1 Musculoskeletal structure & Function

Bone
A mineralised connective tissue. Three main cell types:
Osteoblasts (builders)
o Bone formation, lie in sheets on the surface of bone
trabuculae
Osteoclasts (cutters)
o Bone resorption
o Secrete matrix metalloproteinases (MMPs) and hydrochloric
acid onto the bone surface to remove mineral and matrix
simultaneously
Osteocytes mature, inactive osteoblasts that lie in lacunae within
bone

Osteoclasts & blasts coupled into bone remodelling units to keep adult
bone mass ~ constant
Bone matrix:
Protein matrix of bone type I collagen
Mineral matrix predominantly hydroxyapatite

Bone composed of two subtypes

Woven bone bone that is laid down rapidly (developing fetus,
healing fractures)
Lamellar bone laid down slowly; structurally strong, forms the
adult skeleton
o Cortical or compact bone forms the cortex, makes up 80%
of the skeleton, maximal contribution in long bone shafts
o Trabecullar or medullary (cancellous, spongy) bone
In contact with bone marrow cells between the cortices
At the end of long bones
In vertebral bodies

Cartilage
Articular cartilage avascular & aneural shock absorber
Composed of:
Chondrocytes create a matrix of type II collagen
Proteoglycans can bind water
Adult cartilage has four layers
Superficial, middle, deep and calcified zones (differ in pattern of
collagen fibre deposition, water and cell content

Muscle
Muscle fibres differ in their twitch rate and fatigability
Type 1 muscle fibres
o Slow twitch (red), highly resistant to fatigue

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 o Abundant mitochondria
o Designed to maintain sustained contractions (e.g. posture
control)
Type 2 muscle fibres
o Fast twitch (white)
o Produce greater force and rapidity of contraction
o Fatigue rapidly

Tendons and ligaments

Both composed of type I collagen
Tendons attach muscle to bone, ligaments connect bones to one another,
supplying support to a joint

2 Calcium Homeostasis & Bone Metabolism

The basics
Bone plays a major role in calcium homeostasis (bone is constantly
formed and reabsorbed)
Calcium
Most abundant mineral in the body
99% contained in bone
Half of plasma Ca bound to albumin inactive
Calcium results must be adjusted to account for albumin
o Add or subtract 0.02 mmol/l for each g/l by which albumin is
below or above 40 g/l
Calcium homeostasis and bone metabolism principally governed by
Vitamin D
PTH
bone metabolism also modulated by calcitonin, glucocorticoids, sex
hormones, GH & thyroxine

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Parathyroid Hormone
PTH released in response to low plasma Ca levels
Functions to
Increase plasma Ca
Decrease plasma phosphate
by acting on the gut, bone, and renal tract
Gut: increases intestinal Ca absorption
Bone: increases osteoclastic resorption of bone
Renal:
o Increases calcium resorption & phosphate excretion
o Increases renal hydroxylation of vitamin D precursors

The link between vitamin D & PTH

PTH responds to low vitamin D by increasing renal hydroxylation of
vitD precursors into the active form
High vitD levels inhibit PTH release

Disorders of Calcium homeostasis

Hypercalcaemia
High Ca abdominal pain, nausea, constipation, polyuria,
depression, renal stones
Shorten the QT interval
Most common cause malignancy (myeloma, bony metastases,
PTH-related protein released from some tumours &
1hyperparathyroidism)
Treatment rehydration + furosemide or bisphosphonates
Hypocalcaemia
Main symptoms depression, paraesthesia
Signs
o Trousseaus brachial artery obstruction carpopedal
spasm
o Chvosteks tapping the facial nerve facial muscles twitch
QT interval prolongation
Causes (pseudo)hypoPTH, chronic renal failure, pancreatitis
Treatment Ca supplementation & reversal of the underlying cause

Hyperparathyroidism
Primary hyperparathyroidism
o Inappropriate production of PTH in the presence of raised Ca
levels
o Symptoms of hypercalcaemia

