What is the pathophysiology of osteoporosis?
more break down of bone than formation of bone causing decrease in bone density
what increase osteoclast/ bone resorption and breakdown?
PTH-> increase serum calcium-> osteoclast bone resorption
what increase osteoblast/ bone formation
- calcitonin: produced by C-cells in thyroid, inhibits osteoclast activity and decrease serum calcium
- growth hormone, estrogen, testosterone
- good nutrients: intake of calcium and vitamin D
- strength training
what are the 2 main types of osteoporosis and their causes?
- type 1/ Post menopausal: decrease in estrogen-> increase bone resorption/ breakdown by osteoclast
- type 2/ Senile/ old age: osteoblast loose ability for bone formation
- secondary: corticosteorids
Histological findings of osteoporosis & which change cause increase bone fragility
- fewer trabeculae in spongy/ trabecular bone (inside part of the bone)
- Thickening of cortical bone (outside part of bone)
- Widening of the Haversian canals (hollow center space of osteons that makeup the cortical part of bone, have blood supply of innervation of bone cells): this is the reason of increase risk of fracture/ bone fragility
What are the risk factors of osteoporosis? Any Conditions or medication?
Low estrogen (after menopause)
Low serum calcium
Glucocorticoids (decrease Ca2+ absorption from gut)
Physical inactivity
Cushing’s syndrome, diabetes
Alcohol & smoking
What is the investigation and diagnosis for osteoporosis? and who should be investigated?
DEXA scan: test bone density T score: less than 2.5 or -2.5= osteoporosis
All Female 65+ and male 75+, if they are younger, screen if they have previous fragility fractures, on oral corticosteroids (ie, glucocorticoids for arterial problems)
what are the treatment options for osteoporosis (mode of action)
reduce fragility risk
1. Oral Bisphosphonates: analogue of pyrophosphate that inhibits osteoclast (ie, alendronate & risedronate)
2. Hormone replacement therapy for younger post-menopausal women
what are the side effects and compensations for prescribing bisphophonate
- Side effects: Oesophageal ulcer & reflux, Osteonecrosis of jaw (jaw pain with no scalp tenderness), osteosarcoma (bone pain)
- give vitamin D or calcium if blood test show deficiency
- raised alkaline phosphatase levels
What is the main complication of osteoporosis and its presentation? Any other complications?
FRACTURES
Vertebral/ compression fracture: back pain, height loss, hunches posture
Femoral neck fracture
Distal radius fracture
What is gout? Symptoms, site & causes
- inflammatory arthritis that is severely painful, swollen, and red esp at night
- 70% is in the first MTP but can occur in the ankle, wrist, MCP, knee
- Drugs (thiazide, furosemide)- trauma, infection, surgery. haemolytic anaemia
What is the test & diagnosis for gout? what other level might also be raised?
Test: aspirate for synovial fluid
diagnosis: needle shaped negatively birefringent monosodium urate crystals under polarized light + Uric acid/ urate increase when symptoms settled
What are the treatments of gout? Any cautions/ side effects when perscribing?
- NSAID (prescribe with PPI, not for patients with peptic ulcer)
- Colchicine (SE: diarrhea)
- allopurinol: Urate lower therapy
What is the typical presentation of polymyalgia rheumatica?
- Aching and pain with morning stiffness (45 min+) & worse with movement in the proximal limb muscles but no weakness (ie, painful to move but power is there)
- Bilateral shoulder pain radiating to arm & elbow, Bilateral pelvic girdle pain
- Low grade fever, low mood
- Temporal arteritis symptoms
- 60 female, white
What is the diagnosis of polymyalgia rheumatica? which levels should be normal
- Clinical symptoms + inflammatory marker + response to steroid- Raised ESR, plasma viscosity, CRP
- Dramatic response to steroid should be seen (normal creatinine & anti-CCP)
What is the treatment of polymyalgia rheumatica? any side effects? What other medications may be necessary for long term treatment?
