RHEUMATOLOGICAL AND

MUSCULOSKELETAL DISORDERS
 RHEUMATOLOGICAL AND MUSCULOSKELETAL
DISORDERS
They represent 2030% of the workload of the
primary care physician.
Recognition and appropriate early treatment of
many painful rheumatic conditions may help
reduce the incidence of chronic pain disorders.
Early recognition and subsequent treatment of
inflammatory arthritis by specialist
multidisciplinary teams leads to better symptom
control and prevents long-term joint damage and
disability.
 ANALGESIC AND ANTI-INFLAMMATORY
DRUGS FOR MUSCULOSKELETAL PROBLEMS
 ANALGESIC AND ANTI-INFLAMMATORY
DRUGS FOR MUSCULOSKELETAL PROBLEMS

Simple agents such as paracetamol, aspirin, or codeine

compounds (or combination preparations), used when
necessary or regularly, relieve pain and improve function.
Paracetamol with dextropropoxyphene (co-proxamol) should
not be prescribed
and is being withdrawn. Sleep may also be improved. Side-
effects are relatively infrequent, although drowsiness and
constipation occur with codeine preparations, especially in the
elderly.
Stronger analgesics, such as dihydrocodeine or
morphine derivatives, should be used only with severe pain.
 Non-steroidal anti-inflammatory
drugs (NSAIDs)

NSAIDs have anti-inflammatory and centrally acting analgesic

properties. They inhibit cyclo-oxygenase (COX), a key enzyme in the
formation of prostaglandins, prostacyclins and. There are two specific cyclo-
oxygenase enzymes: COX-1, the constitutive form present in many normal
tissues; and COX-2, the form mainly induced in response to pro-
inflammatory cytokines and not found in
most normal tissues. The latter is associated with oedema and the
nociceptive and pyretic effects of inflammation. COX-2 appears to be
constitutive in the kidney. Most of the older NSAIDs block both enzymes but
with variable specificity; their therapeutic effect depends on blocking COX-2
and their side-effects mainly on blocking COX-1, for example, by the loss of
gastric mucosal protection and a decrease in renal blood flow. COX-2
inhibitors (coxibs) were designed to reduce gastrointestinal toxicity by not
blocking COX-1.
 Uses
Short courses of NSAIDs or coxibs are used occasionally in osteoarthritis
and spondylosis.

Slow-release preparations are useful for inflammatory arthritis and when

more constant pain control is needed.

Consider the patients gastrointestinal and cardiac risks before prescribing

NSAIDs or coxibs.
 Side-effects
The most common with NSAIDs are indigestion or skin rashes. Gastric
erosions and peptic ulceration with perforation and bleeding also occur.
Ibuprofen should be avoided in combination with low dose aspirin as it
significantly increases the risk of severe gastrointestinal bleeding. Proton
pump inhibitors are probably the best drugs to protect those at high risk from
serious gastrointestinal events and also reduce dyspepsia. H2 blockers are less
effective as gastroprotective agents. The value of prostaglandin E2 analogues is
limited by their tendency to cause nausea and diarrhoea.
In the elderly, NSAIDs may cause gastric mucosal damage and gastrointestinal
bleeding without warning symptoms. They may also reduce renal function,
especially in the elderly. They should only be prescribed with a proton pump
inhibitor in this group.
Coxibs produce fewer gastrointestinal side-effects but renal
complications and fluid retention still occur. Rofecoxib was withdrawn because
of an increase in cardiovascular events with prolonged use. It now appears that
this may be a class phenomenon of all NSAIDs and coxibs. Coxibs should be
used in patients with a high risk of gastrointestinal disease and with no
cardiovascular risk. Patients with a high risk of both may be better off taking an
NSAID (diclofenac) and a proton pump inhibitor.
 OSTEOARTHRITIS (OA)

Osteoarthritis is the most common type of arthritis. It occurs in synovial

joints and is characterized by cartilage loss with an accompanying periarticular
bone response.
Factors predisposing to osteoarthritis
Causes of osteoarthritis
Features of nodal OA
 Nodal OA
Joints of the hand

Severe nodal osteoarthritis.