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 o Causes most commonly single adenoma, then carcinoma &
hyperplasia
o Bloods
Raised Ca, unsuppressed PTH (i.e. normal or high
plasma levels)
Reduced phosphate
Elevated alkaline phosphatase
o There can be radiological evidence of bone resorption
Secondary hyperparathyroidism
o Appropriate PTH production in the presence of low Ca
o Chronic renal failure most common cause
o Treatment surgical
Tertiary hyperparathyroidism
o Inappropriate & autonomous production of PTH following
prolonged 2hyperparathyroidism
o Elevated Ca
o Treatment of the underlying disease

Hypoparathyroidism
Primary hypoparathyroidism
o Reduced PTH secretion due to autoimmune destruction of the
parathyroid glands or their surgical removal
o Symptoms of hypocalcaemia
o Bloods
Reduced calcium, elevated phosphate & normal alkaline
phosphatase
o Treatment alfacalcidol (vitD analogue)
Pseudohypoparathyroidism
o Similar symptoms as 1condition
o Due to end-organ resistance to PTH PTH levels may rise
o Features short face & short metacarpals/tarsals
Pseudopseudohypoparathyroidism
o Phenotypic appearance of pseudohypoparathyroidism, but
normal endocrine & biochemical features

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Arm and hand nerves
Median nerve
Course
Function flexion of the wrist & the 1 st & 2nd metacarpophalangeal joints,
opposition of the thumb
Muscles supplied LOAF Lumbricals 1st & 2nd, Opponens pollicis,
Abductor pollicis brevis, Flexor pollicis brevis
Injury thenar eminence atrophy
Motor
FPL & FDP Anterior interosseous n. (AIN) supplies flexor
pollicis longus (FPL thumb) and flexor digitorum profundus (FDP)
ask to make an okay sign
o AIN intact if both bend at the interphalangeal joint
Bend that more and stop me from breaking the ring
o AIN branches of the median just below the antecubital fossa,
so in carpal tunnel syndrome AIN will be spared
Thenar eminence Recurrent motor branch of the median
nerve
o Branches off the median nerve post the carpal tunnel
o Recurrent motor branch opposition Join your little finger
and your thumb together & dont let me break the ring look
for the thenar muscle contracting
o Thenar eminence opponens pollicis, flexor pollicis brevis &
abductor pollicis brevis
Sensory
Test both hands at the same time over the thenar eminence and
does it feel the same

Radial nerve
Course
Function extension of the wrist, supination
Muscles supplied all extensors of the forearm and the hand
Injury at the
Axilla Crutch or Saturday night palsy)

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 o Weakness of supination, loss of extension of forearm, loss of
extension of hand and fingers
o Wrist drop
Mid-arm Mid-shaft humeral fracture
o Weakness of supination, loss of extension of forearm (if lesion
is above the branch for brachioradialis (just above the elbow),
loss of extension of hand and fingers
o Wrist drop
Just below the elbow Neck of radius fracture, elbow dislocation
or fracture, rheumatoid nodules, injections for tennis elbow
o Weakness in extension of hand and loss of extension of fingers
o Finger drop
o Partial wrist drop, since the extensor carpi radialis longus &
brachioradialis are working
Within the distal forearm

Motor
Triceps flex in the elbow and push towards the patient (they are
trying to extend their arm, you try to flex it
Wrist (posterior interosseous nerve - PIN) cock your wrist back and
dont let me push it down
Thumb palm down, lift the thumb and dont let me push it down
Sensory
Test both hands at the same time and does it feel the same

