PassMed Flashcards
(185 cards)
1
Q
How many types of ANCA are there?
A
There are two main types of anti-neutrophil cytoplasmic antibodies (ANCA) - cytoplasmic (cANCA) and perinuclear (pANCA)
2
Q
What is cANCA associated with?
A
- Granulomatosis with polyangiitis, positive in > 90%
- Microscopic polyangiitis, positive in 40%
3
Q
What is pANCA associated with?
A
- Microscopic polyangiitis, positive in 50-75%
- Churg-Strauss syndrome, positive in 60%
- Primary sclerosing cholangitis, positive in 60-80%
- Granulomatosis with polyangiitis, positive in 25%
- Immune crescentic glomerulonephritis (positive in c. 80% of patients)
4
Q
What is the most common target of cANCA?
A
Serine proteinase 3 (PR3)
5
Q
What is the most common target of pANCA?
A
Myeloperoxidase (MPO)
6
Q
ANCA levels and disease activity?
A
- Some correlation between cANCA levels and disease activity
- Cannot use level of pANCA to monitor disease activity
7
Q
Other causes of positive ANCA (usually pANCA)?
A
- Inflammatory bowel disease (UC > Crohn’s)
- CTDs: RA, SLE, Sjogren’s
- Autoimmune hepatitis
8
Q
What is ankylosing spondylitis?
A
- HLA-B27 asociated seronegative spondyloarthropathy
- It typically presents in males (sex ratio 3:1) aged 20-30 years old
9
Q
Features - AS
A
- Typically a young man who presents with lower back pain and stiffness of insidious onset
- Stiffness is usually worse in the morning and improves with exercise
- The patient may experience pain at night which improves on getting up
10
Q
Clinical presentation - AS (on examination)
A
- Reduced lateral flexion
- Reduced forward flexion
- Reduced chest expansion
- Loss of lumbar lordosis
- Schober’s <5cm
11
Q
Schober’s test
A
A line is drawn 10 cm above and 5 cm below the back dimples (dimples of Venus). The distance between the two lines should increase by more than 5 cm when the patient bends as far forward as possible
12
Q
‘A’s’ of AS
A
-Apical fibrosis
-Anterior uveitis
-Aortic regurgitation
-Achilles tendonitis
-AV node block
-Amyloidosis
and cauda equina syndrome
-Peripheral arthritis (25%, more common if female)
13
Q
Ix - AS
A
- Bloods: inflammatory markers (ESR,CRP): typically raised although normal levels do not exclude ankylosing spondylitis
-HLA-B27 is of little use in making the diagnosis as it is positive in:
90% of patients with ankylosing spondylitis
10% of normal patients
-Plain x-ray: key in diagnosis
14
Q
X-ray changes - AS
A
Radiographs may be normal early in disease, later changes include:
- sacroilitis: subchondral erosions, sclerosis
- squaring of lumbar vertebrae
- ‘bamboo spine’ (late & uncommon)
- syndesmophytes: due to ossification of outer fibers of annulus fibrosus
- chest x-ray: apical fibrosis
15
Q
Spirometery - AS
A
May show restrictive deficit due to fibrosis, kyphosis and ankylosis of costovertebral joints
16
Q
Management - AS
A
- Encourage regular exercise such as swimming
- Physiotherapy
- NSAIDs are the first-line treatment (once two courses of NSAIDs have failed, can consider anti-TNF therapy)
- DMARDs haven’t shown to be useful in AS - only useful if there is peripheral joint involvement
17
Q
Antiphospholipid syndrome
A
Acquired disorder characterised by a predisposition to:
1) both venous and arterial thromboses
2) recurrent fetal loss
3) thrombocytopenia
18
Q
APS - primary or secondary?
A
It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
19
Q
APS and APTT levels
A
APS causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade
20
Q
APS - features
A
1) venous/arterial thrombosis
2) recurrent fetal loss
3) livedo reticularis
4) thrombocytopenia
5) prolonged APTT
6) other features: pre-eclampsia, pulmonary hypertension
21
Q
Associations - APS
A
- SLE
- Other autoimmune disorders
- Lymphoproliferative disorders
- Phenothiazines (rare)
22
Q
Rx - APS
A
1) Initial venous thromboembolic events: evidence currently supports use of warfarin with a target INR of 2-3 for 6 months
2) Recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then increase target INR to 3-4
3) Arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
23
Q
Antisynthetase syndrome
A
Antisynthetase syndrome is caused by autoantibodies against aminoacyl-tRNA synthetase e.g. anti-Jo1
24
Q
Antisynthetase syndrome- features (4)
A
1) Myositis
2) ILD
3) Thickened and cracked skin of the hands (mechanic’s hands)
4) Raynaud’s phenomenon
25
Azathioprine - adverse side effects
- Bone marrow depression
- Nausea/vomiting
- Pancreatitis
26
Allopurinol and azathioprine
A significant interaction may occur with allopurinol and hence lower doses of azathioprine should be used
27
Bechet's syndrome - what is it?
