Rheumatology Flashcards
(113 cards)
1
Q
arthropathy
A
disease of joint
2
Q
arthritis
A
inflammation of the joint
3
Q
Arthralgia
A
Pain in the joint
4
Q
seropositive arthritis
A
RA, lupus, scleroderma, vasculitis, sjogrens
5
Q
seronegative
A
AS, psoriatic, reactive and IBD
6
Q
OA
A
• Wear and tear with age. Alongside this, associated inflammation can cause periodic flaring of the OA
generally accepted that an imbalance exists between wear and repair of cartilage within joints
Environmental factors, hobbies and type of work may have an influence and joints with abnormal alignment
o Previous injuries = secondary OA
o No definitive cause for primary OA
7
Q
Risk factors for OA
A
- Age
- Female versus male sex
- Obesity
- Muscle weakness
- Proprioceptive deficits
- Genetic elements
- Acromegaly
8
Q
Secondary causes of OA
A
- Congenital dislocation of the hip
- Perthes
- SUFE
- Previous intra‐articular fracture
- Extra‐articular fracture with malunion
- Osteochondral / hyaline cartilage injury
- Crystal arthropathy
- Inflammatory arthritis (can give rise to mixed pattern arthritis)
- Meniscal tears
- Genu Varum or Valgum
9
Q
OA signs/symptoms
A
- Pain – typically worse on activity and relieved by rest. (mechanical pain)
- May progress to be present with less activity and at rest or at night.
- Stiffness – usually morning stiffness lasts less than 30 mins. Inactivity gelling.
- Pain on very minimal movement
10
Q
OA X ray findings
A
L - loss joint space
O - Osteophytes
S- Sclerosis
S - subchondral cyst
11
Q
Clinical features of OA: hands, knee, hip and spine
A
Hand:
• DIP, PIP and 1st CMC joints
• Bony enlargements: DIPs (Heberdens nodes) and PIPs (Bouchards nodes)
• Squaring of the hand
Knee:
• Osteophytes, effusions, crepitus and restriction of movement
• Genu varus (towards the midline) or valgus (away from the midline) deformities
• Bakers cyst
Hip:
• Pain may be felt in groin or radiating to knee
• Pain felt in hip may be radiating from the lower back.
• Hip movements restricted
Spine:
• Cervical – pain and restriction of neck movement
• Lumbar – Pain on standing or walking for some time, osteophytes can cause spinal stenosis if encroach on spinal canal or pinch the nerve root
12
Q
OA Mx
A
Non-pharmacologic:
o Physiotherapy - muscle strengthening, proprioceptive
o ‘Common sense measures’ - weight loss exercise, trainers, walking stick, insoles
Pharmacologic:
o Analgesia – paracetamol, compound analgesics, topical analgesia
o NSAIDs - topical/systemic,
o Pain modulators – tricyclics e.g. amitriptyline, anti-convulsants eg. Gabapentin
o Intra-articular – Steroids, Hyaluronic acid (injections)
Surgical:
o Arthroscopic washout, Loose body, soft tissue trimming.
o Joint replacement
13
Q
Inflammatory arthritis features
A
- Joint pain with associated swelling
- Morning stiffness lasting more than 30 minutes
- Improvement in symptoms with exercise
- Synovitis on examination
- Raised inflammatory markers (CRP and plasma viscosity)
- Extra-articular symptoms
14
Q
RA
A
- Rheumatoid arthritis is an auto‐immune inflammatory symmetric polyarthropathy which most commonly affects the small joints of the hands and feet.
- Larger joints such as the knees, shoulders and elbows can also be affected as the disease progresses.
- Female x3 > Male
- 35-50 years old
- Potential triggers include infections and cigarette smoking.
15
Q
RA pathogenesis
A
Environmental (smoking) causes epigenetic changes and in combination with genetic predisposition and causes altering in DNA transcribing
• Therefore, susceptibility genes lead to conversion of the amino acid arginine into the amino acid citrulline – occurs in synovium
• This results in protein unfolding due to loss of positive charge (change in protein shape)
• Unfolded protein acts as antigen and foreign
• Citrullinated proteins
are recognized by anti-citrullinated peptide antibodies
• The anti-citrullinated peptide antibodies are distributed through the circulation and form immune complexes with citrullinated proteins produced in an inflamed synovium and release of cytokines
• This is associated with the infiltration and activation of neutrophils
• Inflammatory pannus forms which then attacks and denudes articular cartilage leading to joint destruction
• Tendon ruptures and soft tissue damage can occur leading to joint instability and subluxation.
16
Q
RA signs/symptoms
A
- Morning stiffness >30 minutes
- Involvement of small joints of hands and feet (PIPs/MCPs and MTPs):
- Symmetric distribution
- Positive compression tests of metacarpophalangeal(MCP) and metatarsophalangeal (MTP) joints
- Tenosynovitis
- Prolonged: Atlantial-axial sublaxation – cervical cord compression
17
Q
Extra-articular manifestations of RA
A
- Rheumatoid nodules (RA) – anywhere but can be found on pressure points
- Lungs - Pleural effusions, interstitial fibrosis and pulmonary nodules.
- Cardiovascular morbidity and mortality are increased in patients with RA.
- Ocular involvement is common in individuals with RA and includes keratoconjunctivitis sicca, episcleritis, uveitis, and nodular scleritis that may lead to scleromalacia.
18
Q
RA Ix
A
RF and Anti-CCP antibodies
increase in CRP, ESR and PV
X-Ray:
o Early features can include peri-articular osteopenia (bone thinning) and soft tissue swelling.
o Periarticular erosions can occur later in the disease and subluxation .