Ulnar nerve
Course
Muscles supplied all the interosseous muscles of the hand (palmar and
dorsal) with the exception of the 1st and 2nd lumbricals
Injury most commonly injured nerve in an elbow injury
At the elbow Cubital tunner syndrome, fracture of the medial
epicondyle (causing cubital valgus away from the body)
o Weakness in flexion of the hand at the wrist, loss of flexion of
ulnar half of digits (4th & 5th)
o Claw hand deformity when hand at rest (hyperextension of the
4th & 5th digits at the metacarpophalangeal joints) & flexion of
the interphalangeal joins
o Weakness of adduction of the thumb (Froments test)
At the wrist penetrating wounds, Guyon canal cyst
Motor
Dorsal interossei muscles (deep branch of the ulnar nerve) split
your fingers, dont let me push them in - abduction
Palmar interossei muscles (deep branch of the ulnar nerve) put
a sheet of paper between the pts fingers, close in on the paper,
try to pull the paper out adduction

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 Adductor pollicis (first web space on the dorsum) Froments
sign both palms vertical, lift the thumbs up, put a sheet of paper in
between the thumbs and the hands, close in on the paper and dont
let me pull the paper while keeping your thumb straight
o If ulnar nerve is not intact, the pt will flex his 1 st (thumb)
interphalangeal joint (anterior interosseous nerve) instead of
adducting their thumb
Sensory
Comparing both sides, feel over the ulnar nerve territory, can you
feel my fingers on both sides and does it feel the same

Pathogenesis of Rheumatoid arthritis (RA)

The prototypical inflammatory arthropathy
Primary site of disease is the synovium, which becomes inflamed
and proliferates to form pannus:
o Pannus a mass of T cells, B cells, fibroblasts & activated
macrophages
o The pannus invades cartilage & bone clinical features of
pain & stiffness followed by joint swelling, instability &
destruction
RA a classic autoimmune disease that involves oth the cellular &
humoral components of immunity

Cells
T cells
Basis of cellular immunity, upregulated in RA synovial tissue
CD4+ T helper (TH) cells divided into the subsets TH1, TH2, TH17
o Each has a characteristic cytokine-producing profile
o TH17 cells the dominant cell population in RA, produce
interleukin-17 (IL-17)
IL-17 is responsible for
Cytokine production
Osteoclast activation
Matrix metalloproteinase (MMP) release
T cell activation depends on antigen-presenting cells (e.g. dendritic
cells) & requires two separate signals
o Signal 1
Antigen-specific binding b/w the T cell receptor & MHC
II / antigen complexes on the surface of antigen-
presenting cells
RA ass with HLA-DR4 and DR-1 alleles (contain a
shared AA motif in the MHC II antigen binding site =
shared epitope

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 o Signal 2
Co-stimulatory binding b/w the T cells CD28 protein
with ligands (CD80/86) on antigen-presenting cells
T cells can also express cytotoxic T lymphocyte
antigen 4 (CTLA-4) which binds CD80/86 without
providing a stimulatory signal & acts as an
endogenous inhibitor
Activated T cells are responsible for:
o Induction of pro-inflammatory cytokines (e.g. IL-1, IL-6,
IL-17 and TNF) enlistment & coordination of lymphocytes,
recruitment of macrophages
o Activation of synovial fibroblasts & osteoclasts to erode
cartilage & bone
o B cell proliferation & antibody production

B cells responsible for

Autoantibody production
Cytokine release
Antigen presentation
Modulation of T cells
Main role for B cells in RA the development of antibodies against self-
IgG molecules (rheumatoid factor, RF) and cyclic citrullinated peptides
(anti-CCP antibodies)
Anti-CCP antibodies may play a role in
o Disease pathogenesis and/or perpetuation or
o Merely represent by-products of the inflammatory process
Association between anti-CCP antibodies, the shared epitope and
cigarette smoking
o Smoking may promote the citrullination of self-peptides,
which are then presented to T cells by antigen-presenting
cells with the high-risk HLA-DR shared epitope
o Consequently, cell-mediated immunity against citrullinated
antigens is enhanced (via T cell activation & expansion)
and B cells secrete anti-CCP antibodies

