MUSC Flashcards
Amyloidosis definition
Heterogenous group of diseases characterised by extracellular deposition of amyloid fibrils
Aetiology/ Risk Factors Amyloidosis
- Deposition of amyloid fibrils (polymers of LMW subunit proteins, derived from proteins that undergo conformational changes to adopt an anti-parallel beta-pleated sheet configuration) progressively disrupts the structure and function of normal tissue
- Amyloidosis classified according to fibril subunit proteins:
Type AA - serum amyloid A protein
Type AL - monoclonal immunoglobulin light chains
Type ATTR- genetic-variant transthyretin
Epidemiology of Amyloidosis
AA: 1-1.5% patients with chronic inflammatory disease
AL: 300-600 cases in the UK per year
Hereditary Amyloidosis: 5% of patients with amyloidosis
Presenting symptoms and signs of amyloidosis
- Renal - proteinuria, nephrotic syndrome, renal failure
• Cardiac - restrictive cardiomyopathy, heart failure, arrhythmia, angina
• GI - macroglossia (characteristic of AL), hepatosplenomegaly, gut dysmotility, malabsorption, bleeding
• Neurological - sensory and motor neuropathy, autonomic neuropathy, carpal tunnel syndrome
• Skin - waxy skin and easy bruising, purpura around the eyes (characteristic of AL), plaques and nodules
• Joints - painful asymmetrical large joints, enlargement of anterior shoulder
• Haematological - bleeding tendency
Investigations for Amyloidosis
• Tissue Biopsy • Urine - check for proteinuria, free immunoglobulin light chains (in AL) • Bloods CRP/ESR Rheumatoid factor Immunoglobulin levels Serum protein electrophoresis LFTs U&Es • SAP Scan - radiolabelled SAP will localise the deposits of amyloid
Define Ankylosing Spondylitis
Seronegative inflammatory arthropathy affecting preferentially the axial skeletal and large proximal joints
Aetiology/ Risk Factors for ankylosing spondylitis
• UNKNOWN
• Strong association with the HLA-B27 gene (> 90% of cases are HLA-B27 positive)
• Infective triggers and antigen cross-reactivity with self-peptides have been
hypothesised
Pathophysiology of ankylosing spondylitis
Inflammation starts at the entheses (where ligaments attach to vertebral bodies) Persistent inflammation leads to reactive new bone formation
Changes begin in the lumbar vertebrae and progress superiorly
Vertebral bodies become more square Syndesmophytes (vertical ossifications bridging the margins between adjacent vertebrae)
Fusion of syndesmophytes and facet joints
Calcification of anterior and lateral spinal ligaments
Epidemiology of ankylosing spondylitis
- COMMON
* Earlier presentation in males
Presenting symptoms of ankylosing spondylitis
• Lower back and sacroiliac pain
• Disturbed sleep
• Pain pattern
Worse in the morning - Better with activity- Worse when resting
• Progressive loss of spinal movement
• Symptoms of asymmetrical peripheral arthritis
• Pleuritic chest pain (due to costovertebral joint involvement)
• Heel pain (due to plantar fasciitis)
• Non-specific symptoms (e.g. malaise, fatigue)
Signs of ankylosing spondylitis on physical examination
• Reduced range of spinal movement (particularly hip rotation)
• Reduced lateral spinal flexion
• Schober’s Test (fingers on back, should increase by >5cm when back bent forward)
• Tenderness over the sacroiliac joints
• LATER STAGES:
Thoracic kyphosis, Spinal fusion, Question mark posture
• Signs of Extra-Articular Disease: 5 As
Anterior uveitis, apical lung fibrosis, achilles tendinitis, amyloidosis, aortic regurgitation
Investigations for ankylosing spondylitis
• Bloods
FBC - anaemia of chronic disease Rheumatoid factor - negative ESR/CRP - high
• Radiographs:
Anteroposterior and lateral radiographs of the spine
• May show Bamboo spine
Anteroposterior radiograph of sacroiliac joints
• Shows symmetrical blurring of joint margins
LATER STAGES:
• Erosions
• Sclerosis
• Sacroiliac joint fusion
CXR - check for apical lung fibrosis
• Lung Function Tests
Assess mechanical ventilatory impairment due to kyphosis
Define Anti-phospholipid syndrome
A syndrome characterised by the presence of antiphospholipid antibodies (APL) in the plasma, venous & arterial thrombosis, recurrent foetal loss, and thrombocytopenia
Explain the aetiology/ risk factors of antiphospholipid syndrome
• Antiphospholipid antibodies (APL) are directed against plasma proteins bound to phospholipids
• APL may develop in susceptible individuals following exposure to infectious agents
• Once APL are present, a second event is needed for the syndrome to develop
• APL has effects on a number of coagulation factors (e.g. protein C, annexin V, platelets,
