UAB SSGIM Presentations

1. UAB SSGIM Presentations Selecting the Best Clinical Vignettes: Should our Scoring Tool Criteria be Modified? Jeremiah Newsom MD1 Lisa Willett MD1, Danny Panisko MD, FRCP2, Carlos A. Estrada MD, MS1,3 Herpes Induced Liver Injury James Callaway, MD Martin Rodriguez, MD Don’t Discount Dyspnea Deepa Bhatnagar, M.D. Lisa L. Willett, M.D. Pulmonary Infiltrates in the Non-HIV ImmunocompromisedHost Ricardo M. La Hoz, MD Jason Morris, MD

2. Don’t Discount Dyspnea Deepa Bhatnagar, M.D. Lisa L. Willett, M.D. Division of General Internal Medicine

3. Learning Objectives Identify an unusual cause of shortness of breath Recognize cognitive errors during diagnostic decision making

4. History 53 year old female Sudden onset of shortness of breath History of Congestive Heart Failure Denies Chest pain Cough Lower extremity edema

5. Past Medical History Dilated cardiomyopathy NYHA Class III Secondary to alcohol abuse Iron deficiency anemia Baseline Hemoglobin 9 g/dL Due to gynecologic blood loss Premenopausal

6. Medications Carvedilol Lisinopril Furosemide Potassium Chloride Folic Acid Ferrous sulfate Social History Lives in Birmingham No smoking history No illicit drug use No alcohol use in 10 years

7. Physical Exam T 98.6 F HR 105/min RR 25/min BP 136/79 mm Hg Oxygen saturation 85% (room air) Gen – mild respiratory distress Lungs – diffuse bilateral crackles CV – regular rhythm, no gallop Ext – no cyanosis or edema

8. Chest Radiograph

9. Chest Radiograph

10. Chest Radiograph

11. Chest Radiograph

12. Emergency Department Course Bilateral chest tubes placed Resolution of respiratory distress Laboratory Data Hemoglobin 9 g/dL MCV 62 BNP 817 pg/mL (normal 0-100)

13. Retrospective Review

14. Chest CT

15. Right Lung Biopsy

16. Right Lung Biopsy

17. Lymphangioleiomyomatosis (LAM) <1% of diffuse lung disease Seen in the 3rd or 4th decade Affects almost exclusively women 60% pre-menopausal Pathophysiology Proliferation of smooth muscle Obstruction of bronchioles and lymphatics

18. Clinical Presentation Dyspnea on exertion Often 3-5 years prior to diagnosis Spontaneous Pneumothorax 50% at presentation 80% during illness Chylothorax

19. Diagnosis Clinical Presentation High Resolution Chest CT Numerous thin-walled cysts Diffuse lung involvement +/- Tissue Confirmation Stains for actin, desmin, and HMB-45

20. Delayed Diagnosis

21. Cognitive Errors Cognitive Psychology How we reason, formulate judgments, and make decisions Usually due to shortcuts Goal is to understand How these mistakes are made How to correct them

22. Cognitive Errors Diagnostic Availability Recalling past cases Anchoring Sticking with initial impressions Premature closure Reluctance to pursue alternative possibilities once a commitment is made

23. Cognitive Errors Did the clinical course go as expected? Consider Adherence to therapy Appropriate therapy Correct Diagnosis

24. Take Home Points LAM remains an unusual cause of lung disease Cognitive errors delayed the diagnosis of dyspnea

26. UAB SSGIM Presentations Selecting the Best Clinical Vignettes: Should our Scoring Tool Criteria be Modified? Jeremiah Newsom MD1 Lisa Willett MD1, Danny Panisko MD, FRCP2, Carlos A. Estrada MD, MS1,3 Herpes Induced Liver Injury James Callaway, MD Martin Rodriguez, MD Don’t Discount Dyspnea Deepa Bhatnagar, M.D. Lisa L. Willett, M.D. Pulmonary Infiltrates in the Non-HIV ImmunocompromisedHost Ricardo M. La Hoz, MD Jason Morris, MD

