Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3111_Библиотеки_им_академика_М_И_Перельмана
.pdf
260 Chak Sing LAU
tenderness around involved joints can provide relief
with less hazard [32, 46]. Besides glucocorticoids,
synthetic and naturally occurring hyaluronan
derivatives have also been delivered intra-articularly
in the management of mild to moderate OA of
the knee [33]. ese compounds have so far been
shown to be effective in alleviating joint symptoms.
However, several injections are required and some
patients may experience a flare of symptoms after
injection. Furthermore, additional studies are
needed to evaluate the long-term effects of these
agents [62].
e search for a disease modifying anti-OA drug
has remained an intense pursuit of many clinicians
and OA sufferers. Many patients with OA use
numerous nutriceuticals including glucosamine and
chondroitin sulphate. Both have been reported in
in-vitro studies to stimulate proteoglycan synthesis
and inhibit degradative enzymes. Although quite
different in molecular weight, both appear to be
significantly absorbed after oral administration,
with a low toxicity profile and delayed onset of
action. Unfortunately, despite multiple controlled
clinical trials of the use of these agents, particularly
glucosamine sulphate, in OA (mainly of the knee),
controversies on efficacy related to symptomatic
improvement continue. Differences in results
originate from the differences in products, study
design and study populations. A recent meta-
analysis study shows there is evidence to support
the continued consideration of glucosamine
sulphate in the OA therapeutic armamentarium
and that this agent may reduce the progression of
knee OA [66]. It should, however, be remembered
that the manufacture of nutriceutical/dietary
supplements is not regulated; therefore the various
products available are not standardised and
results obtained with glucosamine sulphate from
controlled clinical trials may not be extrapolated to
other salts (hydrochloride) or formulations (over-
the-counter or food supplements) for which no
warranty exists about content, pharmacokinetics
and pharmacodynamics in the labels.
Rheumatoid arthritis
Epidemiology and pathoaetiology of
rheumatoid arthritis
Rheumatoid arthritis is the commonest form of
chronic inflammatory arthritis. e definition of
RA used in epidemiological studies has changed
Table 16.05 The 1987 American College of
Rheumatology revised classification criteria for
rheumatoid arthritis [4]
Criterion Definition
1 Morning
stiffness
Morning stiffness in or around
the joint, lasting at least 1 hour
before maximal improvement
2 Arthritis of 3
or more joint
areas
At least 3 joint areas
simultaneously have had
soft tissue swelling or fluid
(not bony overgrowth alone)
observed by a physician. The
14 possible areas are the right
or left PIP, MCP, wrist, elbow,
knee, ankle and MTP joints
3 Arthritis of
hand joints
At least 1 area swollen (as
defined above) in a wrist, MCP
or PIP
4 Symmetric
arthritis
Simultaneous involvement
of the same joint areas (as
defined above) on both
sides of the body (bilateral
involvement of the PIPs, MCPs
or MTPs is acceptable without
absolute symmetry)
5 Rheumatoid
nodules
Subcutaneous nodules, over
bony prominences, or extensor
surfaces, or in juxta-articular
regions, observed by a
physician
6 Serum
rheumatoid
factor
Demonstration of abnormal
amounts of serum rheumatoid
factor by any method for
which the result has been
positive in <5% of normal
control subjects
7 Radiographic
changes
Radiographic changes typical
of rheumatoid arthritis on
posteroanterior hand and
wrist radiographs, which
must include erosions
or unequivocal bony
decalcification localised in or
most marked adjacent to the
involved joints (osteoarthritic
changes alone do not qualify)
PIP = proximal interphalangeal; MCP = metacarpophalangeal;
MTP = metatarsophalangeal.
For classification purposes, a patient shall be said to have
rheumatoid arthritis if he/she has satisfied at least four of
these seven criteria. Criteria 1 through 4 must have been
present for at least 6 weeks.
https://t.me/medicina_free
Painful Arthritis and Rheumatic Conditions 261
over time, but the one that is preferred by most
researchers is the classification using criteria
proposed by the ACR (Table 16.05) [4]. A person
shall be said to have RA if he/she has satisfied at
least four of the seven criteria.
(Table adopted with the permission of Dr. Frank
C. Arnett)
Data on the epidemiology of RA derive largely from
studies conducted in Europe and North America
[2, 71]. e annual incidence of RA in developed
countries from these regions has been estimated to
be 20–30 per 100,000 subjects. e commonest
age of onset is between 30 and 50 years. Women
are more often affected, with a female to male ratio
of approximately 3 to 1, although a recent study
suggested a possible decline in the incidence of RA
in women [78]. ere are ethnic and geographical
differences in the prevalence of RA. For example,
few cases or none were found in some countries in
Africa [72]. However, a link to urban living may
exist as RA is found to be more common among
black people living in urban areas, similar to that
in white Europeans; while the prevalence among
black people who live in rural areas is much lower
[71]. Overall, the prevalence of RA in developed
countries is variably reported to be between 0.3–
1% of the population [2, 43, 71].
