MSK Flashcards
A 40-year-old male with long standing Rheumatoid arthritis has generalised lymphadenopathy increasing over the past 4 years, malabsorptive diarrhoea and a restrictive cardiomyopathy. Which of the following statements is most correct?
- The combination suggests superadded Sjogren’s Syndrome
- The combination suggest systemic amyloidosis and may be diagnosed by renal or mouth/rectal biopsy
- The patient should be screened for HIV infection
- The combination suggests a progression of a MALT lymphoma
- The combination suggests scleroderma, particularly if antibodies to the Fc fragment of immunoglobulin are present.
- *The combination suggest systemic amyloidosis and may be diagnosed by renal or mouth/rectal biopsy
Osteoporosis is least likely to be associated with (August 2016)
a. Hypoparathyroidism
b. Multiple myeloma if there are no lucent lesions
DDx for osteoporosis: o Idiopathic o Endocrine - Hypogondism (Ovarian – post menopausal; Testicular – eunuchoidism) - Cushing syndrome - Diabetes - Acromegaly - Addison’s disease - Hyperthyroidism - Mastocytosis - Pseudohypothyroidism - Pseudopseudohypothyroidism o Disuse - Pseudopermeative pattern o Iatrogenic - ie Steroid use; Heparin o Deficiency states - Vitamin D; Protein o Congenital - Osteogenesis imperfecta - Turner syndrome - Homocystinuria - Neuromuscular disease - Mucopolysaccharidoses - Trisomy 13 and 18 - Glycogen storage disease - Progeria
Multiple myeloma has two main patterns of diffuse disease
o Numerous, well circumscribed lytic bone lesions (more common)
o Generalised osteopaenia w vertebral compression fractures +/- vertebra plana
ANSWER: Hypoparathyroidism is least likely to be associated w osteoporosis, although pseudohypoparathyroidism & pseudopseudohypoparathyroidism are
Regarding Paget’s disease of the bone, which is false: (March 2015)
a. Polyostotic form leads to extramedullary haematopoesis
b. Rarely affects the fibula
c. Hearing loss is due to involvement of the external ear canal
d. Can get basilar invagination
e. Can get high output cardiac failure
Hearing loss in Paget’s disease can be sensorineural or conductive
o Sensorineural: Compression of the nerves from bone overgrowth or loss of bone mineral density in the cochlea
o Conductive: fixation of the middle ear ossicles
Complications of Pagets disease o Fractures o Nerve compression o OA o Skeletal deformities e.g. tibial bowing or skull enlargement o High output cardiac failure o Osteosarcoma transformation in 1%
ANSWER: Hearing loss in Paget’s disease is not due to involvement of the external ear canal
What is not a complication in Pagets disease? (September 2013)
a. High output cardiac failure
b. Low output cardiac failure
c. Cranial nerve palsy
d. Platybasia
e. Malignant transformation
ANSWER: Low output cardiac failure
Platybasia - flattening of the skull base. Usually asymptomatic unless assoc w basilar invagination (odontoid projects into foramen magnum)
What lesion is not epiphyseal? (August 2016)
a. Paget disease
b. Osteomyelitis
Pagets in the long bones:
o Lesions begin in the proximal or distal subchondral region & progress towards the diaphysis
- Lesions rarely begin in the diaphysis, however this happens uncommonly in the tibia
o Forms a sharp delineation at the border of the normal bone, forming a ‘blade of grass’ or ‘flame shaped’ pattern
o May develop incomplete horizontal insufficiency fractures
- Form on the convex side of the bone
- Progress to ‘banana’ fractures
- Contribute to abnormal lateral bowing of the femur or anterior bowing of the tibia
Osteomyelitis in the long bones:
o Location of infection relates to the vascular supply of the bone
o Infants <12 months:
- Some metaphyseal vessels perforate the physis & anastomose w epiphyseal vessels - Infections involve the metaphysis, epiphysis & joint - Complications from epiphyseal infections include slipped epiphyses & joint deformities
o Toddlers & older children:
- Blood vessels terminate in loops w/in the metaphysis. Sluggish blood flow in the loops - Develop osteomyelitis in the metaphyses
o Adults:
- Terminal metaphyseal & epiphyseal vessels anastomose across the physeal scar - Adult OM can involve the metaphysis, epiphysis or the joint (more commonly than in children)
o Infection is rarely located in the cortex, unless due to direct inoculation
ANSWER: Both lesions can be epiphyseal in location; OM is more likely to be epiphyseal in adults
What is the most common cause of osteomalacia? (September 2013)
a. Renal failure
b. Vitamin D deficiency
c. Low dietary intake of phosphate
d. Hypophosphataemia
Causes of osteomalacia:
o Vitamin D def from sunlight or diet
o Deficiency of vitamin D metabolism - CRF
o Chronic liver disease
- Disruption of the pathway at 25-hydroxy vitamin D in hepatocytes
- Biliary dysfunction causing decreased absorption
o Decreased absorption of vitamin D
- Malabsorption syndromes (e.g. Crohn disease)
- Partial gastrectomy
o Decreased deposition of calcium in bones
o Defects in phosphate metabolism
- Phosphate deficiency from drugs or malabsorption
- Familial hypophosphataemia
- Fanconi syndrome
ANSWER: Vitamin D deficiency (although renal failure is a common cause of vitamin D deficiency)
Osteonecrosis is least associated with: (August 2016)
a. Gaucher disease
b. Thalassaemia major
c. Subcapital femoral fracture
d. Sickle cell disease
e. Caisson disease
Causes of osteonecrosis (PLASTIC RAGS) o P: Pancreatitis, pregnancy o L: Lupus o A: Alcohol o S: Steroids o T: Trauma o I: Idiopathic, infection o C: Caisson disease, collagen vascular disease o R: Radiation, rheumatoid arthritis o A: Amyloid angiopathy o G: Gaucher disease o S: Sickle cell disease