27. Herpes InducedLiver Injury James Callaway, MD Martin Rodriguez, MD

28. Learning Objectives 1. Recognize herpes simplex virus (HSV) as a cause for acute liver injury in immunocompromised patients 2. Recognize the importance of empiric acyclovir therapy if HSV hepatitis is suspected Thank you for having me here today. I have a very interesting vignette this morning highlighting a case of herpes induced liver injury. The learning objectives from this vignette are to recognize herpes simplex virus as a cause of acute liver injury in immunocompromised patients and to recognize the importance of emperic acyclovir therapy if HSV hepatitis is suspected. Thank you for having me here today. I have a very interesting vignette this morning highlighting a case of herpes induced liver injury. The learning objectives from this vignette are to recognize herpes simplex virus as a cause of acute liver injury in immunocompromised patients and to recognize the importance of emperic acyclovir therapy if HSV hepatitis is suspected.

29. 21 year old Vietnamese woman Nausea & Vomiting X 4 days A twenty-one year old Vietnamese woman presented to her local emergency department with a chief complaint of nausea and vomiting for the past 4 days. She had also been experiencing symptoms of intermittent fever and diarrhea and mild abdominal pain. She sought care for these symptoms and was given a prescription for azithromycin. She began taking this antibiotic but her symptoms did not improve and approximately 4 days later she began noticing increasing abdominal pain and girth which then led to her re-presentation to the same emergency department. A twenty-one year old Vietnamese woman presented to her local emergency department with a chief complaint of nausea and vomiting for the past 4 days. She had also been experiencing symptoms of intermittent fever and diarrhea and mild abdominal pain. She sought care for these symptoms and was given a prescription for azithromycin. She began taking this antibiotic but her symptoms did not improve and approximately 4 days later she began noticing increasing abdominal pain and girth which then led to her re-presentation to the same emergency department.

30. Past Medical History SLE (nephritis) Preeclampsia (2 years prior) Hypertension Hyperlipidemia Osteopenia Medications Prednisone Hydroxychloroquine Diltiazem Rosuvastatin Furosemide Vitamin D/Calcium Her past medical history is significant for lupus and she has biopsy proven lupus nephritis. She is on chronic immunosuppresion including prednisone 30 mg daily and hydroxychloroquine. She also had recently returned from a trip to Vietnam approximately one month prior to her symptoms beginning. She denies other hepatitis risk factors or ingestions including acetominophen, tattoos, intranasal or intravenous drug use, sexual promiscuity, or a family history of liver disease. Her past medical history is significant for lupus and she has biopsy proven lupus nephritis. She is on chronic immunosuppresion including prednisone 30 mg daily and hydroxychloroquine. She also had recently returned from a trip to Vietnam approximately one month prior to her symptoms beginning. She denies other hepatitis risk factors or ingestions including acetominophen, tattoos, intranasal or intravenous drug use, sexual promiscuity, or a family history of liver disease.

31. Physical Exam T 98.4°F Pulse 104/min BP 134/76 mmHg Generalized abdominal tenderness RUQ, no rebound tenderness Flank dullness No jaundice, confusion, or asterixis The patient’s exam at her local emergency department was significant for tachycardia and abdominal tenderness and distension. The tenderness was predominately generalized but there was mild point tenderness in the RUQ. Her flanks were reported to be dull to percussion. Of note, she was not having any confusion, asterixis, or jaundice. The patient’s exam at her local emergency department was significant for tachycardia and abdominal tenderness and distension. The tenderness was predominately generalized but there was mild point tenderness in the RUQ. Her flanks were reported to be dull to percussion. Of note, she was not having any confusion, asterixis, or jaundice.