e aetiology of RA is unknown, but it is thought
to be multifactorial with involvement of genetic and
environmental factors. ere is a familial tendency
and an association with HLA-DR4, with shared
epitope postulated on the third hypervariable
region of HLA-DRB1, in approximately
60% of patients [49]. Histologically, RA is an
inflammatory synovial disease with infiltration of
lymphocytes and macrophages and proliferation of
fibroblasts and endothelial cells. is is followed
by neovascularisation. Over time, the inflamed
synovial tissue grows irregularly, forming invasive
pannus tissue and invades and destroys cartilage and
bone. Multiple cytokines, proteinases and growth
factors are believed to play an important role in
the recruitment of inflammatory cells, synovial cell
proliferation and joint damage [24]. e causative
agent(s) for RA has not been discovered, but
most investigators believe the abnormal immune
response is triggered by some form of extra-articular
infection(s). On the other hand, it is possible that
RA may indeed be multiple diseases defined by
some common clinical manifestations, and that
there may not be a single predominant mechanism
of initiation or perpetuation.
Clinical manifestations of rheumatoid
arthritis
e clinical manifestations of RA are highly
variable. However, the majority of patients
(>70%) present with a bilateral and symmetrical
polyarthritis, usually of insidious onset. All synovial
joints may be affected, but peripheral joints are
more commonly affected. ese include the hand
metacarpophalangeal and proximal interphalangeal
joints, wrists, elbows, foot metatarsophalangeal
and interphalangeal joints, ankles, knees and the
temporomandibular joints. Involvement of the
shoulder, hip, sternoclavicular and cricoarytenoid
joints is less common. e axial skeleton, with the
exception of the cervical spine, is usually spared.
Patients complain of joint pain, stiffness and
swelling which are worse in the early morning.
Oedema and proliferation of the synovium
contribute to stiffness by mechanically interfering
with joint motion. e clinical course is that of
relapse and remission [41].
Although RA is manifested primarily by joint
involvement, it is a systemic inflammatory disease.
Most patients experience constitutional symptoms
with fatigue, malaise, anorexia, low grade fever and
depression. ese symptoms may precede overt
arthritis by weeks or months. Some patients may
also present with extra-articular features which
are associated with a poorer overall prognosis. For
example, subcutaneous nodules are found over bony
prominences that are subject to external pressure,
e.g. extensor surface of the elbow. Vasculitic skin
rashes and nail fold and finger pulp infarcts are not
uncommon. Keratoconjunctivitis sicca (dry eyes)
and episcleritis are common ocular manifestations.
Scleritis and scleromalacia are rare but serious, as
they can lead to eyeball perforation. Other extra-
articular manifestations may include serositis,
fibrosing alveolitis, mononeuritis and renal
amyloidosis [41]. ere appears to be an ethnic
variation in the manifestation of extra-articular
disease. For example, these complications are less
commonly reported in RA patients of Chinese
origin [15].
e diagnosis of RA is based primarily on the
patient’s clinical manifestations. However,
laboratory investigations may reveal the presence of
https://t.me/medicina_free
262 Chak Sing LAU
rheumatoid factor, which is an antibody (typically
IgM but may also be IgG or others) that binds to
the Fc fragment of IgG, in approximately 70%
of patients. It should be noted that rheumatoid
factor is not wholly specific for RA as it may also
be found in patients with non-RA disease such as
systemic lupus erythematosus, Sjögren’s syndrome,
hepatitis B and C infections, and malignancies
[39]. Antibodies to cyclic citrullinated peptide
(anti-CCP) have recently been identified as a more
specific marker for RA with over 95% specificity.
ese antibodies, which can be detected several
years before the development of clinical RA and that
of rheumatoid factor, can be helpful in diagnosing
RA in patients with rheumatoid factor-negative
arthritis. Furthermore, they appear to be associated
with more severe outcomes, with radiographic joint
damage and an overall poorer prognosis [86].
Other common but less specific laboratory
abnormalities include a normochromic, normocytic
anaemia, mild leucocytosis and thrombocytosis,
and elevated erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP). Radiographic
findings vary depending on the duration and
severity of the illness. A normal radiograph does
not exclude a diagnosis of RA, although over
half of patients develop radiographic changes
within 2 years of disease onset. Classically, there is
periarticular osteopenia, joint space narrowing and
juxta-articular erosions. While plain radiographs
are easily accessible, ultrasonography and magnetic
resonance imaging (MRI) are more sensitive in
detecting early disease.
Management of rheumatoid arthritis
Recent evidence suggests that joint destruction in
RA begins within a few weeks of symptom onset and
that early treatment with effective pharmaceutical
agents decreases the rate of disease progression [23,
80]. Patients with suspected RA should therefore
be referred to a rheumatologist within 3 months of
presentation for confirmation of diagnosis, as well
as initiation of DMARDs. e goals of treatment
of RA include relief of pain and inflammation, joint
protection, preservation of function and quality of
life, and control of systemic complications.
