Lowering of pH has a direct action on MSU crystal nucleation but also enhances nucleation by increasing calcium ion activity. Whilst their observations concerning mechanical agitation provide evidence that a physical shock can directly lead to MSU crystal nucleation, the authors hypothesised that local trauma indirectly enhances crystal nucleation by lowering synovial pH [ 22 ].
Hence, the susceptibility of the foot to physical trauma might also help to explain the predilection of gout for the foot. More recently, the deposition of MSU and calcium pyrophosphate dihydrate CPPD crystals in areas of cartilage damage has been described in a cadaveric study which examined adult human tali from donors [ 23 ]. However, where seen, crystal deposits were usually found within or adjacent to a cartilage lesion.
Cartilage lesions tended to be located at sites of biomechanical stress such as the articulation of the margin of the trochlea with the tibia or fibula or where apposition with anterior tibial osteophytes was thought to have occurred.
In a separate study, the epitaxial nucleation and growth of MSU crystals was observed to occur on fragments of articular cartilage [ 24 ]. Thus there appears to be a relationship between cartilage lesions and the anatomical location of MSU crystal deposition.
In support of these observations, clinical and radiographic evidence exists of an association between gout and OA. A Polish hospital-based study of patients with gout found an association of gout and radiographic OA at the first MTPJs, tarsal joints and knees [ 31 ].
A more recent study of patients with gout recruited from primary care found a very strong association between joints that had previously been the site of an acute attack of gout and evidence of OA on clinical examination OR 7. The observations outlined above that MSU crystals tend to deposit at sites of cartilage damage and that clinical and radiographic evidence exists of an association between gout and OA lead to the important question of the mechanism by which gout and OA might be associated.
There are three possible explanations for this association. Firstly, does an association exist between the disease states of gout and nodal generalised OA? These two conditions share the common risk factor of obesity [ 32 , 33 ].
In a related study to the primary care study described above [ 8 ], generalized nodal OA, defined as the presence of Heberden's or Bouchard's nodes on at least two digits in each hand [ 34 ], was no more commonplace in subjects with gout than age-and gender-matched community controls but, as discussed above, hallux valgus and self-reported knee and big toe pain were more frequent in those with gout [ 14 ].
Although this case-control study was underpowered, these findings do not suggest that an association exists between the disease states of gout and generalised OA. The second and third explanations are related and concern the hypothesis that the association of gout and OA occurs at local joint sites and relates to the co-location of MSU crystal deposits and cartilage lesions.
Specifically, they question the direction of this association, namely, does the presence of osteoarthritic cartilage predispose to the local formation and deposition of MSU crystals or do MSU crystals themselves initiate and progress cartilage damage? Evidence to support the deposition of MSU crystals in osteoarthritic cartilage rather than MSU crystals leading to cartilage damage arises from two sources.
Although the primary care study described above was cross-sectional, making it difficult to infer causality, the strength of the association between involvement of gout and OA at individual joint sites did not increase with longer duration of gout [ 8 ].
A further insight into the direction of association between MSU crystal deposition and OA is provided by a recent study which examined the relationship between synovial fluid uric acid levels and the radiographic severity of knee OA [ 35 ]. Although synovial fluid uric acid was found to correlate with baseline knee OA severity, it was not associated with change in OA severity over 3 years.
These two observations do not suggest that the association between the occurrence of gout and OA at individual joint sites is due to MSU crystal-initiated joint damage. Furthermore, certain properties of the osteoarthritic joint are thought to influence urate solubility and predispose to local MSU crystal disposition [ 36 ].
Increased concentrations of chondroitin sulphate and degradation of protein-polysaccharide complexes found within articular cartilage have been shown to reduce urate solubility and lead to the precipitation and growth of MSU crystals [ 37 - 39 ].
However, it is also possible that the association between MSU crystal deposition and OA is bi-directional whereby existing osteoarthritic change predisposes to local formation and deposition of MSU crystals which then initiate further cartilage damage.
The studies discussed above provide clear evidence of an association between MSU crystal deposition and OA. Whilst further studies are required to definitively answer the questions of direction of association and causality, it appears that MSU crystals more readily deposit in osteoarthritic cartilage and that the presence of OA influences the distribution of joints affected by gout. However, OA cannot solely explain the typical distribution of joints affected by gout, as many joints commonly affected by OA such as the knees, finger IP joints, and hips are less frequently affected by gout than the first MTPJ, and other target joints for gout such as the ankle, wrist and elbow are infrequent sites for primary OA.
Simkin proposed a model to explain the clinical observations that acute attacks of gout are commonly precipitated by physical stress and occur overnight, based upon the co-occurrence of gout and OA at the first MTPJ [ 41 ]. In this model, a synovial effusion develops in an osteoarthritic first MTPJ during the day and subsequently resolves when the joint is rested overnight. Synovium is more permeable to water than urate and hence, as the effusion resolves, water leaves the joint more rapidly than urate.
