Osteoarthritis/Rheumatoid/Gout Flashcards
Etiopathogenesis of Osteoarthritis
Most common joint disease and a leading cause of disability in the elderly
Sine qua non is hyaline cartilage loss
Risk Factors for OA
- Age (most important)
- Obesity
- repeated joint use
Manifestations of OA
Activity-related
starting as episodic and progressing continuously with accompanying brief morning stiffness (<30 min) that gradually resolves
Commonly affected Joints
- Cervical
- spine
- lumbosacral
- spine
- Hip
- Knee
- 1st MTP
- distal
- proximal IPs
- base of the thumb
Buckling of the knees may occur due to weakness of muscles crossing the joint
Diagnostics for OA
No blood tests is indicated
Synovial fluid analysis
Management of OA
NON-PHARMACOLOGIC
- Exercise with brief periods of rest
- Weight management (wt loss to 5kg = 50% pain reduction)
- Correction of possible misalignment
- Acupuncture
- Oral standardized
- ginger preparation
- Surgery
Pharmacologic Management for OA
- Non-opiod analgesics
- Opiod-like analgesics
- Traditional NSAIDs
- Oral COX-2 inhibitors
- Intraarticular injections
- Hexosaminases
- Capsaicin
NON-opiod analgesics
Paracetamol 500 mg up to QID
- Initial treatment
Modulates the endogenous cannabinoid system in the brain
Can prolong half life of warfarin
Opiod Analgesics
Tramadol 50-100 mg q4-q6
Binds to the u-opiod receptor
SE: Dizziness, sedation, nasuea/vomiting, Urinary retention, constipation, dry mouth
Traditional NSAIDs
Suppress inflammation by ihibiting both COX-1 and COX-2 activity
Naproxen 375-500 mg BID, taken with food
SE: GI ulceration and bleeding, edema, renal insufficiency
Diclofenac gel 1% gel, 4 g QID Should be rubbed onto joint
- Skin irritation common
- Avoid if with renal disease
Oral COX-2 inhibitors
Inhibits COX-2 activity only
- Celecoxib 100-200mg QD-BID
- Eterocoxib
SE: Increased risk for stroke and MI
Capsaicin
Bind to the vanilloid receptor sybtype 1 (TRPV1) thereby modulating pain sensations.
0.025%-0.075% cream 3-4x day
Can irritatemucous membrane
Etiopathogenesis of Gouty Arthritis
Metabolic disease that usually affects men (30s onwards) and postmenopausal women
- Increased body urate pool with hyperuricemia
- Urate overproduction
- Urate Underexcretion
Precipitants of Hyperuricemia (Gouty)
- Dietary excess
- Trauma,
- surgery
- Excessive ethanol ingestion
- Hypouricemic therapy
- Serious comorbid illnesses such as stroke and MI
Manifestations of Gouty Arthritis
- Acute arthritis usually initially affecting MTP of the first toe (PODAGRA) or ankle or knee, followed by episodes of acute mono-or oligoarthritis and finally chronic nonsymmetric synovitis with topaceous deposits
- Inflamed Heberden’s and Bouchard’s nodes
- Initial attacks mimic cellulitis, subside spontaneously over 3-10 days, and have varying asymptomatic periods until the next attack
Asymptomatic hyperuricemia
Hyperuricemia in the absence of gouty arthritis and uric acid nephrolithiasis
Hyperuricemia
- Men: >7 mg/dL
- Female: >6 mg/dL
Acute Gouty Arthritis
Urate crystal in the joint fluid, and/or
Presence of six of the 12 clinical laboratory, and Xray phenomenon
- Max. Inflammation developed within 1 day
- More than 1 attack of acute arthriitis
- Monoarticular arthritis
- Redness over joints 1st MTP joint pain or swelling
- Unilateral first MTP joint attack
- Unilateral tarsal joint attack
- Suspected Tophus
- Hyperuricemia
- Asymmetric swelling within a joint on X-ray
- Subcortical cysts without erosions on x-ray
- Negative organisms on culture of joint fluid during attack
Intercritical (interval) Gout
Asymptomatic periods between gouty attacks
Chronic Tophaceous gout
- occurs in untreated gouty arthritis
- Low grade inflammation of joints with sporadic flares
- Joint deformities occur due to deposition of urate crystals, forming visible tophi
24-h uric acid urine collection
- >800mg/24h (over producers)
- <600 mg/24 h (under excretors)
Treament goal for gout:
Uric acid <6mg/dL
Medical management of Acute Attacks
Recommended first-line options
- Colchicine
- NSAIDs
- Oral Costicosteroid
- Articular aspiration and injection of steroids
Colchicine
1 mg LD within 12 hours of flare onset followed 1 hour later by 0.5 mg; or TID unil flare subsides.
