Managing Complex Cases My heart is racing Amee Patrawalla, MD April 7, 2017 Case 1 Rutgers, The State University of New Jersey Rutgers, The State University of New Jersey Case 1 29 year old physician from South Asia who presents with palpitations and dizziness while at work Her pulse is 200 beats per minute EKG shows supraventricular tachycardia which coverts to normal sinus rhythm with adenosine Case 1 She had a similar episode 3 years ago In retrospect, she has had a dry cough x 2-3 months but has been too busy to get it evaluated No other symptoms TST negative 6 months previously Routine labs are normal 1
Which of the following would you do? A. Treat for community acquired pneumonia and repeat CXR in 1 month B. Place in respiratory isolation and obtain sputa for bacterial and mycobacterial cultures C. Treat her empirically for tuberculosis disease D. Obtain baseline pulmonary function testing and begin treatment for sarcoidosis Case 1 Induced sputum x 3 AFB smear negative QuantiFERON Gold + Bronchoscopy performed BAL smear negative MTB PCR failed Started on multidrug TB therapy and remained on home isolation for 2 weeks Cultures MTB positive 4 weeks later 2
Smear-Negative TB Sputum smear microscopy sensitivity ~ 50% Even lower in HIV and children 5000-10,000 bacilli = smear positive Increasingly common, especially in high HIV settings 35 40% of US cases Shah, IJTLD, 2012 Tostmann, CID, 2008 Smear Negative TB (1993 2008, US) Smear Negative TB Associated with SNTB Incarcerated Foreign birth Lower mortality HIV Age < 14 Not clear association Homeless IDU Alcohol use Less Likely to have SNTB Hispanic African American Smear negative TB accounts for 13-22% of TB transmission Up to 1/4 the number of cases as smear positive index cases Associated with diagnostic and treatment delays, which may lead to additional transmission Shah, IJTLD, 2012 Tostmann, CID, 2008 (Netherlands) Hernandez-Garduno, 2004 (Vancouver) Behr et al, Lancet, 1999 (San Francisco) 3
Smear-Negative TB Is common and transmissible Infection control measures are necessary Contact tracing is essential, but is often delayed Rapid diagnostic tests are moderately sensitive and can speed up diagnosis, isolation and treatment Treatment similar to smear positive TB Empiric therapy may be needed I m coughing a lot recently Case 2 Rutgers, The State University of New Jersey Case 2 45 y.o. incarcerated woman brought to hospital ED Reports cough, fevers, sweats and weight loss for 2 months History of injection drug use HIV negative No prior treatment for TB AFB Smear negative x 3 4
At this point you would A. Treat for pneumonia and transfer back to prison B. Maintain respiratory isolation and start empiric TB treatment C. Do nothing and await culture results, knowing culture is more sensitive than smear D. Refer to Surgery for an open lung biopsy Case 2 AFB smear negative Started on multidrug TB regimen Cultures remain negative with minimal improvement in CXR Symptoms improve Culture Negative Pulmonary TB Clinical and radiologic picture of active TB Cultures remain negative Paucibacillary Incorrect specimen processing Temporal variation in bacteria shedding Culture negative TB Perform at least 3 quality sputum exams Consider other diagnostics such as bronchoscopy, rapid tests Up to 15-20% of reported TB cases in US 5
Culture negative TB Culture negative TB 4 month regimen of isoniazid and rifampin has been shown to have a 1.2% relapse rate GeneXpert MTB/RIF may have some utility ATS/IDSA/CDC 2003 Dutt, 1989 Marlowe, 2011 Zeka, 2011 Case 3 I have a nagging dry cough Case 3 58 y.o. Filipino woman who underwent orthotopic liver transplantation about 1 year previously Persistent dry cough x 3 months 10 lb. weight loss No fevers, chills or other symptoms Rutgers, The State University of New Jersey 6
Case 3: Past Medical History TST + in past - CXR normal - Not treated Hepatitis B with Hepatocellular carcinoma (HCC) diagnosed 1.5 years ago OLT 1 year previously Recurrent HCC on sorafenib, s/p HACE Other meds: prednisone, sirolimus, tenofovir, trimethoprim/sulfamethoxazole Case 3: Microbiology Smear Culture Sensi 8/4 Doubtful MTB pansens 8/5 Neg Neg 8/7 Neg (BAL) MTB 8/21 1+ MTB Which drug is most likely to significantly interact with patient s current medications? A. Ethambutol B. Pyrazinamide C. Rifampin D. Rifabutin E. None will interact Case 4: Treatment Treatment was complicated by multiple drug interactions, intolerance and underlying active liver disease Multiple treatment interruptions and changes in regimen Additional invasive procedures Unstable, multifactorial liver disease Resulted in tremendous anxiety and disruption for patient 7
U/L Case 4: Lab data 140 120 100 80 60 40 20 HACE RBT, IPE initiated RBT, IPE Meds Held RBT, INH Rad. Worsening: RBT,IPE, Moxi, PAS Meds held AST ALT Solid Organ Transplant and TB TB in SOT patients is 20-74 times higher than general population 1.2%-6.4% prevalence in developed countries Up to 12% in endemic countries Most cases occur in 1 st year after transplant Reported mortality as high as 20-30% Not a well studied field 6/22/2009 7/6/2009 7/20/2009 8/3/2009 8/17/2009 8/25/2009 9/2/2009 9/10/2009 9/17/2009 9/21/2009 10/5/2009 10/19/2009 11/2/2009 11/16/2009 11/30/2009 12/10/2009 12/14/2009 12/16/1009 12/28/2009 1/11/2010 1/25/2010 2/8/2010 2/22/2010 3/15/2010 3/29/2010 4/12/2010 4/26/2010 5/17/2010 5/28/2010 American Journal of Transplantation 2013; 13: 68 76 SOT and TB Disease Recognized risk factors Prior residence in high incidence country Prior untreated TB CXR with evidence of healed TB Transplant rejection resulting in increased immunosuppression Dialysis duration (Renal) Hepatitis C (Renal) SOT and TB Disease Vast majority are reactivation < 5% donor derived infections Up to ½ of cases are disseminated or EP Classic cavitary PTB rare Negative pre-transplant TST common in posttransplant cases Use TST + IGRA in high risk settings Use CXR and CT results in high risk but negative TST/IGRA 8
SOT and TB Treatment TB infection Treat if old, untreated disease, donor TST+ or recent contact, or recipient has recent exposure May not tolerate IPT until after transplant (e.g. liver) Rifampin x 4 months if can complete pre-sot Increase in LFTs may not be due to INH in pts with OLT INH RPT viable option TB disease Rifabutin fewer drug interactions Summary Smear negative, culture negative TB present diagnostic and treatment challenges Maintain index of suspicion, especially in known risk groups Managing comorbidities requires multidisciplinary approach Partner with and educate those in community most likely to see certain risk groups American Journal of Transplantation 2013; 13: 68 76 9