Week 6: Rheumatology (1) (conditions) Flashcards
pathophysiology of rheumatoid arthritis
Citrullination of self-antigens which are then recognised by T and B cells – producing autoantibodies (RF and anti-CCP)
- Stimulates macrophages and fibroblasts release TNFalpha
- Inflammatory cascade leads to proliferation of synoviocytes (bogg joint swelling), these grow over the cartilage and lead to restriction of nutrients and cartilage damage
- Activate macrophages stimulate osteoclast differentiation contributing to bone damage
risk factors of RA
- Female 3:1
- 30-50 years old
presentation of RA
- Progressive, peripheral and symmetrical polyarthritis
- Commonly affected joints: MCP/ PIP/ MTPs (typically spares DIP (OA)). May effect any joint inc hip/knees/shoulders/c-spine
- Hx .6 weeks
- Morning stiffness >30 min duration
- Fatigue/ malaise
RA examination
- Soft tissue swelling and tenderness first
- Ulnar deviation/palmar subluxation of MCP
- Swan-neck and boutonniere deformity to digits
- Rheumatoid nodules- most common on elbows
- Median nerve- carpal tunnel association
RA investigations
- Auto antibodies: RF and anti-CCP
- FBC- normocytic anaemia (chronic disease)
- WCC (septic arthritis)
- Inflammatory markers (CRP and ESR)- elevates
- X-ray changes apparent in established disease- USSS/MRI more sensitive in early disease
treatment of RA
- Initially DMARD monotherapy- Methotrexate
- Consider combination DMARDs (leflunomide, hydroxychloroquine, sulfasalazine)
- Steroids (acutely)= prednisolone
- PO/IM or intra-articular
- Symptoms control with NSAID (PPI cover)
- If disease still severe add biologic- anti-TNFs – Infliximab/ Etanercepts
-
Non-drug
- OT/PT
- podiatry
- psychological
x-ray features of RA
extra-articular presentations of RA
giant cell arteritis
- Chronic vasculitis of large- and medium-sized vessels that occurs among individuals over 50 yr. of age
- Often referred to as temporal arteritis (TA)
- Most commonly causes inflammation of arteries originating from the arch of the aorta
- Occlusive arteritis can result in anterior ischemic optic neuropathy (AION) and acute visual loss
- Visual symptoms are an ophthalmic emergency
- Inflammation of arteries supplying the muscles of mastication results in jaw claudication and tongue discomfort
- GCA may present as CVA
risk factors for GCA
- Rare in patients <50 yr old (mean age 72)
- Increased prevalence in Northern latitude
- 2 to 4 times more common in women
- Rare in African American patients, common in Whites
- There is a strong association with polymyalgia rheumatica (PMR) ∼50%
- Genetic predisposition: HLA-DR4
presentation of GCA
- Headache
- Localised, unilateral, boring or lancinating in quality ove the temple
- Tongue and jaw claudication upon mastication
- Constitutional symptoms common
- Visual findings may develop weeks to months after onset of other symptoms
- Fugax
- Blindness
- Dipoplia
- Blurring
- Scalp tenderness, esp over temporal after
diagnosis of GCA
Presence of any 2 or more of the following in patients >50 years with:
- Raised ESR, CRP or PV
- New onset of localized headache
- Tenderness or decreased pulsation of temporal artery
- New visual symptoms
- 25-50% of patients who present with acute loss of vision in one eye who go untreated will develop bilateral blindness
- Biopsy revealing necrotizing arteritis
management of GCA
DO NOT DELAY INITATION OF STEROID THERAPY IF VISUAL LOSS- do not delay for biopsy if strong clinical suspicion
- Prednisolone 60–100 mg PO per day for at least 2 weeks before considering tapering down slowly
- For acute onset visual symptoms, consider 1g methylprednisolone IV pulse therapy for the 1–3 days
- Low-dose aspirin therapy to reduce thrombotic risks
polymyalgia rheumatica
- Characterized by pain and stiffness of the shoulder, hip girdles, and neck.
