DISEASE OF JOINTS

Types of Joints

1. Fibrous
e.g. Skull sutures

2. Fibrocartilaginous
e.g. * symphysis pubisis
* costochondral joint
* intervertebral joints

3. Synovial
e.g. * Most of limb joints
* TMJ
* Costovertebral
joints
The Articular Cartilage

 Chondrocytes
 Matrix
* Proteoglycans
Aggrecan= core protein+
chondroitin sulphate+Keratan
sulphate
*water
*type II collagen fibres
*Hyaluronan

SYNOVIAL MEMBRANE

1.Type A synoviocytes
2. Type B synoviocytes
 OSTEOARTHRITIS
 It is degenerative joint disease
characterised by
*focal loss of articular cartilage
*simultaneous proliferation of new
bone resulting in new bone formation

 It is the most common type of

arthritis
 It shows great association with
aging
 > 65 % people above the age of 65
years have radiological changes of
OA
 Inflammation is not a prominent
feature

CLINICAL FEATURES
  Insidious onset
 Pain in the affected joint
 No morning stiffness
 Pain on passive movement
 Crepitus over the joint
 Heberden’s nodes
 Bouchard’s nodes
 Genu varus and valgus deformity

 Swelling of joint

 Muscle weakness and muscle

wasting

INVESTIGATIONS
  Plain radiograph
 decrease in joint space
 osteophyte formation
 marginal sclerosis

 Blood examination

 Tests for secondary OA

e.g. haemachromatosis,
alkaptonuria, growth hormone

 Radio-isotope bone scan shows

increased uptake in OA joint

TREATMENT OF OSTEOARTHRITIS

1. Analgesics e.g. paracetamol

2. NSAIDS
3. Local application of NSAIDS and
capsaicin for knee and hand OA.
4. Intra-articular corticosteroids may
be helpful temporarily
5. Sodium hyaluronate can be
injected intra-articularly and may
provide up to 6 months pain relief.
6. Chondroprotectives e.g.
glucosamine and chondroitin
sulphate.
7. Weight reduction
8. Physiotherapy
9. SURGERY
*Arthroplasty e.g. hip and knee
joint replacement
RHEUMATOID ARTHRITIS

DEFINITION
It is idiopathic, chronic,

multisystem, inflammatory disease

mainly affecting the joints as well

as extra articular structures.

EPIDEMIOLOGY, GENETICS, &

ETIOLOGY OF RA

 RA is the most common

inflammatory joint disease
 Prevalence is 1 % of population
 Women are affected three times
more than men
 There is genetic predisposition ,
HLA-DR4 is commonly associated
with RA

 Exact cause of RA is unknown

 There is possibility that some
infectious agent like, mycoplasma
and EB virus initiates the
inflammatory process

PATHOLOGY

 Inflammatory process starts in the

synovial membrane
 Proliferation of synovial membrane
leads to formation of vascular
granulation tissue or pannus.
  The pannus destroys the articular
cartilage and subchondral bone.
 Later on there is fibrous and bony
ankylosis
 The mediators of inflammation
involved are:
*cytokines e.g. IL-I, TNF
*chemokines *leukotriene B4
*prostaglandin E2 *collagenase
*stromelysin
*histamine

CLINICAL FEATURES

 Joint pains
 Red , swollen and hot joints
 Hand joints involved in more
than 85% cases
 Fusiform swelling of fingers
 Morning stiffness
 Radial deviation of hand at wrist
with ulnar deviation of fingers
 Swan neck deformity
 Boutonniere deformity
 Hip, knee, ankle , foot and
atlantoaxial joints are also
involved
 Subcutaneous nodules

EXTRA ARTICULAR FEATURES OF

RA
 Systemic
*fever *anorexia *weight loss *fatigue

 Musculoskeletal
* muscle wasting * bursitis
* tenosynovitis * osteoporosis
  Haematological
* anaemia * thrombocytosis
*eosinophilia

 Lymphatic
*splenomegaly *felty’s syndrome

 Ocular
*episcleritis *scleritis *scleromalacia
*keratoconjuctivitis sicca

 Vasculitis
*digital arteritis *ulcers *visceral arteritis
*pyoderma gangrenosum

 Cardiac
*pericarditis *myocarditis *endocarditis
*conduction defects *coronary vasculitis
*granulomatous aortitis

 Pulmonary
 *nodules *pleural effusion *fibrosing
alveolitis *bronchiolitis *Caplan’s
syndrome