The DIP joints
demonstrate Heberdens nodes
(arrows). The middle finger DIP
joint is deformed and unstable.
The thumb is adducted and the
bony swelling of the first
carpometacarpal joint is clearly
shown the squared hand of
nodal OA.
 INFLAMMATORY ARTHRITIS
Inflammatory arthritis includes a large number of arthritic conditions in
which the predominant feature is synovial inflammation.
In general the pain and stiffness of inflammatory arthritis are worse in the
morning and after rest. This early-morning exacerbation may last several hours.
Inflammatory markers (ESR and CRP) are often raised in inflammatory arthritis, and
there is often a normochromic, normocytic anaemia.
 RHEUMATOID ARTHRITIS (RA)
Rheumatoid arthritis is an autoimmune disease causing a
chronic symmetrical polyarthritis with systemic involvement.

Epidemiology

RA has a world-wide distribution and affects

0.51% (with a female preponderance) of the
population.
 Aetiology and pathogenesis

The cause is multifactorial and genetic and environmental

factors play a part.
Gender. Women before the menopause are affected three times more often
than men. After the menopause the frequency of onset is similar between the
sexes, the use of the oral contraceptive pill may delay the onset of disease.
Familial. The disease is familial with an increased incidence in first degree
relatives
Genetic factors are estimated to account for up to 60% of disease
susceptibility. There is a strong association between susceptibility to RA and
HLA-DR4, which occurs in 5075% of patients, correlates with a poor prognosis,
as does HLA-DRB1. The possession of a specific pentapeptide (Q-K-RAA) in HLA-
DRB1 increases susceptibility; combined with a positive rheumatoid factor it
identifies individuals with a 13 times greater risk for developing bone erosions in
early disease.
 Immunology
Many factors have been implicated but the chronic synovial
inflammation is caused by ongoing T cell activation.

The presence of activated T cells and macrophages and local production of rheumatoid
factor autoantibodies in the joint in RA suggests that immune dysregulation plays a
fundamental role in pathogenesis.
Anti-CCP (anti-citrullinated cyclic peptide) antibodies react with proteins
the inflammation may be maintained by the local production of rheumatoid factors and
continuous stimulation of macrophages via IgG Fc receptors.
Activated mast cells which release histamine and TNF-
CD4-specific antibodies
Temporary CD20 positive B cell ablation
The TNF superfamily of cytokines produced mainly by activated macrophages and T cells
Synovial fibroblasts

The triggering antigen remains unclear, although it is suggested that the

glycosylation pattern of immunoglobulins may be abnormal in RA and lead to their
becoming potentially Antigenic.
Bacterial or slow virus infections have been implicated but are unproven. It has
been suggested that an immune response to any pathogen is to produce autoantibodies
by B cell clonal expansion. In susceptible individuals such clones may persist.
 Rheumatoid factors (RFs) and anti-CCP antibodies

RFs are circulating autoantibodies that have the Fc portion of IgG as their
antigen. The nature of the antigen means that they self-aggregate into immune complexes
and thus activate complement and stimulate inflammation, causing chronic synovitis in RA
they show a much higher affinity and their production is persistent and occurs in the
joints. They are of any immunoglobulin class (IgM, IgG or IgA), but the most common tests
employed clinically detect IgM rheumatoid factor. Around 70% of patients with
polyarticular RA have IgM rheumatoid factor in the serum.
The term seronegative RA is used for patients in whom the standard tests for
IgM rheumatoid factor are persistently negative.
IgM rheumatoid factor is not diagnostic of RA and its absence does not rule the
disease out; persistently high titre in early disease implies more persistently active
synovitis, more joint damage and greater disability eventually.
RF and the antibody to CCP together are more specific. RF indicates persistence
but anti-CCP predicts the development of erosions and a worse prognosis.
 CLINICAL FEATURES OF RA
Typical presentation

The most typical presentation of rheumatoid arthritis (approximately 70% of cases) begins
as a slowly progressive, symmetrical, peripheral polyarthritis, evolving over a period of a
few weeks or months. The patient is usually in her thirties to fifties. Less commonly (15%)
a rapid onset can occur over a few days (or explosively overnight) with a severe
symmetrical polyarticular involvement. These patients often have a better prognosis. A
worse than average prognosis (with a predictive accuracy of about 80%) is indicated by
being female, a gradual onset over a few months, and a positive IgM rheumatoid factor,
and/or anaemia within 3 months of onset. The differential diagnosis of early RA is shown:
CLINICAL FEATURES OF RA
 Symptoms and signs