US: Synovial gout inflammation and synovitis
19
Q
RA Mx
A
DMARD within 3 months
short term: simple analgesia, NSAIDs and Intramuscular/intra-articular and oral steroids.
DMARD: methotrexate (1st line), sulphasalazine, hydroxychloroquine and leflunomide
No responce to DMARD: Biologics
- tender joint count, swollen joint count, CRP/ESR and visual analogue score
need over 5.1 on DAS28 score
At least 2 DMARDs (combination)
Biologic examples
Anti TNF agents- Infliximab, Etanercept, Adalimumab, Certolizumab, Golimumab
T cell receptor blocker-Abatacept.
B cell depletor-Rituximab
IL-6 blocker-Tocilizumab.
JAK inhibitors-Tofacitinib, Baricitinib
Patients can take them in pregnancy – safe to use
20
Q
DMARD side effects
A
o Bone marrow suppression – WBC count – blood tests done regularly and liver is not becoming inflamed o Infection o Liver function derangement o Pneumonitis o Nausea o Teratogenic
21
Q
Biologic side effects
A
o Risk of infection (esp. TB)
o Question over risk of malignancy (esp. skin cancer)
o Contraindicated in certain situations e.g. pulmonary fibrosis, heart failure
22
Q
RA Conservative and surgery Mx
A
• physio, OH, podiatrists and orthotists
Surgery • Synovectomy • Joint replacement • Joint excision • Tendon transfers • Arthrodesis (fusion) • Cervical spine stabilisation
23
Q
Seronegative inflammatory
arthropathies
common extraarticular
A
• Sacroiliitis, uveitis & conjunctivitis, dactylitis (inflammation of a digit) and enthesopathies are common (especially achilles insertional tendonitis and plantar fasciitis)
24
Q
AS
A
- Chronic inflammatory disease of the spine and sacro‐iliac joints which can lead to eventual fusion of the intervertebral joints and SI joints.
- It is part of the seronegative spondyloarthropathy group of conditions relating to the HLA B27 gene.
- Hallmark- Sacroiliac joint involvement (sacroiliitis)
- Over time there is loss of spinal movement and development of a “question mark” spine, with loss of lumbar lordosis and increased thoracic kyphosis
25
AS signs/symptoms
• Back pain (neck, thoracic, lumbar) and stiffness and sacroiliac pain in the buttock region.
o The pain and stiffness is worse with rest and improves with movement.
o It takes at least 30 minutes for the stiffness to improve in the morning and it gets progressively better with activity throughout the day.
• Symptoms can fluctuate with “flares” of worsening symptoms and other periods where symptoms improve.
• Enthesitis
• Peripheral arthritis (shoulders, hips) – rare
• Extra articular features:
o weight loss and fatigue
o Chest pain related to costovertebral and costosternal joints
o Enthesitis is inflammation of the entheses. This is where tendons or ligaments insert in to bone. This can cause problems such as plantar fasciitis and achilles tendonitis.
o Dactylitis is inflammation in a finger or toe.
o Anaemia
o Anterior uveitis
o Aortitis is inflammation of the aorta
o Heart block can be caused by fibrosis of the heart’s conductive system
o Restrictive lung disease can be caused by restricted chest wall movement
o Pulmonary fibrosis at the upper lobes of the lungs occurs in around 1% of AS patients
o Inflammatory bowel disease is a condition associated with AS
26
AS A disease
* Axial Arthritis
* Anterior Uveitis
* Aortic Regurgitation
* Apical fibrosis
* Amyloidosis/ Ig A Nephropathy
* Achilles tendinitis
* Plantar Fasciitis
27
AS Ix
schobers test
• Tragus/occiput to wall
• Chest expansion
• X-rays may show sclerosis and fusion of the sacroiliac joints and bony spurs from the vertebral bodies, known as syndesmophytes, which can bridge the intervertebral disc resulting in fusion, producing a “bamboo spine”.
• MRI shows early disease (bone marrow oedema)
• Inflammatory parameters (ESR, CRP, PV) and HLA B27 -not diagnostic
28
AS Mx
• Physiotherapy (stop spinal fusion), exercise, Bisphosphonates (osteoporosis)
• NSAIDs: can be used to help with for pain. If the improvement is not adequate after 2-4 weeks of a maximum dose then consider switching to another NSAID.
• Steroids can be use during flares to control symptoms. This could oral, intramuscular slow release injections or joint injections.
• DMARDS = no impact on spinal disease, only if peripheral inflammation e.g. MTX, SZP
• anti-TNF inhibitors: Infliximab, Certolizumab, Adalimumab and Etanercept in severe AS
• Only consider biologics if they are not getting vaccination
• Surgery
o reserved for hip and knee arthritis
o Kyphoplasty to straighten out the spine is controversial and carries considerable risk.
29
Psoriatic arthritis
• Inflammatory arthritis associated with psoriasis, but 10 -15% of patients can have PsA without psoriasis
30
Psoriatic arthritis signs/symptoms
asymmetrical oligoarthritis, but may also affect the hands in a pattern similar to RA.
