Background

Definition

Accumulation of calcium salts in the soft tissues

- Dystrophic or Metastatic

Different from bone formation

- calcification is typically amorphous calcium crystals

- ossification has bone organic matrix (Osteoid) & cells

Types

Dystrophic

Metastatic

Dystrophic

Normal serum calcium deposited in damaged tissues

Two phases

Initiation

- exact mechanism uncertain

- necrosis exposes denatured proteins

- binding PO4 exposed

- act as nucleation sites for precipitation of calcium

Propagation

- accentuated by hypercalcaemia

Pathology

Deposits amorphous & non-crystalline

Many forms

- pyrophosphates

- carbonates

- oxalates

- Fe salts

Hydroxyapatite crystals may form

- May progress to Ossification

Degenerative tissues

- atherosclerosis

- damaged heart valves

- infected lymph nodes

- degenerating tumours

- chondrocalcinosis

- CPPD deposition in cartilage

Metastatic

Occur in normal tissue whenever there is hypercalcaemia

- may occur widely

- blood vessels / kidney / lungs / gastric mucosa

HyperCalcaemia

- Primary hyperparathyroidism

- Tertiary hyperparathyroidism / CRF

- malignancy

- immobilisation

- vitamin D Intoxication

- Milk Alkali Syndrome

- Sarcoidosis

Exact mechanism unknown 

-? 2° local high pH

- deposition of basic calcium salts

Calcification v Ossification

Xray

Calcification

- central pattern

- often increased opacity compared with bone

Ossification

- peripheral pattern

- similar density to bone

Histology

Calcification

- calcium salts only

Ossification

- osteoid matrix

Chondrocalcinosis

Definition

The deposition of calcium in joints

- often in degenerative cartilage

- many different causes

Crystals can be salts of

- Calcium pyrophosphate dihydrate (CPPD)

- Dicalcium phosphate hydrate

- Calcium hydroxyapatite

- Calcium oxalate

Differential Diagnosis

WHIP A DOG 

Wilson's

Haemochromatosis, hyperparathyroidism

Hypophosphatasia

Idiopathic

Pseudogout, pernicious anaemia

Amyloid, acromegaly

Diabetes

Ochronosis

Gout

Xray

Calcium in articular cartilage

- fine linear densities

- parallel to subchondral bone

Arthroscopy

DDx Soft Tissue Calcification

DDx Soft tissue calcification

Hemangioma (commonest)

AV Malformation

Synovial sarcoma

Chondrosarcoma

MO / HO

Eptheloid sarcoma

TB calcified LN

Myositis Ossificans

Definition

Pathological bone formation in soft tissues

Epidemiology

In elbow

- 3% of trauma

- 89% if head injury + trauma

Types

Completely different

1.  Myosisitis Ossificans Circumscripta

- post traumatic

- more common

- recognised as a consequence of neurological injury

2.  Myositis (Fibrodysplasia) Ossificans Progressiva

- rare inherited condition

- progressive fibrosis of muscles, ligaments and tendons that is ultimately fatal

Classification

1. Traumatic 

Most common

- deltoid

- quadriceps

- elbow joint

2. Non-traumatic

Adductor tendon in horse riders

Aetiology

Unclear

Progression beyond normal healing to 0ssification

Typically single major traumatic incident

- direct blow to muscle

- joint dislocation ± fracture

Can occur with repeated minor trauma

- adductor Longus in horse riders

Pathology

2° muscle inflammation & repair process abnormal

- extensive cellular infiltration

- collagen laid down

- collagen undergoes dystrophic calcification

- chondroblasts differentiate into osteoblasts 

- osteoid produced

Clinical Features

History of trauma

Initial pain / swelling / warmth

Develop hard mass

- slow resolution of pain

X-ray

Changes occur 2-4 / 52 after injury

Initial cotton candy appearance

- then osseous in appearance

- not attached to bone

- can be resorbed

Mature bone peripherally

DDx 

Osteosarcoma

STS

Hemangioma

MO

- diaphyseal (OS metaphyseal)

- intact cortex (OS fractures)

- mature bone peripheral with central fibrous tissue (OS mature centrally)

- pain and swelling improves with time (OS worsens)

- normal osteoblast on biopsy

Management

Prevention

High risk

- i.e. sports player with trauma to thigh / large haematoma

Minimise haemorrhage & inflammation

- ice & elevation

- active ROM / avoid passive ROM

- 3/52 course of NSAIDS

Resection

Indication

- large mass of bone

- significant pain, stiffness & weakness

Timing

- delayed > 12/12 (usually delay minimum 18 months)

- early resection = Recurrence

- don't resect until neurological recovery complete (i.e. if head injury)

Maturity

- local pain and tenderness resolved

- mature trabecular pattern on xray

- no progression on xray

- alkaline phos normal

- cold bone scan

Prognosis

- poor with in patient with incomplete neurological recovery and spasticity

Myositis Ossificans Progressiva

Definition

Widespread ossification of connective tissue

Epidemiology

AD

Site

Spine

Major joints of upper limb

Histology

Poorly formed bone

Dense scar tissue

Islands of poorly formed cartilage

Clinical

Patients have short 1st metatarsal / metacarpal

Die of restrictive lung disease

Tumoural Calcinosis

Aetiology

Unknown

Epidemiology 

Rare

Black population

1st or 2nd decade

Presentation

Painless firm swellings over joints

- very common at large joints 

- hip and shoulder

Cosmetic & functional problem

- may ulcerate & discharge

Biochemistry

Calcium levels normal

Serum phosphate usually high

Management

Complete surgical excision

- recurrence common

Hypercalcaemia

Definition

> 10 mg / dl

- must be corrected for albumin

Causes

Malignancy

- multiple myeloma / lung cancer / breast cancer

Hyperparathyroidism

- elevated PTH

Issue

High mortality associated with hypercalcaemia of malignancy

Physiology

40% albumin bound

50% ionised and active

Symptoms

Lethargy / confusion

- most commonly seen in malignancy

Kidney stones / abdominal pain / depression

- more likely seen in hyperparathyroidism

Management

Admit patient for medical management

Forced diuresis

- fluids + frusemide / loop diuretic

Bisphosphonates

- IV dose

Calcitonin

- gives rapid but short lived reduction

- need to be coadministered with other medications

Dialysis

- required if kidneys unable to cope with fluid diuresis / renal failure

Hypocalcaemia

Signs

Fall in level promotes tetanus

Chvostek sign

- tapping masseter muscle induces spasm

Trousseau Sign

-  flexion of thumb & wrist with extension of fingers

Carpopedal Spasm

ECG

Prolonged QT interval on ECG

Causes

1. Vit D Deficiency

- lack sunlight

- dietry lack

- malabsorption

- liver / renal disease

- anticonvulsants

2. Hypoparathryoidism

- throidectomy

- infiltrative (carcinoma, haemachromatosis)

- idiopathic

3. Hypothroidism

4. Hypophosphataemia (Vit D resistant Rickets)

5. Hypomagnesemia

Metabolism

Calcium

Source

- ingested in diet

- absorbed in small intestine / duodenum

- under control of vitamin D

Excretion

- through kidney

- majority is reabsorbed

- under control of vitamin D

Storage

- 99% stored in bone

PTH

Source

- produced by parathyroid glands

- in response to hypocalcaemia

Action

1.  Vitamin D

- stimulates activation of Vit D in kidney

- vit D then increases absorption / decreases excretion / increases release from bone

