pulmonary renal syndorme

Pulmonary Pulmonary Renal Renal

SyndromesSyndromesA Rheumatologic A Rheumatologic

EmergencyEmergency

Farhan Tahir MDFarhan Tahir MD

AgendaAgenda

Pulmonary Renal Syndrome Pulmonary Renal Syndrome A Rheumatologic EmergencyA Rheumatologic Emergency ClassificationClassification Characteristic Profile of DiseasesCharacteristic Profile of Diseases Mortality and PrognosisMortality and Prognosis

Interesting Cases and Differential Interesting Cases and Differential DiagnosisDiagnosis

Review of Clinical ManagementReview of Clinical Management SummarySummary

A Rheumatologic A Rheumatologic EmergencyEmergency

The term Pulmonary Renal Syndrome refers to the combination of diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis

There is a broad list of etiologies which can cause this syndrome and significant number of patients will present with rapid clinical deterioration and require admission to the intensive care unit

Presentation is variable and could be related to exacerbation of the disease activity or to infectious complications secondary to severe immunosuppressive treatment

Pulmonary–renal syndromes represent a major challenge since the outcome is based on early and accurate diagnosis and aggressive treatment and mortality can reach 25–50%

Presentation and Presentation and Diagnostic WorkupDiagnostic Workup Fever, cough and dyspnea, often acute or sub Fever, cough and dyspnea, often acute or sub

acute( <1wk)acute( <1wk)

Hemoptysis may be absent in 1/3 of patients Hemoptysis may be absent in 1/3 of patients

When hemoptysis is present, one must exclude When hemoptysis is present, one must exclude infection, left heart failure, severe mitral stenosis, infection, left heart failure, severe mitral stenosis, pulmonary embolism and drug exposure (PTU and pulmonary embolism and drug exposure (PTU and Cocaine) as possible etiologies so thorough history is Cocaine) as possible etiologies so thorough history is extremely importantextremely important

CXR and Chest CT show diffuse bilateral infiltrates CXR and Chest CT show diffuse bilateral infiltrates often impossible to differentiate form infection or acute often impossible to differentiate form infection or acute pulmonary edemapulmonary edema

Early bronchoscopy is most helpful and serves two Early bronchoscopy is most helpful and serves two purpose, document hemorrhage and exclude airway purpose, document hemorrhage and exclude airway lesions as source of bleeding and BAL fluid cultures lesions as source of bleeding and BAL fluid cultures exclude infectionexclude infection

DLCO, Exhaled Nitric oxide DLCO, Exhaled Nitric oxide and Biopsyand Biopsy

TBBX specimen is small and unlikely to help establish TBBX specimen is small and unlikely to help establish diagnosisdiagnosis

VATS or open lung biopsy although invasive is more VATS or open lung biopsy although invasive is more definitivedefinitive

PFT testing particularly DLCO is helpful but impractical PFT testing particularly DLCO is helpful but impractical modalities for sick patientsmodalities for sick patients

Increased intra alveolar hemoglobin binds NO and levels of Increased intra alveolar hemoglobin binds NO and levels of NO are decreased in exhaled breath. Decreased exhaled NO are decreased in exhaled breath. Decreased exhaled Nitric oxide is a promising bedside test but not widely Nitric oxide is a promising bedside test but not widely available available

Patients presenting with pulmonary renal syndrome, renal Patients presenting with pulmonary renal syndrome, renal biopsy with IF has higher yield in identifying underlying biopsy with IF has higher yield in identifying underlying causecause

Basis of ClassificationBasis of Classification

A variety of mechanisms are implicated in the pathogenesis of this syndrome i.e. antibody mediated diseases, immune complex mediated and others i.e. drugs

Underlying pulmonary pathology is small-vessel vasculitis involving arterioles, venules and, frequently, alveolar capillaries

Underlying renal pathology is a form of focal proliferative glomerulonephritis

Immunofluorescence helps to distinguish between antibody mediated and immune complex mediated diseases

Classification Based On Classification Based On Vessels SizeVessels Size

Arch Bronconeumol. 2008;44(8):428-36

Immune Complex DepositionImmune Complex Deposition


Pattern of Pattern of ImmunofluorescenceImmunofluorescence


Antibody mediated VsAntibody mediated VsImmune Complex DiseaseImmune Complex Disease