- Patients may use the term stiffness and pain interchangeably.
- Primarily impacts the elderly, associated with morning stiffness and elevated inflammatory markers.
presentation of polymyalgia rheumatica
risk factors for polymyalgia rheumatica
- Incidence increases with age.
- Average age of onset ~70 years
- Rare in people <50 years of age
- Peak incidence is between ages 70 and 80
- Is associated with GCA
history of polymyalgia rheumatica
- Suspect PMR in elderly patients with new sudden onset of proximal limb pain and stiffness (neck, shoulders, hips).
- Difficulty rising from chair or combing hair (proximal muscle involvement)
- Night time pain
- Systemic symptoms in ~25% (fatigue, weight loss, low-grade fever)
physical exam PR
- Decreased range of motion (ROM) of shoulders, neck, and hips
- Muscle strength is usually normal—may be limited by pain and/or stiffness.
- Muscle tenderness
diagnosis of PR
- Decreased range of motion (ROM) of shoulders, neck, and hips
- Muscle strength is usually normal—may be limited by pain and/or stiffness.
- Muscle tenderness
management of PR
- Dramatic diagnostic response within 5 days of starting prednisolone (15mg daily- then taper slowly)
- Rapid taper is associated with symptoms relapse
- Methotrexate can be steroid-sparing in relapsing patients
Spondyloarthropathies
These are a group of conditions that affect the spine and peripheral joints and are associated with the presence of HLA-B27.
examples of spondyloarthropathies
- Ankylosing spondylitis (most common)
- Enteropathic arthritis
- Psoriatic arthritis
- Reactive arthritis
common clinical features of spondyloarthropathies
- Sacroiliac/axial disease (back/buttock pain)
- Inflammatory arthropathy of peripheral joints
- Enthesitis (inflammation at tendon insertions e.g. tennis elbow, achilles))
- Extra-articular features (skin/gut/eye)
psoriatic arthritis
Psoriatic arthritis is a type of arthritis that affects some people with the skin condition psoriasis.
risk factor for psoriatic arthritis
10% of patients with psoriasis (Male=Female)
typical exam findings of psoriatic arthritis
- Oligo-arthritis with dactylitis or “sausage” digit.
- Can be symmetrical arthritis like RA, or mono-arthritis.
- Severe deformities (arthritis mutilans in 5%).
investigation of psoriatic arthritis
CRP often raised. Central joint erosions seen early on u/sd or MRI leading to ‘pencil in cup’ x-ray appearance.
management of psoriatic arthritis
NSAIDs, DMARDs, anti-TNF, IL-17 inhibitors, IL12/23 inhibitors.
anklosing spondyylitis
Ankylosing spondylitis is an inflammatory disease that, over time, can cause some of the bones in the spine (vertebrae) to fuse. This fusing makes the spine less flexible and can result in a hunched posture. If ribs are affected, it can be difficult to breathe deeply.
RF for ankylosing spondylitits
Usually in young men (teens – mid-thirties)
presentation of ankylosing spondylitis
with bilat buttock pain, chest wall and thoracic pain
examination of ankylosing sponylitis
- often normal.
- Later: loss of lumbar lordosis, exaggerated thoracic kyphosis,
- Schober’s test (mark skin 10cm above and 5cm below PSIS, bend forward with straight legs, distance increase to >20cm is normal), reduced chest expansion
investigations for ankylosing spondylitits
- CRP may be raised but often normal.
- MRI spine and SI joints (more sensitive than X-ray).
*
management of AS
NSAIDs and physio, TNF inhibitors, IL-17 inhibitors.
Reactive arthritis
Sterile synovitis developing after a distant infection either post dysentery (Salmonella / Shigella / Campylobacter) or following urethritis/cervicitis (Chlamydia trachomatis)
presentation Reactive arthritis
- few days – 2 weeks post infection, acute asymmetrical lower limb arthritis develops.
