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General Information on Vasculitides & Article reviews  

Vasculitides are a group of diseases, being all potentially life-threatening and/or affecting vital organs, like heart, lungs or brain, with frequent irreversible damage. With prompt and adapted treatment, the survival at 1 year exceeds 90%, thus the importance to recognize these diseases and refer patients to experienced centers for their management.

Vasculitides are characterized by inflammation of vessel walls , mainly arteries, but sometimes also veins, with or without fibrinoid necrosis and/or granulomas. They can be secondary (to several infections, but also other systemic diseases or cancers, or occur as a reaction to medications or toxic exposures, like levamisole-tainted cocaine). According to the 1994 Chapel Hill nomneclature, primary vasculitides were classified based on the size of the predominantly affected vessels:

      • Large vessel vasculitides affect the aorta and its major branches and include two main conditions: Giant Cell Arteritis which is seen almost exclusively in individuals older than 50 years and which can cause irreversible blindness in up to 15-20 percent of the cases, and Takayasu’s arteritis, which affects mostly women younger than 40 years-old and can cause arterial limb claudication and/or strokes.
  • Medium vessel vasculitides include Polyarteritis Nodosa which can affect individuals of all ages and cause infarctions of multiple organs, including the gut, kidneys, heart, muscle and nerves. Before the development of anti-hepatitis B virus vaccine, and the subsequent massive worldwide vaccination campaigns, more than half the cases of polyarteritis nodosa were due to HBV infection. In contrast, Kawasaki Disease is seen mostly in children younger than 4 years-old it has a predilection for the coronary arteries.
  • Small vessel vasculitides include several entities. The most "famous" ones are associated with the presence of antineutrophil cytoplasm antibodies (ANCA) in the serum of affected patients (at least some of them). These ANCA-related vasculitides include Granulomatosis with Polyangiitis (Wegener’s) , Microscopic Polyangiitis and Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). These diseases can cause pulmonary-renal syndrome which is characterized by lung hemorrhage and rapidly progressive renal failure. Non-ANCA small vessel vasculitides include many different entities, like Henoch-Schönlein purpura, which is usually a self–limited disease mostly seen in children, and cryoglobulinemic vasculitis (most commonly associated with chronic hepatitis C virus infection). Anti-GBM (glomerular basement membrane) antibody disease (sometimes named Goodpasture disease when it affects lungs and kidney) has been recently included officially in the list of these vasculitides mainly affecting small sized vessel and causing renal disease (with linear deposition of antiGBM antibodies in the glomeruli) and/or alveolar hemorrhage.
  • Other vasculitides: Behcet's disease is a particular vasculitis that can affect vessels of all sizes, including the veins. Isolated CNS vasculitis is an extremely challenging condition as it affects the vessels of the brain diffusely and can cause various clinical manifestations. Buerger's disease (obliterans thromboangiitis) causes digital ischemia and gangrenous lesions, due to medium- and small-sized artery vasculitis and thrombosis, but also superficial vein thromboses and concerns almost exclusively smokers (classified as a medium-sized vessel vasculitis in Japan

The 2012 Revised international Chapel Hill consensus conference nomenclature of the vasculitides (link to article) now individualizes:

  • Large Vessel Vasculitis (LVV): Takayasu Arteritis (TAK) and Giant Cell Arteritis (GCA)
  • Medium Vessel Vasculitis (MVV): Polyarteritis Nodosa (PAN) and Kawasaki Disease (KD)
  • Small Vessel Vasculitis (SVV):
    • ANCA-Associated Vasculitis (AAV) including: Microscopic Polyangiitis (MPA), Granulomatosis with Polyangiitis (Wegener’s) (GPA) and Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss) (EGPA)
    • Immune Complex SVV including: Anti-GBM Disease, Cryoglobulinemic Vasculitis, IgA Vasculitis (Henoch-Schönlein) (IgAV) and Hypocomplementemic Urticarial Vasculitis (Anti-C1q Vasculitis) (HUV).
  • Variable Vessel Vasculitis (VVV): Behçet's Disease (BD) and Cogan’s Syndrome (CS).
  • Single Organ Vasculitis (SOV): Cutaneous Leukocytoclastic Angiitis, Cutaneous Arteritis, Primary CNS Vasculitis and Isolated Aortitis.
  • Vasculitis Associated with Systemic Disease: Lupus Vasculitis, Rheumatoid Vasculitis and Sarcoid Vasculitis.
  • Vasculitis Associated with Probable Etiology: Hepatitis C Virus-Associated Cryoglobulinemic Vasculitis, Hepatitis B Virus-Associated Vasculitis, Syphilis-Associated Aortitis, Serum Sickness-Associated Immune Complex Vasculitis, Drug-Associated Immune Complex Vasculitis, Drug-Associated ANCA-Associated Vasculitis and Cancer-Associated Vasculitis.