- Prednisolone 15mg (usually a dramatic respond by 3-4 weeks with normal inflammatory marker, if not give another diagnosis)
- Reduce dosage gradually- SE: avascular necrosis of hip
- give bisphosphonate w/or calcium, vitamin D to reduce osteoporosis risk caused by steroid
- Give PPI for gastric protection
What are some related conditions to polymyalgia rheumatica? MSK/systemic symptoms?
Commonly associated with giant cell/ temporal arteritis (headache & tender at temple, jaw pain)
Carpal tunnel
Pitting edema
what is the pathophysiology of rheumatoid arthritis
- Genetically predisposed individual have immune system that mistakes self-antigens (ie citrullinated protein) as foreign, and immune cells (B and T cells) produce autoantibodies that bind to these self- antigens and triggers a immune response
- Immune response attacks synovial membrane and recruits more immune cells causing inflammation and destruction
what are the symptoms of rheumatoid arthritis?
- Joint swelling, pain, w/ morning stiffness for 30 min +
- effects MCP and PIP
- Gradually worsen as larger joints are involved
what clinical exam is positive and deformity is present in rheumatoid arthritis
- positive squeeze test
- swan neck & boutonniere deformity
What are the diagnostic tests for Rheumatoid arthritis?
- Rheumatoid factor
- anti-CCP: more specific, if rheumatoid factor is negative do this
- X-ray of hands and feet
what is rheumatoid factor
circulating antibody (igM or igA) that react to Fc portion of igG
what is Anti-CCP
anti-cyclic citrullinated peptide antibodies
- formed during a self-citrulllination process in genetically predisposed individual where positively charged arginine amino acid turns into neutral citrulline and body developed Anti-CCP
what is considered bad prognosis for rheumatoid arthritis?
Positive rheumatoid factor, anti-CCP & erosions on x-ray in 2 years means poor prognosis
what criteria is used to measure disease activity?
DAS 28
- assess 28 joints for swelling and tenderness in combination with inflammatory markers
what is the X-ray finding of rheumatoid arthritis, who should get it?
LESS
L: loss of joint space
E: periarticular Erosion
S: soft tissue swelling
S: soft bones/ osteopenia
What are the steps of management for rheumatoid arthritis treatment?
- Monotherapy of oral methotrexate +/- short term corticosteroids: prednisolone for flare ups (oral or intramuscular)
- If methotrexate is not suitable or severe SE-> sulfasalazine, leflunomide, hydroxychloroquine is used
when is TNF inhibitor used when treating rheumatoid arthritist
If patient have tried 2 DMRAD and still inadequate response
What is the first line main rheumatoid arthritis treatments, its side effects/ monitoring when prescribed?
- Methotrexate, Once per week
- prescribed w/ folic acid to be taken a day after due to myelosuppression (bone marrow)
- hepatotoxicity, methotrexate pneumonitis
- Monitor FBC, U&E, LFT
what is the mode of action of methotrexate
inhibit dihydrofolate reductase (enzyme for synthesis of purines & pyrimidines)
what should be avoided when prescribing methotrexate
- Avoid trimethoprim or co-trimoxazole, and aspirin
- avoid pregnancy for 6 months after stopping drug
what are the pros and cons of hydroxychloroquine?
- Bull’s eye retinopathy- visions loss, need annual eye screening
- Can be used in pregnant woman
what are some examples of TNF inhibitors, any side effects?
- etanercept, infliximab
- Risk of reactivation tuberculosis (chest x-ray & TB test first)
what are the respiratory and cardiovascular manifestations of rheumatoid arthritis
- resp: pulmonary fibrosis, pleural effusion, bronchiectasis
- Ischemic heart disease
what are the MSK manifestations of rheumatoid arthritis
MSK: osteoporosis, Carpal tunnel syndrome, De-quervain’s
what is the triad for felty’s syndrome?
rheumatoid arthirist + splenomegaly + low white cell count
what are the histological changes in osteoarthritist
- Progressive damage to a synovial joint causing structure changes and pain
- Loss of cartilage at the ends of bones
- osteophytes (bone growth to compensate for the lost cartilage)
what are the risk factors of osteoarthrisit
genetic factors
age, female
obesity
previous trauma
What is a synovial joint? What does it consist of?
