Post on 02-Jun-2018
transcript
8/10/2019 Immune-Mediated Connective Tissue Diseases
1/68
Irma A. Lee, MD, MHPhEd
Department of Obstetrics and Gynecology
Faculty of Medicine and SurgerySeptember 30, 2011
8/10/2019 Immune-Mediated Connective Tissue Diseases
2/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
3/68
Autoantibodies
- Antibodies directed against self or normal tissues
- Maybe stimulated by bacterial or viral injury ofsusceptible tissues tissue destruction
VIA1. CYTOTOXIC MECHANISM antibody attachment
to specific surface antigen CELL INJURY
2. IMMUNE COMPLEX MECHANISM antigen-antibody complex attaches to susceptible tissues
CASCADE OF CHEMOTACTIC RELEASE
8/10/2019 Immune-Mediated Connective Tissue Diseases
4/68
Human Leukocyte Antigen (HLA) Genetic loci code for cell-surface glycoprotein for
self and non-self recognition
!
Class I HLA-A, HLA-B, HLA-C! Class II HLA-DR, HLA-DQ, HLA-DP
8/10/2019 Immune-Mediated Connective Tissue Diseases
5/68
Systemic Lupus Erythematosus- Heterogenous syndrome with genetic loci is on
1q and 6p
- Overactive !lymphocytes autoantibody
production- Prevalent in women; 1:500 during child-bearing
8/10/2019 Immune-Mediated Connective Tissue Diseases
6/68
Table 54-1
8/10/2019 Immune-Mediated Connective Tissue Diseases
7/68
Table 54-2
8/10/2019 Immune-Mediated Connective Tissue Diseases
8/68
Table 54-3
8/10/2019 Immune-Mediated Connective Tissue Diseases
9/68
Laboratory Tests:1. Antinuclear antibody (ANA) best screening
but not specific
2. Double-stranded DNA (dsDNA) antibodies
Smith (Sm) antigen specific for SLE3. CBC anemia, leukopenia, thrombocytopenia
4. Proteinuria, casts
5. APTT
6. Rheumatoid factor assay
8/10/2019 Immune-Mediated Connective Tissue Diseases
10/68
Table 54-4
8/10/2019 Immune-Mediated Connective Tissue Diseases
11/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
12/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
13/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
14/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
15/68
Goals During Pregnancy1. 6 months remission prior to conception
2. No renal involvement
3. Prevent superimposed pre-eclampsia
4. No APA activity
8/10/2019 Immune-Mediated Connective Tissue Diseases
16/68
Major Complications1. Infection
2. Lupus flares
3. End-organ failure
4. Cardiovascular disease
8/10/2019 Immune-Mediated Connective Tissue Diseases
17/68
DRUG-INDUCED LUPUS- Lupus-like syndrome
- Procainamide
- Quinidine
- Hydralazine- Alpha-methyldopa
- Phenytoin
- Phenobarbital
8/10/2019 Immune-Mediated Connective Tissue Diseases
18/68
SLE Nephritis- Proteinuriais the most common presentation
(75%),followed by hematuriaor aseptic pyuria(40%), and followed by urinary cast (33%)
- Diffuse proliferative glomerulopnephritis mostcommon and most serious histologic category
- "of women experienced renal deterioration
- 50% fetal lossrate if creatinine is >1.5mg/dl
8/10/2019 Immune-Mediated Connective Tissue Diseases
19/68
Preeclampsia vs Lupus Nephritis
- It is difficult to differentiate SLE frompreeclampsia
- HPN and proteinuria common in all womenwith SLE
- Superimposed preeclampsia is encountered inthose with nephropathy
8/10/2019 Immune-Mediated Connective Tissue Diseases
20/68
Fetal Outcome- Pregnancy loss
Associated with APS , LAC
- Preterm delivery
HPN, renal compromise and PROM
- IUGR
- IUFDAPS, hx of fetal death, active disease at the
time of conception, lupus nephropathy, HPN
8/10/2019 Immune-Mediated Connective Tissue Diseases
21/68
