Autoimmune Msk Problems Flashcards
What is the lab work of non-infectious inflammatory myopathies
Positive ANA
Anti-Jo-1 AB
Anti-Mi-2 AB’s
Increased creatinine and aldolase
Give two examples of non-infectious inflammatory myopathies. What are they?
Don’t matter myositis + polymyositis
Immune-mediated disorders with symmetrical muscle involvement and involvement of other organs
What does muscle biopsy show for polymyositis
Necrotic and regenerating muscle with the lymphocytic and macrophage infiltrate
atrophy not prominent
What does muscle biopsies show for dermatomyositis
Inflammatory reaction i.e. lymphocytic
Atrophy of muscle fibres = prominent
Capillary damage + muscle – >ischaemia + atrophy
If a patient presents with the matter my situs what else do you need to consider the possibility of?
Gastric carcinoma
What is the aetiology of dermatomyositis
CD4 cells target capillaries + skeletal muscle
Antibodies + complement damage capillaries
What are the clinical features of the dermato myositis
Rash + upper eyelid = purple = heliotrope/raccoons
Malar rash
Red GOTTRON papules + elbows knuckles knees
Hallmark bilateral proximal muscle weakness – Can’t come hair due to weak shoulders
Morning stiffness fatigue + dysphagia @ upper oesophagus
Inside the muscle fascicle where exactly does the information occur in dermatomyositis?
Inflammation of the perimysium ->
perifascicular atrophy
In polymyositis is their proximal or distal muscle weakness?
Is the skin involved?
Where is inflammation occurring?
What immune cell is hallmark?
Proximal muscle weakness
Skin not involved
Inflammation @endomysium with necrotic muscle fibres
CD8+
What are antibodies directed against in polymyositis?
Transfer RNA synthetases
Nuclear + cytoplasmic antigens @ skeletal muscle
What initiates the CD8 positive cells?
HIV,
HTLV – 1,
coxsackie B
Alter MHC 1 MHC 2 antigens
Give the two types of X-linked muscular dystrophies
Duchenne muscular dystrophy
Becker muscular dystrophy
What is Duchenne muscular dystrophy the characterised by
Muscle wasting: skeletal muscle –> adipose tissue
Explain the genetics of Duchenne muscular dystrophy
X-linked
Frameshift mutation –Deletion of dystrophin gene – >
cannot anchor muscle fibres in skeletal + cardiac muscle– >
Can’t connect intracellular muscle cytoskeleton (actin)
to
transmembrane proteins alpha + beta dystroglycan. Which are connected to the extracellular matrix
What does the truncated dystrophin protein lead to
Inhibited muscle regeneration
Where does the muscle weakness begin from?
@ what age?
where does it progressed to?
Proximal muscle weakness @ 1 year old – >progress to distal muscle
E.g. begins in pelvic girdle muscle – >progress superiorly
Explain the Hallmark issue related to the leg in Duchenne muscular dystrophy
Pseudohypertrophy of the calf
Learn to walk + Proximal muscle starts to we can – >child puts more force on calf muscle to walk – >hypertrophy
Overtime disease progresses – >
Muscle weakens as disease moves distally and affects calf – >convert calf muscle to fat– > calf looks big but is full of fat
What does the damaged muscle cell release into the Serum?
Creatinine kinase + aldolase
Why does the child normally die from Duchenne muscular dystrophy?
Cardiac/respiratory (diaphragm) failure
Explain the difference between Becker muscular dystrophy + Duchenne muscular dystrophy
In Becker muscular dystrophy disorder is due to non-frameshift insertion in dystrophin Jean i.e.
Protein is partially functional instead of truncated like Duchenne
Onset in Beckers is @adolescence/early adulthood
Onset intuitions is before 5 years old
Beckers is milder
Explain the genetics behind myotonic type one muscular dystrophy
Autosomal dominant
CTG trinucleotide repeat @DMPK gene ->
Abnormal expression of mytonin protein kinase – >
atrophy type 1 fibres –>
MytoniA + cAtArAct
my tEsticles – Atrophy
My tIcker - arrhythmia
my tOUpee – Frontal balding
What is the pathogenesis of SLE
Look at pic on 04/03/15
What are the genetic and environmental aetiologies?
Genetic – (HLA–DR 2+3) & (compliment deficiency)
Environmental
Drugs = isoniazid procainamide hydralazine – >
bind to histones –>histones become immunogenic
->
auto-AB against histones = positive ANA test – > lupus like syndrome -
see all symptoms except CNS + renal involvement
Infections e.g. HIV/CMV/EBV -> polyclonal activation of B lymphocytes – >formation of autoAB against host tissue
Estrogen – > DECREASES p(apoptosis of self reactive B cells)
UV light
What is epitope spreading
Self reactive lymphocyte – > react against self-antigen – > destroyed tissue – > expose new antigens immune system hasn't seen before – > produce new self reactive lymphocytes
Who does systemically lupus Erythematosus affect?