2.  Bone

- stimulates release of calcium from bone by indirect inhibition osteoclasts

3.  Kidney

- increases resorption of calcium

- increases excretion of phosphate

Vitamin D

Generation of Vit D

Vitamin D3 ingested and absorbed

- activated by sunlight

- need 10 - 15 minutes 3 x per week

25 hydroxylated in liver

1 alpha-hydroxylase in kidney

- active 1,25 vit D3

- calcitriol

- this is under PTH control

Action Vit D

1.  Intestine

- increases Ca and PO4 absorption

2.  Kidney

- decreases Ca and PO4 excretion

3.  Bone

- increases Ca and PO4 release

Background

Aim of Coagulation

To produce sufficient thrombin to rapidly convert soluble fibrinogen into insoluble mass of fibrin

Coagulation cascade must be localised & limited to site of tissue injury

Three phases

1.  Immediate Control of Blood Loss

Vascular Phase

- damage to blood vessel triggers reflex vasoconstriction

Platelet phase

- damage blood vessels release serotonin and adrenalin

- stimulates vasoconstriction and platelet aggregation

- platelets release thromboxane A2

- stimulates further platelet formation

- platelets form plug

2.  Clot Formation

Formation of fibrin

- red cells & platelets bound together by strands of fibrin

- final common pathway is Factor X activation

- factor X converts Prothrombin to Thrombin

- thrombin converts Fibrinogen to Fibrin

Intrinsic System

- started by activation of factor XII

- secondary to exposed subendothelium

- HMWK & PreKallikrein-->Kallikrein

- ends with activation factor X

Extrinsic System

- tissue Thromboplastins

- released by tissue damage

- activate factor VII

- activates factor X

3.  Removal of Clots

Fibrinolytic enzymes remove clot as vessel wall repaired e.g plasmin

Platelets

Function

- when subendothelial structures are exposed to flowing blood, platelets adhere to subendothelial VWF & collagen

- platelets then release granules

- ADP & Thromboxane A2

- potentiates aggregation & stimulates vasoconstriction

Bleeding time

BP cuff inflated to 40 mm Hg &  incision made

- time until bleeding ceases is noted

- normal < 9 minutes

Prolonged with

- platelet count < 50,000/mm

- platelet function impaired (NSAIDs, aspirin)

- von Willebrand Disease

Thrombolytics

Prostacyclin

- produced in vessel walls

- has antithrombotic effect

- high intimal concentration discourages luminal obstruction by platelets

- antagonist effect to TXA2

Antithrombin III

- circulating protease

- binds & inhibits Thrombin

- inhibits II, IXa, Xa, XIa, XIIa            

- ↑ APTT (Intrinsic)

- heparin globally increases its activity

- LMWH only works against Xa

Protein C & S

- Vit K dependent

- natural anti - Thrombolytics

- activated by Thrombin

- familial lack rare ++ 1: 16 000

- decreased amount associated with spontaneous DVT

Tissue Plasminogen Activator

- converts plasminogen to plasmin

- plasmin degrades fibrin

- e.g. streptokinase, urokinase, TPA

Hemophilia

- occurs almost solely in males

- female carriers usually asymptomatic

- 30% have no family history

Haemophilia A

FVIII deficiency

X-linked disorder

- 1:10 000

- all ethnic groups

- all parts of the world

Reduction in circulating levels of functional FVIII

- decreased amount or defective FVIII

- carriers have 50% of normal levels

- bleeding problem if <5%

FVIII complex protein with 2 forms

- small molecule with coagulant activity (VIII:C)

- larger molecule which circulates with von Willebrand factor (VIII:vWF)

Haemophilia B / Christmas Disease

FIX deficiency

Also X linked recessive

- less common

- 1:30 000

Similar spectrum of disease

- identical to haemophilia clinically

- treat with Factor IX cryoprecipitate

Pathogenesis

Intrinsic pathway

Factor VIII

- an essential cofactor for factor IXa

- catalyses conversion of factor X => Xa

- in the presence of activated factor VIII the rate of factor Xa production is dramatically increased

Without factor VIII activity

- delayed clot formation

- excessive bleeding and poor wound healing

Clinical Features

Orthopaedic Manifestations

1.  Haematomas

2.  Haemarthrosis

3.  Bone cysts and pseudotumours

Depend on level of FVIII

<1%

- frequent spontaneous bleeding in early life (haemarthroses)

<5%

- severe bleeding following injury

>5%

- milder disease post-traumatic bleeding only

Most frequent cause of death is AIDS (transmitted in 1980s)

1.  Haematomas

Haemorrhage into subcutaneous connective tissue or into muscle

- with or without trauma

- superficial or deep

Problems

- expand locally to compress organs, vessels, nerves

- expand distally to retro-peritoneal / retro-pharyngeal

- may cause compartment syndromes

Can lead to muscle contractures / atrophy & nerve palsies

- volkmann forearm contractures

- iliopsoas haematoma and femoral nerve palsy

- recurrent calf bleeds and equinus

2.  Haemarthroses

Acute                       

- rapid tense swollen red tender articulation

- painful and stiff

- fever and leukocytosis

- symptoms decrease quickly

Subacute           

- after 2 or more haemarthroses

- complete recovery of joint not evident

- peri-articular swelling secondary to boggy synovium

- joint motion is restricted

- contractures evident

- muscle atrophy

Chronic                       

- after subacute present for 6-12 months

- severe and persistent contractures

- final stage fibrotic contracted and destroyed articulation

3.  Bone cysts and Pseudotumors

3 types                       

1. Simple cyst

- confined within fascial envelope of muscle

2. Cyst in soft tissues

- interferes with blood supply of adjacent bone and periosteum

- resorption of bone and cyst formation

3. Result of sub-periosteal bleeding

- resultant stripping limited by aponeurotic or tendinous attachments

As cyst increases

- compresses and destroys muscles, nerve and bone

- likely to reform unless completely removed

- tend to become multi-loculated

- erodes through tissues into viscera and skin

- predisposed to infection

- difficult to differentiate from malignant tumours

- needle biopsy with caution

Differential Diagnosis           

- primary and secondary neoplasms

- infection

Also

AVN          

- epiphyseal fragmentation and collapse

- especially hip and ankle

- secondary to intra-osseous bleeding or intracapsular bleeding

- causes increased intra-articular pressure, vascular occlusion and subsequent osteonecrosis

Ectopic Ossification           

- occurs in peri-articular tissues

Fractures           

- fracture healing normal

- pseudotumours may develop at site of fracture

Chondrocalcinosis           

- haemosiderin alters articular mechanics that leads to cartilage calcification

Pathology

- blackish fluid containing clots within recesses of articular cavity

- embedded within synovial membrane or adherent to capsule

- with each bleed resorption less

Synovium

- discolouration of synovial membrane secondary to haemosiderin absorption

- hypertrophy, hyperplasia and increased vascularity

- synovial villi more numerous

- synovial tissue and adjacent capsule/soft tissues undergoes fibrous proliferation

- appears similar to inflammatory pannus

Cartilage

- becomes discoloured

- reveals focal areas of fibrillation, erosion, necrosis

- may expose sub-chondral bone

- modified in several ways           

- loss of subchondral bone plate (therefore calcified cartilage rests on cancellous bone)

