Connective Tissue Diseases Flashcards
1
Q
What are sicca symptoms?
A
- Lymphocytic infiltration of exocrine glands
- Xerophthalmia (dry eyes), xerostomia (dry mouth) these are the symptoms that patients complain about the most
- But you can also get mucosal dryness therefor should ask about: eyes, mouth, larynx, pharynx & vagina
2
Q
What is Sjogren’s syndrome?
A
- antibodies against exocrine glands
- such as tear, saliva and vaginal glands
- the antibodies damage the gland so they can no longer function properly
- BUT extra exocrine can affect any organ
3
Q
List some causes of secondary sjogren’s syndrome:
A
- primary
- secondary
- systemic autoimmune diseases - associated with many of these
4
Q
What are the symptoms of Sjogren’s syndrome?
A
- Sicca
- fatigue
- joint involvement
- but also extra-glandular involvement
- Reynaud’s
- Myalgia
- Resp and GI disease
- renal tubular acidosis
- lymphocytic infiltrates against parotid glands can cause parotid swelling
5
Q
What are risk factors for Sjogren’s syndrome?
A
- female (female to male ratio 9:1)
- 40-50 years
6
Q
Why do you need to follow up patients long-term with Sjogren’s syndrome?
A
- Incidence of non-Hodgkin lymphoma 4.3%
- 18.9 times higher than in the general population
- Median age of diagnosis 58 years
- 20 fold increase in lymphoma
- (MALT) lymphoma
- Mean time to development of lymphoma 7.5 years
7
Q
What investigations would you want to order for Sjogren’s syndrome?
A
- Associated with the following autoantibodies:
- ANA
- RF
- ENA (Ro, La)
- Serial screening of the following can be useful for screening for development of lymphoma
- ESR
- Complement
- Immunoglobulins/EP
- Schirmer’s tear test
- Salivary flow
- Parotid and submandibular gland USS
- Minor labial gland biopsy – particularly useful in Ro and La negative Sjogren’s syndrome
8
Q
How do you manage Sjogren’s syndrome?
A
- symptomatic
- eye drops (& eye surgical techniques)
- saliva replacement (or + to saliva secretion)
- topical oestrogen creams
- immunomodulatory
- hydroxychloroquine - useful for arthralgias or fatigue
- all patients screened for hepatitis and HIV
9
Q
What monitoring for lymphoma is needed in patients with Sjogren’s?
A
- Serial screening of the following can be useful for screening for development of lymphoma
- ESR
- Complement
- Immunoglobulins/EP
- Clinical assessment for signs of lymphoma
- Safety netting
10
Q
What is mixed connective tissue disease?
A
Mixture of RA, SLE, Myositis, Scleroderma
11
Q
What are the signs and symptoms of mixed connective tissue disease?
A
- Raynaud’s, digital ulcers
- Puffy hands
- Fatigue
- Muscle Involvement with inflammatory myopathies
- Skin rashes
- Arthritis
- Interstitial lung disease
-
Pulmonary arterial hypertension
- The bottom two being very worrying, as these are the main causes of morbidity and mortality in patients with mixed connective tissue disease
12
Q
What antibody is associated with mixed connective tissue disease?
A
- It does have its own antibody:
- RNP
- (Anti-U1 RNP)
13
Q
What needs to be screened for in mixed connective tissue disease?
A
- Higher incidence of the following, therefore this is regularly screened for
- Erosive arthritis
- PAH
- ILD
14
Q
What is routinely screened for in patients presenting with autoimmune connective tissue disorders?
A
Antiphospholipid syndrome
15
Q
What is anti-phospholipid syndrome?
A
- Antiphospholipid syndrome (APS) is an acquired autoimmune disorder, characterised by:
- Recurrent venous or arterial thrombosis and/or foetal loss
- Hypercoagulability and recurrent thrombosis can affect virtually any organ system
- Peripheral venous system
- CNS (causing stroke, seizures, chorea, sinus thrombosis and headache)
- Skin: causing the classic rash seen in the image, called ‘livedo reticularis’, which gives the skin a mottled/blotchy appearance
- specific examples of clots:
- obstetric (pregnancy loss, pre-eclampsia)
- PE, PH
- cardiac - MI, dystolic dysfunction, libman-sacks valvulopathy (non-infective endocarditis)
- ocular - amaurosis fugax, retinal thrombosis
- MSK - AVN bone
- derm - livedo reticularis
- adrenal - infarction, haemorrhage
- renal - thrombotic microangiopathy
16
Q
What is the diagnostic criteria of antiphospholipid syndrome?
