Connective tissue diseases - Clinical Medicine Flashcards
a) What is raynaud’s phenomenon?
b) What is it tirggered by?
c) What drug worsens raynaud’s?
d) What are the symptoms
e) Discuss the management
a) Raynauds phenomenon is caused by temporary spasm of blood vessels which block the flow of blood
b) Cold temperatures, anxiety, stress - can be primary or secondary
c)
- Fingers, toes, ears, nose, lips or nipples commonly affected
- Triphasic colour changes: white, blue and red
- Pain
- Numbness
- Pins and needles
- Digital ulceration (severe)
- Digital gangrene (severe)
d) Propanalol - beta blocker
e)
- Keep warm
- Stop smoking (can cause vasoconstriction of blood vessels, worseing Raynaud’s)
- 1st line - Calcium channel blocker (antihypetensive drug which relaxes muscle walls around blood vessels - helps encourage blood flow to peripheries)
- Iloprost (encourages blood flow but requires to be in hospital for 5 days - recommended for those with necrosis)
- Sildenafil/viagra (increases blood flow to peripheries - best for those who have ulcer as it prrevents healing and new ulcers forming)
- IV prostacyclin
What may you see on examination of someone’s with raynaud’s?
- Capillary nail-fold loops (and oil placed on the skin) can show loss of normal loop pattern
- Chrnoic ischaemia may lead to colour change
- Digital ulcers in severe disease
When would you consider secondary Raynaud’s?
- Age at onset over 25 years
- Absence of a family history of Raynaud’s phenomenon
- Male patient
Describe the epidemiology of SLE
- More prevalent in afro-carribeans than caucasians
- More common in females (90% of affected patients are female)
- Peak age of onset is between 20 and 30 years
Discuss the aetiology of SLE
- There are genetic, environmental and hormonal factors thought to be important to the aetiology
- SLE can be induced by drugs e.g., minocycline, hydralazine, and the oral contraceptive pill (drug-induced lupus tends to be mild and does not affect the kidneys)
- Oestrogen is thought to play a role in producing autoreactive B cells
- Environmental triggers include viruses and UV B-light
Give 5 factors that trigger flares of SLE
- Overexposure to sunlight: UV light B > A
- Oestrogen-containing contraceptic therapy
- Drug e.g., hyrdalazine (BP), minocycline (susceptible infections), carbamzepine (epilepsy), chlorpromazine (psychosis), isoniazid (TB), methyldopa (BP) and sulphasalazine (RhA)
- Infection
- Stress
Give 7 drugs that can trigger flares of SLE
- Hyrdalazine (BP)
- Minocycline (susceptible infections)
- Carbamzepine (epilepsy)
- Chlorpromazine (psychosis)
- Isoniazid (TB)
- Methyldopa (BP)
- Sulphasalazine (RhA)
Desrcibe the clinical features of SLE
- Variable
- Systemic features
* Fever, weight loss, mild lymphadenopathy, fatigue and arthralgia - Joints
- Arthralgia with early morning stiffness
- Synovitis (rare)
- Jaccoud’s arthropathy - rheumatoid hands that are reducible in extension
- Raynaud’s phenomenon
- Dermatological features
- Butterly malar rash on cheeks and nose
- Discoid rash
- Diffuse and non-scarring alopecia (hair loss)
- Urticaria (red, itchy welts that result from a skin reaction)
- Livedo reticularis (refers to a netlike pattern of reddish-blue skin discoloration)
- Renal features
- Hallmark of severe disease
- Proliferative glomerulonephritis - most common cause of lupus-realted death
- Presents with heavy haematuria, proteinuria and casts on urine microscopy
- Cardiovascular features
- Heart - pericarditis, myocarditis and Libman-Sacks endocarditis (sterile vegetations - inflammation seen on valves of the heart)
- Arteries - atherosclerosis greatly increased, increasing chances of a stroke and myocardial infarction
- Raynaud’s phenomenon
- Vasculitis
- Pulmonary features
- Pleuritic pain (serositis) or pleural effusion (fluid inside of lungs as a result of inflamed lining of the cell)
