ID Case Conference ID Case Conference April 9, 2008April 9, 2008

Gretchen Shaughnessy, MDGretchen Shaughnessy, MD

Clinical FellowClinical Fellow

Dept of Infectious DiseasesDept of Infectious Diseases

CC: SOBCC: SOB

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

HPIHPI

During admission to Outside Hospital the During admission to Outside Hospital the patient had a normal echo (no pulm HTN), patient had a normal echo (no pulm HTN), chest CT with moderate R pleural effusion and chest CT with moderate R pleural effusion and LLL interstitial process. LLL interstitial process.

Sputum cultures and pleural fluid analysis and Sputum cultures and pleural fluid analysis and cultures were done.cultures were done.

Bronchoscopy with biopsy done day 6 of Bronchoscopy with biopsy done day 6 of hospitalization, complicated by tension hospitalization, complicated by tension pneumothorax requiring chest tube placement.pneumothorax requiring chest tube placement.

Despite broad specturm antibiotics and chest Despite broad specturm antibiotics and chest tube placement his respiratory status declined tube placement his respiratory status declined from 11/14-11/23. Transferred to UNC MICU.from 11/14-11/23. Transferred to UNC MICU.

PMHPMH

HTNHTN DM – type IIDM – type II GERDGERD Hiatial HerniaHiatial Hernia HyperlipidemiaHyperlipidemia h/o R shoulder surgery in 2001h/o R shoulder surgery in 2001 CRI – baseline Cr 1.6CRI – baseline Cr 1.6

MedicationsMedications

Allergies – NKDAAllergies – NKDA

Atenolol 100mg dailyAtenolol 100mg daily Nexium 40mg dailyNexium 40mg daily Glyburide 5mg po BIDGlyburide 5mg po BID

Antibiotic HistoryAntibiotic History

11/4-11/14 Biaxin11/4-11/14 Biaxin 11/14-11/23 Azithromycin & 11/14-11/23 Azithromycin &

Ticaricillin/clavulanateTicaricillin/clavulanate

11/21-11/23 Methylpredisolone 11/21-11/23 Methylpredisolone 60mg IV q8h60mg IV q8h

Social HistorySocial History

No tob, ETOH, or drugs. No tob, ETOH, or drugs. Currently works in construction, former truck Currently works in construction, former truck

driver. A few weeks ago was driver. A few weeks ago was sweeping parking sweeping parking lots and exposed to a lot of dustlots and exposed to a lot of dust..

No recent sick contacts.No recent sick contacts. No recent travel.No recent travel. Frequently Frequently rides in a friend’s van that is used rides in a friend’s van that is used

to transport chickens and rabbitsto transport chickens and rabbits (patient has (patient has never encountered the animals in person)never encountered the animals in person)

History of travel to the southwest as a truck History of travel to the southwest as a truck driver, but none in the past 2 years.driver, but none in the past 2 years.

Denies HIV risk factors, has never been tested.Denies HIV risk factors, has never been tested.

Family HistoryFamily History

Mother - DM type II Mother - DM type II Father – ETOH induced liver diseaseFather – ETOH induced liver disease No family history of autoimmune diseaseNo family history of autoimmune disease Patient’s mother had Mycobacterial Patient’s mother had Mycobacterial

Tuberculosis 15 years agoTuberculosis 15 years ago. He reports 6 . He reports 6 months of treatment for his mother and months of treatment for his mother and the whole family had to get PPDs placed. the whole family had to get PPDs placed. The patient’s PPD was positive but he The patient’s PPD was positive but he does not remember getting LTBI does not remember getting LTBI treatmenttreatment..

ROSROS

Night sweats and weight loss for Night sweats and weight loss for 6 weeks6 weeks

No chest pain, no N/V/D, no No chest pain, no N/V/D, no BRBPR, no hematuria or dysuria.BRBPR, no hematuria or dysuria.

No joint pain or swelling.No joint pain or swelling. No rashes or skin lesions.No rashes or skin lesions. Otherwise negative ROS.Otherwise negative ROS.