Inhibits microtubule polymerization and neutrophil activity/motility, giving its anti-inflammatory effect
Avoid in patients with severe renal impairment and those receiving CYP3A4 inhibitors
NSAIDs in acute flares of GA
- Celcoxib 400 mg BID
- Diclofenac 50 mg TID
- Etoricoxib 120 mg OD
- Indomethacin 25-50 mg TID
- Naproxen 500mg BID
Steroids
Prednisolone 30-35 mg/day (or its equivalent for 3-5 days)`
Anakinra
100 mcg/day SC for 3-5 days
IL-1 Blocker
Indications for Therapeutic Arthrocentesis
- Unable to take oral medications
- Have only 1-2 actively inflamed joints
- Ready access to a clinician with expertise in arthrocentesis
- Can be performed immediately prior to injecting intraarticular medications
Flare Prophylaxis for Gouty Arthritis
Recommended during the first 6 months of ULT or until serum uric acid is <6 mg/dL
Colchicine 0.5-1 mg/day
Urate lowering therapy
Indicated in all patients with
- recurrent flares (>2/year),
- tophi
- urate arthropathy,
- and/or nephrolithiasis
Should be started close to time of first diagnosis in
- patients <40 years old
- SUA >8 mg/dL with commorbidities
Target lifelong SUA: <6 mg/dL
Lower target: <5 mg/dL
Allopurinol
Inhibits xanthine oxidase blockng uric acid production
Initial low dose: 100 mg/day and increased at 100 mg increments every 2-4 weeks
Usual dose: 300 mg/day
Febuxostat
Inhibits xanthine oxidase blocking uric acid production
40-80 mg/day
Indicated if SUA target cannot be reached by Allopurinol or if allopurinol is not tolerated
Benzbromarone
Increases uric acid excretion
50-200 mg/day
Potent inhibitor of CYPC29
Pegloticase
Pegylated recombinant porcine uricase
8 mg IV q2 weeks
Indication:
- patients with crystal proven
- severe debilitating chronic tophaceous gout
Contraindicated in G6PD deficient patients
Etiopathogenesis of Rheumatoid Arthritis
Chronic inflammatory disease of unknown etiology marked by symmetric, peripheral polyarthritis
may result in a variety of extraarticular manifestions, lung ivolvement, pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities
Joint Involvement in RA
- small joints of hands and feet
- Early morning stiffness> 1 hour easing with physical activity
- wrist
- MCP
- PIO
- Swan neck deformity
- Boutonniere deformity
- Z-line deformity
- Flexor tendor tensosynovitis
Swan neck deformity
hyperextension of the PIP with flexion of the DIP joint
Boutonniere deformity
Flexion of the PIP with hyperextension of the DIP joint
Z-line deformity
Subluxation of the first MCP with hyperextension of the 1st IP joint
Hallmark of RA
flexor tenosynovitis
Subcutaneous nodules in RA
benigh, firm,nontender and adherent to periosteum, tendons, or bursae
Pleuritis and pericarditis in RA
most frequent site of cardiac involvment in RA is the pericardium
Vasculitis in RA
Fever of >39.3 during the clinical course should raise suspicion of systemic vascultis
Constitutional symptoms in RA
weight loss, fever, fatigue, malaise, depression, and cachexia in more severe cases
Diagnostic tests for RA
Serum Markers:
- RF
- anti-CCP
Acute phase reactants
CBC
- normocytic normochromic anemia
Synovial fluid Analysis
- Consistent with inflammatory arthritis
Joint imaging
- Juxtaarticular osteopenia (initial finding)
- soft tissue swelling
- Joint effusions
- symmetric joint space narrowing
- Joint subluxation and collapse
Monitoring for RA
every 1-3 months in active disease,
with treatment adjusted if no improvement seen by 3 months or target not reached by 6 months
Remission
defined as having all of the following:
- Tender joint <1 swollen
- joint count <1
- CRP <1 mg/dl
- patient global assessment scale <1
- must have a clinical disease activity index score of <2.8
NSAIDs for RA
adjunctive therapy
Glucocorticoids for RA
low to moderate dose for rapid disease control before the onset of fully effective DMARD therapy
1 to 2 week burst of glucocorticoids for acute disease flares
csDAMRDs
Slow or prevent structural progression of RA
Cornerstone of therapy which should be started as soon as diagnosis of RA is made
