Everything You Need to Know MSS

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ONNAZLI0809

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ONNAZLI0809

OSTEOGENESIS IMPERFECTA/TYPE I COLLAGEN DISEASE/BRITTLE BONE DISEASE

Definition

can be defined as a group of phenotypically related disorder that are caused by deficiencies in the

synthesis of collagen type I. It can be classified to 4 types which the type II is the worst (resulting in

death in the uterus or within days of birth)

Causes

mutation in genes that code α1 and α2 chains of collagen molecules

inherited – autosomal dominant fashion (mostly)

inherited – autosomal recessive fashion (rarely)

Morphology

“too little bone”

Thinning of the cortical part of bone

Attenuation of the trabeculae

Persistent foci of hypercellular woven bone

Clinical features

Multiple fracture from minimal trauma – due to extreme skeletal fragility

Blue sclera – sclera becomes translucent allowing partial visualization of the underlying

choroid due to reduce collagen content of the sclera

Hearing loss – due to both sensorineural deficit and impaired conduction because of the

abnormalities of the middle and inner ear bones

Dental imperfections – due to deficiency in dentin

Heart valve disorder – less collagen component

Hypermobility of joints

Treatments

Bisphosphonates – to enhance the bone cortical thickness



ONNAZLI0809

DEVELOPMENTAL (GENETIC) AND ACQUIRED ABNORMALITIES IN BONE CELLS, MATRIX AND

STRUCTURES

It can be classified to;

1.

Defects in nuclear proteins and transcriptional factors Failure of developmental of the bone (phalanx, rib, clavicle)

Formation of extra bones

Fusion of adjacent digits

Craniorachischissis (failure of closure of spinal column and skull)

2. Defects in hormones and signal transduction

Achondroplasia

Thanatophoric dwarfism

3. Defects in extracellular structural proteins

Type I collagen diseases

Type 2, 10 and 11 collagen disease

4. Defects in folding and degradation of macromolecules

Mucopolysaccharidoses

5. Defects in metabolic pathway (enzymes, ion channels and transporters)

Osteopetrosis

6. Decrease in bone mass

Osteoporosis

7. Osteoclast dysfunction

Paget disease

8. Abnormal mineral homeostasis

Rickets and osteomalacia

Hyperparathyroidisme

Renal osteodystrophy



ONNAZLI0809

OSTEOPETROSIS/MARBLE BONE DISEASE/ALBERT-SCHONBERG DISEASE

Definition

is a rare genetic disease characterized by reduction in osteoclast activity resulting in diffuse

symmetrical skeletal sclerosis

Causes

Autosomal recessive – malignant type

Autosomal dominant – benign type

Pathogenesis

1. Deficiency in Carbonic Anhydrase II (CA II)

2. Mutation of CIC-7 chloride channel gate

Morphology

Gross morphology

1. Lack of medullary canal

2. Bulging end of long bone and misshapen

3. Small neural foramina, compressing the nerve

4. Bones formed are not remodelled and usually woven in architecture

Histology

1. Normal number of osteoclast

1. Osteoclast use CA II to acidify and resorp

bones. Deficiency in CA II prevent

osteoclast to acidify resorption pit and

solubilising hydroxyapatite crystal

2. CIC-7 chloride channel gate located at

ruffled borders of osteoclast. It is

important for proton pump H+/ATPase



ONNAZLI0809

Clinical features

1. Malignant type

Fracture occurs commonly – due to woven bone architecture

Anaemia – lack of medullary canal

Hydrocephalus – due to anaemia

Hepatosplenomegally – increase extramedullary erythropoiesis

Mental retardation

Infections

2. Benign type

Repeated fracture

Infections

Increase level of acid phosphate





ONNAZLI0809

Morphology

1. Postmenopausal osteoporosis

- Usually affects bone that have high surface area – e.g. cancellous compartment of

vertebrae commonly affected

- Thinned osteoporotic trabeculae and lose interconnections (loss of horizontal trabeculae

– thickens of vertical trabeculae)

- Progressive micro fractures – leads to vertebral collapse

2. Senile osteoporosis

- Thinning of osteoporotic cortex by subperiosteal and endosteal resorption

- Widened Harvesian system

Clinical features

1. Fracture2. Vertebral crush fracture leads to severe back pain, radiating to front. Increase kyphosis,

height loss and abdominal protuberance

Investigations

1. Dual energy X-ray absorptiometry – reliable to measure bone density (mineral per surface

area)

