case microscopic polyangiitis
-
Upload
prachya-bung -
Category
Education
-
view
989 -
download
4
Transcript of case microscopic polyangiitis
Interesting case conference
A woman with hemoptysis and renal failure
ประจำ��วั�นที่�� 27 ตุ�ล�คม 2553น��เสนอโดย: นพ.ปร�ชญ�
ภั�สสร�นนที่�
History
ผู้� ป!วัยหญ#งไที่ยโสด อ�ย� 56ป& ไม'ได ประกอบอ�ช�พ ภั�ม#ล��เน� กที่ม.
1st admission 28 ก.ย . 2553
CC: ไอเป*นเล+อด 10 วั�นก'อนม�รพ .
Underlying disease
วั�ณโรคปอดเม+�ออ�ย� 6 ขวับ เคย tracheostomy closed 2 years PTA
acute symmetrical polyarthritis 3 weeks, involve MCP, PIP, DIP, wrist, elbow, shoulder, knee, ankle, no morning stiffness
RF+ 86, ANA+ 1:160 fine-speckled pattern, anti-Sm -ve , anti-Ro 3+
ช�ฝ่!�ม+อขวั� 3½ น#/วั, ช�เที่ �สองข �งถึ1งข อเที่ � FBS 88 Iron def. anemia : ferritin 23 Coomb -ve FeSO4 น�/�หน�กลด 50 40kg Rx : pred 30mg/d 1 wk, Chloroquine 250mg/d 6 mo
loss to F/U Hct 23 MCV 60 RDW 22 Hct 31.2 MCV 93 RDW 12
(27ตุ.ค.52)
Present illness
2 weeks PTA โที่รบอกญ�ตุ#วั'�ไปร�บหล�นไม'ไหวั9 days PTA ไอเป*นเล+อดแดงสดคร�/งละ ½ แก วั
หอบเหน+�อย ไม'ม�ไข เป*น 2 วั�น จำ1งไปรพ.เอกชนแห'งหน1�ง
7 days PTA BT 37.3°c BP 100/60 HR 110 RR 26
fine crepitation RLL5 days PTA ไม'ม�ไข ย�งเหน+�อย ไอปนเล+อด1 day PTA ช�ก GTC 5 น�ที่� ET-tube refer
4.7 7300 N 81% 15 100,000 L 16%
126 5.7 53 97 18 4.3
Past history
ไม'ส�บบ�หร�� ไม'ด+�มเหล � ก#นย�สม�นไพรจำ�น , เห3ดหล#นจำ+อ ร�กษ�โรค
ข อ ปฏิ#เสธประวั�ตุ#คนใกล ช#ดเป*นวั�ณโรค ญ�ตุ#ไม'ส�งเกตุวั'�ม�น�/�หน�กลด , ไอเร+/อร�ง Foot deformity ตุ�/งแตุ'เด3ก เด#น
ล��บ�ก
Physical examination
A middle-aged female, fully conscious, cooperative
BT 36.3°c HR 100 BP 140/90 RR 24 On PSV PS 8 PEEP 5 FiO2 0.4 O2sat =
98%HEENT : mildly pale, no jaundice
nose and nasal septum - normal no cervical lymphadenopathy
Lung : coarse crepitation both lower lungHeart : no heave, no thrill, normal S1S2, no murmur
Physical examination
Abdomen: soft, not tender, no hepatosplenomegaly
no chronic liver stigmataExtremities: no rash, no pitting edema
Neuro : E4M6VT
cranial nerve – intactmotor – gr.V all
Problem list
underlying rheumatoid arthritis?
