Tophi in the articular cartilage, ligaments, tendons, and bursae are pathognomonic of gout. They are formed by large aggregations of urate crystals surrounded by an intense foreign body giant cell reaction (
Fig. 21.42B–C
Gouty nephropathy refers to the renal complications caused by urate crystals or tophi in the renal medullary interstitium or tubules. Complications include uric acid nephrolithiasis and pyelonephritis.
Gout is associated with male sex, obesity, metabolic syndrome, excess alchohol intake, renal failure, and age greater than 30 years. Four clinical stages are recognized:
Asymptomatic hyperuricemia appears around puberty in men and after menopause in women.
Acute arthritis presents after several years as sudden onset excruciating joint pain, localized hyperemia, and warmth. Most first attacks are monoarticular; 50% occur in the first metatarsophalangeal joint. Untreated, acute gouty arthritis may last for hours to weeks, but gradually there is complete resolution.
• Asymptomatic intercritical period: Resolution of the acute arthritis leads to a symptom-free interval. In the absence of appropriate therapy, the attacks recur at decreasing intervals and frequently become polyarticular.
Fig.21.42Gout.(A)Amputatedgreattoewithwhitetophiinvolvingthejointandsofttissues.(B)Goutytophus—anaggregateofdissolveduratecrystalsissurroundedbyreactivefibroblasts,mononuclearinflammatorycells,andgiantcells.(C)Uratecrystalsareneedleshapedandnegativelybirefringentunderpolarizedlight.
• Chronic tophaceous gout develops on average about 12 years after the initial acute attack. At this stage, radio-graphs show characteristic juxtaarticular bone and loss of the joint space.
Treatment of gout aims at lifestyle modification and medication to reduce symptoms (e.g., NSAIDs) and lower urate levels (e.g., xanthine oxidase inhibitor).
Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, usually occurs in individuals more than 50 years old and becomes more common with increasing age. The genders and races are equally affected. CPPD is divided into sporadic (idiopathic), hereditary, and secondary types. The autosomal dominant variant is caused by germline mutations in the pyrophosphate transport channel resulting in crystal deposition and arthritis relatively early in life. Various disorders, including previous joint damage, hyperparathyroidism, hemochromatosis, and diabetes, predispose to the secondary form. Studies suggest that articular cartilage proteoglycans, which normally inhibit mineralization, are degraded, allowing crystallization around chondrocytes. As in gout, inflammation is caused by activation of the inflammasome in macrophages.
MORPHOLOGYThecrystalsfirstdevelopinthearticularcartilage,menisci,andintervertebraldiscs,andasthedepositsenlargetheymayruptureandseedthejoint.Thecrystalsformchalky,whitefriabledeposits,whichareseenhistologicallyinhematoxylin-andeosinstainedpreparationsasovalblue-purpleaggregates(
Fig.21.43A ).Individualcrystalsarerhomboid,0.5to5µmingreatestdimension(
Fig.21.43B ),andarepositivelybirefringent.Inflammationisusuallymilderthaningout.