Immune checkpoint inhibitor associated vasculitis and polymyalgia rheumatica: a case series and systematic review

Abstract

Background

Immune checkpoint inhibitors (ICIs) have been associated with immune-related adverse events (irAEs), including ICI associated vasculitis (ICI-vasculitis) and ICI associated PMR (ICI-polymyalgia rheumatica (PMR)-like syndromes). We sought to describe the characteristics of ICI-vasculitis and ICI-PMR in individuals treated with ICIs through a systematic review and local case series.

Methods

We searched MEDLINE and Embase from inception to July 2023 for cases of ICI-vasculitis and ICI-PMR in ICI-treated individuals. Our series included cases obtained from clinicians at the Universities of Toronto, McMaster, and Western in Ontario, Canada.

Results

One hundred and forty-four patients were identified: 130 from the systematic review in 76 articles and 14 from our case series. This included 73 patients with ICI-vasculitis (14 large vessel, 7 ANCA-associated, 52 other) and 71 with ICI-PMR. Ninety-five per cent of patients were treated with glucocorticoids and 17% received disease-modifying antirheumatic drugs (DMARDs). Among 4 individuals with vasculitis who continued the ICI, two remitted. Of five who paused and restarted ICIs, one experienced a recurrence. Among four individuals with vasculitis who continued ICIs, two remitted. All 11 ICI-PMR cases that continued ICIs remitted; among 3 patients who paused and restarted two did not relapse and one had a relapse that improved with an increase in their dose of prednisone.

Conclusion

ICI-vasculitis and ICI-PMR are underrecognized complications of ICIs. Glucocorticoids are effective for ICI-vasculitis and ICI-PMR. It is unclear if ICIs can be safely continued or restarted after remission of ICI-vasculitis or ICI-PMR. Limited data suggests ICIs may be resumed in individuals with non-severe ICI-vasculitis or ICI-PMR.

Supplementary Information

The online version contains supplementary material available at 10.1186/s41927-025-00528-5.

Introduction

ICIs (immune checkpoint inhibitors) are a form of immunotherapy that have transformed the treatment of malignancies, including metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma [1, 2]. ICIs increase immune activity against cancer cells by blocking intrinsic down-regulators of immunity, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1). These mechanisms are, conversely, critical for maintaining immune self-tolerance, and their loss can lead to immune-related adverse events (irAEs), such as rash, colitis, thyroiditis, and hepatitis [3]. Less frequently, irAEs can manifest as multisystem rheumatologic diseases including vasculitis and polymyalgia rheumatica (PMR)-like syndrome, at reported rates of 2 and 21 per 1000 patients receiving ICIs respectively [4, 5]. A variety of ICI-vasculitis cases have been described which can present as classic vasculitis syndromes like GCA and cryoglobulinemic vasculitis as well as single organ vasculitis (SOV) such as a vasculitic neuropathy or retinal vasculitis [2]. Due to reported differences in presentation, it is unclear if ICI-vasculitis and ICI-PMR are consistent with the classical descriptions of these diseases or are different clinical entities than their primary autoimmune counterparts [1].

The expanded use of ICIs has led to more reported cases, allowing for better characterization of these syndromes. This study will report a case series and perform a systematic review of the literature summarizing the characteristics of ICI-associated vasculitis and PMR-like cases. We will also assess for identifiable risk factors, any atypical features of ICI-associated vasculitis and PMR compared to idiopathic cases, and the management and prognosis of these cases.

Methods

We conducted a systematic review of the literature and collected a case series from three hospitals in Ontario, Canada with experience managing rheumatic irAEs in the context of cancer immunotherapy. Patients were included who had received ICIs and subsequently developed vasculitis and/or PMR without a known prior history of these diseases and were thought to have developed their autoimmune disease due to ICI exposure. The diagnosis of ICI- vasculitis or ICI-PMR was made at the discretion of the treating physician.

Systematic review

The systematic review was performed via the MEDLINE and Embase databases using the search terms “immune checkpoint inhibitor” AND “vasculitis” OR “arteritis” OR “large vessel vasculitis” OR “Takayasu arteritis” OR “aortitis” OR “giant cell arteritis” OR “temporal arteritis” OR “small vessel vasculitis” OR “AAV” OR “GPA” OR “MPA” OR “EGPA” OR “polymyalgia rheumatica” from inception to July 23, 2023. The systematic review, including all screening and data extraction, was conducted (AT and AG) independently. Titles and abstracts were reviewed for relevance, full texts of potentially relevant papers were screened, and data was extracted. Disagreements were resolved by discussion with individuals with expertise in irAEs (MJ and FK). Bibliographies of relevant review articles, systematic reviews, and meta-analyses found throughout the database search were scanned for any missed papers. Papers were excluded if they did not include sufficient data about the case(s), if it was unclear if the complication was considered attributable to ICI exposure, were inaccessible, or were not written in English.