• Sacroiliitis: often asymmetric and may be associated with spondylitis
• Nail involvement (Pitting, onycholysis)
• Dactylitis
• Enthesitis: Achilles tendinitis & Plantar fasciitis
• Extra articular features (eye disease)
• Arthritis of DIP of fingers and toes
• No Rheumatoid nodules
31
Clinical subgroups of psoriatic arthritis
1. Confined to distal interphalangeal joints (DIP) hands/feet
2. Symmetric polyarthritis (similar to RA)
3. Spondylitis (spine involvement) with or without peripheral joint involvement
4. Asymmetric oligoarthritis (2 or 4 joints) with dactylitis
5. Arthritis mutilans – very aggressive and destructive form
32
PA Ix
```
• CRP, PV and ESR, HLA-B27 and negative RF
• X-rays:
o Marginal erosions and “whiskering”
o “Pencil in cup” deformity
o Osteolysis
```
33
PA Mx
• Medical
o NSAIDs
o Corticosteroids/joint injections
o Disease Modifying Drugs (Methotrexate, Sulfasalazine, Leflunomide)
o Anti TNF in severe disease unresponsive to NSAIDs and Methotrexate
o Secukinumab (anti-IL17)
• Non-medical
o Physiotherapy
o Occupational Therapy
o Orthotics, Chiropodist
• Joint replacement can be considered in larger joints which are severely affected and DIP joint fusion can occasionally help.
34
Enteropathic arthritis
inflammatory arthritis involving the peripheral joints and sometimes spine, occurring in patients with inflammatory bowel disease (Crohn’s disease and Ulcerative Colitis).
35
Enteropathic arthritis signs/symptoms
* It tends to be a large joint asymmetrical oligoarthritis
* Worsening of symptoms during flare-ups of inflammatory bowel disease
* GI- loose, watery stool with mucous and blood – up to 20 times per day
* Weight loss, low grade fever
* Eye involvement ( uveitis)
* Skin involvement ( pyoderma gangrenosum)
* Enthesitis ( Archilles tendonitis, plantar fasciitis, lateral epicondylitis)
* Oral- apthous ulcers
36
Enteropathic arthritis Ix
* Upper and lower GI endoscopy with biopsy showing ulceration/ colitis
* Joint aspirate- no organisms or crystals
* Raised inflammatory markers- CRP, PV
* X ray/ MRI showing sacroiliitis and inflammation
* USS showing synovitis/ tenosynovitis – if soft tissue
37
Enteropathic arthritis Mx
* Treat Inflammatory Bowel Disease in order to control arthritis
* NSAID: may exacerbate inflammatory bowel disease. Paracteamol, Cocodamol instead
* Steroids ( oral, intraarticular, intramuscular)
* Disease Modifying Drugs (Methotrexate, Sulfasalazine Azathioprine): agreement with GI
* Anti-TNF- Infliximab, Adalimumab licensed for both Crohn’s disease and inflammatory arthritis – so end up treating both which is good
38
Reactive Arthritis
* Occurs in response to an infection in another part of the body, most commonly genitourinary infections (Chlamydia, Neisseria) or GI infections (Salmonella, Campylobacter).
* Large joints eg the knee become inflamed around 1‐4 weeks following the infection.
* The infection triggers an autoimmune arthropathy.
39
Reactive Arthritis signs/symptoms
* Some patients have a triad of symptoms of urethritis, uveitis or conjunctivits and arthritis known as Reiter’s syndrome (can’t pee, see or climb a tree)
* General Symptoms (fever, fatigue, malaise)
* Asymmetrical monoarthritis or oligoarthritis
* Enthesitis
* Mucocutaneous lesions: Keratodema Blenorrhagica, Circinate balanitis, painless oral ulcer and hyperkeratotic nails
* Ocular lesions (unilateral or bilateral): Conjunctivitis &Iritis
* Visceral manifestations: Mild Renal disease & Carditis
40
Reactive arthritis Ix
* ESR,CRP,PV, FBC, U&Es and HLA B27 (rarely necessary)
* Cultures (blood, urine, stool)
* Joint fluid analysis (rule out infection)
* X-ray of affected joints
* Ophthalmology opinion
41
Reactive arthritis Mx
* Most cases are self‐limiting whilst others (15‐ 30%) are chronic or have frequent relapses.
* NSAIDs
* Corticosteroids: Intra articular (once sepsis ruled out), Oral & Eye drops
* Antibiotics for underlying infection eg respiratory/ GI
* DMARDs (SZP) - If resistant/chronic
* Non medical: Physiotherapy and Occupational therapy
42
Systemic Lupus Erythematosus
* Systemic autoimmune condition that can affect almost any part of the body
* Immune system attacks cells and tissue resulting in inflammation and tissue damage
* Immune complexes form and precipitate causing further immune response
43
SLE Pathogenesis
defect in apoptosis that causes increased cell death and a disturbance in immune tolerance.
• Necrotic cells release nuclear materials which act as auto-antigens
• The defective clearance of the apoptotic cell debris allows for the persistence of nuclear antigens and immune complex production.
• Auto-immunity results from exposure to nuclear and cellular auto-antigens
• B and T cells are stimulated. Autoantibodies are produced
• Complexes of antigens and auto-antibodies form and circulate
• Deposition of immune complexes (clinical manifestations) in basement membrane (skin and kidney) and in small blood vessels
• Activation of complement which attracts leucocytes which release cytokines
• Cytokine release perpetuates inflammation which causes necrosis and scarring
44
SLE signs/symptoms
* Constitutional: fever, fatigue and weight loss
* Musculoskeletal: arthralgia, myalgia (pain) and inflammatory arthritis
* Muco-cutaneous: malar rash, photosensitivity, discoid lupus, subacute cutaneous lupus, oral/nasal ulceration and Raynauds phenomenon.
* Renal: lupus nephritis
* Respiratory: pleurisy, pleural effusion, pneumonitis, pulmonary embolism, pulmonary hypertension, and interstitial lung disease.
* Haematological: leukopenia, lymphopenia, anaemia (may be haemolytic), and thrombocytopenia
* Neuropsychiatric: seizures, psychosis, headache, aseptic meningitis, delirium
* Cardiac: pericarditis, pericardial effusion, pulmonary hypertension, sterile endocarditis and accelerated ischemic heart disease.
