Leseprobe
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Introduction
Gout and pseudogout are believed to the most prevalent crystal-induced arthropathies in
humans. These disorders occur due to the deposition of crystals in the joints and soft tissues. This
results into periarticular and articular inflammation and injury. Some of the most common
crystals that are responsible for arthropathies such as gout and pseudogout include
hydroxyapatite, monosodium urate (MSU), calcium oxalate and calcium pyrophosphate
dehydrate (CPPD) (Rothschild, 2014). In practice, gout and pseudogout are relatively different
despite the fact that they are crystal-induced arthropathies, and their difference can be explained
by their definitions. Gout is defined as a crystal deposition disease that is characterized by the
precipitation and super-saturation of monosodium urate (MSU) in tissues. This deposition of
monosodium urate crystals causes inflammation of the joints and soft tissues, and this is
attributable to tissue damage. Therefore, gout is characterized by sub-acute or acute attacks of
joints or the inflammation of soft tissues resulting from the deposition of monosodium urate. The
clinical course of gout involves an underlying metabolic aberrancy referred to as hyperuricemia
which is defined as the serum urate level of more than 6.8 mg/dL (Al-Ashkar, 2010). On the
other hand, pseudogout is defined as a clinical syndrome that resembles gout, and it is caused by
the deposition of calcium pyrophosphate dehydrate crystals in soft tissues and joints, resulting
into the inflammation and cartilage tissue damage. Therefore, the term pseudogout emanates
from the nature of its clinical presentation in which acute attacks of the joints resembles those
observed in gout (Al-Ashkar, 2010). However, it is worth noting that, in pseudogout,
chondrocalcinosis is the most distinctive feature for the syndrome although some patients with
chondrocalcinosis do not present with pseudogout.
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Epidemiology of Gout and Pseudogout
From an epidemiological perspective, gout appears to exhibit a worldwide distribution,
though its prevalence rates vary significantly from one geographical location to another. In
addition, its epidemiological trends exhibit demographic features, especially regarding sex, age
and race. These variations are attributable to dietary, environmental and genetic influences on
different global populations.
International statistics indicates that the United Kingdom records an incidence rate of
2.68 per 1000 persons. In this population, incidence rates exhibit sex related demographics in
which women have a reduced incidence rate of 1.32 compared to men with 4.42. In Italy, the
prevalence rate of gout is reported to be four times higher in men than in women, in which it was
found to be 9.1 per 1000 populations, in 2009. This was a significant increase in the prevalence
rate of gout from 6.7 per 1000 persons in 2005 (Rothschild, 2014).
In the United States, the prevalence of gout has been increasing, and this is attributable to
the increase of the old population. This is evidenced by epidemiological survey data that indicate
an increase in incidence rates. For instance, the incidence rate of gout is reported to have
increased by 40% from 1990 to 1999 (Terkeltaub, 2008). On the other hand, the population of
adults with self-reported gout increased to 3 million, in 2008 from 2.1 million people recorded in
1995. It is reported that, gout accounted for about 0.2 percent of all emergency department visits
in 2008 (Garg et al. 2013). This corresponded to a prevalence rate of approximately 3.9%,
primarily in adults (Rothschild, 2014).
On the other hand, sex, age and race related demographics exhibit variations. It is
reported that, gout exhibits male predominance in which the global prevalence rate of gout in
men is estimated to be 5.9% compared to a prevalence rate of 2% in women (Zhu, Pandya &
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Choi, 2011). This variation in the prevalence rates of gout between men and women is
attributable to the age at onset in which estrogenic hormones exert uricosuric effects. Ordinarily,
uric acid levels reach the peak within the fourth and sixth decades of age, whereas women
experience a uric acid level increase within the sixth and eighth decades. Therefore, it is apparent
that the peak age of onset determines the prevalence rates of gout among women and men.
However, it is worth noting that, lifestyle risk factors and genetic predisposition have significant
influences on the prevalence of gout (Fravel & Ernst, 2011). It is also worth noting that, gout
occurs more in African American populations than in whites. However, there are no
epidemiological connections between blacks in the US and Africa because; gout is rare in Africa
(Merriman, 2011).
In contrast to gout, epidemiological trends of pseudogout are relatively different because
its prevalence exhibit age demographics, only. Clinical studies indicate that the prevalence of
pseudogout occurs at a rate of 15% in populations aged between 65 and 75 years, whereas
populations aged beyond 84 years record an increased prevalence rate of 40% (Al-Ashkar,
2010).