Data was collected using standardized data collection forms with individualized forms for large vessel vasculitis (LVV) and PMR, ANCA-associated vasculitis (AAV), and non-LVV/non-AVV (non-LVV/AAV) cases respectively. For the LVV and PMR and AAV cases, the standardized data collection considered the components that are used in their classification criteria to ensure all relevant data was collected. For the cases other than LVV/PMR and AAV, data collection forms allowed long form narrative on all clinical information which ensured information would not be missed among many heterogeneous cases. Data was collected on age, sex, comorbidities, immune checkpoint inhibitor exposure, time to onset of symptoms after exposure, malignancy course, as well as clinical manifestations, physical exam findings, investigations, and management relevant to the irAE. The individualized forms were tailored to the disease manifestations seen in that subset of vasculitis. Diagnoses of vasculitis or PMR was made based on the judgement of the treating clinician.

Local case series

The University of Toronto, University of McMaster, and University of Western Ontario participated in collecting cases for the series. Research ethics board approval was obtained from each participating institution for the case series. Patients were included who had previously received ICIs and subsequently developed vasculitis and/or PMR without a known prior history of these diseases. Case series was completed by contacting oncologists and rheumatologists who care for individuals with irAEs at each institution. Data was collected using the same forms as the systematic review. The diagnosis of vasculitis or PMR was made based on the judgement of the treating clinician.

Results

Search results and case series data collection

The systematic review yielded 465 potentially relevant papers, and, after screening, 76 studies were included (Fig. 1). These studies comprised 130 patients, 68 cases of ICI-vasculitis and 62 cases of ICI-PMR (Table 1). Details regarding individual patient data in the systematic review is available in Supplementary Tables 1–5. Of the 14 patients meeting inclusion criteria for our case series, there were five cases of ICI-vasculitis and nine cases of ICI-PMR cases (Table 1, Supplementary Tables 1–5).

Fig. 1.

Flow diagram outlining searching and screening process

Table 1.

Baseline demographics and cancer features for each ICI-vasculitis and ICI-PMR group. Percentages based on total number patients for which the variable was reported on. RCC (renal cell carcinoma), PD-1(programmed cell death protein-1),–(programmed cell death ligand 1, CTLA-4 (cytotoxic T lymphocyte-associated antigen 4)

	LVV (n = 14) [6–17]	AAV (n = 7) [18–20, 21–24]	SOV (n = 46) [4, 25–58]	Other vasculitis (n = 6) [38, 59–63]	ICI-PMR (n = 71) [1, 4, 64–80]
Median Age (IQR)	67 (62–72)	64 (47–65)	64 (52–70)	66 (63–70)	72 (64–76)
Female	4 (31%)	4 (57%)	20 (43%)	1 (17%)	23 (32%)
Malignancy Melanoma Lung RCC Other	8 (57%) 3 (21%) 1 (7%) 2 (14%)	3 (50%) 1 (17%) 1 (17%) 1 (17%)	17 (37%) 11 (24%) 5 (11%) 12 (26%)	4 (67%) 1 (17%) 0 (0%) 1 (17%)	30 (42%) 12 (17%) 10 (14%) 19 (27%)
Type of ICI PD-1/L1 inh. Combination CTLA-4 inh. Unknown	8 (57%) 2 (14%) 3 (21%) 1 (7%)	3 (43%) 3 (43%) 1 (14%) 0 (0%)	27 (60%) 17 (33%) 2 (8%) 0 (0%)	4 (67%) 2 (33%) 0 (0%) 0 (0%)	59 (83%) 9 (13%) 3 (4%) 0 (0%)