A
At least one clinical and one lab criteria:
Clinical
- Vascular thrombosis
- Vascular thrombosis is defined as one or more clinical episodes of arterial, venous, or small-vessel thrombosis in any tissue or organ confirmed by findings from imaging studies, Doppler studies or histopathology
- Pregnancy morbidity
- ≥1 late-term spontaneous abortions
- ≥1 premature births of a morphological healthy neonate at or before 34 weeks’ gestation because of severe pre-eclampsia or eclampsia or severe placental insufficiency
- ≥3 unexplained, consecutive, spontaneous abortions (<10 weeks’ gestation)
Laboratory
- Elevated levels of immunoglobulin G (igG) or immunoglobulin M (igM), anticardiolipin (aCL) and anti-beta-2 glycoprotein I
- Lupus anticoagulant
- On at least two occasions at least 12 weeks apart
17
Q
What principles are followed when thinking about CTD and pregnancy?
A
- pre-planning is key (disease quiescence for at least 6 months prior to conception, contraception)
- all pregnant patients should be monitored by specialist MDT
- disease activity should be measured at baseline and at regular intervals
- maternal Ro/La very important as they are associated with
- 1-2% risk of foetal congenital heart block
- if positive - foetal cardiac screening at 16-20 weeks
- 1-2% risk of foetal congenital heart block
- screen for antiphospholipid syndrome
- early in pregnancy in SLE
- Lupus anticoagulant strongest predictor of aderse pregnancy outcome in SLE
- assess the need for therapeutic LMWH
- majority of patients are started on low dose aspirin therapy (started from 12 weeks and continue until delivery, 75 mg)
- flares of disease should be treated promptly with lowest effective dose of prednisolone
- advise against pregnancy in some women - specifically in patients with severe PAH or stage 4/5 CKD
18
Q
What principles are followed with DMARDs in pregnancy?
A
- withdraw known teratogens if patient becomes unexpectedly pregnant
- mycophenolate, methotrexate and cyclophosphamide
- then counsel patient on continuing vs terminating the pregnancy –> foetal ultrasound helpful in aiding this decision
- hydroxychloroquine in all pregnancies
- azathioprine safe in pregnancy
- in severe refractory maternal disease consider pulsed IV methylprednisolone, IVIg or in very severe disease 2nd or 3rd trimester cyclophosphamide
- rituximab has not been shown to be teratogenic and only second or third trimester exposure is associated with neonatal B cell depletion
- sexually active men should be advised on barrier contraception when taking certain kinds of immunosuppressant medications
19
Q
What is neonatal lupus?
A
- transplacental transfer of maternal antibodies can result in neonatal lupus, which is non-severe but is associated with a lupus like rash that can occur in 1-2% of infants
20
Q
What principles are followed when classifying undifferentiated connective tissue disorder?
A
As mentioned before, patients present with undifferentiated connective tissue disorder. With testing of autoantibodies, screening and appropriate investigations and also time for patterns and symptoms to develop, then the patient may be able to be further diagnosed into a specific syndrome.
21
Q
Quick syndrome summary
Sjogren’s syndrome
A
- Ro/La
- Sicca/fatigue
- Lymphoma
22
Q
Quick syndrome summaries
Mixed connective tissue disease
A
- RNP
- Combination of different multi-system involvement
- PAH/joint erosions
23
Q
Quick syndrome summaries
Anti-phospholipid syndrome
A
- DRVVT (lupus anticoagulant), anti-cardiolipin, anti-beta-2-glycoprotein
- Pregnancy morbidity/loss
- Thrombosis
24
Q
Quick syndrome summaries
Systemic sclerosis
A
- Reynaud’s/digital ulceration
- SCL-70/centromere
- ILD/PH
25
Quick syndrome summaries
## Footnote
**Systemic lupus erythematosus**
* DsDNA, low complement
* Rash, arthritis
* Need to screen for renal involvement
26
Quick syndrome summaries
## Footnote
**Polymyositis**
* Jo-1/ILD
* Proximal muscle weakness
* CK
27
Quick syndrome summaries
## Footnote
**Dermatomyositis**
* Rash
* Is associated with malignancy
* Associated with CK antibody
28
What is Reynaud's phenomenon?
* recurrent vasospasm of the fingers and toes, usually in response to stress or cold exposure
* three phases
* initally white - vasoconstriction
* followed by blue - cyanosis
* then red - rapid blood flow (hyperemia)
* a clear line of demarcation exists between the ischaemic and unaffected areas
* primary is common
* secondary
* associated with most of the CTDs, **however it is the most common first presentation of systemic sclerosis**
* F \> M
29
What is systemic sclerosis?
* characterised by excessive collagen deposition in the skin and in internal organs
* the skin becomes tethered and tight, difficult to pinch the skin
* can be divided into limited and diffuse
* rare
* 1:10000
* multisystem disease
30
What is the clinical presentation of _diffuse_ systemic sclerosis?
* Associated with Scl-70, RNA polymerase III
* Causes more diffuse disease extending beyond elbows and knees:
* Raynaud’s
* Digital ulceration
* Diffuse skin thickening
* ILD
* GI involvement
* Renal involvement
* RNA polymerase III is particularly associated with scleroderma renal crisis
* Cardiac involvement
31
What is systemic sclerosis renal crisis and how is it treated?
