Connective tissue disorder Flashcards
Inheritance pattern of Marfan syndrome
Autosomal dominant
Cause of Marfan syndrome
Mutation in fibrillin 1 gene
Presentation of Marfan syndrome
disproportionally tall and thin
unusually long arms and legs
Arachnodactyly (long fingers)
High arched palate
Pes planus
Pectus excavation
Marfan syndrome is associated with which cardiovascular conditions
Aortic regurgitation
Mitral valve prolapse
Aortic dissection
Aortic aneurysm
What is pectus excavation
When the ribs and sternum grows inward causing a caved-in chest appearance
What are the ocular conditions associated with Marfan’s syndrome
Superotemporal lens dislocation
Blue sclera
Myopia
MSK manifestations of Marfan syndrome
Hypermobility of joints
Protusio acetabuli
Pectus excavatum
Kyphoscoliosis
What is protusio acetabuli
medial displacement of the femoral head into the pelvis
What is kyphoscoliosis
deviation of the normal curvature of the spine in the sagittal (right left) and coronal (front back) planes
What sign is seen in Marfan syndrome
Wrist sign
Thumb sign
What is the wrist sign
asking the patient to grip his wrist with his opposite hand
If the thumb and fifth finger of the hand overlap with each other, the sign is positive
What is the thumb sign
distal phalanx of the adducted thumb extends beyond the ulnar border of the palm
Management of Marfan syndrome
Hypertension management
Surgery for aortic diseases
What drug is avoided in Marfan syndrome due to risk of aortic aneurysm / dissection
fluoquinolone
Risk factors of systemic lupus erythematosus (SLE)
Women
20-40 years old
Afro-Caribbean, Hispanic American, Asian, and Chinese ethnicity
Genetics
What genes are associated with SLE
HLA B8
HLA DR2
HLA DR3
SLE is an autoimmune disease. What type of hypersensitivity is SLE
Type 3
Since SLE is a type 3 hypersensitivity condition, how does it cause symptoms
Immune complex formation
Immune complex deposits at joints / skin / kidneys / nervous system causing inflammatory response
Pathophysiology of SLE
- Loss of immune regulation leading to increase in cell apoptosis
- Necrotic cells release nuclear antigens which act as auto-antigens
- B and T cells activated to produce auto-antibodies
- Form immune complexes with the auto-antigens
- The immune complexes deposit in various sites and trigger inflammation cascade when neutrophils or other antigen-presenting cells come into contact
Symptoms of SLE
Systemic upset - fever / malaise/ weight loss
Cutaneous involvement
MSK involvement
Other organ involvement
What are the cutaneous involvements in SLE
Photosensitive malar rash
Oral / nasal ulcers
Alopecia
Discoid rash
Raynauds phenomenon
Where does the photosensitive malar rash in SLE usually present on
butterfly shaped rash across both cheek
SPARING nasolabial folds
What are the variants of SLE
Subacute cutaneous lupus
Discoid lupus erythematosus
Presentation of subacute cutaneous lupus
Small erythematous lesions on neck, shoulder, chest, forearms
Spares the face
Presentation of discoid lupus erythematosus
Only discoid rash seen
What is discoid rash
scaly, erythematous, well demarcated rash in sun-exposed areas
What are the MSK involvement in SLE
Non erosive arthritis
Arthralgia
Myalgia
Jaccoud’s arthropathy
What kind of arthritis is seen in SLE
Morning stiffness > 30 minutes
At least 2 joints involved
Joint function not affected
Non-erosive
Differences between the arthritis seen in RA and SLE
Arthritis in SLE does not affect joint function whereas RA does
What is Jaccouds arthropathy
Non-erosive arthropathy causing deformity characterized by ulnar deviation of the 2nd to 5th fingers
Similar to deformities in RA but different
Difference between Jaccouds arthropathy and RA
Jaccouds is correctable by physical manipulation whereas RA isn’t
Jaccouds does not cause functional impairment whereas RA does
What are the other organ involvement in SLE
Renal
- nephritis
Heart
- pericarditis
- myocarditis
Lungs
- Pneumonitis
- Pleurisy
Neurological
- seizures, headaches, psychosis
Which heart condition is the most common cardiac manifestation in SLE
Pericarditis
What are the haemotological signs of SLE
Leucopenia
Haemolytic anemia
thrombocytopenia
Lymphadenopathy
What is the most common cause of lupus-related death
Nephritis
SLE follows a relapsing-remitting course. What can trigger acute flares of SLE symptoms
Oestrogen therapies
Overexposure to sunlight.