Pathophysiology
The physiology of gout is explained by the metabolic processes involved in the formation
of monosodium urate crystals and their consequences in the joints and soft tissues. This is why
gout is considered as a metabolic disorder because it is caused by the accumulation of uric acid
precipitates in blood and tissues. Ordinarily, urate crystals are formed after the super-saturation
of tissues with uric acid, a condition referred to as hyperuricemia, resulting into the precipitation
of urate salts. In gout disease, monosodium urate (MSU) accumulate in the joints; thus, forming
crystals under the acidic conditions and low temperatures observed in the peripheral joints. These
5
crystals are relatively insoluble under such conditions, and this leads to the accumulation of urate
crystals in the affected joints as it is the case in the big toe's metatarsophalangeal joints.
Ordinarily, uric acid precipitates at PH 7.4 in body fluids (Al-Ashkar, 2010). This is why high
acidic conditions in the synovial fluid favor the precipitation of uric acid into urate. Polarizing
microscopy shows the needlelike crystals that are formed after the precipitation of urate as light-
retarding, a characteristic feature of urate crystals (Rothschild, 2014).
In theory, the pathogenic effect of the monosodium urate crystals in the soft tissue and
the joints accounts for the inflammatory crystal arthropathy that is observed in the gout disease.
In the body, uric acid is formed from the metabolism of purine nucleotides in which inosine and
hypoxanthine are formed as the precursors of uric acid. In purine metabolism, hypoxanthine is
broken down to xanthine which is, in turn metabolized to uric acid. Ordinarily, uric acid is
formed from the subsequent oxidation of hypoxanthine to xanthine, and then from xanthine to
uric acid under the catalytic influence of the xanthine oxidase enzyme (Al-Ashkar, 2010).
Therefore, uric acid is the final product of purine metabolism in the body.
In gout disease, physiologic conditions in the affected tissues and fluids, especially the
synovial fluid cause the conversion of uric acid to urate which is not required in the human body.
It has been found out that there is no biological pathway for the degradation of urate as it is the
case in other animals such as reptiles and birds. Therefore, its elimination from the body is
relatively difficult, although minimal amounts are eliminated through the intestinal and urinary
tracts. It is believed that the inability of the human body to eliminate large amounts of urate leads
to hyperuricemia. As a result, urate saturates the synovial fluid in the joints and soft tissues
where it precipitates to form crystals which are responsible for the development of tophi and
tissue damage. These changes in the constituents of the synovial fluid, especially the presence of
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urate deposits trigger an immune response in which macrophages and monocytes are mobilized
to clears the urate crystals through phagocytosis. As a result, pro-inflammatory chemicals such
as chemokines and cytokines are released into the surrounding tissues, and this triggers an influx
of neutrophils into the synovial cavity. In addition, the release of these chemicals triggers acute
inflammatory reaction cascade, and this explains why inflammation occurs in the affected
tissues. However, biochemical studies indicate that there is a self-limited inflammatory process
in which cell-mediated anti-inflammatory process is initiated to counter inflammation in the
affected tissues, although the mechanism for this process is not well understood. Therefore, it is
believed that the self-limited inflammatory process explains why the pathological course of gout
resolves spontaneously on average of one to two weeks (Al-Ashkar, 2010).
Another mechanism that explains the pathophysiology of both gout and pseudogout is the
role of interleukin 1 (IL-1) and inflammasome. This mechanism is involved in the inflammation
induced by calcium pyrophosphate dehydrate (CPPD) in pseudogout and monosodium urate
(MSU) in gout. In this mechanism, cryopyrin inflammasome triggers an inflammatory cascade
that involves the activation of interleukin-1 after it detects urate crystals, primarily monosodium
urate and calcium pyrophosphate dehydrate (CPPD) (Choi et al. 2004). As a result, inflammation
occurs in the affected areas.
In general, it is believed that the presence of urate crystals; monosodium urate and
calcium pyrophosphate dehydrate, in the synovial tissues and soft tissues serves as a prerequisite
the gout disease. However, it is worth noting that the presence of urate crystals on the cartilage
surface and the synovial fluid do not necessary mean that joint inflammation occurs. In reality, a
gout attack is usually triggered by two principal factors. In most cases, a gout attack is triggered
by the release of crystals into the synovial tissues owing to the partial dissolution of microtophi
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- Patrick Kimuyu (Autor:in), 2018, Crystal-Induced Arthropathies. Gout and Pseudogout, München, GRIN Verlag, https://www.grin.com/document/388326
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