2. Quantitative ultrasound of calcaeneum

3. Quantitative CT scanning – allows true assessment and distinct between trabecular and

cortical bone

Treatment

1. Exercise

2. 700 – 1000 mg Calcium diet daily

3. Cessate smoking

4. Estrogen replacing agents

5. Bisphophonates

6. Recombinant PTH



ONNAZLI0809

PAGET DISEASE/OSTEITIS DEFORMANS

Definition

Is a chronic focal disorder of bone remodelling

Causes

- Paramyxovirus

- Subacute sclerosing leukoencephalitis

- Measles

Pathogenesis

Morphology

Histological features1. Mosaic pattern of lamellar bone – represent jigsaw puzzle

2. Initial phase – waves of osteoclastic activity and numerous resorption pit

3. Mixed phase – bone surfaces are lined by prominent osteoblast. Marrow contains numerous

blood vessels as well as loose connective tissue (osteoprogenitor cell)

4. Osteosclerotic phase – fills with coarsely trabeculae and cortical that are soft and porous

and lack of structural stability

Measles virus/paramyxovirus/subacute sclerosing

leukoencephalitis infections

1. Initial osteolytic phase – infected cells secrete cytokines

(IL-6) and Pagetic bone produce M-CSF

Both IL-6 and M-CSF are chemotactic to osteoclast leading to

increase in osteoclastic activity

The osteoclast are hyperactive (predispose locus on

chromosome 18q)

2. Mixed phase – compensatory mechanism to increase in

new bone formation, increase in local blood flow as well

as fibrous tissue

Ends with predominantly osteoblastic activity

3. Burnt out quiescent osteosclerotic phase – new bone

formed but structurally abnormal



ONNAZLI0809

Clinical features

1. Bone pain – caused by microfractures and bone overgrowth that compress spinal and cranial

nerve

2. Compression fracture – shows sign like kyphosis or lordoisis

3. Pathological fracture

4. Deformities – anterior bowing of femur and tibia, distorts femoral head leading to arthritis

5. Cardiac hypertrophy – owing to increase blood supply to the bone

Investigation

1. X –ray – 1) in lytic phase – central and endosteal cortical resorption and replacement by less

compact new bone 2) in sclerotic phase – thickened trabeculae, loss of distinction between

cortex and trabeculae

2. Bone scans

3. Serum alkaline phosphatase - increase



ONNAZLI0809

RICKETS AND OSTEOMALACIA

Definition

Rickets (in children) and osteomalacia (in adults) is an inadequate mineralization of bone matrix due

to defects in vitamin D availability or metabolisme.

Causes

Vitamin D deficiency Renal disease Others

Skin synthesis

Malabsorption

Malnutrition

Chronic renal failure

Dialysis

Tubular disorder (ATN, APN)

Vitamin D dependant rickets

Tumor

Pathogenesis

Vitamin D deficiency

Reduce substrate for renal α1 hydroxylase

Reduce formation of 1,25-dihydroxycholecalciferol

Reduce absorption of calcium and phosphate in the gut

Reduce serum level of calcium and phosphate

Activates parathyroid hormone

Increase calcium absorption in the renal but promotes

phosphate excretion via urine

Serum calcium level normal but phosphate level decrease

Impaired mineralization for bone formation

Bone formation abnormal

Rickets (children) and osteomalacia (adults)



ONNAZLI0809

Clinical features

1. Pathological fractures

2. Waddling gait

3. Neonatal – thin deformed skull

4. Widened epiphyses at wrist

5. Beading at costochondral junction

6. Groove in the rib cage (Harrison’s sulcus)

Investigations

1. Increase serum alkaline phosphatise – increase osteoblastic activity

2. Serum phosphate reduce – increase PTH

3. Serum 1,25-DHCC decrease

4. X-ray – showing Looser’s zones (linear area of reduce density surrounded by sclerotic body)

Treatment

1. Oral vitamin D supplement



ONNAZLI0809

OSTEOMYELITIS

Definition

Is an inflammation of bone and bone marrow due to infections. It can be local or systemic

Causes

In adults In neonates

Staphylococcus aureus

Escherichia coli

Pseudomonas sp

Klebsiella sp

Mycobacterium tuberculosis

Haemophilus influenza

Group B streptococci sp

Pathogenesis

Bacteria enters the bones via

1. Direct penetration

Bacterial organism introduced directly into the bone by penetrating the wounds,

fractures or surgery

Staphylococcus sp and streptococcus sp are common

2. Haematogenous spread

Arise from focus (skin pustules, infected teeth and gums etc) elsewhere in the body

and through bloodstream, it reaches the bone.

