cp lec 6 systemic rheumatic diseases
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SYSTEMIC RHEUMATICDISEASES
SYSTEMIC RHEUMATICDISEASES
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Systemic Rheumatic DiseasesSystemic Rheumatic Diseases
1. Systemic Lupus Erythematosus
2. Sjogrens Syndrome3. Progressive Systemic Sclerosis
4. Rheumatoid Arthritis
5. Mixed Connective Tissue Disease
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GENERAL CHARACTERISTICSGENERAL CHARACTERISTICS
1. Unknown etiology
2. Multi-organ involvement
3. B cell hyperactivity4. Autoantibody formation, especially
antinuclear antibodies
5. Overlap syndromes
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(contd)(contd)
6. Genetic predisposition
7. Increased frequency in women of child-
bearing age8. Tissue injury caused by immune
mechanisms, often auto-antibodies or
immune complexes
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SYSTEMIC LUPUSERYTHEMATOSUSSYSTEMIC LUPUSERYTHEMATOSUS
A chronic multi-systemic disease of unknown
etiology
Usually involves the skin, associated withathralgia, fever, glomerulonephritis,
pericarditis, pleuritis, CNS dse, splenomegaly
& lymphadenopathies
Active nephritis most common cause ofdeath
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(contd)(contd)
Circulating autoimmune complexes of
antinuclear antibodies & their antigens are
the majorcauses
of pathologic changes: Immune complex deposition in the
glomerular capillary basement
membranes & at the dermo-epidermal
junction fixation to the site activation of complement system
inflammatory reaction & tissue injury results
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(contd)(contd)
Contributing factors: chronic viral infection,
heredity, environment, hormones
Role of drugs: procainamide & hydralazinecan induce a lupus-like syndrome
ANA & LE cells in 90% of patients
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ARA CRITERIA FOR SLEDIAGNOSIS
ARA CRITERIA FOR SLEDIAGNOSIS
UST-FMS Dept. of Lab. Medicine
Malar or discoid rash False positive test for
syphilis
Photosenstivity Anti-DNA, anti-SM
Oral or nasopharyngeal
ulcers
Urinary casts or
proteinuria
Non-erosive arthritis Pericarditis or pleuritis
Antinuclear antibody Psychosis or seizures
Hemolytic anemia, leukopenia, thrombocytopenia
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COMMON ABNORMALITIESIN SLE
COMMON ABNORMALITIESIN SLE
UST-FMS Dept. of Lab. Medicine
Antinuclear antibody 99%
Arthritis/arthralgia 92%
Fever 84%Dermatitis, photosensitivity 72%
Adenopathy 59%
Anemia 56%
Anorexia, nausea, vomiting 53%
Myalgia 48%
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COMMON ABNORMALITIESIN SLE (contd)
COMMON ABNORMALITIESIN SLE (contd)
UST-FMS Dept. of Lab. Medicine
Renal Disease 46%
Pleuritis 45%
Leukopenia 43%Pericarditis 30%
CNS symptoms 26%
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PATHOLOGICABNORMALITIES IN SLE
PATHOLOGICABNORMALITIES IN SLE
UST-FMS Dept. of Lab. Medicine
Kidney
Proliferative glomerulonephritis, wire
loop common; hematoxylin bodies rare;
occasionally membranous nephropathy
Heart Libman-Sacks (nonbacterial)
endocarditis; pericarditis
Skin Chronic dermatitis with basal cell
vacuolation & fibrinoid degenaration ofconnective tissue
CNS Cerebral vasculitis; focal gliosis
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...PATHOLOGICABNORMALITIES IN SLE...PATHOLOGICABNORMALITIES IN SLE
UST-FMS Dept. of Lab. Medicine
Lung Interstitial pneumonitis; pleuritis
Spleen Onion-skin fibrosis in perivascular
connective tissue
Lymph
nodes
Follicular hyperplasia, plasmacytosis,
focal necrosis
Peripheral blood
Anemia, leukopenia, thrombocytopenia
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ARA REVISED CRITERIA FORCLASSIFICATION OF SYSTEMICLUPUS ERYTHEMATOSUS
ARA REVISED CRITERIA FORCLASSIFICATION OF SYSTEMICLUPUS ERYTHEMATOSUS
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
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(contd)(contd)
Neurologic disorder
Hematologic disorder