Caisson disease: diving related decompression illness
o Arterial gas embolization secondary to pulmonary decompression barotrauma
o Decompression sickness (Caisson disease):
- Mild: arthralgia, skin marbling, small patchy haemorrhages, lymphatic obstruction
- Serious & life threatening: Affecting the brain, spinal cord, inner ear and/or lung
Complications: bone & spinal cord infarction
Gaucher disease: most common lysosomal storage disease in humans
o AR, multisystem disease
o Deficiency of glucocerebroside & beta-glucosidase activity
- Accumulation of glycolipid within the lysosomes of macrophages in the bone marrow, spleen and liver
Types: Type I (most common) • Dx later (mean 21 years) • Skeletal symptoms (bone pain, pathological fractures, osteonecrosis, bone crises) - Osteopaenia, osteonecrosis, pathological fractures - Endosteal scalloping - Erlenmeyer flask deformities - H-shaped vertebrae - Paranasal sinus obliteration • Hepatomegaly & splenomegaly • Haematological disturbances • CNS spared
Type II
• Evident by 6 months
• Progressive neurological deterioration, resulting in death by the age of 2
Type III
• Neurological complications presenting by late adolescence or in early childhood
ANSWER: Thalassaemia is not assoc w osteonecrosis
What is not associated with osteonecrosis? (September 2013)
a. MI
b. Chronic pancreatitis
c. Gaucher’s disease
d. Connective tissue diseases
e. Sickle cell disease
ANSWER: Myocardial infarction is not assoc w osteonecrosis
What is not associated with osteonecrosis? (September 2013)
a. Cirrhosis
b. Chronic pancreatitis
c. Gaucher’s disease
d. Connective tissue diseases
e. Sickle cell disease
ANSWER: Cirrhosis is not assoc w osteonecrosis
Which is most true of osteosarcoma? (August 2016, March 2017)
a. Parosteal osteosarcoma is a lower grade compared to periosteal
b. Better survival for surface compared to central osteosarcoma
c. Periosteal osteosarcoma classically has a cleft between the cortex and the lesion
d. Parosteal typically has a cartilage matrix
PERIPHERAL OSTEOSARCOMA Parosteal osteosarcoma o Usually low grade o Ages 20-30 o F>M o Most common in the posterior aspect of the distal femur
Periosteal osteosarcoma o Intermediate grade o Ages 18-20 o M>F o Most common in the tibial meta-diaphysis
High grade surface osteosarcoma o High grade o Ages 20-30 o M>F o Most commonly in the mid femur, distal femur & mid tibia
CENTRAL OSTEOSARCOMA
• Most central osteosarcomas are high grade
Conventional osteosarcoma
o Osteoblastic (50% of conventional)
o Chondroblastic (25% of conventional)
o Fibroblastic (25% of conventional)
o Other rare subtypes (<1% of conventional)
• Telangectatic osteosarcoma; Small cell osteosarcoma
o Round cell
o Short spindle cell
ANSWER: Parosteal osteosarcoma is a lower grade compared to periosteal osteosarcoma
Which lesion is diaphyseal in location? (August 2014)
a. Osteoblastoma
b. Chondromyxoid fibroma
c. Osteochondroma
d. Chondroblastoma
e. Non-ossifying fibroma
- Osteoblastoma: metaphyseal
- Chrondromyxoid fibroma: metaphyseal (60% in long bones). Rarely can extend to the epiphyseal line or the articular surface
- Osteochondroma: metaphyseal, exophytic & pointing away from the physis
- Chondroblastoma: epiphyseal, occasionally crosses the growth plate
- Non-ossifying fibroma: metadiaphyseal
ANSWER: Non-ossifying fibroma is the most correct answer, although this is considered metadiaphyseal
Which of the following presents as a painless mass? (March 2014)
a. Periosteal osteosarcoma
b. Parosteal osteosarcoma
c. High grade surface osteosarcoma
d. Telangectatic osteosarcoma
e. Small cell osteosarcoma
Clinical presentation of osteosarcoma subtypes:
o Periosteal osteosarcoma: painless or low grade pain
o Parosteal osteosarcoma: sometimes painless
o High grade surface osteosarcoma: very painful, may have pathological fracture
o Telangectatic osteosarcoma: very painful, may have pathological fracture
o Small cell osteosarcoma: painful
ANSWER: Periosteal osteosarcoma more commonly presents as a painless mass
Which is false regarding diaphyseal aclasia? (March 2016)
a. It is sporadic
Hereditary multiple exostoses (aka diaphyseal aclasia);
o AD condition w incomplete penetrance in females
o Characterised by the development of multiple osteochondromas
Clinical:
- Most diagnosed by age 5, almost all diagnosed by age 12
- Multiple large lesions may give significant joint deformity
Complications of lesions: - Vascular impingement - Neural impingement - Fractures - Bursitis - Deformity - Malignant transformation • More common than in sporadic cases
Associations with sarcomatous transformation (GLAD PAST): - Growth after skeletal maturity - Lucency (new) - Additional uptake on NM studies - Destruction of the cortex - Pain after puberty (and) - Soft tissue mass - Thickened cartilage cap (>1.5cm)
ANSWER: Diaphyseal aclasia is an autosomal dominant condition – not sporadic
Chondrosarcoma. Which is not true? (March 2015)
a. Clear cell chondrosarcoma occurs in the pelvis
b. Hyaline chondrosarcoma occurs in the rib
c. Mesenchymal chondrosarcoma occurs in the mandible
d. Myxoid chondrosarcoma occurs in soft tissues
e. Dedifferentiated chondrosarcoma occurs in recurrent tumour
• Malignant tumours which produce cartilage
Histological subclassifiaction (Robbins) o Conventional (hyaline cartilage producing) o Clear cell o Dedifferentiated o Mesenchymal variants
Epidemiology
o Typically 4th & 5th decades