fibrinolysis)
• Complement activation by APL is critical for the complications
Summarise the epidemiology of antiphospholipid syndrome
- More common in YOUNG WOMEN
- Accounts for 20% of strokes in < 45 yrs
- Accounts for 27% of women with > 2 miscarriages
What are the presenting symptoms of anti-phospholipid syndrome
• RECURRENT MISCARRIAGES • History of: Arterial thromboses (stroke) Venous thromboses (DVT, PE) • Headaches (migraine) • Chorea • Epilepsy
Signs of anti-phospholipid syndrome on physical examination
• Livedo reticularis
A skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discolouration of the skin
• Signs of SLE (e.g. malar rash, discoid lesions)
• Signs of valvular heart disease
Investigations for anitphospholipid syndrome
• FBC - low platelets
• ESR - usually normal
• U&Es - can get APL nephropathy
• Clotting screen - high APTT
• Presence of antiphospholipid antibodies may be demonstrated by:
- ELISA testing for anticardiolipin antibodies
- Lupus anticoagulant assays
Define Behcet’s disease
An inflammatory multi system disease that often presents with urogenital ulceration and uveitis
Aetiology/ Risk Factors of Behcet’s
• More common in Turkey, Greece and Central Asia
Presenting symptoms and signs of Behcet’s
- Recurrent ORAL and GENITAL ulceration
- Uveitis
- Skin lesions (e.g. erythema nodosum)
- Arthritis
- Thrombophlebitis
- Vasculitis
- Myo/pericarditis
- CNS symptoms
- Colitis
Investigations for Behcet’s
• Diagnosis is very CLINICAL
• Pathergy Test - a needle prick becomes inflamed and a sterile pustule develops within
48 hours
• You may measure complement levels and check for a positive family history
Define Carpal Tunnel Syndrome
Syndrome refers to the symptom complex brought on by compression of the median nerve in the carpal tunnel
Aetiology/ risk factors of carpal tunnel syndrome
• Symptoms are caused by compression of the median nerve as it runs through the carpal tunnel
• Usually IDIOPATHIC
• May be SECONDARY to:
- Tenosynovitis (e.g. in rheumatoid arthritis)
- Infiltrative diseases of the canal/increased soft tissue (e.g. amyloidosis, acromegaly)
- Bone involvement in the wrist (e.g. osteoarthritis, fracture)
- Fluid retention states (e.g. pregnancy, nephrotic syndrome)
- Other (e.g. obesity , menopause, diabetes)
Epidemiology of Carpal Tunnel Syndrome
- Prevalence: 2.7%
* Lifetime risk of 10%
Presenting symptoms of Carpal Tunnel syndrome
- tingling and pain in the hand and fingers
- weakness and clumsiness of the hand
Signs of Carpal Tunnel syndrome on physical examination
- Sensory impairment in the median nerve distribution
- Weakness and wasting of thenar eminence
- Tinel’s Sign - tapping the carpal tunnel causes symptoms
- Phalen’s Test - flexion of the wrist for 1 min may cause symptoms
- Look out for signs of the underlying cause (e.g. acromegaly, hypothyroidism)
Investigations for Carpal Tunnel Syndrome
• Bloods
TFTs
ESR
• Nerve Conduction Study (not usually necessary)
Shows impaired median nerve conduction across the carpal tunnel
Cervical Spondylitis definition
Progressive, degenerative process affecting the cervical vertebral bodies and intervertebral discs, and causing compression of the spinal cord and/or nerve roots
Explain the aetiology/ risk factors of cervical spondylitis
• Osteoarthritic degeneration of the vertebral bodies leads to the formation of osteophytes
• These osteophytes protrude on to the foramina and spinal canal
• This leads to compression of:
- Nerve roots = radiculopathy - Anterior spinal cord = myelopathy
Summarise the epidemiology of cervical spondylitis
- Mean age at diagnosis = 48 yrs
* More common in MALES
Presenting symptoms of cervical spondylitis
- Neck pain/stiffness
- Arm pain (stabbing or dull ache)
- Paraesthesia
- Weakness
- Clumsiness in the hands
- Weak and stiff legs
- Gait disturbance
- Atypical chest pain
- Breast pain
- Pain in the face
Signs of cervical spondylosis on physical examination
ARMS:
- Atrophy of the forearm and hand muscles
- Segmental muscle weakness in a nerve root distribution (e.g. C5 –> shoulder abduction and elbow flexion weakness)
- Hyporeflexia
- Sensory loss (mainly pain and temperature)
- Pseudoathetosis (writhing finger movements when hands are outstretched, fingers spread and eyes closed)
LEGS:
- (if cervical cord compression)
-Increased tone
-Weakness
-Hyper-reflexia
-Extensor plantar response
-Reduced vibration and joint position sense
• Lhermitte’s Sign - neck flexion causes crepitus (grating sound) and/or paraesthesia down the spine
Investigations for cervical spondylitis