Renal Glomerulus with anti-Renal Glomerulus with anti-GBM DiseaseGBM Disease

Linear staining of the GBM by direct immunofluorescence microscopy using an antibody specific for immunoglobulin G (Ig G)

Granular Granular Immunofluorescence in SLEImmunofluorescence in SLE

Arch Pathol Lab Med—Vol 125, April 2001

Renal and Lung Immunofluorescence microscopy

Pauci-immune VasculitisPauci-immune Vasculitis


Crescentic Crescentic Glomerulonephritis in Glomerulonephritis in

Pauci immune VasculitisPauci immune Vasculitis

WG segmental fibrinoid necrosis and cellular crescent

MPA: cellular crescent at the top of the image and a small irregular (red) focus of fibrinoid necrosis

Direct immunofluorescence of Direct immunofluorescence of ANCA Crescentic GNANCA Crescentic GN

Irregular staining of a large crescent by IF microscopy using an antibody specific for fibrin

Pulmonary Renal Pulmonary Renal SyndromesSyndromes

Critical Care Vol 11 No 3 Papiris et al.

Relative Frequencies of Relative Frequencies of VasculitisVasculitis

Critical Care Vol 11 No 3 Papiris et al.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 4 APRIL 2008

Reaching Diagnosis in Reaching Diagnosis in Challenging Cases Challenging Cases

Hemoptysis and renal failure is not Hemoptysis and renal failure is not equivalent to pulmonary renal syndromeequivalent to pulmonary renal syndrome

Evaluating PAH and Evaluating PAH and HematuriaHematuria

Are you dealing with a systemic vasculitisAre you dealing with a systemic vasculitis Y/NY/N

Is there evidence of oral and nasal inflammationIs there evidence of oral and nasal inflammation Y/NY/N

Any history of Asthma, eosinophila or paranasal Any history of Asthma, eosinophila or paranasal sinus diseasesinus disease

Y/NY/N

Is there palpable purpra, arthritis or/and Is there palpable purpra, arthritis or/and abdominal painabdominal pain

Y/NY/N

Does patient has bilateral pulmonary infiltrates Does patient has bilateral pulmonary infiltrates + bronchoscopy with hemorrhagic BAL+ bronchoscopy with hemorrhagic BAL

Y/NY/N

Oral and genital ulceration, uveitis and skin Oral and genital ulceration, uveitis and skin lesionslesions

Y/NY/N

Is there history of D-penicillamine or PTU use or Is there history of D-penicillamine or PTU use or BMTBMT

Y/NY/N

Risk factors for pneumonia with renal failure, in Risk factors for pneumonia with renal failure, in an immunosuppressed host (bacterial/viral or an immunosuppressed host (bacterial/viral or PCP)PCP)

Y/NY/N

Is there new congestive heart failure with prior Is there new congestive heart failure with prior hx renal diseasehx renal disease

Y/NY/N

Evaluating PAH and Evaluating PAH and HematuriaHematuria

Any evidence of Any evidence of MAHA (HUS/TTP): HPT, MAHA (HUS/TTP): HPT, LDH, DAT, Peripheral smear, Low PLTLDH, DAT, Peripheral smear, Low PLT

Y/NY/N

Possibility of a bleeding diathesis: DIC , Possibility of a bleeding diathesis: DIC , Coags, coumadinCoags, coumadin

Y/NY/N

Is there nephrotic proteinuria Is there nephrotic proteinuria Pulmonary Pulmonary EmbolismEmbolism

Y/NY/N

SerologiesSerologies

Lupus: ANA, ENA, DsDNA, C3,C4Lupus: ANA, ENA, DsDNA, C3,C4

Pauci-Immune: ANCA, Pr3, MPO, AGBMPauci-Immune: ANCA, Pr3, MPO, AGBM

Immune complex Vasculitis: Cryo, RF, viral Immune complex Vasculitis: Cryo, RF, viral hepatitishepatitis

Antiphospholipid syndrome: DRVVT,CAB, Antiphospholipid syndrome: DRVVT,CAB, B2GP1B2GP1

Y/NY/N

Tissue biopsy showing necrosis, vasculitis, Tissue biopsy showing necrosis, vasculitis, granulomatous inflammationgranulomatous inflammation

