Flashcards in Muskuloskeletal Deck (175)
What is amyloidosis?
Disease caused by accumulation of proteins in the form of abnormal, insoluble fibres (amyloid fibres) within the extracellular space in the tissues of the body
What is the aetiology of primary amyloidosis?
- Remains unknown; all are associated with clonal plasma dyscrasia, although in most instances this is of insufficient degree to qualify as multiple myeloma
- No underlying genetic, environmental, or occupational risk factors have been identifies for primary amyloidosis
What is the aetiology of non-familial secondary amyloidosis?
- Inflammatory polyarthropathies. Conditions include rheumatoid arthritis, juvenile arthritis, psoriatic arthritis and ankylosing spondylitis
- Chronic infections e.g. bronchiectasis, subcutaneous injection of illicit drugs, decubitus ulcers, chronic UTIs and osteomyelitis
- Inflammatory bowel disease, esp. Crohn's
- Castleman's disease- lymphoproliferative disorder where plasma cell variant can cause secondary amylodosis
What is the aetiology of secondary amyloidosis (familial fever syndrome)?
- Familial Mediterranean fever
- Tumour necrosis factor receptor-associated periodic fever syndromes
- Muckle-Wells syndrome
- Hyper-IgD syndrome
What is the epidemiology of amyloidosis?
- Median age at diagnosis= 64 yrs
- Can present at any age
- Male to female 2:1
What are the risk factors for amyloidosis?
- Monoclonal gammopathy of undetermined significance
- Inflammatory polyarthropathy
- Chronic infections
- Inflammatory bowel disease
- Familial periodic fever syndromes
What are the presenting symptoms of amyloidosis?
- Weight loss
- Dyspnoea on exertion
- Abdominal cramps
What are the signs of amyloidosis on examination?
- Jugular venous distension
- Lower extremity oedema
- Periorbital purpura
What are the investigations for amyloidosis?
- Serum immunofixation: presence of monoclonal protein
- Urine immunofixation: presence of monoclonal protein
- Immunoglobulin free light chain assay: abnormal kappa to lambda ratio
- Bone marrow biopsy: clonal plasma cells
What is ankylosing spondylitis?
Seronegative inflammatory athropathy affecting preferentially the axial skeleton and large proximal joints
What is the aetiology of ankylosing spondylitis?
- Unknown. Strong linkage with HLA-B27 gene.
- Inflammation starts at the entheses. Persistent inflammation is followed by reactive new bone formation. Changes start in lumbar and progress to thoracic and cervical regions:
- Squaring of the vertebral bodies. Formation of syndesmophytes (vertical ossifications bridging the margins of the adjacent vertebrae). Fusion of syndesmophytes and facet joints. Calcifications of anterior and lateral spinal ligaments
What is the epidemiology of ankylosing spondylitis?
- Earlier presentation in males
- Males: Female 6:1 at 16 yrs, 2:1 at 30 yrs
What are the presenting symptoms of ankylosing spondylitis?
- Low black and sacroiliac pain disturbing sleep (worse in morning, improves on activity, returning with rest). Progressive loss of spinal movement. Symptoms of asymmetrical peripheral arthritis
- Pleuritic chest pain (caused by costovertebral joint involvement). Heel pain (caused by plantar fasciitis). Not specific symptoms malaise, fatigue
What are the signs of ankylosing spondylitis on examination?
- Reduced range of spinal movements (particularly hip rotation)
- Reduced spinal flexion and occipital-wall distance (with pt standing next to wall)
- Schober's test
- May be tenderness over SI joints
- In later stages, thoracic kyphosis and spinal fusion, question mark poster
- Signs of extra-articular disease: Anterior uveitis (red eye), apical lung fibrosis, reduced chest expansion (fusion of costovertebral joints, aortic regurgitation (cardiac diastolic murmur)
What are the investigations for ankylosing spondylitis?
