Muscle Diseases Flashcards
What is polymyositis?
idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness
What is dermatomyositis?
clinically similar to polymyositis but also has typical cutaneous manifestations
What is the aetiology of polymyositis and dermatomyositis?
- Idiopathic, autoimmune
- Higher prevalence in females (2:1)
- Peak incidence age 40-50
What is the pathophysiology of polymyositis and dermatomyositis?
- T cell mediated process against (unidentified) muscle antigens
- CD8+ T cells and macrophages surround, invade and destroy healthy, non-necrotic muscle fibres
- An autoimmune response to nuclear and cytoplasmic autoantigens is detected in about 60-80% of patients with polymyositis and dermatomyositis
What are the signs and symptoms of polymyositis and dermatomyositis?
- Symmetrical, proximal muscle weakness in the upper and lower extremities
- Insidious onset, worsening over months
- Often specific problems e.g. difficulty brushing hair, climbing stairs
- Myalgia in 25-50% (usually mild)
- Muscle wasting
- Confrontational testing - direct testing of power
- Isotonic testing - 30 second sit to stand
What are the signs specific to dermatomyositis?
Gottron’s sign
Shawl sign
Heliotrope rash
What other organ involvement occurs in polymyositis and dermatomyositis?
- Lung
- Interstitial lung disease (10% of patients, especially those positive for anti-Jo-1 antibody)
- Respiratory muscle weakness
- Oesophageal - dysphagia (1/3 patients, poor prognostic sign)
- Cardiac - myocarditis
- Other - fever, weight loss, Raynaud’s phenomenon, inflammatory arthritis
What are the investigations for polymyositis and dermatomyositis?
Bloods
- Muscle enzymes e.g. creatine kinase (often raised 10x normal limit)
- Inflammatory markers
- Electrolytes, calcium, PTH, TSH to exclude other causes
- Autoantibodies:
- Non-specific - ANA, anti-RNP
- Myositis specific - Anti-Jo-1, anti-SRP
Electromyography (EMG)
- Abnormal in almost all patients
- Various abnormalities depending on the stage of the disease
MRI
- Used to localise the extent of muscle involvement
- Show signal intensity abnormalities due to muscle inflammation, oedema, fibrosis and calcification
Muscle biopsy
- Definitive test
- Perivascular inflammation and muscle necrosis
What is the management of dermatomyositis and polymyositis?
- Prednisolone - aim to reduce dose and eventually stop
- Alternative treatments if not responsive:
- Immunosuppression - azathioprine/methotrexate/ciclosporin
- IV immunoglobulin
- Biological therapy e.g. rituximab (B cell depleting therapy)
What are the complications of polymyositis and dermatomyositis?
- Associated increased risk of malignancy
- 15% in dermatomyositis, 9% in polymyositis
- Ovarian, breast, stomach, lung bladder and colon cancers most commonly
- Greatest risk in males > 45 years
What is fibromyalgia?
Neurosensory disorder characterised by chronic MSK pain
What is the aetiology of fibromyalgia?
- Higher prevalence in women (6:1)
- Commonest cause of MSK pain in women 22-50
- 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
What is the pathophysiology of fibromyalgia?
- It is thought to be a disorder of central pain processing or a syndrome of central sensitivity
- Patients tend to have a lower threshold of pain and of other stimuli, such as heat, noise, and strong odours
- Not associated with inflammation
What is the presentation of fibromyalgia?
- Persistent (≥ 3 months) widespread pain
- Pain/tenderness on both sides of the body, above and below the waist, and includes the axial spine
- Fatigue - disrupted and unrefreshing sleep
- Headaches
- Cognitive and memory impairment
- Anxiety, depression
- Non-cardiac chest pain
What are the investigations and diagnosis of fibromyalgia?
Clinical diagnosis:
- Patient experiences widespread pain and associated symptoms (unrefreshed sleep, cognitive symptoms, fatigue etc.)
- Symptoms have been present at the same level for ≳3 months
- No other condition otherwise explains the pain (diagnosis of exclusion - rule out other causes)
What is the management of 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?