Macrophages
Initiate and perpetuate inflammation both in tissue & the circulation
by
o Cytokine production, most notable TNF
o Antigen presentation to T cells
o Promoting adhesion & migration of leucocytes
o Degradation of collagen matrix
o Angiogenesis
Fibroblasts
Majority of the cells in RA synovial tissue
Their uncontrolled growth is a major factor in pannus formation

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 RA synovial fibroblasts lack the normal control mechanisms that
prevent cellular proliferation (e.g. tumour suppressor genes)
Instead, express proto-oncogenes & anti-apoptotic molecules
Synovial fibroblasts produce pro-inflammatory cytokines &
chemokines, thereby attracting activated inflammatory cells into the
joint
Also produce matrix metalloproteinases which erode cartilage

Inflammatory mediators
TNF dominant cytokine in RA
o In high concentrations in synovial fluid & rheumatoid
synovium
o Responsible for:
Key pathological processes, e.g. cellular activation &
cytokine, MMP & prostaglandin release
Systemic effects & weight loss (very active disease)
o TNF blockade using monoclonal antibodies has
revolutionised the treatment of RA
IL-1, IL-6, IL-17 crucial mediators in inflammatory disease; can
block them too

Cartilage & bone loss

Inflammation, cartilage & bone loss are closely linked
Cartilage destruction in RA
Driven by MMPs from synovial fibroblasts, neutrophil polymorphs &
chondrocytes
Osteopenia (bone thinning) & eriosins
By activated osteoclasts; of monocyte/macrophage lineage,
designed for bone resorption
Osteoclastogenesis requires
o Macrophage colony stimulating factor (M-CSF)
o The receptor activator of NFkB ligand (RANKL) from synovial
fibroblasts
o Activated T cells
upregulated by cytokines in inflamed synovial tissue

Osteoprotegerin (OPG) non-signalling decoy receptor for RANKL

o Diminishes osteoclast activation & bone resorption
o The ratio bw RANKL and OPG a crucial determinant of
inflammatory bone loss
Denosumab a monoclonal antibody against RANKL
o Increases bone mineral density in post-menopausal women &
may diminish bone erosion in RA

Summary
T helper 17 (TH17) & T helper 1 (TH1) cells - the dominant T cell
subsets in RA synovium

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 Interleukin-17 regulates many cytokines including TNF and plays a
role in both cartilage & bone loss
TNF most important inflammatory cytokine in RA
o TNF-blockade dominates monoclonal antibody (biologic)
therapy for the disease
B cells generate anti-CCP antibodies which may play a pathogenic
role
The RANKL/OPG axis a crucial pathway in inflammatory bone loss
in RA

Rheumatoid Arthritis
Epidemiology
RA affects 0.5-1% populations worldwide
Average age of onset (AoO) 55 years, but can occur any time,
especially infancy (juvenile idiopathic arthritis)
More common in women and smokers
Risk of premature mortality by 5-10 years due to
o Extra-articular involvement of the renal & respiratory tracts
o Opportunistic infections in the presence of
immunosuppressive drug therapy
o Accelerated atheroma & subsequent coronary artery disease

Aetiology
Unknown, likely to encompass genetic factors, sex hormones & an
unidentified initiating agent
B-cells, T-cells (TH17 and TH1), the pro-inflammatory cytokines
interleukin (IL-1, IL-6, IL-17) & tumour necrosis factor (TNF)