Immunologic disorderPositive LE cell preparation
Anti-DNA in abnormal titer
Anti-Sm antibody to Sm nuclear antigenFalse-positive serologic test for syphilis
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CLASSIFICATION OF LUPUSNEPHRITIS
CLASSIFICATION OF LUPUSNEPHRITIS
UST-FMS Dept. of Lab. Medicine
Nomenclature Frequency Location of deposits
Focal
Proliferative
25% Focal subendothelial
(+mesangial)
Diffuse
proliferative
45% Diffuse
subendothelial
Mesangial 20% Mesangial only
Membranous 15% Subepithelial(+mesangial)
Normal 5% ---
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ANTINUECLEAR ANTIBODYPATTERNS AND SPECIFICITIESANTINUECLEAR ANTIBODYPATTERNS AND SPECIFICITIES
UST-FMS Dept. of Lab. Medicine
PATTERN SPECIFICITY
Diffuse (homogeneous) Double-stranded DNA
Histones
Speckled Ribonucleoprotein(RNP)
Sm antigen
DNA topoisomerase I
Ro/La antigen
Nucleolar Nucleolar RNA (4-6S)
protein
RNA polyisomerase I
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ANTINUECLEAR ANTIBODYPATTERNS AND SPECIFICITIESANTINUECLEAR ANTIBODYPATTERNS AND SPECIFICITIES
UST-FMS Dept. of Lab. Medicine
PATTERN SPECIFICITY
Nucelolar Nucleolar RNA (4-6S)
protein
RNA polymerase I
Fibrillarin
PM-Sc/antigen
Peripheral Double-stranded DNA;Nuclear membrane
antigens
Centromeric Kinetrochore proteins
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SYSTEMIC LUPUSERYTHEMATOSUS
SYSTEMIC LUPUSERYTHEMATOSUS
LABORATORY FINDINGS
Immunologic Abnormalities:
Presence of ANA (98%) Presence of anti-DNA antibodies (ds or
native) highly specific for SLE; active renal
disease (90%) & active disease without
renal involvement (50%)
titers reflect disease activity
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(contd)(contd)
Antibodies against extractable nuclear
antigens
Include nuclear ribo-nucleo protein (nRNP) &nuclear non-nucleic acid glycoprotein (Smith
[Sm] antigen)
The latter appears to be highly specific for
patients with SLE; present in 25% ofpatients with SLE
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(contd)(contd)
Positive test for LE cells (70%-85%) specific
for SLE but not as sensitive as ANA
LE cells may be seen in synovial, pleural &pericardial fluid
Presence of circulating immune complexes &
decrease serum complement indicate
active disease
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(contd)(contd)
Increased K-globulin (80%) reflects
increased immunologic activity
Presence of rheumatoid factor (20% -35%)reflects increased immunoglobulins
False-positive nontreponemal test for syphilis
(15%-20%) reflects increased
immunoglobulins
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Hematologic FindingsHematologic Findings
Mild-normocytic anemia (50% -80%)
Moderate leukopeniaLymphocytopenia due to lymphocytotoxic
antibodies (the most frequent initial
laboratory finding)
Thrombocytopenia
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PLASMA PROTEINSPLASMA PROTEINS
Decreased serum albumin (50%-60%)
reflects chronic renal pathology
seen in lupus nephritis Increased sedimentation rate
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UrinalysisUrinalysis
Hematuria, cellular casts & proteinuria
reflect active lupus nephritis
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SYNOVIAL FLUIDSYNOVIAL FLUID
Low WBC count (
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SPINAL FLUIDSPINAL FLUID
Findings of aseptic meningitis
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BIOPSY OF KIDNEY & SKINBIOPSY OF KIDNEY & SKIN
Immunofluorescent studies show
deposits of immunoglobulins &
complement
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POLYMYOSITISPOLYMYOSITIS
An autoimmune disorder of
unknown etiology
Diffuse inflammation & weakness ofskeletal muscles
May occur alone or in association with
tissue disorders like SLE, Sjogrensor scleroderma
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(CONTD)(CONTD)
DERMATOMYOSITIS is seen in 40% of
cases, usually in children & adults with
occult neoplasms17% of cases are older than 40 yrs old