* Gastrointestinal: less common but include autoimmune hepatitis, pancreatitis and mesenteric vasculitis
45
SLE Ix
• FBC may show anaemia, leucopenia and thrombocytopenia
Anti-nuclear antibody (ANA)
Anti-dsDNA antibody
Anti-Sm
• Anti Ro (neonatal lupus and congenital heart block), anti-La and anti-RNP - may be seen in SLE but may also be seen in other conditions
• C3/4 levels - low when disease active, especially renal disease – good to monitor
• Urinalysis to look for evidence of glomerulonephritis
o Proteinuria >0.5g in 24 hours
o Biopsy proven nephritis
o Red cell casts
o Creatine and urea will be normal
• Imaging studies may be used to look for evidence of organ involvement
o CT chest for interstitial lung disease
o MRI brain for cerebral vasculitis
o Echo for pericardial effusion.
46
SLE Mx
• For skin disease and arthralgia
o hydroxychloroquine, topical steroids and NSAIDs are commonly used.
• If there is inflammatory arthritis or evidence of some types of organ involvement e.g. pericardial disease or interstitial lung disease
o immunosuppression with medication like azathioprine or mycophenolate mofetil may be required.
o Corticosteroids at moderate doses may also be used, ideally for short periods.
• In severe organ disease e.g. lupus nephritis or CNS lupus
o IV steroids and cyclophosphamide.
• In unresponsive cases other therapies such as IV immunoglobulin and rituximab may be necessary.
• It is common practice to check anti-dsDNA antibodies and complement levels regularly, as these vary with disease activity and may give some warning of a disease flare.
47
Sjogrens syndrome
autoimmune condition characterized by lymphocytic infiltrates in exocrine organs.
• Sjogrens syndrome can be a primary condition or can occur secondary to other autoimmune conditions like RA and SLE.
• At INCREASED RISK OF LYMPHOMA
48
Sjogrens syndrome signs/symptoms
* This typically causes dryness of the eyes and mouth (sicca symptoms).
* Other symptoms include arthralgia, fatigue, vaginal dryness and bilateral parotid gland swelling.
* Unexplained increase in dental caries despite good dental care
49
Sjogrens syndrome Dx
1 Ocular symptoms - Dry eyes for more than 3 months, foreign-body sensation, use of tear substitutes more than 3 times daily
2 Oral symptoms - Feeling of dry mouth, recurrently swollen salivary glands, frequent use of liquids to aid swallowing
3 Ocular signs - Schirmer test performed without anesthesia (< 5 mm in 5 min), positive vital dye staining results
4 Oral signs - abnormal parotid sialography findings, abnormal sialometry findings (unstimulated salivary flow < 1.5 mL in 15 min)
5 Positive minor salivary gland biopsy findings
6 Positive anti–SSA or anti–SSB antibody results (Ro or La antibodies)
* Typical features on a lip gland biopsy.
* ESR/Plasma viscosity/IgG raised
50
Sjogrens syndrome Mx
* Lubricating eyedrops are used and saliva replacement products may be tried.
* Regular dental care is important due to the high risk of caries.
* Pilocarpine can stimulate saliva production but causes side effects such a flushing.
* Hydroxychloroquine can sometimes help with arthralgia and fatigue.
* Other immunosuppression would usually only be used in the context of organ involvement e.g. interstitial lung disease.
51
Systemic sclerosis/scleroderma
• Systemic Sclerosis is a multisystem autoimmune disease characterised by vasculopathy, autoimmunity and fibrosis
52
Systemic sclerosis/scleroderma organ involvement
* Pulmonary hypertension, pulmonary fibrosis and accelerated hypertension leading to renal crisis are important organ manifestations.
* Myocardial disease
* Gut involvement may lead to dysphagia, malabsorption, GORD, Gastric Antral Vascular Ectasia (GAVE) – “Watermelon Stomach” and bacterial overgrowth of the small bowel.
* Inflammatory arthritis and myositis may be seen.
* Renal: Scleroderma Renal Crisis
53
SS Classification
• Limited: skin involved tends to be confined to face, hands, forearms and feet. Organ involvement tends to occur later.
o Anti-centromere antibody association.
o In limited SSc (CREST syndrome—calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), patients develop skin tightening over the face and distal to the elbows and knees and may also have gastroesophageal reflux disease. This type is characterized by slow progression and is often complicated by pulmonary hypertension.
Diffuse: skin changes develop more rapidly and can involve the trunk. Early significant organ involvement.
o Anti-Scl-70 antibody association.
o In generalized SSc with diffuse skin involvement, patients have Raynaud phenomenon and GI complications. This type typically evolves rapidly. Interstitial lung disease and scleroderma renal crisis (malignant hypertension and renal failure) are the major complications.
54
SS Ix
* Auto-antibodies: anti-centromere antibody and anti-Scl-70.
* Organ screening is performed regularly and includes pulmonary function testing, echo and monitoring of renal function.
* Renal disease: Anti RNA polymerase III antibody
55
SS Mx
• Raynauds/digital ulcers
o Calcium Channel Blockers: Nifedipine usually first line treatment
o Others: Fluoxetine, ARBs, Nitrates
o PDE-5 inhibitor: Sildenafil
o Prostacyclin Infusion: Iloprost
o Endothelin Receptor Antagonist: Bosentan
• Renal involvement: ACE inhibitors
• GI involvement: proton pump inhibitors for reflux
• Interstitial lung disease: immunosuppression, usually with Mycophenolate Mofetil and cyclophosphamide (very aggressive disease)
• Pulmonary hypertension
o PDE 5 Inhibitor – Sildenafil/Tadalafil/Vardenafil
o ERA – Bosentan/Ambrisentan/Macitentan
o Eproprostenol infusions
o Oxygen
56
Anti-phospholipid syndrome
* Anti-phospholipid syndrome (APS) is a disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss.
