Session 3 Flashcards
Define autoimmunity
Immune response against the host due to the loss of immunological tolerance (state of unresponsiveness to self antigen) of self- antigen(s)
Define autoimmune disease
Disease caused by tissue damage or disturbed physiological responses due to an auto-immune response
Clinical patterns of autoimmune disease
2 types:
Organ specific: One or multiple self antigens within one single organ or tissue. Easier to treat as self antigen is only present in that tissue.
Non-organ specific: Wide distributed self antigens throughout the body so harder to treat.
Thres not a single organ system that cannot be affected by an autoimmune disease e.g nervous system, respiratory disease, endocrine disease, joint diseases, haemotological disease.
Some diseases can overlap e.g lupus.
Common autoimmune diseases and their target autoantigens
Organ specific
Hashimoto’s thyroiditis - Thyroid peroxidase and thyroglobulin
Type 1 diabetes mellitus* - Pancreatic islet cells
Multiple sclerosis - Myelin sheath (nerve fibers)
Goodpasture’s disease - Glomerular/alveolar basement membrane (kidney)
Addison’s disease - Steroid-21 hydroxylase (adrenal cortex)
Graves’ disease - Thyroid-stimulating hormone receptor
Myasthenia gravis - Acetylcholine receptor (neuromuscular junction)
Pernicious anaemia* - Intrinsic factor (terminal ileum)
Non-organ specific
Autoimmune haemolytic anaemia - Red blood cells antigens
Rheumatoid arthritis - Rheumatoid Factor (Fc portion of the IgG)
Systemic lupus erythematosus (SLE)* - Double stranded DNA (dsDNA) + other nuclear proteins (histones)
Sjogren’s syndrome* - Nuclear antigens (Ro and La)
*multiple autoantigens may also be prsent in tissues.
Common autoimmune diseases,their clinical outcome and type of hypersensitivity
Set of criteria for the diagnosis of a disease as autoimmune
- Presence of autoantibodies/autoreactive T cells
- Levels of autoantibodies correlate with disease severity
- Autoantibodies/autoreactive T cells found at the site of tissue damage
- Transfer of autoantibody or autoreactive T cells to a healthy host induces the autoimmune disease
- Clinical benefit provided by immunomodulatory therapy
- Family history
Types of autoantibodies
Primary autoantibodies (rare) : (known as pathogenic)
- Anti-TSHR antibodies in Graves’ disease
- Anti-acetylcholine receptor antibodies in Myasthenia gravis
- Anti-voltage-gated Ca2+ channel antibodies in Lambert-Eaton myasthenia syndrome
- Anti-Glomerular basement membrane antibodies in Goodpasture’s syndrome
Secondary autoantibodies
- Anti-nuclear antibodies in SLE
- Anti-gastric parietal cell antibodies in pernicious anaemia
- Anti-thyroid peroxydase antibodies in Hashimoto thyroiditis
- Anti-Rheumatoid Factor antibodies in Rheumatoid arthritis
Detection of serum autoantibodies and autoimmune disease
This shows not all patients will have autoantibody against the defined self antigen.
Define specificity
Specificity = The % of individuals who do not have condition that the test excludes
Define sensitivity?
Sensitivity = The % of individuals with a condition that the test identifies
Detection of autoantibodies/autoreactive T cells at the site of tissue damage?
IgG transfer during pregnancy and autoimmune diseases
IgG can cross the placenta and cause disease in the neonate. Disease will only last 6 months though as baby forms its own antibodies after this point. IgM doesnt pass the placenta.
What triggers autoimmunity?
Genetic factors
o Increased risk with an affected sibling (8X)
o Increased risk with an affected identical twin (30X)
o AIRE mutations (APECED syndrome) that affect central tolerance
o Autoimmune disease associated with MHC variants (HLADR3/DR4)
Environmental factors
o Hormones
o Infections
o Drugs
Hormonal factors that influence prevalence of auto immune disease
Autoimmune disease more common in females. Nearly all occur during child bearing age except type 1 diabetes.
Infectious factors that affect prevalence of autoimmune disease
Similar to antigens in the body so body can attack both causing autoimmune disease.
Therapeutic drugs that can cause autoimmune disease
These drugs can cause side effects that mimic different autoimmune diseases. When they stop treatment, symptoms stop too.
Current and future therapeutic strategies for autoimmune diseases
Plasma exchange for primary antibody disease and immunosuppressive drugs for autoreactive T cell mediated disease. Monclonal antibodies being developed currently to target specific proteins so will heavily reduce side effects. If drug name ends in mab it means its a monoclonal antibody. Rituximab, belimumab and epratuzumab are against b cells and golimumab against TNF.
Which therapy for autoimmune disease?
What is stocking-glove pattern?
Disease affecting, hands, wrists, feet and legs. Often common presentation for autoimmune disease.
What are autoimmune rheumatic diseases (ARDs)?
- Heterogeneous group of diseases - not the same symptoms
- Immune tolerance breakdown - Not able to tolerate selff antigens
- Production of pathogenic antibodies (Not all antibodies cause disease)
- Multisystemic features
What is the importance of autoantibodies in autoimmune disease?