* rare but life-threatening complication of systemic sclerosis (can be first presentation)
* more associated with diffuse systemic sclerosis
* specifically RNA polymerase III
* characterised by:
* hypertension (although patients can be normotensive)
* rapidly deteriorating renal function --\> positive urine dip with blood and protein in urine
* flash pulmonary oedema
* seizures
* precipitated by:
* steroids
* **ACEi prophylaxis or treatment if renal crisis develops**
32
What is the clinical presentation of _limited_ systemic sclerosis?
* associated with anti-centromere ANA
* key features can be remembered with CREST
* **C**alcinosis (calcium deposits in the skin)
* **R**aynaud’s
* O**e**sophageal dysmotility(GI general)
* **S**clerodactyly
* **T**elangiectasia
* affetcs peripheries distal to the elbows and knees and also affects the neck and face
* associated with
* PH
* fibrotic lung disease
* Mild GI disease
33
How do you treat systemic sclerosis renal crisis?
**_ACEi_**
34
Risk factors for systemic sclerosis:
* female (female:male 10:1)
* age: 30-40
35
What are the three forms of localised scleroderma?
* morphoea
* linear morphoea/scleroderma
* en coupe de sabre
36
What is morphoea?
* This is the name given to localised patches of hardened skin that appear smooth and shiny.
* They usually appear on the trunk, but they can affect any part of the body.
* The condition is painless and there are normally no other symptoms or additional
37
What is linear morphoea/scleroderma?
* Means that the skin is affected in the form of a line, usually along an arm or a leg.
* The skin appears shiny, discoloured or scarred, and often feels tight and uncomfortable.
* In children, this should be monitored carefully because the ongoing growth of the limbs can be affected
38
What is en coupe de sabre?
* Literally means ‘cut of a sword’.
* This form of scleroderma presents on the scalp and temple in children.
* If the affected area is confined to the scalp then the problem is mainly cosmetic, although the underlying bone may be affected
* linear band of atrophy with a furrow in the skin, mainly affecting the frontal/fronto-temporal bone
39
What investigations do you want for systemic sclerosis?
* bloods (LFTs, U&Es, FBC, ESR)
* BP and urine dip - every contact to screen for renal involvement/crisis)
* nail fold capillaroscopy - earliest sign of systemic involvement
* CXR and HRCT
* used at baseline to look for ILD
* can also show dilatation of the oesophagus and evidence of pulmonary hypertension (enlarged right atrium/ventricle)
* serial PFT
* ILD - restritive pattern
* TLCO - PAH
* serial ECHOs
* estimate PASP
* pro-BNP - evidence of pulmonary hypertension
* X-rays of hands - to look for calcinosis
* OGD - dilatation of abdominal vessels can cuase bleeds for these patients
* barium swallow to look for dilatation of oesophagus
40
Overview of management of systemic sclerosis:
41
What therapy is needed in limited systemic sclerosis?
* symptomatic treatment
* vascular treatment
* identification and treatment of organ-based complications
* reno-protective drugs
* ACEi
42
What therapy is needed in diffuse systemic sclerosis?
* symptomatic
* vascular
* immunosuppressive
* active early cases of diffuse ss
* identification and treatment of severe organ-based complications
43
What drugs can be used for symtomatic management of systemic sclerosis?
* Lifestyle advice
* Vasodilatory drugs (preventing digital ulcers/treating PAH)
* Proton pump inhibitors
44
What vascular therapies are used for systemic sclerosis?
* Raynaud’s
* 1st line - **Calcium channel blockers**
* Phosphodiesterase type 5 (PDE-5) inhibitors Sildenafil, Tadalafil
* Prostanoids – intravenous iloprost
* Digital ulcers
* Treatment is same as Raynaud’s except with the addition of **Bosentan**, a dual receptor antagonist : original developed for PH, but now used in severe refractory digital ulceration
* Pulmonary arterial hypertension
* ERA - endothelin receptor antagonst (**ambrisentan, bosentan and macitentan**)
* PDE-5 inhibitors (**sildenafil, tadalafil**) and
* Riociquat have been approved for treatment of PAH associated with CTD
45
What therapies are used for immunosuppression in systemic sclerosis?
* Skin disease, early diffuse
* Methotrexate
* Mycophenolate mofetil (MMF)
* Azathioprine
* ILD
* Cyclophosphamide
* MMF
* There is evidence that haematopoietic stem cell transplantation at a specific point in disease progress can be effective in some patients
46
Is systemic sclerosis a life-limiting disease?
Yes, therefore **early involvment of palliative care** for symptom control is important
47
How does systemic lupus erythematosus present?