Complex multisystem disorder associated with presumed autoimmune mediated inflammation of the arteries and veins
28
Bechet's syndrome - classic triad
Oral ulcers, genital ulcers and anterior uveitis
29
Other features - Bechet's syndrome
- Thrombophlebitis
- Arthritis
- Neurological involvement (e.g. aseptic meningitis)
- GI: abdo pain, diarrhoea, colitis
- Erythema nodosum, DVT
30
Epidemiology - Bechet's
- More common in the eastern Mediterranean (e.g. Turkey)
- More common in men + often more severe
- Tends to affect young adults (e.g. 20 - 40 years old)
- Associated with HLA B5 and MICA6 allele
- Around 30% of patients have a positive family history
31
Diagnosis - Bechet's
- No definitive test
- Diagnosis based on clinical findings
- Positive pathergy test is suggestive (puncture site following needle prick becomes inflamed with small pustule forming)
32
Clinical uses of bisphosphonates
- Prevention and treatment of osteoporosis
- Hypercalcaemia
- Paget's disease
- Pain from bone metatases
33
Adverse effects - bisphosphonates
- Oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
- Osteonecrosis of the jaw
- Increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate
- Acute phase response: fever, myalgia and arthralgia may occur following administration
- Hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant
34
How should one take bisphosphonates?
Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an empty stomach at least 30 minutes before breakfast (or another oral medication); patient should stand or sit upright for at least 30 minutes after taking tablet
35
Chronic fatigue syndrome
- Diagnosed after at least 4 months of disabling fatigue affecting mental and physical function more than 50% of the time in the absence of other disease which may explain symptoms
- More common in females
36
Chronic fatigue syndrome - features (12)
1) Fatigue - central feature
2) Sleep problems, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake cycle
3) Muscle and/or joint pains
4) Headaches
5) Painful lymph nodes without enlargement
6) Sore throat
7) Cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of short-term memory, and difficulties with word-finding
8) Physical or mental exertion makes symptoms worse
9) General malaise or 'flu-like' symptoms
10) Dizziness
11) Nausea
12) Palpitations
37
Chronic fatigue syndrome - Ix
Exclude other pathology:
| FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin*, coeliac screening and also urinalysis
38
Chronic fatigue syndrome - Rx
- CBT
- Graded exercise therapy
- 'Pacing' - organising activities to avoid tiring
- Low-dose amitriptyline may be useful for poor sleep
- Referral to a pain management clinic if pain is a predominant feature
39
What is dactylitits?
Inflammation of a digit (finger or toe)
40
Causes of dactylitis?
- Spondyloarthritis: e.g. Psoriatic and reactive arthritis
- Sickle-cell disease
- Other rare causes include tuberculosis, sarcoidosis and syphilis
41
Dermatomyositis - overview
- Inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions
- May be idiopathic or associated with connective tissue disorders or underlying malignancy
- Polymyositis is a variant of the disease where skin manifestations are not prominent
42
Dermatomyositis - underlying malignancy?