This results in a transient increase in the synovial fluid urate concentration which leads to precipitation of MSU crystals if the saturation threshold of urate is exceeded. The striking predilection of gout for the first MTPJ appears to be multi-factorial in origin and arises from the unique combination of the susceptibility of the joint to OA and local anatomical considerations of temperature, minor physical trauma and biomechanical stress, leading to ideal conditions for MSU crystal formation and deposition in predisposed hyperuricaemic individuals, manifesting as clinical gout.
The author would like to thank Dr George Peat for helpful comments on the manuscript. National Center for Biotechnology Information , U. J Foot Ankle Res. Published online May Edward Roddy 1.
Author information Article notes Copyright and License information Disclaimer. Corresponding author. Edward Roddy: ku. Received Apr 21; Accepted May This article has been cited by other articles in PMC. Abstract This invited paper provides a summary of a keynote lecture delivered at the Australasian Podiatry Conference.
Background Gout is a true crystal deposition disease in which all clinical manifestations are considered to be directly attributable to the presence of monosodium urate MSU crystals. Clinical presentation of gout and involvement of the foot After an often prolonged period of asymptomatic hyperuricaemia, the initial manifestation of gout is usually an acute attack of synovitis affecting a single peripheral joint, most commonly the first metatarsophalangeal joint MTPJ.
Open in a separate window. Figure 1. Figure 2. Factors influencing crystal deposition Gout is one of the best understood inflammatory arthropathies. Figure 3. Temperature As described above, gout tends to affect distal peripheral joints, not only in the foot but also in the upper limb, with central axial joints such as the shoulders, hips and spine only rarely affected. Trauma and pH A further well-recognised clinical feature of gout is the tendency of an acute attack to be precipitated by physical trauma such as stubbing the toe or following physical activity.
Cartilage damage and osteoarthritis More recently, the deposition of MSU and calcium pyrophosphate dihydrate CPPD crystals in areas of cartilage damage has been described in a cadaveric study which examined adult human tali from donors [ 23 ]. Why are gout and osteoarthritis associated? A gout episode can last for a few days or weeks. Some people may experience flares of gout frequently, whereas others may not have a gout flare for years at a time.
Gout occurs due to an excess buildup of uric acid crystals in the joints and soft tissue, causing inflammation and intense pain. Gout attacks involve intense throbbing or burning joint pain, which occurs suddenly, followed by swelling, tenderness, warmth, and redness or discoloration. One article states that for some people, the pain can be so severe that they cannot tolerate the weight of a blanket.
The symptoms are typically at their worst within 6—12 hours. The affected joint, or big toe, will recover in 1—2 weeks. Due to severe pain and swelling, people who experience gout attacks may find it challenging to walk or stand. According to the Arthritis Foundation , if a person experiences a gout flare in the big toe, they should call a doctor to make an appointment.
A person can also use a cane or other mobility aids when they walk to help relieve pressure on the toe. They also recommend cutting the big toe out of a pair of socks so that there is no pressure on the toe. Open toe shoes or sandals are an option. A doctor may recommend lifestyle changes to prevent recurrent gout attacks along with prescribed medications.
A doctor will choose medicines based on your condition. According to NIAMS , medication can treat gout attack symptoms, prevent future attacks, and lower the chance of gout complications, such as tophi development. Tophi occur when the uric acid crystals build up and form small lumps.
They can occur anywhere but commonly develop at pressure points, such as the elbows, or around hand or foot joints. Gout occurs due to an excess buildup of uric acid, or hyperuricemia.
However, a quarter of those with hyperuricemia do not develop gout. When the body breaks down purines, it produces uric acid. Typically, the kidneys remove a certain amount of uric acid in the urine.
However, when they are unable to remove enough uric acid, uric acid crystals can form in the joints and soft tissues, causing swelling and pain. Gout typically affects males more than females. However, females have higher levels of uric acid after menopause. NIAMS state that being older also increases the chance of developing gout.
Normally, uric acid dissolves in your blood and passes through your kidneys into your urine. But sometimes either your body produces too much uric acid or your kidneys excrete too little uric acid.
When this happens, uric acid can build up, forming sharp, needlelike urate crystals in a joint or surrounding tissue that cause pain, inflammation and swelling. You're more likely to develop gout if you have high levels of uric acid in your body.
Factors that increase the uric acid level in your body include:. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Overview Gout is a common and complex form of arthritis that can affect anyone. Gout Open pop-up dialog box Close.
Gout Gout causes intense pain and swelling around one or more joints. Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Gout. Centers for Disease Control and Prevention. Accessed Dec.
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