32. Testing AST 1089 ALT 1022 TBili 0.9 Alk Phos 73 PT/INR 14/1.0 BUN 56 Cr 4.8 Her initial labs at this facility were pertinent for transaminase levels in the low 1000s, a normal total bilirubin. Her CBC revealed a normal white count but a decreased platelet count of 77 thousand. Her basic metabolic profile revealed an increased creatinine from her baseline. Her initial labs at this facility were pertinent for transaminase levels in the low 1000s, a normal total bilirubin. Her CBC revealed a normal white count but a decreased platelet count of 77 thousand. Her basic metabolic profile revealed an increased creatinine from her baseline.

33. Clinical Course With these lab values, the patient was then admitted to her local hospital and her subsequent workup included an abdominal ultrasound revealing increased echotexture in the liver and also patent portal vasculature and surrounding ascites. Further lab workup including acetaminophen levels, hepatitis A, B and C testing, CMV, EBV serologies were all negative. On her second hospital day further workup including ceruloplasmin, antismooth muscle and anti-mitochondrial antibiodies were all negative. Of note, she did have an anti-nuclear antibody titered to 1:80. And thus she was begun on steroids for presumed autoimmune hepatitis. A liver biopsy was also performed that showed areas of hepatocellular necrosis with fragments of preserved hepatocytes. Despite this therapy over the next 6 days her AST and ALT continued to rise dramatically to a peak of 6009 and 4905 respectively. Her platelets also dropped significantly to 8 thousand and her INR was 4. At this point she was then transferred to UAB for liver transplant evaluation. With these lab values, the patient was then admitted to her local hospital and her subsequent workup included an abdominal ultrasound revealing increased echotexture in the liver and also patent portal vasculature and surrounding ascites. Further lab workup including acetaminophen levels, hepatitis A, B and C testing, CMV, EBV serologies were all negative. On her second hospital day further workup including ceruloplasmin, antismooth muscle and anti-mitochondrial antibiodies were all negative. Of note, she did have an anti-nuclear antibody titered to 1:80. And thus she was begun on steroids for presumed autoimmune hepatitis. A liver biopsy was also performed that showed areas of hepatocellular necrosis with fragments of preserved hepatocytes. Despite this therapy over the next 6 days her AST and ALT continued to rise dramatically to a peak of 6009 and 4905 respectively. Her platelets also dropped significantly to 8 thousand and her INR was 4. At this point she was then transferred to UAB for liver transplant evaluation.

34. Differential Diagnosis Acute Hepatitis Although the differential diagnosis for acute hepatitis is broad, the differential for such a dramatic transaminase elevation can be narrowed rather quickly. Acute Viral Hepatitis, Shock liver, Acetaminophen toxicity, and autoimmune hepatitis account for over 90 percent of cases of AST/ALT levels greater than 1000. Now, with Her clinical picture of acute liver failure, markedly elevated transaminases, and profound thrombocytopenia – All in the setting of chronic immunosuppression from her steroid therapy, we also included HSV as a potential cause of her liver injury. Because of this, empiric acyclovir therapy was initiated after transfer to our facility. Although the differential diagnosis for acute hepatitis is broad, the differential for such a dramatic transaminase elevation can be narrowed rather quickly. Acute Viral Hepatitis, Shock liver, Acetaminophen toxicity, and autoimmune hepatitis account for over 90 percent of cases of AST/ALT levels greater than 1000. Now, with Her clinical picture of acute liver failure, markedly elevated transaminases, and profound thrombocytopenia – All in the setting of chronic immunosuppression from her steroid therapy, we also included HSV as a potential cause of her liver injury. Because of this, empiric acyclovir therapy was initiated after transfer to our facility.

35. Clinical Course After being started on empiric IV acyclovir, further throat exams revealed multiple small ulcerations in the posterior oropharynx. Throat culture, along with HSV serum PCR and serologies, all eventually revealed herpes simplex virus type 2. The patient completed a 14 day course of IV acyclovir for disseminated HSV and was able to discharged with much improvement in her transaminases, platelets, and coagulopathy. After being started on empiric IV acyclovir, further throat exams revealed multiple small ulcerations in the posterior oropharynx. Throat culture, along with HSV serum PCR and serologies, all eventually revealed herpes simplex virus type 2. The patient completed a 14 day course of IV acyclovir for disseminated HSV and was able to discharged with much improvement in her transaminases, platelets, and coagulopathy.

