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YR2 BCS Study Points SEM 2 > Block 8 - Musculoskeletal > Flashcards

Block 8 - Musculoskeletal Flashcards

1
Q

What are 7 Risk Factors for Bone Neoplasia?

A

Risk Factors for Bone Neoplasia

  1. Ionising radiation
  2. Paget’s Disease
  3. Fibrous dysplasia
  4. Some chondromas
  5. Chronic suppurative osteomyelitis with SINUS
  6. Rb: bilateral germline mutation: retinoblastoma + osteosarcomas
  7. Li-Fraumeni syndrome: p53 mutation
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2
Q

What are 6 Benign bone tumors that are predominantly osseous?

A

BENIGN BONE TUMOURS - Predominantly osseous tumours

  1. Osteoid osteoma
  2. Osteoblastoma
  3. Giant-cell tumour (osteoclastoma)
  4. Osteoma
  5. Torus palatinus
  6. Myositis Ossificans
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3
Q

What are 4 Benign bone tumors that have cartilaginous components?

A

BENIGN BONE TUMOURS - Tumours with cartilaginous components

  1. (Distal) enchondroma
  2. Chondroblastoma
  3. Synovial chondromatosis
  4. Osteochondroma (cartilaginous exostosis)
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4
Q

What are 3 fibrous bone lesions?

A

Fibrous bone lesions

  1. Non-ossifying fibroma
  2. Ossifying fibroma
  3. Fibrous dysplasia
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5
Q

What are 6 types of cysts and haemangiomas of bone?

A

Bone lesions - Cysts and hemangiomas

  1. Unicameral bone cyst
  2. Aneurysmal bone cyst
  3. Intraosseous hemangioma
  4. Langerhans cell histiocytosis
  5. Ganglion cysts
  6. Synovial cyst
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6
Q

BENIGN BONE TUMOURS - What is an Osteoid Osteoma?

  • Description? (3)
  • Epidemiology?
    • Age & Sex
  • Location?
  • Characteristics? (2)
  • 4 Differential Diagnoses?
  • Treatment? (2)
A
  • Differential Diagnoses for an Osteoid Osteoma
    1. Stress fracture
    2. Brodie’s abscess
    3. Bone island
    4. Osteoblastoma
  • Treatment
    1. NSAIDs or surgical removal if pain is unresponsive to medical treatment
    2. Surgery – CT guided radiofrequency ablation or removal
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7
Q

BENIGN BONE TUMOURS - What is an Osteoid Osteoma?

  • Pathology?
  • Diagnostics?
A

BENIGN BONE TUMOURS -** **Osteoid Osteoma

Pathology

  • Tumour mass (nidus)
    • Good blood supply, comprised of osteoblasts providing osteoid fibrous bone
    • Osteoblasts → ↑prostaglandin E2 → pain
  • Nidus produces/envelopes itself in reactive bone

Diagnostics

  • X-ray: well-defined radiolucent core (osteoid), surrounded by perifocal sclerosis
  • Scintigraphy: usually intense enhancement
    • Double-density sign
    • Intraoperative nuclear imaging using a probe to detect the tumour
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8
Q

BENIGN BONE TUMOURS - What is an Osteoblastoma?

  • Description? (3)
  • Epidemiology?
    • Age & Sex
  • Location?
  • Characteristics? (2)
  • Treatment? (2)
A
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9
Q

BENIGN BONE TUMOURS - What is an Osteoblastoma?

  • Diagnostics?
    • Distinguish from osteosarcoma?
A

BENIGN BONE TUMOURS -** **Osteoblastoma

  • X-ray: central lucent nidus with mild or absent perifocal sclerosis
    • No periosteal reaction (unlike osteoid osteoma)
    • Adjacent sclerosis
    • Inner calcification
  • Biopsy
    • Immature trabeculae with single osteoblast layer
    • High dilated blood vessel number
    • Distinguish from osteosarcoma: Less mitotic activity, less cell atypia, No cartilaginous matrix, Does not imbue surrounding bone
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10
Q

BENIGN BONE TUMOURS - What is a Giant Cell Tumour (Osteoclastoma)?

  • Description? (5)
  • Epidemiology?
  • Location?
  • Characteristics?
  • Treatment? (2)
A
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11
Q

BENIGN BONE TUMOURS - What is a Giant Cell Tumour (Osteoclastoma)?

  • Diagnostics?
A

BENIGN BONE TUMOURS -** **Giant Cell Tumour (Osteoclastoma)

Diagnostics

  • X-ray: multicystic osteolytic lesions (soap-bubble appearance)
  • Nuclear medicine: “Doughnut sign” = increased periphery uptake, reduced centre uptake
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12
Q

BENIGN BONE TUMOURS - What is an Osteoma?

  • Description?
  • Epidemiology?
  • Location?
  • Characteristics?
  • Treatment?
A
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13
Q

BENIGN BONE TUMOURS - What is Myositis Ossificans?

  • Description?
  • Epidemiology?
  • Location?
  • Characteristics?
  • Diagnostics?
  • Differential Diagnosis?
  • Treatment?
A
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14
Q

BENIGN BONE TUMOURS - What is Myositis Ossificans?

A
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15
Q

BENIGN BONE TUMOURS - What is Torus palatinus?

  • Description?
  • Epidemiology?
  • Location?
  • Characteristics?
  • Treatment?
A

BENIGN BONE TUMOURS -** **Torus palatinus

  • Description → Benign bony overgrowth of the hard palate
  • Epidemiology → Peak incidence: young adults
  • Location → Roof of the mouth (midline hard palate)
  • Characteristics → Usually asymptomatic and requires no treatment
  • Treatment → If it interferes with speech or eating, surgery is an option.
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16
Q

BENIGN BONE TUMOURS - What is (Distal) Enchondroma?

  • Description? (1)
  • Epidemiology? (2)
  • Location? (1)
  • Characteristics? (7)
  • Treatment?
A
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17
Q

BENIGN BONE TUMOURS - What is a Chondroblastoma?

  • Description?
  • Epidemiology?
  • Location?
  • Characteristics?
  • Treatment?
A
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18
Q

BENIGN BONE TUMOURS - What is Synovial chondromatosis?

  • Description?
  • Epidemiology?
  • Location?
  • Characteristics?
  • Diagnostics?
  • Treatment?
A

BENIGN BONE TUMOURS -** **Synovial chondromatosis

  • Description
    • Enchondral formation of cartilage as a result of metaplasia of synovial tissue
    • Multiple nodules of hyaline cartilage in subsynovial connective tissue
    • If nodules calcify, is then called osteochondromatosis
  • Epidemiology → Peak incidence: 20–40 years
  • Location → Most commonly the knee joint
  • Characteristics
    • Pain, effusion, knee locking
    • Malignant degeneration to synovial chondrosarcoma in extremely rare cases
  • Diagnostics → Radiographically visible loose bodies
  • Treatment → Removal of loose bodies and synovial tissue
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19
Q

BENIGN BONE TUMOURS - What is Osteochondroma (cartilaginous exostosis)?

  • Description? (3)
  • Causes? (3)
  • Epidemiology? (3)
  • Location?
  • Characteristics?
  • Diagnostics?
  • Treatment?
A

BENIGN BONE TUMOURS - Osteochondroma (cartilaginous exostosis)

  • Description
    • Benign tumour, outgrowth of tubular bone growth plate
    • Bony exostosis with hyaline cartilage cap
    • Types
      1. Single sporadic mass (exostosis)
      2. Multiple osteochondromatosis
  • Causes
    • Mutation of EXT1/EXT2 genes involved in heparan sulfate glycosaminoglycan synthesis → local glycosaminoglycan reduction → disruption of cartilage, normal skeletal growth
    • Radiation-induced
    • Idiopathic
  • Epidemiology
    • Most common primary benign bone tumour
    • Peak incidence: 10–30 years
    • Sex: ♂ > ♀
  • Location → Metaphysis of long bone
  • Characteristics
    • Usually asymptomatic, but can be painful and palpable near the ends of long bones
    • Disease variant: hereditary multiple exostoses (malignant degeneration may occur)
    • Transformation into chondrosarcoma is rare
  • Diagnostics → X-ray: pediculated or sessile mass
  • Treatment → Excision of tumour in symptomatic cases
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20
Q

What does an Osteochondroma (cartilaginous exostosis) look like on x-ray?

A
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21
Q

BENIGN BONE TUMOURS - What is a non-ossifying fibroma?

  • Description? (2)
  • Epidemiology? (2)
  • Location? (1)
  • Characteristics? (1)
  • Diagnostics? (1)
  • Treatment? (2)
A
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22
Q

BENIGN BONE TUMOURS - What is an ossifying fibroma?

  • Description? (1)
  • Epidemiology? (1)
  • Location? (2)
  • Characteristics? (3)
  • Diagnostics? (1)
  • Treatment? (2)
A
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23
Q

BENIGN BONE TUMOURS - What is Fibrous dysplasia?

  • Description? (1)
  • Aetiology? (1)
  • Epidemiology? (3)
  • Location? (1)
  • Characteristics? (1)
  • Treatment? (2)
A

BENIGN BONE TUMOURS -** **Fibrous dysplasia

  • Description → Normal skeletal tissue is replaced by fibrous tissue
  • Aetiology → Post-zygotically acquired, somatic, gain-of-function mutation in GNAS1 gene on chromosome 20q
  • Epidemiology
    • Fibrous dysplasia accounts for approx. 5% of benign bone lesions
    • Age of onset: most commonly presents during adolescence
    • Sex: ♂ = ♀
  • Location → Monostotic fibrous dysplasia: long bones, facial bones (∼ 70% of cases)
  • Characteristics → Often asymptomatic; may cause bone pain
  • Pathophysiology → GNAS1 codes for the α subunit of the Gs protein (Gsα).
    • Mutation → constitutive activation of certain Gs-cAMP coupled pathways → inhibition of mesenchymal differentiation into osteoblasts → lack of osteocytes → skeletal lesions composed largely of mesenchymal cells → weak, imperfect bone with fibrous tissue
  • Treatment
    • Bisphosphonates
    • Management of precocious puberty
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24
Q

BENIGN BONE TUMOURS - What is Fibrous dysplasia?

