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.
Polyarteritis Nodosa - Diagnosis: 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 34 g/l
Which investigation is most likely to reveal the diagnosis?
Hepatitis C serology > Renal angiogram cANCA pANCA Hepatitis B serology
Fever, lethargy, neuropathy, testicular pain and renal dysfunction are consistent with polyarteritis nodosa (PAN).
Whilst the other investigations listed would be appropriate, angiography would be most likely to confirm the diagnosis (sensitivity 89%, specificity 90%).
ANCA is classically negative in PAN. Hepatitis serology would be appropriate as this can be associated with vasculitis however will not reveal the diagnosis in this case.
Microscopic Polyangiitis
Microscopic polyangiitis is a small-vessel ANCA vasculitis
Features
renal impairment: raised creatinine, haematuria, proteinuria
fever
other systemic symptoms: lethargy, myalgia, weight loss
rash: palpable purpura
cough, dyspnoea, haemoptysis
mononeuritis multiplex
Example Ix: Rheumatoid factor negative C3 and C4 levels normal cANCA positive pANCA positive ANA negative
Renal biopsy: focal necrosis, crescent formation, and absence of immunoglobulin deposits on immunofluorescence.
Microscopic Polyangiitis - Diagnosis: Example Question
A 49 year old woman presents with a one year history of joint pain and an intermittent purpuric rash. For the last 3 month she feels more fatigued than usual with malaise, fever and intermittent abdominal pain. She had an appendectomy 10 years ago. Beside that there is no past medical history of significance.
On clinical examination the only abnormality is a purpuric rash involving her calves and thighs.
The results of initial investigations showed a normal full blood count, but impaired renal function with a plasma creatinine of 160 µmol/l.
Another set of investigations were ordered to reach a diagnosis:
Na+ 135 mmol/l K+ 4 mmol/l Creatinine 165 mmol/l Urea 11 mmol/l CRP 50 mg/l ESR 70 mm/hr Urine analysis Protein +,RBCs ++ Rheumatoid factor negative C3 and C4 levels normal cANCA positive pANCA positive ANA negative
Renal biopsy showed focal necrosis, crescent formation, and absence of immunoglobulin deposits on immunofluorescence.
What is the most likely diagnosis?
Rheumatoid vasculitis Mixed cryoglobulinaemia Wegner's granulomatosis (WG) > Microscopic polyangitis (MPA) Systemic lupus erythematosus (SLE)
MPA is a systemic vasculitis affecting the small vessels including arterioles, capillaries, and venules. It usually presents with a long history of constitutional symptoms with multisystem involvement. Note that cANCA, and pANCA could be useful in differentiating WG from MPA but not always.
SLE would be unlikely with a negative ANA, and pauci immunglomerulonephrits.
WG is unlikely with the absence of upper and lower airway involvement. Also the absence of granuloma formation in the kidneys would not favor it.
Usually rheumatoid vasculitis would be clinically apparent because it develops on a background of severe rheumatoid disease. Also the rheumatoid factor would be very high, with low C3 and C4.
Mixed cryoglobulinaemia characteristically would have positive rheumatoid factor. Glomerulonephritis has distinctive features, being characterized by marked deposition of immunoglobulin and complement. C4 would be markedly low in 90% of patients due to classical pathway activation by cryoglobulins. This is in contrast to MPA where the complement levels would be normal or even elevated as an acute phase response.
Chung Strauss Syndrome and pANCA - Diagnosis - Example Question
A 46-year-old gentleman was referred by his GP to the respiratory clinic with deteriorating asthma control. He was diagnosed by his GP 2 years ago following complaints of feeling short of breath on exertion with wheeziness. Unfortunately, his symptoms deteriorated despite a trial of Clenil modulate 1000mcg BD, salmeterol 200mcg BD and montelukast 10mg OD. Upon further questioning, he stated that he had pins and needles in both hands as well as numbness of his fingertips for the last few weeks. His past medical history included hypertension, gout and sinusitis for which he was prescribed ramipril 5mg OD, allopurinol 100mg OD, salbutamol PRN and mometasone nasal spray 50mcg BD. He smoked 20 cigarettes per day and consumed 12 units of alcohol per week.
