MSK Diseases 1 Flashcards
What is OA?
osteoarthiritis
DEGENERATIVE JOINT DISEASE
Patho of OA?
Wear and Tear leads to destroying the T2 collagen and proteoglycans
Chondrocytes will try and rescue by producing T2 collagen and proteoglycans
But after a while it does not work, and instead they start producing type 1 collagen.
T1 collagen and proteoglycans don’t interact and hence the joint loses elasticity
After a while, the chondrocytes cant keep up and undergo apoptosis causing cartilage to flake off and float in the synovial cavity
These flaky segments invite macrophages and pro-inflammatory cytokines to join the party – and they bring their cleaning booze with them
This leads to synovitis and fibrillation aka cracks – these cracks continue to erode – until just bone is remaining.
This bone on bone movement is called eburnation, and makes the bones look like polished ivory. Later this leads to bone stretching laterally producing osteophytes
Classification of OA
Primary where aetilogy is unknown and Secondary where aetilogy is known
In primary the joint has worn out Naturally, age related, normal wear and tear (Genetic, biochemical, Mechanical, Age-related)
Most people after 60 will have some percentage of OA
Secondary: Trauma, Neuropathic Joint disease, Other inflammatory joint disease, previous repeated steroid injections.
WHat is the grading for OA?
Commonly affected joints in OA
- Hips
- Knees
- Sacro-iliac joints
- Distal-interphalangeal joints in the hands (DIPs)
- The CMC joint at the base of the thumb
- Wrist
- Cervical spine
WHat are the four radiological signs seen in OA
What are OA changes in the joints
What are the risk factors for OA?
- AGE is THE BIGGEST RF
- Inflammation increases the progression of OA (some of the factors cause proteolysis and some factors block formation of new cart) : which is usually caused after JOINT INJURY
- Mechanical stress and OBESITY
- Genetics
- Meds
- Neuro Disorders
- Ocuupation
- Female
What are the Important Features seen in OA
Usually bilateral: Usually one joint at a time is affected over a period of several years. The carpometacarpal joints, distal interphalangeal joints are affected more than the proximal interphalangeal joints.
Episodic joint pain: An intermittent ache. Provoked by movement and relieved by resting the joint.
Stiffness: Worse after long periods of inactivity e.g. waking up in the morning. Stiffness lasts only a few minutes compared to the morning joint stiffness seen in rheumatoid arthritis.
Painless nodes (bony swellings): Heberden’s nodes at the DIPJs, Bouchard’s Nodes at the PIPJs. These nodes are the result of osteophyte formation
What are the signs you look for in hands for OA
Herberdens node
Bouchards node
Squaring of the thumbs: Deformity of the carpometacarpal joint of the thumb resulting in fixed adduction of the thumb.
What is this seen in?
OA
How is osteoarthritis different to inflammatory arthritis?
Osteoarthritis presents with joint pain and stiffness. This pain and stiffness tends to be worsened by activity in contrast to inflammatory arthritis where activity improves symptoms. It also leads to deformity, instability and reduced function in the joint.
Treatment for OA
patient education: weightloss, physio, OT
Medical / Conservative
- Oral paracetamol and topical NSAIDs or topical capsaicin (chilli pepper extract).
- Add oral NSAIDs and consider also prescribing a proton pump inhibitor (PPI) to protect their stomach such as omeprazole. They are better used intermittently rather than continuously.
- Consider opiates such as codeine and morphine. These should be used cautiously as they can have significant side effects and patients can develop dependence and withdrawal. They also don’t work for chronic pain and result in patients becoming depending without benefitting from pain relief.
Surgical
- Intra-articular steroid injections provide a temporary reduction in inflammation and improve symptoms.
- Replacement
What is Gout
Inflammatory disease in which monosodium urate crystals deposit into a joint making it red, hot, tender and swollen within hours
Crystals usually develop in areas of fast blood flow like the joints and liver
TRUE OR FALSE
FALSE
Crystals usually develop in areas of slow blood flow like the joints and kidney tubules.
What is uric acid present in?
Uric acid is present in Purines, Foods - shellfish, anchovies, red and organ meat.
WHat joint is affected in gout usually?
1st metatarsal joint is usually affected, its called podagra. person will wake up from sleep, and will feel as if their big toe is on fire.
- Base of the big toe (metatarsophalangeal joint)
- Wrists
- Base of thumb (carpometacarpal joints)
In gout you might find the presence of _____: White, Chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in soft tissues and joints aka permanent deposits of uric acid crystals.
In gout you might find the presence of Tophi: White, Chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in soft tissues and joints aka permanent deposits of uric acid crystals.
Risk factors for gout
Male
Obesity
High purine diet (e.g. meat and seafood)
Alcohol
Diuretics
Existing cardiovascular or kidney disease
Family history
Prophylaxis of Gout
Allopurinol is a xanthine oxidase inhibitor used for the prophylaxis of gout. It reduces the uric acid level.