Epidemiology - Vasculitides are rare diseases. There is no epidemiological study on vasculitides in adults in Canada, and few have been done in the United States. However, based on European, Australian, New-Zealander and Japanese studies, one can estimate the overall prevalence and annual incidence ranges of primary vasculitides as follows: 

Vasculitis Prevalence (per million) Remarks Annual Incidence (per million) Remarks
GCA 850-7,500
(of population >50 y-o)
Crude estimates (no specific study) 90-300
(of population >50 y-o)
Down to 5 in Israel in late 1960s; Up to 370 in Norway in mid 1990s; 20 in subjetcs <60 and up to 520 in those >80 y-o in Minnesota
Takayasu 4-8 4.7 to 7 in the UK in early 2000s; Up to 40 in Japan (no epidemiological data for India, but probably at least the same) 1-2 Down to 0.4 in Germany; Up to 2.6 in Minnesota in late 1970s, and 3.3 in Kuwait
PAN 6-30 Up to >30 in late 1990s before HBV-related PAN almost disappeared 0.9- 6.8 Up to 8 in the UK, 16 in Kuwait in the late 1990s, and 77 in Alaska in late 1980s (HBV endemy)
Kawasaki - Acute disease (in general, but damage)

(of children <5 y-o)

Down to 16 in Czech republic in late 1990s; Up to 2,180 in Japan; in US, 91 in Caucasian vs. 320 in Asian children in early 2000s
GPA 50-135 Down to 23 in Paris in 2000, 30 in NYC in 1990; Up to 135 in the UK in 2013 and 160 in Sweden in 2007 5-14 Down to almost 0 in Japan, 2.9 in Spain; Up to 11 in Australia and Minnesota; and 14 in adults in the UK between 2000-2013.
MPA 25-50 Down to 25 In Paris in 2000; Up to 94 in Sweden in 2007 5-10

Down to 2.7 In Germany;Up to 15 in Japan, and 24 in Kuwait

EGPA 10-15 Down to 7 in Germany in 1994; Up to 22 in Australia in 2004 1-2 Down to 0 in Japan; Up to 2.7 in the UK in late 1990s, and 4 in Minnesota in late 1970s
Behçet 10-500 Extremely wide ethnic variations (from 6 in the UK in late 1970s to 4,200 in Turkey in 2000); 100-300 in US , mainly in immigrants; 24 in European-descent vs. 175 in Asian-descent vs 350 in Norh-African- descent French population - No precise estimation (chronic disease and wide geographical differences); around 4 in Minnesota in mid 2000s
CNS-V - No data 2.4 Only 1 study, in Minnesota

Because research on vasculitides is a rapidly moving field, we do not intend to provide here more information on pathogeny, treatments and outcomes of vasculitides. This would be rapdily outdated and potentially misleading for physicians and/or patients. Excellent reviews are regularly published and will be cited below on this page. Attending the Annual CanVasc conferences and lectures given by its members is another very valuable option to update your knowledge on this topic! (see meetings page ). You can also visit other websites on vasculitis (see links page ).

Selected News and Articles ("CanVasc Journal watch")                                            Go back to top of window

NOTE: Due to copyright policies, we can not directly provide here the full texts of the commented articles. Links will lead you to the Journal pages of the articles, where you will be able to get acces to them, through a single article purchase or through your own subscriber account or that of your institution. In case of major, vital and urgent need to get access to one of the articles, you still may try to contact us by email if you have no other options.

JAKinibs for GCA? 

Whereas the light has been shed in the past months on tocilizumab (and abatacept) for GCA, not all patients achieve remission and/or remain in sustained remission with these agents and research efforts must continue to find other effective agents (as alternative or in combination). The recent research article from the Weyand's group highlights the potential place of JAKinibs (tofacitinib especially) for GCA, based on results obtained in a mouse model of GCA (chimeric mice, engrafted with a human large temporal artery fragment). Studies in humans are on the go, with baracitinib for the moment. CPx, 06 May 2018.

Zhang et al. Circulation. 2018 May 1;137(18):1934-1948. Link

The results of PEXIVAS have been released on May 25th, 2018

The very awaited results of the primary endpoints (mortality and ESRD at 1 year) of the PEXIVAS study have been presented by Michael Walsh at the ERA meeting: there is no difference in these outcomes between the arms with or without PLEX! There is no difference in term of efficacy between the standard and the lighter steroid regimen arm, but those in the latter showed less severe infections during year 1. Let's wait for the article now! CPx, 26 May 2018.

MAINRITSAN 1 long-term and MAINRITSAN 2 articles are published

The results of the 60-month follow-up of the MAINRITSAN (1) study have been published in ARD, and confirm that systematic reinfusions of rituximab (500mg at the time of remission, then 2 weeks later and again 6, 12 and 18 months later) achieved a lower rate of major relapses at 60 months than azathioprine (given until month 22). Major relapse-free survival rates were 71.9% versus 41.9% at 60  months, respectively (P=0.003). Rituximab is not yet approved for maintenance in Canada.