On examination, he appeared unwell. His heart rate was 98 bpm, respiratory rate 18/min, oxygen saturations 94% on air and blood pressure 146/82 mmHg. His heart sounds were normal with a normal JVP and examination of the chest revealed bilateral expiratory wheezes globally. Examination of the abdomen was normal. Examination of the peripheral nervous system demonstrated a peripheral neuropathy with a glove and stocking sensory loss of the upper limbs. Examination of the skin revealed the presence of purpura on his lower legs.
Initial investigations revealed the following results:
Hb 102 g/l Platelets 342 * 109/l WBC 12.1 * 109/l Neutrophils 82% count Lymphocytes 7% count Eosinophils 10% count Monocytes 1% count ESR 42 mm/hr
Na+ 141 mmol/l
K+ 3.9 mmol/l
Urea 6.2 mmol/l
Creatinine 78 µmol/l
Chest x-ray: bilateral scattered pulmonary shadowing in lower zones
ECG: heart rate 97bpm, normal sinus rhythm, QRS interval 112ms, QTc interval 424ms
Which of the following tests is most likely to lead to the underlying diagnosis?
Anti glomerular basement membrane antibodies > p-ANCA antibodies ANA antibodies Anti Jo-1 antibodies c-ANCA antibodies
This gentleman presents with a combination of worsening asthma in combination with sinusitis. He has pulmonary infiltrates on his chest x-ray, as well as polyneuropathy and an eosinophilia. The diagnosis is strongly suggestive of Churg-Strauss syndrome, and of the following options, p-ANCA antibodies are the most sensitive and specific to this condition.
Giant Cell Arteritis - Diagnosis
1990 Criteria - 3 of the following required for GCA diagnosis:
1) Age > 50
2) New onset localised headache
3) Temporal artery tenderness or Decreased pulsation
4) ESR >50mm/hr
5) Temporal artery biopsy +ve
Giant Cell Arteritis - Mx
Uncomplicated GCA (No visual involvement and/or jaw/tongue/claudication): - Treated with PO Prednisolone 40-60mg OD until Sx and Ix normalise
Complicated GCA (Visual involvement and/or jaw/tongue claudication) - IV Methylprednisolone 500-1000mg for 3d b4 starting PO pred
NB: As GCA treatment requires potentially long term steroid therapy, bone sparing agents (bisphosphonates and vitamin D) AND gastroprotective drug (omeprazole) should be co-prescribed
Also consider low dose aspirin as has been shown to reduce rate of visual loss and cerebrovascular accidents
Temporal Arteritis - Diagnosis: Example Question
A 77 year old male presents to the Emergency Department with a two day history of right temporal, throbbing headache, constant in nature and 8/10 severity. He report this being the first ever episode of this headache and is different to his previous migraines, which have been typically on the left occipital region, lasting minutes, and fairly stereotyped over the past 60 years. Apart from migraines, he has no other medical history. On examination, his right scalp is tender and a prominent right temporal artery is noted. He is apyrexic with no skin rashes. His blood tests are as follows:
Hb 13.8 g/dl
Platelets 552 * 109/l
WBC 11.5 * 109/l
ESR 85 mm/hr
Na+ 146 mmol/l K+ 4.4 mmol/l Urea 9.6 mmol/l Creatinine 115 µmol/l CRP 23 mg/l
You empirically start him on 60mg prednisolone. He undergoes temporal artery biopsy within 24 hours of his admission demonstrating no signs of temporal arteritis.
What is the most appropriate next step?
Repeat temporal artery biopsy Continue prednisolone but at reduced dose 10mg OD Discharge > Continue prednisolone at 60mg Start anti-migraine medication
All the clinical features point to right temporal arteritis. Remember that a negative temporal artery biopsy does not rule out temporal arteritis! Shorter lengths of biopsy or removal of a ‘skip lesion’ result in a 9% false negative rate. There is no indication for a repeat temporal artery biopsy on the same or contralateral side, an ultrasound temporal artery may be helpful instead. Someone who has clinical temporal arteritis should thus maintain on high dose prednisolone to protect their vision. This headache is clearly different from the patient’s normal migraines; anti-migraine medication is thus inappropriate.
Mononeuritis Multiplex and Microscopic Polyangiitis- Example Question
A 53 year-old businessman presents to the neurology clinic complaining of weakness and numbness affecting his left hand. One month ago he was irritated when he noticed that the little finger of his left hand was often getting caught when he tried to put his hand in his pocket. Since then he has noticed progressive difficulty using the left hand, associated with an unpleasant tingling sensation.