The majority of patients complain of pain and stiffness of the small joints of
the hands (metacarpophalangeal; proximal and distal interphalangeal) and feet
(metatarsophalangeal). The wrists, elbows, shoulders, knees and ankles are also
affected. In most cases many joints are involved, but 10% present with a
monoarthritis of the knee
or shoulder or with a carpal tunnel syndrome.
The patient feels tired and unwell and the pain and stiffness are
significantly worse in the morning and may improve with gentle activity. Sleep is
disturbed.
The joints are usually warm and tender with some joint swelling. There is
limitation of movement and muscle wasting. Deformities develop as the disease
progresses.
 Other presentations

The presentation and progression of RA is variable.

Presentations are shown in Box. Relapses and remissions occur
either spontaneously or in response to drug therapy. In some
patients the disease remains active, producing progressive joint
damage.
A seronegative, limited synovitis initially affects the
wrists more often than the fingers and has a less symmetrical
joint involvement. It has a better long-term prognosis, but some
cases progress to severe disability.
Palindromic rheumatism is unusual (5%) and consists of
short-lived (2472 h) episodes of acute monoarthritis. The joint
becomes acutely painful, swollen and red, but resolves
completely. About 50% go on to develop typical chronic
rheumatoid synovitis after a delay of months or years. The rest
remit or continue to have acute episodic arthritis. The detection of
IgM rheumatoid factor/anti-CCP predicts conversion to chronic,
destructive synovitis.
Other presentations
Complications
 Complications

Septic arthritis
This is a serious complication. Affected joints are hot and inflamed with
accompanying fever and a neutrophil leucocytosis in the blood. Staphylococcus
aureus is the most common organism. Blood cultures are often positive. Treatment is
with systemic antibiotics and drainage.

Amyloidosis
Amyloidosis is found in a very small number of people with severe rheumatoid
arthritis. RA is the most common cause of secondary amyloidosis.
 Joint involvement in RA
Hands and wrists
Joint damage causes a variety of typical deformities. Most typical is a combination of ulnar drift and
palmar subluxation of the MCPs. Fixed flexion (buttonhole or boutonnire deformity) or fixed
hyperextension (swan-neck deformity) of the PIP joints impairs hand function.
Shoulders
RA commonly affects the shoulders.
Elbows
Synovitis of the elbows causes swelling and a painful fixed flexion deformity.
Feet
One of the earliest manifestations of RA is painful swelling of the MTP joints.
Knees
Massive synovitis and knee effusions occur, but respond well to aspiration and steroid injection. A
persistent effusion increases the risk of popliteal cyst formation and rupture. In later disease, erosion
of cartilage and bone causes loss of joint space on X-ray and damage to the medial and/or lateral
and/or retropatellar compartments of the knees. Secondary OA follows. Total knee replacement is
often the only way to restore mobility and relieve pain.
Hips
The hips are rarely affected in early RA
Cervical spine
Painful stiffness of the neck in RA is often muscular, but it may be due to rheumatoid synovitis affecting
the synovial joints of the upper cervical spine and the bursae which separate the odontoid peg from
the anterior arch of the atlas and from its retaining ligaments.
Other joints
The temporomandibular, acromioclavicular, sternoclavicular, cricoarytenoid and any other synovial
joint can be affected.
Non-articular manifestations
 Non-articular manifestations

Soft tissue surrounding joints

Subcutaneous nodules are firm, intradermal and generally occur over pressure
points, typically the elbows, the finger joints and the Achilles tendon.
The nodules may ulcerate and become infected. They tend to recur.
The olecranon and other bursae may be swollen (bursitis).
Tenosynovitis of affected flexor tendons in the hand.
Muscle wasting around joints is common. Corticosteroid-induced myopathy may
occur.
Lungs
Peripheral, intrapulmonary nodules are usually asymptomatic but may cavitate.
When pneumoconiosis is present (Caplans syndrome), large cavitating lung nodules
develop.
Other manifestations are:
serositis causing pleural effusion
pleural nodules
fibrosing alveolitis (lung fibrosis)
obstructive bronchiolitis
infective lesions, e.g. TB in patients on biological
 Non-articular manifestations

