Gout, Pseudogout, Reactive Arthritis and AS Flashcards
What kind of crystals are seen in gout?
Monosodium urate (uric acid into these crystals)
Cardinal feature of gout
Inflammatory arthritis due to hyperuricemia
Where does the body get uric acid from?
It is a breakdown product of purine metabolism and is excreted by the kidney
What levels constitute hyperuricemia?
> 7.0 mg/dL in males
6.0 mg/dL in females
Either due to being underexcreter (most common) or overproducer
Overproducer
Due to inherited enzyme defects
High cell turnover (psoriasis or myeloproliferative disease)
Increased purine consumption (in diet)
Underexcretors
Renal insufficiency
Diuretics
Volume depletion
Lead nephropathy
Comorbidities of gout
HTN, obesity, CKD, diabetes, hyperlipidemia
Non-modifiable risk factors of gout
Male sex, advanced age, ethnicity (Pacific Islanders), genetic mutations/polymorphisms
Modifiable risk factors of gout
Obesity, diets rich in meat and seafood, ETOH, fructose-rich foods/beverages, diuretic use, transplant recipient status
4 stages of gouty arthritis
Asymptomatic hyperuricemia (15% get gout) Acute gouty arthritis (first attack) Intercritical gout (asymptomatic gout between attacks) Chronic gouty arthritis (tophaceous gout-involved joints will develop chronic swelling and tophi)
Tophi
White chalky material consisting of dense concentrations of MSU crystals
Due to duration and severity of hyperuricemia
Occur on avg 10 yrs after 1st attack if untreated gout
Pathogenesis pathway of gout
Hyperuricemia Deposition of crystals in/around joint Inflammatory cascade (painful joint) Without intervention tophi may develop Chronic gouty arthropathy (eroding bone and cartilage) without treatment
4 clinical manifestations of gout
Recurrent flares of inflammatory arthritis (gout flare)
Accumulation of urate crystals as tophaceous deposits
Chronic arthropathy
Renal complications (uric acid nephrolithiasis, urate nephropathy)
Presentation of acute gout attack
Monoarticular most of the time (can be poly) 1st MTP joint-big toe (Podagra) is most common site Self limiting (2 wks if untreated)
What triggers an acute gout flare?
Acute increases or decreases in urate levels
Ex: acute EtOH ingestion, food overindulgence, trauma, dehydration/starvation, meds (allopurinol or uricosuric agents usually treat gout but can also cause acute)
History of acute gout attack
Rapid onset, severe pain, pain peaks w/in 8-12 hours, redness, warmth, swelling, disability, maybe fever chills malaise
What will you see on the X-ray of established gout?
Bony erosions “punched out” with sclerotic margin and overhanging edges (rat bite erosions)
*early on there is only soft tissue swelling around joint
What does a duel-energy CT do?
ID urate deposits and tophi
What is seen in the ultrasound of gout?
Double contour sign (on artricular cartilage surfaces)
What must be done to diagnose gout?
Arthrocentesis
Arthrocentesis
Needle aspiration of the involved joint
Culture and gram stain it
Microscopic analysis shows MSU crystals and under polarized microscopy they are needle shaped and negatively bifefringent
When is serum uric acid the most accurate test?
> 2 wks after acute gout flare subsides (because might be normal level during acute attack)
Helpful to monitor effects of uric acid lowering therapy
What is 24 hour urinary uric acid used for?
If uricosuric therapy is being considered, then <800 mg is underexcretory and candidate for uricosuric therapy
Treatment vs no treatment for asymptomatic hyperuricemia
No treatment: no prior gouty arthritis, no tophaceous deposits, no nephrolithiasis
Treatment: urid acid excretion > 1100 mg/d, acute overproduction
Tx for acute gout attack
Treat pain and inflammation with NSAIDs, glucocorticoids or colchicine
Others: ice, ACTH, IL-1 inhibitors, Chinese herbs
Do not discontinue ULT
When are NSAIDs contraindicated to treat acute gout?
Chronic kidney disease, active duodenal or gastric ulcer, cardiovascular disease (not controlled), allergy, tx with anticoagulants
*most effected within 48 hours of onset of sx
Reasons to not use glucocorticoids or colchicine to treat gout
Glucocorticoids can increase blood sugar
Colchicine can be toxic when the patient has decreased renal function
When do you use urate lower therapy?
Treat those with an established dx of gout and: Tophi (clinical exam or imaging) Frequent (>2/yr) acute attacks Chronic kidney disease stage > 2 Previous nephrolithiasis
Xanthine oxidase inhibitors in urate lowering therapy
Allopurinol (zyloprim) or Febuxostat (Uloric)
Uricosuric agents in urate lowering therapy
Probenecid
Lesinurad (in combo with XOI)
Others (Losartan, Fenofibrate)
Recombinant uricase in urate lowering therapy
Pegloticase (Krsyexxa) by IV and used by the rheumatologist
For refractory gout
What do xanthine oxidase inhibitors do?
Decrease urid acid synthesis
Allopurinol
DOC for most patients (overproducers and underexcretors) Side effects (rash, hypersensitivity, severe cutaneous adverse rxns like SJS or TENS) *avoid in individuals who are HLA-B 5801 positive
Probenecid
Primarily used for underexcretors
Enhances renal excretion of uric acids
Avoid in pts with hx of nephrolithiasis and take ASA (large doses)
Requires good renal function
When do you initiate urate lowering therapy?
Wait until after acute gout flare has resolved (at least 2 weeks)
Must do anti-inflammatory prophylaxis of low dose Colchicine or NSAIDs for if have an acute flare (must continue for 6 moths after start ULT)
Whats the target level for ULT?
sUA of 6 mg/dL or less (5 for tophaceous gout)
*adjust dose if not at goal
Measure 2-4 wks after adjustment and confirm at 3 months
Then measure every 6 months for a year
Then annually
When to refer for a gout patient?
