Rheuma Flashcards
1
Q
Anti-Ro
A
Sjogren’s syndrome, SLE, congenital heart block
2
Q
Anti-La:
A
Sjogren’s syndrome
3
Q
- Anti-Jo 1
A
polymyositis
4
Q
Anti-SCL-70
A
diffuse cutaneous systemic
sclerosis
5
Q
Anti-centromere:
A
limited cutaneous
systemic sclerosis
6
Q
Gout
A
caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricemia (uric acid > 450 μmol/l) mostly due to ↓ renal execretion of UA (90%).
7
Q
↓ Excretion of uric acid
A
CKD
Lead
drugs (diueretics)
8
Q
↑ Production of uric acid
A
Myeloproliferative/lymphoproliferative disorder * Cytotoxic drugs
* Severe psoriasis
* Chronic kidney disease
* Lead toxicity
9
Q
Lesch-Nyhan syndrome
A
Hypoxanthine-guanine phosphoribosyl transferase deficiency
* Inheritance = X-linked recessive
* Features: gout, renal failure, learning difficulties,
head-banging
10
Q
Tophaceous gout:
A
Associated with renal impairment and prolonged diuretics use.
* Affected joints are hot swollen and knobby appearance.
* Due to deposition of Na+ urate in skin and joint.
* X-ray: punched out bony cys
11
Q
gout management
A
NSAIDs
* Intra-articular steroid injection
* Colchicine has a slower onset of action. (main side-effect is diarrhea and ↑ INR with warfarin)
* If the patient is already taking allopurinol it should be continued
* Rasburicase: is a recombinant version of a urate oxidase enzyme given in acute setting, it allows
allopurinol to be commenced without worsening of symptoms. Only used when other Rx can not be given
12
Q
Gout: start allopurinol if
A
≥ 2 attacks in 12 month period
Allopurinol should not be started until 2 weeks after an acute attack has settled.
* Initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of
< 300 μmol/l
* NSAID or colchicine cover should be used when starting allopurinol
13
Q
Indications for allopurinol* gout
A
Recurrent attacks - the British Society for Rheumatology recommend ‘In uncomplicated gout uric acid lowering drug therapy should be started if a second attack, or further attacks occur within 1 year’
* Tophi
* Renal disease
* Uric acid renal stones
* Prophylaxis if on cytotoxics or diuretics
14
Q
Pseudogout features
A
is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate in the synovium
Features
* Knee, wrist and shoulders most commonly affected
* X-ray: chondrocalcinosis (linear calcification of the articular cartilage)
* Joint aspiration: weakly-positively birefringent rhomboid shaped crystals
15
Q
Pseudogout Investigations:
A
Transferrin saturation (may indicate hemochromatosis, a recognised cause of pseudogout)
Management:
*
*
Aspiration of joint fluid, to exclude septic arthritis and show weakly-positively birefringent brick shaped crystals
NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
16
Q
Pseudogout risk factors
A
Risk factors
* Hyperparathyroidism
* Hypothyroidism
* Hemochromatosis
* Acromegaly
* ↓ magnesium, ↓ phosphate
* Wilson’s diseas
17
Q
Rheumatoid Arthritis:
Epidemiology
A
Peak onset = 30-50 years, although occurs in all age groups
* ♀:♂ ratio = 3:1
* Prevalence in UK = 1%
* Some ethnic differences e.g. High in native Americans
* Associated with HLA-DR4 (especially felty’s syndrome)
18
Q
American College of Rheumatology criteria
RA
A
- Morning stiffness > 1 hr (for at least 6 weeks)
- Soft-tissue swelling of 3 or more joints (for at least 6 weeks)
- Swelling of PIP , MCP or wrist joints (for at least 6 weeks)
- Symmetrical arthritis
- Subcutaneous nodules
- Rheumatoid factor positive
- Radiographic evidence of
erosions or periarticular osteopenia
19
Q
Rheumatoid arthritis what mediates the path
A
TNF
20
Q
NICE recommends that patients with suspected rheumatoid arthritis who are rheumatoid factor negative
A
should be tested for anti-CCP antibodies.
Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before the development of rheumatoid arthritis.
