Causes
The many causes of scoliosis include neuromuscular problems and inherited diseases or conditions caused by the environment.An estimated 65% of scoliosis cases are idiopathic, about 15% are congenital, and about 10% are secondary to a neuromuscular disease.About 38% of variance in scoliosis risk is due to genetic factors, and 62% is due to the environment. The genetics are likely complex, however, given the inconsistent inheritance and discordance among monozygotic twins. The specific genes that contribute to development of scoliosis have not been conclusively identified. At least one gene, CHD7, has been associated with the idiopathic form of scoliosis. Several candidate gene studies have found associations between idiopathic scoliosis and genes mediating bone formation, bone metabolism, and connective tissue structure. Several genome-wide studies have identified a number of loci as significantly linked to idiopathic scoliosis. In 2006, idiopathic scoliosis was linked with three microsatellite polymorphisms in the MATN1 gene (encoding for matrilin 1, cartilage matrix protein). Fifty-three single nucleotide polymorphism markers in the DNA that are significantly associated with adolescent idiopathic scoliosis were identified through a genome-wide association study.Adolescent idiopathic scoliosis has no clear causal agent, and is generally believed to be multifactorial; leading to "progressive functional limitations" for individuals. Research suggests that Posterior Spinal Fusion (PSF) can be used to correct the more severe deformities caused by adolescent idiopathic scoliosis. Such procedures can result in a return to physical activity in about 6 months, which is very promising, although minimal back pain is still to be expected in the most severe cases.
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.Tophi form in the joints, cartilage, bones, and other places throughout the body. Sometimes, tophi break through the skin and appear as white or yellowish-white, chalky nodules. Without treatment, tophi may develop on average about ten years after the onset of gout, although their first appearance can range from three to forty-two years. The development of gouty tophi can also limit joint function and cause bone destruction, leading to noticeable disabilities, especially when gout cannot successfully be treated. When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol, febuxostat) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout (RCG). They are more apt to appear early in the course of the disease in people who are older. Although less common, tophi can also form in the kidneys and nasal cartilage. Pathophysiology
It appears that monosodium urate crystals trigger a distinct physiological NETosis pathway that coats them in DNA. These coated crystals then persist in tissues as a foreign body granuloma constituting gouty tophus.