Introduction, vasculitis 2020 ,

A monogenic autoinflammatory disease with fatal vasculitis: deficiency of adenosine deaminase 2 Purpose of review To recap the expanding clinical spectrum, genotype–phenotype associations and treatment options in the light of recently published articles regarding the deficiency of adenosine deaminase 2 (DADA2). Recent findings Whole-exome sequencing enabled novel clinical phenotypes associated with ADA2 mutations. Since its discovery, the phenotypic spectrum of DADA2 has substantially expanded to cover Diamond–Blackfan anaemia, cytopenia and immunodeficiency syndromes. In addition to elevated TNF alpha levels, increased levels of interferon-stimulated genes were also detected in patients with DADA2. Given the absence of clinical trials until now, no standard treatment strategy exists for DADA2. Currently, anti-TNF alpha agents are the mainstay of treatment, based on the data both from the initial two reports and from subsequent studies. However, it is still unclear how to manage asymptomatic patients with ADA2 mutation and/or with absent ADA2 activity and what is the optimal duration of anti-TNF therapy. Summary Among a total of 206 DADA2 patients described so far, the overall mortality was found as 8.3%. Biallelic homozygous G47R mutations were mostly associated with a vascular phenotype, whereas patients with homozygous R169Q mutations seem to display a mixed clinical phenotype including vascular, haematological and immunological manifestations. HSCT should be reserved as a curative treatment option for DADA2 patients unresponsive to the anti-TNF therapy, as it carries a significant morbidity.

One year in review: Kawasaki disease Purpose of review Kawasaki disease is a childhood vasculitis of unknown origin, whose major complication is the development of coronary artery aneurysms (CAA). The purpose of this review is to provide an overview on the most recent evidence on the pathogenesis, diagnosis and treatment options of Kawasaki disease summarizing the most relevant studies published in the last year. Recent findings Several genetic polymorphisms leading to Kawasaki disease susceptibility have been identified, mostly related to immune system regulation; potential external triggers are being investigated by environmental epidemiology studies. A new diagnostic test based on trascriptomics has been tested with promising preliminary results. With regards to first-line treatments, the real effectiveness of high-dose aspirin remains a matter of debate. For refractory cases, the ones at the highest risk for developing CAA, promising results come from the use of biologic agents, especially TNF and IL-1 blockers. Summary Recent literature has provided interesting insights on the various factors involved in the complex scenario behind the pathogenesis of Kawasaki disease, especially genetic ones. Novel diagnostic tests and new evidence on the use of biologic agents in Kawasaki disease are emerging, but further evidence is needed to permit early diagnosis and effective treatment of this condition.

Common and rare forms of vasculitis associated with Sjögren's syndrome Purpose of review Although uncommon, systemic vasculitis is one of the most severe extraglandular manifestations of primary Sjögren's syndrome (pSS) accounting for the increased morbidity and mortality of the disease. This review aims to describe major previous and recent reports regarding the clinical presentation, prognosis and treatment of systemic vasculitis associated with pSS. Recent findings Both older and recent pSS cohort studies performed over the past several and recent years, have clearly shown that cryoglobulinaemic vasculitis is the most frequent type of systemic vasculitis accompanying pSS. Antineutrophil cytoplasmic antibody-associated, large and medium vessel vasculitis are described only in sporadic cases. In addition to the overt clinical manifestations of cryoglobulinaemic vasculitis, type II cryoglobulinaemia, glomerulonephritis and purpura have been correlated with increased risk for B-cell non-Hodgkin lymphoma (NHL) in pSS. Summary pSS is characterized by autoreactive B and T-cell infiltrates around the epithelial structures of the affected organs, as well as, B-cell hyperreactivity. The latter, is attested by the increased production of autoantibodies, directed against many different organ and nonorgan self-antigens. Vasculitis is a significant and potentially life-threatening complication of the disease depending on the size, localization, histologic type and the pathogenetic mechanisms of the inflammatory process. The potentially irreversible tissue damage, as well as the increased risk for NHL development, prompts the need for early diagnosis and treatment of cryoglobulinaemic vasculitis in pSS.

Venous involvement in inflammatory disorders Purpose of review To review the association of venous thrombosis and inflammatory disorders. Recent findings Various systemic inflammatory diseases of which Behçet's syndrome is the prototype are associated with an increased risk of venous thrombosis. Recent data indicate that venous wall thickness is increased among Behçet's syndrome patients with no history of venous thrombosis and thrombosis in Behçet's syndrome could be a unique model of inflammation-induced thrombosis. Patients with inflammatory bowel disease (IBD) have a two to three time-fold increased risk of developing thromboembolic complications compared with general population. The risk of venous thrombosis is increased after surgical interventions and is higher in ulcerative colitis compared with Crohn's disease. Despite similarities with Behçet's syndrome, anticoagulation is advised as the main treatment in IBD, while there is uncertainty about the duration of antithrombotic prophylaxis. Antineutrophil cytoplasmic antibody-associated vasculitides and ankylosing spondylitis are also other inflammatory disorders associated with a thrombotic risk. Summary Underlying mechanisms of venous thrombosis in inflammatory disorders are not clearly understood. How we might prevent thrombosis, should we screen asymptomatic patients, what should we use for the treatment (immunosuppression or anticoagulation or both) and what should be the duration of this treatment also need to be addressed. Finally, the link between inflammation and thrombosis should be more intensively studied.