Typically ovarian, breast and lung cancer, found in 20-25% - more if patient older
43
Dermatomyositis - skin features
1) Photosensitive
2) Macular rash over back and shoulder
3) Heliotrope rash in the periorbital region
4) Gottron's papules - roughened red papules over extensor surfaces of fingers
5) Nail fold capillary dilatation
44
Dermatomyositis - other features
1) Proximal muscle weakness +/- tenderness
2) Raynaud's
3) Respiratory muscle weakness
4) Interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia
5) Dysphagia, dysphonia
45
Ix - dermatomyositis
Majority of patients are ANA positive, with around 25% anti-Mi-2 positive
46
Drug-induced lupus
In drug-induced lupus not all the typical features of systemic lupus erythematosus are seen, with renal and nervous system involvement being unusual. It usually resolves on stopping the drug
47
Drug-induced lupus features
1) Arthralgia
2) Myalgia
3) Skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
48
Drug-induced lupus - immunology
- ANA positive in 100%, dsDNA negative
- Anti-histone antibodies are found in 80-90%
- Anti-Ro, anti-Smith positive in around 5%
49
Causes of drug-induced lupus
Most common causes
- Procainamide
- Hydralazine
Less common causes
- Isoniazid
- Minocycline
- Phenytoin
50
Ehler-Danlos syndrome
Autosomal dominant connective tissue disorder that mostly affects type III collagen
51
Ehler-Danlos syndrome - features
1) Elastic, fragile skin
2) Joint hypermobility: recurrent joint dislocation
3) Easy bruising
4) Aortic regurgitation, mitral valve prolapse and aortic dissection
5) Subarachnoid haemorrhage
6) Angioid retinal streaks
52
Fibromyalgia - overview
- Characterised by widespread pain throughout the body with tender points at specific anatomical sites
- More common in females (5:1)
- Typically affects those 30-50 years
53
Fibromyalgia - features
- Chronic pain: at multiple site, sometimes 'pain all over'
- Lethargy
- Cognitive impairment: 'fibro fog'
- Sleep disturbance, headaches, dizziness are common
54
Rx - fibromyalgia
A psychosocial and multidisciplinary approach is helpful
- CBT
- Graded exercise exposure
- Education
- Medication: pregabalin, duloxetine, amitriptyline
55
Gout
- Inflammatory arthritis
- Patients typically have episodes lasting several days when their gout flares and are often symptom free between episodes
- The acute episodes typically develop maximal intensity within 12 hours
56
Gout - main features
- Pain: this is often very significant
- Swelling
- Erythema
- Around 70% of first presentations affect the 1st metatarsophalangeal (MTP) joint
- If untreated repeated acute episodes of gout can damage the joints resulting in a more chronic joint problem
57
Other joints affected by gout
- Ankle
- Wrist
- Knee
58
Radiological features - gout
- Joint effusion is an early sign
- Well-defined 'punched-out' erosions with sclerotic margins ina juxta-articular distribution, often with overhanging edges
- Relative preservation of joint space until late disease
- Eccentric erosions
- No periarticular osteopaenia (in contrast to RA)
- Soft tissue tophi may be seen
59
What is gout?
Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricaemia (uric acid > 0.45 mmol/l)
60
What can predispose you to gout?
- Decreased excretion of uric acid
- Increased production of uric acid
- Lesch-Nyhan syndrome
61
Decreased excretion of uric acid
- Drugs: diuretics
- Chronic kidney disease
- Lead toxicity
62
Increased production of uric acid
- Myeloproliferative/lymphoproliferative disorder
- Cytotoxic drugs
- Severe psoriasis
63
Lesch-Nyhan syndrome
- Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency
- x-linked recessive therefore only seen in boys
- Features: gout, renal failure, neurological deficits, learning difficulties, self-mutilation
64
HLA antigens
- Encoded for by genes on chromosome 6. HLA A, B and C are class I antigens whilst DP, DQ, DR are class II antigens
65
HLA-A3
Haemochromatosis
66
HLA-B5
Behcet's disease
67
HLA-B27
- Ankylosing spondylitis
- Reiter's syndrome
- Acute anterior uveitis
68
HLA-DQ2/DQ8
Coeliac disease
69
HLA-DR2
- Narcolepsy
| - Goodpasture's
70
HLA-DR3
- Dermatitis herpetiformis
- Sjogren's syndrome
- Primary biliary cirrhosis
71
HLA-DR4
- T1DM (also associated w/ DR3)
| - RA
72
What is hydroxychloroquine used to manage?
Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus erythematosus
73
Side effects of hydroxychloroquine
- Bull's eye retinopathy - may result in severe and permanent visual loss
- Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart
74
Costochondritis
- Costochondritis is a common condition that leads to non-cardiac type chest pain
- It is often reproducible on palpation and worsened by certain movements
75
What is lateral epicondylitis?
- Follows unaccustomed activity such as house painting or playing tennis ('tennis elbow')
- It is most common in people aged 45-55 years and typically affects the dominant arm
76
What are the typical features of lateral epicondylitis?