 Neurological
*cervical cord compression
*compression neuropathies e.g. carpal
tunnel syndrome *peripheral neuropathy
*mononeuritis multiplex

 Amyloidosis

INVESTIGATIONS

 Blood examination
 Urine examination
 Rheumtoid factor
 Radiographs of affected joints
*decrease in joint space
*bone erosions
*periarticular osteoporosis
 *deformities
 Synovial fluid examination
*usually turbid
*reduced viscosity
*increased protein content
*white cells > 2000/uL
*polys >75%
*decreased/ normal glucose
 X-ray chest
 ECG
 Echocadiography
DIAGNOSTIC CRITERIA FOR RA

1. Morning stiffness for 1hr or

more.
2. Arthritis of three or more joint
areas.
3. Arthritis of hand joints.
4. Symmetric arthritis.
5. Rheumatoid nodules.
6. Positive rheumatoid factor.
7. Radiographic changes

Criteria 1-4 must be present for at

least 6 weeks.

For definite diagnosis of RA 4 of 7

above criteria are required.

Histopathology of
Synovial Membrane
Histopathology of
Rheumatoid Nodule
 CRYSTAL ARTHROPATHIES

 MonoSodium Urate (MSU)

GOUT

 Calcium PyroPhosphate Dihydrate

(CPPD)

PSEUDOGOUT

 Calcium Hydroxy Apatite (HA)

 Calcium Oxalate (CaOx)

 GOUT

It is inflammatory arthritis due to

deposition of MSU crystals in joints

and associated with hyperuricemia.

 Prevalence is 1%

 Males are 10 times more affected

than females
 URIC ACID METABOLISM

DenovoPurin
Synthesis
600-700mg/D

Dietary Purine Tissue

Proteins nucleotides nucleotides
300-600mg/D

Purine
bases

Uric acid
pool
= 1200mg

Renal excretion Intestinal

 600 mg/day uricolysis 200mg
MECHANISM OF HYPERURICEMIA

DenovoPurin
Synthesis
600-700mg/D

Dietary Purine Tissue

Proteins nucleotides nucleotides
300-600mg/D

Purine
bases

Uric acid
pool
= 1200mg
Renal excretion Intestinal
600 mg/day uricolysis 200mg
CLINICAL FEATURES

 First metatarsophalangeal joint affected in >

50% cases.

 Other sites are ankle, mid foot , knee, small

joints of hands, wrist and elbow.

 Affected joint is red, hot , swollen, tender.

 Patient may present with bursitis,

tenosynovitis, and cellulitis.

 Tophi on extensor surface of fingers, hands,

forearm, elbow, Achilles tendon and helix of
ear.

 Uric acid stones in 10% cases.

 Urate nephropathy
INVESTIGATIONS

 Synovial fluid examination and demonstration

of MSU crystals.

 Serum uric acid level

Normal for Males: 2—7mg/100ml
(0.12-0.42 mmol/L)

Normal for Females: 2—6mg/100ml

( 0.12-0.36mmol/L)

 24 hour urinary excretion of uric acid

to differentiate between overproducers and
under excreters of uric acid.

 Blood urea, serum creatinin

 Blood examination

 Urine examination

 X-ray of affected joint

 Abdominal USG
 MANAGEMENT OF GOUT

A. ACUTE ATTACK

 NSAIDS
Naproxen, diclofenac, indomethacin
 Colchicine
1mg stat
0.5mg 6hourly
0.5mg BD or TDS
 Aspiration of joint fluid & intra articular steroid

B. LONG TERM MANAGEMENT

 Weight reduction
 Stopping alcohol
 Low protein diet
 Allopurinol
 Probenecid 0.5-1G BD
 Sulphinpyrazone 100mg TDS

 Salicylates antagonize the effect of uricosuric

drugs and must be avoided

 Uricosuric drugs are contraindicated in

overproducers of uric acid,renal impairment &
renal stones
 PSEUDOGOUT
OR
CHONDROCALCINOSIS

 It is due to deposition of CPPD crystals in

hyaline and fibrocartilage of joints.

 Common sites of deposition of these crystals

are knees, wrists (triangular fibrocartilage) and
pubic symphysis.

 More common in females.

 Increased association with osteoarthrosis.

 Demonstration of CPPD crystals in synovial

fluid.

 Calcification of cartilage on x-rays.

 Treatment is with NSAIDS and joint aspiration.

