Autoimmune and CTD Flashcards
Name two genetic CTD
- Marfans Syndrome - autosomal dominant, faulty collagen that leads to many skeletal changes, Signs = tall, long fingers and toes, chest deformities
- Ehlers Danlos Syndrome = skin hyperelastiicty
Name 5 Autoimmune CTD
- SLE
- Systemic Sclerosis
- Sjögren’s Syndrome (SjS)
- Dermatomyositis/ Polymyositis
- Mixed CTD
Describe pathophysiology of Autoimmune CTD
- Inflammation leading organs scarring +/- failure
- Early systemic involvement may not give rise to any Sx
- Any systems can be affected: commonly skin, joints, kidney, lungs, blood cells and nervous systems
- Although there is no cure and damage is irreversible, inflammation can be treated with immunosuppressive drugs.
What is Raynaud’s Phenomenon?
- Peripheral digital ischaemia.
- Finger or toes change colour from PALE (ischaemia, lack of blood flow) –> BLUE (lack of oxygen) –> RED (blood flow returns)
- It can lead to tissue necrosis.
Primary and Secondary causes of Raynaud’s Phenomenon
- Primary (aka Raynaud’s disease)
- Idiopathic
- Younger age, no underlying disease - Secondary
- CTD (SLE, Scleroderma, derma-polymyositis, RA, primary SjS)
- Drugs = Beta-blockers (slows HR, lower BP)
- Vascular damage: atherosclerosis, frost bite, DIY vibrating tools
Management of Raynaud’s Phenomenon
- Smoking cessation
- Avoid exposure to cold
- Change occupation/DIY habit
- Topical glyceryl trinitrate (vasodilator)
- CCB
What is Mixed CTD and how may they present?
Combined features of systemic sclerosis, SLE, polymyositis
Presentation
- Raynaud’s Phenomenon
- arthralgias, swollen joints
- Dysphagia: oesophageal dysfunction
- muscle weakness
- dactylitis
Pathophysiology of SLE
- SLE is an antigen driven immune mediated disease characterised by activation of autoreactive T and B-cells resulting in production of pathogenic autoantibodies and tissue insult.
- Antigen-antibody complexes are formed and circulate the body until it is able to deposit or stick onto vessels or organs.
- Deposited complexes then initiate inflammatory and complement systems which causes cell damage and death (type 3 hypersensitivity).
- Some SLE individuals develop antibodies against RBC, WBC, platelets causing pancytopenia. This is a Type 2 hypersensitivity reaction.
How are SLE Sx non-specific
Presentation can vary greatly between patients.
- Sx can present suddenly or gradually over time.
- Sx can be general = Joint pain, Rash, Fever, Weight loss
- Sx can be specific depending on organ/tissue damaged
Diagnosis criteria of SLE
Dx: must meet 4 of the 11 key Sx and lab findings
SOAP BRAIN MD
S = Serositis, Pleuritis, Pericarditis, Peritonitis O = oral ulcers A = arthritis P = Photosensitivity B = blood: anaemia, thrombocytopenia, leukopenia R = Renal damage A = +ANA I = Immunological: anti-dsDNA, anti-smith, anti-phospholipid N = Neurological: seizures, peripheral neuropathy M = alar rash D = discoid rash
Investigation of SLE
Serology
- ANA
- Anti-dsDNA, Anti-smith, Anti-phospholipids
- Complements: Dec in C3, C4
Management of SLE - conservative, maintenance, flare-ups
Conservative
(1.) UV protection: Avoid sunlight, cover up, high factor sunblock
Maintenance
(1. ) NSAIDs for joint and muscle pains, headaches
(2. ) Immunosuppressants depending on severity and systems affected, consider:
- Corticosteroids
- Hydroxychloroquine
- Azathioprine
- methotrexate
- Belimumab (add on therapy for autoantibody +ve disease where high activity)
Flare-up Mx
- Hydroxychloroquine or low dose steroids for MILD flares (topical for skin)
- DMARDs or mycophenolate for MODERATE flares (organ involvement)
What is Sjorgen’s syndrome? RF? Aetiology? Triggers?
