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Morning Report September 8 th , 2010

Andrea Pappalardo, MD James McAuley, MD. Morning Report September 8 th , 2010. MKSAP.

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Morning Report September 8 th , 2010

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  1. Andrea Pappalardo, MD James McAuley, MD Morning ReportSeptember 8th, 2010

  2. MKSAP • A 35-year-old man is evaluated in the emergency department for a 1-month history of chronic cough productive of blood-tinged sputum. He admits to frequent encounters with commercial sex-workers while visiting Russia, India, and Thailand. • On physical examination, temperature is 38.8 °C (100.9 °F), blood pressure is 90/50 mm Hg, pulse rate is 95/min, and respiration rate is 30/min. Thrush is noted on oral examination. Crackles are heard over the upper lung fields. • Bilateral upper lobe cavitary lesions are present on a chest radiograph. Acid-fast bacillus is found on the direct sputum smear.

  3. MKSAP • Which of the following is the best treatment option? • A. Ciprofloxacin, pyrazinamide, ethambutol, ethionamide, and cycloserine • B. Isoniazid • C. Isoniazid and rifampin • D. Isoniazid, rifampin, pyrazinamide, and ethambutol

  4. Four-drug therapy is used in patients with suspected, previously untreated TB in whom resistance patterns are unknown to allow coverage for possible multidrug resistance, followed by de-escalation of antimicrobial therapy once drug susceptibility is known. • Isoniazid, rifampin, pyrazinamide, and ethambutol are usually appropriate first-line drugs. • All four drugs are used during the first 2 months of treatment, and, depending on susceptibility testing results, treatment continues with isoniazid and rifampin for the remaining 7 months, for a total of 9 months of treatment. • Multidrug-resistant tuberculosis is resistant to more than one antituberculosis drug and at least isoniazid and rifampin.

  5. 16 yo M with cough x 1 month • Productive of yellow phlegm x 2 weeks • Night sweats x 1 week • Fatigue • Mild frontal headache • Dizziness • Occasional Epigastric pain without n/v/d/c • SOB with walking upstairs • No chest pain, wt loss, fevers, congestion, runny nose

  6. PMH • SLE • Sclerosing lupus nephritis (last biopsy 12/09) • Recent pna (LLL) (5 mo) • FMH: • Mom w/ HTN • Flu-like illness in family members • Medications: • Prednisone 10mg daily • Plaquenil 200mg daily • Famotidine 20mg po daily • Azathioprine 50mg daily • Allergies: none • Social History: Spanish Speaking, no tob/etoh/drugs

  7. Physical Exam • VS: 98, Pulse 82, RR 19, BP 101/56, O2 Sat: 98% on RA. BMI 27 • Gen: Moon facies • HEENT: PERLA, EOMI, conjunctivae clear, nares clear, oropharynx clear, no otitis • CV: RRR, No m/r/g • Pulm: breathing comfortably, CTA B • Abd: obese abdomen, soft, NTND no HSM • Ext: no c/c/e • Skin: cheeks flushed

  8. Top 3? Can’t miss? Age? Differential Diagnosis?

  9. Cough in the Immunosuppressed SLE adolescent • Infection!! • INFECTION!! • INFECTION!!!!

  10. Infectious • Viral • URI bugs • RSV • Parainfluenzae • Metapneumovirus • HIV • CMV • EBV • Parasite • Bacterial • Community Acq PNA • Pertussis • Atypical pneumonia • Fungal • Histoplasmosis • Blastomycosis • Aspergillus • PCP • Tuberculosis

  11. Non-infectious • HONC • Leukemia • Lymphoma • Mets • Pulm • ILD • Histocytosis • Pneumonia • Septic Emboli • Bronchiectasis • Allergic rhinitis • GERD • CV • CHF • Pericarditis • Myocarditis • CHF • Valvular abnormality • Endocarditis • Cardiac tumor • Arrhythmia • Rheum: SLE-related • Second Rheum condition