Neonatal Outcome- Congenital heart block
anti SSA/Ro antibody
anti SSB/La antibody
- Neonatal Cutaneous Lupus
- Hematologic - usually transient
hemolytic anemia, leukopenia,
thrombocytopenia
8/10/2019 Immune-Mediated Connective Tissue Diseases
22/68
Management- Antepartum surveillance
BPS, NST, CST, Doppler velocimetry
- !C3, C4 and CH50 associated with active disease
- Hemolysis (+) Coombs test, anemia, reticulocytosis,unconjugated hyperbilirubinemia
- Thrombocytopenia
- Leukopenia
- Urine test
8/10/2019 Immune-Mediated Connective Tissue Diseases
23/68
Pharmacologic TreatmentAnalgesics
arthralgia, serositis, arthritis, fever- acetaminophen, NSAIDs, aspirin
Corticosteroid therapy- for life threatening manifestations of SLE ex.Nephritis, neurologic involvement,thrombocytopenia, hemolytic anemia, cutaneousmanifestations- Prednisone 1-2mg/kg/day 10-15mg/day
8/10/2019 Immune-Mediated Connective Tissue Diseases
24/68
Pharmacologic TreatmentImmunosuppression
- azathioprine
Antimalarial- interfere with normal phagocytic function andantigen processing, inhibit platelet aggregationand reduce serum lipids
- hydroxychloroquine
8/10/2019 Immune-Mediated Connective Tissue Diseases
25/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
26/68
A P A SAutoimmune disorder characterized by circulating
antibodies against membrane phospholipid andone or more specific clinical syndromes
8/10/2019 Immune-Mediated Connective Tissue Diseases
27/68
Classification
Primary APS
occurs alone with associated
thrombo-embolic phenomena,
thrombocytopenia,
adverse obstetrical outcome
8/10/2019 Immune-Mediated Connective Tissue Diseases
28/68
Classification
APS secondary to:
SLE
Drugs
Infections
Malignancies
8/10/2019 Immune-Mediated Connective Tissue Diseases
29/68
Clinical Manifestations
- Pregnancy wastage due to decidual/placentalthrombosis or immune complex deposition
- Pre-eclampsia in 20-30%- IUGR (50%), associated with moderate to high titer ACA
IgG, history of fetal demise, prednisone therapy- Preterm delivery (25-40%) secondary to PPROM in
patients on steroids- Thrombosis (20-60%)
Venous lower limb 55%Arterial involves the brain in 50%, heart 25%,
renal 25%Vascular occlusion from mitral or aortic valve 49%
8/10/2019 Immune-Mediated Connective Tissue Diseases
30/68
Clinical Criteria for Definite APS
1. Vascular Criteria confirmed by imaging,Doppler, or histopathology
2. Pregnancy Morbiditya. > 1 unexplained death of a normal fetus > 10 weeks
b. > 1 premature births < 34 weeks due to pre-eclampsiaor placental insufficiency
c. > 3 consecutive spontaneous abortions < 10 weeks
International Consensus Statement on
Preliminary Criteria for
Classification of APS
Wilson, Arthritis Rheuma 1999
8/10/2019 Immune-Mediated Connective Tissue Diseases
31/68
Laboratory Criteria for Definite APS
1. Lupus Anticoagulant (LAC)
! > 2 6 weeks apart
! Prolonged phospholipid-dependent coagulation
(aPTT, DRVVT, KCT, DPTT, Textarin Time)
International Consensus Statement on
Preliminary Criteria for the
Classification of APS
Wilson, Arthritis Rheuma 1999
8/10/2019 Immune-Mediated Connective Tissue Diseases
32/68
Laboratory Criteria for Definite APS
2. Anticardiolipin Antibodies (ACA)
! > 2 6 weeks apart
! Medium to high titer IgG or IgM by ELISA
International Consensus Statement on
Preliminary Criteria for the
Classification of APS
Wilson, Arthritis Rheuma 1999
8/10/2019 Immune-Mediated Connective Tissue Diseases
33/68
RESULT IgM (MPL) IgG (GPL)
Negative < 10 < 8
Low Positive 10-19 8-19
*Mid Positive 20-50 20-80*High Positive > 50 > 80