Hemoptysis with anemia Renal failure Generalized tonic clonic seizure
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53
CBC
22/12/51
27/10/52
21/9/53
28/9/53
30/9/53
1/10/53
2/10/53
Hct 22.6 31.2 15 29.1 23.5 26.9 26.1MCV 61 93 83 75.8 75.3 77.3 81.9RDW 22.4 12.3 26.1 26.4 25.9 26.6
WBC
7830
4100
7300
10310
8230
9760
10800
N% 85% 70% 81 84% 91% 91% 93%L% 7% 19% 16 10% 5% 6% 4%
Platelet
225,000
136,000
100,000
30,000
64,000
100,000
103,000
PT 12
PTT 28
BUN/Cr
5.8 / 0.5
53 / 4.3
86 / 4.0
89 / 4.2
89 / 4.3
99 / 4.5
Lab – referer hospital
UA sp.gr 1.025 alb 2+ WBC 5-10 RBC 10-20
UPCI = 2.2 CRP 24 ESR 106 ANA -ve ANCA –ve
Coomb –ve anti-HIV –ve H/C – no growth sputum AFB –ve USG KUB – WNL Rx : PRC 5u, Ceftriaxone, oseltamivir
methylprednisolone 1g iv x 3 day
Lab
E’lyte Na+ 132 K+ 4.4 Cl- 107 HCO3-
23 LFT TB/DB 0.5/0.1 AST / ALT 26 / 22
ALP 62 alb / glb 2.6 / 3.0 Ca 7.7 PO4 4.2Mg 2.1 LDH 649 ABG pH 7.41 pCO2 28 pO2 73 HCO3 18
UA sp.gr 1.010 alb 2+ WBC 2-3 RBC 30-50 glomerular RBC 40%
broad cast 2-3 UPCI = 4.4
Lab
ANA +ve Anti-dsDNA – pending Anticardiolipin – pending Anti-beta-2-GP1 – pending ANCA – pending Anti-GBM – pending H/C – no growth sputum – no bacteria, AFB-ve
What to do next?
Bronchoscope?CT scan?
Dexamethasone?
hemodialysis?
Plasma exchange?
Continue antibiotic?
Kidney biopsy?
Doppler ultrasound?Doppler ultrasound?
Consult nephro?Consult nephro?V/Q scan?
CPR?
Factor VIIa ?
Echo?Cyclophosphamide?
Sputum PCR-TB
28 29 30 1 2 3 4
Pip/Taz
FOB
Bronchoscope (30/9/53)
Finding : mucosal petichiae hemorrhage, no endobronchial lesion
BAL at antr basal RLL
persistent bloody BAL fluid RBC numerous WBC 565 (N 24, L 8, M 1, Eo 2,
macrophage 65) Hemosiderin score =0
What to do next?
Bronchoscope?CT scan?
Dexamethasone?
hemodialysis?
Plasma exchange?
Continue antibiotic?
Kidney biopsy?
Doppler ultrasound?Doppler ultrasound?
Consult nephro?Consult nephro?V/Q scan?
CPR?
Factor VIIa ?
Echo?Cyclophosphamide?
Sputum PCR-TB
Management
Plasma exchange วั�นที่�� 5, 6, 7, 11, 13, 15, 17 ตุ.ค.
Antibiotic VCV ventilator
28 2511 184
Pip/Tazdexa 5q8
meropenemcolistin// colistin
Methyl P x3
GTCPRES
P.Ex x7
WBC, schistocytePT,PTT , haptoglobin <10Sputum – A.baum
tracheostomy
levofloxacin
dexa 5q6vancoampho
dexa 5q12
Sputum – MRSA yeast
Hct
WBC
Plt
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53 ไข้� Sputum – A.baum, S.maltophilia
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53 ยั�งมีเสมีหะปนเลื�อด ,Hct 25 Cr 3.9
21/01/51
28/09/53
30/09/53
3/10/53
11/10/53
16/10/53
21/10/53
26/10/53 รู้��ตั�วด ไมี�มีไข้� Sputum - MRSA
Microscopic polyangiitis
MPA
ANCA-associated vasculitis (AAV) involve small vessels, primarily affects kidneys and lungs.
History
1866 Kussmaul and Maier described a case with “p eculiar mostly nodular thickening of countless arteries of and below the caliber of the liver arte
ry…” which they dubbed periarteritis nodosa1950 Davson recognized microscopic polyarteritis
as a distinct entity of polyarteritis nodosa1954 Godman and Churg noted that the
“microscopic form of periarteritis” was closely related to WG and CSS.