  • Diagnostics?
A

BENIGN BONE TUMOURS -** **Fibrous dysplasia

Diagnostics

  • Laboratory tests
    1. ↑ Alkaline phosphatase (occasionally)
    2. Normal calcium, PTH, and 1,25-dihydroxyvitamin D levels
  • X-ray:
    • Long bones: well-defined, lobulated lytic lesions with a thin cortex and a radi olucent, ground-glass appearance
    • Facial bones: radiodense lesions with a leonine appearance
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25
Q

BENIGN BONE TUMOURS - What is a Unicameral bone cyst?

  • Description? (1)
  • Epidemiology? (1)
  • Location? (1)
  • Characteristics? (2)
  • Treatment? (2)
  • Diagnostics? (3)
A
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26
Q

What kind of bone cyst is this?

A

Unicameral bone cyst

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27
Q

BENIGN BONE TUMOURS - What is an Aneurysmal bone cyst?

  • Description? (1)
  • Epidemiology? (1)
  • Location? (3)
  • Characteristics? (3)
  • Diagnostics? (2)
  • Treatment? (1)
A
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28
Q

What kind of bone cyst is this?

A

Aneurysmal bone cyst

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29
Q

BENIGN BONE TUMOURS - What is an Intraosseous hemangioma?

  • Description? (1)
  • Epidemiology? (2)
  • Location? (2)
  • Characteristics? (2)
  • Diagnostics? (1)
  • Treatment? (1)
A
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30
Q

BENIGN BONE TUMOURS - What is Langerhans cell histiocytosis?

  • Description? (1)
  • Epidemiology? (1)
  • Location? (1)
  • Characteristics? (4)
  • Diagnostics? (4)
  • Treatment? (2)
A
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31
Q

SOFT TISSUE CYSTS - What is a ganglion cyst?

  • Description? (1)
  • Epidemiology? (2)
  • Location? (2)
  • Pathophysiology?
  • Characteristics? (4)
  • Differential Diagnoses? (5)
  • Treatment? (2)
A
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32
Q

What cyst is this?

A

Ganglion

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33
Q

SOFT TISSUE CYSTS - What is a Popliteal/Baker cyst (Synovial cyst)?

  • Description? (2)
  • Aetiology? (2)
  • Location? (1)
  • Characteristics? (3)
A
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34
Q

SOFT TISSUE CYSTS - What is a Popliteal/Baker cyst (Synovial cyst)?

  • Diagnostics? (3)
  • Treatment? (2)
A

SOFT TISSUE CYSTS -** **Popliteal/Baker cyst (Synovial cyst)

  • Diagnostics
    • Usually, a clinical diagnosis
    • Plain x-ray or ultrasound are commonly used as initial imaging modalities and reveal a soft tissue mass (x-ray) or an anechoic lesion (ultrasound).
    • MRI can be helpful in some case
  • Treatment
    • Asymptomatic cysts do not require treatment.
    • Symptomatic cysts
      • Treat underlying pathology of the knee joint
      • If symptoms persist, intra-articular injection of glucocorticoids can control inflammation.
      • Surgical resection for symptomatic cysts that persist despite treatment.
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35
Q

SOFT TISSUE CYSTS - What is a Popliteal/Baker cyst (Synovial cyst)?

  • Complications? (3)
A

SOFT TISSUE CYSTS -** **Popliteal/Baker cyst (Synovial cyst)

Complications

  1. Cyst enlargement and rupture → leakage of synovial fluid caudally into the lower leg muscles
  2. Rupture of a popliteal cyst may mimic a deep vein thrombosis!
  3. Positive Homan’s sign (calf pain during foot dorsiflexion)
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36
Q

What are 6 Malignant Bone Tumours?

A
  1. Ewings sarcoma
  2. Osteosarcoma
  3. Chondrosarcoma
  4. Malignant Fibrous Histiocytoma (Soft Tissue Sarcoma)
  5. Chordoma
  6. Mets/Secondary
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37
Q

MALIGNANT BONE TUMOURS - What is a Ewing’s Sarcoma?

  • Definition? (2)
  • Aetiology? (1)
  • Epidemiology? (3)
  • Localization? (3)
  • Characteristics? (4)
  • Clinical Features? (2)
A
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38
Q

MALIGNANT BONE TUMOURS - What is a Ewing’s Sarcoma?

  • Diagnostics?
    • Xray?
    • Biopsy?
    • Lab findings?
A

MALIGNANT BONE TUMOURS -** **Ewing’s Sarcoma

  • Conventional X-ray
    • Lytic bone lesions
    • Onion skin appearance of the periosteum
  • Biopsy
    • Very little cytoplasm and few mitotic figures
    • Very little matrix produced
    • PAS positive cells
    • Leu-7 and neuron-specific enolase positivity
    • Anaplastic small-blue-round-cell malignancy
    • Tumour cells resemble lymphocytes.
    • Differential diagnoses include lymphoma and chronic osteomyelitis.
    • Chromosomal translocation t(11;22)(q24;q12) which leads to expression of fusion protein EWS-FLI1
    • Cells contain glycogen accumulations and are usually CD99-positive.
  • Laboratory findings: ↑ ESR, ↑ LDH (lactate dehydrogenase), leucocytosis
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39
Q

MALIGNANT BONE TUMOURS - What is a Ewing’s Sarcoma?

  • Treatment? (2)
  • Prognosis? (3)
A
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40
Q

MALIGNANT BONE TUMOURS - What is an Osteosarcoma?

  • Definition? (1)
  • Aetiology? (3)
  • Epidemiology? (3)
  • Localization? (4)
  • Clinical Features? (3)
A
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41
Q

MALIGNANT BONE TUMOURS - What is an Osteosarcoma?

  • Diagnostics?
    • Imaging? (2)
    • Biopsy? (2)
    • Lab findings? (3)
A

MALIGNANT BONE TUMOURS -** **Osteosarcoma

1 - Imaging

  • Conventional x-ray
    • Sunburst appearance of lytic bone lesions and/or Codman triangles
    • Signs of osteolysis adjacent to osteosclerosis (moth-eaten appearance)
  • MRI: assesses the involvement of soft tissue, evaluation in cases of unclear radiographic findings

2 - Biopsy

  • Pleomorphic, malignant osteoblasts that produce osteoid
  • Osteosarcomas always feature woven bone matrix (compared to chondrosarcomas and fibrosarcoma)

3 - Laboratory

  • ↑ Alkaline phosphatase, ↑ LDH, ↑ ESR
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42
Q

MALIGNANT BONE TUMOURS - What is an Osteosarcoma?

  • Histology?
  • Treatment?
  • Prognosis?
A
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43
Q

MALIGNANT BONE TUMOURS - What is a Chondrosarcoma?

  • Definition?
  • Aetiology?
  • Epidemiology?
  • Localization?
  • Clinical Features?
  • Treatment?
  • Prognosis?
A
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44
Q

MALIGNANT BONE TUMOURS - What is a Chondrosarcoma?

  • Diagnostics?
    • Conventional X-ray or CT?
    • MRI?
    • Biopsy?
    • Grading?
A

MALIGNANT BONE TUMOURS -** **Chondrosarcoma

  • Conventional X-ray or CT
    • Osteolysis with a moth-eaten appearance
    • Intralesional calcifications (rings and arcs calcification, popcorn calcification)
    • Endosteal scalloping and cortical breach with infiltration of soft tissue
  • MRI: rim-like contrast enhancement
  • Biopsy
    • Malignant chondrocytes
    • Lobulated appearance (hyaline cartilage nodules with peripheral calcification)
  • Grading
    • Grade I: low cellularity, mostly chondroid matrix
    • Grade II: increased cellularity, decreased chondroid matrix with localized myxoid changes
    • Grade III: high cellularity, prominent nuclear atypia, myxoid matrix
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45
Q

MALIGNANT BONE TUMOURS - What is a Malignant Fibrous Histiocytoma (Soft Tissue Sarcoma)?

  • Definition?
  • Epidemiology?
  • Localisation?
  • Clinical Features?
A

MALIGNANT BONE TUMOURS -** **Malignant Fibrous Histiocytoma (Soft Tissue Sarcoma)

  • Definition
    • Fibrogenic tumour with cells producing collagen fibres but no osteoid
  • Epidemiology
    • Commonest soft tissue sarcoma
    • 15% of soft tissue sarcomata
    • Age 20 – 60 years
  • Localisation
    • Predilection for femur, humerus and tibia
    • Eccentrically placed close to joint
  • Clinical Features
    • Soft tissue mass with bone erosion but without periosteal reaction or sclerotic change
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46
Q

MALIGNANT BONE TUMOURS - What is a Chordoma?

  • Definition?
  • Epidemiology?
  • Localisation?
  • Treatment?
A
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47
Q

MALIGNANT BONE TUMOURS - What are Secondary (bone metastasis)?

  • Definition?
  • Aetiology?
  • Epidemiology?
  • Localisation?
  • Classification?
  • Clinical Features?
A
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48
Q

MALIGNANT BONE TUMOURS - What are Secondary (bone metastasis)?

  • Diagnostics?
    • Approach?
    • Lab findings?
    • Radiographic imaging?
    • Biopsy?
A
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49
Q

MALIGNANT BONE TUMOURS - What are Secondary (bone metastasis)?

  • Treatment?
A
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50
Q

What are 2 categories of Congenital and Developmental Bone Disorders and 2 examples of each?

A

Congenital and Developmental Bone Disorders

  • Dysostoses
    1. Amelia
    2. Phocomelia (“seal extremity”)
  • Dysplasias
    1. Achondroplasia
    2. Osteogenesis imperfecta (brittle bone disease)
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51
Q

What is Dysostoses?

  • Amelia?
  • Phocomelia?
A
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52
Q

DYSPLASIAS - What is Achondroplasia?

  • Definition?
  • Epidemiology?
  • Aetiology?
  • Pathophysiology?
A
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53
Q

DYSPLASIAS - What is Achondroplasia?

  • Clinical Features?
A
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54
Q

DYSPLASIAS - What is Achondroplasia?