Middle-aged females
Africans + Hispanics
Happens to children and OLD ADULTS
@Kids + older adults: 2 females: 1 male
@Middle aged people: 10 females: 1 male
In lupus what does type 3 HSR rxn lead to?
In lupus what does type 2 HSR rxn lead to?
Immune complexes = Information @
skin, BM, glomeruli, joints, vessels
Auto antibodies = cytopenias
E.g. anaemia thrombocytopenia leukopenia
What are the symptoms of SLE
Look at pic on 04/03/15
What are the pregnancy related findings in SLE
Heart block in the newborn as
IgG anti-Ro/SS-A AB crosses placenta and attacks cardiac conduction system
Antiphospholipid antibody binds to proteins on the trophoblast and causes abortion
Explain drug induced lupus in comparison to systemic lupus erythematosus
anti HHHHistone antibodies form decreased IIIIIncidence of renal + CNS issues No AAAAB against native DNA No decreased serum CCCCCompliment SSSSSSymptoms disappear when drugs stop
Treatment for lupus
Corticosteroids NSAIDs immunosuppressants hydroxychloroquine
What are the common causes of death due to lupus
Renal failure
Infection – due to immunosuppressants/auto antibodies against white blood cells
Later on in life = increased p(accelerated coronary atherosclerosis)
What is Sjogren’s syndrome
Autoimmune destruction of exocrine glands especially lacrimal + salivary glands
mediated by lymphocytes type 4 HSR + fibrosis
What does destruction of lacrimal + salivary glands result in?
Kerato conjunctivitis sicca / xerophthalmia -
⬇️ tear production – > dry eyes – > corneal damage
Dental Caries
Xerostomia - ⬇️ saliva production - dry mouth
Like every other autoimmune disease who is most likely to be affected by Sjogren’s syndrome
Older women
Sjögren’s can be a primary or a second airy disorder. As a secondary syndrome what can it be associated with?
Rheumatoid arthritis
What Ab can be present in the blood in sjogrens?
Can this be associated with rheumatoid arthritis
Rheumatoid factor
No not necessarily
What are the extraglandular manifestations of Sjogren’s syndrome
Joint pain CNS/skin issues
What are the lab findings and Sjogren’s syndrome
Rheumatoid factor
Positive ANA
Anti ribonucleoprotein = anti SSA/SSB
Anti-SSA: crosses placenta – >
attack fetus –> neonatal lupus – >
congenital heart block
Is the anti-SSA/SSB enough to make a diagnosis of Sjogren?
What do you need to confirm Sjogrens?
Biopsy of minor saliva gland @lip – >
look for lymphocytic SIALADENTIS =
lymphocytes attack minor salivary glands = MALT
Explain the relationship between Sjogren’s syndrome and parotid gland
Sjogren’s syndrome = inflame parotid gland – >
enlarged parotid gland – >
B cell lymphoma cause unilateral enlargement of parotid gland
How do you treat Sjögren’s syndrome
Artificial tears
Cyclosporine/pilocarpine eyedrops
Civimeline
What does the schimear test and Rose Bengal staying reveal for Sjögren’s
Filterpaper placed inside of lower eyelid
Wetting of <10 mm @ 5 minutes = ⬇️ tear problem
Rose Bengal stain shows
FILAMENARY keratitis + PUNCTATE keratitis
Explain the pathogenesis of systemic sclerosis scleroderma
AI rxn against AG @connective-tissue / endothelial cell – >
endothelial cell dysfunction – >increased expression of Cellular adhesion molecules –>
Th2 enter skin –> the endothelial cell secrete:
PDGF + TGF beta – > activate fibroblast –>
fibrosis around BV –>
organ damage = systemic sclerosis
Endothelin = vasoconstrictor –> ischaemia – >
more fibrosis – >organ damage
What are the two forms of systemic sclerosis
Limited and diffuse
Explain limited systemic sclerosis scleroderma
Skin involvement = minimal = distal to knee + elbow
Late visceral involvement
Calcinosis = calcium deposition @ subcutaneous connective-tissue anticentromere Ab
Raynaud phenomenal
Esophageal dysmotility
Sclerodactyly - fibrosis of skin + hands: tight skin – >lose wrinkles – >constrict blood vessels
Telangiectasia– Dilated capillaries
Explain the pathogenesis of mixed connective-tissue disease
B + T-cell activation – >Ab against U1-ribonucleoprotein
What are the lab findings for mixed connective-tissue disease
Positive ana
Auntie ribonucleoprotein against you U1-RNP
Clinical findings of mixed connective-tissue disease
Hypertension + pleuritis Arthralgia + arthritis of hands Raynaud Pericarditis Oesophageal dysfunction/dysmotility Neuralgia Trigeminal Sclerodactyly
Lab findings for systemic sclerosis
Positive ana
For diffuse scleroderma –
anti DNA topoisomerase 1 Ab = anti-Scl – 70 Ab
