RHEUMATOLOGY

DR. abdulahi samatar

 Rheumatology
• Branch of medicine that deals with diagnosis and
treatment of rheumatic disease
• Auto-immune diseases
• Auto-inflammatory diseases
• Crystalline arthritis
• Metabolic bone diseases
• Pain syndromes
• Vasculitides
• Rheumatism: any disease causing pain and
inflammation of joint, muscle or connective tissue
 Facts in rheumatology
• No single blood test confirms the diagnosis
• The test has to fit with patients history and
physical exam ( pattern recognition)
 Examples of rheumatic diseases
• Auto-immune ( R.A , SLE , sarcoidosis)
• Auto-inflammatory diseases ( familial
mediteranian fever and stills disease)
• Crystalline arthropathy ( gout and pseudogout)
• Metabolic bone diseases ( osteoporosis , paget
diseases)
• Pain syndromes ( fibromyalgia , rotator cuff
tears)
• Vasculitides ( kawasaki , buerger’s)
• Autoimmunity
• Normal immune system recognize self
antigens
• Autoimmunity: antibodies that react with self
antigen ( all people)
• Autoimmune disease: antibodies that react
with self antigens causing pathology.
 Generally
• We can classify Rheumatological diseases into:
• Non-inflammatory ( osteoporosis ,
osteoarthritis , fibromyalgia)
• Inflammatory: ( RA, SLE, seronegative
spondyloarthropathy, gout, etc)
Anatomy
Bones
Joints
• Synovial fluid
• Act as a lubricant
• Comes from the plasma, so
• If you have high level of uric acid in the plasma, uric
acid level in the synovial fluid will be high
• If there’s infection/inflammation in the plasma, you
will have infection in the synovial fluid leading to
synovitis
• If you have septic arthritis, it can spread to the plasma
causing sepsis, so it’s an emergency.
 Vocabulary
• Arthritis: inflammation of joints
• Enthesitis: inflammation of the entheses ( site where
tendon or ligament insert into the bone) e.g. achilles
tendinitis
• Monoarthritis: inflammation of only one joint
• Oligoarthritis: inflammation of 2-4 joints
• Polyarthritis: inflammation of 5 or more joints
• Arthralgia: joint pain , but how to differentiate it from
arthritis? By signs of inflammation
• Signs of inflammation: redness, hotness , swelling , pain
and loss of function
 Extra-articular manifestation of
Rheumatological diseases
• RA  episcleritis, carpel tunnel syndrome.
• SLE  skin rash. Renal insufficiency
• Reactive arthritis  urethritis , conjunctivitis
• Sjogern disease  dry eye, dry mouth
 Facts in rheumatology
• No single blood test confirms the diagnosis
• The test has to fit with patients history and
physical exam ( pattern recognition)
• Example. Lupus patient is a female, young in
child bearing age with facial rash,
photosensitivity with joint stiffness, may have
dark urine , etc. so this is pattern.
• Sensitivity: among the patients, how many have
positive test.
• If the test came back negative, you don’t have the
disease ( true negative ) and the test rule out the
disease.
• Specificity: among the patients, how many have a
negative test.
• If the test came back positive, you do have the
disease ( true positive ) and the test rule in the
disease
 Examples
• Its very unlikely that you have lupus in elderly
male with no symptoms, so we need sensitive
test to rule out the disease  ANA  negative
test  no lupus
• It’s very likely that you have lupus in young
female with symptoms, so we need specific test
to rule in the disease  ant dsDNA, anti-smith
antibodies  positive tests  there’s lupus.
• Always you need to have pattern recognition
• ANA  antibodies that attack component of nucleus
• Reported in titers ( e.g 1:80)  the dilution at which the
antibodies become undetectable
• So the higher the titer  more likely you have an
autoimmune disease
• ANA is positive if the titer is higher than 1:80 ( e.g 1:160,
1:320 etc.)
• ANA titers do not correlate with disease activity
• Healthy people can have positive ANA ( 1/9 healthy women
have positive ANA).
• ESR and CRP increase in any inflammatory disease.
Examples of investigation
Rheumatoid arthritis
• It is a chronic systemic inflammatory disease of
unknown aetiology( autoimmunity plays major
role in its chronicity and progression).
• It affects the synovial membranes of multiple
joints.
• It is common in females with female : male
ratio 3:1.
• usual age of onset 30- 50 years, though
individuals of any age group may be affected.
 Pathological finding

• Chronic synovitis( type 3 hypersensitivity) with

pannus formation. The pannus erodes cartilage,
bone, ligament and tendons.
• In the acute phase effusion and other
manifestations of inflammation are evident; in the
later stages ankylosis of the joint may set in.
• in both the acute and chronic phase, there may be
widespread inflammation of the tissues around the
joint that can lead to significant joint destruction.
 Clinical manifestations

• RA primarily affects joints( articular

manifestations) but problems involving other
organs of the body are known to occur( extra
articular manifestations- evident in 15- 25% of
individuals).
 Joints

• Involvement usually presents insidiously.