Vasculitis
Vasculitis is caused by immune complex deposition in arterial walls. Smoking is a risk
factor.
Other manifestations are:
nail fold infarcts due to cutaneous vasculitis
widespread cutaneous vasculitis
mononeuritis multiplex
bowel infarction
The heart and peripheral vessels
Poorly controlled RA with a persistently raised CRP is a risk factor for premature
coronary artery and cerebrovascular atherosclerosis independent of traditional risk
factors.
Endocarditis and myocardial disease are rarely.
Raynauds syndrome occurs.
The nervous system
Neuropathies are due to vasculitis of the vasa nervorum. Compression neuropathies
such as carpal or tarsal tunnel syndrome are due to local synovial hypertrophy.
 Non-articular manifestations

The eyes
Scleritis and episcleritis occur in severe, seropositive disease and produce painful red
lesions in the eye.
Sicca syndrome causes dry mouth and eyes Sjgrens syndrome.
The kidneys
Amyloidosis causes the nephrotic syndrome and renal failure. Presentation is with
proteinuria.
The spleen, lymph nodes and blood
Feltys syndrome is splenomegaly and neutropenia in a patient with RA. Leg ulcers or
sepsis are complications.
The lymph nodes may be palpable
Anaemia is almost universal and is usually the normochromic, normocytic anaemia
of chronic disease.
There may be a pancytopenia due to hypersplenism in Feltys syndrome or as a
complication of DMARD treatment. A high platelet count occurs with active disease.
 DIAGNOSIS AND INVESTIGATIONS

The American College of Rheumatology (ACR) criteria are shown in Box

Blood count. Anaemia may be present. The ESR and/or CRP are raised in
proportion to the activity.
Serology. Anti-CCP is positive earlier in the disease. Rheumatoid factor is present
in approximately 70% of cases and ANA at low titre in 30%.
X-rays of the affected joint(s) Only soft tissue swelling is seen in early disease.
Aspiration of the joint if an effusion is present. The aspirate looks cloudy owing to
white cells.
Other investigations will depend on the clinical picture.
MANAGEMENT OF RA
 Drug therapy

There is no curative agent available for RA but drugs are now available that
prevent disease deterioration. Symptoms are controlled with analgesia and NSAIDs.
Data now support the use of DMARDs early in the disease to prevent the long-term
irreversible damaging effects of inflammation of the joints, and drugs that block TNF-
and IL-1 and the use of B cell ablation with rituximab are revolutionizing the
management of RA.
 Non-steroidal anti-inflammatory drugs
(NSAIDs) and coxibs

They all act on the cyclo-oxygenase (COX) pathway. Each compound should be given
for at least a week. Start with an inexpensive NSAID with few side-effects and with
which you are familiar.
If gastrointestinal side-effects are prominent, or the patient is over 65 years, add a
proton pump inhibitor. Slow-release preparations (e.g. slow-release diclofenac, 75
mg, taken after supper), or a suppository at bedtime, usually work well. For
additional relief a simple analgesic is taken as required (e.g. paracetamol or a
combination of codeine or dihydrocodeine and paracetamol). Many patients need
night sedation.
 Corticosteroids

There is evidence to suggest that the early use of corticosteroids slows down the
course of the disease.
Intra-articular injections sometimes only short-lived effect.
Intramuscular depot injections (40120 mg depot methylprednisolone) help to
control severe disease flares.
The use of oral corticosteroids has a number of problems
 Disease-modifying anti-rheumatic drugs

Sulfasalazine, methotrexate, leflunomide, TNF- blockers, ciclosporin and rituximab

have all been shown to reduce the rate of progressive joint damage in early and late
disease.
Sulfasalazine
It produces a response in about half the patients in the first 36 months. Serious
side-effects are rare, being mainly leucopenia and thrombocytopenia.
Methotrexate
This is considered by many to be the drug of choice. It should not be used in
pregnancy. It is given at an initial weekly dose of 2.57.5 mg orally, increased up to
15 25 mg if necessary. Oral folic acid should be given in addition to reduce side-
effects.
Leflunomide
This DMARD exerts an immunomodulatory effect. The main side-effects are
diarrhoea, nausea, alopecia and rash. Blood monitoring is obligatory. The onset of
action is 4 weeks. The initial response is similar to sulfasalazine but improvement
continues and is better sustained at 2 years.
 Disease-modifying anti-rheumatic drugs