21
Q
rheumatoid arthritis Early x-ray findings
A
Loss of joint space (seen in both RA and osteoarthritis)
* Juxta-articular osteoporosis
* Soft-tissue swelling
22
Q
rheumatoid arthritis Late x-ray findings
A
- Periarticular erosions (osteopenia and osteoporosis)
- Subluxation
23
Q
A number of features have been shown to predict a poor prognosis in patients with rheumatoid arthritis, as listed below
A
Rheumatoid factor positive
* Poor functional status at presentation
* HLA DR4
* X-ray: early erosions (in < 2 years)
* Extra articular features e.g. Nodules
* ♀sex
* Insidious onset
* Anti-CCP antibodies
24
Q
Extra-articular complications occur in patients with rheumatoid arthritis (RA):
A
Respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans,
methotrexate pneumonitis, pleurisy
* Ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration,
keratitis, steroid-induced cataracts, chloroquine retinopathy
* Osteoporosis
* ISCHEMIC heart disease: RA carries a similar risk to T2DM
* Increased risk of infections
* Depression
25
Felty's syndrome
(RA + splenomegaly + low white cell count)
26
Proteus mirabilis is a (G-ve rod), causes UTI →
predisposes susceptible patients to RA
27
ra Initial therapy
ombination of DMARDs (including methotrexate and at least one other DMARD, plus short-term glucocorticoids)
28
RA. In Pregnancy
Methotrexate and NSAIDs are absolutely contraindicated
Azathiopurine can be used if sulfasalazine and hydroxychloroquine are not controlling
29
RA TNF-inhibitors
The current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate
} Safe in pregnancy
In Pregnancy
Methotrexate and NSAIDs are absolutely contraindicated
Azathiopurine can be used if sulfasalazine and hydroxychloroquine are not controlling
* Etanercept: subcutaneous administration, can cause demyelination }
* Infliximab: intravenous administration, risks include reactivation of
tuberculosis
* Adalimumab: subcutaneous administration
30
Rituximab
Anti-CD20 monoclonal antibody, results in B-cell depletion
* Two 1g intravenous infusions are given two weeks apart
* Infusion reactions are common
31
Abatacept
Fusion protein that modulates a key signal required for activation of T lymphocytes
* Leads to ↓ T-cell proliferation and cytokine production
* Given as an infusion
32
Respiratory Problems in Rheumatoid Arthritis
A variety of respiratory problems may be seen in patients with rheumatoid arthritis:
* Pulmonary fibrosis
* Pleural effusion
* Pulmonary nodules
* Bronchiolitis obliterans
* Complications of drug therapy e.g. Methotrexate pneumonitis
* Pleurisy
* Caplan's syndrome - massive fibrotic nodules with occupational coal dust exposure
* Infection (possibly atypical) secondary to immunosuppression
33
Adult Still's Disease:
Features:
* Arthralgia
* Fever (noticeable at afternoon and evening)
* Elevated serum ferritin
Rash: salmon-pink, maculopapular, pruritic
* Pyrexia
* Lymphadenopathy
* RF and ANA negative (but ANA 25% positive). ↑ ESR and CRP
* Leukocytosis and thrombocytosis
34
Stills management
Management:
* NSAIDs
* Steroids
* Methotrexate
35
Septic Arthritis
Joint aspiration is mandatory in all patients with a hot, swollen joint to rule out septic arthritis. If
this was excluded then intra-articular or system steroid therapy may be considered
36
Septic Arthritis organisism
Overview
* Most common organism overall is Staphylococcus aureus
* In young adults who are sexually active Neisseria gonorrhea should also be considered
* WBC > 50 x 109/L or > 75% of baseline – neutrophils
37
septic arthritis Management
* Synovial fluid should be obtained before starting treatment
* Intravenous antibiotics which cover gram-positive cocci are indicated. The BNF currently
recommends flucloxacillin + fusidic acid 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
* Surgical drainage may be needed if frequent needle aspiration is required
38
Osteoarthritis: most common site
The trapeziometacarpal joint (base of thumb) is the most common site of hand osteoarthri
39
Osteoarthritis analgesia
aracetamol and topical NSAIDs are first-line analgesics. Topical NSAIDs are indicated only
for OA of the knee or hand
* 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 either drug.
These drugs should be avoided if the patient takes aspirin
40
oa glucosamine?
Normal constituent of glycosaminoglycans in cartilage and synovial fluid
The 2008 NICE guidelines suggest it is NOT RECOMMENDED
* A 2008 drug and therapeutics bulletin review advised that whilst glucosamine provides modest
pain relief in knee osteoarthritis it should not be prescribed on the NHS due to limited evidence of cost-effectiveness
41
Reactive Arthritis HLA
Reactive Arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies.
