Connective Tissue Diseases

Question 1

What are 4 key connective tissue diseases?

Answer 1

Lupus
Scleroderma
Sjogren’s
Polymyositis

Question 2

What are the three key symptoms of connective tissue disease?

Answer 2

Arthralgia
Myalgia
Fatigue

Question 3

What are the key history taking points for lupus? (11)

Answer 3

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)

Question 4

What is Lupus?

Answer 4

Autoimmune disease
Multi-system

Question 5

What is the pathology of systemic lupus erythematosus?

Answer 5

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.

Question 6

What are the risk factors for Systemic Lupus Erythematous?

Answer 6

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

Question 7

Complications of systemic lupus erythematosus?

Answer 7

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)

Question 8

Signs and symptoms of SLE?

Answer 8

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

Question 9

What is the treatment for SLE - medications?

Answer 9

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

Question 10

What is non-pharmacological treatment of SLE?

Answer 10

Avoid sun exposure
Physical exercise
Balanced diet
Smoking cessation
Immunisations

Question 11

What is CREST syndrome for scleroderma?

Answer 11

Calcinosis
Raynaud’s
Esophageal dysmotility/hypersensitivity
Sclerodactily
Telangiectasia

Question 12

What is the pathology of scleroderma?

Answer 12

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)

Question 13

What are the risk factors for scleroderma?

Answer 13

Moore common in women
30-50 (average age of onset)
Genetic factors
Environmental factors (viruses, toxins, drugs)

Question 14

What are the complications of scleroderma?

Answer 14

Excessive skin fibrosis - painful ulcers, disfigurement, disability
Severe internal organ involvement - renal, cardia failure, pulmonary insufficiency, intestinal malabsorption

Question 15

what are the signs/symptoms of scleroderma?

Answer 15

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)

Question 16

What are the lab results for scleroderma?

Answer 16

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

Question 17

What is the treatment for scleroderma?

Answer 17

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

Question 18

What are the non-pharmacological diagnostics for scleroderma?

Answer 18

Skin thickening
Swollen fingers
Raynauds
GI reflux
Pulmonary function tests - restrictive ventilator. Defect due to pulmonary interstitial fibrosis

Question 19

What is the pathology of sjogren’s disease?

Answer 19

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.

Question 20

What are the causes of sjogren’s?

Answer 20

Primary - sicca syndrome
Secondary - most commonly RA

Question 21

What are the complications of sjogren’s?

Answer 21

Periodontal complications
Oral infections
Mucosal associated lymphoid issue (MALT) lymphoma
Salivary gland enlargement (parotid, submandibular)
Extra-glandular manifestations - MSK symptoms, rashes, interstitial nephritis, vasculitis

Question 22

What is the diagnostic imaging for Sjogren’s ?

Answer 22

Parotid gland MRI - honeycomb pattern
Salivary gland ultrasound - multiple hypoechoic areas

Question 23

What are the lab results for sjogren’s

Answer 23

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)

Question 24

What are the serologic tests for sjogren’s?

Answer 24

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%

Question 25

What is the Schirmer test?

Answer 25

Measures reflex tear production
Wetting of test paper <5mm indicative of tear deficiency
Symptom of sjogren’s

Question 26

What is the treatment for sjogren’s ?

Answer 26

Mild - secretagogues, local treatment for ocular, oral dryness
Moderate to severe - immunosuppressive treatment

Question 27

What is Levedo reticularis?

Answer 27

Fish net rash seen in lupus

Question 28

What kind of rash is common in polymyositis ?

Answer 28

Helitropic rash

Question 29

What is xerostomia?

Answer 29

Dry mouth
Common in sjogren’s
Increase risk of infection as no disinfecting effect of tears - can lead to blindness due to corneal damage.

Question 30

What is seen on an x-ray of scleroderma?

Answer 30

Calcium deposition (white dots) = calcinosis

Question 31

What is Raynaud’s phenomenon?

Answer 31

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.

Question 32

what are the the key symptoms of Raynaud’s phenomenon?

Answer 32

Pain
Numbness
Pins and needles

Question 33

What is the management for Raynaud’s phenomenon?

Answer 33

Keep warm
Stop smoking
Calcium channel blockers
antihypertensives - Iloprost, Sildenafil

Question 34

What is the difference between Raynaud’s phenomenon and syndrome?

Answer 34

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.

Question 35

What is the presentation of raynauds?

Answer 35

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.

Question 36

What are the investigations for Raynaud’s phenomenon/ syndrome?

Answer 36

Nailfold capillary microscopy to examine capillaries.
Normal = phenomenon
Damaged = syndrome

Question 37

What is the management for raynauds?

Answer 37

Medications: vasodilator - calcium channel blockers
Surgery: if severe, surgery to cut sympathetic nerve fibres supplying affected areas.

Question 38

What are the possible complications of raynauds?

Answer 38

Ulcerations
Infarction
Tissue necrosis
Gangrene if severe

Question 39

What is the pathology of raynauds (phenomenon and syndrome) ?

Answer 39

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.

Question 40

What is the presentation of sjogren’s?

Answer 40

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.