| What are crystal diseases? | Monosodium Urate (MSU) and Gout.
Calcium pyrophosphate (CPD) and pseudogout.
Basic Calcium phosphate (BCP) and periarthritis
Ochronosis. |
| What is gout? | MSU crystal deposition disease, elevated serum urate acid SUA causing hyperuriciemia leading to local conditions.
We first get elevated purines (due to catabolism, tumor lysis syndrome, diet [meat, sea food...]) which lead to increased Xanthine and thus by xanthine oxidase increase urate pool causing hyperuricemia (excreted 30% fecal and 70% urine) causing (joint inflammation, kidney/bladder stones, nephropathy, CVD, metabolic syndrome as we get decreased renal clearance by drugs, fructose, genetics and kidney disease aggravating gout
Risk factors (male, age, obesity, ethnicity pacific, polymorphism, kidney disease) |
| How is gout progression? | Starts asymptomatic, until we get first acute flare, then a period of years of no symptoms to have a second flare, then periods of no symptoms (intercritical perioids getting shorter) and flares which are more intense (Recurrent acute gouty arthritis), and finally we get to start of advanced gout |
| How is etiology of gout? | Depends on age and gender (very low prepubertal and adult women, high post menopausal women and postpubertal men)
3 factors influence hyperuricemia (total amount of produced uric acid, renal clearance of urate, and intestinal excretion of urate) |
| How is hyperproduction and decreased clearance of gout and local conditions causing gout? | Hyperproduction (increased purines [tumors, hematologic disease, chemo, psoriasis, food and beer], enzymatic defects [Lesch-Nyhan in boys, G6PD])
Decreased clearance (most common cause of gout, CKD, metabolic syndrome, HTN, decompensated HF, saturnine gout, alcohol, drugs [diuretics, aspirin, cyclosporine], genetics)
Local conditions (Preference of lower limb [due to repititive microtrauma], osteoarthritis, cold temperature, severe intercurrent disease [hypoxia of tissue], surgery, uricosic drugs, some food? |
| How is pathophysiology of gout? | Formation of MSU crystals (hyperuricemia, precipitation of MCU crystals and deposition in articular and periarticular tissues)
Acute gout attack (phagocytosis of the crystals, cell swelling and inflammation, cytokine production and vasodilation leading to neutrophil and monocyte influx)
Chronic tophaceous gout (neutrophil death by NETosis, packaging of MSU crystals , inactivation of cytokines and resolution of inflammation)
Normal uric acid is 6-6.6 mg/dl in serum, they accumulate in blood and tissues, precipitate in suprasaturated tissues form needle shaped crystals, they are less soluble under acid and low temperature conditions (cool peripheral joints).
Urate crystals are recognized by polarizing microscopy by light retarding characteristic of urate. |
| How is physiopathologic cycle of gout? | Intercritical gout is quiecent, then comes urate crystal recognition by phagocytes, that release inflammasomes (IL1beta, IL6, IL18, TNF alpha, IL10) then amplification phase due to tissue damage, matric metalloproteinases, PGs, TLRs, then comes resolution phase (anti-inflammatory mediators like CD68, PPAR, TGF) |
| How is epidemiology of gout? | No stats, worldwide distribution, regional differences reflect environmental dietary and genetic differences.
Prevalence is 5.9% men and 2% women (difference due to age of onset, estrogen has uricosic effect so gout is unusual in premenopausal women)
Western countries affected 1-2% w/ prevalence with age 7% men >65 and 3% women over 85
uric acid elevated 10-20 years prior to gout. |
| How is clinical presentation of gout? | Typical presentation (monoarthritis, acute excrutiating pain, edema, inflammation of MTP of great toe (podagra initial manifestation 50% of cases, and 90% involved)
Most common sites (ankle, wrist, finger, knee), early gout 1 or 2 joints involved, any pt with acute monoarthritis it is sus.
Polyarticular is in 10% of pt, usually consequetive joints, reach max intensity w/in 8-12 hours, affected joints hot, red, tender, swollen bed sheet, if untreated it resolves w/in 2 weeks |
| How is physical exam of gout? | All joints examined, involved joints signs of inflammation, erythema over joint looks like cellulitis, skin desquamate as the attack subsides, joint capsule quickly swollen loss in ROM, fever, differential with septic arthritis or coexisting acute gouty arthritis, commonly involves small joints of fingers and toes and kness and can cause inflammation in synovial bursae/tendons.
Tophi (collections of urate crystals in soft tissues, develop after a decade of chronic untreated gout, earlier in older women those recieving diuretics, classical located along ear helix, fingers, toes, prepatellar bursa, olecranon. DD rheumatoid nodule. |
| How is complication of gout? | • Severe degenerative arthritis
• Secondary infections
• Increased susceptibility to infection
• Urate or uric acid nephropathy
• Renal stones
• Nerve or spinal cord impingement
• Fractures in joints with tophaceous gout |
| How is gout prognosis? | Good if treated early, considerable morbidity, acute episodes are handicapping, chronic injury to intra-articular cartilage leaves joints susceptible to joint infections, untreated tophi can lead to severe joint destruction, renal impairment, spinal cord impingement when deposition in tissues produces a large mass.
Hyperuricemia and gout are associated with increased mortality
Association with heart and vascular diseases, renal diseases, metabolic disordes, and joint diseases |
| How is gout differential diagnosis? | Septic Arthritis,Cellulitis, Pseudogout, Rheumatoid Arthritis, Arthritis as a Manifestation of Systemic Disease.
Characteristics for gout (male, previous arthritis attack, onset w/in 1 day, joint redness, first MTP, HTN or cardiovascular disease, serum uric acid level higher than 5.88 mg/dl |
| How is dx of gout occurring? | Joint aspiration (Demonstration of intracellular monosodium urate crystals needle-shaped intracellular and extracellular crystals Negatively birefringent urate crystals are seen on polarizing examination in 85% of specimens Sensitivity 84%,specificity 100%)
Exclusion of infection or other crystal types in synovial fluid from inflamed joint |
| What is the work up for gout? | Blood test (SUA [could be normal during attack hx of high level], inflammatory markers, kidney function test)
Renal uric acid measure in high risk pt (renal calculi, strong fam hx, first attack before 25)
Xray
Erosions (overhanging edges, bony erosions, punched out border [cookie cutter], asymmetrical, predilection of distal joints)
US (double contour sign, hyperechoic, irregular line of crystal on surface of cartilage, wet clump of sugar tophi hyper and hypoechoic, bony erosions adjacent to tophi deposits) |
