Muscle Diseases Flashcards
What is tetanus?
Acute disease caused by neurotoxins from the bacterium Clostridium tetani
How does the C. tetani toxin enter the body?
C. tetani spores found in soil, enter the body through broken skin
What is the incubation period of C. tetani?
4 days to several weeks
What does C. tetani do to the body and what does this lead to?
Toxin binds to inhibitory neurons, preventing release of inhibitory neurotransmitters → widespread activation of motor neurons and spasming of muscles throughout the body
What are the symptoms of tetanus?
- Trismus (lock jaw)
- Risus sardonicus (sustained spasm of facial muscles –> grin)
- Autonomic instability
What investigation can you conduct for tetanus?
Culture - anaerobic gram positive with terminal spore
Name treatments for tetanus
- Surgical debridement
- Antitoxin, booster vaccination
- Supportive measures (e.g. benzodiasapines, beta blockers)
- Antibiotics 7-10 days
Name preventative measures for tetanus
- Routine vaccination
- Wound management
What is polymyositis?
Idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness
What is dermatomyositis?
Polymyositis but also has typical cutaneous manifestations
What are the causes of pol-y/dermato- myositis?
Idiopathic, autoimmune
Who is pol-y/dermato- myositis most common in?
-Woman (2:1)
-Age 40-50
What immune cells are involved in pol-y/dermato- myositis? What do they do to muscles?
- T cell mediated process against (unidentified) muscle antigens
- CD8+ T cells and macrophages surround, invade and destroy healthy, non-necrotic muscle fibres (consist of nuclear and cytoplasmic autoantigens in about 60-80% of patients)
What are the symptoms of pol-y/dermato- myositis?
- Symmetrical, proximal muscle weakness in the upper and lower extremities
- Myalgia in 25-50% (usually mild)
Describe how muscle weakness comes on in pol-y/dermato- myositis?
- Insidious onset, worsening over months
- Often specific problems e.g. difficulty brushing hair, climbing stairs
What clinical sign is seen in pol-y/dermato- myositis? How can we test this?
Muscle wasting
- Confrontational testing - direct testing of power
- Isotonic testing (applying constant/uniform resistance to muscle)
What are the skin signs in dermatomyositis?
-Gottron’s sign (red/purple patches or papules on patient’s knuckles/finger joint’s )
-Heliotrope rash (rash on upper eyelids + around eyes)
-Shawl sign (rash across upper back/shoulders)
How can lungs be affected in pol-y/dermato- myositis?
- Interstitial lung disease (10% of patients, especially those positive for anti-Jo-1 antibody)
- Respiratory muscle weakness
Apart from lungs, how are other organs affected in pol-y/dermato- myositis?
- Oesophageal - dysphagia (1/3 patients, poor prognostic sign)
- Cardiac - myocarditis
- Other - fever, weight loss, Raynauds phenomenon, inflammatory arthritis
What blood tests should be conducted in pol-y/dermato- myositis?
- Muscle enzymes e.g. creatine kinase
- Inflammatory markers
- Electrolytes, calcium, PTH, TSH to exclude other causes
- Autoantibodies
What occurs to muscle enzymes in pol-y/dermato- myositis??
Often raised 10x normal limit
- CK and aldolase released due to muscle damage
- Help assess disease activity and response to treatment (high levels usually indicative of significant muscle damage and inflammation)
What auto-antibodies can be present in pol-y/dermato- myositis?
- Non-specific - ANA, anti-RNP
- Myositis specific - Anti-Jo-1, anti-SRP
What tests should you conduct for pol-y/dermato- myositis?
-Bloods
-Electromyography
-MRI
-Muscle biopsy
What will EMG show in pol-y/dermato- myositis?
- Abnormal in almost all patients
- Various abnormalities depending on the stage of the disease
Why is MRI used in pol-y/dermato- myositis?
- Used to localise the extent of muscle involvement
Why is muscle biopsy used in pol-y/dermato- myositis? What will it show?
- Definitive test
- Perivascular inflammation and muscle necrosis
What medications are used first line to treat polymyositis?
- Prednisolone - aim to reduce dose and eventually stop
What medications can you give if first line not responsive in polymyositis?
- Immunosuppression - azathioprine/methotrexate/ciclosporin
- IV immunoglobulin
- Biological therapy e.g. rituximab (B cell depleting therapy)
What are the complications that come with polymyositis? What do these include and who’s at greatest risk?
- Associated increased risk of malignancy (15% in dermatomyositis, 9% in polymyositis)
- Lung, breast, stomach, colon, bladder, ovarian most common
- Greatest risk in males > 45 years
What is viral myositis?
Muscle inflammation due to a viral infection e.g. influenza, enteroviruses, HIV, HTLV, CMV, rabies, dengue
What are symptoms of viral myositis? When do they usually start showing?
- Muscle pain, tenderness, swelling and often weakness
- Typically a few days after the onset of fever
What blood test is key in viral myositis?
Muscle enzyme- CK elevated
What is pyomyositis?
Acute intramuscular infection secondary to haematogenous spread of the microorganism into the body of a skeletal muscle, most commonly caused by Staph. aureus
Who’s most at risk for pyomyositis?