Reiter's syndrome, a term which described a classic triad of urethritis, conjunctivitis and arthritis following a dysenteric illness
42
reactive art Features
Typically develops within 4 weeks of initial infection - symptoms generally last around 4-6
months
* Arthritis is typically an asymmetrical oligoarthritis of lower limbs
* May present as monoarthritis e.g. Knee
* Symptoms of urethritis
* Eye: conjunctivitis (seen in 50%), anterior uveitis
* Skin: circinate balanitis (painless vesicles on the coronal margin of the prepuce), keratoderma
blenorrhagica (waxy yellow/brown papules on palms and soles)
43
Ankylosing spondylitis HLA
evelop in upto 50% of HLA B27 +ve patients
44
reactive arthritis Organisms often responsible for post-dysenteric form
Shigella flexneri
* Salmonella typhimurium
* Salmonella enteritidis
* Yersinia enterocolitica
* Campylobacter
45
reactive arthritis Organisms often responsible for post-STI form
Chlamydia trachomatis
46
reactive arthritis Management
Symptomatic: analgesia, NSAIDs, intra-articular steroids
* Sulfasalazine and methotrexate are sometimes used for persistent disease
* Symptoms rarely last more than 12 months
47
Palindromic Arthritis:
* Rare type of recurrent inflammatory arthritis that causes sudden inflammation in one or several joints (pain, swelling and erythema) followed by complete recovery with no permanent damage.
* Affects articular or periarticular areas, any joint could be affected but mostly large joints
* Lasts < 72 hours before recovering completely
* ♂=♀ - age 20-50 years.
* May progress to RA: incidence of RA may ↑ when RF is present
* Anti-CCP and antikeratin antibodies (AKA) are present in a high proportion of patients
48
The most common cause of recurrent or relapsing arthritis:
Crystal Arthritis (Gout & Pseudogout)
49
Recent-Onset Arthritis
parvovirus-induced arthritis
* Exposure to children with recent febrile illness is known risk
* Affects ♀>♂ - mostly women with contact to children (at home or at work)
* Small hands joints, wrists, elbows, hips, knees, and feet are each affected in > 50% of cases.
* Detection of IgM antibody, produced only in early disease, is a marker of recent infection and
therefore strong evidence in favor of parvovirus being the cause of recent-onset arthritis.
50
Ankylosing Spondylitis HLA
HLA-B27 associated spondyloarthropathies. It typically presents in ♂s (sex ratio 5:1) aged 20-30 years old. It has polygenic inheritance.
51
Ankylosing Spondylitis a associations
Apical fibrosis (CXR)
* Anterior uveitis
* Aortic regurgitation
* Achilles tendonitis
* A V node block
* Amyloidosis
* And cauda equina
52
Ankylosing Spondylitis Features
* Typically a young man who presents with lower back pain and stiffness
* Stiffness is usually worse in morning and improves with activity
* The patient may experience pain at night which improves on getting up
* Peripheral arthritis (25%, more common if ♀)
53
Ankylosing Spondylitis Clinical examination
Reduced lateral flexion (earlier sign)
* Reduced forward flexion - Schober's test - 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
* Reduced chest expansion
54
Ankylosing Spondylitis X rays
X-ray of the sacro-iliac joints is the most useful investigation for diagnosis and monitoring, but changes may not be seen for many years after the onset of symptoms
X-rays are often normal early in disease, later changes include:
* Sacroilitis: subchondral erosions, sclerosis
* Squaring of lumbar vertebrae
* 'Bamboo spine' (late & uncommon)
CXR: apical fibrosis
55
Ankylosing Spondylitis Management
Management
* NSAIDs
* Physiotherapy
* Sulphasalazine may be useful if there is peripheral joint involvement - doesn't improve spinal
mobility
* TNF-α blockers such as etanercept and adalimumab are increasingly used. This approach for
severe ankylosing spondylitis was supported by NICE in 2008
56
Seronegative Spondyloarthropathies Common features
* Associated with HLA-B27
* Rheumatoid factor negative - hence 'seronegative'
* Peripheral arthritis, usually asymmetrical
* Sacroilitis
* Enthesopathy: e.g. Achilles tendonitis, plantar fasciitis
* Extra-articular manifestations: uveitis, pulmonary fibrosis (upper zone), amyloidosis, aortic
regurgitation