Many agents have been shown to have disease
modifying effects on RA. ey include methotrexate,
sulphasalazine, hydroxychloroquine, gold salts,
penicillamine, azathioprine and cyclosporin A.
ese so called DMARDs should be considered
for all patients with RA [8]. Compliance, disease
severity, physician experience and the presence of
various comorbidities guide medication choice. e
DMARDs share many common characteristics.
ey do not provide relief for RA symptoms and
are slow in their onset of action. Besides, they
have a relatively short “life span”. Most patients
who are treated with a single DMARD come off
their treatment after 3 to 5 years, due either to
the loss of efficacy or development of side effects.
Recently, however, it has been possible to better
control RA by combining DMARDs [64]. For
example, combination therapy with methotrexate,
sulphasalazine and hydroxychloroquine has been
shown to be more effective than sulphasalazine
and hydroxychloroquine or methotrexate alone.
It has also been shown that patients with early
RA treated with methotrexate, sulphasalazine
and hydroxychloroquine had a better chance
of remission at 2 years than those treated with
sulphasalazine alone. Results from other trials have
also demonstrated that aggressive initial therapy
with combinations of drugs could benefit patients
without significantly increased toxicity.
Newer DMARDs include leflunomide, which
inhibits pyrimidine synthesis through its inhibitory
effects on the dihydro-orotate dehydrogenase
enzyme. Leflunomide is probably quicker in its
speed of onset of action when compared with
conventional DMARDs. It has been shown to
reduce radiographic progression with efficacy
similar to methotrexate and sulphasalazine in large
clinical studies. Leflunomide may also be combined
with methotrexate and sulphasalazine for patients
with advanced disease without an increase in the
frequency of adverse reactions [16].
It is not within the scope of this chapter to discuss
the side-effect profiles of DMARDs. However,
it is suffice to say that these drugs, including
should be justified and closely monitored.
Glucocorticoids also play an important role in the
treatment of RA. When administered with care,
intra-articular glucocorticoid injections can bring
about remarkable relief to patients’ articular disease,
particularly in patients with a monoarticular flare.
https://t.me/medicina_free
Painful Arthritis and Rheumatic Conditions 263
In addition, during the process, aspiration of the
distended joint and concomitant administration
of local anaesthetics can lead to an immediate
relief. Intra-articular glucocorticoid injection may
help to facilitate physical therapy and avoid the
need to augment systemic treatment. However,
care should be exercised to avoid the abuse of
these injections. For example, it will be unwise to
repeatedly inject the same joint many times when
actually the more appropriate action should be a
change in the systemic therapy or surgery. is is
also true for a polyarticular flare of RA, when the
systemic treatment should be adjusted instead of
multiple joint injections. Systemic glucocorticoids
may also be used as “bridging therapy” during the
period when DMARDs have been initiated but
have not yet taken effect. Chronic administration
of glucocorticoid at dosages equivalent to less than
10 mg of prednisolone per day are highly effective
for relieving symptoms of RA and can slow joint
damage [38, 85]. However, glucocorticoid dosages
should be kept at a minimum because of high risk
of side effects, which include osteoporosis, cataract,
hypertension, Cushingoid symptoms and glucose
intolerance.
Biological agents for rheumatoid arthritis
e outlook of patients with RA has been
markedly improved in the past few years since
the availability of biological therapies, thanks to a
rapid development in the field of immunology and
a better understanding of the immunopathology of
this condition.
Tumour necrosis factor (TNF)-alpha is known
to play a central role in the pathogenesis of RA.
is pro-inflammatory cytokine triggers several
important events that lead to the synovitis and
tissue destruction seen in RA. Besides, activation
of the adhesion molecules promotes recruitment of
inflammatory cells into the joint and causes further
damage. erapeutic intervention is now possible
using agents that antagonise the effects of TNF-
alpha. Etanercept, infliximab and adalimumab
are currently approved for the treatment of active
RA. Etanercept is a soluble TNF-receptor fusion
protein [8], while infliximab and adalimumab
are a chimeric and human IgG1 anti-TNF-alpha
antibody, respectively [48, 89]. All three agents
have been demonstrated to have superior efficacy
when compared with conventional DMARDs.
Initial studies have focused on the use of these
drugs in patients with refractory disease who
have failed conventional therapies including
combination treatment. Not only do these drugs
improve patients’ signs and symptoms of RA,
improvements which become apparent within the
first 2 weeks of treatment, their use is associated
with delayed radiographic changes. Indeed, recent
studies have also shown that these drugs are capable
of reversing bony erosive lesions as demonstrated
by MRI, suggesting that they may be true disease
remitting agents of RA [56].
While anti-TNF-alpha agents are promising, their
use is limited by their prohibitive cost. Few patients
are able to afford these agents long term. Further,
potential adverse reactions associated with their
long-term use have not been fully documented
yet. Of particular concern is the possible increase
in susceptibility to various infections. Tuberculosis
and hepatitis are major worries [56, 60]. Besides,
whether the use of these agents may be associated
with an increased risk of malignancies is not fully
known, although post-marketing surveys have
failed to substantiate this concern thus far.
