“I’m just… really…short of breath”

Wednesday ID Case Conference

Christopher Hurt, MDApril 4, 2007

7/18/07 2

HPIHPI

• SS is a 36yo WM seen 2/14/07, with stage IIBnodular sclerosing Hodgkin’s dz dx’d 11/06

• Now s/p 6 cycles of ABVD (adria/bleo/vin/dacarb)

• Last chemo 1/16, 2-3d after slight DOE (stairs)

• Nonproductive cough, worse at nighttime and withposition change – coughing fits last several mins

• Low-grade temps, never over 100°F

• Oncology f/u 1/31 – CXR with possible RLLinfiltrate, PFTs with drop in FEV1 and DLCO» Levofloxacin 500 daily; albuterol MDI made worse

7/18/07 3

HPI, contHPI, cont’’dd

• Seen again 2/6 – sxs persistent; repeat CXR = noinfiltrate» Levofloxacin upped to 750mg daily

• Over next 3d, DOE rapidly progressed

• On 2/10, woke feeling crappy but was afebrile» In PM, spiked to 102.7°F and he came to UNC

• In ED, started on pip/tazo 3.375gm iv q6h, vanc1.25gm iv q24h, and fluconazole 400mg daily

• Seen by Pulmonology on 2/11, HRCT obtained

• Bronched on 2/12; ID consulted 2/14

7/18/07 4

ROSROS

• Low-grade temps

• No CP/pressure, no pleuritic-type CP

• No N/V/diarrhea

• No chills or sweats

• No dysuria

• No myalgias, arthralgias

7/18/07 5

PMHxPMHx//PSHxPSHx

• Nodular sclerosing Hodgkin’s lymphoma (IIB)» Diagnosed 11/06

» Adriamycin + bleomycin + vincristine + dacarbazinewith interval GCSF support

• No surgical history

7/18/07 6

SocHxSocHx• Lives in Durham with wife, 2 children (6 mo, 4 yo)

» 4yo enrolled in day-care, recently ctr had febrilegastroenteritis circulating – son unaffected

» Infant with runny nose, sneezing for several weeks

• Pediatric social worker; dx interviews of kids aged 3-18• No pets or animal exposures• New office in 11/06, after prior flooded and visible

mould…» Denies any relationship of sxs to work schedule

• Sexually active only with wife• Wife works in elementary school• No tobacco, illicits. Occasional EtOH.

7/18/07 7

FHxFHx

• No significant FHx, perpt

Meds, AllergiesMeds, Allergies

• Pip/tazo (day #4)

• Vanc 1.25gm q12h(upped; day #4)

• Fluconazole 2/11-14

• Voriconazole started2/14 with loading dose

• NKDA

7/18/07 8

PExPEx

Gen: Well-appearing, tallWM. Mild breathlessness.

HEENT: NCAT. Anicteric,noninjected OU. OP clear.

Neck: Supple, full ROM.Chest: R basilar rales clear

after cough, otw CTAB.CV: RRR. I-II/VI SEM @

LLSB, no radiations.

Abd: Soft, NTND. NABS. Noorganomegaly.

Ext: Warm/dry, no c/c/e x4.Skin: No petechiae or

ecchymoses. Back withmany diffuse slightlyerythematous papules.

Neuro: CN II-XII intact.MAEE. Nonfocal.

Tm 38.5 HR 105 BP 135/80 RR 20 Sat 95%1L NC

7/18/07 9

LabsLabs

10.0

28.216.4 308

138

3.2

102

29

5

1.1112

ANC 13.7ALC 1.4

MCV 80RDW 18.4

2/12: CMV, adeno, viral cx, Pneumocystis DFA all pendingQuantitative bronch cx with 400K/cc Micrococcus spp.