- PWIDs
- Diabetes meletus
- Immunosuppressed
Name the causative organisms of pyomyositis
- 90% staphlococcal (some site specific e.g. GNB in perineum)
- Immunosuppressed - psudomonas, beta haemolytic strep. enterococcus
- In tropical climates - MSSA infection in immune competent patients and children
- Clostridium infection possible in contaminated wounds
What are the symptoms of pyomyositis?
- Pain and swelling of the affected area (usually lower extremities)
- Fever
What investigations can you carry out for pyomyositis?
- Imaging - US, CT, MRI
- Pus discharge culture and sensitivity
How can you treat pyomyositis?
Antibiotics and surgery (debridement)
What is fibromyalgia?
Neurosensory disorder characterised by chronic MSK pain (commonest cause of MSK pain in women age 22-50)
Who is fibromyalgia most common in?
Higher prevalence in women (6:1)
What are the causes of fibromyalgia?
- Idiopathic, may begin after emotional or physical trauma
- May occur as a primary condition but is also seen in approximately 25% of patients with RA and approximately 50% of patients with SLE
Describe pathophysiology of fibromyalgia
- Thought to be disorder of central pain processing or a syndrome of central sensitivity so patients tend to have a lower threshold of pain and of other stimuli (heat, noise, and strong odours)
- Not associated with inflammation
What are the symptoms of fibromyalgia?
- Persistent (≥ 3 months) widespread pain
- Pain/tenderness, above and below the waist, can be both sides, and includes the axial spine
- Fatigue - disrupted and unrefreshing sleep
- Headaches
- Cognitive and memory impairment
- Anxiety, depression
- Non-cardiac chest pain
What are the key diagnostic tools for fibromyalgia?
- Widespread pain with associated symptoms
- Symptoms for≳3 months
- No other condition otherwise explains the pain
What are the management options for fibromyalgia?
- Patient education
- Graded exercise programme
- CBT
- Complementary medicine e.g. acupuncture
- Anti-depressants e.g. tricyclics, SSRIs
- Analgesia - atypical analgesia including tricyclics (e.g. amitriptyline), gabapentin and pregabalin may be beneficial
What is myasthenia gravis (MG)?
Severe autoimmune neuromuscular disorder characterised by severe muscular weakness and progressive fatigue
What are the causes of myasthenia gravis?
- Autoimmune (associated with other autoimmune disorders such as SLE, rheumatoid arthritis, and thyrotoxicosis)
- 90% idiopathic (however genetic predisposing factor - HLA associations)
- Thymic tumour - 10%
Who is myasthenia gravis common in?
- Most commonly 60-70
- May first appear during pregnancy, postpartum or with the administration of certain anaesthetic agent
Describe pathophysiology of myasthenia gravis
- Auto-reactive antibodies (auto-IgG) bind with postsynaptic ACh receptors on muscle cells - type II hypersensitivity
Describe how the thymus is involved in myasthenia gravis
- CD4+ TH cells are activated by unfolded AChR subunits expressed by thymic epithelial cells
- CD4+ TH cells stimulate auto-reactive B cells, resulting in the production of anti-AChR IgG auto-antibodies
- Thymic myoid cells that express intact AChRs are then attacked by these antibodies, and then release AChR-immune complexes
- AChR-immune complexes in turn activate antigen presenting cells and diversify the autoantibody response to recognise intact AChRs of normal muscle cells
- AChR auto-antiodies block binding of endogenous ACh ligands to these receptors
- Eventually, AChRs are destroyed:
- Antibody-bound receptors are internalised and degraded
- ACHR antibodies bound to Complement (membrane attack complex), leading to descruction of the muscle endplate
- The number of functional channels in the endplate are reduced → amplitude of endplate potential decreases → impaired signal conduction at the NMJ
What are the symptoms of myasthenia gravis?
- Insidious onset
- Initial symptoms involve ocular muscles in 60% of cases
- Complaints are fatigue and progressive muscle weakness (eyes, face, mouth, throat and neck are usually affected first) (less frequent are neck, shoulder girdle and hip flexors
- In advanced stage all muscles are weak → life-threatening impairment of respiration
What investigations can you conduct for myasthenia gravis?
- Lab tests (Anti-AChR IgG in serum)
- Repetitive nerve stimulation (Gradually reducing responses indicates NMJ dysfunction)
What is first line treatment for myasthenia gravis?
-Anticholinesterases (e.g. pyridostigmine): To increase neurotransmission by increasing the concentration of ACh in the synaptic cleft
What treatment can you give if first line not responsive in myasthenia gravis?
- Reduce autoimmune reactions (second line) - immunosuppressive drugs, corticosteroids
- Surgery - thymectomy if MG is associated with thymic tumour (first line if indicated)
What is myonecrosis?
Life-threatening necrotizing soft tissue infection
What are the symptoms of myonecrosis?
- Disproportionate muscle pain
- Massive edema with skin discoloration that progresses from bronze to red-purple to black and overlying bullae
- Can be no fever or cutanous manifestations
- Can progress to systemic infection within a few hours
What investigations can be done for myonecrosis and what would they show?
- Imaging - X-ray, CT or MRI typically show a characteristic feathering pattern of the soft tissue
- Lab tests - Gram staining, wound culture, blood culture
What is the treatment for myonecrosis?
Immediate surgical debridement and antibiotic therapy