In addition to TNF-alpha, evidence has emerged
supporting the pivotal role of B cells in the
pathogenesis of RA. Rituximab, a chimeric
monoclonal antibody to a specific marker for
mature B cells (CD20) has recently been approved
for treatment of RA refractory to anti-TNF-alpha
therapy [22, 31]. Randomised pilot studies have
shown B-cell depletion is an effective and safe
approach to RA management. e B cell depletion
with rituximab is rapid and may be prolonged for
periods of >1 year. In general, patients tolerate
this agent well with safety comparable to that
of methotrexate, except for increased infections
[31]. Infusion-related reactions are the most
common adverse reactions. ese may sometimes
be severe and may be decreased with intravenous
glucocorticoid pre-treatment at the time of the
infusion.
Other targets for biological therapies include IL-
1 [59], IL-6, adhesion molecules, T-cell activation
molecules and T-B cell interaction molecules [26].
Many of these therapeutic agents have reached phase
II or III stages of their development for human
clinical use. Results have so far been encouraging.
is is likely to further improve the prognosis and
quality of life of patients with RA in future.
https://t.me/medicina_free
264 Chak Sing LAU
Ankylosing spondylitis and
related conditions
Epidemiology and pathoaetiology
of ankylosing spondylitis and other
spondyloarthritis
Ankylosing spondylitis is the prototype of a group
of conditions commonly known as the seronegative
SpA and characterised by inflammation of the
spine, peripheral joints and periarticular structures.
ese conditions are also variably associated with
characteristic extra-articular manifestations such as
anterior uveitis, mucocutaneous lesions, pulmonary
fibrosis, aortic root lesions and cardiac conduction
abnormalities. In addition to AS, other SpA include
Reiter’s syndrome, reactive arthritis, SpA associated
with psoriasis and inflammatory bowel disease, and
a variety of less clearly defined conditions known as
undifferentiated SpA. e underlying pathogenic
mechanisms of SpA are not fully understood but
it is almost certain that genetic factors are involved
as most, though not all, of these disorders show an
increased prevalence among individuals who have
inherited the human leucocyte antigen (HLA)-B27
gene. e frequent demonstration of infection by
microbes such as Chlamydia, Yersinia, Salmonella
and Klebsiella in these genetically predisposed
hosts suggests that interactions between genetic
and environmental factors are pivotal in the
pathogenesis of SpA [42].
Historically, AS was thought to be a disease that
almost exclusively affected young men. However,
cases in females are being increasingly recognised
and the male to female ratio is now believed to be
about 2 or 3 to 1 with considerable geographical
and ethnic variations [42]. In general, female
patients tend to have milder disease. Disease onset
commonly occurs in late adolescence or early
adulthood. e prevalence of AS has been reported
to be extremely rare in Afro-Americans, 0.26–
0.38% in Chinese, 0.1–1.4% in Caucasian whites
and up to 10% of all adult males in circumpolar
Arctic and sub-Arctic populations [10, 42, 70].
Such variations appear to be related to the frequency
of the HLA-B27 gene found in the corresponding
populations, highlighting the importance of this
gene in the development of AS.
Several mechanisms for the pathogenic role
of HLA-B27 in AS and other SpAs have been
proposed. e fact that reactive arthritis and AS
are triggered by genitourinary intestinal infective
agents that share sequence homology with HLA-
B27 has led to the theory of molecular mimicry
with T-cell responses that have been elicited by the
microbial agents’ cross-reaction with a host protein.
An alternative proposed mechanism involves the
primary function of HLA-B27 being antigen
presentation. It is possible that the microbial agents
are presented by HLA-B27 to CD8 T-cells and
initiate an inflammatory response. Persistence of
the microbial infection leads to perpetuation of this
response and subsequent joint damage. Finally, it is
possible that HLA-B27 itself may directly cause AS
and other SpA as HLA-B27 transgenic rats develop
SpA-like features, although many transgenic copies
are needed to transfer disease [52].
Clinical manifestations of ankylosing
spondylitis and other spondyloarthritis
Inflammatory low back pain as a result of sacroiliac
joint involvement is the commonest initial clinical
manifestation of AS. ere is associated morning
stiffness and the pain is worse at rest and often
felt in the buttocks, especially when seated. It
may radiate to the back of the thighs mimicking
sciatica, although the latter is usually unilateral and
relieved by rest. As the disease progresses upwards,
pain is experienced at higher spinal levels. oracic
spine involvement may present with pleuritic chest
pain, but unlike true pleurisy it is usually bilateral.
On examination, there is loss of lumbar lordosis
and a fixed kyphosis usually compensated for by
extension of the cervical spine, eventually producing
the stooped “question mark” posture. Sacroiliac
joints are tender on percussion and springing of the
pelvis. Movements of the spine at various levels are
restricted and so is chest expansion. Changes in the
peripheral joints, usually the larger ones, are similar
to those seen in RA and show signs of inflammation.