& have associated carcinoma
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POLYMYOSITISPOLYMYOSITIS
Laboratory Findings:
Mild to moderately increased in ESR,
correlates with disease activityIncreased in CPK (MM & MB) &
aldolase reflect muscle injury &
disease activity
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POLYMYOSITISPOLYMYOSITIS
LDH & AST usually elevated
Increase LDH isoenzymes LDH2 toLDH5, especially LDH5 indicate
active muscle necrosis
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POLYMYOSITISPOLYMYOSITIS
Slight increased in K-globulin
Occasionally, (+) rheumatoid factorPresence of antibody against PM-1 antigen
(a non-histone acid nuclear antigen often
associated with polymyositis)
Occassionally, presence of ANA
Mild, normocytic anemia
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POLYMYOSITISPOLYMYOSITIS
Muscle biopsy : inflammation & muscle
degeneration & regenerationIncreased urinary creatine-creatinine
ratio, reflects increased release &
excretion of creatine from necroticmuscle
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SCLERODERMASCLERODERMA
Literally hard skin an uncommon multi-
systemic disorder affecting
connective tissues & small bloodvessels of unknown etiology
aka - systemic sclerosis
Skin involvement: most prominent
feature, results to scarring
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SCLERODERMASCLERODERMA
Diverse features: RAYNAUDS
Phenomenon (pallor, cyanosis,
reddening, swelling of toes & fingers);impaired swallowing & GI motility, heart,
lung, kidneys, musculoskeletal &
neurologic system
40% of death: due to malignant
hypertension & renal failure
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Pathogenesis:Pathogenesis:
Immunologically mediated injury to
small blood vessels & capillaries
vascular occlusion decreased bloodflow injury to surrounding connective
tissues stimulating fibroblast
proliferation & increased collagen
deposition
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(contd)(contd)
Presence of small amounts of
cryoglobulins (50%)
Absence of antibodies to native DNA &
Sm antigen
Biopsy of skin late in the disease
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Laboratory Findings that ReflectSpecific Organ InvolvementLaboratory Findings that ReflectSpecific Organ Involvement
Kidney sclerodermal renal disease
Small intestine malabsorption
Heart pericarditis
Lung diminished gas diffusion due to
interstitial fibrosis; pneumonia
Muscle - polymyositis
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SJOGRENS SYNDROMESJOGRENS SYNDROME
Autoimmune; oral & ocular dryness
(associated with SLE, scleroderma,
polymyositis)Partial or complete destruction of the
salivary & lacrimal glands by
lymphocytes & plasma cells50% of patients have RA
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(contd)(contd)
Antigenic alteration of salivary gland
tissue sensitization, lymphocytic
infiltration, production ofautoantibodies against the salivary &
lacrimal glands damage ensue
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SJOGRENS SYNDROMESJOGRENS SYNDROME
LABORATORY FINDINGS
Immunologic Abnormalities
(+) rheumatoid factor (75%-90%)
(+) ANA (50%-80%)
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(cont,d)(cont,d)
Presence of antibody to nonhistone
antigen, SS-B (60%)
Presence of antibody to nonhistoneantigen, SS-A (70%)
Occasionally, salivary-duct antibody
Lip biopsy : lymphocytic infiltration ofthe salivary glands
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(contd)(contd)
Other Laboratory Findings
Mild normocytic anemia
Leukopenia
Increased ESR (>90%)
Markedly increased K-globulins
(50%), esp IgA
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MIXED CONNECTIVE TISSUEDISEASE
MIXED CONNECTIVE TISSUEDISEASE
Unknown etiology, characterized by
varying features of SLE,
scleroderma & polymyositisS/S: polyarthralgia or polyarthritis,
diffuse swelling of the hands,
Raynauds phenomenon, impaired
esophageal motility, myositis,
reduced pulmonary lung capacity.
