Systemic vasculitis involving the kidney: the nephropathologist's point of view.

Kidneys are often targets of systemic vasculitis (SVs), being affected in many different forms and representing a possible sentinel of an underlying multi-organ condition. Renal biopsy still remains the gold standard for the identification, characterization and classification of these diseases, solving complex differential diagnosis thanks to the combined application of light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). Due to the progressively increasing complexity of renal vasculitis classification systems (e.g. pauci-immune vs immune complex related forms), a clinico-pathological approach is mandatory and adequate technical and interpretative expertise in nephropathology is required to ensure the best standard of care for our patients. In this complex background, the present review aims at summarising the current knowledge and challenges in the world of renal vasculitis, unveiling the potential role of the introduction of digital pathology in this setting, from the creation of hub-spoke networks to the future application of artificial intelligence (AI) tools to aid in the diagnostic and scoring/classification process.

Systemic vasculitides and the role of multitechnique imaging in the diagnosis.

Vasculitis, a systemic disease characterised by inflammation of the blood vessels, remains challenging to diagnose and manage. Vessel size has been the basis for classifying systemic vasculitides. Imaging plays a vital role in diagnosing this challenging disease. This review article aims (a) to summarise up-to-date literature in this field, as well as include classification updates and (b) to review available imaging techniques, recent advances, and emphasis on imaging findings to diagnose large vessel vasculitides.

La clasificación de las vasculitis sistémicas: es momento de su renovación / Classification of systemic vasculitis: Time for an update

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Takayasu arteritis: A distinct syndrome of large vessel vasculitis: A view point by late Professor Paul Bacon.

Takayasu arteritis (TA), despite being classified as a large vessel vasculitis, has distinct genetic, pathological and clinical features as compared to giant cell arteritis. It is a rare disease seen more commonly in Asian countries. The challenge lies in assessing the degree of inflammation in a narrowed vessel and immunosuppressive therapy improves inflammatory features but is unable to open up an occluded vessel. It may have a positive effect on retarding further occlusion. Like antineutrophil cytoplasmic antibody-associated vasculitis, TA needs a collaborative effort to do randomized controlled therapy to provide benefit to patients.

Evolving concepts in classification of systemic vasculitis: where are we and what is the way forward?

The classification of the systemic vasculitides has been controversial for several decades. The Chapel Hill consensus Conference definitions originally developed in 1994, but revised and extended in 2012 are now widely accepted. The American College of Rheumatology (ACR) criteria were first published in 1990, are now generally accepted to be out of date and new criteria are needed. More recently the classical division of the ANCA vasculitides using clinical phenotype has come under scrutiny with evidence from epidemiological, genetic and outcome studies that perhaps these conditions should be classified on the basis of ANCA specificity into PR3-ANCA positive and MPO-ANCA positive groups. The traditional distinction between giant cell arteritis and Takayasu arteritis has been questioned and some recent studies of GCA have included patients with only extra-cranial disease. The Diagnostic and Classification Criteria of Vasculitis study (DCVAS) will provide new validated classification criteria for the systemic vasculitides.

Are the 1990 American College of Rheumatology vasculitis classification criteria still valid?

Objectives: Advances in diagnostic techniques have led to better distinction between types of vasculitis, potentially affecting the utility of the 1990 ACR classification criteria for vasculitis. This study tested the performance of these criteria in a contemporary vasculitis cohort. Methods: The Diagnosis and Classification in Vasculitis Study provided detailed clinical, serological, pathological and radiological data from patients with primary systemic vasculitis and clinical context-specific comparator conditions. Fulfilment of six ACR criteria sets and their diagnostic performance was evaluated in patients with a given type of vasculitis and its comparator conditions. Results: Data from 1095 patients with primary systemic vasculitis and 415 with comparator conditions were available. For classification, sensitivities and specificities for ACR classification criteria were, respectively, 81.1% and 94.9% for GCA; 73.6% and 98.3% for Takayasu's arteritis; 65.6% and 88.7% for granulomatosis with polyangiitis; 57.0% and 99.8% for eosinophilic granulomatosis with polyangiitis; 40.6% and 87.8% for polyarteritis nodosa; 28.9% and 88.5% for microscopic polyangiitis; and 72.7% and 96.3% for IgA-vasculitis. Overall sensitivity was 67.1%. Of cases identified by their respective criteria, 16.9% also met criteria for other vasculitides. Diagnostic specificity ranged from 64.2 to 98.9%; overall, 113/415 comparators (27.2%) fulfilled at least one of the ACR classification criteria sets. Conclusion: Since publication of the ACR criteria for vasculitis, the sensitivity for each type of vasculitis, except GCA, has diminished, although the specificities have remained high, highlighting the need for updated classification criteria.