Extra-articular manifestations include iritis which
may affect approximately 30% of patients and may
sometimes precede spinal involvement. About 4%
of patients develop aortitis with signs of aortic
incompetence. Cardiac conduction defects and
pulmonary restriction may also be apparent but are
uncommon.
Blood tests are often not very helpful. e ESR
may be raised but RF is not present in the blood.
HLA-B27 tissue typing is not of diagnostic value
as although over 90% of patients possess this
gene, approximately 6–8% of the population
https://t.me/medicina_free
Painful Arthritis and Rheumatic Conditions 265
(Caucasians) are HLA-B27 positive. However,
a negative test for HLA-B27 often suggests the
patient’s back symptoms are due to other underlying
pathology. Radiological changes of sacro-iliitis
include widening of joint space and juxta-articular
erosions and sclerosis. In the spine, there is squaring
of the vertebral bodies caused by erosion of their
corners. Syndesmophytes (bony depositions) form
at the margin of the vertebrae. ese may join
together and produce the classical appearance of
a “bamboo spine”. ere may also be radiological
evidence of enthesopathy (calcification and new
bone formation in the soft tissues) with erosions,
sclerosis and soft-tissue calcification around the
ischial tuberosities, iliac crests, greater trochanters,
patellae and calcanea. Newer techniques such as
computed tomography (CT) and MRI demonstrate
considerably higher sensitivity in identifying sacro-
iliitis in the early stages of AS. Use of CT appears to
be superior to MRI for the visualisation of chronic
changes. On the other hand, MRI is the only
technique that can image acute and chronic lesions
simultaneously [6, 25].
e clinical manifestations of other reactive
arthritis are similar to those of AS except that
spinal disease may not always be apparent at first
presentation. In Reiter’s syndrome, patients present
with a classical symptom triad that comprises
urethritis, conjunctivitis and arthritis. Extra-
articular complications are common and involve
the skin (keratoderma blenorrhagicum) and
mucocutaneous surfaces — mouth ulcers, circinata
balanitis and cervicitis.
Management of ankylosing spondylitis and
spondyloarthritis
For years, the standard treatment of spinal symptoms
for patients with AS and related conditions has
consisted of physiotherapy with structured exercise
programmes and the use of NSAIDs. While a
recent Cochrane review showed that there is little
evidence for effectiveness of non-pharmacological
intervention [17], there is a strongly positive expert
opinion. e importance of a life-long programme
of regular individual and group exercises, patient
associations and self-help groups is particularly
emphasised in the management of AS and other
SpA. Swimming and hydrotherapy are very helpful.
Warm water helps promote relaxation and reduces
the discomfort of stretching. Furthermore, water
exercises strengthen muscles because of the water’s
resistance, and increase cardiovascular conditioning
and endurance. However, patients with psoriatic
skin lesions should avoid chlorinated water. Deep-
breathing exercises are also encouraged and can
be prepared for by applying local heat or taking
analgesics to relieve pain from costochondritis.
Patients should be advised to avoid smoking.
Non-steroidal anti-inflammatory drugs are the
cornerstone of treatment in patients with AS. A
good response to these drugs has been identified as
a diagnostic sign for AS and other SpA, although
a state of non-responsiveness to NSAIDs might
suggest a poor prognosis [68]. To achieve the desired
therapeutic effects, NSAIDs need to be taken
regularly in full anti-inflammatory doses rather
than the usual on-demand prescription. Previous
studies have shown this to reduce radiographic
progression [88].
e use of traditional DMARDs, including
methotrexate, leflunomide and sulphasalazine,
which are effective in RA, are not recommended
for the treatment of AS axial disease. Sulphasalazine
may be considered for patients with peripheral
arthritis [13]. Bisphosphonates have recently been
suggested to be useful for spinal symptoms of
AS [50], but other studies have not been able to
reproduce similar results [28]. e use of antibiotics
is not supported by evidence from the literature
except for cases of reactive arthritis preceded by
a known bacterial infection, especially Chlamidya
trachomatis [44]. Appropriate antibiotics may
reduce the duration of reactive arthritis, but this
therapy does not seem to alter the natural course
of the disease.
Blockade of the effects of TNF-alpha has markedly
changed the treatment paradigm of AS and
related conditions, and their outlook. TNF-alpha
antagonists are remarkably effective in the treatment
of AS patients with persistently high disease activity
despite conventional therapy. In patients with axial
disease, unlike with RA, there is no need for the use of
DMARDs prior to or concomitant with anti-TNF-
alpha therapy. All three TNF-alpha antagonists,
etanercept, infliximab and adalimumab, have
been approved for AS [11, 19, 84]. ese drugs
are also dramatically effective in treating psoriasis,
psoriatic arthritis and inflammatory bowel disease
(except with etanercept). alidomide, which has
some anti-TNF-alpha properties but is cheaper,
has recently been suggested to be effective in AS in
https://t.me/medicina_free
266 Chak Sing LAU
an open-labelled study [34], but controlled trials
are needed to prove its efficacy and safety in these
patients.
