Autoimmunity and MSK diseases Flashcards
Define MSK disorders and some examples
Musculoskeletal disease encompasses a range of conditions that affect the bones, muscles, and joints, including:
- Rheumatoid arthritis
- Spondylarthritis
- Systemic lupus erythematosus
- Juvenile arthritis
- Inflammatory myopathies
- Osteoarthritis
- Osteoporosis/osteopenia
- Back pain and associated disorders
Define arthritis
Arthritis involves swelling and tenderness of the joint, exemplified by rheumatoid arthritis, where there is inflammation of the synovium lining joint cavities, with potential for erosion of periarticular bone
Enthesitis
Inflammation at the points of insertion of tendons or ligaments into the bone (entheses) affects adjacent bone and soft tissue, seen in conditions like spondylarthritis (SpA).
Define dactylitis
This is a combination of synovitis and enthesitis involving an entire finger, often seen in psoriatic arthritis.
Define tenosynovitis
Inflammation of the lining of the sheath that surrounds a tendon is noted in conditions such as systemic lupus erythematosus.
Define myositis
Inflammation of the muscles can be a primary condition or manifestation of systemic autoimmune disease.
Describe the ways in which arthritis can be classified
Arthritis can be classified by:
- Number of joints affected (single, mono or polyarthritis)
- Acute versus chronic nature
- Additive versus migratory patterns (adding joints here and there versus moving along a line)
- Persistent versus recurrent episodes
- Predominantly proximal versus predominantly distal involvement
- Symmetrical versus asymmetrical presentation
- Presence or absence of inflammatory lower back pain ^[morning stiffness indicates inflammatory lower back pain]
- Presence or absence of systemic manifestations
List some systemic manifestations associated with rheumatic disease
- Constitutional symptoms like fever, weight loss, fatigue e.g. SLE and RA
- Arterial or venous thrombosis, recurrent miscarriage, dysphagia, lymphadenopathy, muscle weakness, seizures, psychiatric presentations, and peripheral neuropathy
- Skin manifestations such as photosensitivity, scleroderma, purpura, livedo reticularis, ulcers, alopecia, telangiectasis, heliotrope rash, and Gottron’s papules
- Mucosal manifestations like orogenital ulceration and keratoconjunctival sicca ^[dry eyes and mouth]
- Serositis and Raynaud’s phenomenon ^[colour changes in peripheries - pain on rewarming]
not assessable in depth
Describe RA
Rheumatoid arthritis is a chronic inflammatory joint disease. Its prevalence is about 0.5%; females are 2-3x more likely than males to have RA.
Peak incidence occurs in the 6th decade.
It is characterized by symmetrical erosive arthritis, including synovitis, progressing to destruction of cartilage and periarticular bone, juxta-articular osteoporosis. It is associated with disability (due to progressive functional and fixed deformity) and is associated with other comorbidities like cardiovascular disease e.g. MI and stroke.
Briefly describe the pathophysiology of RA
The pathophysiology involves infiltration and expansion of the synovial membrane, otherwise known as pannus formation. This entails:
- endothelial cell activation
- neovascularisation
- infiltration by immune cells
- cytokine secretion (TNF, IL-6)
- increased osteoclast activity (leading to osteoporosis and erosive disease)
The ultiamate outcome cartilage and bone destruction.
What does the epidemiology of RA tell us?
The epidemiology highlights:
- the contribution of genetic and environmental factors:
- HLA DRB1 0401/0404 (HLA DR4): shared epitope in peptide binding grove for alleles with association with rheumatoid arthritis – hints at triggers necessary to cause disease
- there are number of other genes with weaker association related to: T cell function, B cell activation, cytokines/receptors and signalling pathways, and matrix metalloproteinase 9 (related to osteoclast activity and activation within the connective tissue)
- environmental factors: smoking, exposure to silica, viral and bacterial infections e.g. P. gingivalis-associated periodontitis
- epigenetic modifications: DNA methylation, histone acetylation, neoepitopes to range of proteins including collagen and vimentin
- formation of autoantibodies
- anti-citrullinated peptide antibodies (ACPAs)
- antibodies to Fc portion of IgG (rheumatoid factor)
note
- presence of ACPAs precede clinical features…but is not a screening tool
List some clinical manifestations of rheumatoid arthritis
Clinical MSK manifestations include:
- symmetrical joint pain and swelling
- distal joints more common than proximal i.e. wrists, MCP, MPT and PIPs
- morning stiffness > 1hr
- constitutional symptoms: fever and fatigue
- fusiform soft joint swelling around the involved joint
- decreased range of motion
- subluxation
- ankylosis
Extra-articular involvement is common, and can include:
- skin e.g. nodules
- ocular e.g. inflammation
- oral e.g. salivary inflammation
- resp e.g. pulmonary fibrosis
- cardiac e.g. pericarditis
- neuro e.g. mononeuritis and nerve entrapment
- hepatic
- haem e.g. anaemia, lymphadenopathy, thrombo/leukocytosis
- vascular
extra articular not nec in detail
Describe lab findings associated with RA
Laboratory findings can include:
- rheumatoid factor
- which is an antibody to Fc portion of IgG
- IgG, IgM, and IgA antibodies might also be found
- with IgM correlating best with disease activity and severity
- Anti-citrullinated peptide antibodies (ACPA)
- these are directed against citrullinated peptides
- they are more sensitive and specific (but RF done more)
- which are associated with a more rapid and progressive erosive joint disease.
50-80% will have RF, ACPA or both.
List some types of spndylarthites
Types and Characteristics
- Reactive arthritis e.g. after STI
- Psoriatic arthritis
- Arthritis related to inflammatory bowel disease
- Ankylosing spondylitis
- M:F ratio 2-3:1 for AS
- Onset usually in 3rd decade of life
- Strong association with HLA B27
Describe the relationship between spondylarthritis and HLA-B27
Disease and HLA-B27 Frequency
Note that there is variation in frequency across ethnic populations, e.g. over-represented in European populations.
- Ankylosing spondylitis: > 90%
- Undifferentiated spondyloarthropathy: 70%
- Reactive arthritis: 30-70%
- Psoriatic arthritis: 40-50%
- Iritis: 50%
- Cardiac manifestations: >80%