Prodromal syndrome of malaise, weight loss
and vague periarticular pain and stiffness may
be seen.
• Less commonly, the onset is acute triggered by
a stressful situation such as infection, trauma,
or in the post partum period.
• The joint involvement is characteristically
symmetrical with associated stiffness, warmth,
tenderness and pain.
• The stiffness is characteristically worse in the
morning and improves during the day.
• Any joint in the body can be affected but the
usual joints involved include the MCP, the PIP,
the wrists, knees, ankles and toes.
After months to years, deformities can
occur( may result in loss of function):
~ Ulnar deviation of fingers.
~ swan neck deformity.
~ boutonniere deformity.
~ Z deformity.
~ valgus deformity of the knee.
~ hammering of toes.
 Skin

• subcutaneous nodules( in 20%- always

seropositive patients) usually seen over bony
prominences but also over tendon sheaths.
• vasculitic skin rash( nail fold infarct, livedo
reticularis)- Raynaud phenomenon.
• pyoderma gangrenosum.
• palmer erythema.
Subcutaneous nodule
Nail fold infarct
livedo reticularis
Raynaud phenomenon
Pyoderma gangrenosum
 Lungs

1- fibrosis of the lung.

2- pleural effusion.
3- bronchiolitis obliterans organising
pneumonia.
4- lung nodules. Caplan syndrome describes lung
nodules with RA.
 Occular

episcleritis which may progress to scleritis and

ultimate scleromalacia perforans in severe
cases.
• keratoconjunctivitis sicca( dryness of eyes and
mouth due to lymphocyte infiltration of
lacrymal and salivary glands).
 Neurological

• mononeuropathy( carpal tunnel syndrome).

• peripheral neuropathy.
• Atlanto axial subluxation which can progress
to quadriplegia.
Heart and blood vessels:
1- endocarditis( valvular lesions), myocarditis
and pericarditis.
2- vasculitis.

GIT:
Felty’s syndrome with splenomegaly,
lymphadenopathy and neutropenia.
Kidneys:
1- vasculitis and GN.
2- nephrotic syndrome.

Hematological:
1- anemia. The most common abnormality of
blood cells.
2- neutropenia in Felty’s syndrome.
 Investigations:

Laboratory:
1- RF( IgM Ab) is seen in 75% of pts with RA. High
titers of RF are associated with severe disease.
If (-)ve, it does not exclude the disease.
2- anti citrullinated protein Abs( like anti CCP Abs)
present in 67% of cases.
2- ANA is found in 25% of pts with RA, though
their titer is lower than in SLE.
3- high ESR; moderate anemia; high platelet
count in proportion to degree of
inflammation.
4- joint fluid examination is valuable. The fluid is
translucent to opaque and has between 3000
and 50000 WBC/ Ml with 50% or more
polymorphs. The culture is (-)ve.
X ray:
• Of all the laboratory tests, X ray changes are most
specific for RA.
• However, they are not sensitive and usually are negative
during the 1st 6 months of the disease.
• The earliest changes occur in the wrist or feet and
consist of soft tissue swelling and juxta articular
osteoporosis.
• Later, diagnostic changes consisting of joint space
narrowing and erosions( juxta articular margin) develop.
American College of Rheumatology Revised criteria
for diagnosis of RA: ( at least 4 of the following:)
1- morning stiffness > 1 hour.
2- synovitis in 3 joints simultaneously.
3- synovitis in wrist or hand MCP or PIP joints.
4- symmetrical arthritis.
All of the above> 6 weeks duration.
5- rheumatoid nodules.
6- serum RF.
7- radiographic changes typical of RA.
 Diagnostic Criteria

Classification of rheumatoid arthritis

American Rheumatism Association Revised Criteria for the Diagnosis of Rheumatoid Arthritis

Morning stiffness in and around the joints, lasting at least 1 h before Morning stiffness .1
maximal improvement
At least three joint areas (out of 14 possible areas; right or left proximal Arthritis of three or more joint .2
interphalangeal, metacarpophalangeal, wrist, elbow, ankle, areas
metatarsophalangeal joints) simultaneously have had soft tissue swelling or
fluid (not bony overgrowth alone) as observed by a physician

At least one area swollen (as defined above) in a wrist, Arthritis of hand joints .3
metacarpophalangeal, or proximal interphalangeal joint
Simultaneous involvement of the same joint areas (as defined in criterion 2) Symmetric arthritis .4
on both sides of the body (bilateral involvement of proximal
interphalangeals, metacarpophalangeals, or metatarsophalangeals, without
absolute symmetry is acceptable)