ICI-vasculitis

The median age of individuals with ICI-vasculitis was 65 years (IQR 53–70), and 44 (60%) were male. The most frequent underlying malignancy was melanoma in 32 (45%) cases (see Fig. 2). Forty-two (58%) cases were associated with anti-PD-1/–, 22 (30%) with combination ICI therapy, 8 (11%) with anti-CTLA-4s, and 1 (1%) was associated with either anti-PD-1/– or anti-CTLA-4 exposure as part of an RCT. There were 14 cases of LVV, 7 cases of AVV, and 52 cases of non-LVV/AAV vasculitis (see Table 2). The most common large vessel vasculitis (LVV) was GCA, with 4 of 6 cases presenting in combination with PMR, 5 of 6 cases being biopsy-proven with classic histopathology findings such as intimal proliferation/hyperplasia, disruption of the internal elastic lamina, and transmural inflammation with giant cells. Of the 7 cases of AAV, 3 had granulomatosis with polyangiitis, 2 had eosinophilic granulomatosis with polyangiitis, 1 had microscopic polyangiitis, and 1 had non-specific AAV. The most common non-LVV/AAV was single organ vasculitis, of which there were 46 (88%). Of these, there were 11 (24%) acral vasculitis, 11 (24%) leukocytoclastic vasculitis, 8 (17%) retinal vasculitis, 6 (13%) renal vasculitis, and 4 (9%) CNS vasculitis cases. Median onset of vasculitis was 12 weeks (IQR 4–32) post exposure to ICIs.

Fig. 2.

Cancer types by clinical presentation

Table 2.

irAE clinical presentations. GCA (Giant cell arteritis), GPA (granulomatous with polyangiitis), EGPA (eosinophilic granulomatous with polyangiitis), AAV (ANCA associated vasculitis), CNS (central nervous system), HSP (Henoch Schonlein purpura)

	LVV (n = 14)	AAV (n = 7)	SOV (n = 46)	Other vasculitis (n = 6)
irAE	GCA 6 (38%) Aortitis 4 (31%) Periaortitis 2 (15%) Other 2 (15%)	GPA 3 (43%) EPGA 2 (29%) AAV 2 (29%)	Acral vasculitis 11 (24%) Leukocytoclastic vasculitis 11 (24%) Retinal vasculitis 8 (17%) Renal 6 (13%) CNS 4 (9%) Neuropathy 3 (7%) Uterine 1 (2%) Testicular 1 (2%) Lymphadenitis/vasculitis 1 (2%)	Cutaneous/renal vasculitis 1 (14%) Cutaneous/bowel vasculitis 1 (14%) Renal/pulmonary vasculitis 1 (14%) HSP 1 (14%) Interstitial granulomatous dermatitis and granulomatous arteritis 1 (14%) Cryoglobulinemic vasculitis 1 (14%)

Individuals with ICI-vasculitis received glucocorticoids as initial therapy for management in 95% (54/57) of cases with a median initial dose of 60 mg (IQR 50–80) of prednisone equivalents per day. Eighteen (25%) patients received DMARDs during their disease course with 4 (5%) patients requiring multiple DMARDs. Eight (11%) required csDMARDs without advanced therapy and 10 (14%) required advanced therapy. Two of fourteen LVV (14%) patients, 4/7 (57%) AAV patients, and 12/52 (23%) non-LVV/AAV patients required DMARDs. One of seven (14%) AAV patients and 3/52 (6%) non-LVV/AAV patients required multiple DMARDs as outlined in Supplementary Table 2 and 3.

ICI therapy was held at presentation in 92% (44/48) of ICI-vasculitis cases. Of the four that had the ICI continued, two achieved remission and two developed further complications related to vasculitis. One with GCA developed scalp necrosis and another with non-LVV/non-AAV died due to an occlusive thrombus in the right atrium causing cardiac arrest. The other two, one with retinal vasculitis and one with interstitial granulomatous dermatitis and granulomatous arteritis, were able to achieve remission without complications. In those that had the ICI held, 24% (6/25) restarted the ICI. Among those with follow up data available, 20% (1/5) had recurrence of their ICI-vasculitis, which occurred in a patient with GCA/PMR.

ICI-PMR

Across the 71 cases of ICI-PMR, the median age was 72 years (IQR 64–76), 48 (68%) were male (Table 1). The most frequent underlying malignancy was melanoma in 30 (42%) cases. There were 59 (83%) cases associated with anti-PD-1/–, 9 (13%) with combination ICI therapy, and 3 (4%) with anti-CTLA-4s. There was variable reporting data concerning presentations of PMR. Of cases reported with further detail, 100% (11/11) had morning stiffness lasting more than 45 minutes, 93% (26/28) had hip pain or restricted range of motion, 91% (30/33) had negative rheumatoid factor and anti-CCP antibody, and 80% (30/38) had absence of other joint involvement. Normal inflammatory markers were present in 15% (5/33) of patients for which these were reported. Patients developed ICI-PMR a median of 9 weeks (IQR 5–22) post exposure to ICIs. Cases in which ICI-PMR occurred with ICI-GCA were considered as ICI-LVV table alone (i.e. a part of the presentation of GCA).