Likely to spread to the metaphyses of the long bones such as ankle, knee, hip etc

Tuberculosis is the commonest bacteria causing osteomyelitis via haematogenous

spread (non-neoplastic metastasis)

3. Direct seeding

Pulmonary tuberculosis affecting the lung and give rise to the formation of

pulmonary focus. This focus can directly transfer the bacteria to the bones such as

ribs and thoracic vertebra.

Morphology

Pyogenic osteomyelitis

1. Cloaca – hole formed in the bone during formation of a draining sinus

2. Sequestrum – fragments of necrotic bones that are embedded in the pus

3. Brodie abscess – reactive bone from periosteum and endosteum whic surrounds and

contains the infections

4. Involucrum – lesion in which periosteal new bone formation forms a sheath around the

necrotic sequestrum



ONNAZLI0809

Morphology

Tuberculous osteomyelitis

1. Granuloma produce caseous necrosis of the bone marrow

2. Slow resorption of bony trabecullae

3. Formation of cystic spaces in the bone

Clinical features

Pyogenic osteomyelitis

1. Fever with chills and rigors

2. Malaise

3. Leukocytosis

4. Throbbing pain at the affected site

Tuberculous osteomyelitis

1. Pain in motion

2. Localize tenderness

3. Low grade fever

4. Loss of appetite

5. Kyphotic and scoliotic deformities – compression fracture of vertebra

Treatment

1. Cloxacillin

2. Fusidic acid

3. Immobilization

Complications

1. Septicaemia – infection disseminated to the blood stream

2. Acute bacterial arthritis – direct ‘digestion’ (cytokines effect) by inflammatory cells destroy

srticular cartilage, producing osteoarthritis

3. Pathological fracture

4. Squamous cell carcinoma

5. Amyloidosis

6. Chronic osteomyelitis



ONNAZLI0809

BONE TUMORS

Character

Diverse in their gross and morphologic features

Behavior – biological innocuous to rapidly fatal

Target group – Benign (10 – 30 years old)

Malignant (later in adult life)

Risk factor

Li Fraumeni syndrome and hereditary retinoblastoma genes (mutations in p53 and RB gene). Bone

infarcts, chronic osteomyelitis, Paget disease, radiation and metal prostheses.

Classification

Base on normal cell tissue of origin (as stated below)

1. Bone forming tumors

2. Cartilage forming tumors

3. Fibro-osseous tumors

4. Miscellaneous tumors

Bone forming tumors Cartilage forming

tumors

Fibro-osseous tumor Miscellaneous tumors

Osteoma

Osteoid osteoma

Osteoblastoma

Osteosarcoma

Osteochondroma

Chondroma

Chondroblastoma

Chondromyxoid fibroma

Chondrosarcoma

Fibrous dysplasia Giant cell tumor

Ewing sarcoma

Metastatic tumor



ONNAZLI0809

Pathogenesis of Bone Tumors

Normal cell

DNA damage

DNA mutation

Mutation in Genome

Activation of Growth Promoting

Oncogenes* (oncogenic product class

1, 2 and 3)

Carcinogenic agents

Acquired DNA

damaging substance

Apoptosis Gene Alteration*

(hereditary)Cancer suppressing gene alteration*

(hereditary)

Oncogenic product class 4 and 5

Expression of altered gene product

Loss of regulatory gene product

Malignant Neoplasia

Successfully repaired

Alteration in gene that

regulates DNA repair*

CANCER RELATED GENES

1. Oncogenenic Products – class 1 to class 5

2. Tumour Supressing genes – p53,pRb genes

3. Genes regulates apoptosis – Bax, Bcl-2, bad, Bcl-xL

4. Genes regulates DNA repairAny defect in this gene, commonly inherited will increase the chances of getting

cancer 4-5 folds



ONNAZLI0809

BONE-FORMING TUMORS

OSTEOMA

Definition A benign bone tumor, an exophytic mass from skull and paranasal sinuses

Character - Most often arise on or inside the skull or facial bones

- Often affecting middle age adults (30-50 years old)

