Connective Tissue Flashcards
What is polymyositis and dermatomyositis both associated with?
Underlying malignancy
What are the clinical features of myositis
- Insidious Weakness: usually over a matter of weeks and it is symmetrical (cannot reach as high to cupboards, getting out of bed etc.)
- Pain is not a predominant feature
- Systemic symptoms: e.g fever, weight loss and fatigue
- Lungs:
respiratory or pharyngeal muscle involvement
(CHECK JO-1 ANTIBODIES- SHOWS WHETHER THEY ARE MORE AT RISK OF DEVELOPING LUNG INVOVLEMENT) - Skin : Gottron’s papules (scaly, violaceous, psoriasiform plaques over PIP AND DIP joints - can be palpated)
- heliotrope rash (violaceous discoloration of the eyelid)
What parts of the body does myositis affect?
Can be upper limb, can be lower limb and it can also be both
Investigations of myositis
- Serum levels of creatine kinase (can be low if the condition had an insidious onset)
- MRI to find abnormal muscle
- Electromyography ( is very useful for highlighting non- autoimmune/non- inflammatory myopathies
- Screening for underlying malignancy e.g history(e.g voice changes), examination, CXR, CT of chest/abdomen/pelvis, PSA mammography)
- Muscle biopsy (best done in surgery under local anaesthesia) - looks for fibre necrosis, regeneration and inflammatory cell infiltrate
Management of myositis
- Oral glucocorticoids (IV if severe
- Maintenance dose (5-7.5 mg)
- Immunosuppressive therapy: methotrexate, MMF. Azathioprine
- Rituximab probably efficacious
- IV immunoglobulin may be effective in refractory cases
Paraneoplastic condition?
- Underlying Malignancy that looks like something else
Define vasculitis
- Inflammation and necrosis of blood vessel walls associated damage to skin, kidney, lung, heart, brain and gastrointestinal tract
- Wide spectrum of symptoms and severity (from mild and transient disease to life- threatening disease0
- Clinical features results from a combination of local tissue ischaemia (due to vessel inflammation and narrowing) and the systemic effects of widespread inflammation
When should you consider vasculitis in anyone?
- could be primary (antibody associated)
- or secondary
Anyone who has a fever, weight loss, fatigue, multisystem involvement, rashes, raised inflammatory markers and abnormal urinalysis
What is giant cell arteritis
Vasculitis `
Why is temporal artery biopsy not preferred?
- can be diagnostic
- skip lesions can occur (some parts of the parts in the biopsy are skipped past)
What is the management of giant cell arteritis
- Steroids e.g prednisolone (15mg as a starting dose)
- dose should be progressively reduced (2-3weeks)
- rate of reduction should then be slowed to 1mg per month
- symptoms might recur and then dose should be increased again
- SAFETYNETTING IS IMPORTANT HERE
- Most patients need glucocorticoids for an average of 12- 24 months
- use bisphosphonates for bones
SEE NOTES FOR COMPARISON BETWEEN POLYMYOSITIS AND POLYMYALGIA RHEUMATICA
!!!!
What conditions can mimic polymyalgia rheumatica?
Calcium pyrophosphate disease
Spondyloarthritis
Hyper-/hypothyroidism
Psoriatic arthritis (enthesopathic)
Systemic vasculitis
Multiple myeloma
Inflammatory myopathy
Lambert–Eaton syndrome
Multiple separate lesions (cervical spondylosis, cervical radiculopathy, bilateral subacromial impingement, facet joint arthritis, osteoarthritis of the acromioclavicular joint)
What is giant cell arteritis? (GCA)
- granulomatous arteritis that affects any large (including aorta) and medium- sized arteries
- it is symmetrical
- included shoulder ,neck and hip girdle pain and stiffness
- often co-exists with polymyalgia rheumatica
- rare under the age of 60 years
- average onset is 70
- more prevalent in females
Clinical features of GCA?`
- headaches localised to temporal or occipital region
- jaw pain when chewing/talking
- scalp tenderness
- visual disturbance
- rarely some neurological involvement e.g brainstem infarcts
- with PMR: stiffness and painful restriction of active shoulder movements on waking but muscles are not tender or weak
What is primary Raynaud’s phenomenon usually triggered by?