ACA (ELISA) : 10-30% of ACA (+) will be LAC (+)
- predictive of adverse fetal outcome
LAC: 70-80% LAC (+) will be ACA (+)
- predictive ofthrombosis
8/10/2019 Immune-Mediated Connective Tissue Diseases
34/68
Prevalence of ACA
- Low titer ACA IgG
0-3% non-pregnant women
2-4% of pregnant women
4-5% with single unexplained early pregnancy
loss
- Moderate to High titer ACA IgG
5 20% > 3 spontaneous pregnancy losses
8/10/2019 Immune-Mediated Connective Tissue Diseases
35/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
36/68
2. Syndrome of low levels of IgG or IgM ACL antibodiesassociated with fetal death or recurrent, pre embryonic orembryonic pregnancy loss
3. Syndrome of APL other than LA and ACL antibodies
associated with fetal death or recurrent pre embryonic orembryonic pregnancy loss
Classification System for Women with APS
d h l
8/10/2019 Immune-Mediated Connective Tissue Diseases
37/68
Proposed mechanisms in pregnancy lossin APS
TARGET
Eicosanoids
Antithrombin III
Protein C & S
Endothelial cells andplatelets
Annexin V
MECHANISM
Decrease prostacyclin & increase inthromboxane production by endothelial cells
Inhibition of heparan sulfateheparin-dependent activation of antithrombin III
Inhibition of the activation of Protein C-Protein
S- pathwayActivation of endothelial cells & platelets;
expression of adhesion molecules
Reduction of annexin V production, inhibitionof its function in placenta by APL antibodies
8/10/2019 Immune-Mediated Connective Tissue Diseases
38/68
Therapeutic approach to APAS inpregnancy
Objectives:
1. Improve maternal and fetal-neonatal outcomeby preventing pregnancy loss, pre-eclampsia,placental insufficiency and preterm birth
2. Reduce or eliminate maternal thrombotic risk
8/10/2019 Immune-Mediated Connective Tissue Diseases
39/68
Management of Classical APS
! Risks of fetal loss
!Thrombosis or stroke
! Preeclampsia
! IUGR
! Preterm delivery
1.
Preconception Counseling
8/10/2019 Immune-Mediated Connective Tissue Diseases
40/68
Management of Classical APS
! Prevention of pregnancy loss
!Thromboprophylaxis
! Prevention of complications of placentalinsufficiency
! Postpartum treatment
2. Treatment Regimens
8/10/2019 Immune-Mediated Connective Tissue Diseases
41/68
Treatment Guidelines
- Low dose aspirin, 80mg daily- blocks the conversion of arachidonic acid to
thromboxane A2 while sparing prostacyclin
- Heparin, 5000-10,000 units SC q 12 hours
- prevent venous and arterial thrombotic episodes
- Glucocorticoids use only if with connective tissuedisorder
- Immunoglobulin therapy 0.4 g/kg daily for 5 days- use when 1stline therapies have failed
8/10/2019 Immune-Mediated Connective Tissue Diseases
42/68
Treatment Guidelines
- Calcium and Vitamin D
- Prevent osteoporosis
- Fetal antepartum surveillance
- Fetal growth monitoring
- Biophysical profile scoring
- NST, CST
- Doppler velocimetry
8/10/2019 Immune-Mediated Connective Tissue Diseases
43/68
Thromboprophylaxis
8/10/2019 Immune-Mediated Connective Tissue Diseases
44/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
45/68
Postpartum Treatment
Sodium warfarin for 6 weeks postpartum
Lifelong Anticoagulation 2.5 to 3.0
International Normalized Ratio (INR)
Woman Diagnosed w/APS d i
8/10/2019 Immune-Mediated Connective Tissue Diseases
46/68
APS desires pregnancy
Preconception consultation w/Obstetrician & rheumatologist;
Inititate low dose aspirin
TVS to confirm liveembryo at 5.5-6.5 wks AOG
Initiate heparin treatment
DIAGNOSTIC TESTSCLINICALCARE