- Younger patients for clear cell & mesenchymal variants
Location:
o Classically arises in the axial skeleton including pelvis, shoulders & ribs
o Clear cell is the exception – occurs in the epiphyses of tubular long bones
o 15% of chondrosarcomas are secondary, arising from pre-existing enchondromas or osteochondromas
Clear cell chondrosarcoma: o 3-5th decades o Epiphyses of long bones, 60% in the femur o Typically low grade o Mimics chondroblastoma on imaging
Hyaline chondrosarcoma/conventional chondrosarcoma:
o Most common subtype
o May be high, intermediate or low grade
o Locations:
- Long bones (45%) – femur most commonly
- Pelvis (25%)
- Ribs (8%)
- Spine (7%)
- Scapula, sternum, skull
o Low grade chondrosarc can mimic enchondroma on imaging
Mesenchymal chondrosarcoma:
o Rare subtype which can occur in the bone or soft tissues. Usually high grade lesions
o Younger patients
Location:
- Bone lesions: mandible & facial skeleton most common
- Soft tissue lesions have a predilection for the head & neck: meninges / brain, orbit, larynx, sinonasal cavity
• Also occur in the soft tissues of the thigh
Myxoid chondrosarcomas:
o Mesenchymal & myxoid chondrosarcomas account for the majority of soft tissue sarcomas
- Usually high grade
- Peak incidence of myxoid chondrosarcomas at age 50
Location:
- Typically involve the extremities, thigh most common
Dedifferentiated chondrosarcoma:
o Combined tumour made up of two components which are sharply demarcated
o Poor prognosis – 0-18% survival at 5 years. 90% will develop lung metastases
ANSWER: Clear cell chondrosarcoma does not occur in the pelvis – seen in the epiphyses of long bones
Which is false of chondroblastoma? (March 2016)
a. Arise in metaphysis
b. Can be associated with a periosteal reaction
Chondroblastoma:
o Benign cartilage tumour arising in the epiphysis of a skeletally immature patient
Location:
>75% in the long bones
Epiphyseal, may extend into the metaphysis
Proximal humerus most common
Characteristics: Geographic lytic lesion 30-50% contain chondroid matrix Majority have a sclerotic margin Eccentric w/in the epiphysis Smooth, thick periosteal reaction in longstanding lesions (50%)
Epidemiology:
10-25 years old
Male > female
o Treated with curettage and bone graft. Consider ablation in small lesions
DDx:
- Clear cell chondrosarcoma (may appear identical)
- Giant cell tumour (arises in metaphysis & extends to epiphysis, skeletally mature)
- Osteomyelitis (rare in epiphysis)
- LCH (rare in epiphysis)
ANSWER: Chondroblastoma typically arises in the epiphysis, but can extend into the metaphysis
Regarding fibrous dysplasia, which is true? (March 2015)
a. McCune Albright includes hypercortisolism
b. Polyostotic form without endocrine effects presents later than the monostotic form
c. Monostotic has more association with osteosarcoma
d. Monostotic form has an association with Café-au-lait spots
Fibrous dysplasia
o Benign, fibro-osseus lesions which can be monostotic or polyostotic
Polyostotic:
- GNAS mutations
- More commonly unilateral (esp McCune-Albright)
- 2/3 present before the age of 10
• Painful if assoc w microfractures, esp the femoral neck or tibia)
McCune-Albright syndrome: • Polyostotic, unilateral • More common in females Associations & presentations: o Coast of Maine Café-au-lait spots o Endocrine abnormalities: - Precocious puberty (Abnormal PV bleeding in 25%) - Hyperthyroidism - Diabetes - Hyperparathyroidism - Rickets - Acromegaly - Cushing’s syndrome – 7%
Mazabraud syndrome:
- Polyostotic fibrous dysplasia & multiple soft tissue myxomas
- Usually in the large muscle groups
- More frequently in women and presents in middle age
o Malignant transformation is very uncommon, but degeneration to osteosarcoma or fibrosarcoma has been reported
Craniofacial appearances of fibrous dysplasia:
Cherubism: symmetric involvement of the maxilla & mandible
- Leontiasis ossea: involvement of the facial & frontal bones, giving a ‘lion-like’ face (severe craniofacial osseous thickening)
- Cranial nerve palsies are assoc w craniofacial FD secondary to bony overgrowth of the foraminae & nerve compression
ANSWER: McCune-Albright includes hypercortisolism
Which is true regarding Ewing sarcoma? (September 2013)
a. Differential includes neuroblastoma
b. Differential includes aggressive chondrosarcoma
c. Arises from the metaphysis
d. Peak age is the third decade
Ewing sarcoma
o Second most common malignant tumour of childhood
o Arise from the medullary cavity
Epidemiology:
- Children and adolescents - Most common in the second decade - Slight male predilection
Clinical:
- Non-specific symptoms - Pathological fracture - ESR elevated
Pathology:
- Small round blue cell tumour (Ewing sarcoma family of tumours) - t(11;22)(q24;q12) rearrangement
Location (geography):
- Lower limb: 45% - Pelvis: 20% - Upper limb: 13% - Spine & ribs: 13% (Sacrococcygeal region most common) - Skull/face: 2%
Location (distribution): - Long bones: 50-60% • Mid-diaphysis – 33% • Metadiaphysis – 44% • Metaphysis – 15% • Epiphysis – 1-2% - Flat bones: 40%
ANSWER: Differential includes neuroblastoma (both small round blue cell tumours)
Regarding Ewing sarcoma, which is false? (March 2017)
a. Spreads to the lymph nodes before haematogenously
b. Is like a PNET elsewhere but more benign
ANSWER: Both statements are false. Spread of Ewing sarcoma is bones > lung > lymph nodes
Small round blue cell tumours are least likely found in: (September 2013)
a. Orbit
b. Kidney
c. Adrenals
d. Bone
e. Testis
- Orbit – retinoblastoma
- Kidney – Wilms tumour (nephroblastoma)