- Pain and tenderness localised to the lateral epicondyle
- Pain worse on wrist extension against resistance with the elbow extended or supination of the forearm with the elbow extended
- Episodes typically last between 6 months and 2 years
- Patients tend to have acute pain for 6-12 weeks
77
Rx - lateral epicondylitis
- Advice on avoiding muscle overload
- Simple analgesia
- Steroid injection
- Physiotherapy
78
Leflunomide - what it is used to treat?
DMARD) mainly used in the management of rheumatoid arthritis. It has a very long half-life which should be remembered considering it's teratogenic potential.
79
Leflunomide - pregnancy?
Effective contraception essential during treatment and for at least 2 years after treatment in women and at least 3 months after treatment in men (plasma concentration monitoring required)
80
Side effects - Leflunomide
- GI, especially diarrhoea
- HTN (need to monitor BP)
- Weight loss/anorexia
- Peripheral neuropathy
- Myelosuppression
- Pneumonitis
81
How to stop Leflunomide
Has a very long wash-out period of up to a year which requires co-administration of cholestyramine
82
What is Marfan's syndrome?
- Autosomal dominant connective tissue disorder
- It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1
- It affects around 1 in 3,000 people
83
Features of Marfan's syndrome
1) Tall stature with arm span to height ratio > 1.05
2) High-arched palate
3) Arachnodactyly
4) Pectus excavatum
5) Pes planus
6) Scoliosis of > 20 degrees
7) Heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, aortic regurgitation, mitral valve prolapse (75%)
8) Lungs: repeated pneumothoraces
9) Eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia
10) Dural ectasia (ballooning of the dural sac at the lumbosacral level)
84
Marfan's syndrome - Rx/monitoring
- The life expectancy of patients used to be around 40-50 years
- With the advent of regular echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved significantly over recent years
- Aortic dissection and other cardiovascular problems remain the leading cause of death
85
Methotrexate - indications
- Inflammatory arthritis, especially rheumatoid arthritis
- Psoriasis
- Some chemotherapy: acute lymphoblastic leukaemia
86
Methotrexate - S.E.
- Mucositis
- Myelosuppression
- Pneumonitis
- Pulmonary fibrosis
- Liver cirrhosis
87
Methotrexate and pregnancy
- Women should avoid pregnancy for at least 3 months after treatment has stopped
- The BNF also advises that men using methotrexate need to use effective contraception for at least 3 months after treatment
88
Features - myopathy
- Symmetrical muscle weakness (proximal > distal)
- Common problems are rising from chair or getting out of bath
- Sensation normal, reflexes normal, no fasciculation
89
Causes - myopathy
- Inflammatory: polymyositis
- Inherited: Duchenne/Becker muscular dystrophy, myotonic dystrophy
- Endocrine: Cushing's, thyrotoxicosis
- Alcohol
90
Overall management - OA
- All pts should be offered help with weight loss, given advice about local muscle strengthening exercises and general aerobic fitness
- Paracetamol and topical NSAIDs are first-line analgesics. Topical NSAIDs are indicated only for OA of the knee or hand
91
Second line - OA
- Second-line treatment is oral NSAIDs/COX-2 inhibitors, opioids, capsaicin cream and intra-articular corticosteroids. A proton pump inhibitor should be co-prescribed with NSAIDs and COX-2 inhibitors
- These drugs should be avoided if the patient takes aspirin
non-pharmacological treatment options include supports and braces, TENS and shock absorbing insoles or shoes
- If conservative methods fail then refer for consideration of joint replacement
92
X-ray: OA
- Decrease of joint space
- Subchondral sclerosis
- Subchondral cysts
- Osteophytes forming at joint margins
93
Osteogenesis imperfecta
- Group of disorders of collagen metabolism resulting in bone fragility and fractures. The most common, and milder, form of osteogenesis imperfecta is type 1
- Autosomal dominant
94
Osteogenesis imperfecta - features
- Presents in childhood
- Fractures following minor trauma
- Blue sclera
- Deafness secondary to otosclerosis
- Dental imperfections are common
95
Osteomalacia - basis
- Normal bony tissue but decreased mineral content
- Rickets if when growing
- Osteomalacia if after epiphysis fusion