- Other features: skin (circinate balanitis, keratoderma blennorrhagica), eye (conjunctivitis, uveitis), enthesitis.
investigations for reactive arthritis
serology/microbiology, inflammatory markers raised, may need joint aspirate to rule out septic/crystal arthritis
treatment for reactive arthritis
- treat infection (this may not improve arthritis). NSAIDs and joint injections. Most will resolve within 2 years. Those that do not (esp if HLA-B27+) may need DMARDs.
enteropathic arthritis
a form of chronic, inflammatory arthritis associated with the occurrence of an inflammatory bowel disease (IBD), the two best-known types of which are ulcerative colitis and Crohn’s disease.
rf for enteric arthritis
10 - 20% of those with IBD develop arthropathy. Of these 2/3 = peripheral arthritis and 1/3 develop axial disease.
enteropathic- how many types of peripheral diseas
- Type 1 = oligoarticular, asymmetric and has a correlation with IBD flares
- Type 2 = polyarticular symmetrical and less correlation with IBD flares
management of enterpathic arthritis
- Remember NSAIDs may flare IBD.
- Consider DMARDs.
- TNF inhibitors will treat both the bowel disease and the arthritis.
systemic lupus erythematous
- autoimmune disease
- inadequate T cell suppressor activity with increased B cell activity
- most patients have antibodies to certain cell nucleus components
- complex multisystem disease with variable presentations
- extremely variable presentations, disease courses, and prognosis
- characterized by remissions and flares.
- can be familial
risk factors for SLE
- 9:1 women (oestrogen)
- Early adulthood
- Black people have worse prognosis
- High CVD risk
common presentation of SLE
- S erositis - Pleurisy, pericarditis
- O ral ulcers - usually painless; palate is most specific
- A rthritis – small joints nonerosive
- P hotosensitivity – or malar or discoid rash
- B lood disorders – low WCC, lymphopenia, thrombocytopenia, hemolytic anemia
- R enal involvement -glomerulonephritis
- A utoantibodies (ANA positive in >90% cases)
- I mmunologic tests e.g. low complements
- N eurologic disorder - Seizures or psychosis
rinvestigations for SLE
- Raised ESR or plasma viscosity
- Anaemia and leukopenia common
- 95% are antinuclear antibody positive
- Anti-Ro and Anti-La are common
- Anti-dsDNA titre increase with disease activity
- Antiphospholipid antibodies increase risk of pregnancy loss and thrombosis
- C3 and C4 fall with disease activity
- Urinalysis for detecting renal disease
- Skin biopsy
- Renal biopsy
treatment for SLE
First line treatments are:
- NSAIDs
- Steroids (prednisolone)
- Hydroxychloroquine (first line for mild SLE)
- Suncream and sun avoidance for the photosensitive malar rash
Other commonly used immunosuppressants in resistant or more severe lupus:
- Methotrexate
- Mycophenolate mofetil
raynauds phenomenon (disease)
This is a condition due to vasospasm of the digits- primary cause. It is painful and is characterized by a typical sequence of colour changes in response to a cold stimulus. It is often also precipitated by stress.
- white- inadequate blood flow
- blue -venous stasis
- red -re-warming hyperaemia.
Raynauds syndrome
- when cause is idiopathic
- young women and may improve when they get older
- may be familial
- avoid smoking
Diseases associated with Raynaud’s phenomenon (secondary)
- RP symptoms developing over age 30 should alert you to underlying disease
- Abnormal nail-fold capillaries or puffy fingers or photosensitive rash suggest rheumatic cause
- Associated with
- Scleroderma
- SLE
- Dermatomyositis and polymyositis
- Sjogrens syndrome
- Physical causes
- Uses of heavy vibrating tools
- Sticky blood e.g. cryoglobulinemia
- Drug induced: b blockers
Treatment of raynauds phenomenon
- Keep warm and don’t smoke
- Nifedipine- CCB first line
- Sildenafil -phosphodiesterase-5 inhibitors (VIAGRA)
complication of raynauds
Complications: digital ulcers, severe digital ischaemia and infection
vasculitis
- Inflammatory blood vessel disorder
- Clinical features result from the damage of blood vessel walls with subsequent thrombosis, ischemia, bleeding, and/or aneurysm formation.