1982 Davies and colleagues discovered ANCA1988 Jennette and Falk reported that serum from
patients with WG, renal-limited vasculitis, and MPA was associated with p-ANCA
Rheum Dis Clin North Am -2010 36 3 54558. Aug; ( ):Rheum Dis Clin North Am -2010 36 3 54558. Aug; ( ):
1990 ACR classification criteria
at least 2 of the 4 criteria Nasal or oral
inflammation (oral ulcers or bloody nasal drainage)
Abnormal chest radiograph (nodules, fixed infiltrates, cavities)
Urinary sediment (>5 RBC/hpf or RBC casts)
Granulomatous inflammation on biopsy (in wall of artery or arteriole, perivascular, or extravascular)
at least 3 of the 10 criteria Weight loss > 4 kg Livedo reticularis Testicular pain or
tenderness Myalgias, weakness, leg
tenderness Mononeuropathy or
polyneuropathy Diastolic BP > 90 Elevated BUN/creatinine Hepatitis B virus Arteriographic
abnormality Biopsy of small or medium
artery containing PMN
Wegener’s granulomatosis
Polyarteritis nodosa
Polyarteritis nodosa vs. microscopic polyangiitis
Small/medium muscular artery
Renal vascular nephropathy
No lung involvement
ANCA negative
Small/medium arteries, arterioles, venules, capillaries
Glomerulonephritis Lungs involved in
up to one third ANCA positive
Microscopic polyangiitis
Polyarteritis nodosa
1994 Chapel Hill nomenclature
Arthritis Rheum - 1994 37 2 18792. Feb; ( ): .
Microscopic polyangiitis
Clincical Dx primary vasculitis
WG surrogate marker
Upper airway- bloody nasal discharge/crusting > 1 mo.- sinusitis, otitis media, mastoiditis > 3 mo.- retro-orbital mass or inflammation- subglottic stenosis- Saddle nose, destructive sinonasal disease
Lower airway- fixed pulm. infiltrates, nodules, cavity > 1 mo.- bronchial stenosis
Ann Rheum Dis 2007. February; 66 2( ): 222–227
classificaton algorithm
What is ANCA ?
Anti-neutrophil cytoplasmic antibody is positive in 50-75% of MPA patients
indirect immunofluorescence assay p-ANCA
ELISA anti-myeloperoxidase (a serine proteases)
20091361101 1111CHEST ; : –
Indirect immunofluorescence assay
cANCA
Granulocyte antigen of ANCA
MPA, SLE, RA, UC, CD, PSC, AIH
-2 0 0 0 : 1 8 : 6 2 9 6 3 5 .
Problem with pANCA detection
Perinuclear staining by ANAgranulocyte-specific ANA?
Epitope conformation
does ANCA has role in pathogenesis ?
A report of pulmonary hemorrhage and glomerulonephritis in neonate which mother had MPA
Remission is often accompanied by decrease in ANCA levels
In a prospective 100 pt with WG, increase in ANCA titer predicts a clinical relapse with sensitivity 79% and specificity 68%, though time period varies from 0–20 mo.
In another study of 106 pt with WG, serial changes in ANCA titers correlated with altered disease status in 64% of patients.
A 156prospective cohort of pat ients wwww wwwwww Ww wwwwwwww wwww wwwwwwwww ww wR -3 ANCA wwwwww were not associated with relapse
Nat Rev Rheumatol - 2010 6 11 65364. Nov; ( ): .
I have no MPO
Anti-MPO
Pauciimmune NCGNSystemic vasculitis
lipopolysaccharide
Now I have MPO
Anti-PR3
and pauciimmune glomerulonephritis !
Normal mice
does ANCA has role in pathogenesis ?
reduced leukocyte
rolling
augmented adhesion
and transmigration
across the
endothelium
Nat Rev Rheumatol - 2010 6 11 65364. Nov; ( ): .