In the last two weeks he has also noticed difficulty walking, and has tripped over on several occasions. When driving he finds that his right foot often becomes stuck behind the accelerator pedal and he struggles to lift it out.
On examination, in the left hand sensation to pin-prick is diminished over the little finger and medial side of the ring finger, as well as the medial side of the palm. There is weakness of finger abduction and adduction, but thumb abduction is normal. On examination of the legs, you note diminished sensation over the lateral aspect of the right calf, as well as the dorsum of the right foot. When asked to walk on his heels, he finds it difficult to do so, and trips over the right foot.
Investigations are as follows:
Haemoglobin 14.2 g/dl
WCC 7.1 x10^9/l
Platelets 420 x10^9/l
ESR 65 mm/hr
Na+ 139 mmol/l K+ 4.3 mmol/l Urea 13.2 mmol/l Creatinine 171 µmol/l Corrected calcium 2.26 mmol/l
ANCA Positive, with perinuclear staining pattern
PR3 antibodies Negative
MPO antibodies Positive
Urine dipstick +++ blood, +++ protein
Urine microscopy Red cell casts
Chest radiograph Clear
What is the most likely diagnosis?
> Microscopic polyangiitis Polyarteritis nodosa Wegeners granulomatosis Diabetes mellitus Entrapment neuropathy
This is mononeuritis multiplex with ulnar and common peroneal neuropathy. The causes of mononeuritis multiplex include vasculitis, diabetes, AIDS, amyloidosis, and rheumatoid arthritis.
The elevated urea and creatinine, haematuria with red cell casts, and proteinuria, all suggest glomerulonephritis. The combination of mononeuritis multiplex with glomerulonephritis strongly suggests systemic vasculitis. This is supported by the raised ESR.
Microscopic polyangiitis is a small-vessel vasculitis which is typically positive for p-ANCA, with antibodies against MPO (myeloperoxidase). Other features may include systemic symptoms such as fever, weight loss, and fatigue, as well as rash.
ANCA is negative in classic polyarteritis nodosa.
Wegeners granulomatosis often features upper airway disease, and is typically positive for c-ANCA, with antibodies against PR3.
Diabetes mellitus is a common cause of many peripheral neuropathies including mononeuritis multiplex, however there is nothing in the history to suggest this. Haematuria and red cell casts are not a typical feature of diabetic nephropathy, and neither is ANCA positivity.
Entrapment is a common cause of both ulnar and common peroneal neuropathy, but for both to occur simultaneously would be unusual.
PAN - Diagnosis: Example Question
A 52-year-old man presents with feeling generally unwell. For the past few weeks he has felt lethargic, lost weight and had troublesome testicular pain. Over the past week he has also noticed a ‘weakness at the ankle’ on the right side.
On examination blood pressure is 164/96 mmHg, pulse 86/min, temperature 37.3ºC. Examination of the cardiovascular system is unremarkable. Foot drop is noted on the right side consistent with a common peroneal nerve palsy. A rash is also noted on his legs:
SEE PASSMED LIVEDO RETICULARIS
A urine dipstick shows blood++. What is the most likely diagnosis?
Henoch-Schonlein purpura Wegener's granulomatosis > Polyarteritis nodosa Amyloidosis Behcet's syndrome
PAN - Example Question
A 23-year-old woman is investigated for abdominal pain and haematuria. She started developing abdominal pain around 2 months ago and it is generally worse after eating. She also reports arthralgia, weight loss of 3kg and general lethargy.
On examination blood pressure is 150/102 mmHg, pulse 84/min and temperature 37.6ºC. Dipstick examination of her urine shows blood+++.
Bloods show the following:
Na+ 142 mmol/l K+ 4.9 mmol/l Urea 8.9 mmol/l Creatinine 123 µmol/l CRP 73 mg/l
An angiogram is performed:
SEE PASSMED PAN
What is the most likely diagnosis?
Renal cell cancer > Polyarteritis nodosa Henoch-Schonlein purpura Antiphospholipid syndrome Granulomatosis with polyangiitis
The combination of systemic symptoms, fever, hypertension and renal failure are supportive of polyarteritis nodosa. The abdominal pain is due to the arteries supplying the gut being affected.
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.