* APS may contribute to an increased frequency of stroke or MI, especially in younger individuals.
* Strokes may develop secondary to in situ thrombosis or embolization that originates from the valvular lesions of Libman-Sacks (sterile) endocarditis, which may be seen in patients with APS.
57
Anti-phospholipid syndrome Dx
* Criteria for antiphospholipid syndrome include pregnancy loss prior to 34 weeks due to eclampsia, pre-eclampsia or with evidence of placental insufficiency.
* Other criteria are 3 pregnancy losses before 10 weeks or one between 10 and 34 weeks with no other explanation.
58
Anti-phospholipid syndrome Ix
* There may be thrombocytopenia and prolongation of APTT (partial thromboplastin time)
* Lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2 glycoprotein may be positive.
59
Anti-phospholipid syndrome Mx
* anti-coagulation for those with an episode of thrombosis.
* In patients with recurrent pregnancy loss low molecular weight heparin is used during pregnancy (warfarin is teratogenic). Sometimes aspirin
* Patients who are found to have positive antibodies but who have never had had an episode of thrombosis do not require anti-coagulation
60
Gout
* Crystal arthropathy (inflammation in the joint) caused by deposition of urate crystals within a joint.
* It is usually due to high serum uric acid levels (hyperuricaemia).
* Uric acid is the final compound in the breakdown of purines in DNA metabolism (adenine & guanine).
* Hyperuricaemia may be due to renal underexcretion (which can be exacerbated by diuretics or renal failure) or due to excessive intake of alcohol, red meat and seafood.
* Inherited conditions: Lesch-Nyhan syndrome (HGPRT)
61
gout signs/symptoms
* intensely painful red, hot swollen joint which may mimic a septic arthritis.
* Symptoms usually last for 7-10 days if untreated then resolve.
* Gouty tophi are painless white accumulations of uric acid which can occur in the soft tissues and occasionally erupt through the skin.
* Chronic gout can result in a destructive erosive arthritis.
62
gout dx
* Uric acid crystals are needle shaped and display negative birefringence (change from yellow to blue when lined across the direction of polarization).
* Raised inflammatory markers
* Serum uric acid raised (may be normal during acute attack)
* X rays
63
Gout Mx
• Acute: NSAIDs, corticosteroids, opioid analgesics
o colchicine for patients who cannot tolerate NSAIDs.
• For sufferers of recurrent attacks or those with joint destruction or tophi
o Allopurinol (xanthine oxidase inhibitor) can prevent attacks but they should not be started until an acute attack has settled as they can potentiate a further flare.
o Febuxostat (xanthine oxidase inhibitor)
o Start 2-4 weeks after acute attack (sUA of under 360 umol/l)
64
Pseudogout
• Another crystal arthropathy causing an acute arthritis but, in contrast to gout, it is caused by calcium pyrophosphate crystals.
• The term chondrocalcinosis is used when calcium pyrophosphate deposition occurs in cartilage and other soft tissues in the absence of acute inflammation.
• Both come under the umbrella of Calcium Pyrophosphate Deposition disease (CPPD).
o CPPD tends to affect the knee, wrist and ankle.
• The exact cause is unknown and it can coexist with hyperparathyroidism, hypothyroidism, renal osteodystrophy, haemochromatosis and Wilson’s disease
65
Pseudogout Dx
* Calcium pyrophosphate crystals- envelope shaped/rhomboid, mildly positively birefringent
* Marked rise in inflammatory markers
* X – ray
66
Pseudogout Mx
* NSAIDs, corticosteroids (systemic and intra‐articular) and occasionally colchicine.
* There are no medications used as prophylaxis to prevent recurrence
67
Calcium Hydroxyapatite crystal disease
“Milwaukee shoulder”
Hydroxyapatite crystal deposition in or around the joint.
Release of collagenases, serine proteinases and IL-1
Females, 50-60 years
68
Calcium Hydroxyapatite crystal disease Mx
NSAIDs
Intra-articular steroid injection
Physiotherapy
Partial or total arthroplasty
69
Inflammatory myopathies
Polymyalgia Rheumatica
Fibromyalgia
* Inflammatory myopathies: Characterised by weakness
* Polymyalgia Rheumatica: Characterised by pain and stiffness
* Fibromyalgia: Characterised by pain and fatigue
70
Polymyalgia rheumatica
* Common chronic inflammatory condition – no unknown aetiology
* Occurs almost exclusively in those over 50 years
* Associated with temporal arteritis/ giant cell arteritis (15%)
71
PR signs/symptoms
• Ache in shoulder and hip girdle – proximal muscle weakness (more than 1 hour)
• Morning stiffness and usually symmetrical
• Fatigue, anorexia, weight loss and fever may occur
• Reduced movement of shoulders, neck and hips
o Active movement (patient moves joint themselves) – it will be sore for patient
o Passive movement (you use move it) – wont be sore as there is not joint issues as it is a muscle disease
• Muscle strength is normal
72
PR Dx and Mx
Dx: raised CRP, pV and ESR
Mx
• Symptoms respond very dramatically to low dose steroids (prednisolone 15mg daily) and this is sometimes used as a diagnostic tool.
• Prednisolone dose is gradually reduced over the course of around 18 months.
73
Giant cell arteritis
* GCA is the most common form of systemic vasculitis in adults.
* It is of unknown aetiology and occurs in older patients.
* GCA is marked by transmural inflammation of the intima, media, and adventitia of affected arteries, as well as patchy infiltration by lymphocytes, macrophages, and multinucleated giant cells.