Infections
Stress
What infection can trigger SLE flare
Epstein-Barre
Investigations for SLE
Autoantibodies
Blood test
Urine dip stick test
Renal biopsy
Imaging / screen for other organ involvements
Which autoantibody is present in most patients with SLE but also present in other conditions
anti-ANA
rheumatoid factor
If Anti-ANA positive in a patient with suspected SLE, what should you do
Test for more autoantibodies that are more specific to SLE
Further investigations - bloods, urinalysis, imaging
Which autoantibodies are specific to SLE
Anti-dsDNA
Anti-Smith
Antiphospholipid antibodies (APLS)
Anti-Ro
Anti-dsDNA and Anti-Smith are high specific but
Low sensitivity
Because even though everyone who has it has SLE, not all SLE patients will have it
Which autoantibody correlates to SLE disease activity and lupus nephritis
anti-dsDNA
The higher the tire, the higher the disease activity and the worse lupus nephritis is
What may be the blood test results for SLE
Leucopenia
Haemolytic anaemia
Low complement level - due to high use of complement system
What may be the urine test result for SLE
proteinuria
When is renal biopsy used in SLE
Positive urinalysis suggesting lupus nephritis
Use biopsy to confirm
General lifestyle management for SLE
Sun protection
Minimize steroid use
Monitor disease activity using SLEDAI score
Avoid triggers - oestrogen / stress / overexposure to sunlight
Drug management for mild SLE
- Hydroxychloroquine
- Short course of NSAIDs for symptomatic control
- Intra-articular steroids for arthritis
- Topical steroid for cutaneous involvement
Drug management for moderate SLE (organ involvement without nephritis / CNS)
Hydroxychloroquine
Oral steroids or immunosuppressants during flares
Treat organ flares appropriately
What immunosuppressants are used to treat flares of moderate SLE
Azathioprine
Methotrexate
What oral steroid is used to treat flares of moderate SLE
Prednisolone
Drug management for severe lupus (nephritis or CNS involved)
IV steroids
IV cyclophosphamide
What are the side effects of long term steroids use
Osteoporosis
Cushing’s
Proximal myopathy
Avascular necrosis
Immunosuppression
Weight gain
What is drug induced lupus
Milder form of SLE triggered by chronic use of certain drugs
Symptoms should resolve after stopping the drug
Presentation of drug induced lupus
Systemic upset - fever / fatigue
Nonerosive arthritis
Arthralgia
Pleurisy
Pericarditis
Differences between drug induced lupus and SLE
Drug induced lupus does not usually present with malar rash or nephritis
Drug induced lupus occurs in females and males equally whereas SLE mostly occurs in females
Drug induced lupus does not have SLE specific autoantibodies
Causes of drug induced lupus (SHIPP)
Sulfasalazine
Hydralazine
Isoniazid
Procainamide
Penicillamine
Investigations for drug induced lupus
Autoantibodies
Bloods
Difference in autoantibodies present in drug induced lupus vs SLE
DIL may be anti-ANA positive as well but it will not have SLE specific autoantibodies (anti-smith / anti-dsDNA)
DIL may be anti-histone positive
Which auto-antibody is specific for DIL
anti-histone
What is sjogren’s syndrome
Inflammatory autoimmune disorder characterised by decrease lacrimal and salivary secretion
Cause of sjogren’s syndrome
Lymphocyte-mediated autoimmune destruction of exocrine glands
Which type of hypersensitivity is Sjogren’s syndrome part of
Type 4
Risk factors for Sjogren’s
Female
Middle age
Autoimmune conditions (causes secondary Sjogren’s)
Which conditions are associated with secondary Sjogren’s
SLE
RA
Systemic sclerosis
Autoimmune thyroiditis
Autoimmune hepatitis
Primary biliary cirrhosis
Signs of Sjogren’s syndrome
Dry, red eyes
Dry mouth
Vaginal dryness
Dry throat
Non-erosive symmetrical polyarthritis
Raynaud’s
Cutaneous vasculitis
Fatigue, fever
Dry eyes can lead to
bacterial conjunctivitis (tears are supposed to wash away bacteria so dry eyes increases risk of infection)
Dry mouth can lead to
Dental caries
Oral candidiasis
Dry throat can lead to
Dysphagia
Oesophagitis
Sjogren’s classic signs
dry mouth and eyes
Presentation of cutaneous vasculitis in Sjogren’s
skin ulcers
purpura - red or purple non blanching spots on skin
Investigations for Sjogren’s
