MSK Pathology For USMLE Step One

MSK
PATHOLOGY
BONE DISEASE
Achondroplasia
Mutation FGFR3 ihibits chondrocyte proliferation no encochondral ossification, membranous spared
85% are sporadic, associated with advanced paternal age
Osteoporosis
Loss of trabecular bone mass with normal Ca and PO3 DXA score < -2.5
Type 1: Menopausal due to reduced oestrogen femoral neck and colles fractures
Type 2: senile men and women over 70
Weight bearing exercise and calcium and vitamin D
Osteopetrosis
Failure of normal bone resorption due to defective osteoclasts dense bones, prone to fracture with
marrow obliteration and pancytopaenia
Mutations in carbonic anhydrase 2 impair acid production by osteoclasts
cranial nerve impingement, palsies, scoliosis
BM transplant
Osteomalacia
Increased ALP (hyperactivity of osteoblasts, need alkaline environment)
Pagets Disease of the Bone

Localised bone remodelling disorder with increased osteoblast and osteoclast activity (increased ALP)
mosaic pattern of woven and lamellar bone
chalkstick fractures
high output HF from AV shunting
OSTEOGENIC SARCOMA
4 stages: 1. Lytic (osteoclasts)
2. Mixed (OB & OC) 3. Sclerotic (OB)
4. Quiescent
Hearing loss and increased hat size
Avascular Necrosis
Infarction of bone and marrow, painful, due to trauma, high dose coritcosteroids, alcoholis, Sickle cell
anaemia
-femoral head due to insufficiency from medial circumflex artery
BONE TUMOURS
Type
Giant cell
tumour
Osteochondrom
a
Osteosarcoma
Ewing sarcoma
Chondrosarcom
a
Epidemiology and location

BENIGN
Epiphysis of long bones
20-40 years
Males <25
MALIGNANT
2nd most common 1 bone tumour after MM
Bimodal (10-20 yrs and >65 yrs)
Pagets, radiation, LiFraumeni, RB are RFs
Metaphysis of long bones-knee
Boys<15
Diaphysis of long bones, pelvis, sternum, scapula,
ribs
Rare
Men 30-60
Pelvis, spine, scapula, humerus, tibia, femur
Characteristic
Locally aggressive, at knee
Soap bubble on X-ray
Mature bone with cartilaginous cap
Codman triangle (raised periosteum)
Sunburst pattern
Resection en bloc
Anaplastic small blue cell
Early mets, v aggressive
T(11;22)
1 or from osteochondroma
expansile glistening mass in medullary
cavity
ARTHRITIS
OSTEOARTHRITIS
Wear and tear disease age obesity, joint deformity, trauma predispose
Feat:
1. Sunchondral cysts
2. Sclerosis
3. Joint cavity narrowing
4. Osteophytes
5. Eburnations
6. Heberden (DIP) and Bouchards (PIP) nodes w/o MCP involvement
Pain that improves with rest, bowleggedness, no systemic symptoms
tx with NSAIDS and steroids
RHEUMATOID ARTHRITIS
Autoimmune type 3 and 4 hypersensitivity and cytokines
Females> males, RF (anti-IgG antibody) in 80% and anti-cyclic citrullinated peptide HLA-DR4
Feat:
1. Pannus in MCP, PIP (no DIP involvement)
2. RNodules (fibrinous necrosis)
3. Ulnar deviation of fingers, subluxation
4. Increased synovial fluid and cavity
5. Bakers cyst in popliteal fossa
Morning stiffness that improves with use 30 mins+, symmetric joint involvement, systemic symptoms
tx NSAIDs, steroid, DMARDs
SJRGENS SYNDROME
ID destruction of exocrine glands xeropthalmia, xerostomia,
Anti nuclear antibodies (SS-A anti RO or SSB anti LA)
1 or 2 disorder, compications include dental caries, MALT (unilateral parotid enlargement)
GOUT
Acute inflammatory monoarthritis monosodium urate crystals YELLOW

Over production: 10% TLS, LeschNyhan, PRPP, Von Gierkes
Underexcretion: thiazides, idiopathic
Needle shaped crystals, birfringent
Tx: NSAIDs, steroids, colchicine
Long term- allopurinol (XO inhibitor)
PSEUDOGOUT
Pain and effusion in large joint (knee) due to deposition of calcium pyrophosphate in joint space
(chondrocalcinosis)
Basophilic, rhomboid crystals BLUE
50+, both sexes, haemochromatosis, hyperparathyroidism/hypo
NSAIDs, Steroids, Colchicine
Infectious arthritis
S. aureus, streptococcus, Neisseria Gonorrhoeae
Gon: migratory, asymmetric
SERONEGATIVE SPONDYLARTHROPATHIES
Type
Psoriatic Arthritis
Ankylosing spondylysis
IBD
Reactive arthritis
(Reiter Syndrome)
Asymmetric patchy involvement in 1/3 of patients