- trabecular thinning and resorption (enlarged marrow spaces which appear cystic)

- granulation tissue extends from bone into overlying cartilage

Sub-chondral cysts

- represent sites of intra-osseous haemorrhage

- cysts common beneath sites of abnormal cartilage

Periosteal bleeding (pseudo-tumours)

- can lead to secondary periosteal bone formation

- creates irregular and expanding bony contours

Immature skeleton

- chronic hyperaemia of epiphyseal cartilage

- leads to accelerated maturation and enlargement of epiphyses

Investigations

Platelet count / Bleeding time normal

APTT increased

PT Normal

Low factor VIII: C Activity

X-rays

Think Haemophilia if destroyed joint & epiphyseal overgrowth + lytic bony lesion

Affects hinge joints

1.  Knee

Widened femoral condyles and intercondylar notch

- distal condylar surface may appear flattened

- squaring of the inferior pole of patella

- subluxation patella and particularly postero-lateral tibia on femur

NB

- not specific for haemophilia

- many of changes similar to those seen in juvenile chronic arthritis

2.  Elbow

3.  Ankle

Arnold Classification Arthropathy

Stage I

- soft tissue swelling + effusion

- periarticular osteoporosis

Stage II 

- overgrowth / widening of epiphysis

- surface irregularity / small erosions

- joint space maintained

Stage III           

- some narrowing of joint space

- extensive bony erosions 

- sub-chondral cysts

Stage IV           

- cartilage destruction

DDx

Trauma

Juvenile onset RA

PVNS

Infection

Other coagulation disorder

Prognosis

Patients treated after 1985 can expect to have normal life spans

- older patients had high incidence of AIDS
- now recombinant

Management

Non Operative Management

Factor VIII

Replacement of missing / defective component

Factor VIII concentrate

- initially pooled / high risk of HIV

- then heat treated to eliminate this risk

- now produced by recombinant technology

FVIII

- has a half life of 12 hours

- 1 u/kg increases VIII by 2%

- given tds

Aim

- 15% for mild bleed

- 30% for severe bleed ~ 1000u tds

- give ASAP at home

Problem

- 10% will develop antibodies

- IgG inhibitor

- use FVII in life threatening emergency

Other options

- FFP: concentrations of FVIII too dilute

- DDAVP produces a rise in FVIII proportional to initial level

Acute Haemarthrosis

Usually managed at home

- IV F VIII 1000U tds if 70kg

- analgesia (Not NSAID)

- splint & compression first 24 hours

- once bleeding stops ice packs & mobilise

Place of washout controversial

- reduces pain & swelling

- no evidence that it decreases risk of arthropathy

Subacute Haemophilia arthropathy

Treatment

1.  Prednisone 5 days

- 2-3 doses FVIII for level > 30%

- physiotherapy

2.  Prednisone 6 weeks                   

- FVIII > 20% 3 x week

- physiotherapy

Operative Management

Indications

- synovectomy

- contractures

- OA hip / knee / elbow / ankle

Perioperative Management

F VIII

Levels

- 100% pre and post op

- > 60% for 2/52

- 30% for 6/52

Haematologist

- close working relationship with surgeon

- adequate reserves of concentrate available in advance

- lab available to perform unlimited assays for the factor

- identify antibody/inhibitor production

- screen for HIV / HBV / HCV

FVIII inhibitor

Increasing problem

- new techniques involving FEIBA

- factor eight inhibitor bypassing activity

Lauroua et al Haemophilia 2009

- FEIBA in 12 patients having major and minor operations

- successful bleeding control

Operative technique

As many procedures at one sitting as the patient can take

- monitor factor VIII intra-operatively

- pneumatic tourniquets

- tight careful wound closure to avoid dead space

- avoidance of diathermy (coagulated areas slough after surgery)

- wound suction to deep wounds minimum 24 hours

- no aspirin platelet inhibitors post operatively

- no intramuscular injections

Post-operatively

- Need F VIII for MUA and ROS

Synovectomy

Indication

Chronic synovitis

- stage 1 or 2

- reduces incidence of bleeding & improves function

- slows progression of disease but doesn't prevent

Results

Rodriguez-Merchan Int Orthop

- 27 surgical synovectomies of the knee

- average age 13

- better results in arthroscopic than open

- reduces incidence of hemarthrosis and improve ROM

- effects diminish with time

- disease progresses, but likely more slowly

Patti et al Arthroscopy 1996

- arthroscopic synovectomy in 9 ankles

- reducing bleeding incidence and improved ROM and function

Contractures

1.  Fixed ankle equinus

- T Achilles equinus

2.  FFD and valgus knee

- supracondylar osteotomy

Arthrodesis

AKJ / STJ

Knee Arthroplasty

Results

- good functional results

- good long term survival

- higher rates of infection

Rodriguez-Merchan JBJS Br 2007

- 35 TKR followed up for average 7.5 years

- average patient age 31

- 97% survival at 7.5%

- 94% good or excellent results

- 1 deep infection requiring 2 stage revision

- 1 patient required embolisation

Silva et al JBJS Am 2005

- 90 TKR in hemophilia

- rate of infection was 16%

- 12 required removal, 9 for late infection

- knee society scores good or excellent in 97%

Hip Arthroplasty

Kelley et al JBJS Am 2005

- 34 patients average age 38 followed up for 8 years

- 3 late deep infections

- 21% rate of aseptic loosening

Elbow

Chapman-Sheath et al JBJS Br

- TER in 7 elbows

- one deep infection

- excellent functional results at 4 year follow up

Other Disorders

Liver Disease

Obstructive disease

- decreased absorption Vitamin K as it is fat soluble

- Vit K dependent factors affected

- II, VII, IX & X 

- raised INR

Hepatocellular Disease

- impairs synthesis of all coagulation proteins

- bleeding episodes treated with FFP or Cryoprecipitate

Vit K Deficiency

Occurs with impaired intake or malabsorption

- Inflammatory Bowel Disease

- blood contains no functional forms of II, VII, IX & X

- reversed in 1/7 of Vit K administration

Antiphospholipid Syndrome

Phospholipid antibodies

- Broad family of autoantibodies that target phospholipids

- can be either procoagulant or anticoagulant

Lupus anticoagulant antibodies 

- procoagulant

- associated with thromboembolic events rather than clinical bleeding

Antiphospholipid syndrome

Need 1 clinical and 1 laboratory for diagnosis

Clinical

- Vascular thrombosis

- Catastrophic antiphospholipid syndrome

- Complications of pregnancy (spontaneous abortions / premature intra-uterine deaths)

Laboratory

- detected on 2 tests 6 weeks apart

- anticardiolipin antibodies

- lupus anticoagulant antibodies

Prevalence

Antiphospholipid antibodies is 1-5% in young adults

SLE : anticardiolipin & lupus anticoagulant – 15-30%

Investigation

All patients with a first thrombotic episode should be screened for anticardiolipin & lupus anticoagulant antibodies