Lifestyle changes can reduce the risk of developing gout. This involves losing weight, staying hydrated and minimising the consumption of alcohol and purine-based food (such as meat and seafood).
TOM TIP: Do not initiate allopurinol prophylaxis until after the acute attack is settled. Once treatment of allopurinol has been started then it can be continued during an acute attack.
Radiological features for gout?
- Joint effusion is an early sign
- Well defined punched out erosions
- Relative presentation of joint space until late disease
- Eccentric (well defined) erosions
- No particular osteopenia (in contrast with RA)
- Soft tissue tophi many be seen
What Can lead to GOUT?
Decreased Uric Acid Excretion
- drugs: diuretics
- chronic kidney disease
- lead toxicity
Increased production of uric acid
- myeloproliferative/lymphoproliferative disorder
- cytotoxic drugs
- severe psoriasis
How do you diagnose Gout?
History and Exam
Serum Urate - may be normal during an attack
Joint aspiration - synovial fluid will show negatively bi-fringent needle shaped crystals under polarized light
Management of Gout
During the acute flare:
- NSAIDs (e.g. ibuprofen) are first-line
- Colchicine second-line
- Steroids can be considered third-line
Colchicine is used in patients that are inappropriate for NSAIDs, such as those with renal impairment or significant heart disease. A notable side effect is gastrointestinal upset. Diarrhoea is a very common side effect. This is dose-dependent meaning lower doses cause less upset than higher doses.
What can increases your chances of getting an acute gout attack?
- Rise or sudden fall in urate level
- Binge drinking
- High protein intake?
- Trauma/ surgery, rapid cell destruction (releases purines)
- Weight loss( increased cell apoptosis)
- Reduced urate clearance - dehydration, renal disease
Compare and contrast gout and pseudogout?
crystal composition
crystal shape
birefringent
Most common joint affect
Radiography
First line treatment
Epidemiology
of SLE
1 in 1000 white females
More common in females than males (>8:1) in childbearing years
More common in black and Hispanic, Asian populations
What is SLE
Systemic lupus erythematosus (SLE) (lupus)
- Autoimmune condition
- Pathogenesis- inflammation gone wrong, Anti nuclear antbodies
- Skin biopsy; lupus band test= immunofluorescent staining of IgG and complement deposits in dermo-epidermal junction
Diagnosis for SLE?
- Skin biposy
- Lupus band test= immunofluorescent staining of IgG and complement deposits in demo epidemal junction
- Positive ANA (anti-nuclear antibodies)
- Full blood count (normocytic anaemia of chronic disease)
- C3 and C4 levels (decreased in active disease)
- CRP and ESR (raised with active inflammation)
- Immunoglobulins (raised due to activation of B cells with inflammation)
- Urinalysis and urine protein:creatinine ratio for proteinuria in lupus nephritis
- Renal biopsy can be used to investigate for lupus nephritis
Pathogenesis of SLE
SLE is characterised by anti-nuclear antibodies. These are antibodies to proteins within the persons own cell nucleus. This causes the immune system to target theses proteins. When the immune system is activated by these antibodies targeting proteins in the cell nucleus it generates an inflammatory response. Inflammation in the body leads to the symptoms of the condition. Usually, inflammation is a helpful response when fighting off an infection however it creates numerous problems when it occurs chronically and against the tissues of the body.
Clinical Features
of SLE
(multi-systemic)
- Fatigue
- Weight loss
- Arthralgia (joint pain) and non-erosive arthritis
- Myalgia (muscle pain)
- Fever
- Photosensitive malar rash. This is a “butterfly” shaped rash across the nose and cheek bones that gets worse with sunlight.
- Lymphadenopathy and splenomegaly
- Shortness of breath
- Pleuritic chest pain
- Mouth ulcers
- Hair loss
- Raynaud’s phenomeno
Management of SLE
First line treatments are:
- NSAIDs
- Steroids (prednisolone)
- Hydroxychloroquine (first line for mild SLE)
- Suncream and sun avoidance for the photosensitive the malar rash
Other commonly used immunosuppressants in resistant or more severe lupus:
- Methotrexate
- Mycophenolate mofetil
- Azathioprine
- Tacrolimus
- Leflunomide
- Ciclosporin
Biological therapies
- Rituximab is a monoclonal antibody that targets the CD20 protein on the surface of B cells
- Belimumab is a monoclonal antibody that targets B-cell activating factor
What is Scleroderma
Scleroderma is an uncommon condition that results in hard, thickened areas of skin and sometimes problems with internal organs and blood vessels.
Multi-systemic disease, unknown cause
• Vascular damage
• Overproduction of collagen
• Immunological features
Scleroderma,
epidemiology
mainly in females
what is Raynaud’s phenomenon
Common affects 3-5% of the UK population;
episodic colour changes in response to cold or
emotion
Raynaud’s phenomenon is a problem that causes decreased blood flow to the fingers. In some cases, it also causes less blood flow to the ears, toes, nipples, knees, or nose. This happens due to spasms of blood vessels in those areas. The spasms happen in response to cold, stress, or emotional upset.
