RHEUMATOLOGY REVIEW Flashcards by MO ROUTH

Degeneration of articular cartilage with hypertrophy of contiguous bone:

DX: joint space loss, subchondral cysts, sclerosis, osteophytes

Osteoarthritis (OA)

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OA: Predisposing Factors (primary)

Age
Obesity
Occupational risks:
Miners: OA hips, knees, shoulders
Weavers: OA hands
Trauma

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Osteoarthritis (OA) Joint Involvement:

DIP (Heberden’s), PIP (Bouchard’s), 1st CMC
Hips and knees
Spine: cervical and lumbar
First MTP

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Osteoarthritis (OA) DX:

joint space loss, subchondral cysts, sclerosis, osteophytes

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OA: Predisposing Factors secondary

Secondary OA:
Inflammatory
Metabolic: hemochromatosis, Wilson’s disease, ochronosis

Sports: in general, no increased risk; exercise may be protective

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**Sports: in general, no increased risk for OA; exercise may be _______

protective

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Collagen: predominantly type II

Proteoglycans (chondroitin and keratin sulfate) linked to hyaluronic acid

Matrix proteins
~Metalloproteinases (MMPs): collagenase, gelatinase, stromelysin
~Tissue inhibitors of metalloproteinases (TIMPS)

Chondrocytes

Water

Cartilage components (avascular, no nerves)

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In OA, the big problem is

cartilage tries to repair itself unsuccessfully

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Cartilage in early Osteoarthritis

↑ inc chondrocytes
↑ inc metalloproteinases
↑ inc water content

dec TIMP
dec proteoglycan

cartilage changes from a spounge into a dish rag

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OA Characteristics

Lacks systemic features

Synovial fluid: noninflammatory, type I fluid (200-2000 WBC/mm3)

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__________ stimulates MMP production, PGE2, nitric oxide (NO), IL-6 in OA

Interleukin-1:

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___________: increases MMP production, inhibits proteoglycan synthesis, induces chondrocyte apoptosis in OA

Nitric oxide

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__________: ↑ production and activation of MMPs in OA

Prostaglandins

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Complement activation
Adipokines
Interleukin-1:
Nitric oxide
Prostaglandins

present in?

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Adipokines

fat cells may produce IL-6

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OA: Knees

Joint space loss
Sclerosis
Subchondral cysts
Osteophytes

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A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, symmetric synovitis which can result in cartilage and bone destruction

Joint involvement:
Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved

X-rays: marginal joint erosions and deformities

Rheumatoid Arthritis (RA)

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Rheumatoid Arthritis (RA): A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, ________________ which can result in cartilage and bone destruction

symmetric synovitis

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Rheumatoid Arthritis (RA) Joint involvement:

Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved

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Rheumatoid Arthritis (RA) Disease susceptibility and severity associated with shared epitope (QKRAA; in antigen binding groove) in subtypes of _____________ other genes are also involved

**HLA-DR4 and HLA-DR1

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Antibody directed against the Fc portion of IgG; RF usually IgM, can be IgG or IgA
RF present in 85% of patients with RA
Not specific for RA or CTDs
Produced locally in the synovial tissue

RF-IgG immune complexes are pathogenic

Rheumatoid factor (RF):

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RF-IgG immune complexes are _______

pathogenic

Rheumatoid factor (RF):
Can cause vasculitis or nodules

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Rheumatoid factor (RF) ispresent in

many disease 
ex
ra
sjordons
sle

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Anti-CCP

Anti-Cyclic Citrullinated Peptide Antibodies

RF not very specific for RA

reactive with synthetic peptides containing the unusual amino acid citrulline (modified arginine residue) are specifically present in the sera of RA patients:

Anti-CCP abs occur more frequently in individuals with the shared epitope; citrullination of peptides enhances binding

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Inflammed tissue of macs, t cells, plasma cells

Pannus in RA

Synovial fluid major cell in RA?

neutrophils

Production of metalloproteinases and other effector molecules Migration of polymorphonuclear cells Erosion of ____________ in RA

bone and cartilage

CD4+ memory T cells related to RA

modulation and amplification of local immune response through antigen recognition (query altered proteoglycans or collagen; citrullinated peptides) unknown antigen sparks RA, by RA start disease is cleared but RA goes on