* Vessel wall thickening can result in arterial luminal narrowing, resulting in subsequent distal ischemia.
74
Giant cell arteritis signs/symptoms
* The headache is usually continuous and located in the temporal or occipital areas.
* Focal tenderness on direct palpation is typically present.
* The patient may note scalp tenderness with hair combing.
* Temporal artery is thickened and prominent/tender to touch
* Jaw claudication is noted as fatigue or discomfort of the jaw muscles during chewing of firm foods such as meat or prolonged speaking. Jaw claudication is almost pathognomonic of temporal arteritis, and it is a result of ischemia of the maxillary artery.
* Unilateral visual blurring or vision loss, often painless, or occasionally diplopia. Alternatively, a partial field defect may progress to complete blindness over days.
* Fatigue, malaise and fever – common
75
GCA dx and Mx
• ESR, CRP or plasma viscosity elevated
• Temporal ultrasound
• Temporal artery biopsy
o mononuclear infiltration or granulomatous inflammation, usually with multinucleated giant cells.
```
Mx
• Prednisolone
o 40mg if no visual impairment
o 60mg if visual symptoms.
• The prednisolone dose is gradually tapered over around 2 years.
```
76
Polymyositis and dermatomyositis
• Polymyositis is an idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness in the upper and lower extremities
o Insidious onset and myalgia
• Dermatomyositis is clinically similar but also has typical cutaneous manifestations.
77
Polymyositis and dermatomyositis pathology
* T-cell–mediated cytotoxic process directed against unidentified muscle antigens.
* CD8 T cells, along with macrophages, initially surround healthy nonnecrotic muscle fibers and eventually invade and destroy them
* Antibodies unique to myositis (anti-Jo-1, anti-SRP antibodies).
78
Polymyositis and dermatomyositis signs/symptoms
* Muscle weakness (Insidious onset, worsening over months). Usually symmetrical, proximal muscles
* Often specific problems eg difficulty brushing hair, climbing stairs, out of chair, higher shelves – difficult to do
* Myalgia in 25-50% (usually mild)
* Lung: Interstitial lung disease (10%) and respiratory muscle weakness
* Oesophageal: Dysphagia: Bulbar weakness – swallowing difficulties
* Cardiac: Myocarditis
* Other: Fever, weight loss (significant indicates possible malignancy), Raynauds phenomenon, inflammatory arthritis
Dermatomyositis: signs/symptoms: same as above however
• Gottrons sign – back of the hand and MCP and PIP joints – rash (papula)
• Heliotrope rash – swelling and purple rash
• Shawl sign – V shaped rash
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dermatomyositis malignancy
breast, ovarian, lung, colon, oesophagus and bladder
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Polymyositis and dermatomyositis Ix and Mx
* Muscle wasting, confrontation and isotonic testing
* Inflammatory markers are often raised e.g. CRP, ESR and PV
* Electrolytes, calcium, PTH, TSH (to exclude other causes)
* Serum creatine kinase (CK) level is usually raised (10 times the normal level)
* Autoantibodies include ANA, anti-Jo-1 and anti-SRP.
* MRI may be useful to localize the extent of muscle involvement and show signal intensity abnormalities of muscle due to inflammation, oedema, or scarring.
* EMG is abnormal is 90% of patients: increased fibrillations, abnormal motor potentials, complex repetitive discharges
* Muscle biopsy (gold standard). Perivascular inflammation and muscle necrosis
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Mx
• Prednisolone (initially 40mg)
• Immunosuppressive drugs (methotrexate or azathioprine)
o Azathioprine
o Methotrexate
o Ciclosporin
o IV immunoglobulin
o Rituximab – B cell inhibitor
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Fibromyalgia
unexplained condition causing widespread chronic muscle pain and fatigue.
• It is commonest in young and middle-aged women but can affect anyone.
• It is thought to be a disorder of central pain processing or a syndrome of central sensitivity.
• Patients tend to have a lower threshold of pain and of other stimuli, such as heat, noise, and strong odours.
• Although the pathogenesis of fibromyalgia is not completely understood, research shows biochemical, metabolic, and immunoregulatory abnormalities.
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Fibromyalgia signs/symptoms
• Persistent (≥ 3 months) widespread pain (pain/tenderness on both sides of the body, above and below the waist, and includes the axial spine
• Fatigue; disrupted and unrefreshing sleep
• Cognitive difficulties
• Multiple other unexplained symptoms, anxiety and/or depression, and functional impairment of activities of daily living (ADLs)
o Associated with depression, IBS and migraine
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Fibromyalgia Ix and Mx
important to rule out other conditions hypothyroidism, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyalgia rheumatica, or another inflammatory or autoimmune disorders
Mx
• learn self-management techniques and understand the condition.
multiple normal investigations , which can be a source of great frustration and can compound symptoms
• Exercise and activity pacing
• Atypical analgesia including tricyclics (e.g. amitriptyline), gabapentin and pregabalin may be of benefit.
• Cognitive behavioural therapy
• Complementary medicine eg. acupuncture
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Vasculitis
vessel wall thickening, stenosis, and occlusion with subsequent ischemia and necrosis
• Primary vasculitis results from an inflammatory response that targets the vessel walls and has no known cause. Sometimes this is autoimmune.
• Secondary vasculitis may be triggered by an infection, a drug, or a toxin or may occur as part of another inflammatory disorder or cancer.
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Large vessel vasculitis
• The term ‘large vessel vasculitis’ applies to primary vasculitis that causes chronic granulomatous inflammation predominantly of the aorta and its major branches
• The two major categories of large vessel vasculitis are temporal (giant cell) arteritis and Takayasu arteritis (TA).