  12. Initial Work-up?

  13. 138 98 16 125 4.2 26 0.8 8.1 4.1 0.1 17 12 85 Labs 11.4 11.8 666 33.9 Differential: 94% N 2% L 4%M MCV 88 RDW 15 “Hypersegmented neutrophils” C3 145 (83-188) C4 29 (18-45) ESR 92 CRP 42 Blood culture: negative x 24 hrs UA: 3+ Blood, no protein, neg LE and nitrites, >20 RBCs, no WBCs, no casts

  14. How does alter your differential?

  15. Mediastinal and HilarLymphadenopathy • Anterior Mediastinal: • Substernal Thyroid Gland • Teratoma • Thymoma • Lymphoma • ALL • Large thymus of child • Disappears by age • Middle Mediastinum • Abnormality of great vessels • Bronchogenic Cyst • Esophageal duplication • Lymph nodes • Posterior Mediastinum • Neurogenic Tumors such as Neuroblastoma • HilarLymphadenopathy • Infectious • TB • Histo • Coccidiomycosis • P. westermanni • Blasto • Atypical Measles • Mononucleosis • Abscess • Metastases • Bronchogenic carcinoma • Sarcoidosis • Lupus • MCTD • Lymphoma • PAN

  16. Initial Management?

  17. Nuestro paciente… • Azathioprine discontinued • Patient had CXR as outpatient, went home • MD sees CXR, orders chest CT for following morning • Hemoptysis with SOB • Outside Hospital ED • CXR and Chest CT done • Told he has tuberculosis and needed to return to the University of Chicago to be treated

  18. Read CT Scan

  19. CT Scan • Chest CT: Hilar lymphadenopathy with central necrosis, suspicious for pulmonary tuberculosis. • Admitted and started on 4 drug therapy for presumed tuberculosis. • ID and Pulmonary were consulted

  20. So, Did you travel? • Originally told not to travel secondary to immunosuppression so withheld information • Grandmother dying in Guatemala so went there from August-September 2009 • Developed LLL pneumonia a month after return but it resolved with amoxicillin (yes this still works in pediatrics …generally… • However, never went back to “himself” and stayed extremely fatigued

  21. Does this change anything? • What infections are endemic to Guatemala?

  22. CDC says… • Malaria • Dengue Fever • Filariasis • Leishmaniasis • Onchocerciasis • Trypanosomiasis (Chaga’s Disease) • Myiasis (botfly) • Roundworms • Leishmaniasis • Hantavirus pulmonary syndrome • Leptospirosis • Histoplasmosis • Coccidiomycosis • Typhoid • Hepatitis A, B • Paragnomius westermanni • Tuberculosis

  23. But 5 months later?? • Tuberculosis • Coccidiomycosis • Histoplasmosis • Paragnomius westermanni • Paragnomius westermanni • Lung Fluke • Food borne-crabs, raw boar meat • Sub-acute and chronic lung inflammatory disease • Pseudotubercles form • Praziquantal treatment

  24. Paragnomius westermanni

  25. And maybe some others from around here: • Blastomyces • Could this be non-infectious? • Sarcoidosis • Interstitial lung disease • Lymphoma

  26. Next steps • Serologies or cultures? • Bronchoscopy vs IR vs VATS? • Bottom line: You need tissue!!!

  27. Surgery consulted for biopsy • CT guided Biopsy of left hilar LN done • Pathologist frantically calls and says to you… • What does this patient have? • I see something there ,an organism, but don’t know what it is.

  28. Final Pathology • Single Granuloma • Fibrinous exudate and interstitial chronic inflammation with lymphocytes and plasma cells. • Possible organism only seen on one level of tissue • Weakly positive with GMS stain • 20.5 mm in size • May be a fungus • AFB stain is negative.