FACTORS PREDISPOSIMG
 TO
HYPERURICAEMIA

A. Diminished Renal Excretion of Uric acid

 Inherited renal tubular defect

 Renal failure

 Chronic drug therapy

Thiazide & loop diuretics

Low dose aspirin
Ciclosporin
Pyrazinamide

 Lead toxicity

 Lactic acidosis

B. Increased production of uric acid

 Increased purine turnover

Leukemia

Lymphomas

Polycythaemia

 Increased de novo purine synthesis

Idiopathic

Specific enzyme defects

e.g. HPRT deficiency

Glucose 6-phosphatase deficiency

 SLE

Systemic Lupus Erythematosus

It is multisystem autoimmune

connective tissue disorder.

Aetiology

There is production of autoantibodies.

Aggravating factors include:

 Exposure to sunlight,

 Exposure to UV light,

 Pregnancy

 Infections
Revised American Rheumatism
Association Criteria for SLE

1. Malar rash

2. Discoid rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

6. Serositis
a. pleuritis
b. pericarditis

7. Renal disorder

a. persistent proteinuria
b. cellular casts
8. Neurological disorder

a. seizure
b. psychosis

9. Haematological disorder

a. haemolytic anaemia or
b. leucopenia or
c. lymphopenia or
d. thrombocytopenia

10. Immunology disorder

a. Anti-DNA antibodies
b. Presence of antiboby to Sm
antigen
c. Positive antiphopholipid
antibodies

11. Antinuclear antibody

Disorder
INVESTIGATIONS

 Blood examination

 Urine examination

 ANF
 Anti dsDNA antibodies
 Anti-Sm antibodies
 Antiphospholipid antibodies
 Anticardiolipin antibodies

 Lupus anticoagulant
 LE cell

 X-ray chest
 ECG
 TREATMENT

1. NSAIDS/COX-2 Inhibitors

2. ANTIMALARIAL DRUGS
eg.chloroquine,hydroxychloroquine

3. STEROIDS

4. IMMUNOSUPRESSENTS
eg. Azathioprine,cyclophosphamide

4. ANTICOAGULANTS
Warfarin and low dose aspirin
In pregnancy heparin,low dose
aspirin,immunoglobins are used

5. Photoprotection
6. R/ of infections

SYSTEMIC SCLEROSIS
(SCLERODERMA)
It is a rare chronic immune disease

of connective tissue and

microvasculature in which collagen

and other matrix elements made by

fibroblasts are deposited in the skin,

adjacent tissues and visceral

organs.

INVESTIGATIONS
 Blood examination
 Urine examination

 Antinuclear antibodies
*antitopoisomerase I

*anticentromere antibodies

*antinucleolar antibodies

 ECG

 X-ray chest
 X-ray of hands

 Pulmonary function tests

 Renal function tests
 Skin biopsy

CLASSIFICATION OF SYSTEMIC
SCLEROSIS
1. Diffuse cutaneous scleroderma

2. Limited cutaneous scleroderma

3. Localized scleroderma

 Morphoea

 Linear

4.Sine scleroderma

AETIOLOGY
 Unknown

 Environmental factors involved in

some c

 +ases

*exposure to silica dust

*vinyl chloride

*trichloroethylene

*infections

CLINICAL FEATURES
 Sclerodactyly

Raynaud’s phenomenon

CREST

C Calcinosis
R Raynaud’ phenomenon
E Esophageal dysfunction
S Sclerodactyly
T Telangiectasia

 Arthralgia
 GERD
 Dysphagia
 Dyspnoea
 Digital ischaemia
 Renal failure

TREATMENT
Avoid exposure to cold

 R/ of infections with higher doses

of antibiotics & longer duration

 Calcium channel blockers and

Angiotensin II receptor blockers for
Raynaud’s phenomenon

 Steroids and cytotoxic drugs for

alveolitis and myositis

 D-penicillamin and interferon

gamma are ineffective

 Mycophenolate and tacrolimus are

under trials
PATHOLOGY

 Infiltration of T lymphocytes

 Activation of fibroblasts

 Overproduction and accumulation of

collagen

 Overproduction and accumulation of

extracellular matrix proteins including

*fibronectin
*tenascin
*fibrillin-I
*glycosaminoglycan
FIBROMYALGIA SYNDROME

It is characterized by diffuse
aches, stiffness, and fatigue,
coupled with multiple, symmetric
tender spots in specific areas.
 CLINICAL FEATURES
*Over 75% of patients are women.
*The peak incidence is between 20 and
60 years of age.
*The cause may actually be related to
a sleep disturbance.