Management of Behçet syndrome Purpose of review New treatment options have been studied over the last several years, with a recent approval, a first for Behçet syndrome, in the United States. New management guidelines have also been published, helping with this nowadays more commonly recognized condition's management. The goal of this review is to summarize the most important and potentially clinically relevant recent developments and discuss their impact in the management of patients with Behçet syndrome. Recent findings Apremilast is now approved for the treatment of oral ulcer of Behçet syndrome in the United States. It's possible benefits in controlling nonoral ulcer features of the syndrome are awaited. Long-term use of tumor necrosis factor inhibitors for the treatment of especially eye disease in Behçet syndrome seems to be safe and efficacious. New treatment options such as ustekinumab, secukinumab, tocilizumab and others have early promising data but more studies are needed to better clarify their role in Behçet management. Summary The last 2 years have not only seen the approval of the first drug specifically labeled for the treatment of Behçet syndrome in the case of apremilast, many groups have also presented and published their findings on promising new therapeutic agents, which may soon be added to our tools in treating this condition. We also know more about other drugs, such as tumor necrosis factor inhibitors as many patients have been on these for long periods of time, and long-term follow-up data seem to confirm their role in Behçet treatment. Lack of placebo controlled, randomized trials, for the most part, are still outstanding issues.

Central nervous system vasculitis: advances in diagnosis Purpose of review The main purpose of this review is to present advances in diagnostics of central nervous system vasculitis (CNS-V). Recent findings Progress in molecular technologies and neuroimaging have added formidably to our knowledge of CNS-V. Next-generation sequencing has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases, making this test attractive and capable of avoiding brain biopsy in cases where CNS infections are suspected. Further the continuum of neuroimaging progress has advanced our ability to diagnose CNS-V. Our capability to visualize the vessel wall have added a great value in differentiating inflammatory from noninflammatory vasculopathies. New genetic variations are being exposed with exome and genome sequences which will aid future diagnosis. Summary We have witnessed tremendous advances in CNS-V mainly by our ability to rule out mimics. Progress in molecular technologies, neuroimaging and genetic studies will continue to enhance the field further.

Vasculitis and the ear: a literature review Purpose of review Systemic vasculitides as a group of inflammatory disorders of blood vessels may show clinical manifestations in the ear. This article reviews the recent literature about vasculitis of the ear or the cochleovestibular system, focusing on giant-cell arteritis, Takayasu's arteritis, polyarteritis nodosa, Kawasaki disease, microscopic polyangiitis, granulomatosis with polyangiitis (GPA), eosinophilic GPA, systemic lupus erythematosus, Cogan's syndrome and Behçet's disease. Recent findings In patients with vasculitis, hearing impairment is a frequent problem, followed by tinnitus and vertigo. The severity of sensorineural hearing loss can range from mild impairment to deafness. Autoimmune diseases can induce a conductive hearing loss as a result of effusions of the middle ear, the inflammation of the mucosa of the Eustachian tube, or the involvement of the ossicular chain. Vertigo may be caused by the temporary or permanent occlusion of the labyrinthine or the anterior vestibular artery. Middle ear inflammation is frequent in GPA and eosinophilic GPA. Summary The progressive sensorineural hearing loss in polyarteritis nodosa or Cogan's syndrome patients may be treated by cochlear implantation.

Immune checkpoint inhibitors and vasculitis Purpose of review Clinical use of immune checkpoint inhibitor (ICI) therapy has revolutionized the therapeutic landscape of cancer. By activating the immune system using monoclonal anti-CTLA-4 and PD(L)-1 antibodies, remission can be induced in previously terminal cancers. However, these breakthroughs come at a price. Multiple de-novo autoimmune illnesses, termed immune-related adverse events (irAEs), have been reported with patients increasingly being referred to rheumatologists with varying diagnoses. Among these are vasculitic syndromes, which may be limited to an organ or systemic and potentially-life threatening. Relatively little is known about the prevalence, mechanisms, and phenotypes of vasculitis occurring in response to ICIs. Here, we review the literature and describe the frequency and patterns of presentation. Recent findings Vasculitis, while infrequent, has been described as an irAE in patients treated with ICI therapy with resultant morbidity and mortality. Summary Recognizing the risk and management of immune checkpoint inhibitor induced vasculitis in patients with cancer is important in the daily practice of rheumatology.