ID Case Conference April 9, 2008

1. ID Case Conference April 9, 2008 Gretchen Shaughnessy, MD Clinical Fellow Dept of Infectious Diseases

2. CC: SOB • 46M presented to PCP with SOB and cough productive of white sputum. No hemoptysis, cough had been progressive over the past 3 weeks. He had been on Biaxin x 10 days without improvement. He’d also noticed some orthopnea, but denied any post-nocturnal dyspnea. Over the past 4-6 weeks he reported a 20lb wt loss and intermittent night sweats. Admitted to Outside Hospital for further workup.

3. HPI • During admission to Outside Hospital the patient had a normal echo (no pulm HTN), chest CT with moderate R pleural effusion and LLL interstitial process. • Sputum cultures and pleural fluid analysis and cultures were done. • Bronchoscopy with biopsy done day 6 of hospitalization, complicated by tension pneumothorax requiring chest tube placement. • Despite broad specturm antibiotics and chest tube placement his respiratory status declined from 11/14-11/23. Transferred to UNC MICU.

4. PMH • HTN • DM – type II • GERD • Hiatial Hernia • Hyperlipidemia • h/o R shoulder surgery in 2001 • CRI – baseline Cr 1.6

5. Medications • Allergies – NKDA • Atenolol 100mg daily • Nexium 40mg daily • Glyburide 5mg po BID

6. Antibiotic History • 11/4-11/14 Biaxin • 11/14-11/23 Azithromycin & Ticaricillin/clavulanate • 11/21-11/23 Methylpredisolone 60mg IV q8h

7. Social History • No tob, ETOH, or drugs. • Currently works in construction, former truck driver. A few weeks ago was sweeping parking lots and exposed to a lot of dust. • No recent sick contacts. • No recent travel. • Frequently rides in a friend’s van that is used to transport chickens and rabbits (patient has never encountered the animals in person) • History of travel to the southwest as a truck driver, but none in the past 2 years. • Denies HIV risk factors, has never been tested.

8. Family History • Mother - DM type II • Father – ETOH induced liver disease • No family history of autoimmune disease • Patient’s mother had Mycobacterial Tuberculosis 15 years ago. He reports 6 months of treatment for his mother and the whole family had to get PPDs placed. The patient’s PPD was positive but he does not remember getting LTBI treatment.

9. ROS • Night sweats and weight loss for 6 weeks • No chest pain, no N/V/D, no BRBPR, no hematuria or dysuria. • No joint pain or swelling. • No rashes or skin lesions. • Otherwise negative ROS.

10. T 37.7 - HR 110 - RR 36 - BP 95/65 – 99% on 100% NRB Tachypnec, on 100% NRB a&ox3, pleasant and cooperative mild errythema seen on the ventral surface of the elbow on the RUE soft NT nabs, no HSM no c/c/e nl tone, full ROM present no focal defecits EOMI, PERRLA, nonicteric no e/e on OP no JVD no LAD appreciated in cervical, supraclavicular, or inguinal regions II/VI systolic murmur decreased breath sounds at the bases. L chest wall is higher than R, crepitus present. chest tube present Physical Exam

12. OSH Labs • Pleural fluid - exudative process, pH was 8 and the glucose was reportedly elevated • Micro from bronch- gram stain many WBCs, yeast, rare GPCs. • aerobic cultures candida albicans only • anaerobic cultures no growth • fungal cultures growing candida albicans only • AFB smear and culture pending at the state lab. • Bronch biopsy – diffuse fibrosis and inflammation, ?UIP

13. OSH Labs • Urine microscopy: granular casts, monomorphic red cells, and yeast with pseudohyphae • urine microalbumin 100 (11/24), UP/C 4.069 • UA 1.010/5.0/1+ protein/3+ blood/7 WBC/148 RBC/4 granular casts/occ bacteria • HgbA1C 8.2 • ESR 68 • SPEP and UPEP negative • ANA, ENA panel negative

14. Radiology

25. Discussion

27. Labs • Serum crypto, urine histo, urine legionella negative • PCP DFA negative from bronch • AFB smears and cultures from bronch, pleural fluid, all negative

28. Further Hospital Course • Patient had slides from lung biopsy sent to UNC • Pathology showed findings concerning for acute interstitial fibrosis. AFB, bacterial, viral, and fungal cultures all negative. • Hypoxia progressed, ARDS, unable to oxygenate • Patient expired on post-transfer day #10

29. “A Diagnostic test was performed…” • Unfortunately, autopsy. (“Pathologists always get the diagnosis… just a little late.”) • Late exudative stage of early organizing stage idiopathic diffuse alveolar damage (acute interstitial pneumonia). • Severe bilateral acute interstitial pneumonia • Nephrotic range proteinuria 2/2 minimal change disease • All cultures and microscopic analysis negative • Diagnosis – Hamman Rich Syndrome

30. Hamman-Rich Syndrome • Acute interstitial pneumonia • Described by Hamman and Rich in 1934 • Rare and fulminant form of rapidly fibrosing lung disease (idiopathic DAD) • Occurs in previously healthy individuals without a history of lung disease, presents within days to weeks of onset of symptoms • Unknown mechanism of the damage to the pulmonary endothelium and epithelium

31. Hamman-Rich Syndrome • Onset usually abrupt, prodromal illness lasts 7 to 14 days • Most common clinical signs and symptoms are fever, cough, and shortness of breath • Not associated with cigarette smoking • Most patients are over the age of 40 years, with a mean age of 50 to 55 years

32. Treatment • Prognosis is poor, mortality rate >60% at initial presentation. • Most patients die within 6 months • Treatment is supportive, attempt to identify any possible cause

33. References • Mandell’s Principles and Practices of Infectious Disease, 6th Ed. • Hamman, L, Rich, AR. Fulminating diffuse interstitial fibrosis of the lungs. Trans Am Clin Climatol Assoc 1935; 51:154. • Vourlekis, JS. Acute interstitial pneumonia. Clin Chest Med 2004; 25:739. • Katzenstein, ALA, Myers, JL, Mazur, MT. Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study. Am J Surg Pathol 1986; 10:256. • Bouros, D, Nicholson, AC, Polychronopoulos, V, du Bois, RM. Acute interstitial pneumonia. Eur Respir J 2000; 15:412.6.Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore) 2000; 79:369. • Fulmer, JD, Katzenstein, ALA. The interstitial lung diseases. In: Pulmonary and Critical Care Medicine, Bone, RC (Ed), Mosby Year Book, St. Louis; 1993, M1.8.Olson, J, Colby, TV, Elliott, CG. Hamman-Rich syndrome revisited. Mayo Clin Proc 1990; 65:1538. • Primack, SL, Hartman, TE, Ikezoe, J, et al. Acute interstitial pneumonia: Radiographic and CT findings in nine patients. Radiology 1993; 188:817. • Johkoh, T, Muller, NL, Taniguchi, H, et al. Acute interstitial pneumonia: Thin-section CT findings in 36 patients. Radiology 1999; 211:859.