- cold temperatures, anxiety and stress
- temporary spasm of blood vessels which blocks the flow blood
What are the clinical features of Raynaud’s phenomenon?
- triphasic (three phases): white, blue, red (paler if dark skin)
- fingers, toes, ears, nose, lips or nipples can be affected
- symptoms:
- pain
- numbness
- pins and needles
How do you manage Raynaud’s syndrome?
- Keep warm
- Stop smoking
- Calcium channel blockers
- Iloprost (medication used to treat conditions where vessels are constricted)
- Sildenafil (viagra)
Connective tissue disease that are characterized by inflammation of tissues (autoimmune diseases)
- Polymyositis
- Dermatomyositis
- RA
- Scleroderma
- Sjogren’s syndrome
- Systemic lupus erythematosus
- Vasculitis
Connective tissue disease characterise due to single-gene defects:
- Ehlers- Danlos syndrome
- Epidermolysis bullosa
- Marfan syndrome
- Osteogenesis imperfecta
Systemic lupus erythematosus (SLE, lupus) epidemiology?
- Prevalence: 0.03% in Caucasians, 0.2% in afro- Caribbean
- 90% of affected patients are female
- peak age is 20 to 30 years
- fivefold increase in mortality compared to age and gender-matched controls (cardiovascular disease)
Clinical features of systemic lupus erythematosus epidemiology?
- Variable
- Secondary raynauds disease
Systemic features include:
— fever
— weight loss
— mild lymphadenopathy
— fatigue
— arthralgia
Continuing symptoms and flares/ exacerbations ‘
Joint involvement: - Arthralgia in joints
- Tenosynovitis might occur
- Synovitis is rare
- Jaccoud’s arthropathy is rare too
Pathophysiology of SLE?
- Not fully known
- monozygotic twins,
polymorphic variants at the HLA locus.
inherited mutations in complement components C1q, C2 and C4, in the immunoglobulin receptor FcγRIIIb or in the DNA exonuclease TREX1.
polymorphisms of genes that predispose to SLE, most of which are involved in regulating immune cell function
Autoantibody production
Usually directed against antigens present within the cell or within the nucleus.
Secondary Raynaud’s syndrome is a symptoms of Lupus. TRUE OR FALSE
TRUE
Secondary Raynaud’s disease is a symptom of Lupus
How does Lupus affect the skin?
- Classic facial rash (20% of patients)
- Discoid rash (hyperkeratosis and follicular plugging which can cause scarring alopecia if it involves the scalp)
- Diffuse, non- scarring alopecia
- Urticaria (hives, which are red, itchy wells)
- Livedo reticularis
- Vasculitis(inflammation of blood vessels)
What other systems does lupus affect?
- Renal system
(Hallmark of severe disease, regular urinalysis and blood pressure is essential, can present with haematuria, proteinuria and casts on urine microscopy) - Cardiovascular disease
Can cause myocarditis, pericarditis( inflammation of the pericardium)
Can cause atherosclerosis which increases risk of stroke and myocardial infarction(Tissue death)
-Lungs
Increased risk of DVT, PE etc especially if ANTIPHOSPHOTLIPID ANTIBDOY IS PRESENT - Pleuritic pain or pleural effusion
-Neurological involvement
Headaches, poor concentration etc. - Gastrointestinal involvement
Mouth ulcers are common
Hepatitis is rare
Mesenteric (continues set of tissues in abdomen) vasculitis is serious - Can cause haematological abnormalities e.g neutropenia, lymphopenia, thrombocytopenia etc.
What are urine casts?
- tiny tube shaped particles
- made up of white blood cells, red blood cells, kidney cells, or substances such as protein or fat.
What is the pleura?
Thin membranes that line the lungs
What is antiphospholipid antibody syndrome?