2/13: EBV PVL (–), CMV PVL (–)Influenza A/B (–)

7/18/07 10Pre-Admit

7/18/07 11Admit

7/18/07 12HD#2

7/18/07 13HD#4

7/18/07 14HD#5

7/18/07 15

Two other consultantsTwo other consultantswere consultedwere consulted……

7/18/07 16

7/18/07 17

Acute reactive lung injuryAcute reactive lung injuryfrom from bleomycinbleomycin

7/18/07 18

Hospital CourseHospital Course• All micro studies unrevealing• VATS on HD#5 with LBx

» Diffuse patchy areas of consolidation, inflammationinvolving alveolar walls; no hemorrhage orgranulomata; no fibrotic airway invasion

• Thoracostomy removed; PTX reaccumulated andhigh-flow O2 initiated

• Respiratory decompensation HD#7 to 8

7/18/07 19PM HD#8

AM HD#7

7/18/07 20

Hospital Course, contHospital Course, cont’’dd• Started on fludrocortisone, hydrocortisone• O2 demands increased, but never intubated• MICU favored cont’d bacterial coverage

» Vancomycin changed to linezolid as vanc troughspersistently subtherapeutic

• Only cxs positive were Micrococcus from BAL(contaminant), Candida from bronch fluid (lowcolony count), and CNStaph in broth from lung bx

• On HD#10, recommended d/c all abx, afx• Cont’d to improve clinically, d/c’d home on HD#18

7/18/07 21HD#18

7/18/07 22

BleomycinBleomycin• Family of macrolides

secreted byStreptomyces verticillus

• Intercalate into DNA• DNA degradation needs

O2 and Fe2+ or Cu+

• DNA scission by onepathway; other makesstrand(s) susceptible toalkylating agents(dacarbazine, e.g.)

Hecht SM. J Nat Prod 2000;63(1):158-68

7/18/07 23

PharmacologyPharmacology• Drug is rapidly eliminated, mostly by kidneys• Resistance to bleomycin correlates with

bleomycin hydrolase» Inhibits iron binding, and ∴ cytotoxicity

• Low conc’n of hydrolase in skin, lung» Mechanism for sensitivity to toxic effects

• Other agents in his regimen (ABVD):» Doxorubicin (adria): anthracycline - inhibits topo II» Vincristine: disassembles microtubules for mitosis» Dacarbazine: cross-links guanine residues in DNA

Dorr RT. Semin Oncol 1992;19(2 Suppl 5):3-8

7/18/07 24

Bleomycin Bleomycin skin toxicityskin toxicity• “Flagellate” dermatitis on

trunk, shoulders within 24hof administration

• Raynaud’s phenomenon» Esp. HIV+ w/KS tx’d w/bleo

• Acral gangrene• Drug-induced scleroderma• Acute generalized

exanthematous pustulosis• Alopecia• Nail pigmentation

Yamamoto T. Br J Dermatol 2006;155(5):869-75

7/18/07 25

Bleomycin Bleomycin lung toxicitylung toxicity• Interstitial edema with influx of inflammatory,

immune cells• Leads to pulmonary fibrosis with enhanced

collagen deposition (fibrosing alveolitis)

Hay J, et al. Arch Toxicol 1991;65(2):81-94

7/18/07 26

Bleomycin Bleomycin lung toxicitylung toxicity• Risk factors? Age, dose, renal function, use of

O2, radiation therapy, and other chemo agents• Clinical presentation

» Develops subacutely btw 1 and 6 months» Nonspecific, overall

• Nonproductive cough• Dyspnea, tachypnea, hypoxemia• Pleuritic or substernal CP• Fever• Rales• Restrictive lung physiology and decreased DLCO

Lasky JA, Ortiz L. Up-To-Date, Bleomycin-induced lung injury. [2/19/07]

7/18/07 27

TreatmentTreatment• Discontinue bleomycin• If fibrosing, short-term improvement

demonstrable w/steroids… but may rebound• No studies addressing dose or duration of tx

• Our pt discharged on 100mg prednisone daily,to be tapered later…

Lasky JA, Ortiz L. Up-To-Date, Bleomycin-induced lung injury. [2/19/07]