- Always associated with Gardner syndrome

Gross morphology Bosselated, round to oval sessile tumors that project from the subperiosteal or

endosteal surfaces of the cortex

Histopathology - Composed of lamellar and woven bone – frequently deposited in a

cortical pattern with Harvesian-like system

- Compact lamellar cortical bone

- Small amount of fibrofatty stromaClinical features - Usually asymptomatic

- Symptomatic if the tumors pressed adjacent structure such as sinus

obstruction, extracranial extension and nerve compression

Radiologic

findings

- Sharply demarcated mass protruding from the bone surface

- No bone destruction and periosteal reaction

- Periosteal osteoma may mimics periosteal osteosarcoma

Prognosis Never change or transform to malignant

Treatment Simple excision



ONNAZLI0809

OSTEOID OSTEOMA AND OSTEOBLASTOMA – benign bone tumors that have identical histologic

features but differ in size, sites of origin and symptoms

OSTEOID OSTEOMA

Definition Tumors which the size of less than 1 cm in greatest dimensionCharacter - Usually occurs in teens or twenties

- Most often rise from appendicular skeleton

- Mostly at tibia, femur and spine

Gross morphology - Is a well circumscribed tumor

- Mostly round to oval masses of gritty tan tissue

Histopathology - Well circumscribed tumor cells

- Composed of randomly interconnecting trabeculae of woven bone

rimmed by fibroblast

- loose vascular stroma

Clinical features - localized pain usually worse at night

- relieved by aspirin

Radiologic

findings

- intracortical nidus

- sclerotic rim of bone reaction

Prognosis Never change or transform to malignant

Treatment - Complete resection

- Removal of nidus

- Bone grafting may needed

OSTEOBLASTOMA

Definition A tumor of bone arises from the osteoblast

Character - Mostly arise from the axial skeleton

- Mostly affecting spine, femur and jaw

Gross morphology - Is a well circumscribed tumor

- Mostly round to oval masses of gritty tan tissue

Histopathology - Well circumscribed tumor irregular cells

- Composed of randomly interconnecting trabeculae of woven bone

rimmed by fibroblast

- loose vascular stroma

- presents of hyaline cartilage mimics the osteosarcoma

Clinical features - dull achy pain

- localize

- not responsive to salicylates

Radiologic

findings

- well-circumscribed tumor cell (irregularly demarcated)

- well defined by a surrounding shell of mature bones

- small extracortical mass

- Radiolucent lesion (20 -100 mm diameter)

- expansile lesion

- variable ossification

- may be aggressive with cortical destruction and soft tissue extension

Prognosis Less than 1 % recorded to be malignant transformation

Treatment Enbloc resection





ONNAZLI0809

CARTILLAGE FORMING TUMORS

OSTEOCHONDROMA

Definition also known as exostosis is a benign cartilage-capped outgrowth that is attached

to the underlying skeleton by a bony stalk

Character - Can be solitary or multiple

- Men are predominantly affected (3:1)

- developed only in bones of endochondral origin

- arise from metaphysis of the growth plate of long tubular bones, about

the knee

Gross morphology - mushroom-shaped (1-20 cm in size)

- cortex of the stalk continuous with the medullary cavity of the

osteochondroma are in continuity

Histopathology - cap of the tumor composed of hyaline cartilage

- appearance of the disorganized growth plate

- echondral ossification occurs at the growth plate

Clinical features - slow growing mass

- pain of the affected area – due to tumor impinge on the nerve or the

stalk of the tumor fractured

- bowing and shortening of bone due to disturbance in epiphyseal

growth

Radiologic

findings

- outgrowth of the bone from normal cortex – which is continuous

- Cap cannot be seen initially. As age increase, the cap undergoes

calcification in a punctuate or nodular fashion

- well-defined peripheral margin without localize bone destruction

Prognosis The stalk usually stop growing at the time of growth plate closure, <1% give rise

to osteosarcoma

Treatment Removal of loose body, synovectomy



ONNAZLI0809

CHONDROMA

Definition Benign tumor of hyaline cartilage. The terms enchondroma implicate the tumor

arise from the medullary cavity while subperiosteal/juxtacortical chondroma

denotes the tumor arise from the surface of the bone

Character - most common intraosseous cartilage tumor

- commonly diagnosed in patient between age 20-50

- no sex predominant

- solitary and often located in the metaphyseal region of the tubular

bones

- multiple chondroma is called chondromatosis occurs in the Oller

disease

Gross morphology - smaller than 3 cm

- enchondroma are gray blue, translucent and have a nodular

configuration

Histopathology - nodules of the cartilage are well circumscribed and have hyaline matrix