ALPS - autoimmune disorder characterized by the presence of abnormal antibodies in the blood associated with abnormal clotting.
Causes migraines, headaches, recurrent miscarriages etc.
- patients that have lupus are more likely to develop APLS aswell
How do you manage ALPS?
- Avoidance of oral contraceptive
- Avoidance of smoking
- Treatment of hypertension, hyperlipidaemia
- Patients that have arterial thrombosis should be treated with anticoagulants (warfarin) - however this medication should be stopped in the event of wanting to conceive
Asymptomatic patients should not be treated
How do you manage lupus>
- Education about SLE is essential
- Use of sun blocks
- Medications
1. NSAIDs
2. Corticosteroids
3. Cytotoxic drugs in combination to corticosteroids
4. Severe lupus - Tacrolimus can be used
Before giving medications for lupus what do you have to assess?
- Risk of osteoporosis and hypovitaminosis D
- Address cardiovascular risk factors (hypertension and hyperlipidaemia)
What is systemic sclerosis?
It is a condition that causes fibrosis of the skin, internal organs and vasculature
- it is also characterized by Raynaud’s, sclerodactyly and cardiac, lung and GI and renal disease
Systemic sclerosis epidemiology
- more common in females
- peak age onset is 4ht and 5th decades
- overall prevalence: 10-20% per 100000
Systemic sclerosis divisions;
- Diffuse cutaneous systemic sclerosis (30% of all cases)
2. Limited cutaneous systemic sclerosis (70%)
What is the pathophysiology of systemic sclerosis
Not fully understood
Clinical features of SS?
- non -pitting oedema of fingers and flexor tendon sheaths
- skin becomes shiny and taunt
- there can be capillary loss
- face and neck are often involved with thinning of the lips
- lcSScl: skin involvement restricted to sites distal to the elbow or knee (also affects the face)
dcSScl: involvement proximal to the knee and elbow and on the trunk is classified as ‘diffuse disease’
Other involvements/ features of systemic sclerosis
-Raynaud’s phenomenon
—-May precede other features by many years.
.When severe and progressive, critical tissue ischaemia, with distal skin infarction and necrosis.
-Musculoskeletal features
.Arthralgia and flexor tenosynovitis are common
.Restricted hand function is due to skin rather than joint disease
.Muscle weakness and wasting can result from myositis
-Gastrointestinal involvement
.Erosive oesophagitis
.Dysphagia
.Malabsorption due to bacterial overgrowth
.Dilatation of bowel
-Pulmonary involvement
.pulmonary hypertension more prevalent in lcSScl than in dcSScl.
complain of shortness of breath on exertion
interstitial lung disease is common
.Renal involvement
.Hypertensive renal crisis
.Rapid increasing hypertension and renal failure
Investigations of SS
- Blood tests
e.g FBC, U&E, LFT, Bone group, Urinalysis = essential.
ANA (usually positive)
.Scl70 positive in 30% of patients with dcSScl
.Anticentromere antibodies in 60% of patients with lcSScl syndrome - Imaging
. Chest x-ray and Chest CT
. Echocardiography (looks at how much pressure the heart is pumping blood etc)
. lung function test (using a pipe you blow into to see elasticity of lungs)
. barium swallow test to see oesophageal involvement
SS management
Nil to stop or reverse fibrosis
Try to slow the effects of the disease on target organs.
Raynaud’s phenomenon and digital ulcers:
Avoid cold, thermal gloves/socks, high core temperature (calcium channel blockers, losartan, fluoxetine, sildenafil. intravenous prostacycline, bosentan
Gastrointestinal complications:
proton pump inhibitors
Hypertension:
ACE inhibitors
Joint involvement
NSAIDs, analgesia
Progressive pulmonary hypertension
bosentan or heart–lung transplant
Interstitial lung disease Glucocorticoids and (pulse intravenous) cyclophosphamide
What is Primary Sjogren’s syndrome? (PSS)
- ## lymphocytic infiltration and fibrosis of salivary and lacrimal glands