[Systemic vasculitides: some debatable aspects of the problem].

A new nomenclature of systemic vasculitides (SV) and current approaches to their treatment have necessitated the discussion of some debatable questions on this condition. The paper gives the data of examining 325 patients with different forms of SV, followed up in the Interregional Consulting Center for SV patients, and the results of testing the American College of Rheumatology classification criteria for SV and the authors' criteria, by taking into account the International Chapel Hill Consensus Conference, USA (1994 and 2011) guidelines for CV nomenclature. It discusses the etiological factors and pathogenetic components of SV, morphological aspects, and relationships between the local and systemic forms of SV. The findings were compared with the data available in the literature. It is concluded that differentially diagnostic criteria for CV should be elaborated to specify the stage of the disease, the activity and use of adapted therapy regimens.

Vasculitides with cutaneous expression in children: clinico-pathological correlations.

The most recent pediatric vasculitis classifications (EULAR/PRINTO/PRES) have proposed the use of an integration of clinical signs and symptoms, laboratory data, imaging and pathologic data. Pediatric vasculitis represent a peculiar clinical-diagnostic model, compared to the corresponding adult pathology chapter, and in particular, dermatopathologic aspects of these diseases identify more specific issues, made contingent by crucial variables such as duration of vasculitis lesion, site of the biopsy, proper biopsy depth, and possibility to correlate histopathological findings with immunopathological results. Possible additional diagnostic difficulties may arise from the fact that, in children, the same systemic disease, such as lupus erythematosus, may present with different clinical manifestations, with histopathological features of a precise type of vasculitis specific for that type of clinical manifestation. Examples are provided by hypocomplementemic urticarial vasculitis, cryoglobulinemic purpura, lymphocytic vasculitis of livedoid lesions. This paper describes the cutaneous histopathological findings of some vasculitis related pediatric diseases, be they pertaining to a systemic vasculitis with corresponding cutaneous vasculitis, to a systemic vasculitis with sporadic cutaneous vasculitic involvement, and to a systemic vasculitis without cutaneous vasculitic involvement. Type and level of histopathological vasculitic involvement, caliber of the vessel, type of vasculitis associated infiltrate, are likewise reliable integration in the complex diagnostic path of vasculitis in childhood. On the basis of these criteria dermatopathologists should be confident in identifying the type of the vasculitis and relate them to a specific pediatric disease.

Vasculitis: do we know more to classify better?

The systemic vasculitides are a heterogeneous group of disorders characterized by the inflammation of blood vessels. The development and implementation of advanced diagnostic tests and genetic studies have resulted in substantial improvement in our understanding of vasculitis pathogenesis, resulting in the revision of the nomenclature and classification for vasculitis. Multicenter, collaborative studies are currently underway to develop improved diagnostic criteria. In this review, the major nomenclature and classification systems for vasculitides are summarized, with special emphasis on those emerging from the recent 2012 Chapel Hill Consensus Conference (CHCC).

Clinicopathological characteristics and outcomes of pediatric patients with systemic small blood vessel vasculitis.

BACKGROUND: Systemic small blood vessel vasculitis (SSV) is uncommon among pediatric patients, and the predictive value of the new histopathological classification for SSV in terms of renal outcomes in these patients is unknown. METHODS: The study cohort comprised 38 pediatric patients and 285 adult patients with SSV who were treated in a medical center between 1993 and 2012. RESULTS: Children accounted for 11.8 % of all patients with SSV diagnosed during the study period. In contrast to the adult patients, the pediatric patients were predominantly female (73.7 vs. 51.9 %; P < 0.05). The prevalence of skin purpura was higher and pulmonary symptoms were less common among pediatric patients than among adult ones (36.8 vs. 13.7 %, P < 0.01 and 26.3 vs. 46.0 %, P < 0.05, respectively). Subtype was correlated with the baseline levels of serum creatinine and treatment response among patients with SSV and was found to have a tendency to predict end-stage renal disease (ESRD) among pediatric patients (hazard ratio 2.273, P < 0.01). The probability of progressing to ESRD was highest in pediatric patients with the sclerotic glomerulonephritis subtype, followed by the mixed, crescentic and focal glomerulonephritis subtypes (in descending order of probability) (P < 0.01). CONCLUSIONS: Estimated histopathological classification has a prognostic value for renal outcome and response to therapy in children with SSV.

[The current classification of systemic vasculitides].

Systemic vasculitides (SV) are severe multiorgan diseases whose early diagnosis and treatment can significantly improve prognosis. Improving the classification of SV may lead to a significant reduction in the likelihood of diagnostic errors. The presented paper deals with the results of the International Consensus Conference on the Nomenclature of SV (Chappel Hill, USA) in 2012. The nomenclature and definitions of the major forms of SV were revised and additional categories of vasculitis were included into the classification, by relying on the current trends in the practical use of terms, on the current ideas on the specific features of manifestations of diseases, and on achievements in studying the pathogenesis.

