Vasculitides Flashcards
Large Vessel Vasculitis
Large vessel
- temporal arteritis
- Takayasu’s arteritis (See Folder in Cardio)
Medium Vessel Vasculitis
Medium vessel
- polyarteritis nodosa
- Kawasaki disease
Small Vessel Vasculitis
Small vessel
- ANCA-associated vasculitides (Wegener’s, Churg-Strauss, microscopic polyangiitis)
- Henoch-Schonlein purpurn
- cryoglobulinaemic vasculitis
*may also affect medium-sized vessels
Churg-Strauss Syndrome
Churg-Strauss syndrome is an ANCA associated small-medium vessel vasculitis.
This is a small vessel vasculitis with eosinophilic infiltration and granulomatous formation that is characterised by chronic sinusitis, asthma and eosinophilia. Systemic features of malaise, myalgia, fever and weight loss are common. Other symptoms and signs depend on other organ systems involved which most commonly are the lung (asthma, pneumonitis) and skin (purpura, subcutaneous nodules); however, any organ system can be affected including the cardiovascular (heart failure, myocarditis), gastrointestinal (gastroenteritis, ischaemia, bleeding), renal (glomerulonephritis, hypertension), and central nervous systems (mononeuritis multiplex). ANCA is positive in approximately 60% of cases and is predominantly P-ANCA.
Features
- asthma
- blood eosinophilia (e.g. > 10%)
- paranasal sinusitis
- mononeuritis multiplex
- pANCA positive in 60%
NB: Leukotriene receptor antagonists may precipitate the disease
Churg Strauss Syndrome - Diagnosis: Example Question
A 39-year-old lady presented to the emergency department acutely unwell with fever, weight loss and malaise. She had been finding it increasingly difficult to mobilise in recent weeks due to weakness in her right ankle. She had diarrhoea and was passing loose brown stool up to five times a day. She had a previous medical history of asthma and sinusitis. Her medications included a salbutamol inhaler, salmeterol inhaler, montelukast and intermittent courses of prednisolone and antibiotics as required.
On examination, she appeared unwell, had petechial purpura in the nail beds of her fingers and on her feet, expiratory wheeze on auscultation of her chest, a soft abdomen with no palpable masses and weakness of dorsiflexion of her right ankle. Her temperature was 37.4 degrees Celsius, her pulse was 115 beats per minute and regular, her blood pressure was 140/95 mmHg, her respiratory rate was 24 breaths per minute and her oxygen saturations were 94% on room air.
Investigations:
Urine dip: blood++, protein+
Haemoglobin 95 g/L White cell count 23.6 x10^9 /L Platelet Count 181x10^9/L Neutrophils 12.3 x10^9/L Eosinophils 9.6 x10^9/L Basophils 0.2 x10^9/L Lymphocytes 1 x10^9/L Monocytes 0.5 x10^9/L Erythrocyte sedimentation rate 65mm/hr INR 0.9
Serum sodium 138mmol/L
Serum potassium 4.6mmol/L
Serum urea 15.4mmol/L
Serum creatinine 220micromol/L
Antinuclear antibody negative
C-terminus antineutrophil cytoplasmic antibodies negative
Myeloperoxidase anti-neutrophil cytoplasmic antibodies positive
What is the most likely diagnosis?
Infective endocarditis Wegener's granulomatosis E.Coli gastroenteritis > Churg-Strauss syndrome Crohn's disease
This lady with a history of asthma and sinusitis has presented systemically unwell with diarrhoea, a right common peroneal nerve palsy, vasculitic rash and has evidence of a nephritis. Investigations show a significant eosinophilia and immunological screen has shown she is P-ANCA positive. The most likely diagnosis is, therefore, Churg-Strauss syndrome. This is a small vessel vasculitis with eosinophilic infiltration and granulomatous formation that is characterised by chronic sinusitis, asthma and eosinophilia. Systemic features of malaise, myalgia, fever and weight loss are common. Other symptoms and signs depend on other organ systems involved which most commonly are the lung (asthma, pneumonitis) and skin (purpura, subcutaneous nodules); however, any organ system can be affected including the cardiovascular (heart failure, myocarditis), gastrointestinal (gastroenteritis, ischaemia, bleeding), renal (glomerulonephritis, hypertension), and central nervous systems (mononeuritis multiplex). ANCA is positive in approximately 60% of cases and is predominantly P-ANCA.