Gouty arthritis
Management of gouty arthritis
Gout is defined by the deposition of monosodium
urate crystals in various tissues, which is usually
the result of hyperuricaemia. However, it should
be noted that while the majority of patients who
develop gout have been hyperuricaemic for about
two decades, the majority of individuals with
hyperuricaemia never develop gout [1] and may
not require treatment. Gout may manifest as one
or more of the following clinical syndromes: gouty
arthritis, subcutaneous tophaceous deposition,
gouty nephropathy and uric acid nephrolithiasis.
Overall, the prevalence of gout increases with
age and serum urate concentrations. It primarily
affects middle-aged men. In the Framingham study
reported in 1988 [1], the overall 2-year incidence of
gout was found to be 0.32% in men and 0.05% in
women, with a mean age of 58 years. Using a self-
reported questionnaire, the estimated prevalence
of gout was found to be 0.84% for all ages; with
the highest prevalence reported in people over age
65 (2.9%) [45]. e prevalence of gout parallels
that of hyperuricaemia, which varies with age, sex,
body mass index, renal function, and ingestion
of alcohol and drugs. Drugs that are responsible
for hyperuricaemia and gout include diuretics,
cyclosporin A, low-dose salicylates, ethambutol,
pyrazinamide and nicotinic acid. Gout is more
prevalent in industrialised countries and is a
growing problem worldwide.
Acute gouty arthritis is generally the first clinical
manifestation of gout. It may be triggered by
a specific event such as trauma, alcohol, drugs
(particularly diuretics), surgical stress, or acute
medical illness. Early episodes of acute gouty
arthritis are typically monoarticular and begin
abruptly, often during the night or early morning
escalating over a 6- to 12-hour period. ere
is severe pain, erythema and swelling, as well as
systemic features such as fever and chills. e
joints of the lower limbs are typically involved and
the first metatarsophalangeal joint is involved in
>50% of initial attacks and over time is affected
in >90% of patients. e shoulder, hip and axial
joints are rarely affected. Early attacks often
spontaneously resolve over 3 to 10 days, although
subsequent attacks can occur more frequently,
become polyarticular and persist longer. e
transition from acute intermittent gout to chronic
tophaceous gout develops over 10 years or more.
is transition is characterised by the intercritical
periods between gouty attacks becoming less
defined, diminished in intensity of the pain and
persistent joint abnormalities [37].
e detection of intra- or extra-cellular needle-
shaped negatively birefringent urate crystals on
a polarised microscopic examination of synovial
fluid establishes the diagnosis of acute gouty
arthritis. e fluid is inflammatory — typically
20,000–100,000 white cells per mm2, with a
predominance of neutrophils. Serum uric acid
levels will be elevated at some time in almost all
patients with gout, but the level can be normal at
the time of an acute gouty attack and should not
be relied on to formulate a diagnosis. A full blood
count may show an elevated ESR, mild neutrophil
leucocytosis, and possibly reactive thrombocytosis.
Infective arthritis is an important differential
diagnosis of acute gout since systemic features and
leucocytosis are common to both conditions, and
septic synovial fluids may contain urate crystals.
Synovial fluid cultures should therefore be obtained
if a clinical suspicion of a septic joint exists. In the
absence of microscopic urate crystal identification,
the presumptive diagnosis of gout can be made
using clinical criteria as has been defined by the
ACR (Table 16.06) [54].
Table 16.06 Diagnosis of acute gouty arthritis in
the absence of microscopic urate identification
• History of more than one attack of acute
arthritis
• Maximum inflammation developed within 1
day
• Monoarticular attack
• Unilateral first metatarsophalangeal arthritis
• Unilateral tarsal arthritis
• Tophus (proven or suspected)
• Hyperuricaemia
• Asymmetrical swelling within a joint on X-ray
• Subcortical cysts without erosions on X-ray
• Joint fluid culture negative for organisms
during attack
Adapted from the 1977 American College of Rheumatology
Preliminary Criteria for classification of acute arthritis of
primary gout [54].
https://t.me/medicina_free
Painful Arthritis and Rheumatic Conditions 267
Non-steroidal anti-inflammatory drugs and
colchicine are effective in the treatment of
acute gouty arthritis. Potent NSAIDs such as
indomethacin, used at regular anti-inflammatory
doses, are generally recommended until the attack
subsides. However, if GI intolerance is a concern,
recent studies have shown that the COX-2
inhibitors are equally effective as indomethacin in
the treatment of acute gout [67, 90]. Colchicine
inhibits leucocyte activation and migration and
is most effective when given in the first 24 to 48
hours of the attack. However, side effects such as
nausea, abdominal pain and diarrhoea are common
and limit its use. It is relatively contraindicated in
patients with renal insufficiency. In patients with
contraindications to NSAIDs and colchicines or
with acute gouty arthritis that is refractory to these
therapies, glucocorticoids may be used. In the case
of monoarthritis, intra-articular injections may
be the treatment of choice. Oral or intramuscular
glucocorticoids may be considered when patients
decline arthrocentesis or present with oligo- or
polyarticular gout. Drugs such as allopurinol and
probenecid that alter serum uric acid levels should
not be started until after complete resolution of the
acute gouty attack, nor should they be stopped if
an acute gouty attack occurs while the patient is on
these medications.
e long-term management of gout consists of life-
style modification and avoidance of use of drugs
that may induce gout. Patients should be advised to
limit their intake of purine-rich foods such as meats,
seafood, some vegetables and legumes. ey should
also be strongly advised against the use of alcohol.
