What is arthralgia?
When a joint hurts but there is no sign of inflammation
when is monoarticular arthritis typically seen?
infections, crystal-induced arthritis, or trauma, septic arthritis, gout, pseudogout, traumatic arthritis, mechanical derangement of joint, osteochondritis dissecans
What is oligoarticular arthritis and when is it typically seen?
seen in several joints (2-4)
often associated with the axial arthropathies such as ankylosing spondylitis, psoriatic arthritis, or reactive arthritis.
often asymmetrical and involves the large joints (although not invariably).
what is polyarticular arthritis and when is it typically seen?
Involves multiple joints, often SYMETRICALLY, and usually
affects both the small and large joints.
** rheumatoid arthritis, systemic lupus erythematosus, and certain viral syndromes.
What is hyaline cartilage composed of?
type II collagen, proteoglycans and chondrocytes which produces collagen and proteoglycans
matrix proteins: metalloproteinases (MMP)
what are polyarticular diseases which can present as a Monoarticular disease?
juvenile rheumatoid arthritis, Reactive arthritis, Sarcoid arthritis, psoriatic arthritis, pseudogout
what are joints involved in osteoarthritis?
-distal interphalangeal joints (DIP), proximal interphalangeal joints (PIP), first carpometacarpal joint (CMC), cervical spine,
lumbosacral spine, hips, knees, first metatarsophalangeal joint (MTP)
which arthritis is worse with rest or in the morning?
rheumatoid arthritis or axial arthropathies.
what arthritis is worse with use?
osteoarthritis
What genetic factor is associated with rheumatoid arthritis?
HLA-DR4 & 1
**QKRAA sequence
How does PRPP synthetase contribute to Gout?
overactivity of PRPP leads to increase uric acid
PhosphoRibosyl-PyrophosPhate
How does HGPRT contribute to gout?
deficiency in HGPRT leads to increase uric acid
Hypoxanthine Guanine PhosphoRibosylTransferase used to convert hypoxanthine –>guanine
Which type of arthritis is noninflammatory?
Osteoarthritis
What cytokines are associated with osteoarthritis?
Interleukin 1 –> MMP, prostaglandins, nitric oxide
nitric oxide –> increases MMP production and chondrocyte apoptosis
Prostaglandins: increase production and activation of MMP
complement activation
adipokines–> cytokines released from fat cells
How does rheumatoid factor contribute to rheumatoid arthritis?
IgM Rheumatoid factor attacks Fc portion of IgG
What other antibodies are associated with rheumatoid arthritis other than RF?
anti citrulline antibodies
These citrulline peptides should not be made and are specifically present in patients with rheumatoid arthritis
What type of cells are present in RA synovium?
CD4+ Tcells, Th17 cells, B cells, and plasma cells
B cells produce antibodies to RF and CCP
macrophages induced to release MMP
What are the joints involved in gout?
1st MTP
cool, peripheral joints of lower and upper extremities
Are majority of gout patients underexcreters of uric acid or overproducers?
UNDEREXCETERS
What treatment would you use to inhibit the conversion of xanthine to uric acid?
allopurinol and febuxostat
How does MSU trigger immune response?
binds to TLR2 and 4
also engages in caspase 1 that activates NLRP3 inflammasome –> production of IL-1beta
Describe the self limiting process of gout?
IgG coats the MSU and triggers phagocytosis by PMNs –> immune response
eventually apolipoprotein B coats it, now inhibiting phagocytosis and the immune response in suppressed.
Describe calcium pyrophosphate dihydrate deposition disease?
You have an abnormal production of pyrophosphate (PPi) due to the over productions of nucleoside triphosphates –> PPi
Nucleoside triphosphate (NTP) is hydrolyzed by NTPPPH generating NMP and PPi
Describe the genetic component with CPPD
there is an ANK GENE mutation that results in a transmembrane PPi transporter protein that allows excess PPi to leave the chondrocyte
What are the important characteristics of CPPD?
rhomboid shape
POSITIVELY birefringent
What is the genetic component of seronegative sponyloarthropathies?
HLA-B27
Which important cytokine would be found in the synovium for seronegative spondyloarthropathies?
tumor necrosis factor
What arthritis has a 20% chance of developing if you have a family history with one first degree relative?
seronegative spondyloarthropathy
Which arthritis is asymmetric, oligoarticular, and affects lower extremities?
reactive arthritis
What is Reiter’s syndrome?
can’t see, pee, or climb a tree
conjunctivitis, urethritis, arthritis
What are some of the hypotheses for reactive arthritis?
molecular mimicry
arthriogenic peptide hat is uniquely presented by HLA-B27
HLA-B27 heavy chains combine and activate NK cells
**unfolded protein hypothesis: ER stress response
Which arthritis is most likely explained by a misfolded protein (ERAP-1) in the ER that stimulates production of IL-23?
seronegative spondyloarthropathy
What is the fundamental defect in systemic lupus erythematosus (SLE)?
misdirected recognition of self as foreign.
A T cell AND B cell process
What is the strongest genetic association with lupus?
HLA-DR3 and C4A null allele
What is the hallmark of systemic lupus erythmatosus?
positive ANA
What type of antibodies are produced in lupus/
anti-dsDNA
anti histone
anti-smith, SSA, SSB
What is the significance of anti-phospholipid antibodies in lupus?
it blocks the prothrombin activation in clotting but INCREASES CLOTTING (counterintuitive)
probably neutralizes the anti-coagulating effect of beta 2 GP1
What is the major target organ in SLE?
The kidneys
What is the classic clinical presentation of Vasculitis?
palpable purpura
What is the presentation of giant cell vascultitis?
temporal : temporal arteries, vessels originating from the aortic arch, other arteries less common; temporal headache, jaw claudication, scalp tenderness, visual loss (ophthalmic artery)
**carotid artery
What is Takayasu’s arteritis?
giant cell vasculitis affecting vessels branching from the aortic arch claudication of upper > lower extremities, CNS events; granulomatous
panarteritis
medium vessel vasculitis affects which arteries?
muscle arteries
Polyarteritis nodosa
medium vessel vasculitis that affects small and medium-sized arteries; may affect any organ, but skin, joints, peripheral nerves, gut, and kidney are most commonly involved; focal but panmural necrotizing arteritis with a predilection for involvement at the vessel bifurcation
Kawasakis disease
medium vessel vasculitis - fever, conjunctivitis, erymatous rash of palms and soles, lymphadenopathy
What are ANCAs?
Antineutrophil cytoplasmic antibodies
What vasculitis is associated with cytoplasmic ANCA?
granulomatosis with polyangiitis
What does c-ANCA stain positive for?
proteinase - 3
What vasculitis is associated with perinuclear ANCA?
microscopic polyangiitis
What does perinuclear ANCA stain positive for?
myeloperoxidase (MPO)
What are signs of polymyositis/dermatomyositis?
muscle weakness that is proximal
low endurance
What skin rashes seen with dermatomyositis?
gottron's papules Heliotrope rash V-sign and shawl sign mechnic's hands periungual changes/erythema
What disease does PM or DM typically present with?
interstitial lung disease 60%
What antibodies are associated with PM or DM?
anti-synthetase antibodies “ANTI-JO-1” which is an ANTI-HISTADYL TRNA SYNTHETASE
What t cell is associated with polymyositis?
CD 8 + T cells
What t cells is associated with dermatomyositis?
CD4+ T cells