  29. Other tests are returning • AFB cultures neg x 3 • Quantiferon neg • PPD negative • Histoplasma Ag neg • Blastomyces Ag neg • Coccidio serologies positive • Strep pneumo Ag negative • Tissue cultures from hilar LN for fungal, viral, bacterial all negative

  30. Coccidiodomycosis • Dimorphic Fungi grow few inches below the desert soil • Higher exposure in dry season followed by rainy • In endemic areas, with rising incidence • Non-specific presenting symptoms • “Fatigue”=desert rheumatism • Chest pain, cough, fever • Hemoptysis if development of pulmonary cavity • Arthralgias • “Valley Fever” • Cocci in pregnancy predicts severe disease • DM and Immunosuppression progress resolve slower and have more pulmonary complications

  31. Pulmonary Cocci • Residual Pulmonary Nodules • Thin walled cavities • Can rupture causing bronchopleural fistula • Chronic fibrocavitary pneumonia • Diffuse reticulonodular pneumonia

  32. Extrapulmonary Manifestions • 4.7% of the time. • More likely in African or Filipinos or IC hosts • Supraclavicular LAN • Drainage from the lung • Retropharyngeal abscesses can occur • Cutaneous lesions • Found on biopsy • Adults: recommend initiating treatment • Children: can observe • Prostatic Infection • Generally asymptomatic • Seen with increased PSA • On biopsy • Monoarticular arthritis • Commonly knee • Can have limited infection of synovium alone

  33. Vertebral osteomyelitis • May require repeat MR imaging to r/o impingement on spinal cord • Serial neurologic exams • May need surgical debridement • Other sites: endocrine gland, eye, liver, genital organs, kidneys, peritoneal cavity

  34. Coccidiodal Meningitis • If untreated, 95% lethal within 2 years of infection • Headache is most common • Kernig and Brudinski signs uncommon • Papilledema uncommon except in children • CSF Findings: • Serology is the best test for IDing • Profoundly low glucose • Profoundly high protein (up to 250!) • Pleocytosis (PMNs or eosinophils) • Imaging with CT or MRI: non specific findings OR vertebral artery anuerysm • Treatment lifelong with azoles +/- intrathecalamphotericin B; voriconazole used as salvage

  35. Detection of bug • Culture • Can grow on many medium, Poses health risk to lab personnel • Takes 6 days to weeks to grow • Cannot tell at this time C. immitis and C. posadasii • Commercially available DNA probes • Direct visualization on histology • “Spherules” on PAS, GMS stain • Serology • Any positive is relevant! If no disease present, with exposure, serologies are lost within a few months • 90% positive by 3 weeks • Latex Agglutination (Sens 51% Spec 89%) Lots of False Postives • Complement Fixation (Sens 89% Spec 89%) • ELISA (Sens 94% Spec 92%) • Immunodiffusion “most specific” and can be quantitative • Skin testing (not very good) • Antigen Detection

  36. IDFA Treatment Guidelines • Infectious Disease Society of America • Oral azole anti-fungal is initial first line therapy • Amphotericin B saved for severe infections or vital sites such as the spine • Surgical Debridement as necessary • Antifungal Azole Therapy • Ketaconazole (Only FDA drug for treatment of Coccidiomycosis) • Fluconazole • Itraconazole • Posaconazole • Voriconazole: Limited use, only a few cases where it is helpful • Amphotericin B has its place in severe cases • Echinocandins not found to be helpful • Adjunctive Interferon-Gamma • In some genetically susceptible patients may be useful • Trials ongoing

  37. Risk of relapse • General Rule: For IC hosts, treatment is lifelong • Galgiani, et al in Annals of Internal Medicine 2000. Comparison of oral fluconazole and itraconazole for progressive, non-meningealcoocidiomycosis: a randomized, double-blind trial. • Relapse rates after 12 months of discontinued therapy was 28% with fluconazole and 18% with itraconazole • Most studies done with AIDS patients, not in SLE • May be able to stop therapy once and check for relapse

  38. Our patient • Tuberculosis drugs discontinued • Fluconazole started presumed for life • LP done and serologies negative • Pediatric ID team following • Discussed case with Valley Fever Center of Excellence in AZ • Treatment for 9 months • Prophylaxis for times of immunosuppression

  39. Thank you for coming Dr Mc Auley!!!

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