Methotrexate
csDMARD of Choice
10-25mg/week PO or SC
Folic acid 1 mg/day given to reduce toxicities
contraindicated in pregnancy
Hydroxychloroquine
200-400 mg/day PO
If with contraindication or early intolerance to metho
Sulfasalazine
500-1500 mg BID PO
SE: granulocytopenia, hemolytic anemia in persons with G6PD deficiency, nausea, diarrhea
Leflunomide
10-20 mg/day
SE: hepatoxicity, myelosuppresion, infection, alopecia, diarrhea Contraindicated in pregnancy
[RA] Infliximab
Chimeric anti TNF
[RA] Adalimumab; Golimumab
Fully humanized anti TNF
[RA] Cetolizumab pegol
Pegylated Fc-free fragment of a humanized monoclonal antibody with binding specificity for TNF
[RA] Etanercept
Soluble fusion protein compromising the TNF receptor-2 in a covalent linkage with the fc portion of IgG1
[RA] Anakinra
IL -1 receptor antagonist
[RA] Abatacept
soluble fusion protein consisting of a domain of human CTLA-4 linked to aportion of human IgG
[RA] Rituximab
Chimeric monoclonal against CD-20
[RA] Tocilizumab
Humanized monoclonal antibody against IL-6 receptor
[RA] Tofacitinib
Small molecule inhibitor that targets JAK1 and JAK3
[RA] Baricitinib
small molecule inhibitor that targets JAK1 and JAK2
[RA] Baricitinib
small molecule inhibitor that targets JAK1 and JAK2
Etiopathogenesis of Infectious Arthritis
Hematogenous route is the most common route in all age groups
Knee is most commonly involved
Acute bacterial infection typically involves a single joint or few
Etiologic agents of Infectious arthritis
- Infants: Group B streptococcus, Gram (-) enteric bacilli, Staph. aureus
- Young adults and adolescents: N. gonorrhea
Staphyloccous aureus accounts for most non-gonoccocal isolates in adults of all ages
manifestations of Infectious arthritis
- Fever
- Moderate severe pain that is uniform around the joint
- MSK: joint effusion, muscle spasm, decreased range of motion
Diagnostics in Infectious arthritis
- Acute Phase reactants
- CBC
- Synovial fluid analysis
- Joint imaging
- Cultures
Non pharma management for Infectious arthritis
Repeated arthrocentesis
Surgical Drainage/arthroscopic lavage usually indicated for:
- Septic hip
- Concomitant osteomyelitis
- Prosthetic joint infection
Recommended Antibiotics
Gram(+) smear, MRSA unlikely
- Oxacillin 2 g IV q4; or Nafcillin 2g IV
Gram (+) smear MRSA likely
- Vancomycin 1 g IV q12
Gram (-) smear or no organisms on smear
- Cefotaxime 1 g IV q8; or Ceftriaxone 1-2 g IV q24
Pseudomonas suspect
- Add aminoglycoside or 3rd gen cephalosporin anti pseudomonal cephalosporin (Ceftazidime 1g IV q8)
Duration of Treatment according to organism
S. Aureus - 4 weeks
Pneumococcus/ Penicillin sensitive Strep - 2 weeks PEN G 2M units q4 or cefotaxime
Haemophilus influenzae/ Penicillin-resistant streptococcus - 2 weeks Cefotaxime or Ceftriaxone
Enteric gram (-) bacilli -3-4 weeks 2nd/3rd gen Cephalosporin IV or quinolone IV/PO
Pseudomonas aeruginosa - at least 2 weeks of aminoglycoside plus extended-spectrum penicillin or anti-pseudomonal cephalosporin
Etiopathogenesis of plantar fascitis
Foot pain originating at or near the site of plantar fascia attachment to the medial tuberosity of the calcaneus
Peak incidence: 40-60 years old
Risk Factors:
- obesity
- pes planus
- pes cavus
- limited ankle dorsiflexion
- prolonged standing
- walking on hard surfaces
- excessive running
- faulty shoes
manifestations of Plantar fascitis
severe pain with the first steps upon arising in the morning or following inactivity during the day Pain
usually lessens with weight bearing activity
Pain worse when walking barefoot or climbing stairs
Maximal tenderness over the inferior heel at the site of attachment of the plantar fascia
symptoms resolve in majority of patients after 1 year
Diagnostics for Plantar fascitis
Plain Xray : heel spurs
Ultrasound: Fascial thickening, edema
MRI: sensitive method but not usually required for diagnosis
Plantar fasciotomy
patients who do not improve of conservative treatment