• TA can also affect pulmonary arteries
• These arteritides differ in the age of onset
o Giant cell (temporal) = over 50
o TA = before the age of 40
• GCA typically affects the temporal arteries but may also (or only) affect the large vessels.
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Large cell vasculitis signs/symptoms
* Early features: Fever, malaise, night sweats, weight loss, arthralgia and fatigue.
* Later: Claudication symptoms – upper and lower limbs
* If untreated, vascular stenosis and aneurysms can occur.
* These large vessels and their branches can swell and form aneurysms or become narrowed and blocked. This leads to it’s other name of “pulseless disease”.
* This results in reduced pulses and bruits (carotid artery
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Large cell vasculitis Dx
* ESR, PV and CRP increase
* CT/MR angiography to detect thickened vessel walls and stenosis
* Doppler ultrasound of the carotids can be useful in detecting carotid disease.
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Large cell vasculitis Mx
• Corticosteroids (40-60mg prednisolone) – reduce gradually
• Methotrexate and azathioprine can be added
o Leflunamide and methotrexate
• Tocilizumab: interleukin-6 receptor (IL-6R).
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Kawasaki Disease with signs/symptoms
Medium vessel vasculitis
children <5 years
no clear cause
* Persistent high fever > 5 days
* Erythematous rash
* Bilateral conjunctivitis
* Erythema and desquamation (skin peeling) of palms and soles
* “Strawberry tongue” (red tongue with prominent papillae)
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Kawasaki Disease Mx
aspirin and IV Immunoglobulins
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Polyarteritis Nodosa
medium vessel vasculitis.
• It is most associated with hepatitis B but can also occur without a clear cause or with hepatitis C and HIV.
• It affects the medium sized vessels in locations such as the skin, gastrointestinal tract, kidneys and heart.
• This can cause renal impairment, strokes and myocardial infarction.
• It is associated with a rash called livedo reticularis. This is a mottled, purplish, lace like rash.
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Small vessel vasculitis common features
* Fever and weight loss
* A raised, non-blanching purpuric rash
* Arthralgia/arthritis
* Mononeuritis multiplex
* Glomerulonephritis
* Lung opacities on x-ray
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Granulomatosis with polyangiitis (GPA) or Wegeners main signs/symptoms
• It affects the respiratory tract and kidneys.
nose bleeds (epistaxis) and crusty nasal secretions, ears causing hearing loss and sinuses causing sinusitis. A classic sign in exams is the saddle shaped nose due to a perforated nasal septum. This causes a dip halfway down the nose.
• In the lungs it causes a cough, wheeze and haemoptysis.
• A chest xray may show consolidation and it may be misdiagnosed as pneumonia.
• In the kidneys it can cause a rapidly progressing glomerulonephritis.
Cutaneous ulcers
Palpable purpra
Mononeuritis multiplex
Sensorimotor polyneuropathy
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Granulomatosis with polyangiitis (GPA) or Wegeners: p or c -ANCA
cANCA
Proteinase-3
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Eosinophilic granulomatosis with polyangiitis (EGPA) – churg strauss syndrome
* Many features of EGPA similar to those of GPA.
* Main difference: This condition is characterised by late onset asthma, rhinitis and a raised peripheral blood eosinophil count.
* Neurological symptoms such as mono neuritis multiplex are common.
ACR criteria (should have 4 or more)
• Asthma (wheezing, expiratory rhonchi)
• Eosinophilia of more than 10% in peripheral blood
• Paranasal sinusitis
• Pulmonary infiltrates (may be transient)
• Histological proof of vasculitis with extravascular eosinophils
• Mononeuritis multiplex or polyneuropathy
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Microscopic polyangiitis
glomerulonephritis, which occurs in up to 90% of patients.
• Microscopic polyangiitis is a small vessel vasculitis.
• The main feature of microscopic polyangiitis is renal failure.
• It can also affect the lungs causing shortness of breath and haemoptysis
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small vessel vasculitis Ix
• FBC, liver and renal profile and inflammatory markers
o SR, PV and CRP and raised
o Anaemia of chronic disease is common
o U+E looking for renal involvement
• Urinalysis (looking for renal vasculitis)
• CXR
• Biopsy of an affected area e.g. skin or kidney is often helpful in confirming the diagnosis
• Nerve conduction studies
• Anti-neutrophil cytoplasmic antibody (ANCA)
o C-ANCA is usually directed against proteinase 3 (PR3)
o P-ANCA is usually directed again myeloperoxidase (MPO).
• C-ANCA is specific to Granulomatosis with polyangiitis (GPA, used to be called Wegener`s granulomatosis) and is the more specific of the two.
• P-ANCA is seen in eosinophilic granulomatosis with polyangiitis (used to be called Churg-Strauss syndrome) & microscopic polyangiitis,
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small vessel vasculitis Mx
• Steroids can be administered to target the affected area:
o Oral (i.e. prednisolone)
o Intravenous (i.e. hydrocortisone)
o Nasal sprays for nasal symptoms
o Inhaled for lung involves (e.g. Churg-Strauss syndrome)
Immunosuppressants that are used include:
o Cyclophosphamide
o Methotrexate
o Azathioprine
o Rituximab and other monoclonal antibodies
Most cases of ANCA associated vasculitis require treatment with IV steroids and cyclophosphamide due to their aggressive disease course.
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Small vessel vasculitis Mx scale
Localised/early systemic: Methotrexate and steroids
Generalised/systemic: Cyclophosphamide + steroids (1st)
Rituximab + steroids (alt)
Plasma exchange if creatine >500
Refractory: IV immunoglobulins + Rituximab
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Henoch-Schonlein purpura
acute immunoglobulin A (IgA)–mediated disorder characterized by a generalised vasculitis involving the small vessels of the skin, the gastrointestinal (GI) tract, the kidneys, the joints, and, rarely, the lungs and the central nervous system (CNS).