- Blood: FBC (anaemia of chronic disease), rheumatic factor (negative), Raised ESR/CRP
- Radiographs: Anteroposterior and lateral radiographs of spine: 'Bamboo spine' may be seen. Anteroposterior radiographs of the SI joints. Symmetrical blurring of joint margins. Later there are erosions, sclerosis and SI joint fusion. CXR: To look for association with apical fibrosis
- Lung function tests: Assesses mechanical ventilatory impairment from kyphosis
What is antiphospholipid syndrome?
Characterised by the presence of antiphospholipid antibodies (APL) in the plasma, venous and venous thromboses, recurrent foetal loss and thrombocytopenia
What is the aetiology of antiphospholipid syndrome?
- APL are directed against plasma proteins bound to anionic phospholipids.
- APL may develop in susceptible individuals following exposure to infectious agents
- Once APL are present, a 'second-hit' is needed for the development of the syndrome
- The procoagulant actions of APL may be mediated by their effect on B2-GP-I (clotting and platelet aggregation inhibitor), protein C, annexin V, platelets and fibrinolysis
- Complement activation is critical for pregnancy complications
What is the epidemiology of antiphospholipid syndrome?
- More common in young females
- Accounts for 20% of strokes in under 45yr olds and 27% of women with more than 2 miscarriages
What are the presenting symptoms of antiphospholipid syndrome?
- Recurrent miscarriages
- History of arterial thromboses (stroke)
- Venous thromboses (DVT, pulmonary embolism)
- Headaches (migraine)
What are the signs of antiphospholipid syndrome on examination?
- Livedo reticularis
- Signs of SLE (malar flush, discoid lesions, photosensitivity)
- Signs of valvular heart disease
What are the investigations for antiphospholipid syndrome?
- FBC: reduced platelets, ESR usually normal, U&E (APL nephropathy), clotting screen (increased APTT)
- Presence of APL may be demonstrated by
1) ELISA testing for anticardiolipin and anti-B2-GPI antibodies
2) Lupus anticoagulant assays: clotting assays showing effects of APL on the phospholipid-dependent factors in the coagulation cascade
- False positive VDRL test for syphillis may be a clue to the presence of any type of APL
What is Behcet's disease?
An inflammatory multisystem disease featuring a triad of orogenital ulceration and uveitis
- It can cause skin and mucosal lesions, uveitis, major arterial and venous vessel disease, and GI and neurological manifestations. These can present in various combinations and sequences in patients over time.
What is the aetiology of Behcet's syndrome?
- Not known
- Increased inflammation and immunological mechanisms play a role
What is the epidemiology of Behcet's syndrome?
- Pts most commonly from Middle East, the Mediterranean region, and eastern Asia, with Japan and South Korea leading the list
- Rare in northern Europe and Africa
- Can affect any age group but rare before puberty and after sixth decade
What are the presenting symptoms of Behcet's syndrome?
- Increased predisposition in certain ethnic/geographic groups
- Oral ulcers
- Genital ulcers
- Acne lesions
- Short duration of symptoms
- Superficial thrombophlebitis
What are the signs of Behcet's syndrome?
- Hypopyn (precipitation of inflammatory cells in the anterior chamber indicates severe inflammation)
- Erythema Nodosum (nodular lesions, usually in lower extremities and tend to resolve in 1-2 weeks)
What are the investigations of Behcet's syndrome?
- Pathergy testing: Formation of pustule within 48 hours)
- RF: negative
- ANA: negative
- Anti-neutrophil cytoplasmic antibodies: negative
- HLA-B51: present
What is carpal tunnel syndrome?
Refers to the symptom complex brought on by compression of the median nerve in the carpal tunnel
What is the aetiology of carpal tunnel syndrome?
Compression of the median nerve within the carpal tunnel (formed by the flexor retinaculum superiorly and the carpal bones inferiorly). Usually idiopathic but may be secondary to
- Tenosynovitis: Overuse, rheumatic arthritis, other inflammatory rheumatic disease
- Infiltrative diseases of the canal/increased soft tissue: Amyloidosis, myeloma myxoedema, acromegaly
- Bone involvement in the wrist: Osteoarthritis, fracture, tumour
- Fluid retention states: Pregnancy, nephrotic syndrome
- Other: Obesity, menopause, diabetes, end-stage renal disease