Age/SexAge/Sex 20 Male20 Male

Prior HxPrior Hx NeurofibromatosisNeurofibromatosis

PresentatiPresentationon

Fevers, Respiratory distress, HemoptysisFevers, Respiratory distress, Hemoptysis

LaboratorLaboratory y

Wbc 15, hb 8, plt 395, creat 0.8, Ur: rbc5, Wbc 15, hb 8, plt 395, creat 0.8, Ur: rbc5, no cast, pr30mgno cast, pr30mg

COAGSCOAGS Normal ptt, inr, hpt, ldhNormal ptt, inr, hpt, ldh

Chest X-Chest X-rayray

Pulmonary edema, pneumonia, pl effPulmonary edema, pneumonia, pl eff

Chest CTChest CT Bilateral opacities multilobar infection, Bilateral opacities multilobar infection, ARDS. No PEARDS. No PE

BAL/BAL/BronchBronch

sub segmental blood clots, no fresh bloodsub segmental blood clots, no fresh blood

MicrobiolMicrobiologyogy

Legionalla and mycoplasma (neg), BAL : GS, Legionalla and mycoplasma (neg), BAL : GS, Tb and fungal negativeTb and fungal negative

ECHOECHO Not doneNot done

ImmunoloImmunologygy

Negative NAB, NCAB,CAB. Positive AGBMNegative NAB, NCAB,CAB. Positive AGBM

BiopsyBiopsy Not doneNot done

Case-1Case-1

DAH in a 20 year old maleDAH in a 20 year old male

Developing Differential Developing Differential DiagnosisDiagnosis

www.medal.org

Differential Diagnosis and Differential Diagnosis and TreatmentTreatment

Goodpastures’s Goodpastures’s diseasedisease

InfectionInfection

Pulse dose steroids Pulse dose steroids x3x3

PlasmapheresisPlasmapheresis IV CytoxanIV Cytoxan Broad spectrum Broad spectrum

antibiotics pending antibiotics pending culturescultures

IVIG for IVIG for hypogammaglobulinehypogammaglobulinemiamia

Resulted in favorable Resulted in favorable outcomeoutcome

Age/SexAge/Sex 61 F recent travel to Mexico61 F recent travel to Mexico

Prior HxPrior Hx Hypertension, Dyslipedemia, BronchitisHypertension, Dyslipedemia, Bronchitis


Acute dyspnea, Fatigue and dry cough Acute dyspnea, Fatigue and dry cough

Laboratory Laboratory Wbc 8.1, hb 9, plt 212, creat 0.9, Ur: rbc Wbc 8.1, hb 9, plt 212, creat 0.9, Ur: rbc 100, no cast, pr100, no cast, pr

COAGSCOAGS Normal ptt, inr. (Hpt, LDH, DAT not done)Normal ptt, inr. (Hpt, LDH, DAT not done)


Pulm edema/ARDS and/or multifocal Pulm edema/ARDS and/or multifocal pneumonia pneumonia

Chest CTChest CT B/L consolidations and ground glass B/L consolidations and ground glass opacities, No PEopacities, No PE


Moderate amount of blood Moderate amount of blood

MicrobioloMicrobiologygy

Legionnella (neg), BAL : G.S,Tb and fungal Legionnella (neg), BAL : G.S,Tb and fungal negativenegative

EchoEcho LVH, EF 60%LVH, EF 60%

ImmunologImmunologyy

Pos: P-anca, +MPO, Negative Pos: P-anca, +MPO, Negative NAB,CAB,AGBMNAB,CAB,AGBM

BiopsyBiopsy Renal: Moderate to severe Renal: Moderate to severe arteriolosclerosis; diffuse tubular arteriolosclerosis; diffuse tubular injury/focal tubular necrosis injury/focal tubular necrosis

Case-2Case-2

Acute Respiratory Distress Acute Respiratory Distress in 61 Fin 61 F

Developing Differential Developing Differential DiagnosisDiagnosis


Microscopic Microscopic polyangitispolyangitis

Churg-Strauss Churg-Strauss SyndromeSyndrome

Pneumonia Pneumonia

Legionalla or PCP, Legionalla or PCP, Nosocomial infectionNosocomial infection

Pulse dose steroids Pulse dose steroids x3x3

PlasmapheresisPlasmapheresis Hold Cytoxan Hold Cytoxan

concern for concern for infection-pending infection-pending culturescultures

Broad spectrum Broad spectrum antibiotics antibiotics

IV Cytoxan started IV Cytoxan started after Renal biopsyafter Renal biopsy

Resulted in favorable Resulted in favorable outcomeoutcome

Age/SexAge/Sex 38/F38/F

Prior HxPrior Hx LupusLupus


SOB, cough with streaks of blood, not frank SOB, cough with streaks of blood, not frank hemoptysishemoptysis