Extra-articular manifestations in RA

RF-IgG immune complex-induced vasculitis | Rheumatoid nodule formation in tissues/organs

The result of tissue deposition of monosodium urate (MSU) crystals due to hyperuricemia (MSU supersaturation of extracellular fluids)

Gout

Gout Joint Involvement:

1st MTP (podagra)GRaet Toe Cool, peripheral joints of lower and upper extremities

Gout Hyperuricemia: over-production or under-excretion of uric acid; _______ (90%) most cases

underexcretors

Uric acid is a product of ______ metabolism

purine

Humans lack ______ which oxidizes uric acid into allantoin (more soluble compound)

uricase

___________of uric acid (X-linked): PRPP synthetase overactivity HGPRT deficiency (complete: Lesch-Nyhan)

Overproduction

Crystal arthritis is ________________ and crystal identification by polarized microscopy (MSU crystals: needle-shaped, negatively birefringent)

diagnosed by arthrocentesis

X-linked inborn errors of Gout

inc PRPP synthetase | dec HGPRT

_______ inhibited by allopurinol and febuxostat, can treat gout

Xanthine oxidase

Overproduction of uric acid (X-linked): __________overactivity HGPRT deficiency (complete: Lesch-Nyhan)

PRPP synthetase

IgG-coating promotes phagocytosis by PMNs | IgG: not specific anti-crystal antibodies

(Proteins coating the crystals modulate the cellular response) These are NOT ANTI CRYSTAL AB

Apolipoprotein B-coating____________phagocytosis

inhibits | Proteins coating the crystals modulate the cellular response

Overproduction of uric acid (X-linked): PRPP synthetase overactivity __________(complete: Lesch-Nyhan)

HGPRT deficiency

___________ includes ligamentous-, tendinous-, fibrous-osseous junctions

Enthesitis | Seronegative Spondyloarthropathies

Phagocytosis of crystals ___________concentration

decrease

Local heat of inflammation __________MSU solubility

increase

Calcium Pyrophosphate Dihydrate Deposition Disease

Abnormal pyrophosphate (PPi) metabolism "pseudogout"

PPi precipitates with calcium forming CPPD crystals in mid-zonal cartilage layers. Crystal release into the joint space. On xray?

Chondrocalcinosis

CPPD crystals:

rhomboid, positively birefringent

Seronegative Spondyloarthropathies hallmark

SI joints (sacroiliitis); morning (am) stiffness

Seronegative Spondyloarthropathies affect

Enthesitis: | ligamentous-, tendinous-, fibrous-osseous junctions

Seronegative Spondyloarthropathies Synovium:

Synovium: increased expression of TNF

HLA-B27 and Ankylosing Spondylitis (AS) Chance of developing AS

2% if HLA-B27 positive | 20% if HLA-B27 positive with a first-degree relative with AS

HLA B27 + has a ___ chance of AS

HLA B27 + w/ AS FDR has a ___ chance of AS

20%

Reactive Arthritis

Asymmetric, oligoarticular, lower ext arthritis

Dactylitis are?

sausage digits?

Reactive Arthritis Unfolded protein hypothesis: ER stress response

in ER HLA b27 misfolds and cannot be released builds up in ER stress response to cell ER stress makes Il-23--> Th17 --> inflammation

Reiter’s syndrome: clinical triad of conjunctivitis, urethritis, arthritis

Former name of Reactive Arthritis

Reiter’s syndrome: clinical triad of ___________

conjunctivitis, urethritis, arthritis

Systemic Lupus Erythematosus (SLE)

A chronic, systemic autoimmune disease which affects multiple organ systems including the skin, joints, serosal surfaces, lungs, kidneys, CNS, and hematologic system

SLE - Fundamental defect is the ________________, resulting in an autoimmune process; T cell and B cell process

misdirected recognition of self as foreign

SLE is a?

