Connective Tissue Diseases Flashcards
What are 4 key connective tissue diseases?
Lupus
Scleroderma
Sjogren’s
Polymyositis
What are the three key symptoms of connective tissue disease?
Arthralgia
Myalgia
Fatigue
What are the key history taking points for lupus? (11)
Maler rash (butterfly)
Discoid rash (scaly, coin shaped)
Serositis - inflammation of cavities
Oral ulcers
Arthralgia
Photosensitivity
Bloods - decreased lymphocytes
Renal
ANA positive
Immunology - decreased complements,
Neurology - headaches, seizures etc
(MD soap brain)
What is Lupus?
Autoimmune disease
Multi-system
What is the pathology of systemic lupus erythematosus?
Environmental triggers damage DNA - causes apoptosis - causes release of nuclear bodies.
Clearance of apoptotic bodies ineffective due to genetic defects - so increased amount of nuclear antigens in bloodstream - initiates immune response - production of antinuclear antibodies - binds to antigens, forms immune complexes.
Complexes deposit in tissues (e.g. kidneys, skin, joints, heart) - type III hypersensitivity reaction
Individual may develop antibodies targeting molecules (e.g. phospholipids) of red, white blood cells - marking them for phagocytosis - type II hypersensitivity reaction.
What are the risk factors for Systemic Lupus Erythematous?
Genetic defects associated with SLE
UV radiation
Smoking
Viral, bacterial infections
Medications (e.g. procainamide, hydralazine, isoniazid, estrogens)
More common in female individuals, of reproductive age
Complications of systemic lupus erythematosus?
Cardiovascular disease - Libyan-Sacks endocarditis, myocardial infarction (MI)
Serious infections
Renal failure
Hypertension
Antiphospholipid syndrome - hypercoagulable state; individuals prone to develop clots(DVT, hepatic vein thrombosis)
Signs and symptoms of SLE?
Fever
Joint pain
rash in sun-exposed areas - malar, discoid rash
Photosensitivity
Weight loss
Ulcers (oral/nasal)
Serositis (e.g. pleuritis/pericarditis)
Libyan-Sacks endocarditis - formation of non bacterial vegetation on ventricular, atrial valve surfaces; mitral; aortic valves
Myocarditis
Renal disorders
Neurological disorders
Haematological disorders - anaemia, thrombocytopenia, leukopenia
What is the treatment for SLE - medications?
Long term therapy - anti malaria agents (hydroxychloroquine)
Mild to moderate manifestations - NSAIDs, low dose corticosteroids
Severe/life-threatening manifestations - high dose corticosteroids, intensive immunosuppressive drugs
What is non-pharmacological treatment of SLE?
Avoid sun exposure
Physical exercise
Balanced diet
Smoking cessation
Immunisations
What is CREST syndrome for scleroderma?
Calcinosis
Raynaud’s
Esophageal dysmotility/hypersensitivity
Sclerodactily
Telangiectasia
What is the pathology of scleroderma?
AKA systemic sclerosis
Chronic inflammatory autoimmune disease, result in widespread damage to small blood vessels, excessive fibrosis
T helper cells activated by unknown antigen - release cytokines- stimulates inflammatory cells, fibroblasts, chronic inflammation, excessive collagen deposition
Mediators released by inflammatory cells - damage micro vascular use - ischaemic injuries, scarring
Primarily affect skin, can involve visceral organs (GI tract, kidneys, heart, muscles, lungs)
What are the risk factors for scleroderma?
Moore common in women
30-50 (average age of onset)
Genetic factors
Environmental factors (viruses, toxins, drugs)
What are the complications of scleroderma?
Excessive skin fibrosis - painful ulcers, disfigurement, disability
Severe internal organ involvement - renal, cardia failure, pulmonary insufficiency, intestinal malabsorption
what are the signs/symptoms of scleroderma?
Raynaud phenomenon
Cutaneous changes of face, extremities - skin thickening, tightening, sclerosis, deems, erythema
GI involvement - esophageal fibrosis (dysphasia, GI reflux), small intestine involvement (abdominal pain., obstructions, constipation, diarrhoea, malabsorption syndrome
Pulmonary with intestinal fibrosis - right-sided cardia dysfunction/pulmonary hypertension
Cardiac involvement - pericardial effusions, myocardial fibrosis - congestive heart failure, arrhythmias
Renal - fatal hypertensive crisis (rare)
What are the lab results for scleroderma?
Serum blood tests:
Increased ANAs - antinuclear antibodies (sensitive for systemic sclerosis, low specificity)
Increased ACAs -anti centromere antibodies (highly specific (limited systemic sclerosis) - confirm diagnosis)
Anti-topoisomerase I antibodies (anti-Scl-70) highly specific (diffuse)
Complete blood count - anaemia due to malabsorption, increased serum creatinine due to renal dysfunction
What is the treatment for scleroderma?