- Adrenal gland – neuroblastoma
- Bone – Ewing sarcoma family of tumours
ANSWER: Small round blue cell tumours are least likely to be found in the testis
Regarding giant cell tumour, which is true? (September 2013)
a. Metastases to the lung have a poor prognosis
b. Malignant transformation is 1%
c. When large, can invade into the surrounding soft tissues
d. Recurrence rate of 10% following curettage
Giant cell tumour: Aka osteoclastomas
o Arise from the metaphysis, typically spread to involve the epiphysis. 99% occur w a closed growth plate
Epidemiology:
- Young adults
• 80% of cases bw age 20 & 50
• Peak incidence age 30
• Minor female predominance (especially spinal lesions)
• Malignant transformation more common in men
Pathology:
- Overexpression of RANK/RANKL causing an overproliferation of osteoclasts
- Thin walled vascular channels, pre-disposing the lesions to haemorrhage
- May occur w an ABC (14%)
- Pathology can often be difficult to interpret
• Relies on the radiographic appearance to assist in Dx
Prognosis:
- Low grade tumours
- Rarely undergo sarcomatous transformation
• More commonly seen in lesions which are treated w radiotherapy (unresectable)
- Lung metastases in 5%
• Excellent prognosis even w these lesions
• ‘Benign, metastasing GCT’
• 40-60% local recurrence w curettage
• 2.5-10% w newer treatments involving thermal or chemical treatment
• Lower recurrence w en-bloc resection/WLE but associated w significant morbidity
ANSWER: When large, giant cell tumours can invade into the surrounding tissues
Regarding aneurysmal bone cysts, which is true? (September 2013)
a. Most are secondary
b. Most are associated with a second bone tumour
c. Arise from the metaphysis
Aneurysmal bone cyst: Expansile tumour-like bone lesion
Epidemiology:
- Mostly children & adolescents, most cases prior to age 20 (80%)
Pathology:
- Blood filled spaces of varying size are separated by connective tissue containing trabecular of bone or osteoid tissue & osteoclast giant cells
- Blood filled spaces are not lined by endothelium
o 1/3 secondary to an underlying lesion: Chondroblastoma, FD, GCT, Osteosarcoma
Location:
- Metaphysis of long bones adjacent an unfused growth plate
Distribution:
• Long bones (50-60%)
o Lower limb 40%
o Upper limb 20%
• Spine & sacrum (20-30%)
o More commonly involving the posterior elements
o Extension into the vertebral body in 40%
• Craniofacial: jaw, basisphenoid, paranasal sinuses
• Epiphyseal or apophyseal lesions are rare but clinically important
ANSWER: ABCs usually arise from the metaphysis
Which of the following associations is false? (September 2013)
a. Lead and sarcoma
b. Mercury and RCC
c. Smoking and oropharyngeal cancer
d. Asbestos and lung cancer
e. Asbestos and mesothelioma
ANSWER: Lead is not assoc w sarcoma
Which is true?
a. All osteogenesis imperfecta is associated with defective dentogenesis
b. OI type I is associated with kyphoscoliosis
c. OI type II is compatible with life
d. OI type III is associated with hearing loss
e. OI type IV has blue sclera
Osteogenesis imperfecta is a heterogenous group of congenital, non-sex linked genetic disorders of type I collagen production
o Affects connective tissue & bone
o Many types, type I-IV most recognised
OI type I: o Most common, 50% of all cases o Mildest form o AD inheritance Clinical features: - General bone fragility, predisposition to fracture - Normal or near normal stature - Loss joints & muscle weakness - Bone deformity absent or minimal - Head and neck features: Blue, purple or grey tinted sclera; Brittle teeth (dentogenesis imperfecta) - Distinguishes type IA (without) & IB (with) - Predisposed to hearing loss
OI type II:
o Perinatal lethal form (death in utero or shortly after birth)
o Death caused by multiple rib fractures & resulting pulmonary hypoplasia
o Caused by a sporadic AD mutation
Clinical features:
- Numerous fractures w severe bone deformity
- IUGR
- Wormian bones
OI type III:
o Progressive deforming
o Most severe type among children who survive the neonatal period
o Usually result from AD mutations. Varying phenotype
Clinical features:
- Birth: limbs mildly shortened & bowed, small chests, soft calvarium
- Bones fracture easily: Fractures often present at birth. X-rays show additional healed fractures which occurred in utero
- Short stature
- Rotoscoliosis & vertebral compression fractures
- Altered growth plate structure: popcorn-like appearance of metaphyses & epiphyses
- Head & neck appearances: Blue, purple or grey tinted sclera, Triangular face, Hearing loss, Dentogenesis imperfecta
OI type IV:
o Moderate-severe phenotype (variable)
Clinical features:
- Bones fracture easily (especially before puberty)
- Short stature
- Mild to moderate bone deformity
- Head and neck features: Light blue sclera in infancy which becomes white (only type to not have persistent blue sclera), Triangular face, Variable dentogenesis imperfect, Hearing loss in some cases
ANSWER: Type III is associated with hearing loss
Frontal bossing is not associated with: (August 2014)
a. Thanatophoric dysplasia
b. Acromegaly
c. Hurler syndrome
d. Alpha thalassaemia
e. Cleiodocranial dysotosis
Conditions associated with frontal bossing: o 18q syndrome o Acromegaly o Achondroplasia o B-thalassaemia o Cleidocranial dysostosis o Gorlin-Goltz syndrome o Greig cephalopolysyndactyly syndrome o Hurler syndrome o Hydrocephalus (before the age of two) o Pyknodysostosis o Russell-Silver dwarfism o Thanatophoric dysplasia
ANSWER: Alpha thalassaemia is not assoc w frontal bossing, but beta thalassaemia is.