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 o Generate persistent cellular activation, autoimmunity &
inflammation of synovial joints & of a number of extra-
articular sites
Diagnosis
Rests on a number of clinical & laboratory features
1987 - American College of Rheumatology (ACT) criteria, at least
four of the following criteria must be met to make a diagnosis of RA
Morning stiffness Duration > 1h (for >6w)
Arthritis of at least three Soft tissue swelling (for
joints >6w)
Arthritis of hand joins MCPs, PIPs or wrist (for
>6w)
Symmetrical arthritis At least one area (for
>6w)
Rheumatoid nodules Positive rheumatoid factor
Radiographic changes Periarticular erosions
Joint symptoms must be present for at least 6 weeks to differentiate
RA from the post-viral arthropathies (e.g. parvovirus) shorter time
course, more benign prognosis
Radiographic features
o Soft tissue swelling
o Periarticular osteopaenia
o Joint fusion or destruction
Rheumatoid factor (RF) present in only 70%, up to 15% of the
normal populations have RF but not RA
Anti-CCP more specific for RA, found only in 3% of the general
population
o Presence of either or both RF and anti-CCP linked to increased
disease severity
2010 new criteria to increase the sensitivity of RA diagnosis
o Presence of synovitis in at least one joint (where there is no
better alternative diagnosis) and a score of >=6 out of 10
from the following
Number and size of joints involved (0-5)
Serologic abnormality (0-3)
Elevated acute phase response (0-1)
Symptom duration (0-1)
Clinical Features
Symptoms
Insidious pain
Swelling, stiffness of the small joints of the hands (MCP & PIP joints)
Characteristic sparing of the DIPs
Cf osteoarthritis, symptoms most severe in the morning, made
worse by rest and improved with activity
In a minority cases, RA can present acutely with widespread
synovitis, migratory arthritis or with marked systemic features of
pyrexia, fatigue, weight loss
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Signs
Joint instability leads to subluxation & persistent deformity
o Subluxation at the MCP joints with palmar and ulnar
deviation of the fingers
o Disease at the PIP joints cause
Boutonniere deformity fixed flexion at PIP,
extension at the DIP
Swan-neck deformity fixed extension at PIP, flexion
at DIP
Z thumb
o Subluxation & radial deviation at the wrist causing prominence
of the ulnar styloid
Stenosing tenosynovitis trigger finger or finger drip if a tendon
body is eroded
o The extensor digiti minimi most vulnerable
Bursitis

Features
Early rheumatoid hand
o Fusiform symmetrical MCP + PIP swelling
o Rheumatoid nodules
o Extensor tenosynovitis
o Wrist tenderness/swelling
o Prominent ulnar styloid
Late rheumatoid hand
o MCP destruction subluxation & ulnar deviation of the fingers
o Swan neck / Boutonniere deformity of the fingers
Clinical examination
Look
o Skin: scars, palmar erythema, vasculitis, evidence of steroid
use
o Soft tissue: muscle wasting, nodules, synovitis
o Bone: Ulnar deviation, swan-neck or boutonniere deformities
of fingers, Z thumb, prominent ulnar-styloid
Feel
o Synovitis, tenosynovitis
Move
o Active & passive ranges of movement
o Tendon integrity
o Hand function & disability

Extra-articular symptoms of RA
Periarticular (Musculoskeletal)
o Rheumatoid nodules
Firm, subcutaneous swellings

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 Develop in areas affected by pressure or friction
(fingers, elbows, Achilles tendon)
In pts +ve for RF
Can be complicated by infection
o Tenosynovitis & bursitis
Tendon sheaths & bursae lined with synovium
Can become inflamed in RA tenosynovitis & bursitis
Tenosynovitis flexor tendons of the fingers commonly
Bursitis olecranon & subacromial bursae commonly
o Carpal tunnel syndrome
Synovitis can cause entrapment of peripheral nerves
Ocular
o Episcleritis
o Scleritis
o Keratoconjunctiva sicca
Neurological
o Mononeuritis multiplex
o Cord compression (atlanto-axial subluxation)
o Sensorimotor neuropathy
Pulmonary
o Nodules
o Effusions
o Basal fibrosis
Cardiac
o Pericarditis
o Conduction defects
o Vasculitis
Renal Reduced GFR due to NSAIDs, Drugs, Amyloid
Splenomegaly Feitys syndrome (RA ass with splenomegaly &
leucopenia, in pts +ve for RF; leucopenia frequent bacterial
infections
Haematological
o Thrombocytosis
o Anaemia: chronic disease, GI blood loss due to NSAID therapy,
bone marrow suppression due to DMARDs, pernicious anaemia
Systemic
o Exhaustion
o Weight loss
o Pyrexia