Symptoms can be vague:
* joint and muscle pain
* fatigue
* rashes - often over the nose and cheeks
* headaches
* mouth sores
* high temperatures
* hair loss
* sensitivity to light (causes rash on exposed skin)
* can be associated with Reynaud's phenomenon
48
What serious complications can arise as a result of SLE?
* kidney failure (lupus nephritis - can be nephrotic or nephritic)
* heart disease (premature coronary heart disease)
49
50
What investigations would you want to do for suspected SLE and what would the expected findings be?
* FBC, U&Es, LFTs, CRP, ESR, urine dipstick
* autoantibodies, immunoglobulines, complement
* X-rays of hands and feet
* if patient presenting to clinic with vague joint pain, may be rheumatoid arthritis, which commonly affetcs hands and feet, so want these to look for signs of RA
* expected findings
* lymphopenia
* elevated dsDNA
* positive ANA titre (strongly positive would be 1:640)
* low C3 and C4 complement
51
What is the pathophysiology of SLE?
**Like many autoimmune and connective disorders, the specific cause of SLE is unknown, although it is likely that a combination of genetic susceptibility and environmental triggers play a part.**
Defective clearance of apoptotic cells results in perpetuation of the immune response in SLE.
52
What are the risk factors for SLE?
* 15-45 years old
* Afro-Caribbean’s and Asians
* Family history
* Tobacco consumption
* Anticonvulsant medications
* also - some mutations in the HLA genes have been linked with a 2-3 fold increase in incidence
53
What mucocutaneous complications need to be monitored in SLE?
* Mouth/nasal/vaginal ulceration
* Malar rash (which spares the nasolabial folds)
* Alopecia
* Photosensitivity
* Raynaud’s phenomenon
* Lupus rashes
* Sicca symptoms
54
What musculocutaneous complications of SLE need to monitored?
* Arthralgia
* Morning stiffness
* Myalgia
* Arthritis
* Jaccoud’s arthropathy (deformities secondary to SLE-associated arthritis
* Osteoporosis
55
What is Jaccoud's arthropathy?
* looks similar to deformities seen in rheumatoid arthritis
* swan neck, ulnar deviation, thumb subluxation, 'boutonniere' and hallux valgus
* 'reversible?'
* absence of erosions on X-ray
56
What renal complications need to be monitored for in SLE?
* Hypertension
* Haematuria
* Nephrotic syndrome (lupus nephritis)
* Renal failure
57
What nervous system complications need to be monitored in SLE?
* Headaches
* Seizures
* Aseptic meningitis
* Psychiatric disorders
* Neuropathy
* Stroke
58
What cardiopulmonary complications need to be monitored in SLE?
* Pleuritis
* Pericarditis
* Non-infective endocarditis
* Lupus pneumonitis
59
What GI system complications have to monitored in SLE?
* Abdominal pain
* Poor appetite
60
What eye complications have to be monitored in SLE?
* Conjunctivitis
* Retinal exudates
* Blindness
* Sicca symptoms
61
What reproductive tract complications have to be monitored in SLE?
* Menorrhagia
* Amenorrhea
* Prematurity
* Stillbirth
* Recurrent miscarriage
* Antiphospholipid syndrome - should be screened for in early pregnancy
* Increased risk of lupus flare during pregnancy
62
What blood abnormalities have to be monitored in SLE?
* Secondary antiphospholipid syndrome (recurrent arterial/venous thrombosis associated with anti-cardiolipin or lupus anticoagulant antibodies)
* Dyslipidaemia
* Haemolytic anaemia
* Leukopenia
* Lymphocytopenia
* Thrombocytopenia
63
How do you manage SLE?
| (four main categories)
* patient education
* pregnancy advice
* monitoring disease activity
* pharmacological
64
What patient education should be given in patients with SLE?
* Sun exposure: regular sunscreen, covering up, sun exposure may provoke a flare
* Smoking cessation (risk of CV event much increased than background population)
* Vigilance for infections and prompt treatment
* Regular exercise and healthy diet
65
What pregnancy advice should be given to patients with SLE?
* Should be planned
* Good disease control prior to conception
* Review of contraction (caution with oestrogen-containing drugs – due to increased risk of DVT)
* Barrier methods or progesterone-only therapy preferred
66
How is SLE disease activity monitored?
* Anti-dsDNA levels
* Complement levels (decreased C3 and C4 suggests active disease)
* ESR
* Blood pressure
* Urinalysis
* Basic blood tests – FBC, U&Es, LFTs, CRP
67
What pharmacological treatment is used in SLE?
* Analgesia e.g. paracetamol, NSIADs
* Cardiovascular risk assessment and reduction therapy e.g. antihypertensives, statin
* Intraarticular steroids – joint involvement
* Hydroxychloroquine – skin and joint involvement
* Note side effect of drug is increased photosensitivity
* Oral glucocorticoids
* Intravenous glucocorticoids
* Steroid-sparing agents e.g. azathioprine, methotrexate, mycophenolate
* Cytotoxic therapy, e.g. cyclophosphamide
Damage accumulates over time as a consequence of the disease and its treatment e.g. T2DM and osteoporosis due to prolonged corticosteroid use.