Which is true regarding rheumatoid arthritis? (March 2014)
a. It has no gender predilection
b. Commonly involves the axial skeleton
c. The joints of the feet are often spared
d. Rheumatoid nodules affect the heart valves
• Rheumatoid arthritis has a female predominance (2-3:1)
• Most commonly affected joints are the hands & wrists initially, then the feet & larger joints
• Rheumatoid assoc valvular heart disease:
o Typically left sided
o Characterised by nodules & valve thickening
ANSWER: Rheumatoid nodules affect the heart valves
Which is most correct regarding rheumatoid arthritis? (March 2014)
a. More commonly seen in females
ANSWER: Rheumatoid arthritis is more commonly seen in females (30-50)
What differentiates rheumatoid arthritis from juvenile idiopathic arthritis? (March 2015)
a. Mononeuritis multiplex
b. Joint effusion
c. Erosions
d. Enthesitis
e. Iritis
f. Uveitis
Morphological features of rheumatoid arthritis o Inflammation o Pannus o Eroding cartilage o Fibrous ankylosis o Bony ankylosis
Compared to RA, JIA more commonly has these features:
o Oligoarthritis
o Systemic disease is more frequent
o Large joints are more affected than small joints
o Rheumatoid nodules & RF are usually absent
o ANA seropositivity is common
Subgroups of JIA: o Systemic o Polyarticular RF positive o Enthesitis-related (involvement at sites of ligament & cartilage insertion on bone) o Oligoarticular
ANSWER: Enthesitis
Which is true regarding juvenile idiopathic arthritis? (August 2014)
a. RF negative, Anti-CCP positive
- JIA patients are usually RF & Anti-CCP negative
- The subgroup of patients who are RF positive often also have a positive Anti-CCP
ANSWER: JIA patients are typically negative for RF AND Anti-CCP
Which is a typical cause of reactive arthritis? (March 2015)
a. Campylobacter
b. Salmonella
c. Shigella
d. Yersinia
Reactive arthritis is a transient arthritis which occurs after infection which typically affects 1 or 2 large joints
o Considered a seronegative arthritis
o HLA-B27 positive in 80%
Classic triad consists of: (<1/3 have the full triad at diagnosis)
o Arthritis - Heel pain is often the most disabling feature
o Conjunctivitis
o Urethritis (or cervicitis in women)
Causes:
o Enteric infections: Yersinia, Campylobacter, Salmonella, Shigella or less commonly E. Coli
o Sexually transmitted: Chlamydia
o Other: Brucellosis
Epidemiology:
o Male predilection (5-6:1)
Location:
o Small joints of the feet: 64%
o Sausage digits: 52%
o Low back pain: 61% (but radiological changes in 20% only)
Radiographic changes:
o Feet: Calcaneus (classic location)
• Early: posterior tubercle deossification
• Later: posterior tubercle erosions & enthesitis. Sausage digit, periostitis (especially toes)
o Axial:
- Bilateral (often symmetric) sacro-illitis
- Bulky paravertebral ossification
• Asymmetric
• May only involve one side
• Skip bodies
ANSWER: All are typical causes of reactive arthritis
Which is true regarding reactive arthritis? (March 2017)
a. Commonly seen following gastrointestinal infections
b. Pharyngitis is part of the clinical triad
c. Commonly involves the shoulder and the elbow
d. Axial involvement is usually symmetrical
e. Typically affects older patients
ANSWER: Reactive arthritis is commonly seen following gastrointestinal infections. Yersina, Campylobacter & Salmonella are most common.