(1. ) AI: immune cells attack exocrine/secretary glands including: saliva, tears, vaginal.
(2. ) As a result, glands do not function leading to dry eyes, mouth, GI tract - leading to irritation of eyes, difficulty swallowing, difficulties having sex.
(3. ) Usually develop as a complication of other autoimmune diseases such as lupus or RA
RF = female of child bearing age, Africa/Asian ethnicity in Europe, Fx of SLE, smoking, sun exposure
Aetiology
- unknown
- genetic (HLA genes) and environmental factors (exocrine gland infection) have a role
Triggers = UV light, Oestrogen, Medication - isoniazid, hydralazine, procainamide, quinidine, etc (Drug-induced Lupus), Smoking, Bacteria, viral infections
Pathophysiology of Sjs
(1. ) In Sjogren’s, ANAs are raised these are anti-SSA & anti-SSB.
(2. ) Antibodies and T-cells enter circulation and reach glands, where cytokines release and inflammation occurs.
(3. ) Cytokines activate fibroblasts in tissue, which produce fibrous tissue that replaces damaged tissue.
(4. ) The end result is a loss secretory cells in the glands.
(5. ) Primary Sjs, occurs alone = sicca syndrome.
- Secondary Sjs occurs with other AI conditions such as RA, SLE, Scleroderma, Primary biliary cirrhosis
Sx of SjS
Dryness of various systems, the following may be present;
(1. ) Keratoconjunctivitis: redness and itching of eye
(2. ) Xerostomia: complain of swallowing difficulty
(3. ) Ulceration, perforation of nasal septum
(4. ) Difficulty speaking
(5. ) Enlargement glands e.g. parotid can cause pinching of nerves
(6. ) Infection is more common due to dryness of epithelium
(7. ) Dryness of skin and vagina
Other Clinical features
- Arthritis
- Rash
- Neurological features
- Vasculitis
- Inc risk of lymphoma
Ix of Sjs (5).
(1. ) Bloods
- FBC, WBC, U&E
- +ve RF in 38%
- +ve ANA in 75%
- +ve Anti-SSA/RO, anti-SS-B/LA*
- -ve dsDNA
- Raised immunoglobulin
(2. ) Schirmer’s test
- Measure conjunctival dryness
(3. ) Sialometry
- measure saliva flow.
(4. ) Biopsy
- shows lymphocytic infiltrate and thickening of the inner duct wall.
- Sialadenitis
(5. ) US
- Abnormal salivary glands
Tx of Sjs
(1. ) Tears and Saliva replacement
- Hypromellose (eyedrops)
- Frequent drinks, sugar free pastilles/gums
(2. ) For organ-threatening extra glandular disease
- Corticosteroids
- Pilocarpine: increase the exocrine secretions.
- Biological therapies
What is Systemic Sclerosis/Scleroderma? RF? Aetiology?
(1. ) Rare multisystem autoimmune condition that causes damage to: internal organs, function + structure of blood vessels, fibrosis of skin
(2. ) There are two types = limited and diffuse cutaneous sclerderma. Limited type is also known as Crest Syndrome.
(2. ) RF = women, Fx, infections - chlamydia, EBV, parvovirus etc, chemicals - pesticides, hair dye, immune dysregulation
(3. ) Cause is unknown, thought to be a combination of genetic and triggers (virus, dust exposure, medication)
Pathophysiology of SS
(1. ) Vessels start expressing adhesion molecules, that causes T-cell to attach.
(2. ) T-cells release cytokines which causes inflammation and fibrosis of vessels
(3. ) Vessels become stiff and causes reduced blood flow leading to ischemic tissue damage
(4. ) B-cells also play a role, although mechanism is unknown, they produce ANA = Anti-SCL70, ARA, ACA
(5. ) Can affect any organs but organs commonly affected: Skin, lung, heart, kidney, GI tract
Clinical Features of SS (hint: remember organs that are affected)
(1. ) Skin fibrosis:
- Sclerodactyly
- Ulcerations
- Telangiectasis - red marks on face, palms, fingers
- Subcutaneous calcinosis
(2.) Raynaud’s Phenomenon
(3. ) GI
- Oesophageal dysfunction
- Gastro-oesophageal reflux
- Reduced GI motility: Malabsorption
(4. ) Lungs
- Pulmonary arterial HTN
- Pulmonary fibrosis
(5. ) Kidney failure
(6. ) Heart failure
Presentation in limited and diffuse scleroderma
Limited Scleroderma/ Crest Syndrome
- Raynaud phenomenon usually 1st sx seen, and internal organ damage comes much later.
