2nd half of red Flashcards
What is Ehlers-Danlos Syndrome
group of connective tissue disorders caused by mutations of connective tissue proteins, with collagen being the most commonly affected.
Rf for EDS
fAMILY HISTORY - AUTOSOMAL dominant is the most common subytype
What does EDS lead to
Weakened connective tissue in the skin, bones, blood vessels, and organs, which accounts for the numerous features of the disorder.
Classical Ehlers-Danlos syndrome
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Classical Ehlers-Danlos syndrome
- Caused by mutation in COL5A1 and COL5A2 genes
- Passed on by autosomal dominant inheritance
Vascular Ehlers-Danlos syndrome
- Mutation in COL3A1
- Decrease in type III collagen weakens blood vessels
- Most dangerous due to risk of aneurysms as well as aortic and organ rupture
Autosomal recessive EDS
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Classical-like Ehlers-Danlos Syndrome
- Mutation in gene that encodes TNXB (causes defect in protein called tenascin X)
- Tenascin-X provides flexibility and also plays a role in regulating production and assembly of certain types of collagen
- Mutation in gene that encodes TNXB (causes defect in protein called tenascin X)
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Kyphoscoliotic Ehlers-Danlos syndrome
- Insufficient lysyl hydroxylase
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Musculocontractural Ehlers-Danlos syndrome
- Defect in collagen peptidase
Clinical manifestations of EDS
Musculoskeletal
- Joint hypermobility and pain
- Recurrent dislocation
- Scoliosis and spinal pain
Skin
- Hyperelasticity
- Easy bruising
- Atrophic skin
Investigations for EDS
- Examine joints and skin
- Genetic testing to identify mutation
- Echocardiogram:assess for mitral valve prolapse and aortic root dilatation
- Spine X-ray:evidence of scoliosis or spondylolisthesis (vertebral misalignment); usually required in patients with spinal pain or scoliosis on examination
Management for EDS
- Physiotherapy
- Orthopaedic instrument e.g. bracing, wheelchair and casting
- Lifestyle advice: avoid contact sports and heavy labour to reduce the risk of tissue damage and joint dislocation
- Analgesia
- Psychological input: due to chronic pain and the impact on quality of life, patients may develop mental illness
Complications
Mitral valve prolapse: mid-systolic click and late-systolic murmur
Aortic dissection
Abdominal aortic aneurysms
Organ rupture
Subarachnoid haemorrhage
Angioid retinal streaks
Abdominal hernia
Gastro-oesophageal reflux disease
Degenerative arthritis due to recurrent joint dislocation
Depression and anxiety
What is Marfans syndrome
genetic disorder that results in defective connective tissue. This can affect the skeleton, heart, blood vessels, eyes and lungs.
Epidemiology of Marfans
he incidence in the European population is estimated to be 3 in 10,000.
Pathophysiology if Marfan’s
- Marfan syndrome is caused by mutations in a gene called FBN1 (fibrillin 1) on chromosome 15. This is autosomal dominant.
- FBN1 gene encodes fibrillin 1 protein. In Marfan syndrome, fibrillin 1 is either dysfunctional or less abundant, which results in fewer functional microfibrils. This also means there is less tissue integrity and elasticity.
- Additionally, TGF-beta doesnt get successfully sequestered so TGF-beta signalling is excessive in these tissues = more growth
Clinical features of Marfans
Features might not always be there
- Tall stature, long arms and long legs due to excessive long bone growth
- Arachnodactyly - long fingers and toes
- Pectus excavatum (chest sinks in) or pectus carinatum (chest points out)
- Scoliosis
- Inability to extend elbows to 180 degrees
- Flexible joints (hypermobility)
- Downward slant of the eyes
- Narrow high-arch palate - crowds teeth
- Stretch marks
Investigations for Marfans
Diagnosis is based on clinical features (diagnose if >2 features)
- Lens dislocation
- Aortic dissection/ dilation
- Dural ectasia - widening of the dural sac
- Skeletal features e.g. long arms, arachnodactyly
- Pectus deformity
- Scoliosis
- Pes planus - flat feet
MRI
DDs of MARFANS
- Ehlers-Danlos syndrome
- Erdheim’s deformity - presents with dilation of aortic root
- Homocystinuria - body cannot process amino acids properly. Presents similar to Marfan syndrome
General Management for Marfans
- Physiotherapy can be helpful in strengthening joints and reducing symptoms arising from hypermobility.
