4.
Vasculitis: vessel wall inflammation
Heterogenous group of diseases
Common histopathologic features of inflammation
and necrosis of blood vessel walls
Different sized vessels
Different vessel beds
Different aetiologies
What is it?
7.
Typically seen with systemic autoimmune diseases
Also with drug hypersensitivity reactions
Viral antigen-antibody complexes (Hep B)
Antibody and complement detected
Exact antigens responsible not always clear
Circulating antigen-antibody complexes may be seen
Immune Complex Deposition
8.
Circulating antibodies directed against neutrophil
granules, monocyte lysosomes and endothelial cells
Cytoplasmic or perinuclear
Myeloperoxidase or Proteinase-3
MPO is a lysosomal granule constituent normally
involved in generating oxygen free radicals
PR3 is a neutrophil azurophilic granule constituent
Direct injury to endothelial cells
Degranulation causes release of ROS
ANCAs
9.
Unclear role
May have direct cytotoxic effects
Association with Kawasaki disease
Anti-endothelial cell antibodies
10.
Chapel Hill
Classification
In 2012, the Chapel Hill Consensus Conference notably replaced
most of the eponymously named diseases with names that
reflected the understanding of the diseases’ pathophysiology.
12. Mikito Takayasu
Ophthalmologist who in 1901 first described arteriovenous anatamosis around the
papilla. He did not describe that patient’s peripheral pulses.
13.
Giant Cell Arteritis
Typically those over 50
Temporal arteries often affected
Associated with polymyalgia rheumatica
Aorta and major branches with predilection for
branches of carotids and vertebrals
Takayasu Arteritis
Typically those under 50
Aorta and major branches
Large Vessel Vasculitis
14. Tomisaku Kawasaki
In 1967, Dr Kawasaki reported 50 cases of children who presented to the Tokyo Red
Cross Medical Centre with fever, rash, conjunctival injection, cervical lymphadenitis,
inflammation of the lips and oral cavity, and erythema over the hands and feet.
15.
Polyarteritis nodosa
Necrotising arteritis of medium or small arteries
No ANCA, doesn’t affect small vessels
Kawasaki disease
Arteritis associated with mucocutaneous syndrome
Coronary arteries often involved
Affects infants and young children
Medium Vessel Vasculitis
16. Friedrich Wegener
In 1936, Dr Wegener, a pathologist, reported three patients with similar clinical
features and published his findings on their distinct histopathologic findings.
17. Jacob Churg and Lotte Strauss
In 1951, Churg and Strauss described 13 patients with asthma, eosinophilia, granulomatous
inflammation, necrotising systemic vasculitis, and necrotising glomerulonephritis.
18. Ernest Goodpasture
In 1919, Dr Goodpasture reported a case of pulmonary haemorrhage and
glomerulonephritis during an influenza epidemic. Anti-GBM antibodies were not
discovered until 1967.
19.
ANCA associated
Microscopic polyangiitis
Granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis
Immune complex mediated
Anti-GBM vasculitis
Cryoglobulinaemic vasculitis
IgA vasculitis
Hypocomplementemic urticarial vasculitis
Small vessel vasculitis
32.
Predisposition to opportunistic infections
Hyperviscosity syndrome
Subglottic stenosis in Wegener’s
Most have constitutional symptoms
Miscellaneous
33.
The emergencies
Emergency (google’s defintion): a serious, unexpected, and often
dangerous situation requiring immediate action.
Emergency room (urbandictionary.com): A place you go when you
think you are going to die, but want somebody else to pay for it.
34.
Constitutional symptoms of: fatigue, malaise, diffuse
pain, arthralgia or arthritis, weight loss
Clinical signs of rheumatologic disease such as:
arthritis, red eyes, Raynaud phenomenon
Young patients or those without typical risk factors
presenting with neurological deficits
Recurrent episodes of erythema nodosum
High inflammatory markers without obvious source
of infection clinically
Red Flags
35.
Older than 50 years old, female > male
Diffuse headache that is new in character
Focal tenderness on direct palpation
Scalp tenderness with combing hair or wearing hat
Jaw claudication with firm foods/long speeches
Visual changes: transient, unilateral, painless visual
blurring or loss and occasionally diplopia
Previous diagnosis of PMR or complaint of neck, torso,
shoulder, pelvic girdle pain
The emergency: undiagnosed, patient goes blind.
Giant Cell Arteritis
36. Temporal Artery Biopsy
Send off FBC, ESR, CRP and if clinical suspicion high, patient should be started on
steroids even with normal ESR/CRP with a view to TAB within the week. They will
need follow up and therefore discussion with rheumatology.
37.
Classical triad of: haemoptysis, drop in haemoglobin and
pulmonary infiltrates on imaging (<50%)
Should have high index of suspicion for patients with
known vasculitic disorders and other autoimmune
diseases though can be ‘bland’
Clinically: dyspnoea, cough, fever
May present with type 1 respiratory failure
The emergency: can rapidly deteriorate, requiring
intubation for adequate oxygenation. Can be mistakenly
treated as pneumonia/sepsis.