*Pain is often aggravated by stress,

cold, and activity. *Fatigability is
often extreme, occurring after minimal
exertion.
*Sleep disturbance. Patients
complain of nonrestorative sleep,
waking unrefreshed. Research has
shown alpha wave intrusion into non-
REM delta wave sleep 70% greater
than controls.
*Headache is common as are
diffuse abdominal pain and
alternating diarrhea or
constipation.

*Miscellaneous. Paresthesias,
numbness, decreased mentation,
feeling of swollen hands and feet.
 *Associated syndromes. Irritable
bowel syndrome (35% to 65%), reflex
sympathetic syndrome (1% to 10%),
female urethral syndrome (urethral
spasm with dysuria and urgency,
12%).
 POLYMYOSITIS
&
DERMATOMYOSITIS
 Idiopathic inflammation of
muscles and skin
 Symmetrical proximal weakness
 Gottron’s papules are scaly
red/violaceous plaques or papules
over the extensor surfaces of
proximal and distal
interphalangeal joints
 the heliotrope rash is a violceous
discoloration of the eye-lid in
combination with periorbital
oedema
 investigations are CPK level,EMG
and muscle biopsy
 Steroids are first line of R/
 Azthioprine,methotrexate 2R/
 18 TENDER POINTS IN
FIBROMYALGIA

Fibromyalgia Syndrome

I. Clinical Features.
A. Characterized by diffuse
aches, stiffness, and fatigue,
coupled with multiple, symmetric
tender spots in specific areas
(Fig. 7-1). Over 75% of patients
are women, and the peak
incidence is between 20 and 60
years of age. There is often
discordance between symptoms
and objective findings. The cause
may actually be related to a sleep
disturbance.
B. Pain is often aggravated by
stress, cold, and activity. Patients
often complain of subjective
swelling of hands and feet, as
well as paresthesia and
dysesthesia of hands and feet.
C. Fatigability is often extreme,
occurring after minimal exertion.
D. Sleep disturbance. Patients
complain of nonrestorative sleep,
waking unrefreshed. Research
has shown alpha wave intrusion
into non-REM delta wave sleep
70% greater than controls. May
have depression and irritability
and be weepy.
E. Headache is common as are
diffuse abdominal pain and
alternating diarrhea or
constipation.
F. Miscellaneous. Paresthesias,
numbness, decreased mentation,
feeling of swollen hands and feet.
G. Associated syndromes. Irritable
bowel syndrome (35% to 65%),
reflex sympathetic syndrome (1%
to 10%), female urethral
 syndrome (urethral spasm with
dysuria and urgency, 12%).

Diagnosis
Fibromyalgia is a diagnosis of
exclusion (normal CBC,
ESR, thyroid functions, rheumatoid
factor, electrolytes,
creatinine, calcium, phosphorus, UA).
Patients must meet the American
College of
Rheumatology (ACR) criteria:
widespread pain of at 3
months' duration in combination with
at least 11 of 18
specified tender points.

The World Health Organization views

the ACR criteria as
primarily for research purposes and
determines that a
patient has FMS based on the history
and the finding of
a nonspecific number of tender points.
 Treatment

Treatment is aimed at controlling

symptoms and
restoring adequate sleep. Exercise
programs and
self-help strategies are the
mainstay of treatment.
Treatment includes reassurance,
education,
graded aerobic exercise, massage,
cognitive
therapy, and increased flexibility.
Patients may be
assured that FMS is generally a
self-limited illness
that typically resolves within 2 to 3
years. Low-
dose amitriptyline , 10 to 75 mg PO
QHS, or other
tricyclic such as doxepin or
nortriptyline taken
before bedtime, as well as an SSRI
in the morning
if needed for depression/ anxiety.
NSAIDs are useful for achiness.
Rheumatology: Figure 7-1

Location of specific tender points in fibromyalgia. (From Schumacher HR Jr, Klippel JH, Koopman
WJ, editors: Primer on the rheumatic diseases, ed 11, Atlanta, 1997, Arthritis Foundation.)