Physical ExamPhysical Exam

T 37.7 - HR 110 - RR 36 T 37.7 - HR 110 - RR 36 - BP 95/65 – 99% on - BP 95/65 – 99% on 100% NRB100% NRB

Tachypnec, on 100% Tachypnec, on 100% NRBNRB

a&ox3, pleasant and a&ox3, pleasant and cooperativecooperative

mild errythema seen on mild errythema seen on the ventral surface of the ventral surface of the elbow on the RUEthe elbow on the RUE

soft NT nabs, no HSMsoft NT nabs, no HSM no c/c/eno c/c/e nl tone, full ROM presentnl tone, full ROM present no focal defecitsno focal defecits

EOMI, PERRLA, EOMI, PERRLA, nonictericnonicteric

no e/e on OPno e/e on OP no JVDno JVD no LAD appreciated in no LAD appreciated in

cervical, supraclavicular, cervical, supraclavicular, or inguinal regionsor inguinal regions

II/VI systolic murmur II/VI systolic murmur decreased breath decreased breath

sounds at the bases. L sounds at the bases. L chest wall is higher than chest wall is higher than R, crepitus present. R, crepitus present. chest tube present chest tube present

OSH LabsOSH Labs

Pleural fluid - exudative process, pH was 8 Pleural fluid - exudative process, pH was 8 and the glucose was reportedly elevatedand the glucose was reportedly elevated

Micro from bronch- gram stain many WBCs, Micro from bronch- gram stain many WBCs, yeast, rare GPCs. yeast, rare GPCs.

aerobic cultures candida albicans onlyaerobic cultures candida albicans only anaerobic cultures no growthanaerobic cultures no growth fungal cultures growing candida albicans onlyfungal cultures growing candida albicans only AFB smear and culture pending at the state AFB smear and culture pending at the state

lab.lab. Bronch biopsy – diffuse fibrosis and Bronch biopsy – diffuse fibrosis and

inflammation, ?UIPinflammation, ?UIP

OSH LabsOSH Labs

Urine microscopy: granular casts, Urine microscopy: granular casts, monomorphic red cells, and yeast with monomorphic red cells, and yeast with pseudohyphaepseudohyphae

urine microalbumin 100 (11/24), UP/C urine microalbumin 100 (11/24), UP/C 4.0694.069

UA 1.010/5.0/1+ protein/3+ blood/7 UA 1.010/5.0/1+ protein/3+ blood/7 WBC/148 RBC/4 granular casts/occ bacteriaWBC/148 RBC/4 granular casts/occ bacteria

HgbA1C 8.2 HgbA1C 8.2 ESR 68 ESR 68 SPEP and UPEP negativeSPEP and UPEP negative ANA, ENA panel negativeANA, ENA panel negative

RadiologyRadiology

Discussion

LabsLabs

Serum crypto, urine histo, urine Serum crypto, urine histo, urine legionella negativelegionella negative

PCP DFA negative from bronchPCP DFA negative from bronch AFB smears and cultures from AFB smears and cultures from

bronch, pleural fluid, all negativebronch, pleural fluid, all negative

Further Hospital Further Hospital CourseCourse Patient had slides from lung biopsy sent Patient had slides from lung biopsy sent

to UNCto UNC Pathology showed findings concerning for Pathology showed findings concerning for

acute interstitial fibrosis. AFB, bacterial, acute interstitial fibrosis. AFB, bacterial, viral, and fungal cultures all negative.viral, and fungal cultures all negative.

Hypoxia progressed, ARDS, unable to Hypoxia progressed, ARDS, unable to oxygenateoxygenate

Patient expired on post-transfer day #10Patient expired on post-transfer day #10

““A Diagnostic test was A Diagnostic test was performed…”performed…” Unfortunately, autopsy. (“Pathologists always Unfortunately, autopsy. (“Pathologists always

get the diagnosis… just a little late.”)get the diagnosis… just a little late.”) Late exudative stage of early organizing Late exudative stage of early organizing

stage idiopathic diffuse alveolar damage stage idiopathic diffuse alveolar damage (acute interstitial pneumonia).(acute interstitial pneumonia).– Severe bilateral acute interstitial pneumoniaSevere bilateral acute interstitial pneumonia

Nephrotic range proteinuria 2/2 minimal Nephrotic range proteinuria 2/2 minimal change diseasechange disease