- Vasculitis is a large, heterogeneous group of diseases classified by the predominant size, type, and location of involved blood vessels
history for vasculitis
- Consider age, gender, and ethnicity.
- Comprehensive drug history
- Family history of vasculitis
- Constitutional symptoms: fever, weight loss, malaise, fatigue, diminished appetite, sweats
- Then use the “Glove and sweater” approach
glove and sweater approach
- (Series of questions from hands to head and down to trunk)
- Ask about Raynaud’s
- Musculoskeletal: arthralgia, myalgia, proximal muscle weakness
- CNS/PNS: headaches, visual loss, tinnitus, stroke, seizure, encephalopathy
- Nose bleeds, crusts, ulcers and oral ulcers
- Heart/lung: pericarditis, cough, chest pain, hemoptysis, dyspnea
- GI: abdominal pain
- Renal: Haematuria
- Limbs: Neuropathy, digital ulcers/ischaemia
physical exam vascultitis
- Vital signs: blood pressure (hypertension) and pulse (regularity and rate)
- Skin: palpable purpura, livedo reticularis, nodules, digital ulcers, gangrene, nail bed capillary changes
- Neurologic: cranial nerve exam, sensorimotor exam
- Ocular exam: visual fields, scleritis, uveitis episcleritis
- Cardiopulmonary exam: Crackles, pleural rubs murmurs, arrhythmias
- Abdominal exam: tenderness, organomegaly
vasculitis mimics
Vasculitis occurs as a primary disorder or secondary to infections, drugs, malignancy, or connective tissue diseases.
Secondary vasculitis is much more common than primary.
diagnostic tests for vasculitis
- Initial tests exclude alternate diagnoses and guide therapy FBC, U&Es, LFTs, CRP, PV, ESR,
- Specific serology: ANA, ANCA, RF
- Complement levels C3, C4 Hepatitis screen for B and C, HIV Cryoglobulins
- Serum and urine protein electrophoresis
- Miscellaneous: CK, Blood cultures, ECG
- CXR, CT scan, MRI, arteriography and CT-PET may be required to delineate extent of organ involvement.
treatment of vasculitis
- General Measures: Rule out infection, stop offending drug in secondary causes
- 1st line: Corticosteroids
- 2nd Line: Cytotoxic medications, immunomodulatory, or biologic agents (e.g., cyclophosphamide methotrexate, azathioprine, leflunomide mycophenolate mofetil, rituximab, IVIG)
small vessel vasculitis
- Microscopic polyangiitis (MPA)
- Granulomatosis with polyangiitis (Wegener’s granulomatosis)
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Medium-vessel vasculitis
- Polyarteritis nodosa (PAN)
- Kawasaki disease (KD)
Large-vessel vasculitis
- Takayasu arteritis (TAK)
- Giant cell arteritis (GCA)
Systemic sclerosis (SSc)
- Multisystem autoimmune disease
- Previously known as scleroderma
- Pathophysiology: increased fibroblast activity resulting in abnormal growth of connective tissue which leads to vascular damage and fibrosis
- 2 subsets
- Limited SSc
- Diffuse SSc3
limited scleroderma
- Diffuse skin tightness below knees and below elbows
- Usually years of raynauds before scleroderma
- Development of Pulmonary arterial (PA) hypertension after a mean of 10 years of symptoms
- CREST syndrome
Calcinosis Cutis
Raynaud’s phenomenon
- Ulcers
- White/blue skin
Oesophageal dysmotility
Sclerodactyly
- Very tight skin
Telangiectasia
Diffuse scleroderma
- Less common
- High risk of mortality
- Sudden onset of skin involvement and proximal to the elbow sand knees (can effect anywhere)
investigations for scleroderma
Investigations
- Inflammatory markers usually normal
- X-ray hands- calcinosis
- CXR, HRCT, PFT- pulmonary disease
- ECG and echo- PA hypertension, HF, myocarditis and arrhythmias
- Antibodies
- Positive ANA in 90% of pts
