Vasculitis issue – introduction

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A concise introduction to systemic vasculitis

The terminology ‘systemic vasculitis’ encompasses an array of conditions characterized by inflammation of blood vessels of varying size that without recognition and treatment can lead to end organ damage and failure with subsequent mortality. Vasculitis disease states are categorized by the size of vessel they involve along with recognition of affiliated age group. Data over the last 40 years estimate varying but overall increasing incidence of vasculitis in the United States (U.S.) [1,2]. Since establishment of more standardized diagnostic tools and the evolution of immunomodulating therapy, survival has increased and mortality has decreased; however, estimated death count in the U.S. remains high at 13,048 individuals with vasculitis contributing to their death from 1999 to 2019. During this same period in the U.S., age-adjusted mortality rate of vasculitis as underlying cause of death has averaged 1.888 per million (CI 1.855–1.921) [2].

Sequalae of systemic vasculitis can include damage to lungs, kidneys, liver, eyes, skin, joints, muscles, nerves, and intestines, whereas complications of the vasculitis itself or treatment can include cardiovascular, stroke, and pulmonary-related deaths. Given severity of progression and complications and prior limited consensual diagnostic criteria, guidelines have been established to assist in early diagnosis and then treatment and identify areas for additional research [3–5]. Treatment has shifted to a ‘triphasic approach’ focused on induction, maintenance of remission, and treatment of relapses while at the same time considering co-morbid conditions [6]. Currently, treatments include corticosteroids, rituximab, plasmapheresis, cytokine-modulating therapy such as inhibitors of TNF-alpha, IL-1, and IL-6 along with other immunosuppressant agents. Evolving data provide increasing evidence to support earlier targeted treatment and use of glucocorticoid sparing immunomodulators and biologic agents to allow for more disease-specific treatment with lessened drug toxicity [7].

The purpose of this issue will be to discuss updates on eight prevalent entities within vasculitis literature.

Within the category of large vessel vasculitis, the following disease states are included: Takayasu’s arteritis and giant cell arteritis. Though both processes are granulomatous in nature, these are differentiated in their large vessel location and demographic distribution. Takayasu’s arteritis is seen to classically involve the aorta and its larger branches and affects younger females of Asian descent, whereas giant cell, though also may involve the aorta, is found mostly within the temporal artery, is seen in individuals greater than 50 years of age and has a predilection for those with polymyalgia rheumatica.

Amongst the medium vessel vasculitis class are polyarteritis nodosa and Kawasaki’s disease. Given this issue will focus primarily on adult pathologies, the focus here will be on polyarteritis nodosa. Polyarteritis nodosa, which can be further sub-categorized into severe and non-severe disease states, is a necrotizing vasculitis of medium vessels (mesenteric, renal, hepatic, etc.) that results in saccular aneurysm formation of the vessels. It differentiates itself from other vasculidities not only by vessel size but by its histological findings of necrosis.

Small vessel vasculitis, however, can be further categorized into two groups: antineutrophil cytoplasmic antibody (ANCA)-associated and immune-complex mediated. ANCA-associated vasculidities affect both small and medium vessels. The term ANCA-associated vasculitis is a broad term as it widely refers to auto-antibody-mediated neutrophil activation that ultimately results in small vessel inflammation and necrosis. This broad classification can further be broken down based on the auto-antibody’s preference for specific neutrophilic protein (myeloperoxidase or MPO versus proteinase 3 or PR3) which highlights that diagnosis of associated vasculidities relies not only on histological specificities but also on immunoassay and immunofluorescence findings. These vasculidities include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), all of which differ based on their pathology. GPA is commonly seen in adults between the ages of 40 and 60, and histology reveals necrotizing granulomatous inflammation. MPA statistically affects men more so than women across the fifth and sixth decades of life and histologically does not demonstrate granuloma formation and is classically associated with MPO antibodies. Lastly within this small vessel classification, is EGPA, which as the name highlights itself, is differentiated histologically by the presence of presence of eosinophilic infiltration along with findings of necrotizing vasculitis.

Newer nomenclature for other vasculidities include variable vessel vasculitis, single-organ vasculitis, vasculitis associated with systemic disease, and vasculitis associated with probable etiology. Among variable vessel diseases are listed Behcet’s disease and Cogan’s syndrome. For the purposes of this issue, our authors will be focusing on Behcet’s disease, a vasculitis that can affect both arteries and veins which predominantly affects a younger population (third and fourth decades), is seen statistically higher in those of Middle Eastern and Eastern Asian descent, is classically known to present with oral and genital ulcers with arthropathy, and histologically reveals perivascular inflammatory infiltrates [8]. Within the classification of single-organ vasculitis include entities such as cutaneous leukocytoclastic angiitis, cutaneous arteritis, and isolated aortitis. Within this issue, our authors shall discuss leukocytoclastic cutaneous vasculitis. This diagnosis is classically suspected following presentation with a palpable purpuritic rash which on biopsy histology reveals a neutrophil predominant inflammatory infiltrate with associated fibrinoid necrosis. This entity can be found in association with either another underlying vasculitis, infection, malignancy, or new drug exposure [9]. Lastly, among vasculidities associated with either systemic disease or probably etiology include lupus vasculitis, rheumatoid vasculitis, sarcoid vasculitis and hepatitis C virus-associated vasculitis, hepatitis B virus-associated vasculitis, syphilis-associated vasculitis, drug-associated immune complex vasculitis, drug-associated ANCA-positive vasculitis, and cancer-associated vasculitis; many of which may be touched upon in various subsections of this issue.

This issue shall dive deeper into previously mentioned disease states and pathologies. These papers written by an international faculty will focus on the current thoughts pertaining to the diagnosis and treatment of systemic vasculitis.

The following topics will be included in this issue:

1. Positive ANCA assay and diagnosis and treatment of ANCA-associated vasculitis

2. Large vessel vasculitis

3. Takayasu’s arteritis

4. EPGA vasculitis

5. Behcet’s disease

6. Polyarteritis nodosa vasculitis

7. Leukocytoclastic cutaneous vasculitis

Declaration of interest

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.