Kawasaki Disease
Kawasaki disease is a type of vasculitis which is predominately seen in children. Whilst Kawasaki disease is uncommon it is important to recognise as it may cause potentially serious complications, including coronary artery aneurysms
Features
high-grade fever which lasts for > 5 days. Fever is characteristically resistant to antipyretics
conjunctival injection
bright red, cracked lips
strawberry tongue
cervical lymphadenopathy
red palms of the hands and the soles of the feet which later peel
Kawasaki disease is a clinical diagnosis as there is no specific diagnostic test
Management
high-dose aspirin*
intravenous immunoglobulin
echocardiogram (rather than angiography) is used as the initial screening test for coronary artery aneurysms
Complications
coronary artery aneurysm
*Kawasaki disease is one of the few indications for the use of aspirin in children. Due to the risk of Reye’s syndrome aspirin is normally contraindicated in children.
Kawasaki Disease - Example Question
A 16 year old Singaporean boy is brought in to A&E by mother after feeling generally unwell and feverish for one week. He has no past medical or significant family history. He has not travelled recently. On examination, he complains of a sore lip, where you note significant peeling. He has red eyes bilaterally, swollen feet bilaterally and prominent lymph nodes on the right side of his neck. What is the most appropriate next management step?
> Intravenous immunoglobulin Intravenous methylprednisolone Intravenous augmentin Anti-tuberculous treatment Ultrasound guided lymph node biopsy
The patient has presented with sufficient clinical features to satisfy the criteria for Kawasakis disease:
Fever of 5 days of more and associated with at least 4 of:
i. Bilateral non-suppurative conjunctivitis
ii. Mucous membrane changes in the pharynx, lips or tongue
iii. Peripheral oedema, periungunal desquamation or generalised desquamation
iv. Polymorphic rash, typically within truncal regions
v. Cervical lymphadenopathy
The key differential in this case is that of scarlet fever, most commonly affecting younger children cause by the toxin of streptococcus pyogenes infection. However, conjunctival and eye symptoms are less pronounced. Intravneous immunoglobulin is the treatment required in this scenario, there is no evidence for corticosteroids in Kawasakis disease. The patient is relatively late in the disease course as peripheral desquamation appears to have taken place. The main concern is the development of coronary arterial aneurysms. Aspirin must also be promptly prescribed.
Kawasaki Disease - Diagnostic Criteria
Fever of 5 days of more and associated with at least 4 of:
i. Bilateral non-suppurative conjunctivitis
ii. Mucous membrane changes in the pharynx, lips or tongue
iii. Peripheral oedema, periungunal desquamation or generalised desquamation
iv. Polymorphic rash, typically within truncal regions
v. Cervical lymphadenopathy
Henoch Schonlein Purpura
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger’s disease). HSP is usually seen in children following an infection.
Features
palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs
abdominal pain
polyarthritis
features of IgA nephropathy may occur e.g. haematuria, renal failure
Purpura
The classical skin rash often precedes clinical presentation. The purpura is typically palpable, over the lower limbs in an extensor and buttock distribution
Arthralgia
Typically the larger joints are affected with pain, swelling and reduced range of movement. The joint pain does not result in permanent damage.
Gastrointestinal
The symptoms can range to colicky abdominal pain to gastrointestinal haemorrhage and intussusception.
Renal
Renal involvement has a wide range including microscopic haematuria, macroscopic haematuria, proteinuria, nephrotic/nephritic syndrome and renal impairment. There may also be hypertension. Most patients with renal involvement will make a fully recovery.
Henoch Schonlein Purpura - Treatment and Prognosis
Treatment
analgesia for arthralgia
treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants
Prognosis
usually excellent, HSP is a self-limiting condition, especially in children without renal involvement
around 1/3rd of patients have a relapse
Henoch Schonlein Purpura - TRIAD
PURPURA
ARTHRITIS
ABDOMINAL PAIN
HSP - Example Question
An 16 year-old presents with a 2 day history of abdominal pain. On questioning, this is a constant ache with no obvious exacerbating or precipitating factors. He is opening his bowels as normal. He is usually well, aside from a cold in the preceding week.
He has an antalgic gait and complains of pain in his left knee. Examination of his left knee is unremarkable. He has bilteral mild periorbital oedema. There is also an extensive purpuric rash, focused around his buttocks and posterior leg. This is non-blanching.