ICI-PMR patients received glucocorticoids as initial therapy for management in 95% (57/60) of cases with a median initial dose of 20 mg (IQR 15–30) of prednisone equivalents per day. Seven (10%) patients also received DMARDs during their disease course. None required multiple DMARDs. Five (7%) required csDMARDs and 2 (3%) required advanced therapy with tocilizumab. Where reported, 64% (21/33) of cases had the ICI held at presentation. Of the 11 patients who had the ICI continued with a reported outcome, all achieved remission without significant adverse events. In the ICI-PMR patients that had the ICI held, 40% (4/10) subsequently restarted the ICI. Among those with follow up data available, 67% (2/3) did not have recurrence after restarting the ICI. One patient who did flare, described in the case series, temporarily had their prednisone increased and was able to continue their ICI for over 2 years while remaining on 5–6 mg of prednisone.

Discussion

Both ICI-vasculitis and ICI-PMR are complications of ICI treatments that respond well to initial glucocorticoid therapy and discontinuation of the ICI. As ICIs are deployed in an increasing diversity of malignancies, awareness of these complications and safety data is needed. With this systematic review and case series, we have pooled the results of 20 additional ICI-vasculitis and 22 additional ICI-PMR cases to the prior published data [1, 2]. While classic vasculitis syndromes were readily reported, 87% of cases in our series were single organ vasculitis affecting various parts of the body.

The cases of AAV appeared to be similar to their primary autoimmune counterparts with 3 cases having biopsy data demonstrating classic features of AAV: 2 renal and 1 skin biopsy showing pauci-immune vasculitis [18–20]. Several cases of SOV can be seen with AAV such as the cases of vasculitic neuropathy or retinal vasculitis, however, the SOV cases we reported were ANCA negative and there were no other reported features to suggest ANCA vasculitis. Cases of LVV were more consistent with the global diagnosis of GCA, however, whether isolated aortitis is considered to be a part of the GCA spectrum or is an independent clinical entity continues to be a source of discussion [81].

Among the PMR cases, the majority of patients for which the components of the 2012 EULAR/ACR provisional classification criteria for PMR were reported had those features with rates of 80–100% for each component. A prior case series and systematic review of ICI-PMR cases by Calabrese et al reported similar issues with insufficient data [1]. They also reported that the features most frequently out of keeping with PMR were normal inflammatory markers (30%) and absence of involvement of other joints (45%). This led the authors to question if ICI-PMR represented the same disorder as the idiopathic form or a new nosologic entity [1]. The additional cases in our review demonstrated lower rates of these atypical features with 15 and 20% respectively, suggesting that previous results may have been affected by selection bias. It is, however, important to note that while our findings do suggest it presents closer to its primary autoimmune counterpart, this is still based on a small number of cases and other prospective studies of irAEs suggest a prevalence as high as 0.2% and 2.1% for vasculitis and polymyalgia rheumatica (PMR)-like syndrome respectively [4, 5]. This disparity in expected prevalence and reporting in our data may suggest misclassification of disease, that cases of ICI-PMR are under-reported, that such complications were not considered sufficiently unique for publication, or a combination thereof.

A prior review had found risk factors for rheumatic irAEs included melanoma, GU cancers, and combination ICI therapy [82]. We also found high rates of melanoma (44%) and combination therapy use (22%) in our patient population with ICI-vasculitis and ICI-PMR compared to the baseline rates of melanoma (21%) and combination therapy (8%) in patients receiving ICIs. We did not find a similar relationship with GU cancers, which may be a result of a small number of patients included with GU malignancies. A separate study found ICI-PMR patients receiving monotherapy to have higher rates of PD-1 exposure compared to CTLA-4 exposure with a reporting odds-ratio of 5.6 compared to the baseline population receiving ICIs [83]. We similarly found higher rates of PD-1 exposure (82%) compared to CTLA-4 exposure (5%) in ICI-PMR patients with prior baseline rates of 84% and 8% reported respectively [82].