Infective endocarditis could account for some of her symptoms however the absence of a heart murmur and the multisystem involvement, in this case, makes it less likely. Wegener’s granulomatosis is another granulomatous small vessel vasculitis which most commonly presents with lesions in the upper respiratory tract (rhinorrhoea, sinusitis, saddle nose deformity), lungs (infiltrates and pulmonary haemorrhage) and kidneys (rapidly progressive glomerulonephritis). It is classically C-ANCA positive. The history of immunological screen of this case is, therefore, more typical of Churg-Strauss syndrome. E.coli gastroenteritis would be unlikely to present in this fashion.
Crohn’s disease is a chronic inflammatory bowel disease that classically presents with abdominal pain, weight loss and change in bowel habit. There are often extra-intestinal manifestations involving the mouth, skin, eyes, joints and episodes of perianal abscess or anal fissure. Crohn’s disease could account for some of this lady’s symptoms but again is less likely than Churg-Strauss syndrome.
Chung Strauss Syndrome - Diagnosis: Example Question
A 35-year-old female with a past medical history of sinusitis and asthma for four years is admitted weigh a pyrexia worsening of dyspnoea and ankle swelling. Two weeks prior to admission she had noticed blood streaks were present in her sputum.
On examination she had widespread wheeze and bi-basal crepitations on auscultation of her chest. Her saturations are 94% without oxygen but come up to 99% after treatment with salbutamol and ipratropium bromide nebulisers and oxygen therapy.
She has a heart rate of 112 beats per minute, normal heart sounds and a raised JVP. She has pitting oedema up to her knees. Examination of her abdominal system is unremarkable.
Haemoglobin 102 g/L White cell count 11.2 × 109/L Eosinophil count 1.9 × 109/L Platelet count 478 × 109/L International normalised ratio 1.3
Serum sodium 135 mmol/L Serum potassium 5.5 mmol/L Serum urea 21 mmol/L Serum creatinine 211 mol/L CRP 22 mg/l Blood cultures Coagulase-negative staphylococci ANCA positive immunostaining awaited
Urine dip- positive for protein and blood
CXR: Bi-basal non specific shadowing
What is the most likely diagnosis?
Churg Strauss syndrome Systematic Inflammatory Response Syndrome Systematic Lupus Erythematous Wegeners granulamatosis Microscopic polyangiitis
This patient has essentially presented with acute kidney injury and is ANCA positive. ANCA may be positive in Wegeners granulomatosis, Churg Strauss syndrome and microscopic polyangitis all of which can affect the kidneys. However the history of asthma and sinusitis coupled with a raised eosinophil count make Churg Strauss syndrome the most likely option.
Systematic Inflammatory response syndrome is unlikely to explain the entire clinical picture. Additionally, although blood cultures are positive this is most likely to be a contaminant considering the organism and the trivial C-reactive protein.
Polymyalgia Rheumatica (PMR) - Pathophysiology
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 rheumatic
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
Investigations
- ESR > 40 mm/hr
- note CK and EMG normal
- reduced CD8+ T cells
Treatment
Prednisolone e.g. 15mg/od - dramatic response
Where diagnosis is unclear, a trial of steroid therapy for likely polymyalgia rheumatica is appropriate. The diagnosis will be confirmed by rapid resolution of symptoms following initiation of treatment. Observational studies suggest a typical starting dose of prednisolone around 15 mg with a median time to stopping therapy of two years.
PMR Diagnosis: Example Question
A 65 year old man presented to his General Practitioner with a 3 month history of bilateral shoulder aches and pains. The symptoms were associated with stiffness in the mornings taking up to two hours to resolve after waking. The patient denied any symptoms of headache, jaw claudication or visual disturbance. The patient had no symptoms of dry eyes or mouth, no skin or hair changes, no weight loss and no fevers.
Past medical history included hypertension and chronic obstructive pulmonary disease. Regular medications included ramipril, simvastatin and inhaled salbutamol as required. The patient was an ex-smoker who drank 25 units of alcohol per week. The patient had recently retired having spent his working life as a train driver.
Examination did not reveal any inflamed joints excepting slight tenderness across the shoulder girdle. There was no evidence of scalp tenderness. Cardiovascular and respiratory examination was unremarkable.
Investigations requested by the General Practitioner are listed below.
Haemoglobin 134 g / dL
White cell count 7.5* 109/l
Neutrophils 6.0 * 109/l
Platelets 356 * 109/l
Urea 8.9 mmol / L
Creatinine 110 micromol / L
Sodium 132 mmol / L
Potassium 4.9 mmol / L
Erythrocyte sedimentation rate 85 mm / h
Rheumatoid factor Negative
Creatinine kinase 121 U / L (reference 5-130)
Calcium (adjusted) 2.25 mmol / L (reference 2.18-2.58)
Alkaline phosphatase 67 U / L (reference 35-100)
Thyroid stimulating hormone 2.5 microU / L
Protein electrophoresis Normal
What is the appropriate next management step for this patient?