All cultures and microscopic analysis All cultures and microscopic analysis negativenegative

Diagnosis – Hamman Rich SyndromeDiagnosis – Hamman Rich Syndrome

Hamman-Rich Hamman-Rich SyndromeSyndrome Acute interstitial pneumoniaAcute interstitial pneumonia Described by Hamman and Rich in 1934Described by Hamman and Rich in 1934 Rare and fulminant form of rapidly fibrosing Rare and fulminant form of rapidly fibrosing

lung disease (idiopathic DAD)lung disease (idiopathic DAD) Occurs in previously healthy individuals Occurs in previously healthy individuals

without a history of lung disease, presents without a history of lung disease, presents within days to weeks of onset of symptomswithin days to weeks of onset of symptoms

Unknown mechanism of the damage to the Unknown mechanism of the damage to the pulmonary endothelium and epitheliumpulmonary endothelium and epithelium

Hamman-Rich Hamman-Rich SyndromeSyndrome Onset usually abrupt, prodromal illness Onset usually abrupt, prodromal illness

lasts 7 to 14 dayslasts 7 to 14 days Most common clinical signs and Most common clinical signs and

symptoms are fever, cough, and symptoms are fever, cough, and shortness of breath shortness of breath

Not associated with cigarette smokingNot associated with cigarette smoking Most patients are over the age of 40 Most patients are over the age of 40

years, with a mean age of 50 to 55 years, with a mean age of 50 to 55 years years

TreatmentTreatment

Prognosis is poor, mortality rate Prognosis is poor, mortality rate >60% at initial presentation.>60% at initial presentation.

Most patients die within 6 monthsMost patients die within 6 months Treatment is supportive, attempt Treatment is supportive, attempt

to identify any possible causeto identify any possible cause

ReferencesReferences

Mandell’s Principles and Practices of Infectious Disease, 6Mandell’s Principles and Practices of Infectious Disease, 6 thth Ed. Ed. Hamman, L, Rich, AR. Fulminating diffuse interstitial fibrosis of the Hamman, L, Rich, AR. Fulminating diffuse interstitial fibrosis of the

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25:739.25:739. Katzenstein, ALA, Myers, JL, Mazur, MT. Acute interstitial pneumonia. A Katzenstein, ALA, Myers, JL, Mazur, MT. Acute interstitial pneumonia. A

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Bouros, D, Nicholson, AC, Polychronopoulos, V, du Bois, RM. Acute Bouros, D, Nicholson, AC, Polychronopoulos, V, du Bois, RM. Acute interstitial pneumonia. Eur Respir J 2000; 15:412.interstitial pneumonia. Eur Respir J 2000; 15:412.6.6.Vourlekis, JS, Brown, Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore) 2000; 79:369.review of the literature. Medicine (Baltimore) 2000; 79:369.

Fulmer, JD, Katzenstein, ALA. The interstitial lung diseases. In: Fulmer, JD, Katzenstein, ALA. The interstitial lung diseases. In: Pulmonary and Critical Care Medicine, Bone, RC (Ed), Mosby Year Book, Pulmonary and Critical Care Medicine, Bone, RC (Ed), Mosby Year Book, St. Louis; 1993, M1.St. Louis; 1993, M1.8.8.Olson, J, Colby, TV, Elliott, CG. Hamman-Rich Olson, J, Colby, TV, Elliott, CG. Hamman-Rich syndrome revisited. Mayo Clin Proc 1990; 65:1538.syndrome revisited. Mayo Clin Proc 1990; 65:1538.

Primack, SL, Hartman, TE, Ikezoe, J, et al. Acute interstitial pneumonia: Primack, SL, Hartman, TE, Ikezoe, J, et al. Acute interstitial pneumonia: Radiographic and CT findings in nine patients. Radiology 1993; 188:817.Radiographic and CT findings in nine patients. Radiology 1993; 188:817.

Johkoh, T, Muller, NL, Taniguchi, H, et al. Acute interstitial pneumonia: Johkoh, T, Muller, NL, Taniguchi, H, et al. Acute interstitial pneumonia: Thin-section CT findings in 36 patients. Radiology 1999; 211:859.Thin-section CT findings in 36 patients. Radiology 1999; 211:859.