- dactylitis (sausage fingers)
- pencil in cup
Chronic inflammatory disease of spine and sacroiliac joints
Ankylosis, uveitis, aortic regurge
Often associated with AS or peripheral arthritis
Conjuncticiviits, urethritis, arthritis
Usually after GI infection (Shigella, salmonella, Yersinia, Campylobacter)
LUPUS
Rash, joint pain and fever in child bearing age woman of African descent
Feat:
- Libman sacks endocarditis
- Rash (discoid or malar)
- Serositis, soft tissue
- Cytopaenias
- Ulcers oral
- Renal disease (nephrotoc and nephritic) and reynauds phenomenom
- Photosensitivity
- Positive VDRL/RPR
- Antinuclear antibodies
- Immunosuppresants
- Neurological disorders
Causes of death: CVS,infections, renal disease
Antinuclear antibodies
Sensitive not specific
Anti dsDNA
Specific, poor renal prognosis
Anti smith
Specific, not prognostic
Anti histone
Drug induced
Anti cardiolipin
False + on syphilis tests, prolonged PTT but increased risk of AV
thromboembolism
Reduced C3,C4 and
Immune complex formation
CH50
Tx: NSAIDs, steroids, hydroxychloroquine
SARCOIDOSIS
Black female Africans
Feat:
1. non caseating granulomas (epithelioid with schaumann and asteroid bodies)
2. ACE^
3. hilar lymphadenopathy, reticular opacities, interstial pulmonary fibrosis
4. erythema nodusum
5. lupus pernio
6. Bells palsy, uveitis
7. hypercalcaemia (1 OH ase in macrophages)
treat with steroids
POLYMYALGIA RHEUMATICA
Pain and stiffness in shoulders and hips in women over 50 associated with GIANT CELL ARTERITIS
Raised ESR, CRP normal CK
rapid response to low dose steroids
FIBROMYALGIA
Wide spread musculoskeletal pain and stiffness associated with paraesthesias and fatigue
anticonvulsants, antidepressants, excerisise
POLYMYOSITIS
Progressive, symmetrical muscle weakness characterised by ENDOmysial CD8+ inflammation-->
shoulders
DERMATOMYOSITIS
As above with malar rash, Gottron papules (scaly erythematous on knuckles, joints), heliotrope rash,
shawl and face rash
PERImysial CD4+ inflammation and atrophy
paraneoplastic, occult malignancy
Feat:
1. ANA, anti-Jo1, anti SRP, anti Mi2
Treat with steroids
Myositis ossificans metaplasia of skeletal muscle to bone at sights of muscular trauma, usually in
extremities may present as mass
NMJ disease
Frequency
Pathophysiolog
y
Clinical
Associated with
AChEi
MG
Most common
Ig to Ach receptor
Lamber Eaton Myaesthenic Syndrome

Rare
Ig to presynaptic Ca+ channesl
Ptosis, diplopia, weakness which

gets worse on muscle use
Thymoma, thmymic hyperplasia
Improves
Proximal muscle weakness, dry mouth,

impotence, improves with muscle use
SCLC
No or minimal change
SCLERODERMA
Excessive fibrosis and collagen deposition throughout the body puffy and taut skin with no wrinkles,
renal, pulmonary, cardiovascular and GI systems
75% female
1. Diffuse scleroderma: widespread skin involvement, rapid progression with early visceral
involvement
anti- Scl-70 antibody (DNA topisomerase1)
2. Limited scleroderma: Limited skin involvement and CREST (calcinosis, Reynauds, oesophageal
dysmotolity, sclerodactyly, telangiectasia anti centromere antibody)
MORE BENIGN
DERMATOLOGY
PIGMENTED SKIN DISORDERS
ALBINISM: normal number of melanocytes but no melanin production due to reduced tyrosinase activity
or defective tyrosine transport
MELASMA: hyperpigmentation of pregnancy/OCP
VITILIGO: Irregular areas of complete depigmentation caused by AI destruction of melanocytes
BLISTERING SKIN DISORDERS

PEMPHIGOUS: IgG to desmogleins of desmosomes
flaccid IE bullae caused by acantholysis
oral mucosa
net like IF
Nikosky +
PEMPHIGOID: IgG against hemidesmosomes
tense blisters containing eosinophils
IF is linear
Nikolsky
DERMATITIS HERPETIFORMIS
Pruiritic papules, vesicles and bullae
IgA at tips of dermal papillae
Coeliac disease

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What are some common bone diseases mentioned?

What are the characteristics of different bone tumors?

MSK

Pagets Disease of the Bone

Epidemiology and location

Acute inflammatory monoarthritis monosodium urate crystals YELLOW

Asymmetric patchy involvement in 1/3 of patients

Lamber Eaton Myaesthenic Syndrome

Ptosis, diplopia, weakness which

Proximal muscle weakness, dry mouth,

BLISTERING SKIN DISORDERS

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