Which is false of SLE arthritis? (September 2013)
a. Erosions
b. Osteoporosis
c. Calcification
Musculoskeletal SLE:
o Present in 75-90% of patients w varying severity
o Symmetric polyarthritis
Locations: • Small joints of the hand • Knees • Wrists • Shoulders
Features:
• Deforming non-erosive arthropathy
- Ligamentous laxity & muscular contracture
- Deformities are frequently reducible & less commonly disabling
• Periarticular osteoporosis
• Preserved joint spaces
• Carpal instability in 15%
o Spine: atlantoaxial subluxation in 10%
o Myositis: 30-50% observed clinically, but true myositis in 4%
o Osteonecrosis:
- Femoral head most common, but any site can be involved
- May be seen as part of the disease (particularly younger patients w Raynaud phenomenon) or as a complication of steroid treatment
o Soft tissue calcification
o Insufficiency fracture
o Osteomyelitis & septic arthritis
- Increased incidence due to steroid use & CRF
ANSWER: Erosions are not seen in SLE arthropathy
What does not typically cause arthritis? (March 2015)
a. CMV
b. Hepatitis B
c. EBV
d. Parvovirus
e. Rubella
More common causes of viral assoc arthritis:
o EBV
o Adenovirus & enterovirus
o Parvovirus B19 – adult presentation may be w arthralgia & arthritis
o Hepatitis A
o Hepatitis B – sudden onset, transient polyarthritis which mimics RA, typically accompanied by a rash
o Hepatitis C – 2-5% of chronic HCV develop an inflammatory oligo or polyarthritis which mimics RA but is not destructive
o Ross River Virus & Barmah Forest Virus
o Measles, mumps, rubella
• CMV, HSV & varicella are uncommon causes of arthritis
ANSWER: CMV does not typically cause arthritis
Regarding gout, which is false? (September 2013)
a. Associated with heavy alcohol intake
b. 10% die of renal failure
c. Patients form calcium oxalate renal stones
d. Tophus doesn’t normally calcify
e. Patients develop punched out erosions before articular erosions
Gout
o Transient attacks of acute arthritis initiated by crystallization of urates around joints
-> Leads to chronic gouty arthritis & tophi w repeated attacks
o Results from abnormalities of uric acid synthesis or excretion
Synthesis:
• Uric acid is the end product of purine metabolism
• Increased uric acid typically reflects abnormal purine metabolism
Excretion:
• Uric acid is filtered from the blood by the glomeruli & almost entirely resorbed by the proximal tubule
• Small fraction is secreted by the distal nephrons into urine
o Primary gout: Increased uric acid biosynthesis
o Secondary gout: Increased production of uric acid (e.g. rapid cell lysis) or decreased excretion (e.g. chronic renal disease)
o Joint disease:
- Deposition of MSU (monosodium urate) crystals in the joint
- Macrophages ingest the crystals & trigger an acute inflammatory response
• Proinflammatory cytokines, cell recruitment
• Urate crystals also activate the complement system
- Acute inflammation which remits following days/weeks
Factors influencing the conversion of hyperuricaemia to gout:
- Patient age - Duration of elevated uric acid - Heavy alcohol consumption - Obesity - Drugs e.g. thiazides - Toxins e.g. lead
Morphology:
Acute arthritis
• Dense neutrophilic infiltrate w/in the synovium & synovial fluid
• Slender, needle-like crystals w POSITIVE birefringence
• Oedematous & congested synovium
• Scattered chronic inflammation
Chronic tophaceous arthritis
• Urates can encrust the articular surfaces - Synovial deposits
• Hyperplastic & fibrotic synovium - Increased inflammatory infiltrates
• Synovial pannus extends from the cartilage to the juxta-articular bone - Erosions, fibrosis, eventual bony ankylosis
Tophi:
• Pathognomonic lesions
• Masses of urates surrounded by an intense mononuclear inflammatory reaction - Foreign body giant cells
• Common locations: ear, olecranon & patella bursae, periarticular ligaments & connective tissue
Gouty nephropathy:
• Deposition of monosodium urate crystals in the renal medulla
• Uric acid stones
• Obstruction can lead to secondary pyelonephritis
Clinical course:
- Chronic gout develops after years of episodes of acute gout (12 years average)
- Accompanying cardiovascular disease common – atherosclerosis & HTN
- 20% of patients die of secondary renal failure
ANSWER: 20% of patients die of renal failure (rather than 10%); calcium oxalate stones are seen in Crohn disease
Regarding CPPD, which is true? (September 2013)
a. Associated with hyperthyroidism
b. Associated with hyperparathyroidism
c. Negatively birefringent
d. More common in males
e. Peak age 40-50
Calcium pyrophosphate crystal deposition disease
Epidemiology:
- Typically occurs after age 50
- Hereditary variants present earlier (e.g. AD form).
- 30-60% prevalence by age 85
Associations with the secondary form: Trauma Hyperparathyroidism Haemochromatosis Diabetes
Clinical: Presentation similar to acute gout
Pathology:
- Altered matrix synthesis & degradation of pyrophosphates
- Crystals initially deposit in cartilage
- Deposits enlarge & rupture into and seed the joint
- Macrophages engulf the crystals & initiate a strong inflammatory response
- Recruitment of neutrophils
- Joint damage in 50%
- Crystals form chalky white, friable deposits. Rarely form large masses
- Crystals stain as oval blue-purple aggregates
- Weak positive birefringence, Geometric shapes
- Chronic lesions show mononuclear cell infiltrates & fibrosis
Location: Knees (most common) Wrists (TFCC calcification) Elbows Shoulders Ankles
ANSWER: CPPD is assoc w hyperparathyroidism
Which is true regarding CPPD? (March 2014)
a. Crystals are negatively birefringent
b. Mainly affects the ankle
c. Secondary CPPD is associated with haemochromatosis
• Crystals are have weak positive birefringence
Joints affected (decreasing order): o Knees o Wrists o Elbows o Shoulders o Ankles
Causes of secondary CPPD: o Trauma o Hyperparathyroidism o Haemochromatosis o Diabetes
Pathology:
o Altered matrix synthesis
o Degradations of pyrophosphates
o Crystals form in the cartilage as aggregates, elicit an inflammatory response when they seed into the joint
ANSWER: Secondary CPPD is assoc w haemochromatosis; the ankles are affected but not the most common joint
A man has severe patellofemoral joint OA, with knee chondrocalcinosis. What is the most likely associated finding? (March 2017)
a. Pubic symphysis calcification
b. Erosions of the CMC joints
c. 1st MTP juxta-articular erosions
ANSWER: Pubic symphisis calcification – the patient has CPPD & there is chondrocalcinosis of the pubic symphysis fibrocartilage.