68
What is the SLICC classification criteria for systemic lupus erythematosus?
_Requirements:_
* \>/= 4 criteria, with at least one from each category (1 clinical, 1 lab)
* OR biopsy-proven lupus nephritis with positive ANA or anti-DNA
_Clinical criteria:_
* acute cutaneous lupus
* chronic cutaneous lupus
* oral or nasal ulcers
* non-scarring alopecia
* arthritis
* serositis
* renal
* neurologic
* haemolytic anaemia
* leukopenia
* thrombocytopenia (\<100,000/mm3)
_Immunological criteria_
* ANA
* Anti-DNA
* Anti-Sm
* Anti-phospholipid Ab (determined by positive test for lupus anticoagulant)
* low complement (C3, C4, CH50)
* direct Coombs' test (do not count in the presense of haemolytic anaemia)
69
What are the risk factors for Reynaud's phenomenon?
* smoking
* female sex
* beta-blocker use
* hypertension
70
What is polymyalgia rheumatica?
* characterised by proximal myalgia of the hip and shoulder girdle, with early morning stiffness lasting over 1 hour
* mainly affects patients over 50
* muscle weakness is not a feature though this can be difficult to assess in the context of pain
* it is associated with an ESR of \>40mm/h and a rapid respoonse to prednisolone
71
What are the other causes of raised ESR?
* Malignancy – most common cause
* Haematological – associated with deranged FBC
* SLE
* Polymyalgia rheumatica
* Rheumatoid arthritis
* Giant cell arteritis
* Systemic sclerosis
* Tuberculosis
* Hepatitis
* Pregnancy – variant of normal
72
What do you need to ask in your history if you think a rash is related to a CTD?
Questions to ask:
* Evolution of the rash: when did the rash first appear, how did it change?
* Is there any itch or bleeding?
* Triggers: does anything make it particularly worse?
* Sunlight: does sunlight affect the rash?
* Have you noticed any medication changes recently?
* Other areas: has the patient noticed any rashes anywhere else on their skin?
* Associated symptoms: has the patient noticed any hair loss, fevers, joint pains, weight loss, dry eyes etc?
73
What is dermatomyositis?
A rare, idiopathic inflammatory myopathy with characteristic skin changes which can occur in children and adults. The systemic disorder may also affect the joints, the oesophagus, the lungs and less commonly the heart.
74
How does dermatomyositis present?
* Proximal muscle weakness
* Dysphagia
* Dysphonia
* Other possible symptoms include respiratory muscle weakness, visual changes and abdominal pain
* Photosensitive rash, that is pruritic and painful
* classically around the eyes, top of back of shoulders (shawl sign) and on knuckles/around nails
75
What investigations would you want to do if you suspected dermatomyositis?
* **Elevated CK**
* Other causes may include
* Polymyositis
* Muscular dystrophies
* Rhabdomyolysis
* Motor neurone disease
* Iatrogenic – statin induced myositis
* **Myositis specific antibodies** can be helpful diagnostically and if positive indicate disease subtypes with specific clinical associations
* **MRI of the muscles** can show muscle oedema indicating inflammation. This will guide site for muscle biopsy
* **Muscle biopsy:** this can be diagnostic and help to differentiate from polymyositis. Biopsy reveals perivascular and interfascicular inflammatory infiltrates with adjoining groups of muscle fibre degeneration/regeneration
* **EMG** is a means of detecting muscle inflammatory and damage and at times been useful in selecting muscle biopsy site
* **Skin biopsy:** epidermis is generally thinned and shows mild hyperkeratosis and parakeratosis. There is florid lichenoid inflammation, with basal cell hydropic degeneration and the formation of numerous cystoid bodies --\> appearance are those of a florid lichenoid dermatitis with epidermal atrophy
76
How do you manage dermatomyositis?
* **Try to induce remission with IV steroids and IV cyclophosphamide**
* If unresponsive can try rituximab and IV immunoglobulin
* If patient develops unsafe swallow:
* Nil by mouth
* IV fluids and NG tube
* Investigation with OGD and barium swallow
* If swallow remains unsafe then PEG tube may be long-term management
* If weakness of thoracic muscles
* Weakness of thoracic muscles is an important cause of acute deterioration in patients with myositis which may be life threatening. Patients should be monitored with serial forced vital capacity measurements whilst on the ward
* An estimated 25% of patients with dermatomyositis have or will develop an associated malignancy, and the risk appears to remain elevated for 3-5 years.
* Therefor **full malignancy screen** taking into account patients risk factors
* If smoker and cachexic then investigate for lung cancer
* CT chest, abdomen, pelvis
* Bronchoscopy should be considered
* If anaemic, then consider OGD and colonoscopy
77
What is Lofgren's syndrome?