- Rickets: knock-knee, bow leg, features of hypocalcaemia
- Osteomalacia: bone pain, fractures, muscle tenderness, proximal myopathy
96
Ix - osteomalacia
- Low 25(OH) vitamin D (in 100% of patients, by definition)
- Raised alkaline phosphatase (in 95-100% of patients)
- Low calcium, phosphate (in around 30%)
- X-ray: children - cupped, ragged metaphyseal surfaces; adults - translucent bands (Looser's zones or pseudofractures)
97
Rx - osteomalacia
Calcium w/ vitamin D tablets
98
Types of osteomalacia
- Vitamin D deficiency e.g. malabsorption, lack of sunlight, diet
- Renal failure
- Drug induced e.g. anticonvulsants
- Vitamin D resistant; inherited
- Liver disease, e.g. cirrhosis
99
Osteoporosis - primary RFs
Advancing age and female sex are significant risk factors for osteoporosis. Prevalence of osteoporosis increases from 2% at 50 years to more than 25% at 80 years in women
100
Osteoporosis secondary causes
- Hx of glucocorticoid use
- RA
- Alcohol excess
- Hx of parental hip fracture
- Low body mass index
- Current smoking
101
Osteoporosis - other RFs
1) Sedentary lifestyle
2) Premature menopause
3) Caucasians and Asians
4) Endocrine disorders: hyperthyroidism, hypogonadism (e.g. Turner's, testosterone deficiency), growth hormone deficiency, hyperparathyroidism, diabetes mellitus
5) Multiple myeloma, lymphoma
6) GI disorders: inflammatory bowel disease, malabsorption (e.g. Coeliac's), gastrectomy, liver disease
7) CKD
8) Osteogenesis imperfecta, homocystinuria
102
Drugs - predispose/worsen OP:
1) Glucocorticoids
2) SSRIs
3) Antiepileptics
4) PPIs
5) Glitazones
6) Long term heparin therapy
7) Aromatase inhibitors e.g. anastrozole
103
Ix - OP:
FBC, U+E, bone markers, TFTs, LFTs, CRP
104
Paget's disease of bone:
Disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity.
105
Paget's disease prevalence
Paget's disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients
106
Paget's disease - predisposing factors
- Increasing age
- Male sex
- Northern latitude
- Family history
107
Paget's bone - clinical features
- Only 5% of patients are symptomatic
- Bone pain (e.g. pelvis, lumbar spine, femur)
- Classical, untreated features: bowing of tibia, bossing of skull
- Raised alkaline phosphatase (ALP) - calcium* and phosphate are typically normal
- Skull x-ray: thickened vault, osteoporosis circumscripta
* Calcium usually normal in this condition but may be raised after long periods of immobility
108
What are the indications for Rx - Paget's?
- Bone pain
- Skull or long bone deformity
- Fracture
- Periarticular Paget's
109
Rx - Paget's
- Bisphosphonate (either oral risedronate or IV zoledronate)
| - Calcitonin is less commonly used now
110
Complications - Paget's
- Deafness (cranial nerve entrapment)
- Bone sarcoma (1% if affected for > 10 years)
- Fractures
- Skull thickening
- High-output cardiac failure
111
Penicillamine - uses?
RA
112
Penicillamine - adverse effects
- Rashes
- Disturbance of taste
- Proteinuria
113
Polyarteritis Nodosa
Vasculitis affecting medium-sized arteries with necrotizing inflammation leading to aneurysm formation. PAN is more common in middle-aged men and is associated with hepatitis B infection
114
Polyarteritis Nodosa - features
1) Fever, malaise, arthralgia
2) Weight loss
3) Hypertension
4) Mononeuritis multiplex, sensorimotor polyneuropathy
5) Testicular pain
6) Livedo reticularis
7) Haematuria, renal failure
115
Polyarteritis Nodosa - immunology
- Perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with 'classic' PAN
- Hepatitis B serology positive in 30% of patients
116
Polymyalgia Rheumatica (PMR)- overview
- Overlaps with temporal arteritis
histology shows vasculitis with giant cells, - Characteristically 'skips' certain sections of affected artery whilst damaging others
- Muscle bed arteries affected most in polymyalgia rheumatica
117
PMR features
- Typically patient > 60 years old
- Usually rapid onset (e.g. < 1 month)
- Aching, morning stiffness in proximal limb muscles (not weakness)
- Also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats
118
Ix - PMR
- ESR > 40 mm/hr
- Note CK and EMG normal
- Reduced CD8+ T cells
119
Rx - PMR
Prednisolone e.g. 15mg/od - dramatic response
120
Pseudogout
Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate in the synovium
121
RFs - pseudogout
- Hyperparathyroidism