Uric acid lowering agents include two classes of
drugs: the xanthine oxidase inhibitors, which block
uric acid synthesis, and the uricosurics, which
increase renal uric acid secretion. In general, uric
acid lowering agents should be used judiciously as
these drugs are costly, inconvenient and potentially
toxic, and should not be offered to patients with
asymptomatic hyperuricaemia [40]. Indications
for long-term use of these drugs are listed in Table
16.07.
Allopurinol is the classical xanthine oxidase and
has been the mainstay of treatment of chronic
gout in the last few decades, although it often fails
to adequately reduce uric acid level and prevent
recurrent gouty attacks. In recent years, a number
of new agents have become available. Febuxostat is
a new xanthine oxidase inhibitor which has been
shown to be an effective hypouricaemic agent,
although its use in patients with renal impairment
and other significant medical conditions requires
further evaluation. Other novel agents include
uricase, which catalyses the conversion of uric acid
to the more readily excreted allantoin. Rasburicase
is a recombinant uricase, which has recently
been approved for the prevention of tumour lysis
syndrome although its use in chronic gout is
limited by antigenicity. A less antigenic PEGylated
uricase is currently being evaluated although
further information with regard to its long-term
risks and benefits is required. It is possible that
uricases may in the future be used as inducing
agents to rapidly deplete uric acid stores in the
short term. is will then be followed by long-term
maintenance therapy with a hypouricaemic agent
to prevent subsequent accumulation of uric acid
and recurrent gouty attacks [79]. Uricosuric agents
include probenecid and benzbromarone, but their
use is limited by their low efficacy in patients with
renal impairment.
Periarticular and regional
rheumatic pain syndromes
Management of common soft tissue
rheumatism
Periarticular and regional rheumatic pain syndromes
are also known as STR syndromes. ese conditions
are commonly overlooked in the planning of the
medical curriculum and that of the provision of
health care. Yet single or multiple lesions of tendons
and their sheaths, fasciae, bursae, joint capsules and
the enthesis (the tenoperiosteal junction) are major
causes of work days lost in the community [83], as
Table 16.07 Indications for long-term uric acid
lowering agents
• Frequent and disabling attacks of acute gouty
arthritis
• Clinical or radiographic signs of chronic gouty
joint disease
• Presence of tophaceous deposits in soft tissues
or subchondral bone
• Gout with renal insufficiency
• Recurrent nephrolithiasis
• Excessive urinary uric acid excretion
• Impending cytotoxic chemotherapy or
radiotherapy for lymphoma or leukaemia
https://t.me/medicina_free
268 Chak Sing LAU
well as rheumatology work load comprising up to
43% of new patient referrals [5].
Most STR conditions are related to chronic
low-grade trauma as a result of excessive and/or
unaccustomed use both at work and at play. e
conditions cause partial interruption of the blood
supply leading to incomplete attempts at healing
and regeneration. Since the vascular supply to
adult tendon is poor, healing of these lesions is
slow. e middle-aged and the elderly are especially
vulnerable, and in whom these lesions predominate.
Periarticular and regional rheumatic pain syndromes
may also be associated with systemic diseases,
notably inflammatory arthropathies, such as RA
and AS, and diabetes mellitus as one of the clinical
sequelae of a generalised vasculopathy associated
with this condition. A neural theory as a possible
cause of STR syndromes has also been proposed
recently based on the observations that tendons are
innervated and that increased levels of substance
P, a nociceptive neurotransmitter which has been
implicated as a proinflammatory mediator, have
been found in rotator cuff tendonitis. Further,
glutamate, a neurotransmitter, has been found
within the ultradialysate in Achilles tendonitis.
Finally, an association between radiculopathy and
tendon disorders has been reported recently [65].
e diagnosis of STR syndromes relies largely on
the physician’s clinical acumen and laboratory tests;
radiological techniques are often not needed. Much
can be done once the diagnosis is made as STR
often responds to a range of treatments including
selective rest of the involved region, use of oral and
topical analgesics and anti-inflammatory drugs,
physiotherapy and intralesional infiltration of
glucocorticoid.
e clinical presentation and diagnosis of common
STR syndromes are summarised in Table 16.08.
Although, numerous forms of treatment are available
for STR syndromes, few, unfortunately, have been
studied in a controlled and prospective manner and
their use remains controversial. Experience with
the use of NSAIDs in STR syndromes is not always
positive and most feel these agents work through
their analgesic rather than anti-inflammatory
effects. Various forms of physical therapy have
been used to treat STR syndromes. ey include
cryotherapy, therapeutic ultrasound and manual
therapy, such as deep transverse friction massage
and eccentric training, which involves active
lengthening of the muscle tendon unit [65]. While
intralesional glucocorticoid injection is not proven,
it is commonly offered when conservative treatment
fails. Table 16.08 describes also the injection site
and recommended dose of glucocorticoids used in
common STR syndromes.