Unclear etiology of hyperuricemia
Difficulty reaching target serum uric acid level
Multiple and/or serious adverse effects from ULT
What crystals are seen in pseudogout?
Calcium pyrophosphate crystals
Where does CPPD start?
Formation is initiated in cartilage located near surface of chondrocytes
Avg age of diagnosis of CPPD
72
What metaboic/endocrine disorders are associated with CPPD?
Hemochromatosis, hyperparathyroidism, hypomagnesemia, hypophosphatasia
*also associated with joint trauma or familial chondrocalcinosis
Acute attacks of pseudogout
Self-limited severe acute inflammation
Knee affected in over 50% (other joints also seen)
Trauma, surgery of severe medical illness often provoke acute attacks
Chondrocalcinosis
Cartilage calcification
Seen with radiographic evidence of CPP crystal deposts
Punctate and linear radiodensities
Synovial fluid aspiration in pseudogout
Positively bifefringent CPP crystals (P, P)
*diagnose with synovial fluid analysis and/or radiographic findings
Acute tx for pseudogout
NSAIDs, intraarticular glucocorticoid injection (after ruling out septic joint), colchicine, oral glucocorticoids, support
Tx for chronic prophylaxis of pseudogout
Colchicine .6 mg twice daily (or another NSAID)
Recommended if >3 attacks per year
Adjust for renal dosing!
2 classifications of spondyloarthritis (SpA)
*family of inflammatory rheumatic diseases that cause arthritis
Predominantly axial disease (ankylosing spondylitis)
Predominantly peripheral disease (reactive arthritis, PsA, arthritis associated with IBD, undifferentiated SpA)
Shared clinical features of SpA
Inflammatory back pain, enthesitis, asymmetric oligoarthritis, dactylitis (sausage digits), uveitis, strong association with HLA-B27, seronegative (negative RF)
Clinical manifestations of SpA
Either axial (sacroilitis or spondylitis) or peripheral symptoms (peripheral arthritis, enthesitis, dactylitis)
Enthesitis
Inflammation around the entheses (site of insertion of ligaments, tendons, joint capsule, or fascia to bone)
Clinical manifestation of enthesitis
“Heel pain”
Swelling at the heels (because of insertion of achilles or plantar fascia into the calcaneus)
Pain, swelling and local tenderness
Saying for reactive arthitis
Can’t see (conjunctivitis/uveitis), can’t pee (urethritis), can’t climb a tree (arthritis in knee)
What is reactive arthritis?
Acute inflammatory arthritis triggered by a preceding GI or GU infection (autoimmune)
GI: shigella, salmonella, yersinia, campylobacter
GU: chlamydia trachomatis
Genetic predisposition for reactive arthritis or ankylosing spondylitis
HLA-B27
Clinical presentation of reactive arthritis
Acute onset
Typically present with asymmetrical oligoarthritis** (predominantly lower extremity)
Usually 1-4 wks following inciting infection (diarrheal illness or urethritis)
Associated/peripheral MSK s/sx in reactive arthritis
Peripheral arthritis, enthesitis, dactylitis, inflammatory low back pain in spine or SI joints
Extra articular manifestations in reactive arthritis
Conjunctivitis/uveitis, urethritis, nail changes, circinate balanitis (nonpainful penis ulcers), oral ulcers, keratoderma blennorrhagicum (thickened pustules)
Diagnostic evaluation of reactive arthritis
Evidence or antecedent or concomitant infection
Elevated ESR or CRP maybe
Positive HLA-B27 in 30-50%
Negative for crystals or infection in synovial fluid analysis
Maybe imaging with enthesitis or arthritis
Tx for reactive arthritis
Initial therapy (NSAIDs)- mainstay of therapy Refer if uveitis
What is ankylosing spondylitis?
Chronic inflammatory disease of the axial skeleton (particularly SI and spinal facet joints)
Manifestation of ankylosing spondylitis
Back pain and progressive stiffness of the spine (seen more in whites and males)
*young males!
Progression of ankylosing spondylitis
Enthesitis with chronic inflammation
Structural damage
New bone formation (ossification)
Ankylosis (fusion)
How does ankylosing spondylitis initially present and how is it seen later?
Initially is SI joints
Moves proximally
Annulus fibrosus undergoes ossification to form syndesmophytes
Progresses to bamboo spine appearance in late advanced disease
History seen with ankylosing spondylitis
Insidious (slow) onset of low back pain in SI joints
Pain and stiffness
Often radiates into buttocks
Symptoms longer than 3 months
Symptoms worse in morning or with inactivity
Onset before age of 40
PE findings for ankylosing spondylitis
Hyperkyphosis
Limited spinal mobility
Loss of lumbar lordosis
Tenderness over insertion sites (SI joints)
*modified Schober test is flexing forward
Extraarticular manifestations and comorbities with AS
Acute anterior uveitis (30%)- immediate referral IBD Psoriasis Restrictive disease pattern Cardiovascular disease Pain, fatigue, sleep disturbance
Lab studies seen in AS
CBC that may show normocytic-normochromic anemia (seen in chronic disease)
Elevated ESR and/or CRP
Negative RF and anti-CCP antibodies
Positive HLA-B27 (85%)
Hallmark imaging study for AS
Radiographic sacroiliitis
Pharmacologic tx of AS
First line: NSAIDs (indomethacin/naproxen)
NSAID resistant disease (sulfasalazine for peripheral joint involvement) or TNF/IL inhibitors