T AND B CELL PROCESS

SLE Antibody responses toward autoantigens are antigen-driven and require ____________

CD4+ T cells

SLE Loss of T cell tolerance permitting autoreactive B cell stimulation: ? central or peripheral abnormality in_____________ lymphocyte deletion or anergy

self-reactive

Association with HLA-DR3 and C4A null allele (greatest risk)

SLE

SLE Association with HLA-DR3 and _________ (greatest risk)

C4A null allele

SLE- Loss of T cell tolerance permitting ___________: ? central or peripheral abnormality in self-reactive lymphocyte deletion or anergy

autoreactive B cell stimulation

Antinuclear Antibodies (ANA)

SLE: > 95% patients have + ANAs Not specific for SLE Antibodies are directed to multiple nuclear antigens CD4 directed

Systemic Lupus Erythematosus (SLE)

Genetics (polygenic): | C4A null allele (greatest risk)

ANA specific for SLE?

NOPE

Anti-dsDNA antibodies:

renal disease

Anti-histone antibodies:

SLE and drug-induced lupus

Anti-phospholipid antibodies: block prothrombin activation in the clotting cascade; associated with increased _______ ? neutralize anticoagulant effect of 2 GP1; do not cause a vasculitis

clotting Specific antibody-mediated disease (Type II):

Inflammation within or through the vessel wall resulting in damage to vessel integrity/flow

Vasculitis

Vasculitis Pathology

Varying degree of infiltrating lymphs, monocytes, histiocytes, eosinophils, and PMNs Granulomas and/or giant cells in vessel wall in some types of vasculitis Fibrinoid necrosis of vessel wall secondary to immune complex deposition Focal and segmental nature of vascular lesions common to all types of vasculitis

Vasculitis Pathology Immune complexes: inflamm→ PAFs→ ↑vascular permeability→ IC deposition; __________

palpable purpura

Vasculitis Pathology- Pathophysiology: Immune complexes: inflamm→ PAFs→ ↑___________→ IC deposition; palpable purpura

vascular permeability

Vasculitis Pathology- Pathophysiology: T cell dependent-mediated endothelial cell injury: (HLA-DR4 and giant cell arteritis; suggests ___________ vascular inflammation)

antigen-driven

HLADR4 in Vasculitis is not related to?

RA HLADR4

Vasculitis- Sources of antigen for immune complexes:

Drugs Bugs: infectious agents Connective tissue disease: autoimmune process Malignancy

ANCA Vasculitis

Antineutrophil Cytoplasmic Antibodies. Seperates small Vasculitis

*Cytoplasmic ANCA (c-ANCA):

Proteinase-3 (PR3) in primary granules of PMNs | Associated with generalized GPA (Wegener’s)

*Perinuclear ANCA (p-ANCA):

Myeloperoxidase (MPO) in primary granules of PMNs | Associated with microscopic polyangiitis (MPA)

``` Inflammatory myopathies are characterized by: Muscle weakness (proximal) and low endurance Usually idiopathic but may occur in association with neoplastic diseases or in “overlap” with CTDs ```

Polymyositis / Dermatomyositis (PM/DM)

-DM presents with typical skin rashes:

``` Gottron’s papules Heliotrope rash V-sign and shawl-sign Mechanic’s hands Periungual changes/erythema ```

*Anti-synthetase Syndrome

PM or DM presenting with: Interstitial lung disease (ILD): 60%***** Anti-synthetase antibodies: Anti-aminoacyl-tRNA synthetases (cytoplasm) Anti-Jo-1 = anti-histadyl-tRNA synthetase Not pathologic or myotoxic antibodies

Anti-synthetase antibodies: Anti-aminoacyl-tRNA synthetases (cytoplasm) Anti-Jo-1 = ______________ Not pathologic or myotoxic antibodies

anti-histadyl-tRNA synthetase (antiJo1) Not pathologic or myotoxic antibodies- IT IS A MARKER OF DISEASE

Endomysial distribution of inflammatory cells (CD8+ T cells) surrounding and invading muscle fibers

Polymyositis

Perivascular (CD4+ T cells) and perifascicular inflammatory infiltrate

Dermatomyositis Around vasical

Polymyositis / Dermatomyositis Evidence suggesting a _________ etiology:

viral Viral particles by EM and viral RNA detected in muscle from PM/DM patients. *NO* live virus has been cultured from muscle

Osteoarthritis (OA) Joint Involvement:

``` Joint Involvement: DIP (Heberden’s), PIP (Bouchard’s), 1st CMC Hips and knees Spine: cervical and lumbar First MTP ```

RHEUMATOLOGY REVIEW Flashcards

(91 cards)