- Aid to diagnosis
- Associated with specific clinical features
- Disease prognosis
- To stratify therapy
An 25yr old Afro-Caribbean lady goes to her GP with a recurrent history of painful hand joints for the last 18 months. She has a 3 year history of raynauds. She had missed a few days at work due to pleuritic chest pain. She is complaining of disabling fatigue. What is the likely diagnosis?
a) Polymyalgia Rheumatica
b) Fibromyalgia
c) Vitamin D deficiency
d) Systemic lupus erythematosus
e) Malingering
D is correct
a) Polymyalgia Rheumatica - It only tends to bein over 50s
b) Fibromyalgia - Not this as this is adiagnosis of exclusion
c) Vitamin D deficiency - No chest pain especially not pleuritic
d) Systemic lupus erythematosus - correct
e) Malingering - Symptoms are fake
What is Systemic lupus erythematosus (Lupus)?
- Female to male ratio: 9:1
- Prevalence: 24/100,000 less in older populations.
- Race: Afro-Caribbean > South Asians > Caucasians
- Genetic factors are important
- Environmental factors - Not a cause but smoking can make it worse
- Constitutional symptoms (Fever, fatigue, weight loss, night sweats, Poor appetite)
“Glove and sweater” approach
- Gloves:
- Raynauds- look for colour change - goes white then blue and red, vasospasm then cyanosis and when it returns you get red. This is called a three phase raynauds pattern or justwhite to red which is two phase / biphasic raynauds or single phase raynauds which is permanently blue despite being in a warm room.
- Joint pains and swelling in hands or wrists then forearms
- Hand rash
- Sweater:
- Proximal muscle weakness > Myalgia - struggle to rise out of a chair or off the toilet, struggle to cob their hair or wash it.
- Hair loss - Do you wake up with locks of hair on your pillow?
- Eye and mouth dryness - sign of Sjogren’s - Does it feel like you have sand in your eyes anddo you need to take sips of water constantly when eating?
- Nose bleeds
- Mouth ulcers
- Pleuritic chest pain
- Pericardial pain
- Truncal Rash/Photosensitivity
- Limb weakness and pins and needles
If none of these present ignore blood test adn send them away to come back in 6 months.
Treatment
- Patient education RE: lifestyle modification, use of sunscreen
- Start DMARDs : Hydroxychloroquine, Azathioprine, Mycophenolate
- Use of steroids: Prednisolone, methylprednislone
- In Severe cases: IV Cyclophosphamide
History taking for RA
Current symptoms
- Pain
- Stiffness
- Swelling
- Pattern of joint involvement
Evolution:
- Acute or chronic?
- Associated events
- Response to treatment/Family history
Involvement of other systems :
- Skin, eye, lung
- Malaise, weight loss, fevers, night sweats?
Impact on patient’s lifestyle
Have you got the S factor? stiffness, swelling and squeezing causing pain (in hands and small joints)
Examination for ARDs
Muscle weekness - oppose muscle movements or ask them to get out of a chair without using their arms.
Investigations for ARDs
C-reactive protein - Will nearly always be normal regardless of how ill they are.
Dont need to know bloods.
Lupus Mnemonic A RASH POINTS Medical Diagnosis
ANA positive
Renal abnormalities
Arthralgia/arthritis
Serositis - inflammation of the serous tissues of the body, the tissues lining the lungs (pleura), heart (pericardium), and the inner lining of the abdomen (peritoneum) and organs within.
Haemaological abnormalities
Photosensitivity
Oral ulcers - aphthous ulcers - every month and problematic
Immunological abnormalities
Neurologic abnormalities
Malar rash / Discoid rash
4/11 criteria items = definite lupus
An 25yr old south Asian lady goes to her GP with a recurrent history of painful bilateral hand joints for the last 3 months. She has no past medical history of note. She has missed a few days at work due to increasing joint pain and swelling also affecting her feet. She is complaining of disabling fatigue. What is the likely diagnosis?
a) Polymyalgia Rheumatica
b) Fibromyalgia
c) Vitamin D deficiency
d) Systemic lupus erythematosus
e) Rheumatoid arthritis
a) Polymyalgia Rheumatica
b) Fibromyalgia
c) Vitamin D deficiency
d) Systemic lupus erythematosus
e) Rheumatoid arthritis - correct diagnosis
Rheumatoid arthritis (RA)
- Female to male ratio: 3:1
- Prevalence: 1%
- No race predilection
- Genetic factors/environmental factors - inherit templates from parent, smoking an imprtnat factor, bad dentition can activate a protein called citrulline which can cause early onset RA
History taking for RA
Current symptoms:
- Pain
- Stiffness
- Swelling
- Pattern of joint involvement
Examination: Swelling in small joints common
Treatment of RA:
- Start DMARDs early!! : Methotrexate,Hydroxychloroquine, Sulfasalazine, Leflunomide (middle two safe in pregnancy)
- Use of steroids: Prednisolone, methylprednisolone (fast action initially but only used for limited time.)
- Combination therapy is usual.
Investigations for RA
Full blood count
Urea, electrolytes and creatinine
Liver enzymes
C-reactive protein
Plasma viscosity and ESR
X-rays ± Ultrasound
Treat the symptoms not the blood test - Patients can sometimes pretend symptoms are there or worse than they are so be careful.
Classification criteria for RA
Panopto
Role of a rheumatologist.
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 patients with ARDs
Whatis the difference between prevalence and incidence?
Prevalence is the disease pool so number of people e.g x/100,000 people have the disease and incidence is new cases added to the pool y/100,000 new cases of the disease every year
What is rheumatoid arthritis called in children?
Juvenile ideopathic arthritis