- Hypothyroidism
- Haemochromatosis
- Acromegaly
- Low magnesium, low phosphate
- Wilson's disease
122
Features - pseudogout
- Knee, wrist and shoulders most commonly affected
- Joint aspiration: weakly-positively birefringent rhomboid shaped crystals
- X-ray: chondrocalcinosis
123
Management - pseudogout
- Aspiration of joint fluid, to exclude septic arthritis
| - NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
124
Psoriatic arthropathy
- Correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions
- Around 10-20% percent of patients with skin lesions develop an arthropathy with males and females being equally affected
125
Types of PsA
- Rheumatoid-like polyarthritis: (30-40%, most common type)
- Asymmetrical oligoarthritis: typically affects hands and feet (20-30%)
- Sacroilitis (axial)
- DIP joint disease (10%)
- Arthritis mutilans (severe deformity fingers/hand, 'telescoping fingers')
126
Management - PsA
- Treat as rheumatoid arthritis
| better prognosis
127
Raynaud's phenomena
- May be primary (Raynaud's disease) or secondary (Raynaud's phenomenon)
- Raynaud's disease typically presents in young women (e.g. 30 years old) with symmetrical attacks
128
Factors suggesting underlying connective tissue disease - Raynaud's phenomena
-Onset after 40 years
- Unilateral symptoms
- Rashes
- Presence of autoantibodies
- Features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent miscarriages
digital ulcers, calcinosis
- Very rarely: chilblains
129
Raynaud's - secondary causes
- Connective tissue disorders: scleroderma (most common), rheumatoid arthritis, SLE
- Leukaemia
- Type I cryoglobulinaemia, cold agglutinins
- Use of vibrating tools
- Drugs: oral contraceptive pill, ergot
- Cervical rib
130
Raynaud's - Rx
- First line: calcium channel blockers e.g. nifedipine
| - IV prostacyclin infusions: effects may last several weeks/months
131
Reactive arthritis
- Reactive arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies
- Classic triad of urethritis, conjunctivitis and arthritis
- Reactive arthritis is defined as an arthritis that develops following an infection where the organism cannot be recovered from the joint
132
Reactive arthritis - epidemiology
- Post-STI form much more common in men (e.g. 10:1)
| - Post-dysenteric form equal sex incidence
133
Reactive arthritis - bowel pathogens
- Shigella flexneri
- Salmonella typhimurium
- Salmonella enteritidis
- Yersinia enterocolitica
- Campylobacter
134
Reactive arthritis - STI
Chlamydia trachomatis
135
Reactive arthritis - Rx
- Symptomatic: analgesia, NSAIDS, intra-articular steroids
- Sulfasalazine and methotrexate are sometimes used for persistent disease
- Symptoms rarely last more than 12 months
136
Conditions w/ positive RF:
- RA (70-80%)
- Sjogren's syndrome (around 100%)
- Felty's syndrome (around 100%)
- Infective endocarditis (= 50%)
- SLE (= 20-30%)
- Systemic sclerosis (= 30%)
- General population (= 5%)
- Rarely: TB, HBV, EBV, leprosy
137
RF - positive RA
RF is positive in 70-80% of patients with rheumatoid arthritis, high titre levels are associated with severe progressive disease (but NOT a marker of disease activity)
138
RA - anti antibodies
- Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before the development of rheumatoid arthritis
- It has a sensitivity similar to rheumatoid factor (around 70%) with a much higher specificity of 90-95%
- NICE recommends that patients with suspected rheumatoid arthritis who are rheumatoid factor negative should be test for anti-CCP antibodies
139
Features - reactive arthritis
- Typically develops within 4 weeks of initial infection - symptoms generally last around 4-6 months
- Arthritis is typically an asymmetrical oligoarthritis of lower limbs
- Dactylitis
- Symptoms of urethritis
- Eye: conjunctivitis (seen in 10-30%), anterior uveitis
- Skin: circinate balanitis (painless vesicles on the coronal margin of the prepuce), keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)
140
Reactive arthritis - prognosis
Around 25% of patients have recurrent episodes whilst 10% of patients develop chronic disease
141
Extra-articular complications - RA
1) Respiratory
2) Ocular
3) Osteoporosis
4) IHD: RA carries a similar risk to type 2 diabetes mellitus
5) Increased risk of infections
6) Depression
7) Felty's syndrome
8) Amyloidosis
142