Kelly’s textbook of Rheumatology, 8th ed.
What does ANCA do with body ?
Nat Rev Rheumatol - 2010 6 11 65364. Nov; ( ): .
Nat Rev Rheumatol - 2010 6 11 65364. Nov; ( ): .
RITUXIVASRITUXIVAS
N Engl J Med - 2010 15363 3 21120. Jul ; ( ):N Engl J Med - 2010 15363 3 22132. Jul ; ( ): .
RAVERAVE
SteroidRituximab x 4 weeks
IVCY x 2 pulses
SteroidIVCY x 3-6 mo.
Azathioprine
New Dx AAV and renal involvementNon-blind RCT
severe new or relapse 148 WG, 24 MPAdouble-dummy, noninferiority db-RCT
Stone JH. M MMMMMMMMMMMM M MMMMMM M MMMMMMM . USAJones RB. MMMMMMMMMMMMM M MMMMMMM. UK
Ritu (33)
Cy (11)
remission
76% 82%
Severe AE
42% 36%
mortality
18% 18%
Pulse + pred 5 mo.Rituximab x 4 weeks
placebo CY
Pulse + pred 5 mo.oral CY x 3-6 mo.
placebo Rituximab
Ritu (99)
Cy (98)
Remission
without pred
64% 53%
relapse pt.
67% 42%*
DAH pt.
57% 41%*
MPA 67% 62%
Placebo Aza Azathioprine
Ritu (99)
Cy (98)
Pulmonary
52% 54%
DAH 27% 24%
Renal 66% 66%
noninferi
or
I
M
Where ANCA come frome ?
Nat Rev Rheumatol - 2010 6 11 65364. Nov; ( ): .
Epidemiology
Rheum Dis Clin North Am -2010 36 3 54558. Aug; ( ):Rheum Dis Clin North Am -2010 36 3 54558. Aug; ( ):
MPA is more prevalent than WG in Asian population.
Clinical presentation
Average age of onset 50-60 years Onset may be hyperacute, with
rapidly progressive glomerulonephri tis and pulmonary hemorrhage
Or can be insidious with several years of intermittent constitutional s
ymptoms, purpura, mild renal disea se, and even periodic bouts of hemo
ptysisMurray and Nadel’s Textbook of Respiratory Medicine, 5th ed.
Autoimmun Rev - 2010 9 12 8129. Oct; ( ):
Clinical presentation
pulmonary
25–55% of patients . 10–30% with diffuse alveolar hemorrhage . Fibrosis, focal infiltrates, effusions, pulmonary arterial hypertension
renal Segmental necrotizing glomerulonephritis and RPGN is almost universal .
Upper airway
5–30% of patients, with sinus disease most common
musculoskeletal
Arthralgias and myalgias in at least 50% of patients
eyes 0–30% of patients . Scleritis, episcleritis, uveitis .
Cardiac 10–15% of patients . CHF and pericarditis have been described .
GI 35–55% of patients . Pain, bleeding, ischemia . Rare visceral aneurysms .
skin 35–60% of patients. Commonly purpura
Neuro 10–50% of patients . Mononeuritis multiplex reported cerebral infarction
Murray and Nadel’s Textbook of Respiratory Medicine, 5th ed.
Pathology
Neutrophilic capillaritis without granuloma, fibrinoid necrosis and arterial wall disruption, intra alveolarRBC - and hemosiderin laden macrophages
Focal segmental necrotizing glomerulonephritis
Murray and Nadel’s Textbook of Respiratory Medicine, 5th ed.
Imaging of pulmonary vasculitis
CXR findings is alveolar infiltrations , most often bilateral diffuse pattern.