Laboratory Laboratory Wbc 15, Wbc 15, Hb 8->6.5Hb 8->6.5 , Plt 155->85, , Plt 155->85, Creat 1.5-Creat 1.5->2.6,>2.6,

Pr/cr : 12 g, Ur: 10rbc , smear 1-3 Pr/cr : 12 g, Ur: 10rbc , smear 1-3 schitiocytesschitiocytes

COAGSCOAGS Normal PTT , INR, Normal PTT , INR, HPT 3HPT 3, LDH 1415, DAT , LDH 1415, DAT negneg


Airspace opacities bilaterally, pulmonary Airspace opacities bilaterally, pulmonary edema, pneumonia and pulmonary edema, pneumonia and pulmonary hemorrhage hemorrhage

Chest CTChest CT Pulmonary hemorrhage or pneumonitis Pulmonary hemorrhage or pneumonitis


RBC 147,000, WBC 1197RBC 147,000, WBC 1197

MicrobioloMicrobiologygy

BAL(9/9) NEG, BAL 9/20: + Staph; neg BAL(9/9) NEG, BAL 9/20: + Staph; neg AFB, FNGAFB, FNG

EchoEcho Globally hypokinetic left ventricle , LVEF Globally hypokinetic left ventricle , LVEF 40%40%

ImmunologImmunologyy

NAB, DsDNA, Low C3,C4. Neg NAB, DsDNA, Low C3,C4. Neg PR3,MPO,AGBMPR3,MPO,AGBM

BiopsyBiopsy Membranous focal necrotizing and Membranous focal necrotizing and proliferative GNproliferative GN

Case-3Case-3

Acute Respiratory Distress Acute Respiratory Distress in 38 Fin 38 F


Lupus nephritis flare Lupus nephritis flare with pulmonary with pulmonary hemorrhage hemorrhage

TTP or HUS TTP or HUS End-stage renal disease End-stage renal disease

with congestive heart with congestive heart failure failure

Legionalla pneumonia Legionalla pneumonia Nephrotic syndrome Nephrotic syndrome

with hypercoagulable with hypercoagulable state causing a state causing a

pulmonary emboluspulmonary embolus

Pulse steroidsPulse steroids PlasmapheresisPlasmapheresis Broad spectrum Broad spectrum

antibioticsantibiotics IVIGIVIG Cytoxan Cytoxan RituxanRituxan IVIGIVIG CellceptCellcept

6 lupus, 2 with alveolar hemorrhage and 1 with diffuse 6 lupus, 2 with alveolar hemorrhage and 1 with diffuse alveolar damage (ARDS), 6/6 active lupus nephritisalveolar damage (ARDS), 6/6 active lupus nephritis

2/3 lung pathology showed bland alveolar wall 2/3 lung pathology showed bland alveolar wall changes and immune complex depositschanges and immune complex deposits

Patient with diffuse alveolar damage had invasive Patient with diffuse alveolar damage had invasive aspergillosisaspergillosis

All 3/6 with pulmonary complications died, 2/6 All 3/6 with pulmonary complications died, 2/6 received pulse steroids and 1 received cytoxan, No received pulse steroids and 1 received cytoxan, No one received plasma exchangeone received plasma exchange

Alveolar and Renal Alveolar and Renal Microangiopathy Microangiopathy

Diffuse Alveolar Diffuse Alveolar Hemorrhage in SLEHemorrhage in SLE

510 lupus patients - 19 admissions for DAH ( 15 510 lupus patients - 19 admissions for DAH ( 15 patients)patients)

14/15 - 14/15 - lupus nephritislupus nephritis, 7/15 on , 7/15 on monthly Cytoxan and monthly Cytoxan and prednisoneprednisone >20mg >20mg

Most episodes treated with pulse dose steroids, 10/19 Most episodes treated with pulse dose steroids, 10/19 IV Cytoxan and 12/19 received plasmapheresisIV Cytoxan and 12/19 received plasmapheresis

