Management of Acute Vasculitis CMT teaching 3 rd June 2015 Caroline Wroe
Vasculitis pub quiz
Match the date with the event Dr Peter McBride, Scottish Otolaryngologist describes a disease of rapid destruction of the nose and face First edition of the Highway code published Dr Walton (from the RVI!) publishes a case series describing a granulomatous disease previously described by Wegener Suffragette Emily Wilding Davison throws herself under the kings horse Wegener describes a granulomatous disease affecting the lungs and kidneys 1958 1897 1931 1913 1936
True or False 1. The mortality of untreated acute vasculitis is >90% at 2 years 2.Takayasu s arteritis is more common in males than females 3. Mr Happy (from the Mr Men) is blue with a red hat 4. canca is more specific and sensitive than panca 5.ANCA +ve vasculitis is associated with an increase risk of thromboembolic disease
Match the name with the face A B C Friedrich Wegener Joeseph Goebels Heinrich Bruining
Odd one out
Vasculitis talk Definition Presentation Diagnosis Pathogenesis and characteristics Treatment Outcome Sample questions..
What is Vasculitis? A group of uncommon multisystem autoimmune disorders that are frequently life and organ threatening. Microscopic polyangitis Wegeners (now Granulomatosis with polyangitis) Churg-Strauss sydrome
Systemic Respiratory Renal/Urological ENT Rhuematological Neurology Skin Ophthalmology Cardiology GIT GUT Presentation
Making the diagnosis History is the most important component (ask about other symptoms) Exclude more common diagnosis (sepsis, malignancy) Check panca (MPO antibody)and canca (PR3 antibody) Look for evidence of granulomas (tissue diagnosis)
Vasculitis: Pathophysiology Inflammation of blood vessels Damage to blood vessels
Vasculitis glomerular damage
Pauciimmune-Glomerular immunostaining LEFT: Granular staining due to immune complex deposition MIDDLE: Linear staining due to antigbm antibody deposition RIGHT: Absent (pauci-immune) no staining for complement or IgG
Grading vasculitis activity BVAS score Stone et al (2001): Arthritis Rheum. 44(4):912 correlates well with physician global assessment of activity sensitive to change good inter-observer reliability weighted: new, worse, persistent Score 0 (complete remission) Major items score 3 immediate risk to life risk vital organ dysfunction Minor items score 1 other disease manifestations
Treatment Principles Aggressive treatments are warranted Untreated GPA has two year mortality of 90% Disease severity influences treatment choice Treatment benefit demonstrated even when presenting with advanced renal disease Hogan et al (2005) Ann Intern Med. 143(9):621, for example; 57% of 96 patients presenting with egfr<10 attained remission following treatment Three treatment target profiles Induction of remission Maintenance of remission Treatment of relapses
Treatment Principles: Induction Therapies Mild Disease Moderate / Severe Disease No evidence for "active" GN (ie, normal serum creatinine and no red cell casts or proteinuria) No organ-threatening or lifethreatening manifestations (ie, absence of pulmonary hemorrhage, cerebral vasculitis, progressive neuropathy, orbital pseudotumor, GI bleeding, pericarditis, or myocarditis) may have organ-threatening or life-threatening manifestations, including (but not limited to) marked pulmonary haemorrhage or rapidly deteriorating renal function Glucocorticoids & Methotrexate/MMF or Rituximab Glucocorticoids & Cyclophosphamide or Rituximab +/-PEX
Induction therapy Steroids oral or IV Which immunosuppressant to chose and why? Disease activity Experience of drug Cost Side effect profile (Malignancy, Infection, Fertility) What about PEX?-generally advocated for patients: with serum creatinine > 5.7 mg/dl(500 micromol/l) who require dialysis who have pulmonary haemorrhage who also have positive anti-gbm antibody.
Remission Remission Resolution of pulmonary infiltrates Inactive urinary sediment & stabilisation of renal function Resolution of systemic symptoms BVAS score of zero Aim for remission within 3-6 months of treatment and continue treatment for 2 years Inadequate control of disease activity in 20% 50% relapse by 5 years Co-morbidities such as sepsis, malignancy, osteoporosis, atherosclerosis and venous thromboembolism contribute significantly to damage accumulation, impaired quality of life, morbidity and premature mortality Treatment is not without cost! Mr LH
Maintenance therapy 1. Steroids 2. Cyclophosusually changed to Azathioprine at 6/12 3. Rituximab therapy Mr LH, Mr RB, Mr PS, Mr AB, Mrs AS
Relapse How can we predict relapse?
Summary Rare disease Clinical diagnosis Characterised by Granulomas and vessel inflammation 90% ANCA positive (PR3 or MPO) Treatment with steroids + immune modulator High relapse rate, significant medication burden
Sample Question 1 A 74-year-old man is admitted having collapsed at home. He complains of general malaise and has lost 4kg in weight over six months. He is a lifelong smoker and had a single episode of haemoptysis 9 days ago. On examination he has a purpuric rash on his legs, BP is 176/90. Dipstick urinalysis showed +++blood and ++protein. Creatinine is 328, Hb 98 and platelets 204. Which of these statements about his condition/ renal failure is correct? A B C D E It is probably due to vasculitis if his canca is positive He should receive plasma exchange It is irreversible It is probably secondary to a bronchoneoplasm Serum ACE levels will be elevated
Sample Question 2 A 45 year old bus driver presents with an 8 month history of increasing cough and SOB associated with weight loss. The CXR reveals a right apical lesion and prominent hilar lymphadenopathy. ANCA is negative. Which one of the following is the LEAST likely diagnosis in this case? A B C D E Small vessel vasculitis Carcinoma of the bronchus Sarcoidosis Non-Hogdkin s lymphoma Tuberculosis