36. Liver Biopsy Review Upon further review of the biopsy, some interesting findings are seen when looked in her particular scenario. The 1st arrow points to an area of preserved hepatocytes and the 2nd arrow identifies a focal area of necrosis with minimal amounts of surrounding inflammation. Although this pattern may seem nonspecific, it is actually helpful when trying to determine the etiology behind this patients liver injury. Different types of insults to the liver affect the liver in different pathological ways – including some types of insults which leave more of a diffuse pattern, versus some types which primariy involve the peri-portal areas, versus some which have the above, focal areas of necrosis with preserved areas as well. Upon further review of the biopsy, some interesting findings are seen when looked in her particular scenario. The 1st arrow points to an area of preserved hepatocytes and the 2nd arrow identifies a focal area of necrosis with minimal amounts of surrounding inflammation. Although this pattern may seem nonspecific, it is actually helpful when trying to determine the etiology behind this patients liver injury. Different types of insults to the liver affect the liver in different pathological ways – including some types of insults which leave more of a diffuse pattern, versus some types which primariy involve the peri-portal areas, versus some which have the above, focal areas of necrosis with preserved areas as well.

37. When looking at higher magnifications, we can see changes that are consistent with HSV induced liver injury. Specifically we see multinucleation of many cells along with margination of their chromatin to the periphery of nuclei. These two features along with a feature called molding or layering of the hepatocytes makes up what are commonly referred to as the 3 M’s of herpes hepatitis by our pathologists. Multinucleation, Margination, and Molding.When looking at higher magnifications, we can see changes that are consistent with HSV induced liver injury. Specifically we see multinucleation of many cells along with margination of their chromatin to the periphery of nuclei. These two features along with a feature called molding or layering of the hepatocytes makes up what are commonly referred to as the 3 M’s of herpes hepatitis by our pathologists. Multinucleation, Margination, and Molding.

38. Herpes Induced Liver Injury HSV-1 or HSV-2 Primary infection or reactivation Conditions: Immunocompromised Pregnancy Neonates Herpes simplex is a rare cause of hepatits or acute liver injury accounting for less than 2% of all cases. It can progress to fulminant hepatic failure and can be from both HSV-1 and HSV-2. It can be the initial presentation of a primary infection or the result of reactivation of a latent infection. When found, herpes hepatitis is primarily in patients with underlying immunosupression or patients in the 3rd trimester of pregnancy. For this reason, suspicion should be high in these patient populations. It also has been documented in the neonatal population and there are a few case reports of immunocompetent patients. Herpes simplex is a rare cause of hepatits or acute liver injury accounting for less than 2% of all cases. It can progress to fulminant hepatic failure and can be from both HSV-1 and HSV-2. It can be the initial presentation of a primary infection or the result of reactivation of a latent infection. When found, herpes hepatitis is primarily in patients with underlying immunosupression or patients in the 3rd trimester of pregnancy. For this reason, suspicion should be high in these patient populations. It also has been documented in the neonatal population and there are a few case reports of immunocompetent patients.

39. Presentation Herpes simplex hepatitis, clinically, can present very similar to the typical viral hepatitis with fever, abdominal pain, and flu-like symptoms. Mucocutaneous lesions, either oral or genital, are only seen in roughly 50 percent of cases which is one of the reasons this diagnosis is often overlooked. From a lab standpoint, the bilirubin may be low or normal – a so called “anicteric hepatitis.” The transaminases are usually markedly elevated – 5, 6, 7 thousand as was seen in our patient. Also leucopenia or thrombocytopenia may be seen in many cases. Herpes simplex hepatitis, clinically, can present very similar to the typical viral hepatitis with fever, abdominal pain, and flu-like symptoms. Mucocutaneous lesions, either oral or genital, are only seen in roughly 50 percent of cases which is one of the reasons this diagnosis is often overlooked. From a lab standpoint, the bilirubin may be low or normal – a so called “anicteric hepatitis.” The transaminases are usually markedly elevated – 5, 6, 7 thousand as was seen in our patient. Also leucopenia or thrombocytopenia may be seen in many cases.