Biological DMARDs
TNF- blockers. The availability of agents that block TNF-
has significantly changed the traditional use of DMARDs.
Etanercept - Around 65% of patients respond well.
Adalimumab - given along with methotrexate.
Infliximab.
These products slow or halt erosion formation in up to 70% of patients with RA and
produce healing in a few.
Side-effects. The evidence to date of increased tumour development is controversial.
A few people become ANA positive and develop a reversible lupus-like syndrome,
leucocytoclastic vasculitis, some extracutaneous involvement or interstitial lung
disease.
Other biological agents
Anakinra is a human recombinant.
Rituximab is a genetically engineered chimeric monoclonal antibody that causes lysis
of CD-20 positive B cells.
Abatacept is a recombinant fusion protein of CTLA4
Tocilizumab, a humanized anti-IL-6 receptor, is currently in clinical trials.
 Drugs used less commonly
Gold is given by deep intramuscular injection.
Hydroxychloroquine, an antimalarial, 200400 g daily, is well tolerated. Retinopathy
is the most serious side-effect.
Penicillamine, 125 g daily for 1 month, then 500750 g daily, is given before food and
for at least 3 months before improvement occurs.
Azathioprine at a maximum dose of 2.5 mg/kg and cyclophosphamide 12 mg/kg
have been used.
Ciclosporin 2.54 mg/kg is used for active rheumatoid arthritis

Physical measures
A combination of rest for active arthritis and exercises to maintain joint range and
muscle power is essential. Exercise in a hydrotherapy pool is popular and effective.

Surgery
Its main objectives are prophylactic, to prevent joint destruction and deformity, and
reconstructive, to restore function. Single-joint disease can be treated by surgical
synovectomy to reduce the bulk of inflamed tissue and prevent damage.
 PROGNOSIS

A poor prognosis is indicated by:

A clinical picture of an insidious rather than an explosive onset of RA, female sex,
increasing number of peripheral joints involved and the level of disability at the
onset.
Blood tests showing a high CRP/ESR, normochromic normocytic anaemia and high
titres of anti-CCP antibodies and of rheumatoid factor.
X-rays with early erosive damage.
 SERONEGATIVE SPONDYLOARTHROPATHIES

Aetiology

The common aetiological thread of these disorders is their striking

association with HLA-B27, particularly ankylosing spondylitis (AS). HLA type
B27 is present in > 90% of Caucasians.
There are clues that infections play a role, possibly by molecular
mimicry, with parts of the organism which are structurally similar to the HLA
molecule triggering crossreactive antibody formation.
The types of arthritis that follow a precipitating infection are called
reactive arthritis
 ANKYLOSING SPONDYLITIS (AS)

This is an inflammatory disorder of the spine affecting mainly young adults. It occurs
world-wide and affects 1% of men and 0.5% of women in Caucasian populations.

Epidemiology and pathogenesis

Environmental factors may also be involved but although Gram-negative

organisms, e.g. Yersinia, Klebsiella, Salmonella, Shigella, can cause a reactive
arthropathy.
 Clinical features

Episodic inflammation of the sacroiliac joints in the late teenage years or early
twenties is the first manifestation of AS. Pain in one or both buttocks and low back
pain and stiffness are typically worse in the morning and relieved by exercise.
Classification criteria. The presence of three of the four following indices in adults <
50 years with chronic back pain indicates AS:
morning stiffness > 30 min
improvement of back pain with exercise but not rest
awakening because of back pain during second half of the night only
alternating buttock pain.
Spinal stiffness can be measured by Schoebers test a tape measure is placed in the
midline 10 cm above the dimples of Venus. Any movement of a marker at 15 cm
during flexion is recorded. A reading of less than 5 cm implies spinal stiffness.
Non-spinal complications (uveitis or costochondritis).
Peripheral joint involvement is asymmetrical and affects a few, predominantly large
joints.
 Investigations
Blood. The ESR and CRP are usually raised.
HLA testing is rarely of value because of the high frequency of HLA-B27 in the
population.
X-rays. The medial and lateral cortical margins of both sacroiliac joints lose definition
owing to erosions and eventually become sclerotic
MRI demonstrates sacroiliitis before it is seen on
X-rays. X-ray of ankylosing spondylitis. The sacroiliac joints are eroded and show
marginal sclerosis (white arrows). There is bridging syndesmophyte
formation at the thoracolumbar junction (black arrows).