57
Spondyloarthropathies
* Ankylosing spondylitis
* Psoriatic arthritis
* Reiter's syndrome (including reactive arthritis)
* Enteropathic arthritis (associated with IBD)
58
Pseudoxanthoma Elasticum
inherited condition (usually autosomal recessive*) characterized by an abnormality in elastic fibers
59
Pseudoxanthoma Elasticum Features
Retinal angioid streaks
* 'Plucked chicken skin' appearance - small yellow papules on the neck, antecubital fossa and
axillae
* Cardiac: mitral valve prolapse, ↑ risk of ischemic heart disease
* Gastrointestinal hemorrhage
60
Systemic Lupus Erythematosus (SLE) risk of developing
Low levels of C4a and C4b have been shown to be associated with ↑ risk of developing systemic lupus erythematous
61
SLE Epidemiology
Much more common in ♀s (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 (3 fold using American College of Rheumatology criteria)
62
Pathophysiology SLE
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; skin, joints, kidneys and brain most
commonly affected
63
Immunology SLE
ANA positive (99% SENSITIVE)
* 20% are rheumatoid factor positive
* Anti-dsDNA: HIGHLY SPECIFIC (> 99%), but less sensitive (70%)
* Anti-Smith: MOST SPECIFIC (> 99%), sensitivity (30%)
* Antihistone positive in drug indiced lupus
* Congenital ↓ C4 is a predisposing factor for SLE
64
SLE monitorijng
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) ↓ C4 is early marker for disease activity
* Anti-DsDNA titers: used for disease monitoring disease activity (but not present in all patients)
65
SLE and Pregnancy:
Unlike many autoimmune diseases systemic lupus erythematous (SLE) often becomes worse during pregnancy and the puerperium
* Risk of maternal autoantibodies crossing placenta
* Leads to condition termed neonatal lupus erythematous
* Neonatal complications include congenital heart block, it is strongly associated with anti-Ro
(SSA) antibodies
66
Drug-induced Lupus features
Features
* Arthralgia
* Myalgia
* Skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
* ANA positive in 100%, dsDNA negative
* Anti-Ro, anti-Smith positive in around 5%
67
Drug-induced Lupus causes
Causes
* Anti-epileptics: phenytoin
* Chlorpromazine
* Hydralazine
* Isoniazid
* Minocycline
* Procainamide
68
Discoid Lupus Erythematous i
benign disorder generally seen in younger ♀s. It very rarely progresses to systemic lupus erythematosus (in less than 5% of cases). Discoid lupus erythematous is characterized by follicular keratin plugs and is thought to be autoimmune in etiology
69
Discoid Lupus Erythematous features
Features
* Erythematous, raised rash, sometimes scaly
* May be photosensitive
* More common on face, neck, ears and scalp
* Lesions heal with atrophy, scarring (may cause scarring alopecia), and pigmentation
Management
* Topical steroid cream
* Oral antimalarials may be used second-line e.g. Hydroxychloroquine
* Avoid sun exposure
70
Temporal Arteritis
is large vessel vasculitis which overlaps with polymyalgia rheumatica (PMR). Histology shows changes which characteristically 'skips' certain sections of affected artery whilst damaging others
71
Temporal Arteritis features
Features
* Typically patient > 60 years old
* Usually rapid onset (e.g. < 1 month)
* Headache (found in 85%)
* Jaw claudication (65%)
* Tender, palpable temporal artery
* Features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
* Also lethargy, depression, low-grade fever, anorexia, night sweats
* Associated with sudden blindness due to the involvement of anterior ischemic optic neuropathy
72
Investigations Temporal Arteritis
* 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 CK and EMG normal
* ↓ CD8+ T cells
73
Temporal Arteritis investigations
* 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 CK and EMG normal
* ↓ CD8+ T cells
74
Treatment Temporal Arteritis
hould be started immediately with high dose steroids (e.g. prednisolone 1mg/kg/day) to ↓ the chance of visual loss. 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
75
Takayasu disease (TD):
is a continuous or patchy granulomatous inflammatory process involving macrophages, lymphocytes, and multinucleated giant cells which cause progressive occlusive disease of the aorta and its branches.