  • Diagnostics?
  • Therapy?
A

DYSPLASIAS - Achondroplasia

Diagnostics

  • Physical examination
  • DNA test
  • X-ray findings
    • Lateral skull: frontal prominence, midface hypoplasia
    • Spine: spinal canal stenosis, scoliosis
    • Extremities: short, thick bones
  • CT/MRI head: indicated in patients with signs of cervicomedullary compression
    • Assessment of brain stem compression
    • Measurement of the size of the foramen magnum

Therapy

  • Early initiation of growth hormone therapy (between 1–6 years of age)
  • Surgical correction of spinal stenosis, secondary scoliosis, genu varum, brain stem compression
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55
Q

DYSPLASIAS - What is Osteogenesis imperfecta (brittle bone disease)?

  • Definition?
  • Epidemiology?
  • Aetiology?
  • Pathophysiology?
  • Diagnostics?
  • Therapy?
A
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56
Q

DYSPLASIAS - What is Osteogenesis imperfecta (brittle bone disease)?

  • Clinical Features?
A

Osteogenesis imperfecta type I (the mildest and most common form)

  • Growth delay
  • Skeletal deformities, brittle bones
  • Bowing of bones and saber shins
  • Fractures during childbirth and recurrently from minimal trauma thereafter
  • Blue sclerae (choroidal veins show through the thin, translucent sclera)
  • Progressive hearing loss due to deformation, fracture, and/or atrophy of the ossicles
  • Brittle, opalescent teeth (dentinogenesis imperfecta; due to a lack of dentin)
  • Ligamentous laxity and joint hypermobility

Osteogenesis imperfecta type II

  • Most severe form; lethal perinatally or within the first year
  • Multiple intrauterine and/or perinatal fractures
  • Underdeveloped lungs and subsequent respiratory problems
  • Laboratory tests: ↑serum alkaline phosphatase & ↑Ca2+ in urine
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57
Q

Inflammatory/Infectious Bone Diseases - What is Osteomyelitis?

  • Definition?
  • Epidemiology?
  • Types?
A
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58
Q

Inflammatory/Infectious Bone Diseases - What is Osteomyelitis?

  • Aetiology?
    • Routes of infection?
    • Risk factors?
A
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59
Q

Inflammatory/Infectious Bone Diseases - What is Osteomyelitis?

  • Most common pathogens causing osteomyelitis?
A
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60
Q

Inflammatory/Infectious Bone Diseases - What is Osteomyelitis?

  • Clinical Features?
    • Acute osteomyelitis and subacute osteomyelitis?
    • Chronic osteomyelitis?
A
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61
Q

Inflammatory/Infectious Bone Diseases - What is Osteomyelitis?

  • Diagnostics?
    • Approach?
    • Lab studies?
    • Imaging?
    • Bone biopsy?
A
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62
Q

Inflammatory/Infectious Bone Diseases - What is a Brodie’s Abscess?

  • Definition?
  • Pathophysiology
  • Clinical features
  • Diagnostics
  • Treatment?
A
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63
Q

Inflammatory/Infectious Bone Diseases - What is Osteomyelitis?

  • Prognosis?
A
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64
Q

Inflammatory/Infectious Bone Diseases - What Osteonecrosis/Avascular (Aseptic) Necrosis?

  • Definition?
  • Aetiology?
  • Subtypes/Variants?
A
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65
Q

Inflammatory/Infectious Bone Diseases - What Osteonecrosis/Avascular (Aseptic) Necrosis?

  • Clinical features?
  • Diagnostics?
  • Treatment?
A
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66
Q

How are Metabolic Bone Diseases classified?

  • Disorders with OSTEOCLAST DYSFUNCTION? (2)
  • Disorders with ABNORMAL MATRIX? (3)
  • Disorders with ABNORMAL MINERAL HOMEOSTASIS? (3)
A

Metabolic Bone Diseases -** **Classification:

  • Disorders with OSTEOCLAST DYSFUNCTION
    1. Paget’s Disease
    2. Osteopetrosis
  • Disorders with ABNORMAL MATRIX
    1. Osteogenesis imperfecta (I-IV)
    2. Mucopolysaccharidoses
    3. Osteoporosis
  • Disorders with ABNORMAL MINERAL HOMEOSTASIS
    1. Rickets & Osteomalacia
    2. Hyperparathyroidism
    3. Renal Osteodystrophy
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67
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Paget Disease of Bone (Osteitis deformans)?
    • Definition?
    • Epidemiology?
    • Aetiology?
    • Pathophysiology?
A
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68
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Paget Disease of Bone (Osteitis deformans)?
    • Stages of Disease?
    • Localisation?
A
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69
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Paget Disease of Bone (Osteitis deformans)?
    • Clinical Features?
A
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70
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Paget Disease of Bone (Osteitis deformans)?
    • Diagnostics - Lab findings?
      • Blood work?
      • Urinalysis?
A

Paget Disease of Bone (Osteitis deformans)

Diagnostics - Laboratory tests

  • Blood work
    • Normal calcium, phosphate, and parathyroid hormone (PTH) levels
    • ↑↑ Serum alkaline phosphatase (ALP) = most common cause of isolated elevated ALP in patients >40 years old.
    • Hyperuricemia
  • Urinalysis: ↑ markers of collagen degradation
    • Deoxypyridinoline
    • N-telopeptide, C-telopeptide
    • Hydroxyproline
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71
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Paget Disease of Bone (Osteitis deformans)?
    • Diagnostics - Imaging?
      • x-ray?
A

Paget Disease of Bone (Osteitis deformans)

Imaging - X-ray

  • Deformed bones with both sclerotic and osteolytic lesions
  • Sclerotic lesion: focus/foci of ↑ density (usually the result of increased mineralization and/or thickening).
  • Osteolytic lesion: focus/foci of ↓ density (usually the result of decreased demineralization).
  • Thickened cortical bone
  • Coarsened trabeculae; expansion or enlargement of a region of the bone.
  • Skull x-ray: thickening of the diploe; osteoporosis circumscripta (cotton wool appearance).
  • Vertebral x-ray: thickening of the upper and lower plates of the vertebral body gives rise to a “picture frame” appearance; diffuse enlargement of the vertebrae (ivory vertebra)
  • Pelvic x-ray: disruption/fusion of sacroiliac joints; thickened iliopectineal line (brim sign)
  • Bone scans (skeletal scintigraphy): to test for additional bony lesions
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72
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Paget Disease of Bone (Osteitis deformans)?
    • Treatment?
      • 1st line?
      • 2nd line?
      • 3rd line?
    • Complications?
A
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73
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Osteopetrosis (marble bone disease)?
    • Definition?
    • Epidemiology?
    • Aetiology?
      • Type I?
      • Type II?
    • Pathophysiology?
A
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74
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Osteopetrosis (marble bone disease)?
    • Clinical Features?
    • Diagnostics?
      • X-Ray?
      • Lab findings?
    • Therapy?
A
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75
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MATRIX

  • What is Osteoporosis?
    • Definition?
    • Aetiology?
    • Subtypes?
    • Clinical features?
    • Diagnostics?
    • Treatment?
A
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76
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Osteomalacia (Adults)?
    • Definition?
    • Aetiology?
      • Vitamin-D dependent forms?
      • Vitamin-D independent forms?
A
77
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Osteomalacia (Adults)?
    • Pathophysiology?
    • Clinical Features?
A
78
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Osteomalacia (Adults)?
    • Diagnostics?
      • Laboratory tests?
      • Imaging?
      • Bone Biopsy?
    • Treatment?
A
79
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Rickets (Children)?
    • Definition?
    • Clinical features?
A
80
Q

Metabolic Bone Diseases - Disorders with ABNORMAL MINERAL HOMEOSTASIS

  • What is Rickets (Children)?
    • Diagnostics?
A

Disorders with ABNORMAL MINERAL HOMEOSTASIS - Rickets

  • Laboratory tests
    • ↓ Calcium and ↓ phosphate
    • ↑ Alkaline phosphatase and ↑ PTH
    • Vitamin D-dependent rickets type 1: ↓ calcitriol concentration
    • Vitamin D-dependent rickets type 2: ↑ calcitriol concentration
  • Imaging
    • ↓ bone density
    • Cortices thinning
    • Growth plates in the metaphysis of the long bones are less defined and show cupping, stippling, and fraying
    • Wide epiphysis
    • In severe cases, Looser zones and fractures
    • Chest X-ray: prominent costochondral junctions
    • Evidence of bone deformities
81
Q

Outline the role of different imaging modalities used to diagnose benign and malignant bone lesions.

Bone pain imaging pathway?

A
82
Q

Terminology - What is:

  • Sclerotic Lesion?
  • Lytic Lesion?
  • Periosteal Reaction (Periostitis)?
  • Benign Periosteal Reaction?
  • Aggressive Periosteal Reaction?
A
  • Sclerotic Lesion: An abnormal increase in density and hardening/thickening of bone, usually from a slow - growing lesion (gain of bone), looks like ‘crazy paving’
  • Lytic Lesion: Destruction of an area of bone (loss of bone), looks ‘moth-eaten’
  • Periosteal Reaction (Periostitis): The formation of new bone in response to injury or other stimuli of the periosteum surrounding the bone. Will occur whenever the periosteum is irritated by a malignant tumour, benign tumour, infection or trauma.
  • Benign Periosteal Reaction: Thick, wavy and uniform callus formation resulting from chronic irritation. The periosteum has time to lay down thick new bone and remodel it into a more normal -appearing cortex.
  • Aggressive Periosteal Reaction: Multilayered, lamellated or bone formation perpendicular to the cortical bone which may be spiculated and interrupted. Sometimes there is a Codman’s triangle which is elevation of the periosteum away from the cortex, forming an angle where the elevated periosteum and bone come together. In aggressive periostitis the periosteum does not have time to consolidate.
83
Q

What are the Radiological Features of Benign and Malignant Bone Lesions?

  • Plain X-ray?
    • Benign = 8
    • Malignant = 12
  • MRI?
  • Technetium scan?
A
84
Q

What are the locations of common bone lesions?

A
85
Q

Role of Investigations of Bone Tumours?

