Western States Pediatric Pulmonary Case Conference May 26 th , 2010

1. Western States Pediatric Pulmonary Case ConferenceMay 26th, 2010 Presented by Kathryn Akong, MD,PhD Pediatric Pulmonology Fellow, UCSD

2. Our Case Setting: December, inpatient consultation requested by UCSD pediatric hospitalist • Patient: 16 yo, presenting with fever, dyspnea and pleuritic chest pain • history of Crohn’s disease • recent admission for fever, abdominal pain; discharged 4d prior to this admission

3. Pertinent History • Diagnosed with Crohn’s disease 15mo prior to admission • diagnosis made by endoscopy, and biopsies (pan-colitis, crypt abscesses) • complicated by recurrent pancreatitis, thought to be related to IBD flares • required chronic steroids and infliximab for remission • started infliximab 6 mo ago, weaned off steroids 4 mo ago • last dose infliximab given 2 mo prior to admission

4. Pertinent History • Recent admission 1 week prior for abdominal pain • No clinical or laboratory evidence of IBD flare • Remained clinically stable, no respiratory distress or hypoxia • Infliximab dose held due to concern for possible infection • Discharged with 3d course of ciprofloxacin for possible UTI

5. Pertinent History • Medications: Amitriptyline qHS, Omeprazole qday, Infliximab IV q2mo • SH: Parents separated, lives with mom and sister. No tobacco smoke exposure. • FH: Maternal grandmother has RA, mother has DM2, uncle has MS

6. CXR at prior admission

7. CT Abdomen—Lung Cuts “Peripheral nodular lung infiltrates, right greater than left, likely due to infectious process, possibly opportunistic”

8. CT Chest

9. CT Chest “Innumerable sub-pleural/peripheral nodular-reticulonodular opacities noted most prominently in the lung bases with more confluent dependent opacification of lung bases” What should be done next?

10. CT-Guided Needle Biopsy “Severe acute and chronic inflammation, with small foci of necrosis consistent with abscess. No micro-organisms identified with special stains”

11. Now What? • No empiric antibiotics given, only 3d course of ciprofloxacin for possible UTI • Discharged home with close follow up in GI and ID clinic

12. Case Continued • Re-admitted 4 days after discharge, for worsening pleuritic pain and dyspnea • Pulmonary consultation on hospital day #1: • new fevers to 102, and non-productive cough at home • denied abdominal pain, diarrhea or hematochezia • normal oxygen saturation on RA, on supplemental oxygen for dyspnea • Afebrile, RR 20’s • decreased breath sounds at bilateral bases

13. CXR “Development of small bilateral pleural effusions and bibasilar opacities representing compressive atelectasis and/or pneumonia”

14. CT chest * * “Multiple mass lesions in lungs with new bibasilar consolidations and bilateral pleural effusions. Many of the masses were not present on previous examination, and masses noted previously have enlarged.”

15. Multiple Lung Nodules Malignancy Metastatic solid tumors Non-Hodgkins lymphoma Primary pulmonary lymphoma Infection • Abscesses • Bacteremia • Recurrent aspiration • Septic Emboli • Septic thrombophlebitis • Endocarditis • Fungi • Histoplasmosis • Coccidioidomycosis • Cryptococcus • Invasive Aspergillosis Inflammatory Wegener’s granulomatosis Rheumatoid Arthritis Lymphomatoid Granulomatosis Amyloidosis Sarcoidosis Pulmonary AVMs Pneumoconioses Paragonimus

16. Laboratory Studies Electrolytes normal ESR >140, CRP 7.0 12 Albumin 3.7 AST 60 ALT 110 Alk phos 602 Amylase, lipase normal 21 555 36 Elevated, stable from prior 80P/1B/12L ANA, other autoimmune serologies all negative

17. Microbiology Studies CT guided needle biopsy: Bacterial culture: negative Fungal culture: negative AFB smear/culture: negative MTD NAAT: negative Cocci serology: negative Quantiferon test: negative HIV antibody: negative Bronchoalveolar lavage fluid: Bacterial,fungal cultures: negative AFB smear/culture: negative MTD NAAT: negative Pleural fluid: Bacterial,fungal cultures: negative AFB smear/culture: negative MTD NAAT: negative

18. Lung Wedge Biopsy * “Granulomatous inflammation with microabscess formation” Pathologist comment: Necrobiotic granulomas in the lung have been reported in the literature in the context of Crohn disease (European Respiratory Review 2009; 18:111, 47-50). The inflammation in the current case shows more necrosis and abscess formation than described in this article, making an infectious etiology more of a consideration. However, histologic stains for bacteria, fungi and acid-fast organisms (AFB and FITE) are negative on the tissue sections. Please correlate with microbiologic culture results.

19. Final Answer? Granulomatous Pulmonary Nodules related to Crohn’s Disease

20. Crohn’s Disease • Immune-mediated inflammatory disease, can affect any portion of GI tract • Clinically characterized by GI manifestations (abdominal pain, diarrhea, hematochezia) • Histologically characterized by non-caseating granulomas in GI tract • Up to 20% present with extra-intestinal symptoms, such as: • arthritis • uveitis • anemia • Pulmonary involvement is rare • pulmonary fibrosis • vasculitis • bronchitis • laryngotracheitis • pulmonary nodules

21. Lung Nodules in Crohn’s Disease • Unclear prevalence, only case reports available (Mayo clinic review estimates 0.1%) • Presenting symptoms include dyspnea (64%), cough (36%), fever (27%) • Can precede diagnosis of IBD • Nodules tend to be peripheral, basilar • Histology usually with some degree of granulomatous inflammation • Important to rule out any infectious etiology • Case series reported resolution of lung pathology after infliximab or steroid therapy Casey et al, Am J Surg Pathol 2003; 27(2): 213–219 Krishnan et al, Pediatrics 2006; 117(4):1440-43

22. Pediatric Case Reports 11yo M with cough, dyspnea 14 yo F with CD, fever/cough/back pain Al-Binali et al, Pediatr Pulmonol 2003; 36:76–80 Krishnan et al, Pediatrics 2006;117:1440-1443

23. Patient Follow Up • No evidence of infectious process • Infliximab resumed, first dose given in hospital • Clinical improvement • Seen in Pulmonary clinic 1mo later, still doing well

24. Follow Up Chest CT 3 wks later 2 mo later

25. Thank You!