X-ray of bamboo spine in ankylosing

spondylitis. In advanced disease there is
calcification of the interspinous ligaments
and fusion of the facet joints as well as
syndesmophytes at all levels. The sacroiliac
joints
fuse.
 Treatment
The key to effective management of AS is early diagnosis so that a regimen
of preventative exercises is started before syndesmophytes have formed.
Failure to control pain and to encourage regular spinal and chest exercises
leads to an irreversible dorsal kyphosis and wasted paraspinal muscles
When the inflammation is active, an evening dose of a long-acting or slow-
release NSAID or an NSAID suppository improves sleep, pain control and
exercise compliance.
Methotrexate is effective for peripheral arthritis but not for spinal disease.
In patients with persistent, active inflammation TNF- blocking drugs
produce rapid, dramatic and sustained reduction of symptoms

Prognosis
With exercise and pain relief, the prognosis is excellent and over 80% of
patients are fully employed.
Patients should be made aware that they risk passing the HLA-B27 gene to
50% of their children. HLA-B27 positive offspring then have a 30% risk of
developing AS.
 PSORIATIC ARTHRITIS
The term psoriatic arthritis describes a variety of different patterns
of arthritis and enthesitis seen in people with psoriasis or with a family history
of psoriasis. Five to eight per cent of individuals with psoriasis develop one of
several different patterns of arthritis for which there is no serological marker.

REACTIVE ARTHRITIS
Reactive arthritis is a sterile synovitis, which occurs following an
infection.
Seronegative spondyloarthropathy develops in 12% of patients after
an acute attack of dysentery, or a sexually acquired infection non-specific
urethritis (NSU) in the male, non-specific cervicitis in the female.

ENTEROPATHIC ARTHRITIS ASSOCIATED WITH

INFLAMMATORY BOWEL DISEASE

Enteropathic synovitis occurs in approximately 1015% of patients with ulcerative

colitis and Crohns disease see. The link between the bowel disease and the
inflammatory arthritis is not clear. Selective mucosal leakiness may expose the
individual to antigens that trigger synovitis.
 CRYSTAL ARTHRITIS
Aetiology
Two main types of crystal account for the majority of crystalinduced arthritis.
They are sodium urate and calcium pyrophosphate
 GOUT AND HYPERURICAEMIA
Gout is an inflammatory arthritis associated with hyperuricaemia and intra-articular
sodium urate crystals.

Epidemiology
The prevalence of gout is increasing mainly in developed countries, and in Europe
and the USA it is approximately 0.2%, although hyperuricaemia in this population
occurs in about 5%. Gout develops in men more than women and rarely occurs
before young adulthood (when it suggests a specific enzyme defect), and seldom in
premenopausal females. The prevalence in older females is increasing with
increased diuretic use. Hyperuricaemia is common in certain ethnic groups (e.g.
Maoris).
Uric acid levels start to rise after puberty and are higher in men than in women until
the female menopause.
Hyperuricaemia is defined as a serum uric acid level greater than two standard
deviations from the mean.
Serum uric acid levels increase with age, obesity, a high-protein diet, a high alcohol
consumption (particularly beer drinkers), a high fructose intake from sweetened
drinks, combined hyperlipidaemia, diabetes mellitus, ischaemic heart disease and
hypertension (metabolic syndrome). There is often a family history of gout.
Pathogenesis

Ninety per cent of patients with gout have

impaired excretion of uric acid, 10% have
increased production also and in less
than 1% an inborn error of metabolism
leads to purine overproduction. One-third
of uric acid is eliminated in the faeces.
 Clinical features

Hyperuricaemia, causes four clinical syndromes:

acute sodium urate synovitis gout
chronic polyarticular gout
chronic tophaceous gout
urate renal stone formation
Acute gout presents typically in a middle-aged male with sudden onset of agonizing
pain, swelling and redness of the first MTP joint. The attack occurs at any time, but
may be precipitated by too much food or alcohol, by dehydration or by starting a
diuretic. Untreated attacks last about 7 days. Recovery is typically associated with
desquamation of the overlying skin. In 25% of attacks, a joint other than the great
toe is affected.
Chronic polyarticular gout is unusual, except in elderly people on long-standing
diuretic treatment
 Investigations

Joint fluid microscopy.

Serum uric acid is usually raised (> 600 mol/L). Acute gout never occurs
with a serum uric acid in the lower half of the normal range below the
saturation point of 360 mol/L.