Urinalysis: Blood 3+, Protein 2+
Hb 135 g/l Na+ 135 mmol/l
Platelets 230 * 109/l K+ 3.5 mmol/l
WBC 11 * 109/l Urea 7 mmol/l
Neuts 9 * 109/l Creatinine 85 µmol/l
What is the most likely diagnosis?
Intussusception > Henoch-Schonlein purpura Idiopathic thrombocytopenic purpura Glomerulonephritis Bacterial meningitis
Henoch-Schonlein purpura (HSP) is an IgA-mediated autoimmune vasculitis, often preceded by an upper respiratory tract infection.
It is characterised by the classic triad of purpura, arthritis and abdominal pain.
Immune mediated thrombocytopenia and bacterial meningitis (with septicaemia), are both differentials of a purpuric rash. They are unlikely in this case due to a normal platelet count, low inflammatory markers and a well patient with no features of meningism.
Granulomatosis with Polyangiitis (Wegener’s_ Diagnosis: Example Question
A 78-year-old female presents to the Emergency Department with confusion, nausea and vomiting. She has been generally unwell with fatigue, weakness and fevers for 4 weeks. On examination her respiratory rate is 26/min, oxygen saturations are 98% on 4 litres of oxygen, blood pressure 100/65 mmHg, pulse 120/min and temperature is 36.3oC. Her airway is patent and crepitations are present at both bases. There are crusting lesions beneath both nostrils, the pulse is thready and regular, heart sounds are normal and her abdomen is soft non-tender. Electrocardiogram shows a sinus tachycardia and urine dip showed 3+ blood and protein. Arterial blood gas on 4 litres of oxygen is as follows:
pH 7.35 pO2 7.79 kPa pCO2 3.52 kPa Bicarbonate 17 mmol/l Base Excess -6.9 mmol/l Lactate 4.5 mmol/l
Venous blood analysis is as follows:
Hb 119 g/l Na+ 129 mmol/l Platelets 511 * 109/l K+ 6.2 mmol/l WBC 19.1 * 109/l Urea 42.1 mmol/l Neuts 17.2 * 109/l Creatinine 497 µmol/l Lymphs 1.8 * 109/l CRP 241 mg/l Eosin 0.04 * 109/l
The patient was resuscitated with fluids and antibiotics although the full septic screen was negative and renal function remained poor. ANA and cANCA pattern were positive with PR3 antibodies found and the renal team were involved. What is the most likely underlying diagnosis?
Lymphoma Churg-Strauss syndrome > Granulomatosis with polyangiitis Acute myeloid leukaemia Goodpasture's syndrome
This patient presents with systemic inflammatory response syndrome (SIRS) as evidence by her tachycardia, tachypnoea and leucocytosis. The most common cause, in this case, would be sepsis, however, history, examination and investigations have not demonstrated a source. The raised lactate suggests end organ hypo-perfusion. Routine biochemistry demonstrates severe renal impairment which must be assumed to represent stage 3 acute kidney injury (AKI) without previous values for comparison. Arterial blood gas demonstrates a compensated metabolic acidosis consistent with acute kidney injury, sepsis or SIRS.
With a negative septic screen we must consider alternative causes of SIRS and in the context of stage 3 AKI and heavy blood and protein on the urine dip, intrinsic renal pathology must be suspected. Granulomatosis with polyangiitis (previously known as Wegener’s Granulomatosis) typically presents with non-specific symptoms, an unwell patient and AKI with active urinary sediment. Nasal crusting due to granulomas and a collapsed nasal septum may also be found. The diagnosis is also suggestive by a positive cANCA with PR3 antibodies although renal biopsy is required to confirm the diagnosis.