* acute & benign form of sarcoid
* triad of:
* erythema nodosum
* arthralgia/arthritis (bilateral ankles)
* bilateral hilar lymphadenopathy
* may have associated systemic features
* mainly self-limiting (NSAIDs and steroids)
* 1% evolve chronic arthritis
* serum ACE may be elevated
78
What is sarcoidosis?
* Sarcoidosis: a Multi-systemic Inflammatory Disorder
* Characterised by epitheliod non-caseating granuloma in involved organs
* Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs.
* Chronic or recurrent erythema nodosum is rare but may occur. Erythema nodosum is presumed to be a hypersensitivity reaction and may occur in association with several systemic diseases or drug therapies, or it may be idiopathic.
* The inflammatory reaction occurs in the panniculus.
79
What are the main primary vasculitides?
* ANCA associated vasculitides
* HSP
* Poly arteritis nodosa
* Giant cell arteritis
* Takayasu’s
* Behcet’s
80
What are the skin signs of vascularis?
* livedo reticularis
* pupuric rash
* nodules
* digital infarction
* ulceration and gangrene
81
Describe what ulcers look like that are associated with vasculitis?
* Deep
* Clear cut edge (punched out appearance
* Edge can have blue-ish or red-ish tinge
* Can be very painful
* Often associated with purpura in the surrounding area
82
What types of ulcers are associated with vasculitis?
* Mouth ulcers – tend to be deeper than regular ulcers, come in clusters and be painful
* Nasal ulcers
* Genital ulcers
83
What eye signs are associated with vasculitis?
* red +/- pain +/- photophobia, also can get anterior or posterior uveitis
84
What musculoskeletal signs can you get with vasculitis?
* arthralgia/arthritis
* myalgia
* wasting muscle
* +/- weakness
85
What ENT signs are associated with vasculitis?
* Epistaxis, crusting, sinusitis, hoarse voice
* Nasal collapse
* Stridor from laryngeal disease
86
What cardio-respiratory symptoms are associated with vasculitis?
* Pain
* Breathless
* Haemoptysis
* Crackles
* Asthma/wheeze
87
What neurological signs are associated with vasculitis?
* Peripheral neuropathy
* Glove and stocking
* Mononeuritis multiplex various nerves are picked off by vasculitis, with the most common ones being:
* CN III, VI, VII, radial, ulnar, median, peroneal, femoral
* Transverse myelitis (sensory, motor and autonomic disturbance, with specific symptoms depending on the level of the lesion)
* If lesion high up in C-spine, then patient at risk of respiratory failure due to involvement of phrenic nerve, which is made up by C3, C4, and C5
* Lower in cervical spine (C5 – T1) you can expect to see UMN and LMN signs in the upper limbs and UMN signs in the lower limbs
* If lesion in thoracic segment, then you will see UMN signs in the lower limbs with a spastic paresis
* If lumbar spine involved, you will see UMN and LMN signs in the lower limbs
88
What abdominal signs are associated with vasculitis?
* Abdominal pain
* Diarrhoea
* +/- blood loss
* Anaemia
Depends on organs involved:
* Liver
* Intestinal (obstruction)
* Peritonitis (local, generalised)
89
How may people with vasculitis present?
* Rash - palpable purpura (commonest)
* PUO and other constitutional symptoms
* Inflammatory arthritis or general arthralgia
* Myositis / myalgia
* Neuropathy - mononeuritis / polyneuritis
* Glomerulonephritis
* End organ ischaemia (abdominal pain / acute visual loss)
* Anaemia / raised inflammatory markers / leucocytosis
* Absent pulses / bruits
* Multi-system features
90
How do you make a diagnosis of vasculitis?
* There are no clear-cut diagnostic criteria
* Guidelines:
* Symptoms and signs of vasculitis and one of
* Positive histology (vasculitis/granuloma)
* +/-
* Positive serology – ANCA (PR3 or MPO)
* Indirect evidence (MRI, CT &angiography)
* **No other disease to explain the symptoms**
* **Key to diagnosis is thinking, ‘could this be vasculitis?’**
91
What is the stepwise assessment of susptected vasculitis?
* _Exclude vasculitis mimics and secondary causes_
* Blood culture
* Echocardiogram
* Hepatitis screen (B&C)
* HIV test
* Antiphospholipid antibodies
* Antinuclear antibody
* _Assess the extent of vasculitis_
* Urine dipstick and microscopy for all patients
* Chest radiograph for all patients
* Nerve conduction studies/electromyography/CK
* _To identify the specific type of vasculitis_
* ANCA
* Cryoglobulin
* Complement levels
* Eosinophils count and IgE levels
* Specific features on biopsy
* _Confirm the diagnosis of vasculitis_
* Angiogram
* PET-CT
* Biopsy
92
What points in a history would point towards a vasculitis mimic instead of true vasculitis?