40. Diagnosis The definitive diagnosis is usually based on the liver biopsy. Typically, there are focal areas of parenchymal necrosis with minimal surrounding inflammation. Nuclear changes as I mentioned before including margination of the chromatin and multinucleation of the cells are often seen. And also characteristic viral inclusions may occur after these nuclear changes are seen. With HSV these inclusions are typically eosinophilic and called Cowdry Type 1 inclusion bodies. PCR can be performed on the biopsy itself or in the peripheral blood or PCR or culture of mucocutaneous lesions can be beneficial. HSV serologies are specific but not sensitive. The definitive diagnosis is usually based on the liver biopsy. Typically, there are focal areas of parenchymal necrosis with minimal surrounding inflammation. Nuclear changes as I mentioned before including margination of the chromatin and multinucleation of the cells are often seen. And also characteristic viral inclusions may occur after these nuclear changes are seen. With HSV these inclusions are typically eosinophilic and called Cowdry Type 1 inclusion bodies. PCR can be performed on the biopsy itself or in the peripheral blood or PCR or culture of mucocutaneous lesions can be beneficial. HSV serologies are specific but not sensitive.

41. Treatment – Prognosis Treatment IV acyclovir Suppressive therapy Prognosis Acyclovir 62-80 % survival No acyclovir 10-20 % survival Treatment should consist of IV acyclovir, empirically, while awaiting confirmation from the biopsy or PCR if HSV is suspected. Also lifelong suppressive doses of acyclovir are likely needed. Especially in patients who remain on immunosuppressant therapy. Suspicion MUST be high for herpes simplex in at risk populations because the mortality without antiviral therapy approaches 90%. Survival reports have ranged between 62-80 % if antiviral therapy is initiated and we know that the sooner it is initiated the better. Treatment should consist of IV acyclovir, empirically, while awaiting confirmation from the biopsy or PCR if HSV is suspected. Also lifelong suppressive doses of acyclovir are likely needed. Especially in patients who remain on immunosuppressant therapy. Suspicion MUST be high for herpes simplex in at risk populations because the mortality without antiviral therapy approaches 90%. Survival reports have ranged between 62-80 % if antiviral therapy is initiated and we know that the sooner it is initiated the better.

42. Take Home Points A quick follow-up on our patient. Although she was able to be discharged with minimal elevations in her liver enzymes she has subsequently had what appears to be recurrent flares of her underlying lupus – these flares, unfortunately appear to be affecting her liver as well and she is now showing some signs of chronic liver disease including recurrent large volume ascites. The take home points for this vignette are first to recognize HSV as a potential cause for liver injury – especially in patients who are immunosuppressed. Also look for markedly elevated transaminase levels, possible mucocutaneous lesions, or hematologic abnormalities as a possible guide. Second, is to have a high suspicion in at risk populations and to use empiric acyclovir therapy if HSV is suspected. The prognosis is poor if HSV is not treated. Lastly, although what we may consider to be nonspecific with regards to a pathology report – we should not forget the clinical scenario in which the specimen was obtained. Thank you very much. If there are any questions I will take them now. A quick follow-up on our patient. Although she was able to be discharged with minimal elevations in her liver enzymes she has subsequently had what appears to be recurrent flares of her underlying lupus – these flares, unfortunately appear to be affecting her liver as well and she is now showing some signs of chronic liver disease including recurrent large volume ascites. The take home points for this vignette are first to recognize HSV as a potential cause for liver injury – especially in patients who are immunosuppressed. Also look for markedly elevated transaminase levels, possible mucocutaneous lesions, or hematologic abnormalities as a possible guide. Second, is to have a high suspicion in at risk populations and to use empiric acyclovir therapy if HSV is suspected. The prognosis is poor if HSV is not treated. Lastly, although what we may consider to be nonspecific with regards to a pathology report – we should not forget the clinical scenario in which the specimen was obtained. Thank you very much. If there are any questions I will take them now.