- neoplastic chondrocytes that reside in the lacunae are cytologically

benign

- nodules characteristic – peripheral undergoes enchondral ossification,

central undergoes calcification and dies

Clinical features - usually is asymptomatic

- local pain

- pathological fracture

- deformities occurs when the cartilage tumor is numerous and large

Radiologic

findings

- presence of ‘O ring sign’, an unmineralized nodules of cartilage produce

well circumscribed oval lucencies surrounded by thin rim of dense bone

- expansile growth of the cortex with size between 10 – 30 mm

Prognosis Tumor growth usually stable, if associated with chondromatosis, it has high

probability to become sarcomatous

Treatment Complete excise (but may recur)



ONNAZLI0809

CHONDROBLASTOMA

Definition A tumor derived from chondroblast which is very rare and accounts for less

than 1 % of the primary bone tumors

Character - occurs in young patients in their late teens

- male to female ratio 1:2

- mostly occurs at knee, in older patient, the tumor may occurs at pelvis

and ribs

Gross morphology - not stated

Histopathology - cellular tumor which composed of sheets of compact polyhedral

chondroblast that have well defined cytoplasmic border

- highly cellular lesion which is composed of chondroblast and giant cell

- nuclei are hyperlobulated with longitudinal groove

- moderate amount of pink cytoplasm

- surrounded by scanty amount of hyline matrix which are deposited in a

lace-like configuration

- prominent haemorrhagic cystic degeneration

Clinical features - local pain – if joint are affected

- joint effusion

- reduce joint (affected) range of movement

Radiologic

findings

- well-defined geographic lucency that has spotty calcifications

- round and well-defined calcific margin

Prognosis Rarely distant metastases to lung, recurrence common after surgical excision

Treatment Surgical excision



ONNAZLI0809

CHONDROMYXOID FIBROMA

Definition Is a rare benign tumor that accounts of less than 0.5 % of biopsied primary

tumor of the bones which composed of various tissue combination; fibrous,

cartilaginous and myxoid

Character - mostly occurs between 10-30 years old patient

- male are predominantly affected

- Usually arise in the metaphysis of long tubular bones – proximal 3rd

of

tibia (25 %), bones of leg and distal femur (50 %)

Gross morphology - tumor size 3-8 cm in greatest dimension

- well circumscribed, solid and glistening tan gray

Histopathology - nodules of poorly formed hyaline cartilage and myxoid tissue

delineated by fibrous septa

- cellularity varies, greatest at the periphery nodules

- tumor cell located in the lacunae at the cartilaginous region

- tumor cells are stellate and their delicate cell processes extend through

the mucinous ground substance and in contact with neighbouring cell

- varying degree of cytologic atypia – presence of large hyperchromatic

nuclei

- small foci of calcification of the cartilaginous matrix and scattered non-

neoplastic osteoclast-type giant cell

Clinical features - localize dull and achy pain

Radiologic

findings

- eccentric geographic lucency that is well delineated from adjacent bone

by a rim of sclerosis

- punched out lesion involving cortex and medulla

- presence of soap bubble appearance

Prognosis Tumor may recur but it doesn’t pose a threat for malignant transformation

Treatment Simple curettage



ONNAZLI0809

CONVENTIONAL CHONDROSARCOMA

Definition A malignant tumor of cartilage cell in which the cancerous cell produce

cartilage matrix and occurs in the bone

Character - occur at patient age 40 and above

- affecting male twice than female

- risk factor are enchondroma, osteochondroma, chondroblastoma,

fibrous dysplasia and Paget diseae

Gross morphology - composed of malignant hyaline and myxoid cartilage

- myxoid is viscous and gelatinous and the matrix oozes from the cut

surface

- presence of spotty calcification and central necrosis creating cystic

spaces

- adjacent cortex is thickened and eroded

Histopathology - poorly differentiated sarcoma – dedifferentiated chondrosarcoma

- sheets of large malignant chondrocytes that have abundant clear

cytoplasm, numerous osteoclast-tyoe giant cell and intralesional

reactive bone formation – clear cell chondrosarcoma

- island of well differentiated hyaline cartilage surrounded by sheets of

small round cell

- cellular anaplasia, bizarre shaped nuclei, chromatin clumping and

mitoses

Clinical features - painful lesion

- progressively enlarge masses

Radiologic

findings

- poorly demarcated between normal and abnormal bones

- presence of calcification which may be stippled, nodular or

englomerate (‘popcorn’) in a pattern of flocculent density

- nodular growth pattern of cartilage produces prominent endosteal

scalloping

Prognosis Depends on the grading, higher the grade and larger the size, poorer the

prognosis (chance of survival reduce)

