Arthritis/ Spondylopathies Flashcards
characterized by progressive fissuring, flaking, and erosion (fibrillation) of articular cartilage
Osteoarthritis
The etiology of Osteoarthritis is multifactorial, with excessive biomechanical stress and increased intraarticular ______ activity as the major contributors to cartilage destruction
metalloproteinase
Better in the morning Worse at end of day Crepitus Normal Range of Motion No swelling/Warmth
Osteoarthritis
Calcium pyrophosphate deposition disease presents with an acute inflammatory arthritis
pseudogout
an inflammatory arthritis associated with synovial hyperplasia.
Rheumatoid arthritis
symmetric joint involvement
prolonged morning stiffness
most commonly affects the PIP and MCP,
wrist, knee, and ankle joints.
Rheumatoid arthritis
The preferred treatment to prevent recurrent gout attacks is _______, which decrease uric acid production.
Prophylactic therapy is usually initiated during between attacks because acute changes in serum ____ levels can worsen an acute attack.
xanthine oxidase inhibitors
(eg, allopurinol, febuxostat)
uric acid
Oral or intraarticular _______ can be used for acute gout in patients who cannot tolerate NSAIDs or colchicine
glucocorticoids
second-line drugs for chronic management of gout. These drugs increase renal excretion of uric acid and are therefore contraindicated in patients with a history of renal stones.
Uricosuric agents
probenecid
Inflammatory back pain (onset at age <40)
morning stiffness that is better with activity and worse with rest
+/- fusion of the sacroiliac joints.
NSAIDs may help
ankylosing spondylitis (AS).
inflammation at the bony insertions of tendons, ligaments, and joint capsules
a prominent manifestation of spondyloarthritis ( like ankylosing spondylitis)
Enthesitis
*can happen in achilles tendon, plantar fasciitis, dactyilitis
COX-2 is an inducible enzyme that is undetectable in most tissues under normal conditions. During inflammation, infiltrating cells secrete cytokines
(___, ____)
that cause COX-2 upregulation in the inflamed tissue. COX-2 then drives the synthesis of pro-inflammatory arachidonic acid metabolites.
interleukin-1
TNF-α
PTs with a PHx of PUD & GERD for acute gout attack should be treated with an agent that provides prompt pain relief without exacerbating GI problems.
Non-seletive NSAIDs can damage the gut.
Instead use:
Selective COX-2 inhibitors
(celecoxib)
*PUD co-morbidity CAME UP ALOT
presents with localized swelling at the olecranon (ex: posterior elbow)
Range of motion is preserved and pain-free
Olecranon bursitis
Preceding infections causing Reactive arthritis (5)
Chlamydia trachomatis Salmonella, Shigella, Yersinia, Campylobacter, C. difficile
The classic triad of ______ is nongonococcal urethritis, conjunctivitis, and arthritis.
HLA ___-associated arthropathy that occurs within several weeks following a genitourinary or enteric infection.
seronegative spondyloarthropathies that can cause:
reactive arthritis
HLA-B27
sacroiliitis (20%)
middle-aged woman with polyarthritis, morning stiffness, and systemic symptoms =
rheumatoid arthritis (RA)
1st line treatment for RA
a folate antimetabolite that halts purine and pyrimidine synthesis through competitive inhibition of dihydrofolate reductase.
Methotrexate
List 5 adverse effects of Methotrexate which affects tissues with rapid cellular turnover
Methotrexate causes toxicity to tissues with rapid cellular turnover, such as oral and gastrointestinal mucosa (ulcerations), hair follicles (alopecia), and bone marrow (pancytopenia). Methotrexate can also cause hepatotoxicity (hepatitis, fibrosis, cirrhosis) and pulmonary fibrosis.
Hydroxychloroquine is a well-tolerated antirheumatic drug used in mild RA and systemic lupus erythematosus. Its most significant toxicity is
irreversible retinopathy
is characterized by stiffness and fusion (ankylosis) of the axial joints. The sacroiliac and apophyseal joints of the spine are the most commonly affected, leading to restricted spinal mobility.