Lung fibrosis in relapsing alveolar inflammation
J Comput Assist Tomogr - - 2004 28 5 7106. Sep Oct; ( ):
CT finding in 51 MPO-ANCA patients
Radiology -2010 255 2 32241. May; ( ):
Radiographics - -2002 22 4 73964. Jul Aug; ( ):
consolidation with interlobular septal thickeningGround-glass opacity
fine reticular pattern superimposed on a background of groundglass - attenuation that is the crazy paving pattern
J Comput Assist Tomogr - - 2004 28 5 7106. Sep Oct; ( ):
F 74y MPO. F/U HRCT show new honeycombing at 5 months
3 mo.
M 60Y MPO resemble IPFCT show GGO and reticulation in subpleural regionVAT Bx shows irregular interstitial fibrotic thickening, hemosiderin ladenmacrophages
Radiology -2010 255 2 32241. May; ( ):
Prognosis of MPAPrognosis of MPA
prognostic five-factor score proteinuria (>1 g/24 hours) serum creatinine greater than 1.58 mg/dL Gastrointestinal involvement Cardiac involvement central nervous system involvement
The 5-year survival with a score of 0 is 88%, while a score 2 is associated with 54% survival
Relapses after successful induction therapy are common (25-33% ) but usually less severe and responsive to therapy Murray and Nadel’s Textbook of Respiratory Medicine, 5th ed.
Arthritis Rheum - 1999 42 3 42130. Mar; ( ):
Prognosis of MPA with DAHPrognosis of MPA with DAH
alveolar hemorrhage tends to be severe and is often life-threatening
Early mortality rate 25%. 5-year survival 65%
Murray and Nadel’s Textbook of Respiratory Medicine, 5th ed.
Treatment – systemic vasculitisTreatment – systemic vasculitis
Chest - 2006 129 2 45265. Feb; ( ): .
Remission induction phase and maintenance phase
Titrate immunosuppression to control disease while minimizing the potential for adverse side effect
Treatment - MPATreatment - MPA
prednisone 1 mg/kg/d (often preceded by pulse of m ethylprednisolone 1 g/d x 3 days ) pl us
cycl ophosphami de ar e t he usual appr oach t oinduce remission.
Cyclophosphamide may be administered orally ( 2mg/kg/d ) or intravenously ( 15mg/kg iv q 2-3 weeks )
Activity of disease = Birmingham Vasculitis Activity Score (BVAS)
After remission, patients may be switched to either azathioprine ( up to 2 mg/kg per day ) or methotrexate ( up to 25 mg/week).
optimal duration of maintenance is not clear. 1 year is reasonable.
Refractory case : IVIG, infliximab, mycophenolate mofetil, rituximab, deoxyspergualin, Antithymocyte globulin
Induction Maintenance
WG
MPA
oral cyclophophamide+bactrimsteroid oral CY
Induction Maintenance
WG
MPA
oral cyclophophamide+bactrimsteroid
pulse IVCY less SE
Azathioprine = oral CY
Methotrexate = Aza
MTX = oral CY non-organ threatening AAVNORAM 2005
CYCLOPS 2009
Rituximab = IVCYRITUXIVAS 2010
Rituximab > oral CYrelapse AAV, DAHRAVE 2010
PE > methylpredsevere renal AAVMEPEX 2007
Etanercept add-on WGET 2005
oral CY
CYCAZAREM 2003
Pagnoux 2008
Leflunomide > MTXmore AEMetzler 2007
MMF > IVCYmild renal MPA
IMPROVE(terminated)
Weixin 2010open RCT n=35
MMF < Aza
Bactrim add on
Nat Rev Rheumatol. 2010 Nov;6(11):653-64 .
Treatment - DAHTreatment - DAH
Pulse methylprednisolone + steroid + cyclophosphamide
Induction + Plasma exchange Induction with Rituximab + steroid
Factor VIIa Extracorporeal membrane oxygenation
Thank You
Further readings
ANCA-associated vasculitides--advances in pathogenesis and treatment . Nat Rev Rheumatol - . 2010 Nov;6(11):653 64.
Imaging of pulmonary vasculitis .Radiology -. 2010 May;255(2):322 41.
Microscopic polyangiitis : Clinical presentation . Autoimmun Rev . 2010 Oct;
- 9(12):812 9.