* Presence of a heart murmur
* Necrosis of lower extremity digits
* Splinter haemorrhages
* Prominent liver dysfunction
* History of recreational drug use
* History of high-risk sexual activity
* Prior diagnosis of neoplastic disease
* Unusually high fevers
**Always rule out the mimics!**
* Presence of a heart murmur
* Necrosis of lower extremity digits
* Splinter haemorrhages
* Prominent liver dysfunction
* History of recreational drug use
* History of high-risk sexual activity
* Prior diagnosis of neoplastic disease
* Unusually high fevers
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What medications can be used in vasculitis (pending clinical context)?
* Corticosteroids \* (induction then taper)
* High dose – often IV initially
* Consider steroid sparing strategies for maintenance
* Cyclophosphamide/rituximab (induction)
* Methotrexate/azathioprine (maintenance)
* Plasma exchange (rescue/severe disease)
* Rituximab (for relapsing disease)
* Anti-cytokine biologics (for relapsing disease)
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What does cutaneous small vessel vasculitis look like?
* numerous petichiae present
* see image
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What are the three types of vasculitis associated with ANCA?
* Granulomatosis with polyangiitis (GPA) – formerly known as Wegener’s granulomatosis
* Eosinophilic granulomatosis with polyangiitis (EGPA) – formerly known as Churg-Strauss syndrome
* Microscopic polyangiitis (MPA)
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What vasculitides are associated with immune complexes?
* Henoch-Schonlein Purpura (HSP) – IgA vasculitis
* Cryoglobulinaemic vasculitis
* Anti GBM vasculitis – formerly known as Goodpasture’s syndrome
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What are the two presentations of granulomatosis with polyangiitis (GPA)?
* systemic/'vasculitic' 67%
* localised/'granulomatosis' 33%
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What is the systemic/vasculitic pattern of presentation of GPA?
* immediately organ threatening
* alveolar haemorrhage
* pulmonary nodules
* may cavitate so important to rule out other causes
* glomerulonephritis
* rapidly progressive GN
* crescentic/sclerosing GN
* high urinary protein creatinine ratio (PCR)
* scleritis
* mononeuritis multiplex
* systemic symptoms
* fever
* weight loss
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What is the localised/granulomatous pattern of presentation of GPA?
* Not immediately organ threatening
* Upper respiratory tract
* ENT (sinusitis)
* Episcleritis
* Skin
* only 5% will remain localised
* more often affects female/younger
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What deformities can be seen in localised GPA (chronic granulomatous inflammation)?
* Nasal cartilage ‘saddle nose deformity’
* Skull base erosion
* Pseudotumour
* Upper airway stenosis
_Investigations_
* CT or MRI of the base of the skull and sinuses
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What antibodies are associated with granulomatous polyangiitis?
* most commonly PR3 (or c-ANCA)
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What is microscopic polyangiitis (MPA)?
* ANCA in 2/3 of patients
* pANCA \>\> cANCA
* MPO \>\>\> PR3
* Raised acute phase response
* CRP/ESR/Platelets
* Anaemia/low albumin
* Rapidly deteriorating renal function
* Urinary red cell casts
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How does MPA present?
* Constitutional symptoms (anorexia/weight loss & fever, myalgia and arthralgia)
* RENAL – glomerulonephritis
* SKIN – maculopapular purpura : lower limbs
* NEUROPATHY – mononeuritis multiplex
* PULMONARY – haemorrhage, infiltrates & effusions
* GI tract – abdominal pain, bleeding, ischaemia, ulceration
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What is eosinophilic GPA?
* formerly churg-strauss
* ANCA +ve
* Long prodromal period – 30yrs +
* **Late onset asthma,** allergic rhinitis
* _Key is that they are associated with peripheral eosinophilia_
* Necrotising small vessel vasculitis with granulomas
* Systemic vasculitis typically 6-9 years after onset of asthma
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How does EGPA present?
* ENT – sinusitis/polyposis
* NEUROLOGY – mononeuritis multiplex
* SKIN – (biopsy shows eosinophils/granulomas)
* CARDIAC (25%) – (myocarditis) – CCF (congestive heart failure) \>\> angina
* GI – abdo pain/bleeding/ (poor prognostic sign)
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What is HSP?
* ANCA -ve
* Diagnosis – usually clinical
* Biopsy may be indicated – skin & renal
* Immune complex deposition disease
* Linear IgA deposits in dermis/renal biopsy
* Leucocytoclastic vasculitis with extravasation of erythrocytes
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How does HSP present?
* Usually affects children, often triggered by strep infection:
* Rash (extensor surfaces) - non blanching palpable purpura
* Inflammatory arthritis (knee / ankle typically)
* Abdominal pain
* Renal – microscopic haematuria
* Streptococcal trigger often found
* **Usually self-limiting (analgesia only)**
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What are adverse prognostic features in HSP?