- Anti-centromere antibody strongly associated with limited SSc
- Scl-70 (topoisomerase) and anti RNA polymerase III antibodies strongly associated with diffuse SSc
scleroderma treatment
Treatment
- No cure
- Psychological support
- Calcium antagonist /sildenafil/iloprost infusion for Raynaud’s
- Methotrexate and mycophenolate mofetil may reduce skin thickening
- ACEi prevent hypertensive crisis and reduce mortality from renal failures
- Short courses of prednisolone for flares
- PPI for GI symptoms
Sjogrens syndrome
- Chronic autoimmune inflammatory disorder
- Immune system e.g. lymphocytes target glands that make tears and saliva (maybe triggered by particular virus or bacteria)
- Characterised by diminished lacrimal and salivary gland secretion
- Primary form- not associated with other diseases
- Secondary form- associated with another underlying rheumatic disease
- 80% female
sjogrens presentation
(MADFRED!)
Most pts present with sicca symptoms – xerophthalmia (dry eyes), xerostomia (dry mouth) and fatigue
- Myalgia
- Arthralgia
- Dry mouth
- Fatigue
- Raynauds phenomenon
- Enlarged parotids
- Dry eyes
investigations for sjogrens
- Anti RO and anti La antibodies (90%)
- RF and anti ds-DNA antibodies
- Schirmer’s test- measures tear volume
- Salivary gland biopsy may be needed
treatment for sjogrens
- Symptomatic treatment
- Avoid dry or smoky atmosphere
- Dry eyes- artificial tears
- Dry mouth- artificial saliva, sugar free gum, pastilles
- Skin emollients, vaginal lubricants
- Immunosuppressants/steroids rarely needed
Gout
- Inflammatory arthritis related to a hyperuricemia.
- Acute gout can affect ≥1 joint but the 1st metatarsophalangeal joint is most commonly involved at presentation (podagra).
pathophysiology of gout
- Deposition of monosodium urate (MSU) crystals that accumulate in joints and soft tissues, result in acute and chronic arthritis, soft-tissue masses called tophi, urate nephropathy, and uric acid nephrolithiasis
prognosis of gout
- After an initial flare, a second flare occurs in ~60% of patients within 1 year and 78% within 2 years of the initial attack.
management of gout
- Management involves treating acute attacks and preventing recurrent disease by long-term reduction of SUA levels through medication and lifestyle adjustments.
- Gout is associated with a high risk of CVD.
investigations for gout
- Joint aspiration (MSU crystals- negatively bifringement)
- Blood tests for uric acid
- X-ray
- Urate crystals are negatively birefringent through polarised light (microscope)
risk factors
- Non modifiable: >40 and male
- Modifiable
- Increased purine (meats and seafood)
- Alcohol intake (esp beer)
- High fructose intake
- Obesity
- CHF
- CAD
- Dyslipidaemia
- Renal disease
- Organ transplant
- Hypertension
- Smoking DM
- Urate-elevating medications e.g. diuretics
treatment of acute gout
- General prevention: lose weight, exercise, reduced purine in diet, reduce alcohol consumption, smoking cessation, avoid dehydration
During the acute flare:
- NSAIDs (e.g. ibuprofen) are first-line
- Colchicine second-line
- Colchicine is used in patients that are inappropriate for NSAIDs, such as those with renal impairment or significant heart disease.
- diarrhoea common side effect
- Steroids can be considered third-line
Prophylaxis
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).
treatment of chronic gout
-
Chronic cases: commence urate lowering therapy (ULT) after acute attack
- E.g. allopurinal and febuxostat (xanthine oxidase inhibitors and reduce urate formation)
- Aim to reduce SUA to <360 micromol/L