Treatment
RA requires a multidisciplinary approach
Specialist nurse patient education, support, self-care groups
Physiotherapy exercise, joint protection

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 Occupational therapy adaption, aids, splints
Pharmacotherapy pain and disease control
Surgery joint replacement, arthrodesis, tendon repair

Disease assessment
DAS28 (Disease Activity Score 28)
Swollen joint count, tender joint count, ESR, CRP, patients global
assessment of their health
The 28 joints: MCPs, PIPs, plus both wrists, elbows, shoulders, knees
Basis for assigning biologic therapy and is widely used in clinical
trials

Pharmacotherapy
RA treated aggressively as early as possible to prevent deformity &
disability; the aim of treatment is total remission

Non-steroidal anti-inflammatories (NSAIDS)

COX-specific inhibitors good gastric safety profile, but avoid in heart
disease

Disease-modifying antirheumatic drugs (DMARDs)

Aim to halt disease progression.
Well tolerated, but a number of SEs pts need close monitoring
Pts with difficult disease may require a combination of two or three
DMARDs
Methotrexate (folic acid antagonist) + folix acid:
o SE: myelosuppression, pneumonitis, hepatitis
Hydroxychloroquine (inhibition of cellular enzyme release)
o SE: macular damage
Sulfasalazine (mechanism unknown)
o SE: myelosuppression, rash, hepatitis
Leflunomide (arrests activated lymphocytes)
o SE: myelosuppression, hepatitis, diarrhoea
Other DMARDS azathioprine, gold, penicillamine, cyclosporine,
cyclophosphamide

Steroids
Systemic steroids effective in active disease or during flare
Can be used to control symptoms until DMARDs have taken effect
High dose steroids reserved for refractory RA and for extra-
articular complications not responding to immunotherapy
Intra-articular steroid injections useful in acute flares, effect short-
lived and no impact on eventual outcome

Biological Therapy

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Anti-TNF & anti-B cell therapy
TNF blockers highly effective, divided into
o Monoclonal antibodies against TNF
Infliximab (chimeric human-murine monoclonal antibody
against TNF)
Adalimumab (fully humanised monoclonal antibody)
Golimumab (fully humanised monoclonal antibody)
Certolizumab (PEGylated Fab fragment of humanised
monoclonal antibody)
o TNF:Fc fusion protein Etanercept
TNF blockade risks opportunistic infection & reactivation of
latent TB
all pts screened with a CXR prior to biological therapy
TNF blockade restricted to patients with active disease (DAS28 >
5.1 on at least two occasions) who have failed treatment with at
least 2 DMARDs, of which one must be methotrexate
Anti-B cell therapy
o Rituximab in those who have not responded to TNF inhibition
o Effective in up to 50% of those pts with refractory disease

Summary
Not all pts with RA have a +ve RF
Not all pts with a +ve RF have RA
Anti-CPP more specific for RA
DMARDS may halt disease progression but will not reverse dmg
already done
TNF blockers effective, but risk of susceptibility to infection &
reactivation of latent TB
Anti-B cell therapy reserved for TNF-blockade non-responders

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The spondyloarthropathies
Any joint disease of the vertebral column
Ankylosing spondylitis the commonest spondyloarthropathy
Psoriatic, reactive and enteropathic arthritis referred to as
spondyloarthropathies if they involve inflammatory spinal pain at
some course during their natural history

Psoriatic arthritis
Psoriasis a long-lasting autoimmune disease characterised by patches of
abnormal skin
These patches typically red, itchy and scaly
A high cell turnover state, so hyperuricaemia and gout also possible
causes for arthropathy in this population