It was reassuring that 95% of individuals responded to glucocorticoid monotherapy and 59% of ICI-vasculitis cases and 84% of ICI-PMR cases did not require DMARDs. When DMARD therapy was required, DMARDs used were similar to those used in primary autoimmune cases of vasculitis and PMR as outlined in Table 3. This included the use of tocilizumab in GCA, methotrexate and tocilizumab in ICI-PMR, and rituximab, cyclophosphamide, and mepolizumab in AAV. Notably, there were no cases of patients on abatacept, a CTLA analog, which would antagonize the effects of immune checkpoint inhibitors. These treatment considerations are only based on the impact of treatment on the irAE. The effect that treatment of the irAE with immunosuppressive therapy has on oncologic outcomes is an emerging area of research [84]. Prior studies have shown that baseline glucocorticoid use prior to starting ICI’s is associated with worst oncologic outcomes but the effect of adding glucocorticoids after an irAE has occurred are conflicting [84]. Data for initiating DMARD use for irAE’s is limited but have thus far not showed increased risk of malignancy progression with their use [84].

Table 3.

irAE management, and outcomes for each ICI-vasculitis and ICI-PMR group. Percentages based on total number patients for which the variable was reported on except for patients treated with DMARDs in which percentages were reported as a percentage of the total population

	LVV (n = 14)	AAV (n = 7)	SOV (n = 46)	Other vasculitis (n = 6)	ICI-PMR (n = 71)
Median ICI Duration Prior to irAE (IQR)	36 weeks (16–60)	9 weeks (2–14)	10 weeks (4–26)	13 weeks (4–24)	9 weeks (5–22)
Treatment - Steroids - DMARDs	10 (100%) 2 (14%)	6 (100%) 4 (57%)	37 (80%) 12 (26%)	5 (83%) 0 (0%)	57 (95%) 7 (10%)
Median prednisone equivalent initial dose (IQR)	60 mg (60 − 80)	40 mg (30–100)	60 mg (45–80)	80 mg (75–80)	20 mg (15–30)
DMARD used in patients receiving DMARDs	Tocilizumab 2 (100%)	Rituximab 2 (33%) Mycophenolate 1 (17%) Cyclophosphamide 1 (17%) Mepolizumab 1 (17%) Infliximab 1 (17%)	Mycophenolate 4 (33%) Hydroxychloroquine 3 (25%) Methotrexate 2 (17%) Rituximab 2 (17%) Adalimumab 1 (8%) Dapsone 1 (8%) IV immunoglobulin 1 (8%) Cyclophosphamide 1 (8%)	None	Methotrexate 4 (57%) Tocilizumab 2 (29%) Hydroxychloroquine 1 (14%)
ICI management Continued Held Unknown	1 (7%) 6 (43%) 7 (50%)	0 (0%) 6 (86%) 1 (14%)	1 (2%) 29 (63%) 16 (35%)	2 (33%) 3 (60%) 1 (17%)	12 (17%) 21 (30%) 38 (54%)
ICI restarted? Restarted Not restarted Unknown	1 (17%) 3 (50%) 2 (33%)	2 (33%) 3 (50%) 1 (17%)	2 (7%) 12 (41%) 15 (52%)	1 (33%) 1 (33%) 1 (33%)	4 (19%) 7 (33%) 10 (48%)
irAE outcome Remission Complications Improvement Active disease Unknown Death	9 (64%) 2 (14%)* 1 (7%) 0 (0%) 2 (14%) 0 (0%)	5 (71%) 1 (14%)** 0 (0%) 0 (0%) 1(14%) 0 (0%)	27 (59%) 3 (7%)** 8 (17%) 1 (2%) 7 (15%) 0 (0%)	5 (83%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (17%)	30 (42%) 0 (0%) 10 (14%) 3 (4%) 28 (39%) 0 (0%)

* Complications included one patient with GCA who developed permanent vision loss and scalp necrosis. Another who required amputation as a complication of LVV.

** Complication was GPA patient who developed CKD because of vasculitis and steroid induced diabetes.

*** Complications were one patient testicular vasculitis requiring an orchiectomy and two patients with acral vasculitis requiring amputation of multiple distal digits.

Data concerning the safety of resuming ICIs was limited but suggested that in ICI-vasculitis, continuing or restarting ICIs may present an ongoing risk of ICI-vasculitis. Data with ICI-PMR was also poorly reported, rendering certain conclusions difficult. Until more comprehensive data is available, clinicians should consider the severity of the initial clinical presentation and engage in shared decision making with patients when deciding on whether or not to continue the ICI.