Patho of raynauds phenomenon
Pathology: increased vasoconstriction,
smooth muscle more reactive, damage to
endothelial cells, fibrosis
What is primary and secondary raynauds phenomenon
Primary RP- no underlying cause
• Secondary RP- associated with connective
tissue disease ie systemic sclerosis, vasculitis,
malignancy or peripheral vascular disease
Diagnosis for RP
Diagnosis made clinically- digits turn white (pallor) then blue with deoxygenation and or red with reperfusion
CREST syndrome- type of limited cutaneous systemic
sclerosis
what does CREST stand for?
WHat is Systemic Sclerosis
Name the two types
Systemic sclerosis is an autoimmune inflammatory and fibrotic connective tissue disease. The cause of the condition is unclear. It most notably affects the skin in all areas but it also affects the internal organs.
There are two main patterns of disease in systemic sclerosis:
- Limited cutaneous systemic sclerosis (CREST)
- Diffuse cutaneous systemic sclerosis
What is Polymyositis and dermatomyositis
Polymyositis and dermatomyositis are autoimmune disorders where there is inflammation in the muscles (myositis). Polymyositis is a condition of chronic inflammation of muscles. Dermatomyositis is a connective tissue disorder where there is chronic inflammation of the skin and muscles.
Antibodies associated with Polymuosititis and Dermatomyositis
- Anti-Jo-1 antibodies: polymyositis (but often present in dermatomyositis)
- Anti-Mi-2 antibodies: dermatomyositis.
- Anti-nuclear antibodies: dermatomyositis.
WHat is a marker for Polymyositis and Dermatomyositis
Creatine Kinase
The key investigation for diagnosing myositis is a creatine kinase blood test. Creatine kinase is an enzyme found inside muscle cells. Inflammation in the muscle cells (myositis) leads to the release of creatine kinase. Creatine kinase is usually less than 300 U/L. In polymyositis and dermatomyositis, the result is usually over 1000, often in the multiples of thousands.
Other causes of a raised creatine kinase include:
- Rhabdomyolysis
- Acute kidney injury
- Myocardial infarction
- Statins
- Strenuous exercise
Dermatomyositis Skin Features
- Gottron lesions (scaly erythematous patches) on the knuckles, elbows and knees
- Photosensitive erythematous rash on the back, shoulders and neck
- Purple rash on the face and eyelids
- Periorbital oedema (swelling around the eyes)
- Subcutaneous calcinosis (calcium deposits in the subcutaneous tissue)
Anti-Smith (highly specific to SLE but not very sensitive)
Anti-centromere antibodies (most associated with limited cutaneous systemic sclerosis)
Anti-Ro and Anti-La (most associated with Sjogren’s syndrome)
Anti-Scl-70 (most associated with systemic sclerosis)
Anti-Jo-1 (most associated with dermatomyositis)
Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE
What does seronegative mean?
giving a negative result in a test of blood serum, e.g. for the presence of a virus.
More inflammaory than autoimmune
Examples of inflammatory arthiritis (seronegative)
Spondyloarthropathies:
- Psoriatic arthritis
- Ankylosing spondylitis
- Reactive arthritis
- Seronegative RA
- Juvenile idiopathic arthritis
Examples of inflammatory arthritis (autimmune)
Rheumatoid arthritis
Patho of RA
Rheumatoid Factor (RF) is an autoantibody presenting in around 70% of RA patients. It is an autoantibody that targets the Fc portion of the IgG antibody. This causes activation of the immune system against the patients own IgG causing systemic inflammation. Rheumatoid factor is most often IgM however they can be any class of immunoglobulin.
Cyclic citrullinated peptide antibodies (anti-CCP antibodies) are autoantibodies that are more sensitive and specific to rheumatoid arthritis than rheumatoid factor. Anti-CCP antibodies often pre-date the development of rheumatoid arthritis and give an indication that a patient will go on to develop rheumatoid arthritis at some point.
Triggeres for RA?
- Smoking
- Infection
- Susceptible genes (PTPN22 gene) (HLA_DR1, HLA-DR4)
- Women: Pregnancy, oral contraceptives, HRT, sex hormones
What is the genetic trigger for RA
Epigenetic changes & post-translational modifications in collagen => conversion of amino acid arginine to citrulline
HLA DR4 (a gene often present in RF positive patients)
HLA DR1 (a gene occasionally present in RA patients)
What is this seen in?
RA
Management for RA
DMARD
NICE guidelines for Disease Modifying Anti-Rheumatic Drugs (DMARDs):
- First line is monotherapy with methotrexate, leflunomide or sulfasalazine. Hydroxychloroquine can be considered in mild disease and is considered the “mildest” anti rheumatic drug.
- Second line is 2 of these used in combination.
- Third line is methotrexate plus a biological therapy, usually a TNF inhibitor.
- Fourth line is methotrexate plus rituximab
- Sulfasalazine and hydroxychloroquine are considered as DMARDs in pregnancy.