  • Plain x-ray?
  • MRI?
  • CT?
  • Nuclear medicine?
A
86
Q

Staging Investigations for Bone Tumours:

  • X-Ray?
  • MRI?
  • Bone Scan (Technetium)?
  • CT Chest Scan?
A

Staging Investigations for Bone Tumours:

  • X-Ray: To evaluate the primary lesion and the joint above and below
  • MRI: To plan surgery or biopsy (or sometimes CT)
  • Bone Scan (Technetium): To assess for bony secondaries (+/- PET)
  • CT Chest Scan: To assess for lung mets (osteosarcoma usually spreads to lungs, not LNs)
  • NB: Do staging before biopsy! Biopsy is either CT-guided core or open biopsy by orthopaedic surgeon, not FNA!
87
Q

What are the 10 steps in a normal fracture healing process?

A
88
Q

What are 5 risk factors for poor fracture healing?

A

Risk factors for poor fracture healing:

  1. Unstable
  2. Comminuted
  3. Severely displaced
  4. Infected
  5. Poorly vascularised fracture
89
Q

What are 4 Early and 6 Late complications of fractures?

A
90
Q

What is Compartment Syndrome?

  • Definition?
  • Pathophysiology?
  • 5 Ps?
  • Treatment?
A
91
Q

What are 4 Types of Fractures?

A

Types of Fractures:

  1. Acute Traumatic: Fracture caused by an accident, fall or other kind of force e.g. MVA
  2. Pathological: Fracture caused by a disease process e.g. tumour, osteomyelitis, osteonecrosis, Paget disease or osteoporosis
  3. Stress: Fracture due to normal bone but abnormal (repetitive) stress e.g. runners or obese people
  4. Insufficiency: Fracture due to normal stress (physiological load) but abnormal weak bone e.g. osteoporosis or long-term bisphosphonate use commonly causing lumbar crush and sacral/pelvic fractures
92
Q

Patterns of Fractures:

  • Greenstick Fracture?
  • Linear Fracture?
  • Transverse Fracture?
  • Oblique Fracture?
  • Spiral/Rotation Fracture?
  • Comminuted Fracture?
  • Segmental Fracture?
  • Open/Compound Fracture?
  • Closed/Simple Fracture?
  • Complete Fracture?
  • Incomplete Fracture?
  • Stable Fracture?
  • Unstable Fracture?
A
93
Q

What is the Salter-Harris classification of physeal fractures?

A
94
Q

What are 3 mechanisms of fractures?

A

Mechanism of Fractures:

  • Impacted Fracture: When the broken ends of the bone are jammed together by the force of the injury
  • Compression Fracture: When an excessive axial load compresses the bone beyond its limits (vertebral bodies)
  • Depressed Fracture: A localised force breaks and depresses one segment below the level of surrounding bone
95
Q

What are the 6 steps/aspects of describing a fracture?

A
96
Q

Staging for osteosarcomas?

A
97
Q

What is the management for limb fractures?

  • Acute?
  • Intermediate?
  • Late?
A
98
Q

What are 7 differentials for lumps of the knee?

A
99
Q

Identify different cell types involved in the immune response and discuss their function.

  • What are the 7 myeloid progenitor cells that are involved in the innate immune response?
A

Myeloid Progenitor Cells

  1. Neutrophils
  2. Eosinophils
  3. Basophils
  4. Mast cells
  5. Monocytes
  6. Dendritic cells
  7. Macrophages
100
Q

What are Macrophages/Monocytes?

A

Cells of Innate Immune Response - Myeloid Progenitors

Macrophages/Monocytes: A large mononuclear phagocytic cell type important as scavenger cells, pathogen recognition cells, source of pro-inflammatory cytokines in innate immunity, antigen presenting cells and as effector phagocytic cells in humoral and cell-mediated immunity. MOs derive from bone marrow precursors and are found in most tissues of the body. Precursors found in the blood are known as monocytes.

101
Q

What are Dendritic cells?

A

Cells of Innate Immune Response - Myeloid Progenitors

Dendritic Cells: Bone marrow derived cells found in most tissues, including lymphoid tissues. Conventional DCs take up antigen in peripheral tissues and travel to the peripheral lymphoid organs, where they are the most potent stimulators of T-cell responses.

  • phagocytes, antigen-presenting cells
  • release cytokines to recruit other cells
  • circulate in lymph, blood tissue
  • consume large proteins in interstitial fluid
  • break blood-borne pathogens into small amino-acid chains → move to lymph node → present antigen to T cells
102
Q

What are neutrophils?

A

Cells of Innate Immune Response - Myeloid Progenitors

Neutrophils: The most numerous type of WBC in human peripheral blood. NOs are phagocytic cells with multilobed nucleus and granules that stain with neutral stains (light pink). They enter infected tissues and engulf and kill extracellular pathogens.

103
Q

What are eosinophils?

A

Cells of Innate Immune Response - Myeloid Progenitors

Eosinophils: A type of WBC containing granules that stain eosin (red). It is thought to be important chiefly in defence against parasitic infections, but is also important as an effector cell in allergic reactions.

104
Q

What are Basophils?

A

Cells of Innate Immune Response - Myeloid Progenitors

Basophils: A type of WBC containing granules that stain with basic dyes (blue-purple). It is thought to have a function similar to mast cells.

105
Q

What are Mast Cells?

A

Cells of Innate Immune Response - Myeloid Progenitors

Mast Cells: A large granule-rich cell found in connective tissues throughout the body, most abundantly in the submucosal tissues and the dermis. The granules store bioactive molecules including vasoactive amine histamine, which are released on mast-cell activation. Mast cells are thought to be involved in defences against parasites and they have a crucial role in allergic reactions.

106
Q

What are Natural Killer Cells?

A

Cells of Innate Immune Response - Myeloid Progenitors

Natural Killer Cells: Large granular lymphocytes which kill virus-infected cells and some tumour cells. NK cells bear a wide variety of invariant activating and inhibitory receptors, but do not rearrange immunoglobulin or T-cell receptor genes. NK cells are important in innate immunity to viruses and other intracellular pathogens and in antibody-dependent cell-mediated cytotoxicity (ADCC).

107
Q

What are lymphocytes?

A

Lymphocytes: A class of WBC that bear variable cell-surface receptors for antigen and are responsible for adaptive immune responses, which include B and T cells. On antigen recognition, a lymphocyte enlarges to form a lymphoblast and then proliferates and differentiates into an antigen-specific effector cell.

108
Q

What are B cells/lymphocytes?

A

Cells of Innate Immune Response - Lymphoid Progenitors

B Cells/Lymphocytes: Generated in the bone marrow and mediate humoral immunity. Antigens bind to a B cell receptor (BCR) causing B cells to proliferate and differentiate into plasma cells which produce antibody.

109
Q

What are T cells/lymphocytes?

4 types?

A

Cells of Innate Immune Response - Lymphoid Progenitors

T Cells/Lymphocytes: Originate in the bone marrow, but develop and mature in the thymus and are responsible for cell-mediated immunity. The highly variable T cell receptor (TCR) recognises peptide-antigen complexes bound to MHC molecules on cell surfaces. Effector T cells perform a variety of functions including activation of macrophages (Th1), activation of B cells (Th2) and the killing of virus-infected cells (CTL).

  • Types
    1. CD4 Type 1 T Helper (Th1) Cell
    2. CD 4 Type 2 T Helper (Th2) Cell
    3. CD8 Cytotoxic T Cell (CTL)
    4. Suppressors (Treg) Cells
110
Q

Describe the 4 types of T cells?

A

Cells of Innate Immune Response - Lymphoid Progenitors

  1. CD4 Type 1 T Helper (Th1) Cell: Part of cell-mediated immunity which acts to secrete cytokines such as INF-y, IL-2 and TNF-b to activate CLT and macrophages
  2. CD 4 Type 2 T Helper (Th2) Cell: Part of humoral immunity and acts to promote B cell maturation following antigen-MHC II complex recognition and costimulatory signals
  3. CD8 Cytotoxic T Cell (CTL): Part of cell-mediated immunity which act to kill cells expressing anitgen- MHC I complex by releasing granules that contain perforin and granzyme for cell lysis and proteases to induce an apoptosis response within the cell
  4. Suppressors (Treg) Cells: Have an immunosuppressive effect that inhibits cell-mediated immunity at the end of a response and destroys autoimmune T cells that aren’t filtered out by negative selection in the thymus (induced by IL-10, IL-35 and TGF-b)
111
Q

What are memory cells?

A

Memory Cells: B and T lymphocytes that mediate immunological memory. They are more sensitive than naïve lymphocytes to antigen and respond rapidly on re-exposure to the antigen that originally induced them.

112
Q

What do each of the immune cells look like under a microscope?

A
113
Q

List the immune cells in Order of Cell Abundance in Plasma.

A

NB: Order of Cell Abundance in Plasma is Neutrophils -> Lymphocytes -> Monocytes -> Eosinophils -> Basophils (Never Let Monkeys Eat Bananas)

114
Q

What are the 3 classifications of immune cells?

A
115
Q

What do phagocytes do?

A
116
Q

What are the 5 stages in the innate immune response?

  • What are PRRs? (3)
  • What are PAMPs? (6)
  • What do mast cells release? Effect?
  • What 4 things do NOs, DCs and MOs release?
  • 6 components of leukocyte migration? (MRAADC)
  • Role of selectins?
  • Role of integrins?
A
117
Q

What is involved in the adaptive immune response?

  • Which cells are involved in antigen presentation of exogenous/extracellular antigens?
    • Which MHC class?
    • Which T cell type?
  • Which cells are involved in antigen presentation of endogenous/intracellular antigens?
    • Which MHC class?
    • Which T cell type?
  • 4 steps in the T cell independent response?
A

Adaptive Immune Response:

  • Antigen Presentation (Exogenous/Extracellular Antigens): Dendritic cells recognise extracellular pathogenic proteins and internalise, process and present Ag on MHC II to CD4 T cells at the lymph nodes, activating T helper cells.
  • Antigen Presentation (Endogenous/Intracellular Antigens): Intracellular antigens (viruses or intracellular bacteria) are processed by pathogen ‘target cells’ for the eventual presentation on MHC I to CD8 T cells, activating T killer cells (CTL).
  • T-Cell Dependent Response (Protein Antigen)
  • T-Cell Independent Response (Carbohydrate/Lipid/DNA Antigen):
    1. B cells are able to pick up and present soluble Ag in the lymph node independent to T cell interaction.
    2. Carbohydrate or lipid Ag bind to IgM or IgD of naïve B cell.
    3. Highly repetitive structures cause BCR crosslinking (strong clustering) which provides a signal to activate the B cell.
    4. B cell upregulates production and release of IgM. No T helper cell means no class switching, only monoclonal Abs, no memory and only modest affinity.
118
Q

Describe the steps in humoral immunity?