Wegener’s vs Churg Strauss
Wegener’s
- Renal F
- Epistaxis/Haemoptysis
- cANCA
Chung-Strauss
- Asthma
- Eosinophils
- pANCA
BOTH:
- Vasculitis
- Sinusitis
- Dyspnoea
Behcet’s TRIAD
Behcet’s TRIAD
Oral Ulcers + Genital Ulcers + Anterior Uveitis
Also DVT and Aseptic Meningitis
Ocular involvement is most feared Cx:
- retinal vasculitis
- iridocyclitis
- chorioretinitis
Assoc with defect in HLA-B gene
Behcet’s Syndrome
= a complex multisystem disorder assoc w presumed autoimmune mediated inflammation of arteries and veins
The presence of aetiology has to be elucidated
Classic Triad of Oral ulcers, Genital ulcers, and anterior uveitis
Epidemiology:
- more common in eastern Mediterranean e.g. Turkey
- more common in men and more severe in men
- tends to affect young adults (20-40)
- assoc w HLAB5 (specifically HLAB51) and MICA6 allele
- around 30% patients have positive FHx
Features:
- classically 1) oral ulcers 2) genital ulcers 3) anterior uveitis
- thrombophlebitis
- neuro involvement eg aseptic meningitis
- GI - Abdo pain, diarrhoea, colitis
- Erythema nodosum
- DVT
Diagnosis = no definitive test, based on clinical findings
Positive pathology test = suggestive - puncture site following needle prick becomes inflamed w small pustule forming
Wegener’s Granulomatosis
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 with PR3 positive antibodies
PAN
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.
Also 30% Positive Hep B Serology
Churg Strauss
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.
Remember = Chucky P - p-ANCA
Wegener’s/Granulomatosis with Polyangiitis - RPGN: Example Question
A 56-year-old gentleman was admitted to the Emergency Department with a two-week history of progressively increasing shortness of breath, with frank haemoptysis for the last couple of days. He had recently returned from a holiday in Turkey a few weeks ago. By the point of admission, he was short of breath on minimal exertion and at rest and was unable to complete full sentences. He also complained of increasing orthopnoea for the last few weeks. He had a long history of recurrent epistaxis, rhinitis and sinusitis, as a well as a past medical history of diabetes, hypertension, hypercholesterolaemia and gout. His medication regimen comprised of mometasone nasal spray, allopurinol 100mg OD, ramipril 2.5 mg OD, amlodipine 5mg OD, simvastatin 40mg OD, metformin 500mg TDS and gliclazide 80mg OD. He smoked 20 cigarettes per day and did not consume alcohol.
On examination, he appeared very unwell with obvious respiratory distress. His respiratory rate was 28/min, his oxygen saturations were 90% on air, his blood pressure was 108/72 mmHg, his heart rate was 129 and his temperature was 37.9 degrees celsius. Examination of his cardiovascular system revealed normal heart sounds with a JVP of 3cm. Examination of the respiratory system revealed the use of accessory muscles with bibasal fine crackles. Examination of the gastrointestinal and neurological systems was unremarkable.
Initial investigations revealed the following:
Hb 82 g/l
Platelets 342 * 109/l
WBC 14.2 * 109/l
ESR 88 mm/hr
Na+ 128 mmol/l K+ 6.1 mmol/l Urea 28 mmol/l Creatinine 762 µmol/l CRP 42 mg/l Glucose 5.6 mmol/l
Chest x-ray: bilateral patchy infiltration
ECG: heart rate 132 bpm normal sinus rhythm, no other changes
Urinalysis blood ++++ protein +++ leuc/nit negative glucose negative
ABG on 15 l/min oxygen:
PaO2 16.9 kPa
PaCO2 2.8 kPa
HCO3 18.2 mmol/l
pH 7.49
He was catheterized, commenced on an intravenous infusion of normal saline, as well as co-amoxiclav 625mg TDS and quickly transferred to the Intensive Care Unit. A decision was made to institute immediate haemodialysis, for which preparations were being made.
Further investigations revealed the following:
Urine MCS: nil grown
Blood culture - interim results: nil grown
Transoesophageal echocardiogram: normal systolic function, valvular appearances and no vegetations seen
C3 1.22 (NR 0.65 1.65g/L) C4 0.32 (NR 0.16 0.60 g/L) ANA negative ENA negative dsDNA negative cANCA positive pANCA negative Rheumatoid factor negative
Given the likely underlying diagnosis, which of the following interventions is the next best step whilst awaiting haemodialysis?
Stop IV augmentin, commence IV meropenem
Commence IV immunoglobulins
> Commence high dose IV methylprednisolone and cyclophosphamide
Institute immediate plasma exchange
Commence intravenous activated protein C
This patient has granulomatosis with polyangiitis, with severe pulmonary and renal involvement. He requires urgent immunosuppression. Of the available options, the next best step is therefore to institute cyclophosphamide and methylprednisolone. The options may serve a role, but this question is asking what the most appropriate next best step is. Therefore the best option is option 3.