5-10% with psoriasis develop arthritis

Peak incidence b/w 20-40 years
Clinical patterns vary
o Distal hand disease affecting mainly the DIP joints
o Symmetrical polyarthritis similar to RA
o Spondyloarthropathy
o Asymmetrical oligoarthritis
o Arthritis mutilans due to osteolysis of the small joints in the
hand
o Dactylitis (so-called sausage finger), tenosynovitis,
enthesitis
Diagnosis
Difficult to differentiate RA in a patient with co-existing psoriasis from true
psoriatic arthritis (PsA), esp since up to 10% of those with PsA are RH +ve
ACPA (anti-CCP) antibodies generally absent
The presence of disease at the DIP joint and/or psoriatic nail
changes (pitting, ridging, onycholysis, salmon-pink patches) would
indicate PsA rather than RA
Radiological indicators of PsA rather than RA include
Absence of juxta-articular osteopaenia
Whittling of the terminal phalanges (acro-osteolysis)
Pencil-in-cup deformity (erosion of the proximal and expansion of
the distal portion of an interphalangeal joint)
Ankylosis

Treatment
NSAIDS, occasional intra-articular steroid injection
Methotrexate and/or leflunomide (may also improve skin)
Sulfasalazine, azathioprine, penicillamine, gold and cyclosporin in
severe cases
Avoid use of hydroxychloroquine (may produce flares of skin
disease)

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 Biologic therapy (anti-TNF) for those with refractory joint disease
(>= 3 tender & >=3 swollen joints despite trials of at least two
DMARDs) very effective

Reactive arthritis/Reiters syndrome

a reactive arthritis that happens as a reaction to a bacterial infection in
the body. The infection usually happens in the intestines, genitals, or
urinary tract

Any spondyloarthropathies reactive if there is a Hx of

urethritis/cervicitis or diarrhoea
Urethritis commonly due to Chlamydia, may be asymptomatic
The Diarrhoeal illness usually occurred within the preceding
month, commonly due to Shigella, Salmonella, Campylobacter
The syndrome may develop acutely with fever, weight loss, and
polyarticular involvement
More commonly pts present with
o a mono- or oligoarthritis &
o either a low grade or absent fever
Additional features may be present
Painless ulcers on the palate
Balanitis circinata: painless plaques on the glans or shaft of the
penis
Keratoderma blennorrhagica: a painless papular/postular rash on
the palms or soles of the feet
Conjunctivitis: may be followed by uveitis
Enthesitis

Diagnosis
Relies on a careful Hx/examination and the combination of
o raised inflammatory markers
o Results of serologic testing, cultures, swabs
Joint aspirate rules our a septic or crystal arthropathy
No classical radiological features
HLA-B27 not helpful with diagnosis, but B27+ve patients tend to
have a more prolonged severe course to their arthritis

Treatment
NSAIDS & local corticosteroid injections suffice for many patients
(majority in remission within 2 years)
Persistend disease (esp in B27+ve patients) may require DMARDs,
such as sulfasalazine

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 Antibiotic therapy against the precipitating infection may not have
any impact on the arthropathy

Enteric arthropathy
Up to 20% of Crohns or UC pts develop an arthropathy
o Of those, 2/3 have peripheral symptoms and 1/3 develop AS-
like disease
Peripheral disease: slightly higher incidence in Crohns
o Type I: oligoarticular & asymmetric, it may coincide with the
onset of bowel disease & has a close association with GI
exacerbations
o Type II: polyarticular & symmetric & less closely ass with
flares of bowel disease
Sacroiliitis (inflammation of one or both of your sacroiliac joints)
o In both forms of inflammatory bowel disease
o Not clearly ass with either the onset or exacerbations of bowel
pathology

Treatment
NSAIDs if tolerated & intra-articular &/or oral steroids
Sulfasalazine the DMARD of choice as it has beneficial effects on
bowel disease
Methotrexate occasionally used second-line
Biologic therapy for those with refractory arthritis due to Crohns
very effective