- Less common: pneymonitis, ateletasis, reduced lung volume and pulmonary fibrosis that leads to breathlessness
- Increased risk of thromboembolism (DVT, pulmonary embolism), especially if antiphospholipid antibodies present
- Neurological
- Headache and poor concentration are common
- Less common: visual hallucinations, chorea (a movement disorder that causes involuntary, irregular, unpredictable muscle movements), organic psychosis, transverse myelitis and lymphocytic meningitis
- Neuropsychiatric e.g., seizures, stroke, movement disorder, transverse myelitis, cranial neuropathy, peripheral neuropathy, psychosis, anxiety, depression
- GI tract
- Mouth/nose/genital
- Peritoneal serositis (inflammation of lining of abdominal cavity) can cause acute pain
- Mesentric vasculitis is serious (abdominal pain, bowel infarction or perforation)
- Hepatitis is rare
- Haematological abnormalitis
- Neutropenia
- Lymphopenia
- Thromobocytopenia
- Haemolytic anaemia
Describe the late complications of SLE
- Glomerulonephritis - end stage renal disease, dialysis and transplantation
- Vasculitis - atherosclerosis, pulmonary embolism
- Arthritis - osteonecrosis
- (Cerbral lupus) Cerebritis - neuropsychiatric dysfunction e.g., fits, psychosis, raised ESR and anti-dsDNA titre, low complement C3 and C4
- Pneumonitis - shrinking lung syndrome
Lupus glomerulonephritis and cerebral lupus are the two main emergencies in SLE
a) Describe the clinical symptoms, treatment and prevention of lupus glomerulonephritis
b) Describe the clinical features, signs and treatment of cerebra lupus
- Lupus glomerulonephritis
- Clinical features - nephritis (proteinuria, hypoalbuminemia and oedema)
- Treatment - high dose steroids plus immunosuppression
- Prevention - urinalysis to assess for proteinuria
- Cerebral lupus
* Clinical features - different presentations e.g., fits, psychosis, severe unremitting headaches or impairment of consciousness + other signs of active SLE disease.
Signs: ESR and anti ds-DNA antibody titres will be raised whereas the complement C3 and C4 levels will be low. The C-Reactive Protein (CRP) levels will often not be markedly raised. Sometimes, the blood markers of active SLE disease and the MRI scan can be normal.
Treatment- high dose steroids and immunosuppression (Cyclophosphamide/Azathioprine).
How are kidneys in patient with SLE monitored?
Regular urinalysis and blood pressure monitoring is essential
a) What factors can lead to neonatal lupus in babies?
b) What are the symptoms
a)
- Pregnancy loss
- Preterm birth
b)
- Pericardial effusion and conduction effects
- Skin rash
Name the diagnostic criteria for SLE
Presence of ≥4 supports the diagnosis:
A RASH POINTs MD
- Arthritis/arthralgia
- Renal disease
- ANA +ve
- Serosits (pericardits/pleurisy/pleural effusion)
- Haemotological (haemolysis/low WCC/platelets/lymphocytes)
- Photosensitivity rash
- Oral ulcers
- Immunological tests positive (anti-dsDNA/anti-Sm,anti-phospholipid)
- Neuropsychiatric (seizures, migraines, psyhosis)
- Malar rash
- Discoid rash
Describe the initial investigations andother investigations undertaken for SLE and the findings
Initial investigations
- Immunological (Autoantibodies) e.g., ANA, anti-Ro/La, anti-DsDNA may be detected
- U+E’s and urinalysis - look for haematuria and proteinuria which are signs of nephritis
- FBC - look for anaemia, leukopenia, thrombocytopenia
- ESR- high during flare up
- CRP- normal/mildly elevated unless infection, synovitis or serositis present
- Complement levels (C3 and C4) - lower in SLE
Other investigations
- Plain X-rays - show inflammation of affected joints
- Coombs test - positive in patients with autoimmune haemolytic anaemia
- Skin biopsy - shows deposition of IgG and complement at the dermal–epidermal junction in patients with rashes (lupus band test)
- Renal biopsy - sometimes performed to aid diagnosis or to establish prognosis in patients with abnormal renal function + most sensitive and specific test for lupus nephritis