Treatment

Antiphospholipid antibodies

- no thrombosis

- modify 2° risk factors if have antibodies

- aspirin is not protective against thrombosis

Antiphospholipid syndrome

- warfarin 2-2.9 decreases thrombosis rate

Thrombocytopaenia

Definition

Platelet count < 50,000 x 10.6/L

Causes

1.  Defective production

- disturbane of bone marrow

- i.e. secondary to medication

2. Excessive destruction

Drug-Induced Thrombocytopaenia

- Quinine, Sulphonamides, Digoxin, Morphine & H2 antagonists

- drug binds to platelets & acts as Hapten

- form antigenic substances

- complement activation and Platelets lysis

HITS

- 2° AB- heparin-platelet complexes formed & cause platelet aggregation

- thrombocytopaenia from thrombosis

- rapidly reversed once heparin ceased

- should monitor platelet count in patients on heparin

Idiopathic Thrombocytopenic Purpura

- relatively common disorder

3. Excessive splenic pooling

4. Massive transfusion

Effects

Spontaneous bleeding if < 20,000

Post-traumatic bleed increased if < 100,000

Von Willebrand's Disease

Incidence

Most common of the bleeding disorders

- 1:100

Function

vWF            

- needed for platelet adhesion and platelet-platelet interactions

- also carrier for factor VIII / protects it from rapid breakdown

Aetiology

Gene on chromosome 12

1.  Reduced production VWF

2.  Increased proteolysis VWF

Leads to diminished platelet adherence at sites of vascular injury

3 types

Type I      

- quantitative deficit

- mild reduction in VIII:vWF / AD

Type II     

- qualitative deficit

- reduction in proportion of HMW multimers / AD

- mild clinical features, bleeding post-surgery, epistaxis

Type III    

- barely detectable FVIII:vWF (= VIII:C) / AR

- clinically resembles Haemophilia A

Investigations

Bleeding times

- prolonged with normal platelet count

APTT

- slightly increased

vWF assay

- Ag based test

VIII:C

- decreased levels

Clinical

Positive FHx

Common history

- easy bruising

- bleeding post circumcision

- menorragia / post partum bleeding

- nose bleeds, gum bleeding

- bleeding post dental extraction

Severe hemarthrosis

- type III

Management

Mild disease

Desmopressin / DDAVP

- stimulates release of vWF from endothelial cells

- useful only in type 1 / quantitative deficit

Surgery

Cryoprecipitate

- 1 bag / 10 kg bd

- several days after major operation

Gout

Definition

Heterogeneous group of diseases characterised by

- hyperuricaemia

- recurrent attacks of acute arthritis

Diagnosis confirmed by

- crystals of Monosodium Urate in synovial fluid

- tophi ("Porous stone") urate in soft tissues

- renal urate stones

Epidemiology

Adult men

- M:F = 20:1

- peak 40-60 years

Part of metabolic syndrome

- obese / HTN / high cholesterol / diabetes

Often have positive FHx

Physiology

Prerequisite is hyperuricaemia at some stage

- determined by balance between production & excretion

Production

- breakdown of nucleic acids

- oxidation of Purine bases (Guanine & Adenine)

- converted Inosine > Hypoxanthine > Xanthine > Uric Acid

Excretion

- 2/3 excreted into urine

- 1/3 into GIT

- uric acid filtered at glomerulus

- reabsorbed in PCT 

- secreted in subsequent PCT

Classification

A.  Overproducers ~ 10%

Primary

Disturbance of Purine biosynthesis secondary to heritable error of metabolism

- usually idiopathic

- some specific enzyme known eg Lesch-Nyhan syndrome

Lesch-Nyhan Syndrome

- rare 

- X-linked recessive

- absence of enzyme in purine pathway HGPRT

- leads to excessive uric acid formation & gout

- young boys with mental retardation and self-mutilation

Secondary

Diet high in purines

- alcohol / meat / seafood

Myeloproliferative disease

- leukaemia

Chronic hemolysis

Chemotherapy

Drugs eg salicylates, thiazide diuretics

Starvation, ketoacidosis

Alcoholism

B.  Under-excretors ~ 90%

Secondary abnormal renal excretion of Uric acid

- diuretics

- CRF

Pathogenesis

Acute Gouty Arthritis

Sustained hyperuricaemia 

Develop monosodium urate deposits

- in synovial lining cells & in cartilage on PG which are inert

- subsequently released into synovial fluid & CT 

- precipitates at > 8 mg/dl (trauma, low pH)

Sufficient number of crystals in joint precipitates acute inflammation

- phagocytosis of crystals

- release of chemotactic factors & inflammatory mediators

- activate complement & platelets

- disrupt lysosomes in leucocytes with cell rupture 

Chronic Gouty Arthritis

Tophi of Monosodium Urate Monohydrate Crystal aggregates

- deposited in synovium, cartilage & tendon sheaths

- lead to cartilage destruction & periarticular cyst formation

4 stages

1. Initial asymptomatic hyperuricaemia

2. First attack of acute gouty arthritis

3. When this settles, hyperuricaemia persists

- recurrent attacks

- frequency of attacks varies, may increase

4. Chronic gout

- joints no longer recovering from acute attacks

- arthritis & tophi develop

NHx

Hyperuricaemia

- in men begins at puberty

- in women starts at menopause

Risk of gout increases with

- serum urate level

- duration of hyperuricaemia

- usually develops after 20-30 years

Only 5% of hyperuricaemic patients develop gout

Takes days / weeks to resolve

- pain-free intervals of variable length

Clinical presentation

Acute Gouty Arthritis

Predominantly affects distal lower limb

- 70% initially attack 1st MTPJ (Podagra)

May also involve

- Other joints in foot

- ankle

- knee

- hands

Usually monoarticular, rapid onset 

- excruciating night pain

- hot red shiny swollen joint

- very painful to touch

- may have systemic features

- fever / leucocytosis / raised ESR

Onset may be spontaneous

May be precipitated by

- trauma

- excessive activity

- diet excess

- alcohol consumption

- diuretics

- systemic illness

- surgery

Chronic Gouty Arthritis

Arthritis

- after repeated attacks of gout

- asymmetric destructive arthropathy

- often involves small joints in hand

Tophi

- 20% of cases

- white mass of sodium urate crystals

- visible underlying thinned-out skin

- may necrose overlying skin

Sites

- periarticular subcutaneous tissue

- helix of ear

- tendon sheaths especially Achilles

- olecranon / prepatellar bursae

Renal Stones

- 15% of cases

- radiotranslucent uric acid stones

Investigations

Serum Uric Acid

Attacks of gout occur when levels of serum uric acid change

- not necessary to have increased serum urate during acute attack

- elevated serum urate in patient with painful joint not diagnostic of gout

Synovial fluid

Specimen must be anticoagulated

- must be very careful with sample as any water or alcohol put into it will dissolve the crystals

Monosodium urate crystals 

- diagnostic if found in synovial fluid 

- needle-shaped crystals 10um long

- lying free or in neutrophils 

Test

- negatively birefringent under polarised light & parallel to 1st order red compensator

- bright yellow when parallel to compensator

Synovial fluid analysis 

- WCC of 1000 to 70 000 x 10.6/ L 

- predominantly neutrophils (< 70%)

Note

- presence of crystals doesn't exclude infection

- infection precipitates urate

24 hr Urinary Uric Acid Secretion

> 1100mg /day 

- 50% chance renal stones

- treat with Allopurinol

X-ray

Chronic Gouty Arthritis

- usually in feet in phalangeal heads 

- characteristic periarticular bony defects 

- punched out lytic appearance 

- overhanging sclerotic margin (Martell's sign)

