connective tissue disorders i

8/4/2019 Connective Tissue Disorders I

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Connective Tissuedisorders


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Connective Tissue

disorders Heterogenous disorders with common

features:

inflammation of skin, joints, and otherstructures rich in connective tissue

alteration of immunoregulation production of autoantibodies and

abnormalities of cell-mediated immunity


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Outlines Rheumatoid Arthritis

Sjogrens Syndrome

Systemic Lupus Erythematosus Progressive Systemic Sclerosis

Ankylosing Spondylitis

Reiter

s Syndrome Psoriatic Arthritis


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Rheumatoid Arthritis


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A chronic multisystem disease ofunknown etiology, characterized by

persistent inflammatory synovitis( usually involving peripheral joints ina symmetric fashion)


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Rheumatoid Arthritis Etiology

Genetic: association with HLA-DR4 Environmental factors also plays a role

Prevalence 0.8% of population women affected 3 times more often than men prevalence increased with age onset: more frequent in fourth and fifth decades

Pathology Immunologically mediated event:

Synovial hyperplasia, lymphocytic infiltration of synovium Local production of cytokines and chemokines


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HLA Human Leukocyte Antigen

Any one of 4 genetic markers on ch. 6

HLA-A,B,C,D ( several alleles on each) Associated certain diseases

HLA is also used to assess tissuecompatibility

WBC are used for testing


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Rheumatoid Arthritis -

Clinical manifestations 1.Articular manifestations

Symmetricpolyarthritis of peripheral jointswith pain, tenderness and swelling of affected

joints Morning stiffness ( > 30 min) or after

prolonged inactivity

Proximal interphalangeal joints (PIP) and

metacarpophalangeal joints (MCP) Metatarsophalangeal joints( MP), wrists,

elbows and ankles

Joint deformities


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- Clinical manifestations Extra-articular manifestations Cutaneous- subcutaneous rheumatoid nodules, vasculitis

( leg ulcers) Pulmonary- nodules, interstitial disease, bronchiolitis,

pleural disease Ocular-scleritis Hematologic- anemia, splenomegaly and neutropenia

( Feltys syndrome, 1-2%) Cardiac- pericarditis, myocarditis Neurologic- myelopathies secondary to cervical spine

disease Fever ( low grade)


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Feltys syndrome

Hypersplenism occurring in R.A.

Manifested by: Splenomegaly, leukopenia, frequent

infection

Cause: unknown


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Fever of Unknown Origin Infection

Autoimmune disease

Malignancy


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Rheumatoid Nodule


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Diagnosis Physical exam with careful exam of all joints CBC: anemia

Rheumatoid factor: 85% ( RF correlated with severe disease, nodules, extra-

articular features)

ESR elevation ( 90%) Synovial fluid analysis: rule out infection

Radiograph ( X-ray) juxta-articular osteopenia, joint space narrowing,

marginal erosions Only soft tissue swelling without bony change in 1st

months of disease


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Rheumatoid Arthritis Typical erosion

Narrowing joint

space juxta-articular

osteopenia


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Criteria for rheumatoid arthritis ( anyfour of the following) Morning stiffness > 1h ( > 6month)

Arthritis of three or more joints Arthritis of hand joints Symmetrical arthritis Rheumatoid nodule Serum rheumatoid factor Radiographic changes


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Rheumatoid Arthritis Treatment

Physical therapy Aspirin or NSAIDs Intra-articular glucocorticoids Systemic glucocorticoids

Disease-modifying antirheumatic drugs(DMARD) Methotrexate: block folate reduction ( toxicity of

BM, liver, kidney) Gold salts: ineffective ( pancytopenia,hepatitis) Hydroxychloroquine ( anti-malarial) Sulfasalazine ( anti-inflammation) D-penicillamine

Immunosuppressive therapy Azathioprine, cyclosporine, cyclophosphamide ( for

pts failing DMARD)


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Sjogren

s Syndrome


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Sjogren

s Syndrome A chronic, systemic inflammatory disorder

of unknown cause, characterized bydryness of the mouth, eyes and othermucous membranes (and often associatedwith rheumatic disorders sharing certain

autoimmune features)


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Sjogren

s Syndrome (SS) Epidemiology

An association between HLA-DR3 antigens andprimary SS

Prevalence: RA> Sjogrens syndrome > SLE

Pathology Atrophy of secretory epithelium of lacrimal

glands causing dryness of cornea and

conjuntiva Lymphocyte infiltration


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Sjogren

s Syndrome Classification:

