Metabolic and Endocrine Diseases Associated With Rheumatic Disorders
Metabolic and endocrine diseases may be associated with rheumatic disorders. These include biochemical abnormalities (amyloidosis and scurvy), endocrine diseases (diabetes mellitus and acromegaly), immunodeficiency diseases (HIV infection, AIDS), and other hereditary disorders (hypermobility syndromes). The most common conditions, however, are the crystal-induced arthropathies in which crystals, such as monosodium urate (gout) or calcium pyrophosphate (calcium pyrophosphate dihydrate disease [CPPD] or pseudogout), are deposited within joints and other tissues.
Gout is a heterogeneous group of conditions related to a genetic defect of purine metabolism resulting in hyperuricemia. Over-secretion of uric acid or a renal defect resulting in decreased excretion of uric acid, or a combination of both, occurs. The prevalence of gout is reported to be 1.6 to 13.6 per thousand. The incidence increases with age and body mass index. It occurs more commonly in males than females (Ruddy et al., 2001).
In primary hyperuricemia, elevated serum urate levels or man-ifestations of urate deposition appear to be consequences of faulty uric acid metabolism. Primary hyperuricemia may be due to se-vere dieting or starvation, excessive intake of foods that are high in purines (shellfish, organ meats), or heredity. In secondary hy-peruricemia, gout is a clinical feature secondary to any of a num-ber of genetic or acquired processes, including conditions in which there is an increase in cell turnover (leukemia, multiple myeloma, some types of anemias, psoriasis) and an increase in cell breakdown. Altered renal tubular function, either as a major ac-tion or as an unintended side effect of certain pharmacologic agents (diuretics such as thiazides and furosemide), low-dose sal-icylates, and ethanol can contribute to uric acid underexcretion.
Hyperuricemia (serum concentration greater than 7 mg/dL [0.4 fmol/L]) can but does not always cause monosodium urate crystal deposition. However, as uric acid levels rise, risk increases (Ruddy et al., 2001). Attacks of gout appear to be related to sud-den increases or decreases of serum uric acid levels. When the urate crystals precipitate within a joint, an inflammatory response occurs and an attack of gout begins. With repeated attacks, accu-mulations of sodium urate crystals, called tophi, are deposited in peripheral areas of the body, such as the great toe, the hands, and the ear. Renal urate lithiasis (kidney stones) with chronic renal disease secondary to urate deposition may develop.
The finding of urate crystals in the synovial fluid of asympto-matic joints suggests that factors other than crystals may be related to the inflammatory reaction. Recovered monosodium urate crys-tals are coated with immunoglobulins that are mainly immuno-globulin G (IgG). IgG enhances crystal phagocytosis, thereby demonstrating immunologic activity.
Manifestations of the gout syndrome include acute gouty arthritis (recurrent attacks of severe articular and periarticular inflamma-tion), tophi (crystalline deposits accumulating in articular tissue, osseous tissue, soft tissue, and cartilage), gouty nephropathy (renal impairment), and uric acid urinary calculi. Four stages of gout can be identified: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout, and chronic tophaceous gout. The subsequent development of gout is directly related to the dura-tion and magnitude of the hyperuricemia. Therefore, the com-mitment to lifelong pharmacologic treatment of hyperuricemia is deferred until there is an initial attack of gout.
For hyperuricemic people who are going to develop gout, acute arthritis is the most common early clinical manifestation. The metatarsophalangeal joint of the big toe is the most commonly affected (75% of patients). The tarsal area, ankle, or knee may also be affected. Less commonly, the wrists, fingers, and elbows may be affected. The acute attack may be triggered by trauma, alcohol ingestion, dieting, medications, surgical stress, or illness. The abrupt onset often occurs at night, awakening the patient with se-vere pain, redness, swelling, and warmth of the affected joint. Early attacks tend to subside spontaneously over 3 to 10 days even without treatment. The attack is followed by a symptom-free period (the intercritical stage) until the next attack, which may not come for months or years. With time, however, attacks tend to occur more frequently, involve more joints, and last longer.
Tophi are generally associated with more frequent and severe inflammatory episodes. Higher serum concentrations of uric acid are also associated with more extensive tophus formation. Tophi most commonly occur in the synovium, olecranon bursa, sub-chondral bone, infrapatellar and Achilles tendons, subcutaneous tissue on the extensor surface of the forearms, and overlying joints. They have also been found in the aortic walls, heart valves, nasal and ear cartilage, eyelids, cornea, and sclerae. Joint enlarge-ment may cause a loss of joint motion. Uric acid deposits may cause renal stones and kidney damage.
A definitive diagnosis of gouty arthritis is established by polarized light microscopy of the synovial fluid of the involved joint. Uric acid crystals are seen within the polymorphonuclear leukocytes within the fluid. Colchicine (oral or parenteral) or an NSAID such as indomethacin is used to relieve an acute attack of gout. Management of hyperuricemia, tophi, joint destruction, and renal disorders is usually initiated after the acute inflammatory process has subsided. Uricosuric agents, such as probenecid, cor-rect hyperuricemia and dissolve deposited urate. Allopurinol is also effective, but its use is limited because of the risk for toxicity. When reduction of the serum urate level is indicated, the urico-suric agents are the medications of choice. When the patient has, or is at risk for, renal insufficiency or renal calculi (kidney stones), allopurinol is the medication of choice. Corticosteroids may be used in resistant cases. If the individual experiences several acute episodes or there is evidence of tophi formation, prophylactic treatment is considered. Specific treatment is based on serum uric acid level, 24-hour urinary uric acid excretion, and renal function (Table 54-5).
Historically, gouty arthritis was thought to be a condition of the royalty and the very rich, with the disease attributed to “high living.” This has not been shown to be entirely true. While severe dietary restriction is not necessary, patients should be encouraged to restrict consumption of foods high in purines, especially organ meats, and to limit alcohol intake. Maintenance of normal body weight should be encouraged. In an acute episode of gouty arthri-tis, pain management is essential. During the intercritical period, the patient feels well and may abandon preventive behaviors, which may result in an acute attack. Acute attacks are most effectively treated if therapy is begun early in the course.