- also joint space narrowing & secondary OA 

- no osteopenia compared with RA

DDx 

Pseudo-gout

Septic arthritis

Acute bursitis

Cellulitis

RA

OA

Seronegative spondyloarthropathy

Management

Acute Gout

Medications

Colchicine

Action is as anti-inflammatory

- inhibits activation of inflammatory mediators by crystals

- very effective

- rapid response strongly suggestive of diagnosis

- 1 mg then 0.5 mg q2h up to maximum 6 mg / day

- continue till patient improves / diarrhea occurs / maximum dose

- 80% of patients unable to tolerate optimum dose because of GIT side-effects

NSAID

Usually better tolerated than colchicine

- indomethacin most commonly used

- 50 mg t.d.s

- side effects include GIT toxicity / Sodium retention / CNS disturbance

ACTH

Adrenocorticotrophic Hormone

- good for acute attack

- minimal side effects

- single 40 IU IM injection

Glucocorticoids

Oral Prednisone

- if colchicine not tolerated / NSAID contraindicated

Intra-articular steroids

- may be used for severe monoarticular attack

- especially knee

Prophylaxis

3 Tier Approach

Initial 

Lose weight

Increase fluids intack

Aim to decrease Purine intake and avoid precipitating factors

- alcohol

- diuretics

- diet - meat, seafood

2nd Stage

- Probenecid

3rd Stage

- Allopurinol

- beware hypersensitivity / bone marrow suppression

Antihyperuricaemics

Absolute indications

- CRF secondary to kidney stones 

Relative indications

- > 3 acute attacks / year

- polyarticular gout

- tophi

- uric acid > 500 mmol/l

Options

1. Increase Renal Uric Acid Excretion / Uricosuric

- Probenecid

- require good renal function

2. Decrease Uric Acid Synthesis

- Allopurinol

Allopurinol

Inhibits Xanthine Oxidase

- 300 mg/day (150 if CRF) 

- hypersensitivity side effects in 20% 

Causes decrease in serum uric acid & this may precipitate acute attack of gout

- initiation of treatment should be accompanied by Colchicine or NSAIDS

- never used in acute gouty attack

- can shrink tophi if keep serum urate < 0.4mmol/l

Side effects can be fatal

- rash

- alopecia

- marrow suppression

- hepatitis

Hydroxyapatite Deposition

Types

Dystrophic or Metastatic

1.  Metastatic 

- hypercalcaemia / hyperphosphatemia

2.  Dystrophic 

- more common

- onto damaged connective tissue

- tendon / ligament / cartilage

- calcific tendonitis shoulder

- Pellegrini-Steida lesion MCL

Pathology

Deposited around chondrocytes & into avascular portion of CT

- crystals grow by accretion

- early on like cream

- later like chalk

- can be inert or surrounded by inflammatory reaction

- crystal shedding into joint causes synovitis

Clinical Features

Two syndromes

1.  Acute or Subacute Periarthritis

Pain near a large joint

- not intra articular

- after minor trauma

- warm & swollen tendon / ligament

- calcific tendinitis rotator cuff

- Pellegrini-Stieda lesion MCL

2.  Chronic Destructive Arthritis

HA crystals found in association chronic erosive arthritis

- unknown if cause or effect

- destructive arthropathy seen in shoulder with cuff arthropathy

- i.e. Milwaukee shoulder

- whether related to HA unknown

Aspiration

Crystals too small to be seen with light microscopy

- hence will not see on aspiration

X-ray

Periarthritis seen as calcium in tendon

- especially rotator cuff

- chronic HA arthritis doesn't show on xray as well as CPPD

Management 

Non operative

Periarthritis

- RICE

- NSAID

- HCLA

Operative

Surgical removal

- calcific tendonitis

- problematic Pellegrini Steida

Chronic Arthritis

- treat as OA

- early arthroplasty if rapid bone destruction

Ochronosis

Definition

Degenerative arthropathy due to Alkaptonuria

Metabolics

Rare hereditary disorder of tyrosine and phenylalanine breakdown

Homogentisic acid enzyme deficiency

- accumulate Homogentisic Acid

- product of tyrosine breakdown

Homogentisic acid deposited in cartilage & other soft tissues

- polymerises 

- pathology probably due to a disruption of collagen cross links by metabolites of homogentisic acid

Clinical

Urine turns dark on standing 

- also when alkalised

- hence the name

Sweat stains clothes

Cartilage & connective tissue stained grey

- brownish-black pigment in connective tissue

- calcified cartilage

- deposits in virtually all cartilages

- discs, sclera, skin

Arthropathy

- early OA secondary to  brittleness 

- presents 4th decade 

- back pain then knees / shoulders / hips

- most common presenting complaint

Spondylosis

- especially affects spine

- difficult to differentiate from ankylosing spondylitis

- dense calcification of discs with narrowing of intervertebral space

Pseudogout

Definition

Pseudogout 

- Calcium Pyrophosphate Dihydrate (CPPD) crystals

- inflammatory arthritis of older individuals 

Chondrocalcinosis

- refers to any calcium in cartilage / menisci

Epidemiology 

M:F 2:1

Patient > 50

Sometimes familial

Association

DM

Hypothyroidism

Gout

Hyperparathyroidism

Haemochromatosis

Pernicious Anaemia

Onchronosis

Pathology

CPPD deposited in

- joint capsule

- articular cartilage

- fibrocartilage / meniscus

Crystals seen at margin of degenerating cartilage

- pyrophosphate generated at chondrocyte surface in abnormal cartilage

- combine with calcium to form crystals

Occasionally the crystals are released into the joint & an acute arthritis results