43. UAB SSGIM Presentations Selecting the Best Clinical Vignettes: Should our Scoring Tool Criteria be Modified? Jeremiah Newsom MD1 Lisa Willett MD1, Danny Panisko MD, FRCP2, Carlos A. Estrada MD, MS1,3 Herpes Induced Liver Injury James Callaway, MD Martin Rodriguez, MD Don’t Discount Dyspnea Deepa Bhatnagar, M.D. Lisa L. Willett, M.D. Pulmonary Infiltrates in the Non-HIV ImmunocompromisedHost Ricardo M. La Hoz, MD Jason Morris, MD

44. Selecting the BestClinical Vignettes: Should our Scoring Tool Criteriabe Modified? Jeremiah Newsom MD1 Lisa Willett MD1, Danny Panisko MD, FRCP2, Carlos A. Estrada MD, MS1,3 1The University of Alabama at Birmingham, 2University of Toronto, 3Birmingham VA Medical Center

45. Background Peer review process important in choosing clinical vignettes for presentations Limitations with current scoring tools Variation Interpretation Not standardized Psychometric properties unknown

46. Study Aim To compare two scoring tools used in clinical vignettes selection Psychometric properties Determine which elements of the scoring tool were most helpful

47. Methods Design Prospective observational study Setting Abstract vignette submissions SGIM: 2006 Los Angeles, 2007 Toronto Scoring tools (7-point Likert scale) SGIM 2006: 3 items SGIM 2007: 5 items, more descriptors

48. Statistical Analysis Cronbach’s alpha (internal consistency) Factor analysis (concepts/ constructs) STATA 10.1 software

49. Cronbach’s Alpha Measures internal consistency (reliability) Acceptable: > 0.70 – 0.80 SF-36 ® Quality of Life Domains: physical/social functioning, role limitations, vitality, mental health… Cronbach’s alpha 0.76-0.90

50. Factor Analysis Use to validate a scale Does it measure one or more concepts? SF-36 ® Quality of Life Physical, mental health Clinical vignette scoring tool Does it measure one concept? ? Quality

51. SGIM 2006 Clarity of Presentation Brevity, pertinent, grammar Significance of learning objectives Unique teaching points Relevance to clinical practice

52. SGIM 2007 Clarity Concise, complete, organized, well-written… Significance Contributes to science, unique… Relevance Impact on practice, education, research, …

53. Results Variable N SGIM 2006 484 SGIM 2007 454 Countries 2 (USA, Canada) States/ provinces > 40

54. Results

55. Cronbach’s Alpha

56. Cronbach’s Alpha

57. Cronbach’s Alpha

58. Factor Analysis 2006 One domain explained 73% of the variability 2007 One domain explained 83% of the variability

59. Limitations Different reviewers Secular trends Single academic society

60. Conclusions The two clinical vignettes selection scoring tools performed well Excellent internal consistency Measured a single domain ? quality Addition of criteria (teaching value, overall assessment) better than refinement 2007 5 item tool performed better

62. Results Inter-item correlationToronto 2007

63. Los Angeles SGIM 20063 items Clarity of Presentation Brevity, pertinence of data, grammatically structured Significance of learning objectives Unique teaching points that may not be generally known or understood Relevance of the topic to the clinical practice of general internal medicine

64. Toronto SGIM 20075 items, more descriptors Clarity of Presentation Concise, complete, organized, well-written, focused objectives Significance Clinically important, contributes to scientific knowledge, unique, interesting Relevance to general internal medicine Describes impact on clinical practice, teaching/education, or future research, places case in context

65. Toronto SGIM 20075 items, more descriptors Teaching value Offers an important diagnosis, physical examination, or management pearl Overall assessment Overall evidence of scholarship, potential for publication

66. Cronbach’s Alpha Assesses internal consistency If all scores are identical, then a = 1. If all scores are independent, then a = 0.