- Brain MRI - patients with suspected cerebral lupuss
- Echocardiogram - can show pericarditis, pericardial effusion, pulmonary hypertension
- Pulmonary function tests - show a restrictive pattern
- Pleural aspiration - may be performed in patients to identify cause of pleural effusion and shows exudate
a) What is the main autoantibody associated with SLE
b) What other autoantibodies is SLE associated with?List the autoantibodies associated with SLE
a) Anti-nuclear antibodies (ANA) - detected in >95% patients
b)
- Anti-Ro and anti-La antibodiees
- Anti-dsDNA antibodies
- Antihistone antibodies (+ve in drug-induced SLE)
- Antiphospholipid and anticardiollpin antibodies
List the 6 immmunological SLICC (Systemic lupus international collaborating clinics) classification criteria for SLE
- ANA
- Anti-DNA
- Anti-Sm
- Antiphospholipid Antibody
- Low complement (C3, C4, CH50)
- Direct Coomb’ test (do not count in the presence of hemolytic anaemia)
Describe the management of lupus
- Educate the patient - control symptoms to prevent organ damage and maintain normal function
- Avoid sun exposure and use sun block (spf 50), avoid oestrogen containing contraceptive pill
- Medicines - NSAIDs and hydroxychlorquine for mild disease, long-term corticosteroids for prominent organ involvement, high dose corticosteroids and immunosuppressants - usually cyclophosphamide for severe flares that cause serious renal, neurological or haematological effects
Name drug therapies that can be given to treat skin and joint disorder in SLE
- NAIDs + hydroxycholoquine (also protective against heart)
- Prednisolone
- Mycophenolate mofetil (immunosuppressant)
- Methotrexate
- Azathioprine
- Belimumab (monoclonal antibody targets the β-cell growth factor BLyS)
Name drug therapies (aggressive treatment) that can be given to treat end organ disease SLE
- High-dose glucocorticoids and immunosuppresants
- IV methylprednisolone (10mg/kg IV) plus IV cyclophosphamide for six cycles
- Rituximab and belimumab may benefit in some (used in refractory lupus)
Describe maintenance therapy of SLE
- Taper prednisolone - long term low dose
- Immunosuppresants - azathioprine, methotrextae, mycophenolate mofetil (MMF)
- Address cardiovascular risk factors
- Patients should be advised to stop smoking
- Anticoagulation with warfarin if thrombosis and antiphospholipid antibody syndrome
- Assess risk of osteoporosis and hypovitaminosis D
Which rheumatological conditions are known to frequently occur secondary to SLE?
- Secondary Sjogren’s syndrome.
- Secondary anti-phospholipid syndrome.
- Mixed connective tissue disease (features of SLE, systemic sclerosis and poly/dermatomyositis).
a) What is antiphospholipid syndrome (APS)
b) Name 3 things it is associated with
a) The antiphospholipid syndrome (APS) is a systemic autoimmune condition characterized by arterial and venous thrombosis, fetal loss and thrombocytopenia associated with persistent levels of antiphospholipid antibodies.
b)
- SLE
- Repeated miscarriages
- Fetal death
Describe the clinical features of antiphospholipid syndrome
Major features
- Venous thrombosis - DVT and pulmonary emboli
- Arterial thrombosis - cerebral ischaemia and periperal sichaemia
- Fetal complications - spontaneous abortion, premature births
- Thrombocytopenia
Associated clinical features
- Livdeo reticularis
- Leg ulcers
- Cardiac valve abnormalities
- Chorea
- Epilepsy
- Migrane
- Haemolytic anaemia
What are the antibodies associated with anti-phospholid syndrome?
- Anti-cardiolipin
- Lupus anticoagulant
- Anti-beta 2 glycoprotein-1
Describe the investigation/diagnosis of antiphospholipid syndrome
- Diagnosis is based on the detection of anticardiolipin antibodies or a positive lupus anticoagulant assay on at least two occasions separated by at least a 12-week interval.
