CONNECTIVE TISSUE

DISORDERS (CTD)
Codrina Ancuta,
MD, PhD, lecturer
Rheumatology-Rehabilitation

Systemic Lupus Erythematosus (SLE)

Systemic sclerosis (SSc)

Polymyositis/ Dermatomyositis (PM/DM)
Mixed Connective Tissue Disease (MCTD)
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Overview

Definition
Pathogenesis
Presentation
Investigations
Management

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SYSTEMIC LUPUS ERYTHEMATOSUS: DEFINITION

Multi-system

inflammatory CTD, in which inflammation,

auto-antibodies production, immune complex deposition
result in organ damage

Subsets:
SLE;
Chronic cutaneous lupus;
Subacute cutaneous lupus;
Drug-induced lupus;
Neonatal lupus;
Overlap syndromes
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SLE PATHOGENESIS
Genetic predisposition
(HLA, non-HLA)
Trigger factors (UV,
infections, drugs)
Hormonal status
(estrogens)

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Immune abnormalities
Polyclonal B activation
Pathologic antibody production
Impaired immune complexes
clearance & tissue deposition
Complement activation
Distrubed apoptosis

Organ damage

 Skin

SLE PRESENTATION

(lupus specific & non-specific; butterfly;

photosensitivity; oral ulcerations)
Musculo-skeletal (non-erosive arthritis RA-like)
Cardio-vascular (pericarditis, myocarditis, Liebmann
Sachs endocarditis, early accelerated atherosclerosis)
Renal (nephritis - 6 WHO classes)
Respiratory (pleuritis, pleuresy, pneumonitis,
alveolitis, embolism, etc)
Neurologic (neuro-lupus; peripheral neuropathy)
ACR 1997 Diagnostic Criteria
Negative prognostic factors

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SLE INVESTIGATIONS
Inflammatory syndrome (ESR; CRP level)
Hematologic assessment (cytopenia)
Immune abnormalities (total ANA, anti-dsDNA, -Sm, -Ro,

La, -phospholipids, total complement and fractions, etc)

Renal assessment (including Addis & proteinuria; kidney
biopsy)
Pulmonary,
cardio-vascular,
neurologic,
muscular
assessment s
Osteodensitometry (chronic glucocorticoid administration!)
Disease activity versus organ damage
(SLEDAI, BILAG scores)
Therapeutic response

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SLE MANAGEMENT

Chronic

corticosteroids (iv, oral): high doses

according to different visceral involvement

Immunosuppressives

(Methotrexate,
Azathioprine, Cyclophosphamide, Cyclosporine
A, mycofenolat mofetil) and immunomodulators (antimalarials)

Biological
agents

therapy: inhibitors Blys, anti-CD20

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SYSTEMIC SCLEROSIS: DEFINITION

Multi-systemic chronic
characterized by:

inflammatory

CTD

Vascular abnormalities (structural & functional)

Skin and internal organs excessive fibrosis
Immune system activation

Classification:

diffuse cutaneous SSc, limited

cutaneous SSc (CREST); scleroderma sine
scleroderma

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SSc PATHOGENESIS
Genetic predisposition

Immune system
activation

Environmental
factors

endothelial cell
activation /damage

Fibroblast activation
End-stage pathology
Obliterative vasculitis
Fibrosis

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SSc PRESENTATION
Vascular involvement Raynaud phenomenon; pitting scars
Skin involvement sclerodactyly, SSc facies, RODNAN score
Musculo-skeletal involvement non-erosive RA pattern;

myositis; acroosteolysis; calcinosis

Digestive involvement specific esophageal involvement
Pulmonary involvement: diffuse fibrosis; pulmonary
hypertension
Cardiac involvement
Renal involvement scleroderma renal crisis

ACR diagnostic criteria

LeRoy & Medsger criteria
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SSc INVESTIGATIONS
IMMUNOLOGY

Digestive

Anti-Scl70 antibodies
Anti-centromere antibodies

Anti-U3RNP antibodies
Anti-RNA polymerase III

antibodies
Characteristic clinical pattern
with different antibodies
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tract assessment
(endoscopy,
manometry,
barium)
Chest
X-ray,
(high
resolution) CT, spirometry
Capillaroscopy
Cardiac ultrasound, right
heart catheterism
Skin biopsy

SSc MANAGEMENT
Immunosuppressants

& anti-fibrotics: methotrexate,

azathioprine, cyclosporine A, cyclophosphamide
Corticosteroids limited indications (early edematous
SSc, pulmonar involvement)
Vasodilators: calcium channel blockers, i.v. prostaglandins
(Iloprost, Epoprostenol); 5-phosfodiesterase inhibitors
(Sildenafil); endothelin receptor inhibitors (Bosentan,
Sixtasentan)
Other symptomatic therapy

Aiming to improve

Vascular & immune abnormalities

Excessive fibrosis

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POLY/DERMATOMIOSYTIS: DEFINITION
chronic inflammatory immune-mediated muscular disorder
characterized by:
non-suppurative chronic inflammatory infiltrate affecting
skeletal muscle

proximal myalgias & muscle weakness

Classification
Idiopathic inflammatory myopathies (PM, DM, juvenile DM,
myositis associated with other CTD)
Myositis associatis with malignancies
Inclusion body myositis
other: eozinophylic myositis, ossifiant myositis, localized myositis,
giant cells myositis
Infectious myopathies
Drug-induced and toxic myopathies

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PM/DM PATHOGENESIS

Genetic susceptibility
Environmental factors
Infections retroviruses
Drugs: corticosteroids, antimalarials, etc
Immune factors
Cells ( TCD4+, CD8+, Mo/Mf)
Cytokines (TNF, IL1, IL6, etc)
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PM/DM PRESENTATION

Muscle findings: Myalgias & muscle weakness

Skin findings: heliotrope rash, shawl sign and V sign,
Mechanic's hands, Gottron's sign

Articular: RA non-erosive pattern

Visceral: digestive, pulmonary (diffuse

interstitial
lung disease & anti-synthetase syndrome), cardiac;
General

1975 Bohan & Peter Criteria

Malignancy in up to 20% DM
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PM/DM INVESTIGATIONS
Serum muscle enzymes
Creatine kinase, lactate
dehydrogenase,
aldolase,
aspartate
aminotransferase
(AST)
and
alanine
aminotransferase (ALT)
Electromyography (EMG)
Increased insertional activity
and spontaneous fibrillations
Abnormal myopathic low
amplitude,
shortduration
polyphasic motor potentials
complex repetitive discharges
Muscle biopsy
Inflammator infiltrate + fiber
necrosis, regeneration, atrophy

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Auto-antibodies
Myositis-specific auto-antibodies

Anti-synthetase : Jo1, PL7, PL12,

OJ, EJ, etc

Anti-Mi2, anti-SRP
Myositis profile!

myositis associated autoantibodies

ANA, RF, anti-PM-scl

PM/DM MANAGEMENT
1. Corticosteroids (CS)
2. Immunosuppressives including methotrexate,
azathioprine, cyclophosphamide (for CS nonresponders or side effects)

clinical (muscle force), enzymatic & EMG

improvement

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