Severe autoimmune neuromuscular disorder characterised by severe muscular weakness and progressive fatigue
What is the aetiology of myasthenia gravis?
- Autoimmune
- Also associated with other autoimmune disorders such as SLE, rheumatoid arthritis, and thyrotoxicosis
- 90% - no known cause
- Genetic predisposing factor - HLA associations
- Thymic tumour - 10%
- Can occur at any age but usually presents at after middle age - most commonly 60-70
- May first appear during pregnancy, postpartum or with the administration of certain anaesthetic agent
What is the pathophysiology of myasthenia gravis?
- Autoimmune disease in which auto-reactive antibodies (auto-IgG) bind with postsynaptic ACh receptors on muscle cells - type II hypersensitivity
- Involvement of CD4+ TH cells and AChR self-antigens in activating auto-reactive B cells
What is the thymus involvement of myasthenia gravis?
- CD4+ TH cells are activated by unfolded AChR subunits expressed by thymic epithelial cells
- Cde4+ 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 destruction 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 is the clinical presentation of myasthenia gravis?
- Onset typically insidious
- Initial symptoms involve ocular muscles in 60% of cases
- Complaints are fatigue and progressive muscle weakness
- Muscles of the eyes, face, mouth, throat and neck are usually affected first
- Less frequently involved are the muscles of the neck, shoulder girdle and hip flexors
- In advanced stage all muscles are weak → life-threatening impairment of respiration
What are the investigations of myasthenia gravis?
- Lab tests - anti-AChR IgG in serum
- Repetitive nerve stimulation - gradually reducing responses indicates NMJ dysfunction
What is the management of myasthenia gravis?
- Increase neurotransmission (first line) - anticholinesterases (e.g. pyridostigmine)
- Increase the concentration of ACh in the synaptic cleft
- 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 commonly caused by the rapid proliferation and spread of Clostridium perfringens from a contaminated wound
What is the presentation 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 cutaneous manifestations
- Can progress to systemic infection within a few hours
What are the investigations of myonecrosis?
- 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 management of myonecrosis?
Immediate surgical debridement and antibiotic therapy
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
What are the risk factors of pyomyositis?
- PWIDs
- Diabetes mellitus
- Immunosuppressed
What are the causative organisms of pyomyositis?
- 90% staphylococcal
- Some site specific e.g. GNB in perineum
- Immunosuppressed - pseudomonas, beta haemolytic strep. enterococcus
- In tropical climates - MSSA infection in immune competant patients and children
- Clostridium infection possible in contaminated wounds
What is the presentation of pyomyositis?
- Pain and swelling of the affected area (usually lower extremities)
- Fever
What are the investigations of pyomyositis?
- Imaging - US, CT, MRI
- Pus discharge culture and sensitivity
What is the management of pyomyositis?
Antibiotics and surgery (debridement)
What is viral myositis?
Muscle inflammation due to a viral infection e.g. influenza, enteroviruses, HIV, HTLV, CMV, rabies, dengue
What is the presentation of viral myositis?
- Muscle pain, tenderness, swelling and often weakness
- Typically a few days after the onset of fever
What are the investigations of viral myositis?
Bloods - elevated CK
What is the management of viral myositis?
Symptomatic
What is tetanus?
Acute disease caused by neurotoxins from the bacterium Clostridium tetani
What is the aetiology of tetanus?
C. tetani toxin
What is the pathophysiology of tetanus?
- C. tetani spores found in soil, enter the body through broken skin
- Incubation period - 4 days to several weeks
- Toxin binds to inhibitory neurons, preventing release of inhibitory neurotransmitters → widespread activation of motor neurons and spasming of muscles throughout the body
What is the presentation of tetanus?
- Trismus (lock jaw)
- Risus sardonicus
- Autonomic instability
What are the investigations of tetanus?
Culture - anaerobic gram positive with terminal spore
What is the management of tetanus?
- Surgical debridement
- Antitoxin, booster vaccination
- Supportive measures (e.g. benzodiazepines, beta blockers)
- Antibiotics 7-10 days
What is the prevention measures for tetanus?
- Routine vaccination
- Wound management
