connective tissue disorders i
TRANSCRIPT
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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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Rheumatoid Arthritis
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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Rheumatoid Arthritis
- 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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Rheumatoid Arthritis
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
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Rheumatoid Arthritis Typical erosion
Narrowing joint
space juxta-articular
osteopenia
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Rheumatoid Arthritis
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%