Summary
Nail changes a characteristic feature of those with psoriatic
arthritis
Most patients with reactive arthritis in remission within 2 years
B27 positivity a poor prognostic factor
Spinal & bowel disease run independent course in enteric
arthropathy

Osteoarthritis
Results from breakdown of joint cartilage & underlying bone
OA most common form of arthritis
Symptoms often episodic
Goals of treatment provide pain relief, minimize disability &
improve quality of life
Non-pharm treatments as important as pharmacological ones for OA
Criteria for JR uncontrolled pain & severe impairment of function
despite conservative treatment

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Most common condition to affect synovial joints & the most important
cause of locomotor disability
OA increases with age
Now viewed as a metabolically dynamic process (instead of a
degenerative one) characterized by an imbalance of joint
breakdown in association with a maladaptive & insufficient repair
process
Cause
From abnormal biochemical stresses (severe injury, repetitive excessive
loading) superimposed on normal joint physiology
or From normal stresses applied to an inherently compromised joint
with abnormal physiology (weakened collagen due to a gen mut in
collagen type II
Final common pathway of a number of interacting RFs & processes
(genetic factors, age, gender, excess weight, injury, joint deformity &
occupational exposures)

Presentation
Primary or secondary
Typically joins in characteristic locations
Pain, loss of joint motion & function, minimal (<30 min) morning
stiffness, short-lived stiffness after resting (gelling)
o All in the absence of systemic symptoms (fatigue, fever) or
other system involvement
Joint stiffness due to
o Accumulation of hyaluronan (joint lubricant & most abundant
constituent of synovial fluid)
o Hyaluronan fragments in the deep layers of arthritic synovium
during periods of rest, excluding water within the synovial
tissue
o Joint movement mobilizes hyaluronnan from the tissue to the
lymphatics & blood hydration of synovial tissue &
improvement in joint stiffness symptoms
Cartilage changes accompanying OA encourages deposition
of crystals
o Calcium crystals (calcium pyrophosphate & basic calcium
phosphates) (esp the knee)
o Urate crystals
Pts with OA may developed superadded acute pseudogout (mainly
knees & wrists)
At increased risk of 2 gout if on long-term diuretics or have chronic
renal impairment

Examination
Pain from several sites in & around an OArthritic joint
o Increased intra-capsular & intra-osseous pressure,
subchondral microfracture & enthesopathy or bursitis 2to
muscle weakness & structural alteration

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 Crepitus, bony enlargement, deformity, instability & restricted
movement may occur together
Synovitis (warmth, effusion & synovial thickening)
Muscle weakness or wasting

Diagnosis
By Hx and examination alone
Main investigation to confirm OA plain X-ray
o Focal joint-space narrowing (cartilage loss)
o Marginal osteophyte or spur formation
o Subchondral sclerosis of bone
Biochem joint abnormalities precede radiographic abnormalities by
as much as decades

Management
Goals to:
Provide patient education & information access
Relieve pain
o Exercise (e.g. local quadriceps-strengthening exercise)
o Reduction of adverse biomechanical factors (e.g. spreading
physically hard jobs at intervals through the day)
Optimize function
Minimize disease progression

European & US guidelines for OA management

The management plan must be individualized, taking into account
the site & severity of OA symptoms, any co-morbidity, concurrent
medications & patient acceptability
Non-pharmacological treatments are central drug treatments are
adjuncts

Pharmacological treatments
OA management must take into account co-morbid conditions and
their potential drug interactions
Pain relief main reason patients seek help (long-term, non-
pharmacological lifestyle measures can all reduce pain)
Regular paracetamol +/- topical NSAIDs
If ineffective, use codeine or short-term oral NSAID
Topical capsaicin (derived from chillies) may help
Intra-articular steroid injections may temporarily relieve pain
Intra-articular hyaluronic acid injections as effective as NSAIDs or
steroid injection (more expensive)
Glucosamine & chondroitin not recommended

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