- Genetic counselling is important in considering the implications of having children that may be affected by the condition
Eye and CVD related management for Marfans
Eye-related
- Replacement of dislocated lens with artificial lens
Cardiovascular-related
- Lifestyle changes, such as avoiding intense exercise and avoiding caffeine and other stimulants - minimise stress to help cardiac complications
- Beta blockers can also be used to stop aortic dilation
- Angiotensin receptor blocker e.g. losartan - decreases tgf-beta signalling and can also decrease aortic dilation
- Surgical repair of wide aorta.
Complications for Marfans
- Retinal detachment and lens dislocation
- Joint dislocations and pain due to hypermobility
- Bulla formation on lungs - leading to pneumothorax
- Cardiovascular:
- Aortic dilation causing aortic valve insufficiency
- Cystic medial necrosis (tunica media of aortic wall degenerates)
- Increased risk of aortic dissection, aneurysm and rupture
- Mitral valve prolapse
- Aortic valve prolapse
Prognosis of Marfans
The average life expectancy used to be only 32 years but, due to early surgery, it is now approaching that of the general population.
Long-term survival is excellent with beta-blocker control and surgery when indicated. **Once aortic dissection occurs, survival is considerably reduced to between 50% and 70% at 5 years.
What do we mean by mechanical
Mechanical means that the source of the pain may be in your spinal joints, discs, vertebrae, or soft tissues.
Epidemiology of mechanical back pain
Common in young people: 20-55 years
Aetiology of mechanical back pain
- Strain
- Heavy manual handling
- Stooping and twisting whilst lifting
- Pregnancy
- Trauma
- Lumbar disc prolapse
- Spondylolisthesis (one vertebrae slips out of place causing back pain)
- Osteoarthritis
- Fractures
- Exposure to whole body vibration
RF for mechanical back pain
- Female
- Increasing age
- Pre-existing chronic widespread pain - fibromyalgia
- Psychosocial factors e.g. high levels of psychological distress, poor self-rated health, smoking and dissatisfaction with work
Physiology of mechanical back pain
Spinal movement occurs at the disc and the posterior facet joints - stability is normally achieved by a complex mechanism of spinal ligaments and muscles. Any of these structures may be a source of pain.
Where do the main lesions occur
in an intervertebral disc - a fibrous structure whose tough capsule inserts into the the rim of the adjacent vertebra. This capsule encloses a fibrous outer zone and a gel-like inner zone
Disc allows rotation and bending
When do changes in discs start?
- occasionally start in teenage years or early twenties and often increase with age
- The gel changes chemically, breaks up, shrinks and loses its compliance
- The surrounding fibrous zone develop circumferential or radial issues
What happens when discs become thinner and less compliant
- These changes cause circumferential bulging of the intervertebral ligaments
- Reactive changes develop in adjacent vertebrae; the bone becomes sclerotic and osteophytes form around the rim of the vertebra
Most common site for lumbar spondylosis
L5/S1 & L4/L5
Spondylosis (mostly symptomless) but can cause
- Episodic spinal pain
- Progressive spinal stiffening
- Facet joint pain
- Acute disc prolapse, with or without nerve irritation
- Spinal stenosis
Facet Joint Syndrome
- Lumbar spondylosis causes secondary osteoarthritis of the misaligned facet joints
- Pain is typically worse on bending backwards and when straightening from flexion - it is lumbar in site, unilateral or bilateral and radiates to the buttock
- Facet joints are well seen on MRI and may show osteoarthritis, an effusion or a ganglion cyst
- Treatment consists of direct corticosteroid injections under imaging
- Physiotherapy and help to reduce weight may also be offered
Fibrositic nodulosis
- There are tender nodules in the upper buttock and along the iliac crest
- This condition causes unilateral or bilateral lower back and buttock pain
- Local intralesional corticosteroid injections may help
Clinical manifestations of mechanical lower back pain
- Stiff back
- Scoliosis
- Muscular spasm
- Pain worse in the evening
Investigations for mechanical lower back pain
- MRI - imagine modality of choice. Can see disc prolapse, cord compression, cancer, infection or inflammation.
- Bone scans
- Examine patient to exclude pathologies e.g. nerve root lesions affecting reflexes
- Spinal X-rays
Differential diagnossi for mechanical lower back pain
- Polymyalgia rheumatica (PMR): in elderly, ESR and CRP will distinguish this from mechanical back pain
- Sinister causes of back pain e.g. malignancy, infection or inflammatory causes. Must be excluded with spinal x-ray.
Management for mechanical lower back pain
- Analgesics - NSAIDs paracetamol, codeine
- Acupuncture
- Avoid excessive rest
- Comfortable sleeping postions