Autoantibodies
Blood
Schimers test
Salivary flow rate
Salivary gland biopsy
What is Schimer’s test
Use strip of filter paper on lower eyelid
wetting <5mm = positive (reduced tear)
Autoantibodies present in Sjogren’s
anti- ANA (non-specific)
Rheumatoid factor (non-sepcific)
anti-Ro (non-specific)
anti-LA (specific but not sensitive)
Management of Sjogren’s
Artificial tears (hypromellose)
Artificial saliva
Topical lubrication for vaginal dryness
Hydroxychloroquine for arthritis
Why should patients with Sjogren’s be investigated promptly if they develop a lymphadenopathy
Because Sjogren’s increases risk of B cell lymphoma in glands and organs
Complications of Sjogren’s
Interstitial lung disease
Renal disease
Seizures
Lymphoma
What is used if interstitial lung disease / renal disease develop in a patient with Sjogren’s
Immunosuppressants
Risk factors for systemic sclerosis
Females
30-50 years old
Genetic predisposition
Environmental triggers
What is systemic sclerosis
Autoimmune disease causing fibrosis in skin and organ
Types of systemic sclerosis
Limited cutaneous systemic sclerosis
Diffuse cutaneous systemic sclerosis
What is limited cutaneous systemic sclerosis
Skin fibrosis only occur in face, hands, feet, forearms and organ involvement occurs later on
Characteristics of limited systemic sclerosis (S CREST)
Skin fibrosis
Calcinosis
Raynaud’s phenomenon
oEsophageal dysmotility - dysphagia / gord
Sclerodactyly
Telangiectasia
What is sclerodactyly
Bright shiny skin of hands and feet (due to build up of fibrous tissue)
With reduced mobility and function
What sign cannot be done by patients with sclerodactyly
Prayer sign due to reduced mobility
What is calcinosis
Calcium deposits under the skin / muscles
Skin fibrosis of limited cutaneous sclerosis only occurs on
Hands
Forearns
Feet
Face
What symptom usually occurs before any others in limited systemic sclerosis
Raynaud’s
Investigation for limited cutaneous systemic sclerosis
Autoantibodies
Which autoantibody is specific to limited cutaneous systemic sclerosis
Anti-centromere antibodies
Characteristics of diffuse cutaneous systemic sclerosis
Vasculopathy
Fibrosis of widespread areas of skin and internal organs
Presentation of skin fibrosis in systemic sclerosis
Lack of wrinkles
Hypo/hyperpigmented / shiny
Flexion contractures (cannot be fully straightened or extended)
Microstomia
Puckered lips
Telangiectasia
What is microstomia
Restricted mouth opening
Describe the progression of diffuse systemic sclerosis
Faster than limited systemic sclerosis
1. Joint contractures
2. Skeletal myopathy
3. Interstitial lung disease
4. Myocardial involvement
5. Renal crisis
What does raynaud cause and why
Ischaemic digital ulcers because of vascular spasms during triggers, reducing blood supply to fingers.
Autoantibodies present in diffuse systemic sclerosis
Anti-SCL-70
Anti-RNA-polymerase III
Differences between diffuse and limited systemic sclerosis
Limited only affects face, hand, feet, forearms whereas diffuse affects everywhere
Limited has later organ involvement whereas diffuse has early organ involvement
Limited has anti-centromere antibodies whereas diffuse has anti-scl-50 and anti-RNA polymerase III
What are the cardiovascular features in systemic sclerosis
Pericarditis
Myocarditis
Myocardial fibrosis -> HF and arrhythmias
RVF (due to pulmonary hypertension)
What are the pulmonary features in systemic sclerosis
Pulmonary hypertension
Interstitial lung disease
What can be heard on auscultation in patient with interstitial lung disease
Bilateral fine inspiratory crackles
What are the renal features in systemic sclerosis
Renal dysfunction due to vasculopathy and fibrosis
Scleroderma renal crisis
What is scleroderma renal crisis
Uncontrolled hypertension + proteinuria + rapidly worsening renal function
Management of systemic sclerosis
Monitor regularly
Smoking cessation
Avoid triggers for Raynaud’s
Specific to issues
What should be monitored regularly in patients with systemic sclerosis
Blood pressure
Renal function
Echo
Spirometry
What can be used to treat Raynaud’s
Nifedipine (CCB)
Which vaccines should not be given to immunosuppressed patients
Yellow fever
MMR
Smallpox
Rotavirus