Subcutaneous nodules over bony prominences or extensor surfaces, or in Rheumatoid nodules .5

juxta-articular regions as observed by a physician
Demonstration of abnormal amounts of serum rheumatoid factor by any Serum rheumatoid factor .6
method for which the result has been positive in less than 5% of normal
control subjects

Radiographic changes typical of rheumatoid arthritis on posteroanterior Radiographic changes .7

hand and wrist radiographs, which must include erosions or unequivocal
bony decalcification localized in, or most marked adjacent to, the involved
joints (osteorarthritis changes alone do not qualify)
 Treatment

• There is no known cure for RA, but many

different types of treatment can alleviate
symptoms and modify disease process.
• Goal of treatment:
~ alleviation of the current symptoms.
~ prevention of future destruction of joints with
consequent deformities and handicap.
 Symptomatic treatment

• analgesics( paracetamol) and non steroidal

anti inflammatory agents like aspirin,
Ibuprofen.
• NSAIDs are associated with a number of S/Es
including GI irritation and peptic ulcers+ renal
damage.
 DMARDs( disease modifying anti rheumatoid drugs):

• methotrexate. Considered to be the drug of

choice for RA.
• It is given once wkly( 7.5- 15 mg) and
produces beneficial effect in 2- 6 wks.
• S/Es include hepatotoxicity, bone marrow
suppression and pulmonary fibrosis.
sulphasalazine. A good 2nd line agent for RA.
• azathioprine. Anti metabolite which is
reserved for use in case of severe disease.
• corticosteroids produce immediate and
dramatic anti inflammatory benefit but are
limited by their many S/Es.
• Biological agents like TNF blockers like
infliximab and etanercept( TNF plays central
role in pathogenesis of RA)
 o n
nti
tte
r a
s fo
nk
ha
T
Systemic Lupus Erythematosus
• SLE is a chronic autoimmune Connective tissue
disease that can affect any part of the body.
• The immune system attacks the body’s cells
and tissue, resulting in inflammation and
tissue damage.
• The course of the disease is unpredictable,
with periods of illness( flares) alternating with
remissions.
• The disease occurs more often in women than
men( 9:1), especially between the ages of 20-
40 and it is more common in those of non
European descent.
• There is no one specific cause of SLE.
• There are, however, a number of
environmental triggers and a number of
genetic susceptibilities.
• SLE may run in families, but no single causal gene has
been identified.
• Multiple genes appear to influence a person’s chance
of developing lupus when triggered by environmental
factors.
• Drug induced lupus is a generally reversible condition
that usually occurs in people being treated for a long
term illness.
• There are many drugs that can cause this condition,
especially INH, procainamide, quinidine, hydralazine,
penicillamine, phenytoin, chlorpromazine…
• Sun light( UV radiation) has been shown to
trigger the photosensitive skin rash.
• Sex hormones such as estrogen play an
important role in the occurrence of SLE and it
is observed that during reproductive years,
the frequency of SLE is 10 times greater in
females than in males.
• No specific bacterial or viral infection has
been consistently linked to the disease.
 Pathophysiology:

• The environmental triggers cause the

destruction of cells and expose their DNA and
other nuclear Ags.
• The immune system attacks these nuclear
related proteins and produces Abs against
them.
• These Ag / Ab complexes damage blood
vessels in critical areas of the body( SLE mainly
type 3 hypersensitivity reaction).
 Clinical features:

1- systemic manifestations:
• Fever, fatigability…
2- dermatological features:
• Butterfly( malar) rash, discoid rash, mouth
ulcers, alopecia, photosensitive rash in any
area exposed to sun light, livido reticularis,
Raynaud’s phenomenon…
3- musculoskeletal manifestations:
• Arthritis especially small joints of the hand
and wrist.
• Unlike RA, lupus arthritis is less disabling and
usually does not cause severe destruction of
joints.
• Myositis , proximal muscle weakness and a
vascular necrosis of the femoral head is
encountered in some patients.
4- pulmonary manifestations:
• Lung and pleura inflammation can cause pleuritis
with pleural effusion, lupus pneumonitis, chronic
diffuse interstitial lung disease, pulmonary HTN,
pulmonary emboli…
5- cardiac manifestations:
• Pericarditis- myocarditis- endocarditis( non infective
Libman Sacks endocarditis). Atherosclerosis advances
more rapidly than in the general population.
6- neuropsychiatric manifestations:
• Due to involvement of central and peripheral
nervous system.
• Headache, depression, CVA, seizures,
psychosis, polyneuropathy, mononeuritis
multiplex, aseptic meningitis, movement
disorder( chorea), myelopathy…
7- renal manifestations:
• Painless hematuria or proteinuria may often
be the only presenting renal symptom.
• Acute or chronic renal failure may develop
with lupus GN.
8- hematological manifestations:
• Anemia may develop in up to 50% of cases.
• Low platelets and white blood cell count may
also occur.
• People with SLE may have an association with
antiphospholipid Antibody syndrome (
recurrent abortion and thrombotic tendency).
Diagnostic criteria:
• Some physicians make a diagnosis on the basis
of the American College of
Rheumatology( ACR) classification criteria( 4
out of 11 required):
1- photosensitivity.
2- oral ulcers.
3- malar rash on the cheeks.
4- discoid rash( red scaly patches on skin that
cause scarring).
5- arthritis.
6- serositis ( pleuritis and pericarditis).
7- neurological disorder. Seizures or psychosis.
8- renal disorder. Proteinuria and hematuria
with cellular casts.
9- blood disorder. Hemolytic anemia or
leukopenia( < 4000 / Ml), lymphopenia( <
1500 / Ml) or thrombocytopenia( < 100000 /
Ml).
10- positive ANA test.
11- positive anti- ds DNA or anti Smith Abs.
Lab. Tests:
1- ANA testing. It is useful screening test. (+) ve
in > 95% of pts. They are also (+) ve in many
Connective tissue disorders and other
autoimmune diseases.
2- subtypes of ANA include:
~ anti ds DNA Abs. it is highly specific for SLE.
~ anti smith Abs, anti Ro and anti La Abs. anti
histone Abs( linked to drug induced lupus).
3- other tests routinely performed in suspected
SLE are complement system levels( low levels
suggest consumption by immune system),
CBC, RFT and electrolytes.
Treatment:
• Being a chronic disease with no known cure,
the treatment of SLE is symptomatic .
• It also involves preventing flares and reducing
their severity and duration when they occur.
1- mild or remittant disease can some times be
safely left untreated. If required, NSAIDs and
antimalarials may be used.
2- in more severe cases, medications that
modulate the immune system( corticosteroids
and immunosuppressants) are used to control
the disease and prevent recurrence of
symptoms.
• They are mainly used for severe GN and other
organ damaging complications.
Life style changes:
• Avoiding sunlight is the primary change to the
lifestyle of SLE sufferers, as it is known to
exacerbate the disease.
Renal transplantation:
• Is the treatment of choice for ESRD, which is
one of the complications of lupus nephritis,
but the recurrence of the full disease is
common in up to 30% of pts.
Ankylosing spondylitis
• It’s a chronic inflammatory arthritis most often
affects the spine
• It affects joints in the spine and sacroilium in
the pelvis causing eventual fusion of the spine.
• Complete fusion of the spine results in a
complete rigidity of the spine, a condition
known as bampoo spine.
• AS is a systemic rheumatic disease and is one
of the seronegative spondyloarthropathies.
• The typical patient is young aged between
18-30 yrs old.
• Men are affected more than women by a ratio
of 3:1.
• The cause of AS is unknown, but a tendency to
develop the condition may be genetic.
• HLA-B 27 is positive in 90% of patients.
• HLA-B 27 is strongly associated with a certain
set of auto-immune diseases referred to as
the seronegative arthropathies.
Ankylosing process
 Syndesmophyte
bony outrgrowth from the spinal ligaments
 Clinical presentation
• Mild to moderate or severe back and buttock pain
that is often worse in the early morning hours.
• This pain usually gets better with activity.
• There’s continued inflammation of the ligaments,
tendons, joint capsule and joints of the spine,
causing the spine to fuse together ( ankylose) as
the joints and disc spaces are replaced by bone
leading to less motion in the neck and lower back.
• As the spine fuses, or become stiff , the neck and
lower back lose their normal curve
• The mid-back curves outward ( kyphosis) and a
fixed bent-forward position can result leading to
significant disability.
• Inflammation of the small joints joining the ribs and
collarbone to the chest cause less expansion of the
chest wall with breathing.
• Less commonly it can cause aortitis, apical lung
fibrosis.
 Diagnosis
• Blood test for HLA-B27 gene
• Spine and pelvic xray showing characteristic
spinal changes and sacro-ilitis.
• Schober’s test which is useful clinical measure
of flexion of the lumber spine performed
during clinical examination.
 Treatment
• No cure is known for ankylosing spondylitis
• Treatment and medications are available to
reduce symptoms and pain.
• Anti-inflammatory drugs ( NSIADs) to reduce
inflammation and consequently pain
• DMARDs used to reduce the immune system
response through immunosuppresion.
• TNF alpha blockers slowing the progress of the
disease especially spinal arthritis.
 Surgical treatment
• Deformity correction using multiple corrective
osteotomy.
• Occasionally, hip or knee arthroplasty can be
used if there’s severe arthritis of these joints