76
Takayasu disease (TD):
* Very rare in the Western world with an annual incidence of between 2 and 3 per million.
* Approximately 80% of patients are women, and the mean age of onset is 30 years.
* Presentation may be with constitutional symptoms such as fever, malaise, and weight loss;
neurological symptoms such as transient ischemic attacks; or vascular symptoms such as
claudication.
* Cardiac features include angina, heart failure, and aortic regurgitation.
* Renal manifestations may include mesangial proliferative glomerulonephritis.
* Corticosteroids with the addition of steroid sparing second agents such as methotrexate or
azathioprine are the mainstay of therapy.
* With good care, 15-year survival rates approach 90%.
77
Polyarteritis Nodosa (PAN)
a 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
78
Polyarteritis Nodosa (PAN) features
* Fever, malaise, arthralgia
* Hypertension
* Mononeuritis multiplex, sensorimotor polyneuropathy
* Hematuria, renal failure
* Testicular pain
* Abdominal pain (e.g. From mesenteric ischemia)
* Perinuclear-antineutrophil cytoplasmic antibodies (pANCA) are found in around 20% of
patients with 'classic' PAN
79
Polyarteritis Nodosa (PAN Diagnostic Criteria:
. Weight loss ≥ to 4.5 kg.
2. Livedo reticularis
3. Testicular pain or tenderness. (Occasionally, a site biopsied for diagnosis).
4. Muscle pain, weakness, or leg tenderness.
5. Nerve disease (either single or multiple).
6. Diastolic BP > 90mmHg
7. ↑ Kidney function tests (BUN and Creatinine)
8. Hepatitis B positive (surface antigen or antibody).
9. Abnormal arteriogram (angiogram)
10. Biopsy of small/medium size artery (typically inflamed arteries).
80
Wegener's Granulomatosis
is an autoimmune condition associated with a necrotizing granulomatous vasculitis, affecting both the upper and lower respiratory tract as well as the kidneys.
The combination of pulmonary and renal involvement combined with a history of chronic
sinusitis points towards a diagnosis of Wegener's granulomatosis
81
Wegener's Granulomatosis features
Upper respiratory tract: epistaxis, sinusitis, nasal crusting
* Lower respiratory tract: dyspnea, hemoptysis
* Glomerulonephritis ('pauci-immune', 80% of patients)
* Saddle-shape nose deformity
* Also: vasculitic rash, eye involvement (e.g. Proptosis), cranial
nerve lesions
82
Wegener's Granulomatosis Investigations
cANCA positive in > 90%, pANCA positive in 25%
* Chest x-ray: wide variety of presentations, including cavitating lesions
83
Wegener's Granulomatosis
Management:
* Steroids * Plasma exchange
* Cyclophosphamide (90% response)
* Median survival = 8-9 years
84
Churg-Strauss Syndrome
is an ANCA associated small-medium vessel vasculitis
85
Asthma + eosinophilia + nerve lesion
Churg-Strauss Syndrome
86
Churg-Strauss Syndrome features
Features
* Asthma and sometimes pulmonary esinophilic infiltrate
* Blood eosinophilia (e.g. > 10%)
* Paranasal sinusitis
* Mononeuritis multiplex
* pANCA positive in 60% - Anti myeloperoxidase antibody
87
Henoch-Schonlein purpura (HSP)
is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Buerger's disease). HSP is usually seen in children following an infection
88
Henoch-Schonlein purpura (HSP) features
Palpable purpuric rash (with localized edema) over buttocks, extensor surfaces of arms and legs
* Abdominal pain, non-bloody diarrhea.
* Polyarthritis
* Features of IgA nephropathy may occur e.g. Hematuria, renal failure
89
hrombangiitis Obliterans (Buerger’s disease)
is a disease of small and medium- sized arteries and veins resulting in inflammation and ulceration.
No excessive atheroma
* Does not involve the coronary arteries like atherosclerosis.
* Occurs mainly in cigarette smokers; it has not been documented in non-smokers.
* Patients present with symptoms of arterial ischemia.
* Migratory phlebitis in the superficial vein is present in 40% of cases.
* The disease progresses proximally, resulting in gangrene of the digits.
* Diagnosis is usually clinical. Arteriogram is also of benefit and will show occlusion of distal
arteries of the hands and feet.
* Treatment is supportive and patients should stop smoking.