AS
Ankylosing spondylitis: back pain onset ____ age
better with movement, not with rest. Pain at night
<40
3 Extra-skeletal complications of Ankylosing Spondylitis
limited chest wall expansion, leading to hypoventilation (restricted lung disease)
ascending aortitis, which can lead to dilation of the aortic ring and aortic insufficiency.
Uveitis pain, blurred vision, photophobia, and conjunctival erythema
Pt with hand joint pain and stiffness. Pain wakes them at night. Chronic fatigue and poor sexual performance (Hypopituitarism). X-rays reveal bilateral erosions and joint deformities involving the second and third MCP joints and calcifications. +/– Elevated liver enzymes/hepatomegaly, Heart problems
Hemachromatosis
iron depositionin the articular cartilage and synovium, free radical damage and crystal deposition.
X-ray findings include hook-like osteophytes)and deposition of calcium pyrophosphate dihydrate in the articular cartilage (chondrocalcinosis).
Hemachromatosis associated arthritis
Polyarticular arthritis mostly of the small hand joints ulnar deviation of the digits (fingers lean towards pinky)
rheumatoid arthritis (RA)
anti-CCP antibodies
C-reactive protein & ESR correlate with disease activity
X-ray: soft tissue swelling, joint space narrowing, bony erosions
rheumatoid arthritis (RA)
may also involve the wrists, elbows, knees, and ankles.
Cervical spine involvement common in longstanding disease causing:
pain, disability,
Cord compression
Hips and lumbosacral joints usually spared
rheumatoid arthritis (RA)
symmetric, polyarticular arthritis with joint swelling and stiffness
rheumatoid arthritis (RA)
Cervical spine involvement: subluxation, cord compression
rheumatoid arthritis (RA)
Activation of T lymphocytes in response to rheumatoid antigens (2) ______-.
Activated T cells release cytokines (__ &__) that cause _____
The accelerated metabolic rate of the inflamed synovial tissue leads to local hypoxia and increased production of hypoxia-inducible factor 1 and ____ by local MQs and fibroblasts, resulting in __________.
This facilitate expansion of inflammed synovium into a rheumatoid ______, an invasive mass composed of fibroblast-like synovial cells, granulation tissue, and inflammatory cells.
Over time, the mass encroaches into the joint space and can destroy the articular cartilage and erode the bone.
Ossification of the mass can lead to ____ of the bones across the affected joint (bony ankylosis).
citrullinated peptides type II collagen
IL-1 & TNF-alpha
synovial hyperplasia
vascular endothelial growth factor (VGEF)
synovial angiogenesis (neovascularization)
pannus
fusion
Osteoarthritis vs RA age of onset
OA: >40
RA: 40-60 or younger
Osteoarthritis vs RA joints involved
OA: knees, hips, DIPs
RA: Wrists, MCP, PIP
Osteoarthritis vs RA length of morning stiffness
OA: none/less than 30 min
RA: greater than 30 min
Osteoarthritis vs RA systemic symptoms
OA: none
RA: Fever, Fatigue, Weight loss
Osteoarthritis vs RA exam findings
OA: hard bony masses/joints
RA: Soft, spongy bones
Patients with OA of the hands may also have osteophyte formation leading to bony enlargement of the:
distal interphalangeal (DIP) joints ( \_\_\_\_\_ nodes) and proximal interphalangeal (PIP) joints ( \_\_\_\_\_ nodes)
Heberden
Bouchard
Pt with recurrent acute severely painful monoarthritis
and
history of a myeloproliferative disorder (ET, PCV, Myelofibrosis, CML)
Diagnosis of acute painful joint=
Gout attack
Needle shaped, negative biorefringent crystals
Gout
Tumor Lysis syndrome can cause
because of
Gout
increased uric acid production
Chronic kidney disease
Volume depletion
Diuretics (eg, thiazide, loops)
Cyclosporine & tacrolimus (immunosuppresants)
Risk factors for
GOut
firm, nontender, subcutaneous nodules that occur at pressure points such as the elbows or forearms.
Rheumatoid Nodules
an antibody (typically IgM) specific for the Fc component of IgG.
Rheumatoid factor
Anticentromere antibodies are found in the majority of patients with …
CREST syndrome
Calcinosis, Raynouds, Esophageal Dysmotility, Scleradactyly, Talengtasias
Antiphospholipid antibodies can be found in patients with ____& ____.
cause a hypercoagulable state with paradoxical PTT prolongation.