Describe the treatment/management of antiphospholipid syndrome
- Asymptomatic/those with high cardiovascular risk factors or with a concurrent separate autoimmune disease should receive low-dose aspirin prophylaxis = main treatment
- Venous thrombosis or arterial thrombosis - conventional anticoagulation e.g., warfarin
- Recurrent fetal loss- warfarin should be stopped before conception because it is tetragenic and S/C heparin and aspirin should be given throughout pregnancy to reduce risk of fetal loss
- Treatment of hypertension, diabetes and hyperlipidaemia
- Avoidance of the oestrogen oral contraceptive pill- prevents venous and arterial thrombosis
- Avoidance of smoking - prevents venous and arterial thrombosis
a) What is systemic sclerosis (SScl)?
b) What is SScl characterised by?
a) System sclerosis causes fibrosis, affecting the skin, internal organs, vasculature
b)
- Raynaud’s phenomenon (+/- digital ischaemia)
- Sclerodactyly
- Cardia disease
- Lung dsease
- GI disease
- Renal disease
Describe the epidemiology of systemic scelorsis
- Peak age of onset is 4th and 5th decades
- Overall prevalence is 10-20/100,000
- More common in females - F:M = 4:1
What are the two sub divisions of systemic sclerosis and include the percentage of cases it makes us
- Diffuse cutaneous systemic sclerosis (dcSScl) - 30% of cases
- Limited cutaneous systemic scleosis (lcSScl) - 70% of cases
a) What is limited cutaneous systemic sclerosis (lcSScl) characterised by?
b) How does this differe to diffuse systemic sclerosis
a) CREST
- Calcinosis
- Raynauds’s
- oEsophageal involvement
- Sclerodactyly (skin tightening)
- Telangiectasia (small, widened blood vessels on the skin)
b) In diffuse system sclerosis you get skin involvement in regions other than the face and lower arms
Describe the prognosis of diffuse cutaneous systemic sclerosis (dcSScl)
Prognosis is poor - 5 year survival rate is 70%
Describe the clinical features of systemic scelorosis
- Skin
- Non-pitting oedema of fingers and flexor tendon sheats
- Shiny and taught
- Capillary loss
- Face and neck are often involved, with thining of the lips and radial furrowing
- Tethering of skin to underlying structures
- Skin hypo- and hyper-pigmentation
- lsSScl - skin involvement restricted to sites distal to the elbow or knee (apart from the face)
- dsSScl: involvement proximal to the knee and elbow and on the trunk is classified as diffuse disease
2.Cardiovascular
- Rayanud’s phenomenon- if there is thumb involvemnt expect secondary Raynaud’s
- Cardiac disease - myocardial fibrosis, pericarditis
- MSK
- Arthralgia and flexor tenosynovitis are common
- Restricted hand function due to skin being tight rather than joint disease
- Muscle weakness and wasting can result from myositis
- GI
- Erosive oesophagitis
- Dysphagia - difficulty swallowing
- Malabsorption due to nacterial overgrowth
- Dilatation of bowel
- Pulmonary
- Pulmonary fibrosis is common
- Interstitial lung disease is common
- Pulmonary hypertenions more prevalent in lcSScl than in dcSScl
- Shortness of breath on extertion
- Pulmonary disease most common cause of death
- Renal
* Scleroderma renal crisis - kidney tissue replaced by fibrosis causes hypertensive renal crisis - rapid increasing hypertenion and renal failure (cause of death) - Neurological
* Central and peripheral neuropathies can develop
What are the main causes of death in systemic sclerosis
- Pulmonary involvement - pulmonary hypertension, intersitital lung disease
- Renal involvement - Scleroderma renal crisis (rapid increasing hypertension and renal failure)
Describe screening forcomplications in systemic sclerosis
Monitoring pulmonary function tests, echocardiography, blood pressure and renal function help to detect complications early in systemic sclerosis.