Respiratory complications - RA
- Pulmonary fibrosis
- Pleural effusion
- Pulmonary nodules
- Bronchiolitis obliterans
- Methotrexate pneumonitis
- Pleurisy
143
Ocular complications - RA
- Keratoconjunctivitis sicca (most common)
- Episcleritis/scleritis
- Corneal ulceration
- Keratitis
- Steroid-induced cataracts
- Chloroquine retinopathy
144
Felty's syndrome
RA + splenomegaly + low white cell count
145
RA - features
- Swollen, painful joints in hands and feet
- Stiffness worse in the morning
- Gradually gets worse with larger joints becoming involved
- Presentation usually insidiously develops over a few months
- Positive 'squeeze test' - discomfort on squeezing across the metacarpal or metatarsal joints
- Swan neck and boutonnière deformities are late features of rheumatoid arthritis and unlikely to be present in a recently diagnosed patient
146
RA - prognostic features
- Rheumatoid factor positive
- Poor functional status at presentation
- HLA DR4
- X-ray: early erosions (e.g. after < 2 years)
- Extra articular features e.g. nodules
- Insidious onset
- Anti-CCP antibodies
147
Radiological features
Early x-ray findings:
- Loss of joint space
- Juxta-articular osteoporosis
- Soft-tissue swelling
Late x-ray findings
- Periarticular erosions
- Subluxation
148
Septic arthritis - Kocher criteria
- Fever >38.5 degrees C
- Non-weight bearing
- Raised ESR
- Raised WCC
149
Septic arthritis: causative agents
- Most common organism overall is Staphylococcus aureus
| - In young adults who are sexually active Neisseria gonorrhoeae should also be considered
150
Management - septic arthritis
- Synovial fluid should be obtained before starting treatment
- Intravenous antibiotics which cover Gram-positive cocci are indicated (the BNF currently recommends flucloxacillin or clindamycin if penicillin allergic)
- Antibiotic treatment is normally be given for several weeks (BNF states 6-12 weeks)
- Needle aspiration should be used to decompress the joint
- Arthroscopic lavage may be required
151
Sjogren's syndrome
- Autoimmune disorder affecting exocrine glands resulting in dry mucosal surfaces
- It may be primary (PSS) or secondary to rheumatoid arthritis or other connective tissue disorders
152
Secondary Sjogren's syndrome
Usually develops around 10 years after the initial onset
153
Sjogren's syndrome - epidemiology
- Sjogren's syndrome is much more common in females (ratio 9:1)
- There is a marked increased risk of lymphoid malignancy (40-60 fold)
154
Sjogren's syndrome - features
1) Dry eyes: keratoconjunctivitis sicca
2) Dry mouth
3) Vaginal dryness
4) Arthralgia
5) Raynaud's, myalgia
6) Sensory polyneuropathy
7) Recurrent episodes of parotitis
8) Renal tubular acidosis (usually subclinical)
155
Sjogren's syndrome - Ix
- Rheumatoid factor (RF) positive in nearly 100% of patients
- ANA positive in 70%
- Anti-Ro (SSA) antibodies in 70% of patients with PSS
- Anti-La (SSB) antibodies in 30% of patients with PSS
- Schirmer's test: filter paper near conjunctival sac to measure tear formation
- Histology: focal lymphocytic infiltration
- Hypergammaglobulinaemia, low C4
156
Sjogren's syndrome - Rx
- Artificial saliva and tears
| - Pilocarpine may stimulate saliva production
157
Sulfasalazine - indications
- RA
| - IBD (UC mostly)
158
Sulfasalazine - cautions
- GP6D deficiency
| - Allergy to aspirin or sulphonamides (cross-sensitivity)
159
Sulfasalazine - adverse effects
- Oligospermia
- Stevens-Johnson syndrome
- Pneumonitis / lung fibrosis
- Myelosuppression, Heinz body anaemia, megaloblastic anaemia
- May colour tears → stained contact lenses
160
SLE pathophysiology
- Autoimmune disease
- Associated with HLA B8, DR2, DR3
- Thought to be caused by immune system dysregulation leading to immune complex formation
- Immune complex deposition can affect any organ including the skin, joints, kidneys and brain
161
SLE epidemiology
- Much more common in females (F:M = 9:1)
- More common in Afro-Caribbeans and Asian communities
- Onset is usually 20-40 years
- Incidence has risen substantially during the past 50 years
162
SLE general features
1) Fatigue
2) Fever
3) Mouth ulcers
4) Lymphadenopathy
163
SLE - skin features
1) Malar (butterfly) rash: spares nasolabial folds
2) Discoid rash: scaly, erythematous, well demarcated rash in sun-exposed areas. Lesions may progress to become pigmented and hyperkeratotic before becoming atrophic
