Classification and classification criteria for vasculitis: achievements, limitations and prospects

REVIEW C URRENT OPINION Classification and classification criteria for : achievements, limitations and prospects Alfred Mahr a,b and Mathilde de Menthon a Purpose of review The classification of s reveals the relationships between conditions that are linked in some way. Such classification has been a challenge for because of the heterogeneous and protean nature of the illnesses. Classification criteria are critical to homogenize patient populations with who are included in basic and clinical research studies. Recent findings The most recent advance in classification has been the revised 2012 Chapel Hill Consensus Conference (CHCC) nomenclature of that, although mainly focusing on nomenclature, also included classification elements. Whereas still maintaining the caliber of the predominantly involved vessels as the main categorization criterion for primary systemic, the 2012 CHCC nomenclature introduced a new category variable-vessel to include Behçet s and Cogan s syndrome in the spectrum. Another important feature was the expansion of the classification to secondary and single-organ. Similarly, classification criteria for several entities have been altered and new criteria published, namely for Behçet s and cryoglobulinemic. Summary The classification of continues to be amended to account for advances in the general understanding of the nature of and our ability to diagnose them. The relevance of the prevailing classification system, relying on affected vessel size as the primary discriminator of entities, is still questionable for clinical practice. Clinically sound, widely accepted classification criteria are available for most entities, although some areas remain ill-defined: polyarteritis nodosa, microscopic polyangiitis and adult immunoglobulin A (Henoch Schönlein). Keywords classification, classification criteria, INTRODUCTION Disease classification is the process of categorizing illnesses in a larger framework of medical conditions. The principle of classifying s is important for highlighting links between s and creating schemes for diagnostic approaches, thus guiding treatment decisions (Fig. 1). Classification differs from nomenclature, which essentially deals with names and definitions of s without focusing on their arrangement. While classification establishes the general concepts, classification criteria provide working schemes that, based on one or more than one characteristics combined, allow the dichotomous classification of a given against all others with high confidence. Classification schemes can be based on histology, cause, biology or clinical characteristics, or may use a mixture of these characteristics to subcategorize s. To create mutually exclusive subsets, the most distinctive features should be ranked highest in the hierarchy of classification, but such choices are not necessarily straightforward, and variations in the types and order of classification features used eventually result in dissimilar classification schemes. Practitioners may want a classification system that is functional for daily care and allows a sound approach to diagnosis and management. a Department of Internal Medicine, Hospital Saint-Louis and b ECSTRA Team, Epidemiology and Biostatistics, Sorbonne Paris Cité Research Center UMR 1153, Inserm, University Paris Diderot, Paris, France Correspondence to Professor Alfred Mahr, Department of Internal Medicine, Hospital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP- HP), 1 avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. Tel: +33 1 42499780; fax: +33 1 42499769; e-mail: alfred.mahr@sls.aphp.fr Curr Opin Rheumatol 2015, 27:1 9 DOI:10.1097/BOR.0000000000000134 1040-8711 ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-rheumatology.com