Diffuse Alveolar Haemorrhage
38. Bronchoalveolar lavage
Diagnosis is confirmed with progressively haemorrhagic BAL aliquots from the
same location showing haemosiderin-laden macrophages. Need treatment with
high dose steroids +/- cyclophosphamide.
39.
Patients with first episode psychoses that may have
other constitutional symptoms of SLE
Consider in young patients with ischaemic stroke
Headache and altered mental status most common
Extremely rare, and even other rarer causes are
significantly more common
The importance: first episode psychosis or delirium
should prompt consideration of an organic cause for
the presentation before being labeled psychiatric.
Cerebral Vasculitis
40. Brain biopsy
Ultimately the gold standard and will also help diagnose other rare causes of CVA.
Risks of neurosurgical procedure is weighed up against risk of treating the patient
empirically with steroids for presumed cerebral vasculitis.
41.
Vasculitis is rare but it should be considered when
patients present with atypical symptoms
Remember the red flags
Remember the emergencies
Conclusions
42.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1798473/
http://www.medscape.com/viewarticle/407580_1
http://emedicine.medscape.com/article/329255-overview
http://link.springer.com/article/10.1186/2110-5820-2-31
http://www.emdocs.net/the-emergency-medicine-approach-to-vasculitides/
https://emergency.unboundmedicine.com/emergency/view/5-
Minute_Emergency_Consult/307249/all/Vasculitis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029362/
http://emedicine.medscape.com/article/332483-treatment
http://www.medscape.com/viewarticle/740972_8
http://ard.bmj.com/content/64/5/784
Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid
involvement with specific desquamation of the fingers and toes in children].
Arerugi. 1967 Mar. 16(3):178-222. [Medline].
References
Editor's Notes
Large, medium, small
Arterioles, capillaries, venules
Chemical injuries – irradiation, mechanical trauma, toxins
Each one in turn
Lupus, PAN – anti DNAse
Antibodies against drug modified proteins (penicillin) or foreign molecules – in drug hypersensitivity reactions
Hepatitis B and PAN (30% of patients have hep B and have complexes of Hep B surface antigen and antibody)
Complexes can form elsewhere then deposit or antigen in vessel wall then antibody binding
Sometimes no complexes seen – late diagnosis or pauci-immune vasculitis
ANCA (anti-neutrophil cytoplasmic antibodies)
P-ANCA is MPO (microscopic polyangiitis and churg strauss)
C-ANCA is PR3 (wegener)
Drugs or microbes may have cross reactivity and incite ANCA formation in susceptible hosts- PTU can do this with p-anca
Infections or endotoxin exposure elicit cytokines that induce surface expression of MPO or PR3
ANCA react with antigen and cause vessel injury
Useful as diagnostic markers and rise with recurrent disease
Schematic showing large vessel, medium vessel and small vessel vaculitides – those associated with ANCA and those associated with other immune complex deposition
Both are granulomatous disease
Main distinguishing feature is age
TA – pulseless disease, transmural fibrous thickening of aorta, luminal narrowing of major branch vessels – strokes, aortic dissections
PAN typically spares lung, associated with hep B
80% younger than 4 years old with kawasaki, triggered by infection, auto-antibodies to endothelial cells, T/B cell hypersensitivity reaction
Fever for 5 days or more plus: 1. polymorphous rash 2. bilateral non-purulent conjunctival injection 3. mucous membrane changes 4. desquamative rash, palmar erythema 5. cervical lymphadenopathy
CREAM mnemonic – conjunctivitis, rash, edema, adenitis, mucosal involvement
Need ECHOs and IVIG as treatment
Granulomatosis with polyangiitis (GPA) – wegener recurrent RTIs in adults, with ophthalmic/sinusitis/pulmonary infiltrate/renal involvement (complex diagnosis)
Eosinophilic granulomatosis with polyangiitis (EGPA) – churg strauss severe asthma, blood and tissue eosinophilia, sinusitis, pulmonary infiltrate, mononeuritis multiplex/polyneuropathy
Anti GBM – goodpastures (acute GN, haemoptysis)
IgA vasculitis – HSP children, palpable purpura, arthirtis, abdominal pain, haemoproteinuria
Hypocomplementemic urticarial vasculitis – anti-C1q antibodies
Others: thromboangiitis obliterans (buerger’s disease), rheumatoid, SLE, cancer, APLs, systemic sclerosis
Wegener (GPA)
Diagnosis made with CXR, CT and usually need BAL to show red cells
Triage of haemoptysis, anaemia and type 1 resp failure
Most commonly wegener’s, (30%), but also goodpastures, microscopic polyangiitis, idiopathic pulmonary haemosiderosis, collagen vascular disorders
Be hesitant to diagnose a new psychiatric disorder in a patient who has any autoimmune disease
Membranoproliferative GN most common manifestation of renal disease
Opportunitic infections – steroids and other immunosupresive therapy
Hyperviscosity syndrome (mucosal bleeding, visual changes, neurologic symptoms) in those with cryoglobulinaemia – CCF, ischaemic ATN, pulmonary oedema
Subglottic stenosis
Up to 20% patients have normal ESR/CRP
TAB results remain positive for characteristic GCA pathology at least 2 weeks after treatment is started
British guidelines 40 – 60mg for 4 weeks at least then taper dose down