Stop statin therapy and review in 6 weeks Ultrasound study of shoulders and hips Referral for specialist rheumatology opinion > Prednisolone 15 mg daily with dose tapering over 2 years Prednisolone 40 mg daily with dose tapering over 1 year
This patient presents with a classical history for polymyalgia rheumatica and a raised ESR. There are no factors in the history or investigations that suggest an alternative diagnosis (for example, giant cell arteritis, other connective tissue disease, myeloma, malignancy or occult infection). The normal CK would make statin-induced myopathy unlikely.
In such cases, a trial of steroid therapy for likely polymyalgia rheumatica is appropriate. The diagnosis will be confirmed by rapid resolution of symptoms following initiation of treatment. Observational studies suggest a typical starting dose of prednisolone around 15 mg with a median time to stopping therapy of two years.
Musculoskeletal ultrasound often identifies inflammation around the shoulders and hips although these findings are not unique to polymyalgia rheumatica. The usefulness of this technique is yet to be determined outside of specialist settings.
Temporal Arteritis
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.
Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
headache (found in 85%)
jaw claudication (65%)
visual disturbances secondary to anterior ischemic optic neuropathy
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
Investigations
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
Treatment
high-dose 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
Temporal Arteritis - Diagnosis: Example Question
A 77-year-old lady is reviewed in the Rheumatology Clinic with a 4-week history of malaise and bilateral hip pain.
The pain is poorly localised and affects the anterior and posterior aspects of the pelvis as well as the upper thighs. It is typically worse in the mornings and associated with feelings of stiffness that take several hours to improve.
She also reports the recent onset of a right-sided headache, which is constant and has been present for the past 2 weeks. 24 hours ago, she developed an episode of transient visual darkening although she is unable to recall which eye was affected.
Her past medical history is remarkable for hypertension and hypothyroidism. Her regular medications include amlodipine 5mg once daily and levothyroxine 75 micrograms once daily.
On examination, her visual acuity is 6/9 in both eyes. Her temperature is 37.3ºC, her pulse is 73bpm and her blood pressure is 143/81mmHg. Neurological examination reveals no focal abnormality although the pulsation of her right temporal artery is difficult to feel.
Her blood results are as follows:
Hb 124 g/l Na+ 141 mmol/l Platelets 444 * 109/l K+ 3.9 mmol/l WBC 11.2 * 109/l Urea 4.3 mmol/l Neuts 8.1 * 109/l Creatinine 78 µmol/l Lymphs 2.3 * 109/l CRP 102 mg/l Eosin 0.02 * 109/l
A temporal artery biopsy is performed and a 0.8cm sample is obtained. It is reported as being ‘negative for giant cell arteritis (GCA)’.
What is the most appropriate treatment strategy?
> IV methylprednisolone 1 gram once daily Prednisolone 15mg once daily Amitriptyline 10mg once daily Explanation, reassurance and referral to physiotherapy for graded aerobic exercise Prednisolone 60mg once daily
This lady’s presentation is consistent with GCA. The picture is complicated by additional features of polymyalgia rhuematica (PMR) although it is important to bear in mind that the two often occur together in clinical practice.
A normal temporal artery biopsy does not rule out GCA due to the possibility of skip lesions giving rise to a false negative result. 7-44% of patients with GCA will have a negative temporal artery biopsy and such falsely reassuring results are more likely to occur when shorter arterial specimens are obtained. For this reason, the British Society for Rheumatology (BSR) recommends that biopsy specimens should no less than 1cm in length.
Transient visual loss can herald the onset of permanent blindness and the BSR recommend that these patients receive IV methylprednisolone 500-1000mg daily for 3 days.
Those with established visual loss or uncomplicated GCA should receive 60mg prednisolone daily.
Prednisolone 15mg daily is the treatment for isolated PMR and would not be appropriate in this case. The remaining options are treatments for fibromyalgia and are therefore incorrect.
Polyarteritis Nodosa (PAN)
Polyarteritis nodosa (PAN) is 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
Features
fever, malaise, arthralgia
weight loss
hypertension
mononeuritis multiplex, sensorimotor polyneuropathy
testicular pain
livedo reticularis
haematuria, renal failure
perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with ‘classic’ PAN
hepatitis B serology positive in 30% of patients
PAN - Angiogram Example
SEE PASSMED PAN ANGIOGRAM
Angiogram from a patient with polyarteritis nodosa. Both kidneys demonstrate beading and numerous microaneurysms affecting the intrarenal vessels. Similar changes are seen affecting the intrahepatic vessels with a few small microaneurysms noted. The proximal branches of the SMA appears normal; however there are no normal straight arteries from the jejunal arteries and lack of normal anastomotic arcades and loops. This is associated with multiple microaneurysms.