A
119
Q

What are the 6 steps involved in the T-Cell Dependent Response to a Protein Antigen?

  • 4 steps in B cell activation?
    • What is clonal expansion?
    • What is SMH?
    • Affinity maturation?
    • CSR?
A

T-Cell Dependent Response (Protein Antigen):

  1. Peptide Ag binds to BCR of B cell in lymph node
  2. Ag is internalised and processed and peptide antigens are presented on MHC II for Th2 cell recognition at paracortex of lymph node (here BCR acts as APC)
  3. Th2 recognises antigen-MHC complex via TCR
  4. CD80/86 (or B7) binds to CD28 on T cells and provides a signal to activate T cell
  5. T cell upregulates expression of CD40L which binds to CD40 to activate B cells and also expresses cytokines IL-4, IL-5, IL-6, IL-10 and IL-13 for B cell activation and differentiation
  6. Activated B cell migrates to germinal centre of lymph node for proliferation and differentiation into Ab-secreting B cells (plasma cells) and memory cells
    1. Clonal Expansion: Proliferation of activated B cell in dark zone of germinal centre of secondary lymphoid tissue.
    2. Somatic Hypermutation (SMH): The phenomenon in which a high frequency of point mutations are generated within the variable region of expressed immunoglobulin genes in response to the presence of an antigen, in the dark zone of germinal centres. Produces functional and non- functional Ab with a range of high/low affinity for Ag, so Ab must go through a selection process to determine those with greatest affinity to Ag.
    3. Affinity Maturation: The positive selection of Ab with greatest affinity for Ag via a process in which follicular dendritic cells (FDCs) or Th2 cells (follicular T helper cells) present Ag to light zone germinal centre B cells and B cells with highest/improved affinity Ab-Ag complexes compete more effectively for survival signals from FDCs. FDCs and Th2 interact via costimulatory signals (CD80/86-CD28 and CD40-CD40L) and cytokines IL-4, IL-5, IL-6, IL-10 and IL-13 which induce B cell activation, growth and differentiation (same as initial interaction with Th2)
    4. Class Switch Recombination (CSR): B cell with improved Ag affinity undergo change in Fc region of chain to change into a different immunoglobulin (IgM to IgG, IgE or IgA) in light zone germinal centre, influenced by cytokine environment produced by T helper cells. B cells differentiate into plasma cells or memory cells.
120
Q

What are the 6 Inflammatory (“Seropositive”) Joint Diseases?

A

Inflammatory (“Seropositive”) Joint Disease:

  1. Rheumatoid Arthritis (RA)
  2. Systemic Lupus Erythematosus
  3. Sjögren’s Syndrome
  4. Idiopathic Juvenile Arthritis
  5. Progressive Systemic Sclerosis & CREST Syndrome
  6. Inflammatory Myopathies
121
Q

Describe the overall Pathogenesis of Inflammatory (“Seropositive”) Joint Disease.

A

Pathogenesis of Inflammatory (“Seropositive”) Joint Disease: Autoimmune!

  • There is persistent synovitis, causing chronic symmetrical polyarthritis and systemic inflammation.
  • Initially, non-specific inflammation affects the synovial tissue, which is later amplified by activation of T cells (autoimmune response).
  • With time, it may lead to inflammatory joint effusion and synovial hypertrophy, as well as progressive destruction and deterioration of cartilage and bone.
    • Synovial lining hyperplasia
    • Pannus formation (proliferative granulation tissue) along the synovial tissue, production of proteinases and destruction/erosion of cartilage extracellular matrix (articular cartilage and bone)
    • Extra-articular manifestations
122
Q

What is the pathogenesis of Rheumatoid Arthritis (RA)? (9 steps)

  • Which 2 genes make you more susceptible to RA?
  • Which 2 environmental factors can increase RA susceptibility?
  • Which 2 self-antigens do autoantibodies get produced against?
  • Which 2 cytokines to T cells initially secrete to recruit macrphages? Which 3 cytokines do the macrophages then produce?
  • What is a pannus?
  • 2 antibodies?
A

NB1: The triggering antigen, which leads to self-maintained inflammation in RA, remains unclear. Triggers for anti- citrullinated peptide antibodies (ACPA) production include filaggrin, type II collagen and vimentin. There is little evidence that collagen type II is the triggering antigen, although it is a cause of arthritis in animal models of RA. Smoking is a potential trigger, particularly in ACPA positive RA.

NB2: Citrullination is the process where arginine amino acid residues can be enzymatically converted into citrulline residues in proteins such as vimentin or fibrinogen during inflammation.

123
Q

Discuss the extra-articular manifestations of RA? (9)

A

Extra-articular effects of Rheumatoid Arthritis

  1. Acute phase response
  2. Normochromic normocytic anaemia
  3. Vasculitis
  4. Lymphadenopathy
  5. Serositis – includes pericarditis
  6. Granuloma Rheumatoid nodules
  7. Amyloidosis
  8. Pulmonary fibrosis
  9. Felty’s syndrome - hypersplenism
124
Q

Describe the pathogenesis and joint features of RA.

A
125
Q

What are the x-ray manifestations of RA?

A
126
Q

Classification criteria of RA?

List and describe 3 specific deformities of the hand caused by RA.

A
127
Q

Role of Immune System in Inflammatory Joint Disease

  • Which 6 cell types hold critical positions in sustaining synovitis in RA?
A
128
Q

What role do the following cells play in the pathogenesis of RA?

  • Plasma (B) Cells
  • CD4+ T Helper Cells
  • TH1 Cells
  • TH17 Cells
  • Macrophages
  • Osteoclasts
  • Synovial Cells
A

Role of Immune System in Inflammatory Joint Disease (Example of RA)

  • Plasma (B) Cells: Produce autoantibodies to Fc portion of IgG (rheumatoid factor) and to citrullinated cyclic peptide.
  • CD4+ T Helper Cells: May initiate the autoimmune response by reacting with an arthritogenic agent, perhaps microbial or a self-antigen
  • TH1 Cells: Produce IFN-y to activate macrophages and resident synovial cells
  • TH17 Cells: Produce IL-17 to recruit neutrophils and monocytes
  • Macrophages: Produce TNF-a and IL-1 to stimulates resident synovial cells to secrete proteases that destroy hyaline cartilage. Overproduction and overexpression of TNF-a is a key inflammatory element in RA, leading to synovitis and joint destruction. Interaction of macrophages and T and B lymphocytes drives this overproduction. TNF-α stimulates overproduction of interleukin-6 and other cytokines.
  • Osteoclasts: RANKL expressed on activated T cells stimulates bone resorption
  • Synovial Cells: In chronic rheumatoid synovitis, are predominantly abnormally behaving fibroblast-like Synoviocytes and macrophage-like synoviocytes which produce pro-inflammatory cytokines.
129
Q

What role do the following cells play in the pathogenesis of RA?

  • Abnormal Fibroblast-Like Synoviocytes?
  • Synovial fibroblasts?
  • Complement?
  • Mast cells?
A

Role of Immune System in Inflammatory Joint Disease (Example of RA)

  • Abnormal Fibroblast-Like Synoviocytes: Appear to circulate between joints and may be the trigger for the polyarthritis
  • Synovial Fibroblasts: Have high levels of the adhesion molecule, vascular cell adhesion molecule (VCAM-1: a molecule which supports B lymphocyte survival and differentiation), decay accelerating factor (DAF: a factor that prevents complement-induced cell lysis) and cadherin-II (which mediates cell to cell interactions). These molecules may facilitate the formation of ectopic lymphoid tissue in synovium.
  • Complement: Activated by immune complexes of RF and anti-CCP antibodies in synovial joints. As RFs have the Fc portion of IgG as their antigen they have the potential for self-aggregation and immune complex formation in the synovium. These may then trigger complement (classical pathway) and macrophages via IgGFc receptors and potentiate the inflammatory response.
  • Mast Cells: Release of histamine which contributes to increased vascular permeability and vasodilation, potentiating the inflammatory response.
130
Q

Describe the Mechanisms and Classification of Hypersensitivity Reactions.

A
131
Q
A
132
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Pathogenesis and clinical findings of Type I hypersensitivity?
A

Type I Hypersensitivity

  • Specific IgE is constitutively present bound to its receptor on mast cells
  • One new element results in pathology - antigen
  • One class of antibody - IgE
133
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Common Type I hypersensitivity reactions?
  • 5 Clinical features?
A

Clinical features of Type I hypersensitivity reactions

  1. Anaphylaxis
  2. Angioedema
  3. Bronchospasm
  4. Urticaria (hives)
  5. Hypotension
134
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Pathogenesis and clinical findings of Type II hypersensitivity?
A

Type II Hypersensitivity

  • The antigen is part of the target cell or tissue
  • Two things are needed - antibody + an effector
  • Can be one of 2 sorts of Ig - IgG or IgM
  • Can be one of 2 sorts of effector - cell or complement
  • Type II hypersensitivity is mediated by antibodies of the IgG and IgM classes
  • Antibodies are directed against cellular or ECM proteins
  • Antigen-bound immunoglobulin induces
    1. Effector cell activation via Fc receptors
    2. Complement activation
  • Intracellular antigens mainly do not provoke a Type II hypersensitivity response.
135
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Common types of of Type II hypersensitivity?
  • Clinical features?
A
136
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Pathogenesis and clinical findings of Type III hypersensitivity?
A

Type III Hypersensitivity

  • Disease is caused by deposition of immune complexes in tissues that are or may be unrelated to the antigen
  • Three new things are needed
    1. Antigen
    2. Antibody
    3. Complement
  • Antibodies may be produced against free and/or soluble antigen
    • Microbial
    • Self antigens
    • Inhaled antigens
  • Usually but not exclusively IgG and fix complement.
  • Damage to tissues is initiated by complement.
  • Circulating immune complexes (CICs) are solubilised by complement
  • Circulating immune complexes are removed by complement binding especially to CR1 on RBCs
  • Clearance mainly occurs in liver and spleen
  • Clearance is mediated by tissue macrophages.
  • Failure of clearance may occur with
    • Over-production of CICs
    • Complement deficiency
    • CR abnormalities
  • Excess CICs are deposited in tissues
  • Complement induces an inflammatory response with tissue damage
137
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Common types of Type III hypersensitivity?
  • Clinical Findings?
A
138
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Pathogenesis and clinical findings of Type IV hypersensitivity?
A

Type IV Hypersensitivity

  • Different to I, II and III
  • T cell mediated response
  • Variously mounted by cells and cytokines that result in pathological changes
139
Q

Mechanism and Classification of Hypersensitivity Reactions

  • Common types of Type IV hypersensitivity?
A
140
Q

What is the definition of hypersensitivity?