- activation of vasoactive & chemotactic factors

- neutrophils attracted & phagocytose crystals

- release of lysosomal enzymes into joint fluid

Chronic chondrocalcinosis predisposes to development of 2° OA 

- crystals embedded in articular cartilage have desiccating effect

Clinical presentations

1. Asymptomatic Chondrocalcinosis

Majority of people

- incidental finding

- calcium of menisci

- usually involved with degenerative changes

2. Pseudogout

Rapid onset inflammatory arthritis

- peak in 24/24

- subsides in 1/52

May be provoked by

- trauma

- surgery

- illness

Usually affects large joints

- Knee > Shoulder > Wrist

- typically monoarticular

- less pain than gout

3. Chronic CPPD Arthropathy

OA 2° CPPD

Pseudo-Osteoarthritis

- polyarticular disease like OA

- in hips & knees

- due to CPPD in cartilage altering the biomechanics

In more unusual joints for OA

- ankles, shoulders, elbows

- very common in PFJ

- has radiodense crystals

4. Pseudo- Rheumatoid Arthritis

Acute synovitis & chronic arthritis

- rapidly progressive joint destruction

Synovial Fluid

CPPD crystals seen extracellular & in neutrophils

- rhomboidal

- weakly positively birefringent 

- IE Blue parallel to 1° order red filter & 135° to polarizer

X-ray

Chondrocalcinosis

Calcium in fibrocartilage & CT 

- punctate densities

- menisci / TFCC / pubis / annulus

Findings of OA usually present

Unusally joints

- PFJ

Screening Bloods

Ca / PTH

U&E

Serum Fe / Fe studies

TFT

Serum Alk Phos

Differential Diagnoses

Hyperparathyroidism          

X-rays show subperiosteal erosions

Blood tests show hypercalcemia / increased PTH

Ochronosis 

Often severely affects spine / shoulders / hips / knees

Hemochromatosis

Disorder where iron deposited in many tissues including articular cartilage

- concomitantly get cirrhosis of the liver / CCF /diabetes / bronze skin

- chondrocalcinosis often prominent feature

- calcification of multiple joints and discs

- serum Fe and IBC raised

Management

Options

1.  NSAIDS

2.  HCLA

3.  Colchicine

- 80% response 

4.  Joint washout

Joint washout

Don't debride / perform synovectomy

Worsens symptoms

Basic Science

Pathogenesis

Virchow's Triad

1. Venous stasis

2. Hypercoagulability

3. Endothelial damage

Starts as platelet nidus at valves

- thrombogenic materials elaborated by platelets

- leads to development of fibrin thrombus

- thrombus grows

Thrombus may 

- detach as embolus

- be completely dissolved / recanalise

- organise with valve incompetence

Risk factors

1.  Patient

Previous DVT

Increasing Age

Obesity

Varicose veins

Immobility

Pregnancy

OCP / HRT

Smokers

Inherited Thrombophilia

Paralysis

Malignancy

Recent MI

2. Disease / Surgery

Trauma or surgery

Malignancy

Infection

Risk Groups

High Risk

Family history

Past History DVT/PE

OCP / Pregnancy / HRT

OT to pelvis & hip

Obesity

Hypercoagulable state

Varicose veins

Moderate Risk

Major surgery in age > 40

Major medical illness

Any large surgical procedure

Obese

Low Risk

Minor surgery < 30 min

Immediate mobilization

Rates without Prophylaxis

DVT rates without prophylaxis

- THR 50-70%

- TKR 50%

PE rates without prophylaxis

- asymptomatic PE 10 - 20%

- symptomatic PE 2%

- fatal PE 0.1 - 0.2%

Timing

DVT

- peak Day 3

- 80% of DVT occur during inpatient stay

- can occur as late as day 40

PE

- 50% fatal PE's > 3/52 i.e. occur at home

Fatal PE & Theory of Propagation

Calf DVT

- calf DVT has 20% chance of propagation

- ? PE less likely

Proximal thrombi 

- are at greatest risk of embolism 

- 50% chance PE

Screening DVT 

Issue

- should all high risk patients get regular ultrasound?

- i.e early diagnosis and treatment to avoid PE

Problem

- 80% PE without clinical evidence DVT

- 2/3 patients with fatal PE die in 30min

Effect

PE leads to hypoxaemia from

- VQ mismatch 

- Right Heart Failure

Diagnosis DVT

1.  Clinical

- inaccurate

- non specific & non sensitive

- 50% patients with DVT have no clinical signs

- 50% with suggestive clinical signs have negative venogram

2.  Venography

Gold standard

- sensitivity & specificity >95%

- outlines entire deep venous system of leg

Disadvantage

- invasive

- expensive

- 5% can't cannulate foot

- requires expertise

- risk of inducing DVT 1%

- contrast reaction 0.02%

- doesn't visualise pelvic veins

3.  Duplex Ultrasound Scanning

Real-time US combined with colour imaging

- veins visualised

- femoral & popliteal veins visualised

- presence of lumen, compressibility & flow assessed

- sensitivity & specificity for proximal thrombi 95%+

- sensitivity only 70% calf DVT

Advantage

- non-invasive

- rapid & inexpensive

- use only above the knee

Disadvantage

- poor test if poor equipment & inexperienced user

Results

Schellong et al J Thromb Haemost 2007

- VENUS study

- compared venography to compression ultrasound in same patient

- 1100 orthopedic patients on oral anticoagulant

- venography rate of DVT was 19%

- ultrasound rate of DVT was 11.5%

- US sensitivity 31%  specificity 98%

Diagnosis Pulmonary Embolus

Clinical

- unhelpful

- symptoms & signs non-specific

D Dimer

- always raised post op

- useful in low risk patient

- negative D dimer in this group excludes DVT

ECG

- usually sinus tachycardia

- right heart strain - S1 Q3 T3 (20%)

CXR

- usually normal

- exclude pneumonia

ABG's

- sensitive but not specific

- hypoxemia / hypocapnia / respiratory alkalosis

VQ Scan

Te99 labelled Albumin spheres trapped in capillaries /  Xenon33 Gas in alveoli

- both detected by scintiscan

- compared with each other for mismatch

Advantage

- non-invasive

Disadvantage

- results not always clear-cut

- intermediate and high risk

- require further investigation

- low probability - 2% risk PE

CT Pulmonary Angiogram

Advantage

- definitive

Disadvantage

- difficult & expensive

- risk of contrast reactions

MRI

Useful for pelvic DVT

- patient with entire leg swollen

- negative ultrasound

- particularly post THR / pelvic / acetabular surgery

Management

DVT / PE 

Established DVT & PE

- treat with anticoagulation

- prevent further clot propagation / embolisation

- allows fibrinolytic system to act unopposed

- does not directly dissolve thrombus

Calf DVT 

- treatment debatable

- risk PE low but not zero

- 20% propagation rate

- usually treat for 3 months

- can give aspirin and repeat US in 7 - 10 days

Screening for Thrombophilia

Protein C / Protein S deficiency

Anti-thrombin 3 deficiency

Factor 5 Liaden (activated protein C / APC)

Lupus anticoagulant

Cardiolipin

Prophylaxis

Can be divided into

- mechanical prophylaxis & chemoprophylaxis

- preoperative, intraoperative, & postoperative

Mechanical

Early mobilisation

TEDS

Sequential Compression Devices

Foot pumps

Chemoprophylaxis

LMWH / Heparin / Warfarin / Aspirin / Oral Factor X inhibitors

Preoperative

Screen for high-risk groups

- obesity 

- Family Hx

- previous DVT/ PE

- varicose veins

- yypercoagulable states

- OCP / HRT / smoking

Stop smoking & HRT

Preoperative clinic to encourage exercises & post-op regimen (education)