PAN - Diagnosis and Vasculitis Differentials : Example Question
A 52-year-old man presents with lethargy and reduced sensation in both feet. He reports a 2 month history of fevers and 4kg weight loss. He also reports intermittent testicular pain.
On examination there is livedo reticularis on both legs and reduced light touch and pain sensation on both feet.
Blood tests reveal:
Hb 116 g/l Na137 # mmol/l Bilirubin 18 µmol/l
Platelets 487 * 109/l K+ 4.8 mmol/l ALP 92 u/l
WBC 8.3 * 109/l Urea 12.8 mmol/l ALT 102 u/l
Neuts 6.3 * 109/l Creatinine 182 µmol/l γGT 16 u/l
MCV 89 fL ESR 78mm/hr Albumin 35 g/l
What is the most likely diagnosis?
Cryoglobulinaemia Granulomatosis with polyangiitis Eosinophilic granulomatosis with polyangiitis > Polyarteritis nodosa Microscopic polyangiitis
Fever, lethargy, neuropathy, testicular pain and renal dysfunction are consistent with polyarteritis nodosa (PAN).
All systemic vasculitides can present with fever and lethargy, however polyarteritis nodosa is the systemic vasculitis most frequently associated with testicular involvement.
Chung Strauss - Ix: Example Question
A 30-year-old man presents to the Emergency Department with severe shortness of breath, cough and ongoing weight loss. He has a past medical history of asthma and nasal polyps.
He has seen his general practitioner (GP) 3 times in the last 6 months for chest infections and been given antibiotics.
Given the likely underlying diagnosis, what would you expect to see on his blood results?
Low lymphocyte count Iron deficiency anaemia Raised neutrophil count > Raised eosinophil count Low platelet count
Although a raised neutrophil count is a potential here, a raised eosinophil count is classical of Churg-Strauss, and is required for diagnosis. Nasal involvement is more commonly associated with Wegener’s granulomatosis, but it is also seen in a variety of other vasculitides.
Churg-Strauss syndrome (also known as eosinophilic granulomatosis with polyangiitis) is a vasculitis that affects small and medium-sized blood vessels.
It is commonly seen in patients with a history of atopy. It is often described to occur in three stages - the allergic ‘prodromal’ stage, the eosinophilic stage and the final vasculitic stage.
The mainstay of treatment includes steroids and other immunosuppressant drugs.
Granulomatosis with Polyangiitis (Wegener’s Granulomatosis)
Granulomatosis with polyangiitis is now the preferred term for Wegener’s granulomatosis. It is an autoimmune condition associated with a necrotizing granulomatous vasculitis, affecting both the upper and lower respiratory tract as well as the kidneys.
Features
upper respiratory tract: epistaxis, sinusitis, nasal crusting
lower respiratory tract: dyspnoea, haemoptysis
rapidly progressive glomerulonephritis (‘pauci-immune’, 80% of patients)
saddle-shape nose deformity
also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions
Investigations
cANCA positive in > 90%, pANCA positive in 25%
chest x-ray: wide variety of presentations, including cavitating lesions
renal biopsy: epithelial crescents in Bowman’s capsule
Management steroids cyclophosphamide (90% response) plasma exchange median survival = 8-9 years
Granulomatosis with Polyangiitis (Wegener’s) - Diagnosis: Example Question
A 40-year-old banker, recently returned from a business trip to Hong Kong presented to the Emergency Department with a four-week history of fever, nasal crusting, haemoptysis and dyspnea. His CXR showed patchy air space shadowing in the right and left mid-zone with possible cavitation.
Blood tests showed:
Hb 100g/L WCC 7 x 10^9/L Platelets 625 x 10^9/L CRP 56 mg/l Urea 8.1mmol/L Creatinine 138µmol/L ANA Positive cANCA Negative
What is the most likely diagnosis?
Pulmonary embolism > Granulomatosis with polyangiitis Pulmonary TB Churg-Strauss syndrome Microscopic polyangiitis
This patient has a positive ANA, which demonstrates the presence of autoantibodies. This makes PE, TB and HIV less likely diagnoses. There is involvement of the upper and lower respiratory tract with cavitating lung lesions and mild renal impairment which makes granulomatosis with polyangiitis the most likely diagnosis. A small proportion of patients with granulomatosis with polyangiitis are cANCA negative. These patients typically have symptoms and signs limited to the ear, nose, throat and lungs. Involvement of the upper respiratory tract is spared in in microscopic polyangitis. In Churg-Strauss the patient would not have upper respiratory tract involvement and the patient would have a positive pANCA.