3) Photosensitivity
4) Raynaud's phenomenon
5) Livedo reticularis
6) Non-scarring alopecia
164
SLE - MSK features
1) Arthralgia
| 2) Non-erosive arthritis
165
SLE - CVD features
1) Pericarditis: the most common cardiac manifestation
| 2) Myocarditis
166
SLE - respiratory features
1) Pleurisy
| 2) Fibrosing alveolitis
167
SLE - renal features
1) Proteinuria
| 2) Glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)
168
SLE - neuropsychiatric feaures
1) Anxiety and depression
2) Psychosis
3) Seizures
169
SLE - immunology
- 99% are ANA positive
- 20% are rheumatoid factor positive
- Anti-dsDNA: highly specific (> 99%), but less sensitive (70%)
- Anti-Smith: most specific (> 99%), sensitivity (30%)
also: anti-U1 RNP, SS-A (anti-Ro) and SS-B (anti-La)
170
SLE - disease monitoring
- ESR: during active disease the CRP is characteristically normal - a raised CRP may indicate underlying infection
- Complement levels (C3, C4) are low during active disease (formation of complexes leads to consumption of complement)
- Anti-dsDNA titres can be used for disease monitoring (but note not present in all patients)
171
Systemic sclerosis - patterns of disease
1) Limited cutaneous systemic sclerosis
2) Diffuse cutaneous systemic sclerosis
3) Scleroderma (without internal organ involvement)
172
Limited cutaneous systemic sclerosis
1) Raynaud's may be first sign
2) Scleroderma affects face and distal limbs predominately
3) Associated with anti-centromere antibodies
4) Subtype of limited systemic sclerosis is CREST syndrome
173
CREST syndrome
Calcinosis, Raynaud's phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
174
Diffuse cutaneous systemic sclerosis
1) Scleroderma affects trunk and proximal limbs predominately
2) Associated with scl-70 antibodies
3) Hypertension, lung fibrosis and renal involvement seen
4) Poor prognosis
175
Scleroderma (without internal organ involvement)
1) Tightening and fibrosis of skin
| 2) May be manifest as plaques (morphoea) or linear
176
Scleroderma - abs
- ANA positive in 90%
- RF positive in 30%
- Anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis
- Anti-centromere antibodies associated with limited cutaneous systemic sclerosis
177
DEXA scan - OP
- T score: based on bone mass of young reference population
- T score of -1.0 means bone mass of one standard deviation below that of young reference population
- Z score is adjusted for age, gender and ethnic factors
178
DEXA scan values (T-scores)
> -1.0 = normal
-1.0 to -2.5 = osteopaenia
< -2.5 = osteoporosis
179
Temporal arthritis (GCA)
- Large vessel vasculitis which overlaps with PMR
| - Histology shows changes which characteristically 'skips' certain sections of affected artery whilst damaging others
180
GCA - features
1) Typically patient > 60 years old
2) Usually rapid onset (e.g. < 1 month)
3) Headache (found in 85%)
4) Jaw claudication (65%)
5) Visual disturbances secondary to anterior ischemic optic neuropathy
6) Tender, palpable temporal artery
7) Around 50% have features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
8) Lethargy, depression, low-grade fever, anorexia, night sweats
181
GCA - Ix
- Raised inflammatory markers: ESR > 50 mm/hr (note ESR < 30 in 10% of patients), CRP may also be elevated
- Temporal artery biopsy: skip lesions may be present
- Note creatine kinase and EMG normal
182
GCA - Rx
- HD prednisolone - there should be a dramatic response, if not the diagnosis should be reconsidered
- Urgent ophthalmology review (patients with visual symptoms should be seen the same-day by an ophthalmologist - visual damage is often irreversible)
183
Adult Still's disease
- Typically affects 16-35 year olds
184
Adult Still's disease - features
1) Arthralgia
2) Elevated serum ferritin
3) Rash: salmon-pink, maculopapular
4) Pyrexia: typically rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rash
5) Lymphadenopathy
6) Rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative
185
Adult Still's - Rx
- NSAIDs should be used to manage fever, joint pain and serositis in the first instance
- They should be trialled for at least a week before steroids are added
- Steroids may control symptoms but won't improve prognosis
- If symptoms persist, the use of methotrexate, IL-1 or anti-TNF therapy can be considered