- admit day of surgery

Keep well-hydrated

Intraoperative

Regional anaesthesia

Planes et al JBJS Br 1991

- RCT of GA v Spinal with enoxeparin in patients with THR

- 6% proximal DCT in each group

- 0% distal DCT in GA group v 5% rate distal DVT in spinal group

- enoxeparin 40 mg sc day before GA

Intraoperative mechanical prophylaxis

- compression on other leg

Consider

Tourniquet

- cuff width at least 30% diameter of leg

- tapered low-pressure cuff if possible

- minimal tourniquet time

Minimal tissue damage & bleeding

- activates coagulation cascade

Avoid extremes of flexion for long periods

Avoid extrinsic pressure to limb

- care of position & extrinsic pressure to other leg

Postoperative

1.  Early mobilisation

2.  Early chemoprophylaxis

3.  Early mechanical prophylaxis

- TEDS

- foot-pumps & Sequential Compression Devices

- applied in OT

- until mobile

Check calves daily for tenderness & swelling

Spinal surgery

FDA

- does not approve chemoprophylaxis for any spinal procedure

Epidurals

Epidural haematoma

- most often on removal of epidural

- 1:2 000 without chemoprophyaxis

- 3: 1 000 with Clexane

- not within 24 hours of insertion or removal

Chemoprophylaxis

Heparin

Biochemistry

Naturally occurring anticoagulant

- mixture of sulphated mucopolysaccharide chains

- heterogenous molecular weights

- average ~ 15 000 daltons

Found in granules of mast cells

- mast cells have IgE receptors on surface

- discharge when IgE-coated antigens bind to receptors

- mediate allergic reactions

Action

Facilitates action of Anti-Thrombin III

- binds to it & causes conformational change 

- increased affinity for thrombin (x 1000) & Xa

- also inhibits aggregation of platelets

Pharmacology

Calcium / Sodium heparin 

Half-life

- 2 hours

Reversed with Protamine

Treatment Dose

Bolus 5000 units IV

Maintenance 1000 u /hr

Maintain APTT 70-120

Levels

- check after 6 hours

- 6 hours after any change in infusion rate

- daily APTT otherwise

Prophylaxis Dose

Fixed low-dose heparin

- 5000 units s/c bd or tds

Complications

Wound haematoma

Heparin Induced Thrombocytopenias / HITS

- paradoxical thrombosis 

- occurs in 10-15% of patients receiving heparin

- due to drug-antibody binding to platelets

- resolves promptly with ceasing heparin

- 80% cross-reactivity with LMWHs

LMWH (Low Molecular Weight Heparin)

Definition

Fractionated heparin

- derived from heparin by chemical / enzymatic depolymerisation 

- MW 5000

Action

Pure Anti Xa 

- to inactivate thrombin the chain has to attach to antithrombin III & heparin simultaneously

- because LMWH are too short to do this they only inhibit Xa

- less platelet interaction

Increased anti-thrombosis 

Decreased bleeding

- because no anti-thrombin action

Pharmacology

Longer T1/2 x4

Increased bioavailability 90% vs 30%

- doesn't bind to plasma proteins as heparin does

Clexane / Enoxeparin

Derived from the intestinal mucosa of pigs

Dosing

- 0.5 mg/kg od for prophylaxis

- 1mg/kg od therapeutic dose

No monitoring required

Reduce dose

- GFR < 30

Reversal

- protamine has some, but reduced effect

Fragmin / Dalteparin

Dose

- 5000IU od

Results

Hull et al Arch Int Med 2000

- RCT of 1000 THR of warfarin v dalteparin

- warfarin had rates total DVT 24%, proximal DVT 1% and symptomatic DVT 4.5%

- dalteparin had rates total DVT 13%, proximal DVT 1% and symptomatic DVT 1.5%

- dalteparin preoperatively had slightly decreased rates of total DVT but increased bleeding

Oral Factor Xa inhibitors

Mechanism

Act directly on Factor X

- do not use ATIII as an intermediate

Advantage

Oral administration

- make OPD dosing more simple

- don't require monitoring

Interaction

Statins

Xarelto / Rivaroxaban

Dose

- 10 mg od

Results

Kakkar et al Lancet 2008

- RCT of 2500 THR patients

- 35 days of rivaroxaban v 14 days enoxeparin

- incidence DVT and non fatal PE 2% in rivaroxaban v 9% in enoxeparin (significant)

- incidence of bleeding was 6% rivaroxaban and 5% enoxeparin (non significant)

Turpie et al Lancet 2009

- RCT of 3100 TKR patients

- rivaroxaban v enoxeparin 10 - 14 days

- incidence of DCT / non fatal PE 7% rivaroxaban v 10% enozeparin (significant)

- incidence of bleeding 0.7% rivaroxaban v 0.3% enoxeparin (non significant)

Warfarin

Mechanism

Structural analogue of vitamin K 

- blocks the activation of vitamin K

- factors II, VII, IX, X & Protein C + S are vitamin K dependent 

Disadvantage

1.  Paradoxical procoagulant effect

- initial period

- needs cover with another anticoagulant

2.  Teratogenic

- contraindicated in pregnancy

3.  Delayed Effect

- half-life of factors ranges between 6 and 60 hours

- FVII has the shortest half-life and is the first to be affected

- decrease of FVII increases PT

- there is a window period of 3/7 with increased PT but no true anticoagulation exists

- must cover patient for the first 3 days

4.  Requires monitoring

Metabolism

Oral warfarin is readily absorbed & almost entirely albumin-bound

Metabolised in liver

Potentiators

- Cimetidine

- Phenytoin

- Trimethoprim

- Cephalosporins 

- Tramadol 

Inhibitors

- Rifampicin

- Phenobarbitone

Reversed with parenteral Vit K or FFP

Dosing

Starts simultaneously

- 5 mg nocte for 2 days

- then daily dose as per INR 

- usually 3 - 5 mg

Treatment INR

- 1.5-2.5 DVT

- 2.5-4.0 PE

Prophylaxis INR

- 1.5 - 2

Results

Mismetti et al J Thromb Hemost 2004

- meta-analysis

- vitamin K antagonists less effective than LMWH in preventing total or proximal DVT

- no significant difference in rates of major bleeding or haematoma

Aspirin

Mechanism

- irreversibly inhibits cyclo-oxygenase in platelets & megakaryocytes

- blocks thromboxane A2 formation

Dosing

150 - 300 mg od

Disadvantages

GI bleeding

Results

PEP Trial

- RCT aspirin v placebo after 13 000 hip fractures and 4000 TKR/THR

- > 99% follow up for 35 days

IVC Filter

Indications

- complications of anticoagulation therapy

- recurrence of PE whist fully anticoagulation

- high rate of death if subsequent event / further embolic load on right ventricle