53 % overall mortality ( 53 % overall mortality ( concurrent infection 78%, no concurrent infection 78%, no infection 20%, prior Cytoxan use 70%, poor infection 20%, prior Cytoxan use 70%, poor prognostic factors Mech. ventilation and infectionprognostic factors Mech. ventilation and infection

6/19 - 6/19 - Primary lung infectionPrimary lung infection (HSV and Legionalla, (HSV and Legionalla, CMV, staph)CMV, staph)

Patients on Cytoxan, 4/6 (had primary infection versus Patients on Cytoxan, 4/6 (had primary infection versus only 2 patients among 8 who were not on Cytoxan)only 2 patients among 8 who were not on Cytoxan)

3/19 episodes were associated with 3/19 episodes were associated with nosocomial nosocomial infectioninfection (Ecoli, MRSA and Candida) (Ecoli, MRSA and Candida)

Medicine Issue: Volume 76(3), May 1997, pp 192-202 , ZAMORA, MARTIN R. etalMedicine Issue: Volume 76(3), May 1997, pp 192-202 , ZAMORA, MARTIN R. etal

Review of TreatmentReview of Treatment

Use of Immunosuppression and Plasma Use of Immunosuppression and Plasma Exchange in PRS - 13 case series and 1 RCTExchange in PRS - 13 case series and 1 RCT Goodpastures's SyndromeGoodpastures's Syndrome Small Vessel VasculitisSmall Vessel Vasculitis SLESLE Antiphospholipid SyndromeAntiphospholipid Syndrome

Non Immunosuppressive Treatment Modalities Non Immunosuppressive Treatment Modalities in DAHin DAH

71 patients with positive anti GBM antibody disease71 patients with positive anti GBM antibody disease presented presented who with pulmonary hemorrhage and rapidly progressive GNwho with pulmonary hemorrhage and rapidly progressive GN

Followed in three categories based on renal function at Followed in three categories based on renal function at presentationpresentation Creatinine <5.6mg/dl (<500mgUmol/l), n=19Creatinine <5.6mg/dl (<500mgUmol/l), n=19 Creatinine >5.6mg/dl(>500mgUmol/l) but no dialysis dependent, n=13Creatinine >5.6mg/dl(>500mgUmol/l) but no dialysis dependent, n=13 Dialysis dependent with in 72 hours, n=39Dialysis dependent with in 72 hours, n=39

All treated with IS including oral prednisone 1mg/kg( or 60mg All treated with IS including oral prednisone 1mg/kg( or 60mg max), Cytoxan (2-3mg/kg/day) for 2-3 months, No Pulse max), Cytoxan (2-3mg/kg/day) for 2-3 months, No Pulse steroidssteroids

Plasma exchange (50ml/kg or 4L)daily for at least 14daysPlasma exchange (50ml/kg or 4L)daily for at least 14days

Ann Intern Med. 2001;134:1033-1042.

Survival at 1 YearSurvival at 1 Year

Long-Term Survival Long-Term Survival

20 pts with DAH and confirmed Pauci-immune SVV20 pts with DAH and confirmed Pauci-immune SVV 17MPA, 2 WG,1 CSS at UNC17MPA, 2 WG,1 CSS at UNC Treated with pulse dose steroids x3 days, 18/20 received Treated with pulse dose steroids x3 days, 18/20 received

intravenous cytoxan (0.5g/m2) and plasmapheresis daily intravenous cytoxan (0.5g/m2) and plasmapheresis daily until DAH improved, Mean number of apheresis 6( range 4-until DAH improved, Mean number of apheresis 6( range 4-9)9)

Average time to admission and first exchange was 2 daysAverage time to admission and first exchange was 2 days DAH had 100% response rateDAH had 100% response rate 14/20 (70%) had abnormal renal function on admission14/20 (70%) had abnormal renal function on admission Creatinine (4.5+/- 4.5)at baseline and on discharge 2.4=/- Creatinine (4.5+/- 4.5)at baseline and on discharge 2.4=/-

0.8.0.8.