- Joint that allows movement
- enclosed by articular cartilage (end of bones) and synovial membrane on the side forms a joint cavity filled by synovial fluid
- protected on the outside by a joint/ articular capsule.
What are the symptoms of osteoarthritis?
- Swelling of Carpometacarpal (CMC, squaring of thumb), and DIP (heberden’s nodes)
- Bilateral Knee and hip pain
- Joint pain on movement, relieved by resting, Morning stiffness that only last few minutes
What is the investigation for osteoarthritis? What are the results?
X-ray
- Loss of Joint space
- Osteophytes (new bone formed to compensate cartilage loss)
- Subchondral sclerosis (dense bone formed in cartilage loss)
- Subchondral cysts (cyst formed beneath cartilage when it’s degenerating)
What is the management and treatment for osteoarthritis?
- Weight Loss, muscle strengthening exercise
- Paracetamol, topical NSAIDs/ COX-2 inhibitors (avoid if patient takes aspirin, topical NSAID only for hand and knee)
- add codeine
What is the management for osteoarthritis of the hip?
Oral analgesia
Intra-articular injections
Total hip replacement (aseptic loosening is common)
What is the cause of ankylosing spondylitis?
- Having the HLA-B27 gene causing inflammation for sacroiliac joint (sacrum= below vertebrae attaching it to pelvis, ilium= pelvis)
what is the typial patient profile and presentation of ankylosing spondylisit
- Male 20-30 years of age + lower back pain/stiffness that is worse in the morning & improve with exercise
- Pain at night that’s relieved when getting up
What are the investigations and treatment for ankylosing spondylitis?
- X-ray, clinical examinations, HLA-B27 gene (90%), raised inflammatory markers
- Exercise like swimming, NSAID, physiotherapy
What are the X-ray symptoms of ankylosing spondylitis?
- Sacroiliitis: loss of joint space & denser bones in sacroiliac joint
- Squaring of lumbar vertebrae
- Syndesmophytes: bony outgrowth in edge of vertebrae
What are the clinical examinations done for ankylosing spondylitis? What are the results?
Lumbar exam: reduced lateral flexion
Schober’s test: reduced forward flexion
Reduced chest expansion
what are the ocular, MSK, and hematological manifestations of ankylosing spondylitis
- Anterior uveitis: inflammation of front eye
- Achilles tendonitis: inflammation of tendon that connects calf muscle and heel bone
- Amyloidosis: build up of protein amyloid in organs and tissues
what are the respiraotry and cardiovascular manifestations of ankylosing spondylitis
- Apical fibrosis: scarring of apex of lung
- Aortic regurgitation: aortic valve cant close properly
- AV node block: delayed electrical signal at av node
What is vasculitis? What are the 2 main types?
Inflammation of the blood vessels
- Primary vasculitis: inflammatory response that targets the vessel walls and has no known cause
- Secondary vasculitis: infection, drug, toxin and may occur as part of another inflammatory disorder or cancer
What does vasculitis cause? What are some general symptoms?
- Inflammation -> thickening of vessel wall-> stenosis & ischemia
- Palpable purpura (raised, non-blanching when pressed)
What are the symptoms & typical presentation of temporal arteritis/ giant cell arteritis?