Which is false regarding hydroxyapatite deposition disease? (March 2016, March 2017**)
a. Occurs at the tendon insertions in psoriatic arthritis
b. Occurs in the fingers in scleroderma
c. Is in the calcification in dermatomyositis
d. Has a characteristic appearance in the supraspinatus and the biceps tendons
e. Can occur at the gluteal muscle insertion in a patient presenting with hip pain
HADD – broad spectrum of musculoskeletal pathology due to deposition of hydroxyapatite deposition
o Homogenous calcification located at a tendon or a bursa
o Generally monoarticular
Location:
- Shoulder (most common): supraspinatus & biceps tendon
- External rotators of the hip: Gluteus medius tendon most common, may also involve gluteus maximus
- Less common: spine (longus coli & ligamentum flavum), elbow, knee, wrist & ankle
Characteristics of calcifications change overtime:
- Faint, Dense, May eventually resorb
Primary vs secondary:
Primary: tendinosis & bursitis
Secondary: end-stage renal disease, collagen vascular disease (dermatomyositis & scleroderma), vitamin D intoxication, tumoral calcinosis
o Assoc w osteoarthritis
- Milwaulkee shoulder is an extension of this, which causes rapid destructive arthropathy of the shoulder joint
ANSWER: HADD does not occur at the tendon insertions in psoriatic arthritis. Scleroderma & dermatomyositis are causes of secondary hydroxyapatite deposition. The shoulder and hip flexors are common sites of involvement.
**May be “which is true” – most correct is progressive destruction in the shoulder (Milwaulkee shoulder)
Regarding giant cell tumour of the tendon sheath: (March 2015)
a. When localised, it is usually confined to the hand
b. When diffuse…
Localised giant cell tumour of the tendon sheath
o Circumscribed proliferation of synovial like mononuclear cells w osteoclast like giant cells, foam cells, siderophages & inflammatory cells
- Usually in the fingers
- Second most common tumour of the hand after ganglion cysts
- Slow growing, painless mass (usually 2-5cm)
Epidemiology:
- 30-50 years. Females more commonly
Diffuse giant cell tumour of the tendon sheath
o Extra-articular, destructive villonodular hyperplasia w synovial mononuclear cells, multinucleated giants cells, foam cells, siderophages & inflammatory cells
o Soft tissue counterpart of pigmented villonodular synovitis (PVNS) -> PVNS occurs near a joint
Epidemiology:
- Rare. Females, <40 years
Features:
- Most commonly around the knee (80%) - Almost always mono-articular - May be locally aggressive & invade underlying bone & cartilage (hypoplastic, not neoplastic)
ANSWER: When localised, giant cell tumour of the tendon sheath is usually confined to the hand
What is the most common intracellular accumulation finding in muscle denervation?
a. Fat
b. Collagen
c. Lipofuscin
d. Haemosiderin
ANSWER: Fat
What is associated with inclusion body myositis? (March 2015)
a. Heliotrope rash
b. Cancer
c. Glomerulosclerosis
d. Myoglobinuria
Inflammatory myopathies
o DERMATOMYOSITIS
- Autoimmune disease of the skin & muscle
• Capillaries are the primary target of autoantibodies, including Jo1, Mi2 and PI55/P140
Early findings:
• Heliotrope rash: lilac rash of upper eyelids
• Periorbital oedema
Later disease manifestations:
• Weakness - Insidious onset, bilateral & symmetric. Proximal muscles affected first. Dysphagia in 1/3
• Scaling of the skin
• Gottron papules: erythematous patches over knuckles, elbows & knees
• Other: ILD, vasculitis & myocarditis
Associations:
• Calcinosis in 1/3
• Paraneoplastic syndrome in 15-25% of adults
• GI symptoms in children - Responsive to immunosuppressive therapy
o POLYMYOSITIS
- Primarily affects adults
- Similar features to dermatomyositis but no cutaneous involvement
- Driven by T-cell mediated myocyte damage
- Responsive to immunosuppressive therapy
o INCLUSION BODY MYOSITIS
- Begins as distal muscle involvement, particularly the quadriceps & distal upper limbs
• Dysphagia 50%
• Insidious onset
Epidemiology:
• Patients usually over 50
• Most common acquired neuropathy in patients >50
• Male predominance
Pathology:
• Thought to be due to intracellular deposition of abnormally folded proteins. Form inclusion bodies in the nuclei & cytoplasm of affected cells
• Most myositis antibodies are absent - Immunosuppressive therapies are of limited benefit
Associations:
• Diabetes mellitus (20%)
• Other autoimmune conditions (15%)
• Inflammatory myositis is a rare cause of myoglobinuria, more commonly assoc w rhabdomyolysis
ANSWER: Glomerulosclerosis may be the correct answer as it is assoc w diabetes (as is inclusion body myositis); helitrope rash & ‘cancer’ (paraneoplastic syndromes) are assoc w dermatomyosits; myoglobinuria is rare
What is the most common retroperitoneal malignancy? (March 2014)
a. Leiomyosarcoma
b. Myxofibrosarcoma
c. Liposarcoma
Most common primary retroperitoneal malignancies: o Liposarcoma o Myxofibrosarcoma o Leiomyosarcoma o Rhabdosarcoma o Fibrosarcoma
Retroperitoneal sarcoma may occur secondary radiotherapy or treatment for neuroblastoma
ANSWER: Lipsarcoma is the most common retroperitoneal malignancy
Which of the following associations is least correct? (March 2014)
a. Nodular fasciitis has irregular margins
b. Nodular fasciitis presents in the forearm
c. Nodular fasciitis is associated with trauma
d. Myositis ossificans has well defined margins
e. Myositis ossificans involves the proximal extremity
Nodular fasciitis
o Non-neoplastic lesions which are either idiopathic or develop in response to trauma (25%)
o Can grow rapidly & may have high cellularity, mitotic rate & numbers of reactive mesenchymal cells
