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Crystalline Arthropathies (Gout (Signs/symptoms (Acute, severely painful,…
Crystalline Arthropathies
Gout
Crystal type
monosodium urate (MSU)
needle-shaped
Negatively birefringent: yeLLow in paraLLel
Epidemiology
2.7/1000 incidence
9:1 male:female (postmenopausal)
Signs/symptoms
Acute, severely painful
Monoarticular (first flare & most flares). Later flares can be polyarticular.
First flare great MTP (podagra)
Warm, swollen, often erythematous.
Tender to palpation
Pathophysiology
MSU crystals internalized by monocytes, activating NALP3 inflammasome
Triggers increase/decrease serum uric acid (acute illness, trauma, surgery, EtOH, seafood, red meat, change in urate therapy)
Intercritical period
Time b/w flares
Avg length to second attack = 12-18 mos
Disease progression yields less time b/w attacks, eventually continuous.
Diagnosis
Elevated serum uric acid:
not diagnostic
Joint aspiration:
Rule-out infection, find/type crystals
Treatment
Acute
Self-limited & PAINFUL attacks. Treatments cover acute symptoms and DO NOT prevent future attacks.
NSAIDs
(indomethacin): high dose, short time
Colchicine
Abort flare
Inhibits tyrosine phosphorylation in PMNs in resp. to crystals
Blocks activation of NALP3 inflammasome
Inhibits neutrophil adhesion
SEs
Diarrhea
Vomiting
Nausea
Bone marrow suppression (renal failure pts)
Steroids
Oral for polyarticular disease
IA injection for monoarticular disease
Don't start/stop urate-lowering therapy during flare b/c can worsen flare!
Chronic
Description
Symptom-free periods shorten. Attacks incompletely resolve.
Oligo-/poly-articular arthritis, ongoing symps, less painful than acute attack
Incr. involvement of UE joints
Tophi
~10 yrs of disease
Fingers/toes/olecranon
Treatment
Goal = lower serum (/tissue) uric acid.
Promote crystal dissolution/prevent crystal formation: serum urate
<6.0 mg/dl.
For asymptomatic pts?
Uric acid >13 in men
Uric acid >10 in women
Uricosuria >1000 mg/dl
Pre-chemotherapy
Xanthine Oxidase (XO) Inhibitors
Allopurinol
SEs
Rash (3-10%)
Hypersensitivity Synd (20-30%) HLA-associated, Hahn Chinese
Interactions
Theophylline
Warfarin
AZA/6-MP
Febuxostat
Non-purine XO inhib
Metabolized in liver (OK for decr renal function)
$$$
Periodic LFTs
Remember to add therapy to prevent flare when starting XO inhib (colchicine, low-dose pred)
Recombinant Uricase
Pegloticase
PEGylated recombinant (porcine-baboon) uricase
IV q2 wks
Tophi debulking
Infusion rxn common -- pre-treat w/ steroid + histamine
$ $ $ $
Rasburicase
Non-PEGylated recombinant fungal enzyme
Short half-life, highly immunogenic
Uricosuric
Probenecid
Under-excretors (<1000 mg/dl)
Good renal function necessary.
Losartan (HTN + gout)
Dietary modifications (lower by ~1 mg/dl)
CPPD Arthropathy ("Pseudogout")
Crystal type
calcium pyrophosphate dihydrate (CPD
small, rhomboid-shaped
Positively birefringent = blue in parallel
Epidemiology
Incr prevalence w/ incr age
Pathophysiology
Commonly affects
knee
hip
triangular fibrocartilage of wrist
Often asymptomatic
Potential causes wide-ranging
Symptoms
Acute
Inflamm 1-2 joints,
asymmetric
Knees, wrists
Provoked by trauma, surgery, illness, etc.
Chronic
Polyarticular,
symmetric
Wrist, MCP, maybe C1
Flexion contracture
(-) RF (-) CCP
Diagnosis
Clinical picture + Aspiration
Treatment
NSAIDs
Steroids -- acute
Colchicine -- less effective than in gout. Low-dose prophylaxis.
Basic Calcium Phosphate
Crystal type
basic calcium phosphate
"Shiny coin"
Non-birefringent
Alizarin red stain to visualize: binds Ca++. Alternatively, scanning EM.
Deposits in tendons, discs, joint capsule, synovium, cartilage, skin, arteries, etc.
Milwaukee Shoulder Synd
Clinical
Elderly female (80%)
Dominant shoulder (95%)
Knee (50%)
Radiographic
Rapid glenohumeral joint destruction
High-riding humerus b/o rotator cuff tear
Soft-tissue calcification
Synovial fluid
Low WBC (<500)
BCP crystals
Calcific Tendonitis
2.7% Caucasian office workers
40% symptomatic
F>M
Age 31-40
In poorly vascularized portion of supraspinatus laterally
Calcific Periarthritis
Hand joints
Pain, swelling
Younger patients
Resolves over weeks
Pseudo Podagra
Looks just like gout
Younger patients
Resolves over weeks