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MIXED CONNECTIVE TISSUEDISEASE (contd)MIXED CONNECTIVE TISSUEDISEASE (contd)
Increased K-globulin (75%)
(+) rheumatoid factor (50%)
Increased ESR reflects activeinflammation.
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MIXED CONNECTIVE TISSUEDISEASE (contd)MIXED CONNECTIVE TISSUEDISEASE (contd)
Occ, moderate anemia
Occ, moderate leukopeniaIncreased AST, aldolase & CPK reflect
muscle involvement
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RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS
PATHOGENESIS: Unknown antigenic stimulus synovial tissue in susceptible patient (+) IgGproduction reacts with unknown antigen altered &unrecognized as self formation of IgM (RF) whichbecomes the antibody against the altered IgG (+)soluble immune complexes in synovium activationof complement system chemotactic factors (+)leukocytes leukocytes ingest immune complexestriggers enzymes (e.g. colagenase) & mediators of
inflammation inflammation of synovial liningintermittent course or proliferative synovitis bone-cartilage erosion or tendon destruction permanent
joint damage
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(contd)(contd)
Extra-articular manifestations:subcutaneous rheumatoid nodules,
Feltys syndrome (splenomegaly &neutropenia) vasculitis, lung disease,
pericarditis, Sjogrens syndrome, ocular,lymphoid & neuromuscular disorders
Biopsy of gum, liver, kidney & rectalmucosa shows amyloidosis in 25% ofcases
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RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS
LABORATORY FINDINGS
Synovial Fluid
Yellow to white; turbidityreflects increased WBC; fibrinclot indicates chronicity
Mucin clot may be fair or
poor; a poor clot & decreasedviscosity indicates thathyaluronic acid is decreased
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(contd)(contd)
WBC usually 5,000/ul reflects the
degree of inflammation
Differential WBC 65% neutrophilsGlucose normal or low, interference
in glucose transport
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(contd)(contd)
(+) rheumatoid factor
Decreased complement
Ragocytes neutrophils with ingestedimmune complexes
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(contd)(contd)
Peripheral Blood
WBC: normal or slightly elevated
(
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(contd)(contd)
Other Laboratory Findings
(+) rheumatoid factor (IgM)
75% of patientsPresence of ANA (10%-50%), titers
are lower than in SLE
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(contd)(contd)
Increased C-RP, fibrinogen & ESR:
reflect disease activity
Increased w1 & w2 globulins:acute phase reactants
Increased K-globulin: reflects
accelerated protein breakdown inchronic disease
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(contd)(contd)
decreased complement in the
presence of severe extra-articular
disease, such as vasculitispresence of circulating immune
complexes: frequently when there
are systemic manifestations
PREVA ENCE OFPREVA ENCE OF
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PREVALENCE OFRHEUMATOID FACTOR (%)PREVALENCE OFRHEUMATOID FACTOR (%)CONDITION FACTOR (%)
Mixed cryoglobulinemia 90-100
Sjogrens syndrome 75-90
Mixed connective tissue disease 50-60Systemic lupus erythematosus 20-30
Scleroderma 20-30
Juvenile rheumatoid arthritis 20Polymyositis 5-10
Hypersensitivity vasculitis 5-15
Tuberculosis 10-20
PREVALENCE OFPREVALENCE OF
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PREVALENCE OFRHEUMATOID FACTOR (%)PREVALENCE OFRHEUMATOID FACTOR (%)
CONDITION FACTOR (%)
Leprosy 10-60
Sarcoidosis 5-33Syphilis 10
Subacute bacterial endocarditis 25-50
Salmonellosis 15-40
PREVALENCE OFPREVALENCE OF
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PREVALENCE OFRHEUMATOID FACTOR (%)PREVALENCE OFRHEUMATOID FACTOR (%)CONDITION FACTOR (%)
Acute rheumatic fever Rare
Acute viral infections (rubella,
mumps, influenza, infectiousmononucleosis)
15-65
Parasitic infections
(schistosomiasis, malaria,
trypanosomiasis
20-90
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Thank you..