- C = Calcinosis
- R = Raynaud phenomenon
- E = Esophageal Dysmotility
- S = Sclerodactyly
- T = Telangietasia
Diffuse Scleroderma
- Skin of face, arms, legs, trunk are effected
- Organ damage occurs earlier
Examination of SS
(1. ) Chest auscultation
- Dry crackles at lung bases
(2. ) Hand examination
- Non-pitted swelling, curling of fingers
- Reduction in ROM and power
- may be unable to grip fully and make prayer signs with hand.
- Firm hard lumps (calcinosis) may also be noted.
(3. ) Presence of Telangiectasia
(4. ) Salt and pepper skin appearance due to areas of hypopigmentation and hyperpigmentation
(5. ) Dry skin and reduced hair
(6. ) Restriction in joint ROM
(7. ) Muscle atrophy may be seen
Ix of SS
(1. ) Serology
- ANA +ve (90%)
- Anti-SCL70 - strongly associated w/lung fibrosis and renal disease
- ARA - kidney involvement
- ACA
Additional tests
(2. ) FBC
- may be normal
- microcytic anaemia (in chronic GI bleed)
- Haemolytic anaemia (in scleroderma renal crisis)
(3.) BP, upper endoscopy, pulmonary function tests
Treatment and Management of SS (4.)
(1. ) Conservative
- Physiotherapy
- Smoking cessation
- Nutritional advice
(2. ) Immunosuppressants - cyclophosphamide
- Slows down disease for Diffuse Scleroderma
(3. ) Relive Sx
- PPI = gastric-oesophageal reflux
- CCB = for Raynaud phenomenon
- NSAIDs = for pain
- ACEi = for HTN, prevention of renal crisis
- Emollients, topical steroids = for skin issues
(4. ) Monitor BP, renal function, annual ECHO and pulmonary function tests
- For early detection of pulmonary arterial HTN
What is Dermatomyositis and Polymyositis? Aetiology?
(1. ) Autoimmune mediated disease that attacks striated muscle and skin causing rash and muscle weakness
(2. ) Cause is unknown, implication of genetic (HLA DR3,5) and environmental trigger (coxsackivirus, ovarian, lung, breast tumour)
Sx of Dermatomyositis and Polymyositis (related to muscle, skin, others)
Related to muscle
- Muscle wasting, weakness, tenderness of proximal muscles
- Dysphagia
Related to skin
- Heliotrope rash (purple rash on upper eyelids)
- Malar Rash
- Gottron’s Signs (red, scaly itchy papules)
Other Sx
- Fever
- Arthralgia
- Raynaud’s phenomenon
- Interstitial lung fibrosis
- Myocardial involvement - myocaridits, arrhythmias
Investigations of Dermatomyositis and Polymyositis
Combination of skin and muscle findings (if specific to muscle this will be polymyositis)
(1. ) Autoanitbodies
- ANA
- Anti-Jo-1
- Anti-Mi-2
(2. ) Elevated muscle enzymes
- aldolase or creatine kinase.
(3. ) Abnormal electromyography
- detect regions of dead muscle cells that cause abnormal electrical signals conduction.
(4. ) Muscle biopsy [diagnostic]
- inflammation and necrosis.
(5.) Screen for malignancy PET, Chest Xray, PFTs, High resolution CT lungs
Tx of Dermatomyositis and Polymyositis (5).
- Corticosteroids
- Exercise therapy: help maintain muscle function
- Topical Hydroxychlorquine: May be used for skin rashes
- Sun avoidance
- Screen for cancers