- Old female 60+ have rapid onset unilateral headache, jaw pain
- Blurring, double vision
- Scalp tenderness and pain esp when brushing hair
- Patient might have polymyalgia rheumatica
What are the investigations for temporal arteritis
- Temporal artery biopsy (skip lesions is possible showing normal result)
- Raised ESR
what are the treatments for temporal arteritis
- Urgent high dose prednisolone for no visual loss in suspected patients
- IV methylprednisolone for evolving visual loss
- Urgent refer to ophthalmology
What is a major complication of temporal arteritis? What test should be done
- Anterior ischemic optic neuropathy: occlusion of posterior ciliary artery (branch of ophthalmic artery) causing ischemia of optic nerve head
- Fundoscopy: swollen pale disc and blurred margins
What is the typical presentation of kawasaki disease
- child with high grade fever for 5+ day and not responding to antipyretics
- conjunctival injection ( red inside eyelid),
- bright red and cracked lips with
- strawberry tongue
(Clinical diagnosis can be made with above symptoms)
What are the management and complications of kawasaki disease?
- High dose aspirin (rare instance its used in children)
- Intravenous immunoglobulin
- Coronary artery aneurysm
what is ANCA associated vasculitis?
autoimmune condition affecting small blood vessels caused by ANCA (anti-neutrophilic cytoplasmic autoantibodies)
what are the 2 types of ANCA vasculitis?
- pANCA: targets myloperoxidase protein
- cANCA: targets proteinase 3
what are examples of ANCA associated vasculitis
- granulomatosis w/ polyangiitis
- eosinophilic granulomatosis w. Polyangiitis
- microscopic polyangiitis
what are the symptoms of ANCA vasculitist?
- Renal impairment
- resp symptoms
- systemic
- vasculitic rash
what are the investigations necessary for ANCA vasculitist
- Urinalysis for hematuria & proteinuria
- U&E for renal
- ANCA testing
- CXR
what is the treatment for ANCA vasculitis
- Steroids
- cyclophosphamide
What are the symptoms, investigation and treatment of wegener’s granulomatosis (granulomatosis with polyangiitis)
- Renal failure, epistaxis/ haemoptysis (nose bleed & coughing up blood)
what are the investigations of wegener’s granulomatosis (granulomatosis with polyangiitis)
- Bloods (cANCA), CXR (lesions), renal biopsy (cluster of inflammatory cells/ granulomas)
What are the symptoms, investigation and treatment of churg-strauss syndrome (eosinophilic granulomatosis with polyangiitis)
- Bizarre asthma is adult
- paranasal sinusitis
What are the investigations of churg-strauss syndrome (eosinophilic granulomatosis with polyangiitis)
- Bloods: P-ANCA with eosinophilia
- Biopsy: granulomatous and necrotizing vasculitis
What is polyarteritis nodosa? Describe the typical presentation
- Vasculitis in medium sized arteries
- Common in middle age men with hepatitis B
- Systemic nerve damage, abdominal pain, testicular pain
What are the investigation for polyarteritis nodosa?
- Angiogram, tissue biopsy
- hepB serology might be found
What are the treatment of polyarteritist nodosa
- Corticosteroids
- cyclophosphamide
What is the pathophysiology of systemic lupus erythematosus?
- Type 3 hypersensitivity
- Immune system dysregulation leading immune complex deposition in variety of organs
What are the cutaneous/ dermatological symptoms of systemic lupus erythema?
- Malar rash in nasolabial folds-> butterfly rash
- Raynaud’s phenomenon (fingers turn white or blue)
- Mouth ulcers
What are the MSK manifestations of systemic lupus erythematosus?
- Arthritis: synovitis or tenderness at 2+ joints with 30 min morning stiffness (deformities are reducible and should not affect joint function, ie, patient can make fist)
- Arthralgia, myalgia
How are the investigations and monitoring used in systemic lupus erythematosus?
- Antibodies: ANA and anti-dsDNA
- Inflammatory marker (high means underlying infection)
- Complement level C3 and C4 are low during active disease
What are the antibodies associated with systemic lupus erythematosus?
- Highly specific and sensitive: anti-dsDNA
- anti-smith but has lower sensitivity
- Highly sensitive: ANA (used to exclude lupus but not very specific)
What are the treatments of systemic lupus erythematosus?
- NSAID, sun block
- Hydroxychloroquine
- Prednisolone if internal organ involvement