Prenatal visit q 2-4 wksuntil 20-24 wks then q
1-2 wks, thereafter
Monitor for fetal death,Preeclampsia & IUGR
Rheumatology visit q 2-4 wks
Obstetric ultrasound q 3-4weeks from 17-20 wks ofgestation
Assess fetal growth and AFI
Fetal surveillance weekly fr30-32 wks earlier if placental
Insufficiency is suspected
8/10/2019 Immune-Mediated Connective Tissue Diseases
47/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
48/68
SYSTEMIC SCLEROSIS (SCLERODERMA)
Multisystem disease with fibrosis and
thickening of the skin and visceral organ
due to accumulation of collagen
8/10/2019 Immune-Mediated Connective Tissue Diseases
49/68
TYPES OF SYSTEMIC SCLEROSIS
1. Overlap Syndrome Systemic Sclerosis withfeatures of other connective tissue disease
2. Mixed Connective Tissue Disease Syndrome
with Lupus, Systemic Sclerosis, Polymyositis,Rheumatoid Arthritis, high titers of Anti-RNPantibodies
8/10/2019 Immune-Mediated Connective Tissue Diseases
50/68
CLINICAL MANIFESTATIONS
- Reynauds Phenomenon
- Swelling of distal extremities and face
- Fullness & epigastric burning pain
- Dyspnea- Renal
- CREST
8/10/2019 Immune-Mediated Connective Tissue Diseases
51/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
52/68
FETAL COMPLICATIONS
1. Preterm deliveries
2. Fetal growth restriction
3. Increase perinatal deaths
8/10/2019 Immune-Mediated Connective Tissue Diseases
53/68
GOALS OF THERAPY
1. Improve organ function
2. Relieve symptoms
8/10/2019 Immune-Mediated Connective Tissue Diseases
54/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
55/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
56/68
TABLE 5-3 page 137
8/10/2019 Immune-Mediated Connective Tissue Diseases
57/68
URINARY TRACT INFECTIONS
1. Asymptomatic bacteriuria
2. Cystitis/Urethritis
3. Pyelonephritis
8/10/2019 Immune-Mediated Connective Tissue Diseases
58/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
59/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
60/68
CYSTITIS AND URETHRITIS
- Dysuria, urgency and frequency
- Pyuria, bacteriuria, hematuria
- 3 day regimen
- Chlamydia Trachomatis!cause of urethritis w/o growth on culture
8/10/2019 Immune-Mediated Connective Tissue Diseases
61/68
ACUTE PYELONEPHRITIS
- Occurs at the 2ndtrimester unilaterally and right-sided
- Characterized by fever, chills, and lumbar pain"CVA tenderness
- Organisms! E.Coli 75-80%! Klebsiella 10%! Enterobacter 10%! Proteus 10%
8/10/2019 Immune-Mediated Connective Tissue Diseases
62/68
ACUTE PYELONEPHRITIS
- Bacteremia!Sepsis syndrome
- Ampicillin + Gentamicin, Cefazolin orCeftriaxone
8/10/2019 Immune-Mediated Connective Tissue Diseases
63/68
FIGURE 42-4 page 994
8/10/2019 Immune-Mediated Connective Tissue Diseases
64/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
65/68
NEPHROLITHIASIS DURING PREGNANCY
- Pregnancy does not increase risk for stoneformation
- Presents with gross hematuria
- Sonography confirms suspected stone
- Intravenous Hydration & Analgesics- Lithotripsy
8/10/2019 Immune-Mediated Connective Tissue Diseases
66/68
8/10/2019 Immune-Mediated Connective Tissue Diseases
67/68
ACUTE NEPHRITIC SYNDROME
- Characterized by hematuria and proteinuria withrenal insufficiency and salt-water retention!edema, hypertension and circulatory congestion
-
Acute poststreptococcal glomerulonephritis
- Membranous IgA and mesangial glomerulonephritisare seen on renal biopsy
- Associated with fetal loss and perinatal mortality,
preterm delivery and growth restriction
8/10/2019 Immune-Mediated Connective Tissue Diseases
68/68