Serum urea and creatinine are monitored for signs of renal impairment.
 Treatment

The use of NSAIDs or coxibs in high doses rapidly reduces the pain and
swelling.
naproxen: 750 mg immediately, then 500 mg every 812 hours
diclofenac: 75100 mg immediately, then 50 mg every 68 hours
indometacin: 75 mg immediately, then 50 mg every 68 hours. Although
regarded as the gold standard treatment by some, the frequency of side-
effects is unacceptably high with indometacin.

Caution: NSAIDs may cause renal impairment. In individuals with renal

impairment or a history of peptic ulceration, alternative treatments include:

colchicine: 1000 g immediately, then 500 g every 612 hours, but this
causes diarrhoea
corticosteroids: intramuscular or intra-articular depot methylprednisolone
 Dietary advice
Individuals should be advised to reduce their alcohol intake,
especially beer, which is high in purines and fructose. A diet which reduces
total calorie and cholesterol intake and avoids such foods as offal, some fish
and shellfish and spinach, all of which are rich sources of purines, is advised.

Treatment with agents that reduce serum

uric acid levels
Allopurinol should only be used when the attacks are frequent and severe
(despite dietary changes) or associated with renal impairment or tophi, or
when the patient finds NSAIDs or colchicine difficult to tolerate.
Allopurinol (300600 mg) blocks the enzyme xanthine oxidase, which
converts xanthine into uric acid. It reduces serum uric acid levels rapidly and
is relatively non-toxic but should be used at low doses (50100 mg) in renal
impairment.
Febuxostat (80120 mg) is a new non-purine analogue inhibitor of xanthine
oxidase and available in some countries. The angiotensin I-receptor
antagonist, losartan, is uricosuric in hypertensive patients on diuretics.
 Chronic tophaceous gout

In chronic tophaceous gout, sodium urate forms smooth white deposits (tophi) in
skin and around joints. They occur on the ear, the fingers or the Achilles tendon.
Tophaceous gout is often associated with renal impairment and/or the long-term
use of diuretics. There may be acute or chronic urate nephropathy or renal stone
formation.

Gout with tophi.

 AUTOIMMUNE RHEUMATIC DISEASES

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

SLE is an inflammatory, multisystem disorder with arthralgia and rashes as the

most common clinical features, and cerebral and renal disease as the most
serious problems.

Epidemiology

The prevalence varies from country to country, with the most

common prevalence of 1 : 250 being in African American
women.
 Aetiology

The cause is unknown but there are several predisposing factors:

Heredity

Genetics

Sex hormone status. Premenopausal women are most frequently affected.

Drugs such as hydralazine, isoniazid, procainamide and penicillamine can

induce a form of SLE which is usually mild

Ultraviolet light can trigger flares of SLE

Exposure to EpsteinBarr virus

 Pathogenesis
When cells die by apoptosis the cellular remnants appear on the cell surface as
small blebs which carry self-antigens.
These antigens include nuclear constituents (e.g. DNA and histones) which are
normally hidden from the immune system. In patients with SLE, removal of these
blebs by phagocytes is inefficient so that they are transferred to lymphoid tissues
where they can be taken up by antigenpresenting cells.
Leads to the following immunological consequences.
Development of autoantibodies that either form circulating complexes or
deposits by binding directly to tissues.
This leads to activation of complement and influx of neutrophils causing
inflammation in those tissues.
Abnormal cytokine production

Pathology

SLE of the skin and kidneys is characterized by deposition of complement and

IgG antibodies and influx of neutrophils and lymphocytes.
 Clinical features
Most patients suffer fatigue, arthralgia and/or skin problems.

Clinical features
of systemic lupus
erythematosus
(SLE).
 Clinical features

General features

Fever is common in exacerbations. Patients complain of marked malaise

and tiredness and these symptoms do not correlate with disease activity or
severity of organ-based complications.

The joints and muscles

Joint involvement is the most common clinical feature ( 90%). Joints are
painful but characteristically appear clinically normal.
Myalgia is present in up to 50% of patients.