In parallel, the results of the MAINRITSAN 2 study were also published and showed that the rate of (major and minor) relapses at 28 months was 9.9% with the MAINRITSAN 1 regimen (500mg at the time of remission, then 2 weeks later and again 6, 12 and 18 months later) compared to 17.3%  (P=0.22) with a tailored-infusion regimen (500mg at remission, then up to every 3 months depending on the ANCA titer and the B cell count). Patients in the tailored-infusion arm received less infusions (median of 3), which would make it a cost-saving strategy, although it requires a close monitoring (every 3 months) and an efficient action plan (to give a rapid infusion when indicated). The difference observed in the relapse rate is not significant, but may be worrisome for some patients who are "forced" to chose the tailored-infusion regimen (and pay out of pocket for their rituximab infusions). Again, rtuximab is anyhow not yet approved for maintenance in Canada, using any of these two strategies. CPx, 06 May 2018.

Charles et al. Ann Rheum Dis. 2018 Apr 25. Link

Terrier et al. Ann Rheum Dis. 2018 May 3. Link

Health Canada now also approves tocilizumab for the treament of GCA

On October 27th, 2017, Health Canada has approved tocilizumab for the treatment of GCA, following the FDA approval. Let's now see who will be covered (the criteria) in each province precisely. CPx, 28 October 2017.

FDA approves tocilizumab for the treament of GCA

On May 22nd, 2017, the U.S. Food and Drug Administration expanded the approved use of subcutaneous Actemra (tocilizumab) to treat adults with giant cell arteritis, based on the positive outcome of the Phase III GiACTA study evaluating tocilizumab in patients with GCA (and a previous smaller study from Switzerland). Let's now what will happen in other countries, including in Canada, then at each provincial level regarding the criteria for coverage and reimbursement (i.e. the practical indications). CPx, 03 June 2017.

Link to FDA:

ARChiVe's pediatric cohort of GPA and MPA.

Congratulation to David Cabral (a CanVasc core member) and colleagues (including from Canada, UK, USA, Italy, Russia and India), who report the largest cohort of children with GPA (n=183) or MPA (n=48) published thus far. The ARChiVe initiative enrolled these patients into the online RedCap registry between March 2007 and November 2015 (and it is still running!). Previous largest cohort from another group (PRINTO) reported on 56 patients.

Main findings of this first descriptive analysis (there will likely be other papers soon, including on follow-up and outcomes) shows that, using the EMA algorithm (which often led to the re-classification of the diagnoses of MPA to GPA made by the treating physicians, or, but less often, from GPA to MPA), children with MPA are younger at diagnosis than those with GPA (13.4 versus 11.2 years), have less frequent lung involvement (44% versus 74%), with less alveolar hemorrhage (15% versus 42%) but more often renal failure requiring dialysis at disease onset (25% versus 13%). Subglottic stenosis occurred in 10% of GPA patients (none in MPA, based on the EMA algorithm), and nasal collapse in 8%. Von Willebrand antigen was elevated in >60% of patients, in both groups (this dosage is not routine in adults). Most children (76%) received cyclophosphamide-based induction, 10-13% received rituximab-based induction (for new diagnosis), and 21% had plasma exchange therapy. Female represented 64% of the patients, 55% were white and mean diagnosis delay was 1.6 months for MPA and  2.1 months for GPA (shorter than in adults by almost 4 months).  CPx, 10 Oct 2016.

Cabral DA et al. Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study. Arthritis Rheumatol. 2016;68(10):2514-26.  Link 

EUVAS-EULAR recommendations for ANCA-associated vasculitides.

A few months after the publication (in November) of the first Canadian recommendations for the management of ANCA-associated vasculitides (link), the equivalent European EUVAS-EULAR updated recommendations are now out (they had to be named EULAR/ERA-EDTA for some internal reasons, out of the topic of this post, but all of us will likely refer to them as the "updated EUVAS guidelines").

Whereas most points are pretty similar, which is reassuring, there are a couple of subtle differences. The CanVasc recommendations included more points and covered more aspects of the diseases, including discussion on pregnancy and pediatric issues, whereas the EUVAS-EULAR ones do not. On the other hand, the EULAR-EUVAS recommendations mention MMF as an alternative to MTX for the treatment of limited GPA, which CanVasc did not at all (this was considered and discussed but at that time, available data were lacking to support MMF as an equivalent to MTX -- available data remains of limited convincing value, as somehow underscored between the lines in the EULAR-EUVAS explanatory text). Whereas CanVasc mentioned rituximab as an "alternative to AZA for maintenance, especially for patients with PR3-ANCA GPA", EULAR-EUVAS goes a little bit farther and lists directly AZA, MTX and rituximab (and MMF) as maintenance treatments, at the exact same levels, for patients with ANCA-associated vasculitides. This latter point sounds great to our Canadian ears and may help supporting applications for rituximab for maintenance (and hopefully its coverage for maintenance, earlier than [too] late) in Canada! The results of the ongoing RITAZAREM study should not be available before late 2018... it is a long time to wait (unless this study does not confirm the superiority of rituximab over AZA found in several retrospective studies and in the French RCT MAINRITSAN study...). - CPx, 15 July 2016.

Yates M, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Jun 23. doi: 10.1136/annrheumdis-2016-209133. [Epub ahead of print]. Link 

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This Web Page was updated the 26 May 2018 by Dr Christian Pagnoux