67. UAB SSGIM Presentations Selecting the Best Clinical Vignettes: Should our Scoring Tool Criteria be Modified? Jeremiah Newsom MD1 Lisa Willett MD1, Danny Panisko MD, FRCP2, Carlos A. Estrada MD, MS1,3 Herpes Induced Liver Injury James Callaway, MD Martin Rodriguez, MD Don’t Discount Dyspnea Deepa Bhatnagar, M.D. Lisa L. Willett, M.D. Pulmonary Infiltrates in the Non-HIV ImmunocompromisedHost Ricardo M. La Hoz, MD Jason Morris, MD

68. Pulmonary Infiltrates in the Non-HIV ImmunocompromisedHost Ricardo M. La Hoz, MD Jason Morris, MD Division of General Internal Medicine

69. Learning Objectives To outline the diagnostic approach to the immunocompromised host with pulmonary infiltrates. To review the clinical presentation of Rhodococcosis and its treatment. Put on flip chartPut on flip chart

70. History of Present Illness 52 yo WF s/p kidney transplant due to Wegener’s Granulomatosis on immunosupressive therapy

71. Past Medical History ESRD 2/2 Wegener’s Granulomatosis 03/2003 Deceased donor kidney transplant 02/2008 Hypertension Hyperlipidemia Say something like: She developed ESRD 2/2 WG’s and received a kidney transplant Dependiendo valdria la pena…. Incluir la exacerbacion de Wegeners????!!!! ESRD 2/2 Wegener’s Granulomatosis 03/2003 Fatigue, hematuria, hemoptysis Renal failure and non-nephrotic range proteinuria C-ANCA 1:640 Renal Biopsy: Pauci immune focal necrotizing granulomas Say something like: She developed ESRD 2/2 WG’s and received a kidney transplant Dependiendo valdria la pena…. Incluir la exacerbacion de Wegeners????!!!! ESRD 2/2 Wegener’s Granulomatosis 03/2003 Fatigue, hematuria, hemoptysis Renal failure and non-nephrotic range proteinuria C-ANCA 1:640 Renal Biopsy: Pauci immune focal necrotizing granulomas

72. Medications & Allergies Medications Prednisone 40mg daily Tacrolimus 6mg BID Cyclophosphamide 75mg daily TMP/SMX PJP prophylaxis Valgancyclovir CMV prophylaxis Enalapril Amlodipine Simvastatin Allergies: No NKDA Say Something like: She is on immunosuppresive therapy, PJP & CMV prophylaxis. Explicar bien para q esta en cada medicamento!!! Suena a una combinacion extrana… Prednisona, Tacrolimus y Cyclophosphamida???? Say Something like: She is on immunosuppresive therapy, PJP & CMV prophylaxis. Explicar bien para q esta en cada medicamento!!! Suena a una combinacion extrana… Prednisona, Tacrolimus y Cyclophosphamida????

73. Social History Married. Lives on a farm in Tupelo, MS. In contact with dogs, cattle and horses. No travel history. No TB risk factors. Denies tobacco, alcohol or drugs.

74. Physical Exam BP 122/62, HR 62, RR 22, T 99.9ºF, O2 Sat 89% on RA ? 95% on 2L NC Cushingoid fascies HEENT: OP clear. CV: Normal heart sounds, JVP 6cmH20 Lungs: Clear, no crackles. Her vital signs were notable for tachypnea and hypoxemia at room air. Heart and Lung exam unremarkable.Her vital signs were notable for tachypnea and hypoxemia at room air. Heart and Lung exam unremarkable.