- Clonal proliferation, but limited. t(17;22)
Locations: flexor forearm, chest, back or elsewhere
Morphology:
- Large, nodular neoplasms w ill-defined margins
Microscopic:
- Cellular & highly mitotic - Plump immature fibroblasts & myofibroblasts - Myxoid stroma & scattered lymphocytes
Myositis ossificans
o Focal intramuscular lesion composed of fibrous tissue & metaplastic bone
Epidemiology:
- Young, active males - 60-75% have a history of recent trauma - Also occur after elective surgery, severe burns & neurologic impairment
Sites: upper extremity flexors, quadriceps, thigh adductors, gluteal muscles, soft tissues of the hand
ANSWER: ?d – myositis ossificans may not have well defined borders in the acute phase
Which is false? (March 2015)
a. Plantar fibromatosis rarely causes contractures
b. Fibromatosis of the penis is often ventral
c. Abdominal fibromatosis can occur after surgery
d. Fibromatosis is associated with adenomatous polyposis
e. Extra-abdominal fibromatosis is most commonly seen in the shoulder
FIBROMATOSIS:
o Encompasses a wide range of soft tissue lesions which share an underlying histopathological pattern of fibrous tissue proliferation
o Vary in behaviour, from benign to malignant
Examples
- Benign: nodular fasciitis, proliferative fasciitis & myositis, myositis ossificans, elasto-fibroma, fibromatosis coli
- Intermediate (locally aggressive): superficial fibromatoses (palmar & plantar), dermoid type fibromatoses
- Intermediate (rarely metastasizing): solitary fibrous tumour, haemangiopericytoma, inflammatory myofibroblastic tumour
- Malignant: myxofibrosarcoma
PLANTAR FIBROMATOSIS:
o Benign fibroblastic proliferation of the plantar fascia - Musculoskeletal fibromatosis
o Children & adults, more common in males
Clinical:
- Middle or medial aspect of the plantar arch
- Symptomatic from mass effect or local invasion of the muscle or adjacent neurovascular bundle
- Flexion deformities do not usually occur (as w palmar fibromatosis)
Associations:
- Dupuytren’s disease (plantar fibromatosis) – 40% - Keloids - Peyronie disease
PEYRONIE DISEASE (fibromatosis of the penis): o Fibrous plaques form in the tunica albuginea which causes painful shortening & deformity of the penis - Plaques are usually seen on the dorsal aspect, but less commonly are present ventrally - Radiology used to examine the extent of the plaques & for possible involvement of the penile septum & the neuromuscular bundles (but Dx is clinical) - Cause of erectile dysfunction, esp if there is neuromuscular bundle involvement
Epidemiology: males 50-60 years
Associations: Plantar fibromatosis Dupuytren’s disease Penile trauma Diabetes Beta-blockers Paget’s disease of bone Phenytoin
INTRA-ABDOMINAL FIBROMATOSIS:
o Mesenteric, pelvic or retroperitoneal
Associations:
Post surgical
Gardner’s syndrome
Pregnancy – during or after, may see w C-section scar
EXTRA-ABDOMINAL FIBROMATOSIS: o Outside the abdomen & abdominal wall o Shoulder (20%), chest wall & back (17%), thigh o Genders affected equally o Head & neck more common in children
ANSWER: Fibromatosis of the penis is often dorsal – uncommonly ventral
Regarding fibromatosis, which is least likely? (March 2014)
a. Intra-abdominal fibromatosis is associated with Gardner syndrome
b. Palmar fibromatosis is commonly seen in the 4th and 5th metacarpal region
c. Penile fibromatosis is commonly associated with constriction of the urethra
d. Plantar fibromatosis is commonly seen in females
e. Abdominal fibromatosis is seen in post partum women
• Peyronie disease causes urethral narrowing
- Typically affects the dorsal surface of the penis
• Plantar fibromatosis is more common in men (2:1)
• Dupuytron contracture (palmer fibromatosis) most commonly affects the ring finger
ANSWER: Plantar fibromatosis is not more common in females (male predominance)
What is the commonest soft tissue sarcoma of the extremities? (August 2014)
a. Eosinophilic fibrosis
b. Myxoid sarcoma
c. Pleomorphic sarcoma
d. Synovial sarcoma
Pleomorphic sarcoma (formerly malignant fibrous histiocytoma) o Aggressive sarcoma, poor prognosis
Epidemiology:
- Slight male predilection
- Adults, peak age 59 years
- Most common type of soft tissue sarcoma
- 25-40% of all adult soft tissue sarcoma
- Most frequent sarcoma seen secondary to radiotherapy
- Can also arise secondary to Paget disease of bone
Location: retroperitoneum & proximal extremities
Synovial sarcoma:
o Intermediate to high grade soft tissue sarcoma
- Often has a more indolent course
Epidemiology:
- Young adults (15-40 years)
- Slight male predominace
- Second most common soft tissue sarcoma (2.5-10%)
- Usually arises in the soft tissues adjacent to large joints (e.g. around the knee in the popliteal fossa)
- Arise near joints, however very rare to arise from the joint
- Do not arise from synovial structures e.g. joints, tendon sheaths or bursae
ANSWER: Pleomorphic sarcoma is the most common soft tissue sarcoma of the extremities. Synovial sarcoma is the second most common.
Which is least likely to occur in a peripheral location in deep tissues? (August 2014)
a. Liposarcoma
b. Synovial sarcoma
c. Angiosarcoma
ANSWER: Angiosarcoma – more likely to be superficial or subcutaneous
Which is false regarding synovial sarcoma? (March 2016)
a. Contains multiple calcifications
b. Tumours larger than 5cm have a low 10 year survival rate
c. Tumours arise from the joint
- 30% of synovial sarcomas contain calcifications
- Tumours larger than 5cm have a poor prognosis
- Tumours arise near joints, but very rarely from the joint
ANSWER: Synovial sarcoma does not typically arise from the joint