This study has multiple strengths and limitations. By combining a systematic review and case series with collaboration across three hospital sites, we present the largest known collection of ICI-vasculitis and ICI-PMR cases reported to date. These cases, however, may represent primary autoimmune diseases onset concurrent with treatment rather than irAE as older individuals are more likely to develop cancer and require ICI therapy as well as develop PMR and/or other forms of vasculitis. In seeking to describe the outcomes of rare diseases, reporting bias around case reports will often affect rates of outcomes and as such the data can only be used for hypothesis generation and to inform the structure of future research. Standardized prospective studies are required to have unbiased ascertainment of outcomes. While a case series was used to bolster these results, which cases were included was also subject to recall bias. Data interpretation was limited by the availability and heterogeneity of data reporting with cases in the literature, for example concerning the safety of restarting ICIs. As such, it as difficult to draw many conclusions from the data. Prospective follow up is needed to better characterize these diseases and their outcomes. Furthermore, diagnosis of vasculitis and PMR was left to the discretion of the treating clinician potentially leading to overdiagnosis or misclassification based on classification criteria; for example, differentiating PMR with normal inflammatory markers from other musculoskeletal complaints may be difficult.

Our data suggests that ICI-vasculitis and ICI-PMR appear to present with similar features to their primary autoimmune counterparts, however, our knowledge of their presentation and epidemiology continues to be limited to date. Single organ vasculitis may also be a more frequent manifestation than previously considered. Both ICI-PMR and ICI-vasculitis respond well to initial glucocorticoid monotherapy and most do not require DMARD therapy. Data concerning continuing or restarting ICIs is sparse but suggest that, similar to other irAEs, it may be reasonable to continue or restart ICIs in cases of mild irAEs, while more caution is needed for severe irAEs. The decision to hold or continue ICIs should involve shared decision-making with both the patient and specialists experienced in managing these challenging cases. Further information from real world registries will help inform future clinical decision making.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

ICIs

Immune checkpoint inhibitors

irAEs

Immune-related adverse events

ICI-vasculitis

ICI associated vasculitis

ICI-PMR

ICI associated PMR

DMARDs

Received disease-modifying antirheumatic drugs

CTLA-4

Cytotoxic T-lymphocyte antigen 4

PD-1

Programmed cell death 1

SOV

Single organ vasculitis

RCC

Renal cell carcinoma

GCA

Giant cell arteritis

GPA

Granulomatous with polyangiitis

EGPA

Eosinophilic granulomatous with polyangiitis

MPA

Microscopic polyangiitis

AAV

ANCA associated vasculitis

CNS

Central nervous system

HSP

Henoch Schonlein purpura

LVV

Large vessel vasculitis

non-LVV/AAV

Non-LVV/non-AVV

Author contributions

Study conceptualization was peformed by A.T., S.G., C.A., A.S., N.K., M.J., and F.K. Methodology was developed by A.T., S.G., C.A., A.S., N.K., M.J., and F.K. Investigation and extraction of case series data was performed by A.T., A.G., and Y.L. Validation, formal analysis, and data curation was performed by A.T. and A.G. for the case series and systematic review. Supervision and guidance was provided by M.J. and F.K. throughout. Writing of the initial manuscript was performed by A.T. All authors reviewed manuscript.

Funding

This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.

Data availability

The datasets and materials generated and/or analyzed during the current study are available from the corresponding author on reasonable request, for non-commercial use, in accordance with BMC data sharing policies.

Declarations

Ethics approval and consent to participate

This study received ethics approval from Western University’s Research Ethics Board (REB), the University of Toronto REB, and Hamilton Integrated Research Ethics Board (HiREB). The research was conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2) and the principles outlined in the Declaration of Helsinki. Consent to participate was obtained from patients from case series.

Consent for publication

Not applicable.

Competing interests

Aaron Teel: none. Adrian Grebowicz: none. Yuliya Lytvyn: none. Stephanie Garner: Advisory boards, grants, etc. for Otsuka, UCB, Sanofi, Novartis, AbbVie, UCB Vasculitis foundation. C. Thomas Appleton: Consultant for Abbvie, Amgen, Bristol Myers Squibb, Celgene, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Hoffman LaRoche, Sandoz, Sanofi-Genzyme, and UCB. Alexandra P. Saltman: none. Nader Khalidi: Grants, consulting fees, honoraria etc. for BMS, AbbVie, Sanofi, Roche, Otsuka, GSK, Mallinckrodt. Mats Junek: Consulting fees from Abbvie and educational support from Roche. Faiza Khokhar: Ad boards, speaker honoraria, or support for conferences etc. for Abbvie. Janssen, Fresenius Kabi, Pfizer, UCB, JAMP pharma corporation.