Clinical Parameters in SVVClinical Parameters in SVV

American Journal of Kidney Diseases, Vol 42, No 6 (December), 2003

RCT: Plasmapheresis and Pulse RCT: Plasmapheresis and Pulse SteroidsSteroids

Study Design and ResultsStudy Design and Results 137 patients with ANCA-associated systemic 137 patients with ANCA-associated systemic

vasculitis, biopsy confirmed and creatinine vasculitis, biopsy confirmed and creatinine >5.8mg/dl were randomized >5.8mg/dl were randomized

One arm received seven plasma exchanges (n=70), One arm received seven plasma exchanges (n=70), second arm received Pulse steroids (total 3g)second arm received Pulse steroids (total 3g)

All received oral prednisone and Cyclophosphamide All received oral prednisone and Cyclophosphamide (details not clear)(details not clear)

Renal survival follow up, HR for PE vs IVPS: Renal survival follow up, HR for PE vs IVPS: 0.47(P+0.03)0.47(P+0.03)

DuratioDurationn

Pulse Pulse steroidsteroid

ApheresiApheresiss

P P valuevalue

3Month3Month 49%49% 69%69% 0.020.02

12Mont12Monthh

43%43% 59%59% 0.0080.008

Clinical and Serologic Clinical and Serologic CharacteristicsCharacteristics

Renal Function and Renal Function and Vasculitis ActivityVasculitis Activity

Adverse Effect Profile in Each Group were comparable

7 lupus nephritis - 9 episodes DAH7 lupus nephritis - 9 episodes DAH Serologic evidence of flare and lung biopsy c/w IC Serologic evidence of flare and lung biopsy c/w IC

depositsdeposits Treated pulse dose steroids and IV Cytoxan (3/9) Treated pulse dose steroids and IV Cytoxan (3/9)

and oral 1mg/kg Cytoxan in 6/9 with and oral 1mg/kg Cytoxan in 6/9 with no plasma no plasma exchangeexchange

Mortality 57%, higher mortality associated with Mortality 57%, higher mortality associated with infectionsinfections PCP and actinobacter, PCP and actinobacter, severe anemiasevere anemia at at presentation and presentation and longer duration of mechanical longer duration of mechanical ventilationventilation

22 active lupus22 active lupus pts (SLEDAIs mean 12) who p/w pts (SLEDAIs mean 12) who p/w respiratory distress and hemoptysis and all in the respiratory distress and hemoptysis and all in the early course of lupusearly course of lupus

Preceding month of presentation there was rise in Preceding month of presentation there was rise in SLEDAI and DLCO SLEDAI and DLCO

19 received pulse steroids and cytoxan(500mg/m2), 19 received pulse steroids and cytoxan(500mg/m2), 11/22 received plasmapheresis(2-6 times11/22 received plasmapheresis(2-6 times)) but no but no added benefit from plasmapheresisadded benefit from plasmapheresis

4/22 had concurrent infection4/22 had concurrent infection Mortality 36%Mortality 36%

Semin Arthritis Rheum 33:414-421

Three patients with biopsy proven acute alveolar Three patients with biopsy proven acute alveolar capillaritiscapillaritis

All patient received All patient received pulse dose steroids and IV cytoxan pulse dose steroids and IV cytoxan and plasma exchange and 2/3 improved with first and plasma exchange and 2/3 improved with first treatmentstreatments

One patient also received One patient also received IVIG for recurrent hemorrhageIVIG for recurrent hemorrhage Very favorable outcome with plasmapheresis but catious Very favorable outcome with plasmapheresis but catious

for infection and procedure related complications which for infection and procedure related complications which are reported as high 67% and 12%are reported as high 67% and 12%

Seminars in Arthritis andRheurnatism, Vo124, No 2 (October), 1994

Primary APS can cause DAH and alveolar capillaritis Primary APS can cause DAH and alveolar capillaritis through APL antibody mediated endothelia cell through APL antibody mediated endothelia cell activation in the absence of thrombosis activation in the absence of thrombosis

All All 4 patients with DAH4 patients with DAH treated with treated with pulse dose steroids pulse dose steroids and IV monthly cytoxan (0.5 -1 g) for three monthsand IV monthly cytoxan (0.5 -1 g) for three months, two , two responded well to treatmentresponded well to treatment

2/4 had recurrent pulmonary hemorrhage on switching 2/4 had recurrent pulmonary hemorrhage on switching intravenous to oral cytoxan and initiated intravenous to oral cytoxan and initiated IVIG ( IVIG ( 400mg/kg x5 days)400mg/kg x5 days)