Spinal X-ray (lateral)
Definition of fibromyalgia
Chronic pain disorder with an unknown cause
Aetiology/ Risk Factors of fibromyalgia
- UKNOWN aetiology
* Thought to be something to do with altered pain perception
Epidemiology of fibromyalgia
- COMMON
- 10 x more common in WOMEN
- Usual age of presentation: 20-50 yrs
Presenting symptoms and sings of fibromyalgia
- Pain at multiple sites (MAIN SYMPTOM)
- Fatigue
- Sleep disturbance
- Morning stiffness
- Paraesthesia
- Feeling of swollen joints
- Problems with cognition
- Headaches
- Light headedness
- Anxiety
- Depression
- Urinary problems (dysmenorrhea in women)
Investigations for fibromyalgia
• CLINICAL diagnosis
• Key features of fibromyalgia:
-Widespread pain involving both sides of the body, above and below the waist for at least 3 months
- Presence of 11 tender points among the 9 pairs of specific sites shown in the diagram below
Definition of Giant Cell Arteritis (Temporal Arteritis )
Granulomatous inflammation of large arteries, particularly branches of the external carotid artery, most commonly the TEMPORAL ARTERY
Aetiology/ Risk Factors of Giant Cell Arteritis
- UNKNOWN
- More common with increasing age
- Some associations with ethnic background and infections
- Associated with HLA-DR4 and HLA-DRB1
Epidemiology of Giant Cell Arteritis
- More common in FEMALES
* Peak age of onset: 65-70 yrs
Presenting symptoms of Giant Cell Arteritis
• Subacute onset (usually over a few weeks)
• Headache
• Scalp tenderness
• Jaw claudication
• Blurred vision
• Sudden blindness in one eye
• Systemic: malaise, low-grade fever, lethargy,
weight loss, depression
• Symptoms of polymyalgia rheumatica - early
morning pain and stiffness of muscles of the shoulder and pelvic girdle
NOTE: 40-60% of GCA has polymyalgia rheumatica
Signs of giant cell arteritis on physical examination
- Swelling and erythema overlying the temporal artery
- Scalp and temporal tenderness
- Thickened non-pulsatile temporal artery
- Reduced visual acuity
Investigations for giant cell arteritis
• Bloods:
- High ESR
- FBC - normocytic anaemia of chronic disease
• Temporal Artery Biopsy:
- Must be performed within 48 hrs of starting corticosteroids
- Negative biopsy doesn’t necessarily rule out GCA
Management plan for giant cell arteritis
• High dose oral prednisolone IMMEDIATELY to prevent visual loss
• Reduce the dose of prednisolone gradually
• Many patients will need to be kept on a maintenance dose of prednisolone for 1-2 yrs
• Low dose aspirin (with PPIs and gastroprotection) - reduces risk of visual loss, TIAs and
stroke
• Annual CXR for up to 10 yrs to look for thoracic aortic aneurysms
Complications for Giant Cell Arteritis
- Carotid artery aneurysms
- Aortic aneurysms
- Thrombosis
- Embolism to the ophthalmic artery leading to visual disturbance and loss of vision
Summarise the prognosis for patients with giant cell arteritis
• In most cases the condition will last for around 2 years before complete remission
CXR:
- Can detect osteoarthritic change
Rarely diagnostic if non-traumatic
• MRI
o allows assessment of root and cord compression
o helps exclude spinal cord tumour and nerve root infiltration by granulomatous tissue
• Needle Electromyography (EMG)
Definition of Gout
A disorder of uric acid metabolism causing recurrent bouts of acute arthritis caused by deposition of monosodium urate crystals in joints, and also soft tissues and kidneys
Aetiology/ Risk Factors of Gout
- The main metabolic disturbance is hyperuricaemia
- This may be caused by:
Increased urate intake or production via :
• Increased dietary intake
• Increased nucleic acid turnover (e.g. lymphoma, leukaemia, psoriasis)
• Increased synthesis of urate (e.g. Lesch-Nyhan syndrome)
Decreased Renal Excretion via:
• Idiopathic
• Drugs (e.g. ciclosporin, alcohol, loop diuretics)
• Renal dysfunction
Epidemiology of gout
- 10 x more common in MALES
- Very rare pre-puberty
- Rare in pre-menopausal women
- More common in HIGHER social classes
Presenting Symptoms and Signs of an acute attack of Gout
- Precipitating factors:
• Trauma
• Infection
• Alcohol
• Starvation
• Introduction or withdrawal of hypouricaemic agents Symptoms:
• Sudden excruciating monoarticular pain - Usually affecting the metatarsophalangeal joint of the great toe (podagra)
• Symptoms peak at 24 hrs
• They resolve over 7-10 days
• Sometimes, acute attacks can present with cellulitis, polyarticular or
periarticular involvement
• Attacks are often recurrent
• Patients are symptom-free between attacks
(INTERCRITICAL GOUT: - asymptomatic period between acute attacks )