A

Hypersensitivity = Any immune response that gives rise to an excessive or inappropriate reaction or that is more damaging than the antigen or pathogen that induced the response.

141
Q

Type II hypersensitivity reactions

What is Goodpasture syndrome?

A

Goodpasture syndrome

  • Antibodies are directed against the basement membrane – collagen type IV
  • N terminus region of collagen type IV shared by lung and kidney (especially glomerulus) after alternate RNA splicing
  • Goodpasture described the association of lung haemorrhage with severe necrotising GN.
142
Q

Type II hypersensitivity reactions

What is Pemphigus?

A

Type II hypersensitivity reactions - Pemphigus

  • Antibody is directed against the intercellular junctions of skin and mucous membrane (desmoglein-1 and -3).
  • Antibodies cause loss of intercellular adhesion (acantholysis) and breakdown of the epidermis or epithelium.
  • Vesicular disorder that may lead to death.
143
Q

Type II hypersensitivity reactions

What is Myasthenia gravis?

A

Myasthenia gravis

  • Mediated by an antibody directed against the AChR at the neuromuscular synapse.
  • Neurotransmission results in internalisation of the receptor which is then not re-expressed in an appropriate time frame.
  • The result is fewer and fewer functional synapses with use & progressive weakening = fatiguability.
144
Q

Type III hypersensitivity reactions

What is Serum sickness?

A

Serum sickness

  • Follows administration of foreign Immunoglobulin
  • Symptoms develop 7 -10 days after injection
  • Clinical features are due to tissue deposition of insoluble immune complexes
    1. Chills, fever
    2. Rash, especially urticaria
    3. Arthritis
    4. Glomerulonephritis
145
Q

Inflammatory Joint Diseases

What is Rheumatoid Arthritis?

A

Inflammatory Joint Diseases:** **Rheumatoid Arthritis

  • Chronic, systemic autoimmune disease (type III HSR) which classically arises in women of late childbearing age and associated with HLA-DR4.
  • Hallmark is synovitis leading to formation of a pannus (inflamed granulation tissue) which leads to destruction of cartilage and ankylosis (fusion) of the joint.
  • Clinical features include arthritis with morning stiffness that improves with activity, symmetrical involvement of PIP joints of the fingers (deformities), wrists (radial deviation), elbows, ankles and knees, and joint-space narrowing, loss of cartilage, and osteopenia seen on x-ray.
  • Also includes fever, malaise, weight loss, and myalgias, Rheumatoid nodules (central zone of necrosis surrounded by epithelioid histiocytes in skin and visceral organs), vasculitis, Baker cyst, pleural effusions, lymphadenopathy, and interstitial lung fibrosis. Important to diagnose early to prevent joint deformity!
  • Diagnose via serology (rheumatoid factor and anti- CCP), elevated ESR/CRP, joints involved and duration of synovitis.
146
Q

Inflammatory Joint Diseases

What is Septic Arthritis?

A

Septic Arthritis: Due to an infectious agent, usually bacterial such as N. gonorrhoeae in young adults (most common) or S. aureus in older children and adults. Classically involves a single joint, usually the knee. Presents as a warm joint with limited range of motion with fever, increased WCC, elevated ESR and purulent synovial fluid. Requires joint aspiration for urgent diagnosis!

147
Q

Inflammatory Joint Diseases

What are Crystal-Induced Arthritis (Gout/Pseudogout)?

A

Crystal-Induced Arthritis (Gout/Pseudogout):

  • Deposition of monosodium urate (MSU) crystals in tissues, especially the joints due to hyperuricemia related to overproduction or decreased excretion of uric acid. Uric acid is derived from purine metabolism and is excreted by the kidney.
  • Primary gout is the most common form but etiology of hyperuricemia is unknown.
  • Secondary gout is seen with leukemia and myeloproliferative disorders (increased cell turnover leads to hyperuricemia), Lesch-Nyhan syndrome-X-Iinked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (presents with mental retardation and self- mutilation), renal insufficiency (decreased renal excretion of uric acid).
  • Acute gout classically manifests as painful MTP joint of big toe (podagra) because MSU crystals deposit in the joint, triggering an acute inflammatory reaction. Alcohol, red meat, seafood, dehydration often lead to acute attacks.
  • Chronic gout leads to development of tophi-white, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue and joints, and renal failure as urate crystals may deposit in kidney tubules (urate nephropathy). Synovial fluid shows needle-shaped crystals with negative birefringence under polarised light.
  • NB: Pseudogout resembles gout clinically, but is due to deposition of calcium pyrophosphate dihydrate (CPPD), where synovial fluid shows rhomboid-shaped crystals with weakly positive birefringence under polarised light.
148
Q

Inflammatory Joint Diseases

  • Gout on xray?
  • Treatment goals for gout?
A
149
Q

Inflammatory Joint Diseases

What are 4 Seronegative Spondyloarthropathies?

A

Seronegative Spondyloarthritis: Group of joint disorders characterised by lack of rheumatoid factor, axial skeleton involvement and HLA-B27 association.

  1. Psoriatic Arthritis
  2. Ankylosing Spondylitis
  3. Reactive Arthritis (Reiter Syndrome)
  4. Inflammatory Bowel Disease
150
Q

Inflammatory Joint Diseases -** **Seronegative Spondyloarthropathies

What is Psoriatic Arthritis?

  • Pathogenesis?
  • Clinical Findings?
  • Complications?
A

Psoriatic Arthritis: Associated with skin psoriasis and nail lesions (pitting). Involves axial and peripheral joints, asymmetric and patchy involvement. Dactylitis (sausage fingers and toes) and “pencil-in-cup” deformity of DIP of hands and feet on x-ray. Seen in fewer than 1 ⁄3 of patients with psoriasis.

151
Q

Inflammatory Joint Diseases -** **Seronegative Spondyloarthropathies

What is Psoriatic Arthritis?

  • Complications?
A
152
Q

Inflammatory Joint Diseases -** **Seronegative Spondyloarthropathies

What is Ankylosing Spondylitis?

  • Pathogenesis?
  • Clinical Findings?
  • Complications?
A

Ankylosing Spondylitis:

  • Presents with low back pain due to involvement of vertebral bodies and joint fusion (ankylosis) of the vertebrae (looks like ‘bamboo spine’).
  • Patients may be unable to rotate spine.
  • Involves symmetric involvement of spine and sacroiliac joints.
  • Extra-articular manifestations include uveitis and aortitis (leading to aortic regurgitation).
  • Can cause restrictive lung disease due to limited chest wall expansion (costovertebral and costosternal ankylosis).
  • More common in young males.
153
Q

Inflammatory Joint Diseases -** **Seronegative Spondyloarthropathies

What is Ankylosing Spondylitis?

  • Extra-articular manifestations?
A
154
Q

Inflammatory Joint Diseases -** **Seronegative Spondyloarthropathies

What is Reactive Arthritis (Reiter Syndrome)?

  • Pathogenesis?
  • Clinical findings?
A

Reactive Arthritis (Reiter Syndrome): Characterised by the triad of arthritis, urethritis and conjunctivitis. Arises in young adults (usually males) weeks after a GI or Chlamydia trachomatis infection (can’t see, can’t pee, can’t bend my knee).

155
Q

What is Sjögren Syndrome?

  • Epidemiology?
  • Pathogenesis?
  • Which 3 genes is it associated with?
  • Clinical presentation?
  • Antibodies?
  • Complications?
  • Lab findings?
A

Sjögren Syndrome

  • Autoimmune disorder characterised by destruction of exocrine glands (especially lacrimal and salivary) by lymphocytic infiltrates.
  • Predominantly affects females 40–60 years old.
  • Associated with HLA-DRW52, DQA1 and DQB1 genes and exocrine (salivary and lacrimal) gland infections.
  • Normally presents with xerostomia (dry mouth), parotitis, dysphagia, xerophthalmia (dry eyes), red, itching and burning eyes and blurred vision, as well as nasal (nosebleeds, rhinitis), pharyngeal, tracheal, bronchial (persistent cough) and vaginal dryness (dyspareunia).
  • Findings include inflammatory joint pain, keratoconjunctivitis sicca (decreased tear production and subsequent corneal damage), xerostomia (decreased saliva production), presence of antinuclear antibodies, rheumatoid factor, antiribonucleoprotein antibodies SS-A (anti-Ro) and/or SS-B (anti-La), bilateral parotid enlargement.
  • A common primary disorder or a secondary syndrome associated with other autoimmune disorders (RA, SLE, systemic sclerosis).
  • Complications include dental caries and mucosa-associated lymphoid tissue (MALT) lymphoma (may present as parotid enlargement). Labial salivary gland biopsy can confirm diagnosis.
156
Q

What is Systemic Lupus Erythematosus?

