Week 2 - E - Muscle diseases (not incl P.M.R) - T cell, Poly / dermato / inclusion body myositis, Fibromyalgia Flashcards
What is muscle pain known as? What are two examples of idiopathic inflammatory myopathies?
Muscle pain is known as myalgia
Two examples of idiopathic inflammatory myopathies (diseases of the muscle) are polymositis and dermatomyositis
In polymyositis and dermatomyositis, what is thought to mediate the inflammatory process and how are healthy muscle fibres destroyed?
It is thought that the conditions are a T cell mediated cytotoxic process against unidentified muscle antigens
* CD8 Tcells and macrophages initially surround healthy non-necrotic muscle fibres and eventually invade and destroy them
T cells are so called because they are predominantly produced in the thymus They recognize foreign particles (antigens) by a surface expressed, highly variable T cells receptor Which type of T cells are known as cytotoxic t cells and which are known as T helper cells?
Cytotoxic t cells - CD8 T cells - kills the virally infected cells and tumours
T helper cells - CD4 T cells - helps the other cells of the immune response
Unlike antibodies, the T cell receptor cannot bind antigen directly. Instead it needs to have broken down peptides of the antigen presented to it by the antigen presenting cell (APC). The molecules on the APC that present are called major histocompatibility compexes (MHC). There are two types of MHC - class 1 and class 2 Which type of MHC presents to which T cells?
MHC Class 1 presents to cytotoxic T cells (CD8)
MHC Class II presents to T helper cells (CD4)
Once the MHC Class II complex on the antigen presenting cells bind to the T helper cells, how does this activate the immune response?
Both the T helper cell and the antigen presenting cell release cytokines which causes the T cell to clone itself
The cloned T cells release cytokines which activate B cells and CD8 cells
How do the CD8 T cells act when interacting with the MHC class 1 complexes on an infected cell? * What are the proteins released by the CD8 cells?
The CD8 T cells produce and release cytotoxic granules known as perforins and granzymes
Perforins form pores in the cell membranes
Granzymes enter the cell and break down cell proteins causing cell lysis
What are the presenting features of myositis?
* Insidious onset
* progressive symmetrical proximal muscle weakness in upper and lower extremities
* autoimmune-mediated striated muscle inflammation (myositis)
* Associated with myalgia and arthralgia
What differentiates polymyositis from dermatomyositis? Which gender is more common for the conditions? What does an increase in age bring the risk of?
Dermatomyositis has
* the myositis symptoms (insidious onset progressive symmetrical bilateral proximal muscle weakness and myalgia/arthralgia)
* PLUS
* Cutaneous features (none in polymyositis)
Polymositis and dermatomyositis are more common in women (2:1) An increase in age increases the risk of malignancy
Again which are the typical muscles that are weak in myositis? What are some examples of tasks that are made difficult to perform?
It is typically the proximal muscles in the upper and lower extremities
Patients typically complain of difficulty brushing hair and climbing stairs
What is seen in roughly one third of patients with polymyositis due to oropharyngeal and oesophageal involvement?
Dysphagia secondary to oropharyngeal and esophageal involvement occurs in about one third of patients with polymyositis and is a poor prognostic sign.
Dyshponia may also occur (poor phonation due to intrinsic muscle moving the vocal cord)
Dermatomyositis is clinically similar to polymyositis other than the addition of typical cutaneous features. What are the cutaneous manifestations seen in dermatomyositis?
Heliotrope (lilac/purple) rash on eyelids often with oedema
Gottron’s papules - roughened red papules over the knuckles, also seen on elbows and knees
Macular V-shaped rash over the chest
Shawl sign if rash over back and shoulders
What is the crucial investigation for diagnosing poly/dermatomyositis and ruling out other mimicking conditions? What is the risk of myositis developing to malignancy?
Muscle biopsy is crucial for confirming myositis diagnosis and excluding other conditions
There is a 25% risk of developing cancer (more in dermato than in poly myositis)
Common cancers include breast, ovarian, lung, colon, oesophagus and bladder.
What markers are raised in the bloods in a patient with poly/dermato myositis? What autoantibodies are found in patients with poly/dermatomyositis?
Inflammatory markers may be raised - elevated CRP and ESR
Serum creatinine kinase is raised (raised CK + muscle weakness should make you think myositis)
Autoantibodies found - Anti-Jo1, anti-SRP, anti-Mi2, also ANA positive in majority of cases
What is seen on MRI and on electromygraphic studies in a patient with myositis?
MRI scans show muscle odema
Electromyographic (EMG) findings are abnormal in almost all patients (90%) with polymyositis - increased fibrillation (increased contraction) and abnormal motor potentials
What test is done to directly test the power of a patients muscle? Describe the test
Confrontational testing
* The patients holds elbows at 90 degrees and you push down to see if they can resist your force - this tests muscle weakness
Isotonic testing - patients sits down for 30 seconds and then stands up - tests strength of leg muscles
What is seen on muscle biopsy in inclusion body myositis?
Inclusion bodies are seen on muscle biopsy -
muscles fibres that contain empty-bubble like spaces (vacuoles) and clumps of cellular material (inclusion bodies)
Just like in polymositis, inflammatory cells are seen between the muscle fibres
What is the fibromyalgia cycle?
The firbomyalgia cycle shows how symptoms are made worse on exertion, stress and fatigue which leads to worsening mental health