Author also suggested empiric antibiotic coverage for Author also suggested empiric antibiotic coverage for infectioninfection

DAH of unclear etiology, negative auto antibodies and DAH of unclear etiology, negative auto antibodies and absence of systemic vasculitis or concurrent infection (?absence of systemic vasculitis or concurrent infection (?IPH)IPH)

Recurrent hemorrhage non responsive to 10 daily Recurrent hemorrhage non responsive to 10 daily treatments of plasmapheresis and pulse steroids x 3d treatments of plasmapheresis and pulse steroids x 3d and transient response to IV bolus of recombinant factor and transient response to IV bolus of recombinant factor

Responded to 4 day course of IVIG( 2g/kg/d) and Responded to 4 day course of IVIG( 2g/kg/d) and pulmonary hemorrhage pulmonary hemorrhage

8 days later readmitted for pulmonary embolism, treated 8 days later readmitted for pulmonary embolism, treated with heparin products without bleedingwith heparin products without bleeding

6 patients with DAH treated with intrapulmonary 6 patients with DAH treated with intrapulmonary administration of 50ug rFVIIa via BALadministration of 50ug rFVIIa via BAL

DAH was attributed to sarcoidosis, WG, AIDs, AML DAH was attributed to sarcoidosis, WG, AIDs, AML and post stem cell transplantand post stem cell transplant

Complete and sustained hemostasis in 3/6 with Complete and sustained hemostasis in 3/6 with single dose and rest required second dosessingle dose and rest required second doses

Use of intravenous forms of rFVIIa is approved for Use of intravenous forms of rFVIIa is approved for hemophiliahemophilia

Mortality Associated with Mortality Associated with Pulmonary Renal SyndromePulmonary Renal Syndrome

Mortality Associated with Mortality Associated with Pulmonary VasculitisPulmonary Vasculitis

Poor Prognostic FactorsPoor Prognostic Factors

THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES October 2008 Volume 336 Number 4

Poor Prognostic FactorsPoor Prognostic FactorsVariableVariable P valueP value

Mean Age - 60y Mean Age - 60y <0.05<0.05

Mean BUN - 53Mean BUN - 53 <0.05<0.05

Low Hemoglobin -9.8%Low Hemoglobin -9.8% =0.05=0.05

Elevated WBC count -Elevated WBC count -15.4 15.4

=0.05=0.05

Fio2 54%Fio2 54% <0.05<0.05

ICU length of stay – ICU length of stay – 16days16days

<0.05<0.05

Mech. Ventilator use Mech. Ventilator use <0.0001<0.0001

Need for Blood Need for Blood transfusiontransfusion

<0.0002<0.0002

Secondary infectionSecondary infection <0.005<0.005

THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES October 2008 Volume 336 Number 4

Summary of Diagnostic Summary of Diagnostic WorkupWorkup

It is a life threatening condition which It is a life threatening condition which requires early intervention to prevent requires early intervention to prevent high mortalityhigh mortality

Concurrent infection, severe anemia Concurrent infection, severe anemia and long mechanical dependence are and long mechanical dependence are poor prognostic markerspoor prognostic markers

Aim for an early bronchoscopy to Aim for an early bronchoscopy to document hemorrhage and exclude document hemorrhage and exclude infectioninfection

Biopsy (open lung or renal with IF) can Biopsy (open lung or renal with IF) can be extremely helpful and reassuringbe extremely helpful and reassuring

Summary of TreatmentSummary of Treatment

Common practice to use of Pulse dose Common practice to use of Pulse dose steroids and Cytoxan in life threatening steroids and Cytoxan in life threatening renal and pulmonary involvementrenal and pulmonary involvement

There is good data early use of plasma There is good data early use of plasma exchange followed by IVIG in life exchange followed by IVIG in life threatening and treatment resistant threatening and treatment resistant casescases

Plasma exchange has been helpful in Plasma exchange has been helpful in situations with concomitant need for situations with concomitant need for anticoagulationanticoagulation

pulmonary renal syndorme

Health & Medicine

lupus patients

term pulmonary renal

pulmonary complications

whowith pulmonary hemorrhage

diffuse alveolar hemorrhage

pulse steroids plasma

pulmonary edema

pulse steroids total