  • Pathogenesis?
  • Epidemiology?
  • Which HSR type is it?
  • Which antibodies? (4)
  • Which complement is low? (2)
  • Tx?
  • MSK manifestations?
A

Systemic Lupus Erythematosus:

  • Chronic, systemic autoimmune disease where flares and remissions are common.
  • Classically arises in middle‐aged females, especially African American and Hispanic women. May also arise in children and older adults (less dramatic gender bias).
  • Antigen‐antibody complexes damage multiple tissues (type III HSR).
  • Classic presentation is rash, joint pain, and fever and almost any tissue can be involved (RASH OR PAIN).
  • Findings include:
    1. Antinuclear antibodies (ANA)
    2. Anti-dsDNA antibodies
    3. Anti-Smith antibodies
    4. Antihistone antibodies
    5. Low C3 and C4 due to immune complex formation.
  • Treat with NSAIDs, steroids, immunosuppressants and hydroxychloroquine.
  • Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of numerous autoantibodies and involvement of skin, joints, kidneys, brain, serosal surfaces, blood vessels, blood cells, lungs and heart.
  • SLE in humans is heterogeneous and affects different individuals with a wide range of disease courses and manifestations are believed to emerge from a more global abnormality in immunoregulation
  • In situ immune complex formation → Deposition of autoantibody (anti-dsDNA) in tissues followed by local complement activation, especially in renal glomerulus
  • Direct antibody induced tissue damage → Anti-SSA (anti-Ro) antibodies may bind to skin in subacute cutaneous LE or in neonatal LE.
157
Q

What is Crest Syndrome?

  • Pathogenesis?
  • Clinical Findings?
A
158
Q

What is Diffuse Systemic Sclerosis (Scleroderma)?

  • Pathogenesis?
  • Clinical Findings?
A
159
Q

What is Polymyalgia Rheumatica (Giant cell arteritis)?

  • Pathogenesis?
  • Clinical Findings?
A
160
Q

What is the most common degenerative joint disease?

  • Pathogenesis?
  • Clinical findings?
  • Major risk factors?
  • Joints affected?
  • Classic presentation?
A

Most Common Degenerative Joint Disease = Osteoarthritis

  • Progressive degeneration of articular cartilage. Wear and tear destroys articular cartilage resulting in inflammation with inadequate repair.
  • Specifically, joint damage/stress results in inflammation which activates proteases, causing cartilage destruction.
  • Major risk factors include age (common after 60 years), obesity and trauma (i.e. previous joint injury).
  • Affects a limited number of joints (oligoarticular) including hips, lower lumbar spine, knees, and the distal interphalangeal joints (DIP) and proximal interphalangeal joints (PIP) of fingers are common sites.
  • Classic presentation is joint stiffness in the morning that worsens during the day. Also includes joint pain, muscle wastage, joint effusion, reduced joint movement and crepitations. Pathologic features include disruption of the cartilage that lines the articular surface, fragments of cartilage floating in the joint space called ‘joint mice’, joint space narrowing, subchondral sclerosis and cysts, eburnation of the subchondral bone and osteophyte formation (reactive bony outgrowths, bone spurs) which classically arises in the DIP (Heberden nodes) and PIP (Bouchard nodes) joints of the fingers.
161
Q

RA vs. OA on x-ray?

A
162
Q

Compare degenerative vs. inflammatory joint disease.

A
163
Q

Describe the patterns of joint involvement in different forms of polyarthritis:

  • RA?
  • Psoriatic arthritis?
  • Ankylosing spondylitis?
  • OA?
A
164
Q

Outline the classes of anti-inflammatory and immunosuppressant drugs.

  • List 3 anti-inflammatory drugs and their MOA?
    • Examples of each?
A

Anti-Inflammatory Drugs

  • Non-Selective NSAIDs: Block COX-1 and COX-2 enzymes which lowers the levels of circulating prostaglandins and thromboxanes thus reducing prostanoid-mediated inflammation and pain. Has analgesic, antipyretic, anti-inflammatory and antiplatelet actions by preventing synthesis of prostaglandins by non-competitively and non-selectively inhibiting both COX-1 and COX-2 (preventing prostaglandin synthesis inhibits inflammatory mediators which inhibits pain (from odeama and chemoreceptors)
    • Examples: Aspirin (salicylates), diclofenac, sulindac and indomethacin (arylalkanoic acids), ibuprofen, ketoprofen, naproxen and ketorolac (profens), mefenamic acid (fenamic acids) and piroxicam (oxicams).
  • Selective NSAIDs: Selectively inhibit COX-2 enzymes which results in anti-inflammatory and analgesic action. Although selective COX-2 inhibitors have little or no effect on COX-1 at therapeutic doses, they are still associated with GI adverse effects.
    • Examples: Celecoxib, Etoricoxib and Parecoxib (coxibs) and Meloxicam (oxicam).
  • Acetaminophen (Paracetamol): Generally considered to be a weak inhibitor of the synthesis of prostaglandins in the CNS. Does not appear to inhibit the function of COX enzymes outside the CNS which is why it is not useful as an anti-inflammatory.
165
Q

Immunosuppressant Drugs

What are glucocorticoids?

Examples?

A

Glucorticosteroids: Regulate gene expression, which results in gluconeogenesis, proteolysis, lipolysis, suppression of inflammation and immune responses. Some corticosteroids (hydrocortisone) also have mineralocorticoid effects which include hypertension, sodium and water retention, potassium loss. Inhibit phospholipase A2 and reducing the levels of arachidonic acid

Examples: Prednisolone and Dexamethasone

166
Q

List 5 Disease Modifying Antirheumatic Drugs (DMARDs).

  • MOA?
  • Examples?
A

Disease Modifying Antirheumatic Drugs (DMARDs)

Methotrexate (Immunosuppressant): Folic acid antagonist. Inhibits the enzyme dihydrofolate reductase, and hence the final production of tetrahydrofolate. Mechanism of immunomodulatory effects in autoimmune diseases is unclear and may differ from its action as a folic acid antagonist in cancer treatment. It suppresses inflammation and immune responses. Indicated for RA, psoriasis, JIA and Chron’s disease. Give with folic acid!!

Leflunomide (Immunosuppressant): Inhibits pyrimidine synthesis in leucocytes and other rapidly dividing cells by inhibiting activity of dihydro-orotate dehydrogenase. It has immunosuppressive, immunomodulating and antiproliferative properties. Also has uricosuric effects. Indicated for RA and psoriatic arthritis.

Hydroxychloroquine: Anti-inflammatory. May also have immunosuppressive effects. Indicated for RA, SLE and JIA.

5-Aminosalicylates (Sulfasalazine/Mesalazine): Anti-inflammatory, immunosuppressant. Exact mechanism unknown. Indicated for ulcerative colitis and Chron’s disease (limited role).

TNF-α Inhibitor (Biological Agent/Cytokine Modulator): Bind to TNF-α and inhibit its activity. TNF alpha is a cytokine involved in inflammatory and immune responses and in the pathogenesis of rheumatoid arthritis, psoriasis and inflammatory bowel disease. Indicated for RA, psoriatic arthritis, ankylosing spondylitis and plaque psoriasis. Examples: Infliximab and Adalimumab

167
Q

Explain the rationale for drugs used in the treatment of gout.

  • Which drugs are used to prevent attacks?
A

Urate-Lowering Agents (Prevent Attacks):

  • Xanthine Oxidase Inhibitors: Inhibit xanthine oxidase which reduces production of uric acid, lowering serum urate concentration and allowing acute flares and crystal deposits to resolve if long-term serum urate
    <0.36 mmol/L.
    • Examples: Allopurinol or Febuxostat (is allopurinol cannot be taken)
  • Uricosurics: Reduce serum urate by increasing renal excretion of uric acid. They require an adequate fluid intake to prevent formation of uric acid stones; avoid use with a history of urolithiasis. If unable to reach target serum urate with xanthine oxidase inhibitor treatment, a uricosuric may be added to increase its effect.
    • Examples: Probenecid or Benzbromarone
168
Q

Explain the rationale for drugs used in the treatment of gout.

  • Which drugs are used to treat attacks? (3)
A

Acute Flares (Treat Attacks):

Colchicine: Relief of pain in acute gout and prophylaxis of gout flares (preferred prophylaxis). Reduces inflammation as it inhibits neutrophil migration, chemotaxis, adhesion and phagocytosis in inflamed tissue. In gout it reduces inflammatory reaction to urate crystals.

NSAIDs (Except Aspirin): For acute attacks. Consider risks from long-term treatment. Note, aspirin competes with uric acid for the organic acid secretion mechanism in the proximal tubule of the kidney

Corticosteroids: For acute attacks. Consider only if colchicine and NSAIDs are contraindicated.

169
Q

Which drug can be used to treat High Uric Acid Caused by Cytotoxic Drugs in gout?

A

Treat High Uric Acid Caused by Cytotoxic Drugs:

• Rasburicase: Recombinant urate oxidase enzyme that catalyses the enzymatic oxidation of uric acid into allantoin, which is more water soluble than uric acid and less likely to precipitate in the renal tubules.

170
Q

What 10 factors are considered in the diagnosis of inflammatory arthritis?

A

Diagnosis of Inflammatory Arthritis:

  1. Number of joints and specific joints involved
  2. Pattern of joint involvement (symmetrical or asymmetrical and large or small)
  3. Associated features
  4. Presence of non-articular disease
  5. Past medical history
  6. Family history
  7. Periodicity of the arthritis (single acute, relapsing, chronic and progressive)
  8. Evidence of recent viral illness (rubella, hepatitis B or erythrovirus), rheumatic fever or a tick bite and skin rash (Lyme disease)
  9. Pain and stiffness is worse in the morning (often for 30 minutes to several hours)
  10. Inflammatory markers (ESR and CRP) are often raised and there is often normochromic, normocytic anaemia
171
Q

Differential Diagnoses of Monoarthritis and Polyarthritis?

A
172
Q

Which investigations should you perform for distinguishing between monoarthritis and polyarthritis?