Conclusion
In conclusion, arthritis and rheumatic diseases
encompass a wide spectrum of syndromes ranging
from degenerative diseases such OA to immune
mediated deforming conditions such as RA and
AS, and remediable conditions such as some cases
of gout and STR syndromes. ey are major causes
of pain, physical disability and socioeconomic loss
in developed countries. is is underlined by the
WHO’s declaration of the years 2000–2010 the
Bone and Joint Decade. Management of these
conditions requires an in-depth knowledge of the
underlying pathology and the various modalities of
treatment available. It requires a multidisciplinary
approach involving many medical and non-medical
personnel. e use of drugs has a major role in
the treatment of chronic arthritis. e ideal drug
should provide symptomatic relief and eradicate the
underlying condition without causing side effects.
While such a drug(s) is not yet available and there
is still no cure, progress made in recent years in our
understanding of arthritis and the mechanism of
actions of anti-rheumatic drugs has provided much
hope for patients with rheumatic diseases. It is now
possible to keep arthritis symptoms under good
control with judicious use of therapeutic agents that
are well tolerated. In addition, thanks to research
advances in the immunopathology of conditions
such as RA and AS, some previously treatment
refractory diseases may now respond to the use of
biological agents. ese agents may also induce a
prolonged remission in patients with early disease.
https://t.me/medicina_free
Painful Arthritis and Rheumatic Conditions 269
Table 16.08 Clinical features and glucocorticoid injection site/dose of common soft tissue rheumatism
syndromes
Soft tissue syndrome Presenting feature(s) Physical findings Injection site and steroid dose (in
mg methylprednisolone or equiv.)
Shoulder region
Supraspinatus Pain in deltoid
region during
shoulder abduction
and at night when
lying on the affected
side
Normal passive shoulder
movement. Painful arc
(70–120
o
) during active
abduction and a “catch”
of pain as the shoulder
is lowered. Resisted
shoulder abduction
increases pain
Anterior edge of the acromion
with the forearm resting on the
thigh, or with the elbow bent
at 90
o
and the forearm placed
behind the back
(20–40 mg)
Infraspinatus As for supraspinatus
tendonitis
As for supraspinatus
tendonitis but pain
increase is elicited during
resisted shoulder external
rotation
Posterior to the acromial head
with the patient sitting upright or
lying face downwards, propped
up on their elbows
(20–40 mg)
Biceps
tendonitis
Often associated
with rotator cuff
tendonitis. Pain over
the anterior aspect
of the shoulder
with radiation into
the biceps muscle
during overhead
activities
Tenderness over the
tendon as it runs in the
bicipital groove
Along the biceps tendon (AVOID
DIRECT INJECTION)
(20–40 mg)
Subacromial
bursitis
Often associated
with rotator cuff
tendonitis with
similar symptoms
Passive shoulder
movement may be
limited. Resisted
abduction is painful from
45–90
o
. Passive rotation
of the shoulder in the
fully abducted position
may be painful
Mid-point of the subacromion
laterally. Aspirate any excess fluid
(20–40 mg)
Elbow region
Lateral
epicondylitis
(Tennis elbow)
Pain over lateral
epicondyle. Hand
grip may be
impaired
Lateral epicondyle
tenderness. Worse by
resisted wrist extension
with the elbow extended
Over the lateral epicondyle
(20 mg)
Medial
epicondylitis
(Golfer’s
elbow)
Pain over medial
epicondyle. Hand
grip may be
impaired
Medial epicondyle
tenderness. Worse by
resisted wrist flexion with
the elbow extended
Over the medial epicondyle.
KEEP INJECTION ANTERIOR TO
AVOID ULNAR NERVE DAMAGE
(20 mg)
Wrist and hand region
de Quervain’s
tenosynovitis
(Diaper wrist)
Pain on using the
thumb or wrist
Maximal tenderness in
the anatomical “snuff
box”. Visible tender
swelling over the radial
styloid
Site of maximum tenderness.
AVOID DIRECT INJECTION.
Avoid long acting steroids
(25–50 mg)
Carpal tunnel
syndrome
Pain and
paraesthesia of
the lateral 3 1/2
fingers. Worse in
the morning and
relieved by shaking
the hand/forearm
Arm elevation or
hyperflexion of the
wrist produces pain and
paraesthesia. Tinel’s test
may be positive. There
may be thenar eminence
wasting
Midpoint between the pisiform
and scaphoid tubercle distal to
the middle skin crease. Needle is
directed at ~60
o
to the forearm.
AVOID LOCAL ANAESTHETICS
(20–40 mg)
https://t.me/medicina_free
Соседние файлы в папке Библиотека им академика М.И. Перельмана