Disadvantage

Surgical procedure

- inserted through groin

- need to be removed

Results

Bicalo et al J Arthroplasty

- filter vs IV heparin

- 3 of 28 complications for heparin

- 1 of 26 for filter

Mechanical Prophylaxis

Options

Early Mobilisation +

Compression Stockings

Pneumatic Compression Devices

Foot Pumps

1.  Graduated Compression Stockings

Mechanism

Antiembolism stockings

- apply graded compression

- highest at ankle

- lowest above knee

- attempt to increase flow

- may cause venous stasis if improperly fitted or roll down

Precaution

Check pulses

- not to be used if vascular compromise

- ABI < 1.0

Size correctly

Results

Sachdeva et al Cochrane Database Review 2010

- 8 x RCT's of GCS alone v no GCS

- rates DVT 13% v 26%

- 10 x RCT's of GCS + another method v other method alone

- rates DVT 4% v 16%

2. Pneumatic Compression Devices

Results

Kakkos et al Cochrane Database Review 2008

- RCT of PCD alone v PCD + another method

- PCD alone had incidence symptomatic PE 3% and DVT 4%

- PCD + another method incidence symptomatic PE 1% and DVT 1%

- pharmacological alone had DVT 4% v pharmacological + PCD DVT 1%

3.  Foot pump

Disadvantage

Not tolerated by some patients

- uncomfortable

- disturbs sleep

Results

Warwick et al JBJS Am 1998

- RCT of enoxeparin v foot pumps

- DVT rate of 13% enoxeparin and 18% foot pumps

- no major proximal DVT in either group

Infection Prevention

Microbes & Antibiotics

Osteomyelitis

Septic Arthritis

Definition

Joint inflammation secondary pyogenic organism

Epidemiology

All age groups

Usually children

- 50% < age 3

M= F

Any joint

- Infants = Hip

- Children = Knee

- Adults = Large Joints

IVDU - SCJ & SIJ

Pathogenesis

Two Routes

1.  Haematogenous

- distant focus

- seeds synovial membrane 

2.  Direct Extension

A.  Osteomyelitis

- neonates & children

- from adjacent focus of OM 

(i) Via Trans-physeal vessels in neonates

- Haversian & Volkmann's canals in children

(ii)  Intra-articular metaphysis

- proximal & distal femur 

- humerus

- proximal tibia

- ? distal fibula

B.  Overlying Soft tissue Infection

C.  Inoculation

- penetrating injury

- iatrogenic

Predisposition

Host

- immunodeficiencies

Joint

- previous joint trauma

- RA

- previous HCLA

Bacteraemia

Aetiology

Microbes vary with age

Neonates  < 1/12

60% hospital acquired

- premature or unwell

- group B streptococci most common

- E coli & other Gram negative bacilli

- S aureus

Infants & Children <3 years

S Aureus 

S. pneumoniae / pyogenes

H Influenzae 

- reduced by immunisation

Children > 3 years

As above

Adults

S Aureus > Strep > G -ve 

N. gonorrhoeae 

- most common in young healthy adult / 70%

- may be polyarticular / associated with rash

- urethral swab / joint fluid PCR

- can treat with antibiotics alone

- usually no need for drainage unless fail to respond

IVDU - Gram negative

Community-Acquired

- S Aureus / MRSA

- Group B Strep

Kingella kingae

- Gram negative coccobacillus

- previously unrecognised

- because is slow and difficult to grow

- colonises nasopharynx, spread through blood stream

- take 14 days to culture

- put in specific BACTEC culture bottle

- sensitive to penicillin

Pathology

Synovium oedematous & hyperaemic

- cloudy synovial fluid

> 2/7 frank pus 

- cartilage destruction

- starts at areas of joint contact 

Synovial membrane replaced by granulation tissue

- adhesions wall off pockets of pus

- fibrous ankylosis

Physis destroyed if intracapsular i.e. hip

- joint dislocation

- AVN femoral head

- Tom Smith OA

Cartilage Destruction

1.  Proteolytic Enzymes

- Lysosomal - Collagenase / protease

- from neutrophils / microbes / synovium

2.  Inflammatory cascade

3.  Pressure 

- degrades cartilage

- AVN / dislocation

Clinical Features

Infant

History prior infection

- Eg umbilical sepsis

Irritability / failure to thrive

Low fever ~ Beware

Joint warm & swollen

Decreased active ROM 

- pseudoparalysis

Intra-articular pressure high

- joints held in position to maximise joint volume

- hip abducted / flexed / ER

- knee flexed

Painful and decreased ROM

Child 

As above

- easier to localise

Psoas sign

- pain on extension and IR

Bloods

ESR

Erythrocyte sedimentation rate

- stickiness of RBC

- reflects fibrinogen concentration

- centrifuge blood tube and measure time to settle

- > 30

Not reliable in first 48/24 / Neonate / Steroids

Takes weeks to drop (3/12)

- lags behind resolution

CRP

Acute phase protein synthesised by liver

- > 10

WCC + differential

Elevate in 40 - 60%

- PMN leukocytosis

- left shift

Blood Culture

Positive 40 - 60%

Aspiration

Indications

- knee / ankle

- shoulder / elbow

- ASAP

Contra-indications

- neonate hip

- aspiration difficult & need GA

- drain ASAP

MCS & Cell count

WCC > 50 000 per ml

Neutrophils > 75%

Gram stain Positve 30%

Culture positive 60%

X-ray

Neonate Hip 

- wide joint space

- subluxed 

- 1° OM in metaphysis

Sequelae of hip septic arthritis

- Tom Smith's arthritis of infancy

- 6mth old with dislocated hip & normal acetabulum 

- indicating recent onset injury to hip

- complete AVN of head

Te Scan 

DDx focal metaphyseal OM 

Identify AVN femoral head

US

100% sensitive at detecting fluid in joint

- useful to diagnose hip effusion

MRI

DDx

- OM

- psoas abscess

Diagnosis

Transient synovitis v Septic Arthritis

Kocher criteria (for child with painful hip)

- fever

- Inability to weight bear on affected side

- ESR > 40

- WCC > 12000

4/4 criteria

- 99% chance that the child has septic arthritis

3/4 criteria

- 93% chance of septic arthritis

2/4 criteria

- 40% chance of septic arthritis

1/4 criteria 

- 3% chance of septic arthritis

DDX

Infants & Child

1. Acute OM - Can get symptomatic effusion

2. Cellulitis

3. Transient Synovitis - Afebrile / ESR normal

4.  Psoas abscess

5. JRA 

6. Trauma

7. Perthes / SUFE in hip

8. Haemophilia

Adults

1. Gout 

2. Pseudogout 

3. RA / other inflammatory arthritis

Management

1.  Surgical Drainage

Surgical emergency

- arthrotomy or arthroscopy

- Washout pus +++

- ± Synovectomy

- closure over drain

Hip

- anterior approach / Smith Petersen approach

- preserves blood supply to femoral head

- allows inspection of femoral metaphysis for OM

- between TFL and sartorius / G. med and RF

- 1 cm capsulotomy

- +/- drill neck (MRI useful to detect OM)

- leave capsule open

- close over drain

- assess hip stability

- may need brace or POP

2.  Antibiotics

Start after MCS

- start broad spectrum bacteriocidal

- gram stain as guide

Choice

- Flucloxacillin & Gentamicin adults

- Flucloxacillin & Ceftriaxone paeds

Timing

- IV AB until systemic toxicity & local swelling subside & CRP normal

- ~ 2/52

- usually continue oral antibiotics for further 4/52

Complications

Joint destruction - ankylosis / OA

Neonate Hips 

- dislocation / subluxation

- destroyed epiphysis - Growth disturbance / LLD / coxa vara / breva

- absence of head / AVN

- pseudoarthrosis of femoral neck

Synovial Fluid Analysis

Cell Counts x 10⁶/L

Done by a grid system per HPF

- x40

- averaged over 10 fields

Normal

- 0-200

Non Inflamm (Trauma / OA)

- 50 - 500

Inflamm (RA / Crystals)

- 1500 - 50 000

Infection

- > 50 000

- exception is gonococcal arthritis

Different Units

Standard now SI Units 10 x 10⁶/ L  

= 10 cells / mm³

= 10  x  10³ /ml 

= 10  x  10³ /cc

= 10  x  10⁵ /dl

= 10  x  10⁵ /100ml

= 10  x  10⁶ / L

Cell Differential

Polymorph % 

- normal 0-25 %

- non inflammatory = 0- 25 %

- inflammatory = 30- 70 %

- infection  > 75 %

Viscosity

- will decrease as inflamation increases

- effect of hyluronate lost

- hence sepsis = Low viscosity

Additional

Glucose < BSL

± Crystals as acid Ph decreases solubility

- presence of crystals does not exclude infection

Gram stain positive 30%

Culture positive 60%

Weinstein

WCC > 50,000 + > 90% PMN leukocytes

- should be considered infectious regardless of the culture results 

Fink Clin Rheum Dis 1986;12:423. 

- large series of culture-proven cases of bacterial septic arthritis

- only 44% had cell counts > 100,000 per mm3

- 34% of cases having counts of < 25,000 per mL

Unusual Infections