• It commonly affects children.
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Henoch-Schonlein purpura signs/symptoms
* Commonly a history of an upper respiratory tract infection (most common is group A streptococcus) predates the symptoms by a few weeks.
* Purpuric rash typically over buttocks and lower limbs
* Colicky abdominal pain
* Bloody diarrhoea
* Joint pain +/- swelling
* Renal involvement (50%)
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Investigations for HSP
Urine dipstick
FBC, liver and renal profile and inflammatory markers
ANCA and specific antibodies, connective tissue disease, complement levels
Imaging – CT
Nerve conduction tests
Tissue biopsy
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HSP Mx
Usually self-limiting
Symptoms tend to resolve within 8 weeks
Relapses may occur for months to years
Essential to perform urinalysis to screen for renal involvement
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Osteoporosis
reduction in the density of the bones.
• Progressive systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
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Osteoporosis Risk factors
• Older age
• Female
• Reduced mobility and activity
• Low BMI (<18.5 kg/m2)
• Rheumatoid arthritis
• Alcohol and smoking
• Long term corticosteroids
• Other medications such as SSRIs, PPIs, anti-epileptics and anti-oestrogens
• Post-menopausal women
o Oestrogen is protective against osteoporosis.
o Unless they are on HRT postmenopausal women have less oestrogen.
o They also tend to be are older and often have other risk factors for osteoporosis
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assessing osteoporosis
FRAX tool: 10 year percentage probability of major oseto fracture or hip fracture
- women > 65
- men >75
- Younger patients with risk factors such as a previous fragility fracture, history of falls, low BMI, long term steroids, endocrine disorders and rheumatoid arthritis.
Results
o Low risk – reassure
o Intermediate risk – offer DEXA scan and recalculate the risk with the results
o High risk – offer treatment
DEXA Scan
• Z scores represent the number of standard deviations the patients bone density falls below the mean for their age.
• T scores represent the number of standard deviations below the mean for a healthy young adult their bone density is.
Bloods: U&E, LFTs, bone biochem, FBC, PV and TSH
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Consider:
o Protein electrophoresis/Bence Jones proteins – myeloma
o Coeliac antibodies – malabsorption
o Testosterone
o 25OH Vitamin D
o PTH
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Osteoporosis Mx
Lifestyle changes
Vitamin D and Calcium supplementation
Bisphosphonates e.g. Alendronate 70mg weekly, risedronate 35mg orally weekly
Zolendronic acid 5mg IV yearly
Denoxumab: blocks osteoclasts
Strontium ranelate: stimulates osteoblasts and blocks osteoclasts but increases the risk of DVT, PE and myocardial infarction.
Raloxifene is used as secondary prevention only. It is a selective oestrogen receptor modulator that stimulates oestrogen receptors on bone but blocks them in the breasts and uterus.
Hormone replacement therapy should be considered in women that go through the menopause early.
Teriparatide: Recombinant parathyroid hormone (1-34)
Stimulates bone growth rather than reducing bone loss – anabolic agent
Consider if severe osteoporosis - particularly if high risk of vertebral fracture. Daily injection
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Osteoporosis follow up
* Low risk patients not being put on treatment should be given lifestyle advice and followed up within 5 years for a repeat assessment.
* Patients on bisphosphonates should have a repeat FRAX and DEXA scan after 3-5 years and a treatment holiday should be considered if their BMD has improved and they have not suffered any fragility fractures.
* This involves a break from treatment of 18 months to 3 years before repeating the assessment.
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Osteomalacia
* Osteomalacia is a condition where there is defective bone mineralisation causing “soft” bones.
* This results from insufficient vitamin D.
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Osteomalacia pathology
* The kidneys are essential in metabolising vitamin D to its active form, therefore vitamin D deficiency is common in chronic kidney disease.
* Vitamin D is essential in calcium and phosphate absorption from the intestines and kidneys. Vitamin D is also responsible for regulating bone turnover and promoting bone reabsorption to boost the serum calcium level.
* Inadequate vitamin D leads to a lack of calcium and phosphate in the blood. Since calcium and phosphate are required for the construction of bone, low levels result in defective bone mineralisation.
* Low calcium causes a secondary hyperparathyroidism as the parathyroid gland tries to raise the calcium level by secreting parathyroid hormone.
* Parathyroid hormone stimulates increased reabsorption from the bones. This causes further problems with bone mineralisation
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Osteomalacia signs/symptoms
* Asymptomatic
* Fatigue
* Bone pain
* Muscle weakness
* Muscle aches
* Pathological or abnormal fractures
* Looser zones are fragility fractures that go partially through the bone.
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Osteomalacia Ix
Serum 25-hydroxyvitamin D
o <25 nmol/L – vitamin D deficiency
o 25 – 50 nmol/L – vitamin D insufficiency
o 75 nmol/L or above is optimal
• Serum calcium is low
• Serum phosphate is low
• Serum alkaline phosphatase may be high
• Parathyroid hormone may be high (secondary hyperparathyroidism)
• Xrays may show osteopenia (more radiolucent bones)
• DEXA scan shows low bone mineral density
Treatment
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Osteomalacia Mx
• Treatment is with supplementary vitamin D (colecalciferol).
o 50,000 IU once weekly for 6 weeks
o 20,000 IU twice weekly for 7 weeks
o 4000 IU daily for 10 weeks
• A maintenance supplementary dose for of 800 IU or more per day should be continued for life after the initial treatment.
• Patients with vitamin D insufficiency can be started on the maintenance dose without the initial treatment regime.