90
Behcet's Syndrome
is a complex multisystem disorder associated with presumed autoimmune mediated inflammation of the arteries and veins. The precise etiology has yet to be elucidated however. The classic triad of symptoms is oral ulcers, genital ulcers and anterior uveitis
91
Behcet's Syndrome HLA
Associated with HLA B51 and MICA6 allele
92
Antiphospholipid syndrome: blood
(paradoxically) prolonged APTT + low platelets
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.
93
Behcet's Syndrome features
Features
* Classically: 1) oral ulcers 2) genital ulcers
3) anterior uveitis
* Thrombophlebitis
* Arthritis
* Neurological involvement (e.g. Aseptic
meningitis)
* GI: abdo pain, diarrhea, colitis
* Erythema nodosum, DVT
94
ntiphospholipid syndrome
Antiphospholipid Syndrome (Hughes syndrome) is an acquired disorder characterized by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
95
Antiphospholipid syndrome features
Features
* Venous/arterial thrombosis
* Recurrent fetal loss
* Livedo reticularis
* Thrombocytopenia
* Prolonged APTT
* Other features: pre-eclampsia, pulmonary hypertension
96
Antiphospholipid syndrome Management
Initial venous thromboembolic events: evidence currently supports use of warfarin with a target
INR of 2-3 for 6 months
* Recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin
then ↑ target INR to 3-4
* Arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
97
Antiphospholipid syndrome pregnancy
In pregnancy the following complications may occur:
* Recurrent miscarriage
* IUGR
* Pre-eclampsia
* Placental abruption
* Pre-term delivery
* V enous thromboembolism
98
Antiphospholipid syndrome management
Low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
* Low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually
discontinued at 34 weeks gestation
* These interventions ↑ the live birth rate seven-fold
99
Polymyalgia Rheumatica:
Pathophysiology
* 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
100
Polymyalgia Rheumatica: features
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
101
Polymyalgia Rheumatica: investigtions
Investigations
* ESR > 40 mm/hr
* Note CK and EMG normal
* ↓ CD8+ T cells
102
Anti-ribonuclear protein (anti-RNP)
mixed connective tissue disease
103
Cryoglobulinemia:
immunoglobulins which undergo reversible precipitation at 4°C, dissolve when warmed to 37°C. One third of cases are idiopathic
Three types
* Type I (25%): monoclonal
* Type II (25%): mixed monoclonal and polyclonal: usually with RF
* Type III (50%): polyclonal: usually with RF
104
Cryoglobulinemia: Type I
Monoclonal - IgG or IgM
* Associations: multiple myeloma, Waldenström macroglobulinemia
105
Cryoglobulinemia: Type II
Mixed monoclonal and polyclonal: usually with RF
* Associations: hepatitis C, RA, Sjogren's, lymphoma
106
Cryoglobulinemia: Type III
* Polyclonal: usually with RF
* Associations: RA, Sjogren's
107
Cryoglobulinemia: symptoms
Symptoms (if present in high concentrations)
* Raynaud's only seen in type I
* Cutaneous: vascular purpura, distal ulceration, ulceration
* Arthralgia
* Renal involvement (diffuse mesangiocapillary glomerulonephritis)
108
Cryoglobulinemia: tests
Tests
* Low complement (esp. C4)
* High ESR
109
Secondary causes raynauds
* Connective tissue disorders: scleroderma (most common), rheumatoid arthritis, SLE with bilateral symptoms
* Leukemia
* Type I cryoglobulinemia, cold agglutinins
* Use of vibrating tools
* Drugs: oral contraceptive pill, ergot
* Cervical rib
110
Management raynauds
Management
Calcium channel blockers
* IV prostacyclin infusions
111
Morphea
form of localized scleroderma that may be circumscribed or generalized.
In circumscribed morphea, there may be just one or two lesions with no generalized spread.
* Changes often begin with small, violaceous, or erythematous skin lesions, which enlarge and
progress to firm hidebound skin with a variable degree of hypo- or hyperpigmentation.
* Lesions eventually settle into a waxy, white appearance with subsequent atrophy.
* Lesions vary in diameter between 1 and 10 cm.
* Condition generally resolves within 3-5 years, although sometimes a patch may persist for over
25 years.
* Auto-antibodies such as anti-nuclear antibody (ANA) are only rarely positive in localized forms
of scleroderma, as against systemic subtypes where a positive ANA is one of the hallmarks of the disease.
