S3 L2 Clinicial approach to autoimmunity Flashcards
What are autoimmune rheumatic diseases (ARDs)?
Heterogenous group of diseases
Immune tolerance breakdown → self antigens and proteins, recognises own body as foreign, develops antibodies that attach to individual and cause disease
Production of pathogenic antibodies
Multisystemic features → affects more than one system
Why are autoantibodies important?
- Aid diagnosis
- Associated with specific clinical features
- Disease prognosis
- To stratify therapy - see how aggressive the disease is, guide to management +ve serology or -ve serology
What are examples of autoimmune rheumatic disease?
Rheumatoid arthritis
Systemic lupus erythematosus
Systemic sclerosis
What is the epidemiology of systemic lupus erythematosus?
F:M → 9:1
Prevalence → 24/100,000
Race → Afro-Caribbean > south asians > caucasians
Genetic factors are important - monozygotic twins (if one has it the other more likely to have it)
Environmental factors - UV light mediated (cytokine and humoral mediated factors from skin causing systemic features), Smoking
When taking a history of someone with suspected autoimmune rheumatic disease (ARD) what features would you look for and ask about?
Current symptoms - Pain - SQITARS/SOCRATES - Stiffness - whole body stiffness, worse in the mornings, eases throughout the day - suggests presence of inflammatory cytokines (different to mechanical stiffness) - Swelling - warm swelling - Pattern of joint involvement - small joints/ non weight bearing joints normally affected first (wrists, hands, ankles) Evolution - Acute or chronic? - Associated events - Response to treatment - Family history Involvement - Skin, eyes or lungs - Malaise, weight loss, fevers, night sweats Impact on patients lifestyle
What are the constitutional symptoms?
Symptoms that are systemic and affect the whole body - Fever - Fatigue - Weight loss - Night sweats - Poor appetite Cancer has to be excluded
What is the glove and sweater approach?
Systematic approach to areas to look at when trying to determine whether someone has ARD
Gloves - hands
Sweater - arms and trunk
What are you looking for when examining the glove area?
- Raynauds (hyper exaggerated response to cold, stress etc) → colour of hand? pale/yellow (vasospasms of digits) → cyanotic digits → red (return of circulation) - (triphasic pattern of raynauds)
- Joint pain and swelling
- Hand rash
What are you looking for when examining the sweater area?
- Proximal muscle weakness → myalgia (difficulty washing hair- inflammation of muscles causes more weakness than pain)
- Hair loss → bald patches, hair on pillow on waking
- Eye and mouth dryness → red eyes, difficulty looking at bright lights, uveitis
- Nose bleeds → vasculitis
- Mouth ulcers → sjogrens
- Pleuritic chest pain
- Pericardial pain
- Truncal rash/ photosensitivity
- Limb weakness - nerve involvement
What other investigations would you do for ARD?
Bloods
- FBC
- U&E and creatinine
- Liver enzymes
- C-reactive protein (lupus- CRP normal, infection raised)
- Plasma viscosity and ESR
- Autoantibodies / lupus associated bloods
What would you expect to see on examination of a patient with Lupus?
Swollen joints
Facial rash - mallor rash
Hair loss (significant loss)
Bloods- low WCC, antinuclear antibodies, anti-Smith antibodies
What is the treatment for SLE?
Patient education- life style modification, use of sunscreen (SPF= 50 at least)
Start DMARDs: Hydroxychloroquine, Azathioprine, Mycophenolate
Use of steroids: Prednisolone, methylprenisolone
In severe cases: IV cyclophopamides
What is a good mnemonic for Lupus?
A RASH POINts Medical Diagnosis A- ANA positive R- Renal abnormalities A- Arthralgia/arthritis S- Serositis H- Haematological abnormalities P- Photosensitivity O- Oral ulcers I- Immunological abnormalities N- Neurological abnormalities M- Malar rash/ D- Discoid rash 4/11 criteria = definite lupus
What is the epidemiology of rheumatoid arthritis?
F:M → 3:1
Prevalence → 1%
No race predilection
Genetic factors/ environmental factors → genetically predisposed
What are the 3 things to look out for in a history of someone with suspected Rheumatoid arthritis?
S, S, S
Stiffness → early morning joint stiffness lasting over 30 mins
Swelling → persistent swelling of one joint or more, especially hand joints
Squeezing → squeezing the joints is painful in inflammatory arthritis
What would you expect to see on examination of someone with rheumatoid arthritis?
Swelling in hands
Swelling in feet
What other investigations are carried out for rheumatoid arthritis?
Blood test - confirm diagnosis and tell you about prognosis
- Full blood count
- U&Es, and creatinine
- Liver enzymes
- CRP
- Plasma viscosity and ESR (erythrocyte sedimentary ratio)
- Autoantibodies → ANA, rheumatoid factor Ab, anti-CCP Ab, anti Ro and La antibodies
X-ray and/or ultrasounds
What is the classification criteria for RA?
Points given for joint distribution, serology, symptom duration, acute phase reactants
>/= 6 point definite RA
- More points given for joint involvement than serology results
How is RA treated?
Start DMARDs early: Methotrexate hydroxychloroquine, sulfasalazine, leflunomide
Use of steroids: prednisolone, methylprednisolone
Combination therapy is usual
What is the role of a rheumatologist?
- Prompt diagnosis of patients with suspected ARDs/ non- ARDs
- Oversee use of DMARDs in these patients
- Holistic/long term management of patient with ARDs
What is RA?
- Autoimmune disease with autoantibodies to the Fc portion of immunoglobulin G (rheumatoid factor) and citrullinated cyclic peptides
- Persistent synovitis causing chronic symmetrical polyarthritis with systemic inflammation
- Can develop non articular problems affecting all parts of the body
How does RA present?
Approx 70% cases progressive, symmetrical, peripheral polyarthritis evolving over a period of a few weeks or months in patients 30-50yrs
How do the symptoms of RA occur?
- Primarily a synovial disease and synovitis occurs when chemoattractants produced in the joint recruit circulating inflammatory cells
- Over production of tumour necrosis factor TNF- alpha leads to synovitis and joint destruction
- Interaction of macrophages and T and B lymphocytes drives this over production
- TNF alpha stimulates the over production of IL-6 as well as other cytokines
How do some of the targeted biological therapies work?
Blockade of TNF-alpha and IL-6 has produced marked improvements in synovitis and systemic malaise
Indicating the pivotal role of these cytokines in chronic synovitis
What is the D-dimer test?
Level of D-dimer can be used to assess the level of clotting
How does the D-dimer test work?
- Blood clotting (coagulation) → stop bleeding from a damaged blood vessel → maintain a constant blood volume- hemostasis
- Coagulation → formation of a clot, thrombus, consisting of a plug of platelets and meshwork of the protein fibrin
- Clots are temporary patches that must be removed once wound repair has begun
- Fibrin clot cleaved by the protein plasmin to fibrin degradation products
- D-dimer is a fibrin degradation product - two cross-linked D domains released by the action of plasmin
What is needed for the D-dimer test?
Blood based assay that uses antibodies to the d-dimer protein to measure the presence of level of circulating d-dimer
What are elevated levels of D-dimer associated with?
- Elevated fibrin or clot somewhere in the body
- Can occur for a variety of reasons - acute PE, DVT, malignancy, pregnancy, chronic inflammatory conditions, recent surgery, infection, stroke, myocardial infarction, advance age
What is a negative test useful for?
Ruling out PE or other significant clot
