalmology during TB treatment No cultures available Treat same as pulmonary TB TB of the Skin 35
Dermatologic TB May be hematogenous or direct spread May be injection: accidents in pathology or microbiology lab Treatment same as pulmonary TB What s left?? 36
TB Everywhere Miliary or Disseminated TB Tiny lesions spread throughout the body Distinctive pattern on CXR or CT 37
Miliary TB Pulmonary involvement may not be present Frequently subacute presentation with fever and weight loss More rarely can be a fulminant sepsis like presentation with acute onset and rapid deterioration (usually fatal) Liver biopsy may be helpful Blood cultures may be positive if acid fast studies done All AFB may be negative Treatment of Disseminated TB Prolonged treatment needed: 12 months or more Cultures may be negative: paucibacillary disease Don t let negative cultures or normal CXR tempt you to shorten therapy 38
Thank you Don t forget to get sputum AFB even if you think only extrapulmonary TB 39