SLE
antiphospholipid antibody syndrome
The Monospot test assesses the serum’s ability to agglutinate ____.
Positive in the presence of heterophile antibodies
(Mono–EBV diagnosis)
sheep erythrocytes
a disease caused by tissue deposition of monosodium urate crystals.
Gout
occurs with increased frequency in patients with activating mutations involving phosphoribosyl pyrophosphate synthetase (PPRP) due to increased production and degradation of purines
Gout
____ are first-line therapy for treating acute gouty arthritis.
If they are contraindicated (eg, peptic ulcer disease, renal impairment), ______ is useful in the acute management of gout
as it inhibits neutrophil chemotaxis and phagocytosis by preventing _______ formation.
NSAIDs –> inhibits neutrophils.
colchicine –> Inhibit microtubules
In RA:
The proteases ( ___ & ___ ) contribute to cartilage destruction.
Cytokines indirectly activate ____, resulting in bony erosions.
Monoclonal antibodies that inhibit TNF-alpha ( __ & ___) or IL-1 receptors (___) are widely used to slow progression of the disease.
collagenase, metalloproteinase
osteoclasts
adalimumab, etanercept
Anakinra
Digital clubbing
Joint pain
Periostosis (tender thickening of periosteum)
Joint effusions
Hypertrophic OA
Associated with
Malignant: lung adenocarcinoma, metastases
Nonmalignant lung disease
(eg, cystic fibrosis, bronchiectasis, lung abscess)
Cyanotic heart disease (ToF, TA, TGV, TAPVR)
Hypertrophic OA
Pathogenesis of HOA:
Due to AV shunting, ____ bypass lung and skip fragmentation into platelets & deposit in peripheral tissues & distal bone
casuing focal hypoxemia & release of _____
leading to fibrovascular hyperplasia & _____
Megakaryocytes
PDGF & VEGF
abnormal bone formation
a syndrome characterized by painful bone and soft tissue enlargement in the distal extremities
hypertrophic osteoarthropathy (HOA)
Avascular necrosis (AVN) of the femoral head can be caused by
glucocorticoids
Decreased spinal range of motion & chest expansion
Stiff or stooped posture
Tenderness at spine & peripheral tendon insertions
(Achilles, plantar fasciitis)
Dactylitis (swelling of fingers & toes)
Uveitis
AS
Due to:
Increased osteoclast activity & bony erosions
due to cytokines __ & __
Increased bone/syndesmophyte formation causing a bamboo spine appearance
AS
TNF, IL-17
Elevated ESR & CRP
HLA-B27
AS
Intervertebral disc protrusion and thickening of the ligamentum flava can lead to _____.
The pain in this disorder typically radiates to the posterior thighs and legs and
is relieved by sitting and flexion of the spine
spinal stenosis
Intervertebral disc protrusion and thickening of the _____ can lead to spinal stenosis
ligamentum flava
In spinal stenosis the pain in this disorder typically radiates to the ______ and
is relieved by sitting and ____ of the spine
posterior thighs and legs
flexion
In Pseudo-gout synovial fluid analysis shows rhomboid-shaped crystals (looks like a rectangles toppling over to one side) formed from _____
These crystals are ____ birefringent under polarized light. The knee joint is involved in >50% of cases.
calcium pyrophosphate
positively
Clochicine causes gastrointestinal mucosal function to also be impaired by microtubule disruption, leading to _____ and, less commonly, nausea, vomiting, and abdominal pain.
diarrhea
Swan neck deformity (hyperextension of PIP and flexion of DIP).