Rheumatology: Chronic Fatigue Syndrome

 I. A condition clinically characterized
by severe disabling fatigue and a
combination of symptoms
described in Box 7-2. The patient is
classified as having idiopathic
chronic fatigue if diagnosis is
suggested but inclusion criteria are
not meet.
II. Laboratory evaluation. CBC with
differential, ESR/CRP, ALT, protein,
albumin, globulin, alkaline
phosphatase, calcium, phosphorus,
glucose, BUN, electrolytes,
creatinine, TSH, urinalysis, and
laboratory tests based on specific
findings to exclude other
diagnoses.
III. Treatment is beyond the scope of
this manual.
Rheumatology: Box 7-2

BOX 7-2: Criteria for Chronic Fatigue Syndrome

Chronic fatigue defined as

self-reported persistent or
relapsing fatigue lasting 6
or more consecutive
months with four or more of
the following symptoms
concurrently present.
Impaired Multi-joint
memory or pain
consciousness
Sore throat New
headaches
Tender cervical Un-
or axillary refreshing
adenopathy sleep
Muscle pain Post-
exertion
malaise

Exclusion Criteria

Active medical conditions

that may explain fatigue
(e.g., hypothyroidism)
Previously diagnosed
condition whose
resolutions is not
documented (e.g., hepatitis
C)
Numerous psychiatric
conditions (e.g., major
depressive disorder,
schizophrenia, dementia,
anorexia, etc.)
Current alcohol or
substance abuse or within
the last 2 years
Unexplained physical,
laboratory, or radiographic
finding suggestive cause of
fatigue
Rheumatology: Polymyalgia Rheumatica and Giant Cell
Arteritis

Polymyalgia rheumatica (PMR) and giant cell arteritis form a spectrum of disease and affect
patients of >50 years of age; up to 15% of patients with PMR have giant cell arteritis and 40% of
patients with active giant cell arteritis have symptoms of PMR.

I. Polymyalgia Rheumatica.
A. Clinical features.
1. Pain and stiffness in the neck,
shoulder, and pelvic girdle.
Symptoms are bilateral and
symmetric and more
 prolonged in the morning.
May have diffuse aching.
2. Systemic features may be
present such as low-grade
fever, fatigue, and weight
loss.
3. ESR and C-reactive protein
are elevated with ESR
elevation of 50 to 100 mm
common. However, 15% of
those with PMR may have a
normal sedimentation rate
and C-reactive protein.
B. Diagnosis.
1. Rule out other causes such
as claudication, disk disease,
hypothyroidism, and myositis.
In PMR thyroid functions are
normal, CPK and aldolase are
not elevated, ANA should be
 "normal" for age, and
rheumatoid factor usually will
be negative. Patients may
have normocytic,
normochromic anemia.
2. Giant cell arteritis should be
excluded.
C. Treatment. Prednisone: initial
dose of 10 to 20 mg PO QD for 1
month and then reduce by 2.5
mg every 2 to 4 weeks until the
lowest dose is reached that
controls symptoms. Most
patients require treatment for 3
to 4 years, but withdrawal after 2
years is worth attempting. Low-
dose treatment should not be
used in patients with symptoms
suggestive of temporal arteritis.
II. Giant Cell Arteritis (Temporal
Arteritis).
A. Clinical features.
Predominantly affects persons
>50 years of age with early
symptoms of headache, fever,
fatigue, and perhaps upper-limb
girdle pain. May have associated
ocular symptoms including
partial visual loss and field cuts,
diplopia, ptosis, and blindness.
Tongue or jaw claudication may
occur.
B. Laboratory abnormalities.
Greatly elevated ESR, but 10%
may have normal ESR and CRP,
moderate normochromic
anemia, and thrombocytosis.
C. Diagnosis. Temporal artery
biopsy is most useful within 24
 hours of starting treatment;
however, steroids have little
effect on the sensitivity of the
biopsy, and treatment should not
be delayed. A positive result
helps to prevent later doubt
about the diagnosis. Sensitivity
of a biopsy is determined by
length of artery taken and
thinness of sections on
microscopy.
D. Treatment. Prednisone: initial
dose of 20 to 40 mg PO QD for 8
weeks. Patients with ocular
symptoms may need up to 80
mg PO QD. Reduce the dose by
5 mg every 3 to 4 weeks until it
is 10 mg QD and then taper
slowly, based on symptoms and
ESR. Treatment should last 24
 to 30 months, at which time a
trial off of steroids may be tried.

Rheumatology: Raynaud’s Phenomenon

I. Overview.
A. Episodic, biphasic or triphasic
color change: white (ischemia),
then often blue (stasis), then red
(reactive hyperemia), of fingers
or toes in response to cold or
emotion.
B. More than 90% of patients with
Raynaud's phenomenon are
female.
II. Types.
A. Raynaud's disease (primary
Raynaud's phenomenon). The
cause is unknown, and the
symptoms are usually stable.