75. Laboratory Data 11 3.3 219 33 N 89 L 4 M 7 E 5 Her CBC showed mild leucopenia and anemia. BMP with a baseline Creatinine of 1.4Her CBC showed mild leucopenia and anemia. BMP with a baseline Creatinine of 1.4

76. Imaging – Chest X-Ray

77. Imaging – Chest CT ""

78. Multiple Pulmonary Nodules

79. Multiple Pulmonary Nodules Non-Infectious Wegener’s Granulomatosis Infectious Infective endocarditis Opportunistic Infections Bacterial: TB, nocardia and rhodococcus Fungal: Cryptococcus, histoplasma, moulds and invasive aspergillosis. Our patient underwent an extensive workup for all of this conditions … all of which was negative.Our patient underwent an extensive workup for all of this conditions … all of which was negative.

80. Transbronchial Biopsy

81. Update on Microbiology BAL Culture: Rhodococcus Blood Culture: Rhodococcus Sensitive to azithromycin, vancomycin and imipenem BAL Cx 1 week after the procedure Grew Rhodococcus Admission Bc’x that where initially NGTD also grew Rhodococcus ¼.BAL Cx 1 week after the procedure Grew Rhodococcus Admission Bc’x that where initially NGTD also grew Rhodococcus ¼.

82. Pulmonary Infiltrates in the Non-HIV ImmunocompromisedHost

83. Why is this topic important? High mortality Expanded pool of immunocompromised hosts Treatments available for patients with malignancies The increase use of SOT and HSCT Prolonged survival of immunosuppressed patients with autoimmune diseases Most common infection in this type of host Mortality rates for bone marrow transplant recipients with pulmonary infiltrates and requiring mechanical ventilation approach 90%. Mortality rates for bone marrow transplant recipients with pulmonary infiltrates and requiring mechanical ventilation approach 90%.

84. General Approach Broad differential diagnosis Host risk factors Underlying disease, pre transplant serologies, organ transplanted, immunosuppresive therapy. Epidemiological and radiological clues Be aggressive in pursuing a specific diagnosis. For example, diffuse alveolar hemorrhage (DAH) rarely complicates SOT, while it is more common following therapy for acute leukemia or after HSCT. Similarly, graft-vs-host disease (GVHD), by definition, is only seen in allogeneic HSCT and not autologous HSCT.For example, diffuse alveolar hemorrhage (DAH) rarely complicates SOT, while it is more common following therapy for acute leukemia or after HSCT. Similarly, graft-vs-host disease (GVHD), by definition, is only seen in allogeneic HSCT and not autologous HSCT.

85. Rhodococcus Infection

86. Introduction Increasingly been recognized as an opportunistic pathogen. Intracellular gram positive bacteria Is a soil organism carried in the gut of many herbivores and widespread in the environment. Inhalation of soil contaminated with herbivore manure is the likely route of acquisition. Inhalation of soil contaminated with herbivore manure is the likely route of acquisition.

87. Clinical Features Sites of infection Pulmonary Blood CNS Mortality: 20-25%

88. Treatment Immunocompromised hosts 6 months 2-3 agents guided by in vitro data Commonly used drugs Macrolides: azithromycin, clarithromycin Fluorquinolones: levofloxacin, ciprofloxacin Others: rifampin, vancomycin or imipenem Since there’s a risk for the development of resistance during treatment 2-3 drugs.Since there’s a risk for the development of resistance during treatment 2-3 drugs.

89. Patient Follow Up The patient was treated with a 6 month course of azithromycin, vancomycin and imipenem. Her symptoms improved with this regime. CT chest after treatment showed complete resolution of the multiple cavitary nodules.

90. Take Home Points Pulmonary Infiltrates in the non HIV Immunocompromised Host. Use host risk factors, epidemiological and radiological clues. Be aggressive in pursuing a specific diagnosis Rhodococcus Subacute pneumonia with nodules Treatment with 2-3 drugs for 6 months.