Primary SS (Sicca syndrome)

Affect only eyes or mouth Secondary SS

Generalized collagen vascular disease


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Sjogrens Syndrome Symptoms and Signs (secondary SS)

Arthritis (33%) Similar distribution to RA; but joint S/S are milder

and rarely destruction

Parotid glands enlargement and saliva

diminished (in 1/3) Firm, fluctuating sized, mild tender

Inhibit chewing and swallowing and promote toothdecay

Dryness of skin and mucous membranes of nose,throat, bronchi and vagina

Dryness of respiratory tract -> lung infection

GI effects ( dysphagia)

Chronic hepatobiliary disease and pancreatitis


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Sjogrens Syndrome

Diagnosis Eye is tested for dryness

Schirmer test measures the quantity of tears

A young person moistens 15mm of each paper strip;SS patients moisten < 5mm in 5 min

Salivary gland evaluation: sialography radiography of the salivary tract after injection of a

radiopaque substance

Biopsy

RF present in >70% ESR elevated in 70%

Anemia (1/3); Leukopenia (1/4)


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Sjogren

s Syndrome Prognosis and Treatment Related to the associated connective tissue

disorder

No specific treatment for basic process Local manifestations: treated symptomatically Connective tissue involvement:

Usually mild and chronic

Corticosteriods and immunosuppressive drugsindicated only occasionally


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Systemic Lupus

Erythematosus (SLE)


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Systemic Lupus

Erythematosus

Disease of unknown etiology in which

tissues are damaged by deposition ofautoantibodies and immune complexes


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Systemic Lupus

Erythematosus Epidemiology Genetic Environmental

Sex hormone: 90% are women (usually of child- bearing age) After menopause, flare is rare

More often in blacks than in whites

May involve any organ system and have a widerange of disease severity

SLE


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SLE Clinical manifestations

Constitutional- fatigue, fever, malaise, weight loss

Cutaneous- rashes ( malar butterfly rash) Photosensitivity, vasculitis, alopecia, oral ulcers

Arthritis- (inflammatory, symmetric, nonerosive, 90% pts before

other S/S) Hematologic-

anemia, leukopenia (


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Diagnostic Criteria: 4/11( 1982 revised criteria )

Malar rash

Discoid rash

Photosensitivity

Oral ulcer Arthritis

Serositis

Renal disorder

Neurologic disorder

Hematologic disorder

Immunologic disorder Antinuclear antibody


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Mucocutaneous lesions

ystem c upus


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ystem c upusErythematosus

Classification Spontaneous SLE

Drug- induced lupus


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Systemic Lupus

Erythematosus-- Evaluation History and physical exam ANA(+)

A cardinal feature, >98%, screening for SLE, but not

specific for SLE Anti-DS DNA antibody: more specific for SLE CBC ESR Complement levels: low level in C3,C4 Urinalysis Radiographic studies


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Immune Complex Circulating Antigens -> Ab produced to attack Ag->

Immune complex formed in blood Immune complex deposit in tissues

(e.g. glomeruli or blood vessels ) ->

Complement activated-> Tissue injury

ystem c upus


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ystem c upusErythematosus--

Drug- induced lupus

A clinical and immunologic picture similar to spontaneousSLE may be induced by drugs procainamide, hydralazine, isoniazid, cholorpromazine,

methyldopa Clinical features:

Constitutional Joint Pleuropericardial (CNS and renal disease are rare)

Lab ANA (+) in all pts Antihistone antibodies may be present Antibody to dsDNA and hypocomplementemia are uncommon

Prognosis Most pts improve following withdrawal of offending drug


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Systemic Lupus

Erythematosus Treatment Goals: control acute, severe flares

Develop maintenance strategies 1.NSAIDs

2.Antimalarials Hydroxycholoroquine; improve constitutional, cutaneous,

articular manifestations, but ophthalmologic evaluation dueto ocular toxicity

3.Systemic glucocorticoids for life-threatening or severely disabling manifestations

Needed in doses of 40 mg/d or more during severe flares,tapered to low doses 10-15mg/d during disease inactivity 4.Cytotoxic agents :

cyclophosphamide, azathioprine 5.Anticoagulation

indicated in thrombotic complications


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Systemic Lupus

Erythematosus Prognosis The more severe the disease, the greater the

risk of drug-induced complications, which

increase morbidity and mortality Flares are rare after menopause. Infections have become the leading cause of

death

Late onset SLE occur and difficult todiagnose 10-yr survival in most developed countries

is > 95%

connective tissue disorders i

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