connective tissue disorder

8/10/2019 Connective Tissue Disorder

1/51

Connective TissueDisorders

Irma A. Lee, MD, MHPEdDepartment of Obstetrics and Gynecology

March 2, 2011


2/51

Systemic Lupus

Erythematosus

! Multisystemic autoimmune rheumatic

diseases with protean and often

complex manifestations

! Chronic or of a relapsing or remitting

form

! Has serious muskuloskeletal, renal

and cardiovascular effects


3/51

Pathogenesis

! SLE occurs when a patient develops

persistent pathogenic autoantibodies

and immune complexes

! These alter the normal anatomy and

function of target tissues and organs

! These gives rise to a constellation of

signs and symptoms


4/51

Autoantibodies

! Antibodies directed against self or normal

tissues

! Maybe stimulated by bacterial or viral injury of

susceptible 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


5/51


6/51

Table 54-1


7/51

Clinical Findings

! May be confined initially to one organ

system, with others being involved as the

disease progresses.

! Alternatively, the disease may initially

manifest by multisystem involvement.

! Common findings are malaise, fever,

arthritis, rash, pleuropericarditis,

photosensitivity, anemia, and cognitive

dysfunction.


8/51

Table 54-3


9/51

Table 54-2


10/51

Laboratory Findings

! Screening

- Antinuclear antibody (ANA) highly

sensitive but not specific

! Specific test for Lupus

- Double stranded DNA (dsDNA)

- Smith (Sm)


11/51

Effect of SLE on Pregnancy

! If no HPN, renal impairment or APS ---

pregnancy outcome is better

! Renal disease HPN developed and

proteinuria worsened! Increase incidence of preeclampsia


12/51

SLE Nephritis

! Require intense fetal and maternal

surveillance

! Pregnancy outcome is better if lupus activity

has been quiescent for at least 6 months

before pregnancy

! Pregnancy outcome is better if at conception

creatinine


13/51

SLE Nephritis

! Proteinuriais the most commonpresentation (75%),followed by hematuriaor aseptic pyuria (40%), and followed byurinary cast (33%).

!

Diffuse proliferative glomerulopnephritismost common and most serious histologiccategory.

! !of women experienced renal deterioration

! 50% fetal lossrate if creatinine is >1.5mg/dl


14/51


15/51

Fetal Outcome

! Pregnancy loss

associated with APS , LAC

! Preterm delivery

HPN, renal compromise and PROM

! IUGR

! IUFD

APS, hx of fetal death, active disease atthe time of conception, lupusnephropathy, HPN


16/51


17/51

Management

! Antepartum surveillance

- BPS, NST, CST, Doppler velocimetry

! !C3, C4 and CH50 associated with activedisease

!

Hemolysis (+) Coombs test, anemia,reticulocytosis, unconjugated hyperbilirubinemia

! Thrombocytopenia

! Leukopenia

! Urine test


18/51

Pharmacologic Treatment

! Analgesics arthralgia, serositis, arthritis, fever

- acetaminophen, NSAIDs, aspirin

!

Corticosteroid therapy- Prednisone 1-2mg/kg/day 10-15mg/day

- for life threatening manifestations of SLEex. Nephritis, neurologic involvement,thrombocytopenia, hemolytic anemia,cutaneous manifestations


19/51

Pharmacologic Treatment

! Immunosuppression

- azathioprine

!

Antimalarial

- interfere with normal phagocyticfunction and antigen processing, inhibit

platelet aggregation and reduce serum

lipids

- hydroxychloroquine


20/51

SYSTEMIC SCLEROSIS

(SCLERODERMA)

! Multisystem disease with fibrosis and

thickening of the skin and visceral

organ due to accumulation of collagen


21/51


22/51

CLINICAL MANIFESTATIONS

! Reynauds Phenomenon

! Swelling of distal extremities and face

!

Fullness & epigastric burning pain

! Dyspnea! Renal

!

CREST


23/51

MATERNAL COMPLICATIONS

1. Hypertension

2. Renal Failure

3.

Cardio-pulmonary complications as a

result of pulmonary interstitial fibrosiswith vasculopathy"Pulmonary

hypertension


24/51

FETAL COMPLICATIONS

1. Preterm deliveries

2. Fetal growth restriction

3.

Increase perinatal deaths


25/51

GOALS OF THERAPY

1. Improve organ function

2. Relieve symptoms


26/51

DRUG THERAPY

1. Corticosteroids myositis,

pericarditis, hemolytic anemia

2.

ACE Inhibitors relief of hypertension

and renal failure


27/51

A P A S

Autoimmune disorder characterized by

circulating antibodies against

membrane phospholipid and one or

more specific clinical syndromes


28/51

Classification

! Primary APS

# occurs alone with associated thrombo-

embolic phenomena, thrombocytopenia,

adverse obstetrical outcome

! APS secondary to SLE, drugs, infections,

malignancies

-


29/51


30/51

Proposed mechanisms in pregnancy loss inAPS

TARGET

! Eicosanoids

! Antithrombin III

! Protein C & S

! Endothelial cells

and platelets

! Annexin V

MECHANISM

Decrease prostacyclin & increase inthromboxane production by endothelial

cells

Inhibition of heparan sulfate heparin-

dependent activation of antithrombin III

Inhibition of the activation of Protein C-Protein S- pathway

Activation of endothelial cells & platelets;

expression of adhesion molecules

Reduce annexin V production, inhibition of

its function in placenta by APLantibodies


31/51

Clinical Manifestations

! Pregnancy wastage due to decidual/placental

thrombosis or immune complex deposition! Pre-eclampsia in 20-30%

! IUGR (50%), associated with moderate to high titerACA IgG, history of fetal demise, prednisonetherapy

!