Diagnostic imaging. CT scans of the brain sometimes show infarcts or

haemorrhage with evidence of cerebral atrophy. MR can detect lesions in
white matter
 Management
General measures
Symptomatic treatment
Arthralgia, arthritis, fever and serositis all respond well to standard doses of
NSAIDs. Topical corticosteroids are effective and widely used in cutaneous
lupus. Antimalarial drugs (chloroquine or hydroxychloroquine) help mild skin
disease, fatigue and arthralgias
Corticosteroids and immunosuppressive drugs
Single intramuscular injections of long-acting corticosteroids or short courses of
oral corticosteroids are useful. Renal or cerebral disease and severe haemolytic
anaemia or thrombocytopenia must be treated with highdose oral
corticosteroids. Cyclophosphamide was most commonly. Azathioprine is also
used to maintain remission. Newer agents such as rituximab reduces levels of
autoantibodies.
Patients with SLE have an increased long-term risk of developing some
cancers, especially lymphoma.
Pregnancy and SLE
Fertility is usually normal except in severe disease and there is no major
contraindication to pregnancy.
 SYSTEMIC SCLEROSIS
Systemic sclerosis (SSc) is a multisystem disease.
Environmental risk factors for scleroderma-like disorders include exposure to vinyl
chloride, silica dust, adulterated rapeseed oil and trichlorethylene. Drugs such as
bleomycin also produce a similar picture.

Vascular features
An early lesion is widespread vascular damage involving small arteries,
arterioles and capillaries. There is initial endothelial cell damage with release of
cytokines, which causes vasoconstriction. There is continued intimal damage
with increasing vascular permeability.
The damage to small blood vessels also produces widespread obliterative
arterial lesions and subsequent chronic ischaemia.

Fibrotic features

Stimulate fibroblasts to cause fibrosis.

 Clinical features
Raynauds phenomenon

Raynauds phenomenon is seen in almost 100% of cases and can

precede the onset of the full-blown disease by many years.

Limited cutaneous scleroderma (LcSSc) 70% of cases

This usually starts with Raynauds phenomenon many years. The skin
involvement is limited to the hands, face, feet and forearms. The skin is
tight over the fingers and often produces flexion deformities of the fingers.
Involvement of the skin of the face produces a characteristic beak-like
nose and a small mouth (microstomia). Painful digital ulcers and
telangiectasia with dilated nail-fold capillary loops are seen. Digital
ischaemia. Gastrointestinal tract involvement. Pulmonary hypertension.
The CREST syndrome (Calcinosis, Raynauds phenomenon, Esophageal
involvement, Sclerodactyly and skin changes in the fingers, Telangiectasia)
was the term previously used to describe this syndrome.
 Diffuse cutaneous scleroderma (DcSSc) 30% of cases

Diffuse swelling and stiffness of the fingers is rapidly followed by more

extensive skin thickening. Early involvement of other organs occurs with
general symptoms of lethargy, anorexia and weight loss.
Heartburn, reflux or dysphagia, Malabsorption
Renal involvement is acute or chronic
Lung disease, both fibrosis and pulmonary hypertension
Myocardial fibrosis leads to arrhythmias

Investigations

Full blood count

Urea and electrolytes
Autoantibodies
Urine microscopy
Imaging:
Hands
Barium
High-resolution CT
 Management

Education, counselling and family support are essential.

Regular exercises and skin lubricants
Raynauds
Oesophageal symptoms
Symptomatic malabsorption requires nutritional supplements and
rotational antibiotics
Renal involvement requires intensive control of hypertension
Pulmonary hypertension is treated with oral vasodilators, oxygen and
warfarin
Pulmonary fibrosis is currently treated with immunosuppression
 POLYMYOSITIS (PM) AND DERMATOMYOSITIS (DM)
Polymyositis is a rare disorder of unknown cause, in which the clinical
picture is dominated by inflammation of striated muscle, causing proximal
muscle weakness. When the skin is involved it is called
dermatomyositis. The aetiology is unknown, although viruses (e.g.
Coxsackie, rubella, influenza) have been implicated and persons with
HLA-B8/DR3 appear to be genetically predisposed.
SJGRENS SYNDROME
The syndrome of dry eyes (keratoconjunctivitis sicca) in the absence of
rheumatoid arthritis or any of the autoimmune diseases is known as
primary Sjgrens syndrome. Dryness of the mouth, skin or vagina may
also be a problem. Salivary and parotid gland enlargement is seen.
Associated systemic features include:
arthralgia
Raynauds phenomenon
dysphagia
renal tubular defects
pulmonary diffusion
polyneuropathy
vasculitis
increased incidence of non-Hodgkins B cell lymphoma