* Severe abdominal pain / bloody diarrhoea
* Renal impairment (can progress to renal failure) – IgA nephropathy
* Persistent rash \> 1/12
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What is polyarteritis nodosa?
* ANCA negative
* can be associated with staph/strep or hepatitis B, as well as other viral causes such as parvo/CMV/HIV
* also idiopathic variants
* affects mainly medium muscle-suppling vessels, but also small vessels
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How does polyarteritis nodosa present?
* CNS - stroke
* PNS - mononeuritis multiplex
* cutaneous - nodules/purpura
* renal - reno vascular disease/hypertension
* GI - ischaemia --\> perforation/haemorrhage
* orchitis
* constitutional (fever, weight loss)
* myalgia/arthralgia
* raised inflammatory markers
* anaemia/ leukocytosis
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What is the main concern with polyarteritis nodosa?
Main concern is that it can lead to pulmonary artery or renal artery aneurysm
* screened for with ECHO
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What is Kawasaki disease?
* Usually affects children under the age of 5
* Present with fever, lymphadenopathy, rash
* Later – desquamation of hands and feet
* can also get conjunctivitis and cracked red lips
* But want early diagnosis and treatment with steroids and immunoglobulins as may cause coronary artery aneurysms
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What is the presentation of giant cell arteritis (cranial)?
* Temporal headache
* Jaw claudication
* Scalp tenderness
* Polymyalgia
* Neck ache (not associated with movement – just a sore neck)
* VISUAL SYMPTOMS
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What clinical signs might you find with giant cell arteritis?
* absent pulses or bruits
* tender pulseless or thickend temporal arteries
* pale retina or optic disc on fundoscopy
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What investigations would you want for giant cell arteritis and what would you expect the results to be?
* ESR \>100 ; CRP high, Alk phos, Platelets - all elevated
* Hb often reduced (normochromic normocytic)
* Ultrasound Temporal arteries
* +/- Temporal artery biopsy: however beware of skip lesions
* Would treat this patient on presentation whilst waiting for results
* ANCA NEGATIVE
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What would you see on biopsy for giant cell arteritis?
* giant multinucleated cells are hallmark of histopathology (disrupted elastic lamina)
* you can see masive thickening and infiltration of T cells and macrophages causing a very narrow lumen
* easy to see why these arteries can easily become blocked and cause visiom changes (vision loss in 7-20%, hence need for low threshold to start treatment)
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What kind of eye problems can giant cell arteritis cause?
* anterior ischaemic optice neuropathy
* central retinal artery occlusion
* cranial nerve palsies
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What symptoms would you find with anterior ischaemic optic neuropathy?
* diffuse pale disc swelling
* haemorrhage
* cotton wool spots
* irreversible blindness
* high probability of imminent involvement other eye
* **emergency admission for IV methylprednisolone to protect the other eye**
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What signs and symptoms would you find with central retinal artery occlusion?
* 4-14% ophthalmic GCA
* Amaurosis fugax (transient vision loss)
* Vision loss
* Sudden onset
* Decreased visual acuity
* Fundoscopy
* ‘Cherry red spot’
* Pale retina
* Bright spot at fovea
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What might you see if GCA was causing a cranial nerve palsy?
* Compromised blood supply to extraocular muscles/cranial nerves
* Permanent/transient diplopia
* Ophthalmoplegia (CNVI palsy)
* Unequal pupils and ptosis if 3rd nerve involved
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What are the criteria for diagnosing giant cell arteritis?
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What is takayasu's arteritis?
takayasu’s arteritis
* Granulomatous pan-arteritis (throughout the wall of the artery) – affecting large vessels, the aorta & branches
* much more common in Japan, relatively rare in the UK
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What are the three phases of takayasu's arteritis?
* Inflammatory (pre-pulseless)
* Constitutional symptoms
* Ischaemic pulseless phase
* Limb claudication/dizziness/hypertension
* 'Burnt out’ phase
* Persistent symptoms of vascular insufficiency --\> damage has been done but there is no active inflammation
* STENOTIC LESIONS (90%), ANEURYSMS (25%)
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What investigations would you want for takayasu's arteritis?
* CTA
* MRA
* Doppler USS
* US in general would show narrowed lumen and thickened wall of carotid artery
* CT PET
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Why are labelled glucose uptake scans (PET) used for large vessel vasculitis?
* can show extent of disease activity
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How do you treat large vessel vasculitis?
* **Immunosuppression**
* Steroids (high doses initially for induction) – most GCA patients are treated with steroids and average treatment length is 2 years
* Methotrexate or cyclophosphamide (maintenance) – used if complex disease or difficulty withdrawing steroids
* Tocilizumab (IL-6R blockade) also for refractory GCA
* **Manage cardiovascular risk factors** BP/lipids
* **Monitor for cardiac complications**
* Consider endovascular surgery / stenting as last resort for INACTIVE disease only
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