  • 4 blood tests? Why?
  • Which imaging?
A

Investigations of Monoarthritis and Polyarthritis:

  • Examination: Clinical examination of joints is key to diagnosis and distinguishing between monoarthritis and polyarthritis.
  • Synovial Fluid Analysis: Acute monoarthritis is a medical emergency, where joint aspiration and synovial fluid (SF) analysis are mandatory to exclude septic arthritis and gout. Both conditions can produce turbid SF. Macroscopic examination of the SF is also helpful in excluding a haemarthrosis, as in the case of trauma and haemophilia. Microscopy is essential to determine the white cell count, to detect bacteria by gram stain and to look for uric acid crystals under polarised light. Synovial fluid culture is indicated in cases where infection is suspected.
  • Bloods:
    1. FBC and Iron Studies: Anaemia is common in inflammatory arthritis, mostly due to anaemia of chronic disorders, but can also result from iron deficiency secondary to non-steroidal anti-inflammatory drug-induced peptic ulcer disease, and rarely Coomb’s positive haemolytic anaemia as in systemic lupus erythematosus (SLE). Leucocytosis is a feature of septic arthritis, acute gout and juvenile arthritis. Leucopaenia, and especially lymphopaenia, in a patient presenting with polyarthritis, is very suggestive of SLE. Reactive thrombocytosis is common with active chronic inflammatory arthritis, like RA and juvenile idiopathic arthritis, whereas thrombocytopaenia can be a presenting feature of SLE.
    2. ESR and CRP: Elevation of acute phase reactants aids in the differentiating inflammatory from non- inflammatory arthritis. It generally lacks specificity, except when the CRP is greater 100 mg/L, in which case septic arthritis or gout should be excluded.
    3. Autoantibodies: Screening for rheumatoid factor and antinuclear antibodies (ANA) is indicated in the patient presenting with polyarthritis to assess for rheumatoid arthritis or SLE.
    4. Hyperuricaemia: A feature of gout, however 30–45% of patients have a normal serum uric acid level during an acute attack of gout.
  • Imaging:
    1. X-Ray: The imaging method of choice to distinguish between inflammatory arthritis (RA) and degenerative arthritis (OA).
    2. Ultrasound: Can confirm presence and size of joint effusion.
    3. MRI: Only in exceptional cases is MRI indicated to better define the nature and the extent of joint, bone and surrounding soft tissue changes.
173
Q

What is Fibromyalgia?

  • Pathophysiology?
  • Epidemiology?
  • Diagnosis?
A

Fibromyalgia:

  • A neurosensory disorder characterised by chronic musculocutaneous pain.
  • The pathophysiology of is still not fully understood, but its aetiology is likely multifactorial including genetic predisposition, environmental triggers (stress) and neuroendocrine and autonomic nervous system dysregulation.
  • Most commonly seen in women 20–50 years old. It is commonly associated with SLE, RA, functional syndromes such as IBS and chronic fatigue, and depression and generalised anxiety disorder.
  • It is a clinical diagnosis (characteristic tender points often allow for diagnosis) and treatment includes lifestyle modification (diet recommendations, sleep hygiene and regular exercise), education of coping strategies, medication (TCAs, SSNRIs and anticonvulsants) and multidisciplinary pain management. Although the syndrome is benign, it causes the patient significant psychological strain and discomfort.
174
Q

What is Raynaud disease?

A
175
Q

Symptoms of fibromyalgia?

A

Symptoms of fibromyalgia

  1. Chronic, widespread pain, primarily at points where muscles and tendons attach to bone (tender points)
  2. Headache
  3. Fatigue
  4. Morning stiffness
  5. Non-refreshing sleep
  6. Cognitive dysfunction such as poor memory, attention and clarity of thought (“fibro fog”)
  7. Paresthesias
  8. Symptoms of autonomic dysfunction such as digestive problems, weight fluctuation, palpitations, sexual dysfunction and night sweats
176
Q

What are 3 features of fibromyalgia that contradict it as an organic pathology?

8 differential diagnoses for fibromyalgia?

A

Fibromyalgia Features Contrary to Organic Pathology:

  1. Functional complaints (symptoms above)
  2. On physical examination, there is no notable swelling, deformity, or erythema
  3. Laboratory values and imaging are normal (no inflammation)

Differential Diagnosis:

  1. Myofascial pain syndrome
  2. Polymyalgia rheumatica
  3. Complex regional pain syndrome
  4. Hypothyroidism
  5. Sleep apnea
  6. Rheumatoid arthritis
  7. Systemic lupus erythematosus
  8. Malignancy
177
Q

Outline the management of arthritis.

A
178
Q

What is joint aspiration?

  • 6 Indications?
  • 4 Contraindications?
  • 5 classifications of synovial fluid?
A

Joint Aspiration:

  • Examination of joint (or bursa) fluid is used mainly to diagnose septic, reactive or crystal arthritis.
  • The appearance of the fluid is an indicator of the level of inflammation.
  • The procedure is often undertaken in combination with injection of a corticosteroid. Corticosteroids are believed to modify the vascular inflammatory response to injury, inhibit destructive enzymes, and restrict the action of inflammatory cells.
  • Aspiration alone is therapeutic in crystal arthritis.
  • To establish a diagnosis, relieve discomfort, drain off infected fluid or deliver medication

Indications for Joint Aspiration:

  1. Acute/Unexplained Monoarthritis: To diagnose/exclude septic arthritis (medical emergency!). Produces a turbid SF and allows for microscopy.
  2. Crystal-Induced Arthropathy: To diagnose/exclude gout and other diseases. Produces a turbid SF and allows for microscopy and the observation of uric acid crystals under polarised light.
  3. Hemarthrosis: To determine presence of RBCs upon macroscopic examination. Can be due to trauma or haemophilia and indicate the presence of a fracture or other anatomic disruption.
  4. Symptomatic Relief of Large Effusion: Allows for drainage and deliverance of medication.
  5. Unexplained Joint Effusion: Allows for macroscopic, microscopic and laboratory analysis to confirm diagnosis.
  6. Limiting Joint Damage from an Infectious Process: Allows for microscopy, culture and sensitivity. Prompt treatment of a joint infection can preserve the joint integrity.

Contraindications for Joint Aspiration:

  1. Bacteremia
  2. Inaccessible joints
  3. Joint prosthesis
  4. Overlying infection in the soft tissue
179
Q

Discuss the therapy for spondyloarthorpathies.

A
180
Q

What is IL-2? Functions?

A
181
Q

What is Calcineurin? Functions?

A
182
Q

What is Tumour Necrosis Factor alpha (TNF-α)?

A
183
Q

What is Cyclosporin?

  • Role in immune suppression?
  • MOA?
  • Negatives?
  • Drug interactions?
A

Cyclosporin

  • It is a natural metabolite produced by the fungus species Beauveria nivea
  • Is an immunosuppressive drug used to prevent graft rejection, and to treat some autoimmune diseases e.g. rheumatoid arthritis
  • It inhibits the actions of calcineurin by binding to intracellular proteins called immunophilins
  • By inhibiting the actions of calcineurin it reduces the production of interleukin 2, and reduces the growth, activation and differentiation of T cells
  • Increases the risk of developing lymphomas and other malignancies, particularly those of the skin
  • Predisposes patients to the development of a variety of bacterial, fungal, parasitic and viral infections, often with opportunistic pathogens
  • Regular monitoring of renal function, hepatic function, blood pressure, potassium and cyclosporin blood levels
  • Drug interactions - CYP3A4 and p-glycoprotein inhibitors (note grapefruit juice) and inducers
184
Q

What is Methotrexate?

  • Class of drug?
  • MOA?
  • Indications?
  • Adverse effects?
A

Methotrexate

  • Class of Drug: Methotrexate is a DMARD and DMARD therapy is often commenced with methotrexate e.g. treatment of rheumatoid arthritis
  • MOA
    • Methotrexate is a folic acid antagonist. It inhibits the enzyme dihydrofolate reductase which is the enzyme that reduces folic acid to tetrahydrofolic acid. Inhibition of tetrahydrofolic acid results in interference with DNA synthesis and cellular reproduction.
  • Indications: Can be used in the treatment of a number of cancers
    • When used in the treatment of cancer it is often taken on a daily basis (with rest periods)
    • In the treatment of autoimmune diseases such as rheumatoid arthritis it is taken on a weekly basis
    • Both GPs and pharmacists must stress to the patient the importance of the weekly dosage - mistaken daily use may cause life-threatening toxicity and death
  • DMARDs reduce or eradicate synovial inflammation and thus prevent joint damage in rheumatoid arthritis.
  • Adverse effects:
    1. Methotrexate has a Black Box warning - May depress the bone marrow and reduce both red and white blood cell counts
    2. Malignant lymphomas may occur in patients taking methotrexate
    3. Potentially fatal opportunistic infections, especially Pneumocystis carinii pneumonia, may occur with methotrexate therapyClose monitoring is mandatory
185
Q

What is Infliximab?

  • Class of drug?
  • MOA?
  • Adverse effects?
A

Infliximab

  • bDMARDS primarily inhibit the actions of tumour necrosis factor alpha (TNF-α)
  • Infliximab is an example of a bDMARD
  • It is a chimeric human murine monoclonal antibody that binds to human tumour necrosis factor alpha (TNFα)
  • They exert an anti-inflammatory effect and produce a reduction in the number of T cells
  • Infliximab is used in the treatment of
    • Crohn’s disease
    • psoriasis
    • rheumatoid arthritis
  • Therapy with tumour necrosis factor alpha (TNF-α) inhibitors may - increase the risk of lymphoma and leukaemia-increase the risk of skin cancers-increase the risk of infection (bacterial, fungal and viral)
186
Q

Corticosteroids

  • 3 examples?
  • MOA?
A

Corticosteroids

  • Examples include hydrocortisone, dexamethasone and prednisolone
  • Produce an anti-inflammatory effect
  • Mechanism of action is complex:
    • Inhibit phospholipase A2 and the release of arachidonic acid leading to reduced levels of prostaglandins and leukotrienes
    • Bind to intracellular nuclear receptors and modulate gene transcription and protein synthesis
    • Reduce the synthesis of cytokines and tumour necrosis factor alpha (TNF-α)
187
Q

What are 7 problems associated with long-term corticosteroid therapy?

A

Long-term corticosteroid therapy

  1. Masking of the signs of infection
  2. Increase in blood pressure (salt and water retention)
  3. Worsening of heart failure (salt and water retention)
  4. Increase in blood glucose levels (hyperglycaemia)
  5. Reduced bone mineral density and osteoporosis
  6. Cushing syndrome
  7. Adrenocortical insufficiency
188
Q

What are Monoclonal Antibodies (mAbs)?

  • What are they used to treat? 2 examples?
  • What are they made of?
A

Monoclonal Antibodies (mAbs)

  • A monoclonal antibody is an antibody made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell
  • They are used to treat some autoimmune diseases, cancer and infections
    • Secukinumab binds to interleukin-17A and is used in the treatment of psoriasis
    • Tocilizumab binds to interleukin-6 receptors and is used in the treatment of rheumatoid arthritis

YR2 BCS Study Points SEM 2 (4 decks)

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