Validation of the classification criteria for cryoglobulinaemic vasculitis.

OBJECTIVE: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV). METHODS: Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria. RESULTS: The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers. CONCLUSION: Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease.

Validation of the consensus methodology algorithm for the classification of systemic necrotizing vasculitis in Indian patients.

AIM: Many patients with systemic necrotizing vasculitis (SNV) satisfy classification criteria of different disease entities when different classification systems are used. A new classification algorithm has been proposed recently by using the American College of Rheumatology criteria, Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers for a more uniform classification of patients suffering from these rare disorders. METHODS: We applied this algorithm to patients diagnosed as having systemic vasculitis between 2007 and 2011. We also analyzed the data using this algorithm by incorporating the recently proposed revised CHCC nomenclature of vasculitis in place of the older criteria. RESULTS: Seventy-nine patients with SNV were studied. One patient diagnosed as microscopic polyangiitis (MPA) had to be excluded from analysis as she had previously been diagnosed as having Behcet's disease. All patients of eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA) and MPA were reclassified to the same diagnostic subcategory after application of the algorithm. Three (16.7%) of 18 polyarteritis nodosa patients were unclassifiable after application of the consensus algorithm while two (11.1%) were reclassified as MPA. All previously unclassifiable patients could be classified either as MPA or GPA after application of the new algorithm. There was no difference in the results when the CHCC 2012 nomenclature was used instead of the older CHCC in the consensus algorithm. CONCLUSION: The new classification algorithm is a reliable method for classification of SNV for epidemiological purposes in our population.

ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS).

The systemic vasculitides are a group of uncommon diseases characterized by blood vessel inflammation. There are currently no diagnostic criteria for the primary systemic vasculitides and physicians must rely on experience and disease definitions. The absence of validated criteria can result in delays in making the correct diagnosis and starting appropriate therapy. With the increased understanding of the pathophysiology of vasculitis and newer diagnostic tests in widespread clinical use, it is an appropriate time for classification criteria for primary vasculitis to be revised. The Diagnostic and Classification Criteria for Vasculitis (DCVAS) study is a multinational observational study designed to develop and validate diagnostic criteria and to improve and validate classification criteria for primary systemic vasculitis. The analytic approach will be based on the traditional approach of vessel size for classification of vasculitis but will also incorporate detailed clinical data, evaluation of anti-neutrophil cytoplasm antibody diagnostic testing, biopsy and imaging data. The study is following the guidelines for the development of classification criteria established by the American College of Rheumatology and the European League against Rheumatism. The study will incorporate the use of pre-defined cases of each condition to reduce the inherent circularity when developing new classification criteria and will explore alternative approaches to deriving reference standards by creating data-driven classification algorithms. We anticipate recruiting >2,000 patients with primary systemic vasculitis and 1,500 patients with autoimmune diseases and other conditions that mimic vasculitis. As of June 2013, >100 medical centers across 31 countries in Asia, Australasia, Europe, North America, and South America were contributing data to the study. The DCVAS study provides a unique opportunity to increase generalizability and collate a large dataset on the occurrence, presentation, and outcome of vasculitis in different populations.

Epidemiology and clinical features of systemic vasculitis.

Different vasculitic syndromes present in different age groups. Immunoglobulin (Ig)A vasculitis and Kawasaki disease usually present in children whereas giant cell arteritis (GCA) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually present in the middle aged/elderly. In Northern Europe, granulomatosis with polyangiitis (GPA; Wegener's) is commoner than microscopic polyangiitis (MPA) and MPA is more common than eosinophilic granulomatosis with polyangiitis (EPGA; Churg-Strauss syndrome). In Southern Europe, MPA is commoner than GPA and in Japan MPA is much more common than GPA. Major differences exist worldwide in ANCA specificity which are not entirely related to different phenotypes. GPA, like GCA, has a cyclical pattern of onset suggesting possible infection as an aetiological agent. International studies have given important clues to possible aetiology including silica dust and infection and genetic influences, as shown by the recently published genome-wide association study which revealed that single-nucleotide polymorphisms associate more strongly with ANCA than clinical syndromes. A brief description of the main clinical features of ANCA-associated vasculitis is also given.

Systemic vasculitis: a critical digest of the recent literature.

Herewith we provide a critical digest of the recent literature on systemic vasculitis. In this manuscript, we reviewed all the articles published during the last 12 months on large-, medium- and small-vessel vasculitis and selected the most relevant studies regarding the epidemiology, pathogenesis and management of systemic vasculitis. In particular we focused the attention on giant cell arteritis, ANCA-associated vasculitis and cryoglobulinemia.