Treatment Chemotherapy



ONNAZLI0809

OSTEOARTHRITIS

Definition

Is a degenerative joint disease characterized by progressive erosion of articular cartilage

Classification

Classify based on the causes of osteoarthritis

Primary Secondary

Idiopathic Metabolic

Ochronosis

Acromegaly

Haemochromatosis

Calcium crystal deposition

Anatomic

Slipped femoral epiphysis

Epiphyseal dysplasia

Congenital dislocation of the hip

Leg length inequality

Hypermobility syndrome

Traumatic

Motor vehicle trauma

Fracture through joint or osteonecrosis

Joint surgery

Inflammatory

Acute inflammatory arthropathy Septic arthritis

Pathogenesis

Idiopathic caused

Degeneration of chondrocytes

Decrease local synthesis of collagen

type II, proteoglycan produced is withinnormal range

Water absorption normal (PG normal)

but collagen network production less

Unstable osmolarity between collagen

network and water content leads to

increase breakdown of the pre-existing

collagen

Osteoarthritic cartilage produce

molecular messenger (IL-1, TNF-α and

nitric oxide)

PRIMARY OSTEOARTHRITIS

Erosion of the articular cartilage

Production of molecular messenger

predominate the compensatorymechanism

Compensatory mechanism –

chondrocytes in the deeper layers

proliferate and attempt to repair the

destroyed cartilage

Reduction of functional chondrocytes

Apoptosis increase

Trigger inflammatory reaction as well as

apoptosis



ONNAZLI0809

Morphology

Gross morphology

1. Vertical and horizontal fibrillation and cracking of the matrix at the superficial layers of the

cartilage which are degraded2. Granular articular surface softer than normal

3. Bone eburnation – friction smoothes and burnish the exposed bones

4. Mushroom shaped osteophytes (bony outgrowth) develop at the margins of articular

surface which capped by fibrous and hyaline cartilage

Histology

1. Synovium is congested and fibrotic

2. Scattered chronic inflammatory cell

Clinical features

1. Joint pain and tenderness

2. Joint swelling (stiffening and pain after immobility)

3. Joint instability

4. Crepitus on movement

5. Limitation of range of movement

6. Joint effusion

7. Heberden nodes – prominent osteophytes at DIP joint

Investigation

1. X-rays – abnormal only when the damage is advanced

2. MRI – demonstrate early cartilage and subchondral bone change

3. Arthroscopy – reveals each fissuring and surface area of the cartilage

Treatment

1. NSAID

2. Total replacement arthroplasty

3. Realignment osteotomy of knee and hip

4. Weight loss and exercise for strength

5. Local heat, ice packs and massage



ONNAZLI0809

RHEUMATOID ARTHRITIS

Definition

Chronic systemic inflammatory disorder which principally attacks the joint, producing a non-

suppurative proliferative and inflammatory synovitis that often progresses to destruction of thearticular cartilage and ankylosing of the joint

Pathogenesis

Morphology

1. Synovial edematous, thickened and hyperplastic forming villous configuration2. Infiltration by dense perivascular inflammatory cells such as B-cells, T-cells, plasma cell and

macrophages

3. Increase vascularity

Unknown antigen

Bind to MHC class II (genetic susceptibility)

Induce CD4+ T cells to release cytokines

B-cell activation

Formation of rheumatoid factor

Immune complex formation and

deposition inside joint cavity

Joint injury

Induce macrophage to release

cytokines

Proliferation of fibroblasts,

chondrocytes and synovial cells

Release of collagenase,

stromelysin, elastase, PGE2, and

other enzyms

Endothelial activation

Expression of adhesion

molecules

Accumulation of inflammatory

cells

Pannus formation; destruction of bone,

cartilage leading to fibrosis and

ankylosing



Clinical course

1. slowly progressive, symmetrical and peripheral polyarthritis evolving over a period of few

weeks and months

2. pain and stiffness of small joints of hands – PIP, DIP and feet (MTP)

3. pain and stiffness in the morning improve with physical activity

Investigations

1. Blood count – anaemia

2. Increase in ESR

3. Increase in C-reactive protein

4. Serology test – Presents of Rheumatoid factor and ANA at low titre

5. X-rays – soft tissue swelling

6. Aspiration – effusion presents and cloudy owing to white cells

Treatment

1. NSAID

2. Disease modifying anti-rheumatic drugs that inhibit cytokines and reduce inflammatory

response – TNF-a, corticosteroid, methotrexate etc

Documents

Everything You Need to Know MSS