Preterm delivery (25-40%) secondary to PPROM inpatients 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%


32/51

Clinical Criteria for Definite APS

1. Vascular Criteria confirmed by imaging,

Doppler, or histopathology

2. Pregnancy Morbidity

a. > 1 unexplained death of a normal fetus > 10 weeks

b. > 1 premature births < 34 weeks due to pre-eclampsia

or placental insufficiencyc. > 3 consecutive spontaneous abortions < 10 weeks

International Consensus Statement on

Preliminary Criteria for

Classification of APS

Wilson, Arthritis Rheuma 1999


33/51

Classification Criteria for the

Antiphospholipid Antibody Syndrome

Clinical! Thrombosis

# Unexplained venous arterial, or small vesselthrombosis in any organ or tissue

! Pregnancy#

One or more unexplained fetal losses after 10weeks

# 3 or more consecutive abortions before 10weeks

# Preterm delivery for severe preeclampsia

# Placental insufficiency before 34 weeks


34/51

Classification Criteria for the

Antiphospholipid Antibody Syndrome

Laboratory

! Anticardiolipin antibodies

# IgG or IgM isotypes in medium to high titers at

least 6 weeks apart

! Lupus anticoagulant#

Partial thromboplastin time, dilute Russel viper

venom test (dRVVT) and the plateletneutralization procedure

# Identified twice at least 6 weeks apart


35/51


36/51

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 of thrombosis


37/51

! Low titer ACA IgG

0-3% non-pregnant women

2-4% of pregnant women

4-5% with single unexplained early pregnancyloss

! Moderate to High titer ACA IgG

5 20% > 3 spontaneous pregnancy losses

Prevalence of ACA


38/51

Indications to Identify Lupus Anticoagulant andAntiphospholipid Antibodies

! Recurrent pregnancy loss! Unexplained 2ndor 3rdtrimester loss

! Early onset severe preeclampsia

! Venous or arterial thrombosis! Unexplained fetal growth restriction

! Autoimmune or connective tissue disease

! False positive serological test for syphilis

! Prolonged coagulation studies

! Positive autoantibody test


39/51


40/51

Management of Classical APS

# Risks of fetal loss

# Thrombosis or stroke

# Preeclampsia

# IUGR

# Preterm delivery

1.

Preconception Counseling


41/51

Management of Classical APS

# Prevention of pregnancy loss

# Thromboprophylaxis

# Prevention of complications of placental

insufficiency

# Postpartum treatment

2. Treatment Regimens


42/51

Treatment Guidelines

! Low dose aspirin, 80mg daily

- blocks the conversion of arachidonic acid tothromboxane A2 while sparing prostacyclin

! Heparin, 5000-10,000 units SC q 12 hours

- prevent venous and arterial thromboticepisodes

! Glucocorticoids use only if with connective

tissue disorder

! Immunoglobulin therapy 0.4 g/kg daily for 5days

- use when 1stline therapies have failed


43/51

Treatment Guidelines

! Calcium and Vitamin D

- prevent osteoporosis

!

Fetal antepartum surveillance

- fetal growth monitoring- Biophysical profile scoring

- NST, CST

- Doppler velocimetry


44/51

Recurrent Pregnancy Loss with Antiphospholipid

Antibody:

A Systematic Review of Therapeutic Trials

! Combination therapy with Aspirin and Heparin may reduce

pregnancy loss in women with antiphospholipid antibodies

by 54%. Further large, randomized controlled trials with

adequate allocation are necessary to exclude significantadverse events

Empson et al

ACOG January 2002


45/51

Rheumatoid Arthritis

! Chronic inflammatory/autoimmune disease

! Characterized by symmetrical polyarthritis of

the small joints of hands and feet

! Cardinal feature is inflammatory synovitis

that usually involves the peripheral joints.! The disease has a propensity for cartilage

destruction, bony erosions, and joint

deformities.


46/51

Rheumatoid Arthritis

! Genetic predisposition

!

Cigarette smoking increase the

risk

! Protective effect of pregnancy


47/51

Clinical Manifestations

! Prodromal phase malaise, weight

loss, arthralgias, or joint stiffness

! The onset is insidous with pain and

swelling in one or more joints in the

upper extremities

! Progression is usually centripetal (from

small joints to large joints)

!

Clinical improvement during pregnancy


48/51


49/51

Management

! Pain relief

! Reduction of inflammation

! Protection of articular

structures

! Preservation of function


50/51

Management

! Systemic and articular rest

! Use of heat and cold modalities

! Physical and occupational therapy

! Aspirin or NSAIDs

! COX-2 inhibitors

! Disease modifying antirheumatic drugs

(DMARDs)

! Glucocorticoid therapy


51/51

Thank You

connective tissue disorder

Documents