Meds are usually symptomatic - analgesics for msk pain
PPIs for gastroesophageal reflux
Calcium channel blockers for raynauds
Angiotensin converting enzyme (ACE) for renal hypertensive crisis
Immunosuppressive therapy initiation - diffuse skin/severe internal organ involvement
What are the non-pharmacological diagnostics for scleroderma?
Skin thickening
Swollen fingers
Raynauds
GI reflux
Pulmonary function tests - restrictive ventilator. Defect due to pulmonary interstitial fibrosis
What is the pathology of sjogren’s disease?
Chronic autoimmune inflammatory disease; lymphocytic infiltration, destruction of exocrine glands of eyes, mouth.
Proposed mechanisms:
- immune reactions against antigens of viral infection of exocrine glands
- autoimmmune T cell reaction against unknown self antigen expressed in salivary, lacrimal glands.
What are the causes of sjogren’s?
Primary - sicca syndrome
Secondary - most commonly RA
What are the complications of sjogren’s?
Periodontal complications
Oral infections
Mucosal associated lymphoid issue (MALT) lymphoma
Salivary gland enlargement (parotid, submandibular)
Extra-glandular manifestations - MSK symptoms, rashes, interstitial nephritis, vasculitis
What is the diagnostic imaging for Sjogren’s ?
Parotid gland MRI - honeycomb pattern
Salivary gland ultrasound - multiple hypoechoic areas
What are the lab results for sjogren’s
Complete blood count - leukopenia, thrombocytopenia, anaemia
Elevated ESR
Urinalysis - proteinuria, hematuria - reflecting glomerulonephritis
Labial salivary gland biopsy - focal lymphocyte foci (collections of tightly aggregated lymphocytes)
What are the serologic tests for sjogren’s?
Raised ANAs (antinuclear antibodies in 95%)
RF factor in 50-75% of pts with/without RA
Anti-sjogren’s syndrome A (SSA) (Ro)- in 55%
Anti-sjogren’s syndrome B (SSB) (La) - in 40%
What is the Schirmer test?
Measures reflex tear production
Wetting of test paper <5mm indicative of tear deficiency
Symptom of sjogren’s
What is the treatment for sjogren’s ?
Mild - secretagogues, local treatment for ocular, oral dryness
Moderate to severe - immunosuppressive treatment
What is Levedo reticularis?
Fish net rash seen in lupus
What kind of rash is common in polymyositis ?
Helitropic rash
What is xerostomia?
Dry mouth
Common in sjogren’s
Increase risk of infection as no disinfecting effect of tears - can lead to blindness due to corneal damage.
What is seen on an x-ray of scleroderma?
Calcium deposition (white dots) = calcinosis
What is Raynaud’s phenomenon?
Triggered by cold temperatures, anxiety or stress.
Temporary spasm of blood vessels which blocks the flow of blood.
Triphasic colour change - white, blue, red (paler is dark skin).
Affects fingers, toes, ears, nose, lips or nipples.
what are the the key symptoms of Raynaud’s phenomenon?
Pain
Numbness
Pins and needles
What is the management for Raynaud’s phenomenon?
Keep warm
Stop smoking
Calcium channel blockers
antihypertensives - Iloprost, Sildenafil
What is the difference between Raynaud’s phenomenon and syndrome?
Phenomenon - affects hands, fingers, toes symmetrically, severity remains constant (primary raynauds). Common in pregnancy and people who work in jobs involving vibration.
Syndrome - asymmetrical, progressive severity. (Secondary raynauds). Caused by connective tissue disorders (SLE, scleroderma). Caused by disorders affecting blood vessels - Buerger’s disease, Takayasu’s arteries, thromboangitis obliterans.
What is the presentation of raynauds?
Vasospasm - changes in skin colour of hands, finger, toes etc. White = ischaemia, blue=hypoxia, red = reactive hyperaemia (oxygenated blood rushes into tissue).
Swelling, numbness, tingling, pain.
What are the investigations for Raynaud’s phenomenon/ syndrome?
Nailfold capillary microscopy to examine capillaries.
Normal = phenomenon
Damaged = syndrome
What is the management for raynauds?
Medications: vasodilator - calcium channel blockers
Surgery: if severe, surgery to cut sympathetic nerve fibres supplying affected areas.
What are the possible complications of raynauds?
Ulcerations
Infarction
Tissue necrosis
Gangrene if severe
What is the pathology of raynauds (phenomenon and syndrome) ?
Vasospasm of skin arteries in response to triggers resulting in kin colour transitions.
Exposure to trigger leads to stimulation of sympathetic nerves in arteriolar walls eating to vasospasm of arterioles which decreases blood flow.
What is the presentation of sjogren’s?
Dry eyes - irritation, itching, foreign body sensation, keratoconjunctivitis.
Oral dryness reflecting salivary hypofunction.
Salivary gland enlargement.
Extra glandular manifestations - arthralgia, arthritis, rashes, interstitial nephritis, vasculitis.