Ulnar deviation of fingers (MCP joints)
Radial deviation of knuckles
RA (advanced)
Calcific degeneration of the articular cartilage (______) is a characteristic feature of calcium pyrophosphate dihydrate deposition disease (pseudogout)
chondrocalcinosis
Autoimmune complex deposition (type III hypersensitivity) plays a significant role in the arthritis associated with
systemic lupus erythematosus
Diuretics (eg, hydrochlorothiazide, furosemide)
Salicylates (eg, low-dose aspirin)
ACE inhibitors (eg, lisinopril)
Cyclosporine
cause GOUT via
decreased Uric acid urinary excretion
Dietary sources
Purine-rich foods (eg, seafood, red meat)
Fructose-containing & alcoholic beverages (beer)
↑ Cell turnover (eg, tumor lysis syndrome)
Lesch-Nyhan syndrome (deficiency of HGPRT)
↑ Phosphoribosyl pyrophosphate activity
cause GOUT via
Increased Uric acid productions
In treating gout
____ is used in patients with contraindications to both NSAIDs and colchicine
(due to renal dysfunction, the elderly)
but it is CONTRAINDICATED in patients with _____
Glucocorticoid
Diabetes
Uric acid-lowering therapy with
uricosuric agents (probenecid)
or
xanthine oxidase inhibitors (allopurinol, febuxostat)
is used to prevent acute attacks in patients with recurrent gouty arthritis and those with
macroscopic tophi
*These drugs should not be initiated during an acute gout attack as they can exacerbate acute arthritis.
____ binds to the intracellular protein ___ and inhibits its polymerization into microtubules.
This, in turn, disrupts cytoskeletal-dependent functions such as chemotaxis and phagocytosis.
Its administered initially at the first signs of a gout flare
It may also be used for prophylaxis
Colchicine
tubulin
Associated with:
keratoderma blennorrhagicum (keratinized skin lesions on palms and soles that can ooze or spread)
circinate balanitis (dick skin inflammation- tip)
Oral ulcers
conjunctivitis, anterior uveitis
urethritis, cervicitis, prostatitis
Reactive Arthritis
Can’t see, Can’t pee, Can’t climb a tree
Patient with Bell’s Palsy in the past and presents with asymmetric large joint arthritis (painful knee swelling) probably has:
Late Lyme disease can cause chronic asymmetric large joint arthritis and encephalopathy.
- Early Lyme disease= flu-like symptoms and erythema chronicum migrans (Target).
- Second stage of Lyme disease may involve atrioventricular block and facial palsy
Tumor necrosis factor-alpha (TNF-α) inhibitors impair cell-mediated immunity. All patients beginning treatment with TNF-α inhibitors for RA should be evaluated for
latent tuberculosis
Tumor necrosis factor-alpha (TNF-α) inhibitors impair cell-mediated immunity. All patients beginning treatment with TNF-α inhibitors for RA should be evaluated for
latent tuberculosis
The foundation of management for RA is disease-modifying antirheumatic drugs (DMARDs), which alleviate pain and inflammation and reduce long-term joint destruction and disability.
Examples of DMARDS are
Methotrexate (typically first-line), Sulfasalazine, Hydroxychloroquine, Minocycline, TNF-alpha inhibitors
DMARDs can alleviate pain and inflammation and reduce long-term _____ and disability in RA
joint destruction
For RA, DMARD therapy typically takes weeks therefore, short-term treatment with ____ (2) can provide rapid, temporary relief.
Glucocorticoids (prednisone)
NSAIDs
Colchicine disrupts cytoskeletal-dependent functions such as _______ (3).
It also reduces the formation of ____.
chemotaxis, phagocytosis, and degranulation
*leukocyte attraction
leukotriene B4
Altered gut biome/defective mucosal barrier
Increased production of IL-17, TNF-α &______
what disease?
Ankylosing Spondylitis
prostaglandins
What is the most sensitive test to diagnose AS?
X-rays of the spine and pelvis
Can see sacroiliitis (eg, joint erosions with subchondral sclerosis and eventual ankylosis)
and bridging syndesmophytes (heterotopic ossification affecting vertebral body margins).
In AS common X-Ray findings include
_____ (joint erosions with subchondral sclerosis and eventual ankylosis)
____ (heterotopic ossification affecting vertebral body margins).
sacroiliitis
bridging syndesmophytes
_____ is an autosomal-recessive disorder caused by a deficiency in an enzyme involved in tyrosine metabolism that can cause osteoarthropathy of the spine and large joints.
Alkaptonuria
____ causes erythema infectiosum (fifth disease) in children and arthritis in adults.
It can mimic rheumatoid arthritis but is usually self-resolving
Parvovirus B19