Describe the investigations to be undertken for systemic sclerosis
Blood tests
- FBC
- U&E (renal function)
- LFTs
- Bone group
- Urinalysis
- Sereological tests - ANA (+ve in 70%), Scl70 (+ve in 30% of patientd with dsSScl), Anti-centromere antibodies (in 60% of patients with lcSScl syndrome)
Imaging
- Chext x-ray/CT chest
- ECG
- Lung function test
- Barium swallow can assess oesophageal involvement
Describe the managment of systemic sclerosis
- No agent/drug to stop or reverse fibrosis so try to slow the effects of the disease or target organs
- Joint involvement - NSAIDs, analgesia
- Raynaud’s phenomenon and digital ulcers - avoid cold, thermal gloves/socks, high core temperature, calcium channel blockers (1st line after conservative e.g., nifedipine)
- Pulmonary fibrosis/intersitial lung disease - prednisolone, with or without cyclophosphamide
- Pulmonary hypertension - anti-coagulation vasodilators e.g., bosentan or heart-lung transplant
- GI complications - Proton pump inhibitor
- Renal crisis - antihypertensive (given immediately) e.g., ACE inhbititors, calcium-channel blockers such as, captopril
- Cardiac problems/hypertension - Diuretics and ACE inhibitors
Discuss the antibodies associated with systemic sclereosis
- ANA is +ve in 70%
- Diffuse cutaneous systemic sclerosis = Scl70 antibodies (+ve in 30% patients with dcSScl)
- Limited cutaneous systemic sclerosis = Anti-centromere antibodies (+ve in 60% of patients with lcSScl)
a) What is mixed connective tissue disease
b) What antibodies do most patients with mxied connective tissue disease have?
c) How is it generally managemed?
a) A condition in which some clinical features of systemic sclerosis, myositis and SLE all occur in the same patient
b) anti-RNP antibodies
c) Managment focuses on treating the components of the disease
What is Sjörgen’s syndrome?
- A chronic autoimmune disease, characterized by inflammation of exocrine glands.
- This causes lymphocytic infiltration and fibrosis of salivary and lacrimal glands
- Sjörgen’s syndrome can be primary or secondary.
Name diseases associated with secondary Sjörgen syndrome
- RhA
- SLE
- Systemic sclerosis
- Polymyotosis
- Primarly biliary cirrhosis
- Chronic active hepatitis
Describe the epidemiology of Sjörgen syndrome
- Typical age of onset is between 40 and 50
- More common in females- F:M = 9:1
- May occur with other autommune diseases (secondary Sjogren’s syndrome)
Describe the clinical features of Sjörgen’s syndrome
- Systemic fetures: fatigue, weight loss and fever
- Dry or gritty eyes with conjuctivits and blepharitis and damage to cornea
- Xerostomia (dry mouth) - difficulties swalling dry foo,talking for long periods of time and associated with dental caries (tooth decay)
- Small joint pain
- Circulation - Raynaud’s phenomenon
- Respiratory - interstitial lung disease (rare0
- Renal - Interstitial nephritis (rare)
- Neurological- peripheral neuropathies, cranial neuropathies, hemiparesis, seizures and movement disorders
- Malignancy - 40x increases lifetime risk of lymphoma (typically presents with painless parotid swelling and lymphodenopathy. Most commonly histology shows mucosa-associated lymphoid tissue (MALT) low grade B-cellnon hodgekin lymphoma)
Describe the investigations undertaken for Sjörgen syndrome
Blood tests
- FBC
- U&E
- ESR - usually elevate
- Rheuamtoid factor (non-specific, howevere it is higher in Sjörgen syndrome than RhA)
- Antinuclear antibody (ANA) may be +ve
- Sjörgen syndrome type A (SS-A) - anti-Ro antibody may be +ve
- Sjörgen syndrome type B (SS-B) - anti-La antibody may be +ve
- Schirmer’s test (6mm + 5 after mins) - to measure dry eyes
Discuss the Schirmer’s test
- To measure dry eyes : non-specifc but gives a feel whether someone has dry eyes. It can be used in combination with other investigations to investigate for Sjörgen syndrome
- Small blotting paper put into eyes and left there for 5 minutes - tear production is expected
- Wetting he paper by less than 5 minutes suggests reduced tear secretion
Describe the investigation undertaken for polymyalgia rheumatica and giant cell arteritis and the findings
PMR
- ESR/CRP - typically raised in both
GCA
- ESR - 1st line investigation
- Temporal artery biopsy - diagnostic test + multiple biopsies should be taken as skip lesions could occur
- Ultrasound of temporal arteries - ‘affected temporal arteries show a ‘halo’ sign
- PET scan
Compare polymyositis and polymyalgia rheumatica
Describe the role of the reconstructive ladder inwound healing and also the components of the ladder
- The reconstructive ladder is a systemic approach to close a wound, restore function, and restore form
- It starts with tthe simplest methods and culminating in the most complex methods