112
Psoriatic Arthropathy
correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions. Around 10% of patients with skin lesions develop an arthropathy with ♂s and ♀s being equally affected
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Psoriatic Arthropathy Types*
Types*
* Rheumatoid-like polyarthritis: (30-40%, most common type)
* Asymmetrical oligoarthritis: typically affects hands and feet (20-30%)
* Sacroilitis
* DIP joint disease = arthropathy (10%)
* Arthritis mutilans (severe deformity fingers/hand, 'telescoping fingers')
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Dactylitis
escribes the inflammation of a digit (finger or toe).
Causes include:
* Spondyloarthritis: e.g. Psoriatic and reactive arthritis
* Sickle-cell disease
* Other rare causes include tuberculosis, sarcoid and syphilis
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Limited cutaneous systemic sclerosis:
Raynaud's may be first sign
* Scleroderma affects face and distal limbs predominately
* Associated with anti-centromere antibodies
* CREST syndrome is a subtype of limited cutaneous systemic sclerosis: Calcinosis, Raynaud's
phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia. In CREST MALABSORPTION can develop secondary to bacterial overgrowth of the sclerosed small intestine. Unfortunately pulmonary hypertension is one of the more common late complications seen in such patients.
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Diffuse cutaneous systemic sclerosis:
Scleroderma affects trunk and proximal limbs predominately
* Associated with SCL-70 antibodies
* Hypertension, lung fibrosis and renal involvement seen
* Poor prognosis
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Scleroderma (without internal organ involvement):
Tightening and fibrosis of skin
* May be manifest as plaques (morphoea) or linear
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Systemic Sclerosis Antibodies
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
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Scleroderma Management:
Topical treatment for skin changes do not alter the disease course, but may improve pain and ulceration.
o NSAIDs
o Limited benefit from steroids
o Episodes of Raynaud's sometimes respond to nifedipine or other calcium channel
blockers. Dual endothelin-receptor antagonist (bosentan) may be beneficial.
o Severe digital ulceration may respond to prostacyclin analogue iloprost
o The skin tightness may be treated systemically with methotrexate and ciclosporin
* Scleroderma renal crisis: benefit fro ACE-I to control BP and delay progression to CRF
* Active alveolitis is often treated with pulses of cyclophosphamide, often together with a small
dose of steroids. The benefit of this intervention is modest
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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 (found in 20-25% - more if old patient)
* Polymyositis is a variant of the disease where skin manifestations are not prominent
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Dermatomyositis: features
Skin features
* Photosensitive
* Macular rash over back and shoulder
* Heliotrope rash over cheek
* Gottron's papules - roughened red papules over extensor
surfaces of fingers
* Nail fold capillary dilatation
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Familial Mediterranean Fever features
Features - attacks typically last 1-3 days
* Pyrexia (on-off)
* Constipation/Diarrhea may occur with or after the fever
* Abdominal pain (due to peritonitis) – many times appendectomy scar is seen due to multiple
admissions due to abdominal pain
* Pleurisy
* Pericarditis
* Arthritis
* Nephrotic syndrome due to renal amyloidosis (that might even need transplantation)
* Erysipeloid rash on lower limbs
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Relapsing Polychondritis (RP)
inflammatory condition that involves cartilaginous structures, predominantly those of the pinna, nasal septum and larynx
General symptoms include intermittent fever and weight loss, but other more specific symptoms
include sudden onset of ear pain with an inability to sleep on the affected side, diminished hearing, monoarthritis or polyarthritis, back pain, myalgias, mild epistaxis, saddle-shaped nose, redness of the eyes indicative of conjunctivitis, episcleritis and/or scleritis, hoarseness of the voice and recurrent respiratory infections.
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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, where it usually develops around 10 years after the initial onset. Sjogren's syndrome is much more common in ♀s (ratio 9:1). There is a marked ↑ risk of lymphoid malignancy (40-60 folds)
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Sjogren's syndrome features
Features
* Dry eyes: keratoconjunctivitis sicca
* Dry mouth
* Vaginal dryness
* Arthralgia
* Raynaud's, myalgia
* Sensory polyneuropathy
* Renal tubular acidosis (usually
subclinical)
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Sjogren's syndrome investigations
Investigation
* 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 → (marked ↑ risk of lymphoid malignancy)
* Also: hypergammaglobulinemia, low C4
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