Vasculitis syndromes KEY POINTS The classification of is challenging because of the heterogeneous and protean nature of these illnesses. The 2012 revision of the Chapel Hill Consensus Conference nomenclature for retained the primary reliance on the size of the affected vessels, but added several important categories, subcategories and individual s. An important limitation in the current concept of classification, which is mainly pathologybased, is its relatively little practicability to guide diagnostic decisions at the bedside. Generally accepted sets of operational classification criteria are yet available for most of the main entities, but for some entities, there is an unmet need for effective criteria. the nomenclature of [7 && ]. This international collaborative effort evolved from the 1994 CHCC nomenclature [8] and provides a comprehensive and updated view on the naming and definitions of entities. The nomenclature also provided a fairly detailed subcategorization scheme and therefore included elements for the classification of. Similarly, the field of classification criteria for is evolving and has resulted in the publication of new classification criteria for cryoglobulinemic [9] and Behçet s [10 && ]. Here, we review the current state of knowledge in the fields of classification and classification criteria for. Particular emphasis is placed on the analysis of the strengths and limitations of current classification concepts and their usefulness in clinical practice. Multiple classification systems for have been generated over the past 60 years [1 6]. The numerous iterations of classification schemes reflect the complexity involved in establishing a simple classification scheme. Because of the heterogeneous and protean nature of, identifying natural subgroups is difficult and we have limited knowledge about their causes. Also, improved diagnostic techniques have led to reappraising the boundaries of s, thus prompting the need for revisiting outdated classifications and adding further complexity to represent the diverse diagnostic approaches in a simple classification scheme. The field of classification has recently been invigorated by the publication of the revised 2012 Chapel Hill Consensus Conference (CHCC) for menclature GENERAL CONCEPT OF VASCULITIS CLASSIFICATION Table 1 summarizes the entities classified as and the main subcategories according to the 2012 CHCC nomenclature. This system recognizes a dozen entities that newly incorporate a few s, such as Behçet s, Cogan s syndrome and hypocomplementic urticarial [7 && ]. The highest-order classification level used in the 2012 CHCC nomenclature distinguishes primary systemic, secondary and single-organ. This separation has practical implications, because the latter two categories require distinct management approaches. This separation leads to the situation, although seemingly illogical, that a given entity (e.g. polyarteritis nodosa, cryoglobulinemic ) can appear in both classes of primary and secondary. Even though single-organ is considered a separate group, this form can also be primary or secondary in nature; thus, single-organ and secondary are not mutually exclusive. Classification and classification criteria Diagnosis FIGURE 1. Schematic representation of the intimate and bidirectional relationships among classification, nomenclature and diagnosis. Change in any one construct affects the two others. Primary systemic Primary systemic has long been subcategorized by the size of vessels mainly involved in the inflammatory process and this pays tribute to the predilection of specific entities for particular compartments of the vasculature. The 2012 CHCC nomenclature continued to adopt this main compartmentalization scheme. In addition to the three classical categories of large, medium and small-vessel, the 2012 CHCC nomenclature created a class for various vessel-size 2 www.co-rheumatology.com Volume 27 Number 1 January 2015

Classification of Mahr and de Menthon Table 1. Vasculitis classification Vasculitis category, subcategory or entity Primary systemic Large-vessel Takayasu arteritis Giant-cell arteritis Medium-vessel Polyarteritis nodosa Kawasaki Small-vessel ANCA-associated Microscopic polyangiitis Granulomatosis with polyangiitis (Wegener s) Eosinophilic granulomatosis with polyangiitis (Churg Strauss) Immune-complex small-vessel Antiglomerular basement membrane (anti-gbm) Cryoglobulinemic Immunoglobuling (Ig) A (Henoch Schönlein) Hypocomplementemic urticarial (anti-c1q ) Variable-vessel Behçet s Cogan s syndrome Single-organ Vasculitis associated with systemic Vasculitis associated with probable cause Characteristic features Granulomatous aorto-arteritis usually occurring before age 50 years Granulomatous aorto-arteritis predominantly involving the carotid and vertebral arteries occurring after age 50 years and often associated with polymyalgia rheumatica Arteritis of medium/small arteries without small-vessel involvement, glomerulonephritis or antineutrophil cytoplasmic antibodies (ANCAs) Childhood mucocutaneous lymph node syndrome with arteritis often involving coronary arteries Vasculitis of small/medium vessels and frequent pauci-immune glomerulonephritis and ANCAs Granulomatous inflammation of the respiratory tract with of small/ medium vessels and frequent pauci-immune glomerulonephritis and ANCAs Asthma, eosinophilia and eosinophilic granulomatous inflammation frequently involving the respiratory tract with of small/medium vessels and sometimes ANCAs Pulmonary and glomerular capillaritis with deposition of anti-gbm antibodies Vasculitis with frequent skin, glomerular and peripheral nerve involvement associated with serum cryoglobulins Arthritis with frequent skin and gastrointestinal with IgA deposits and possible IgA nephropathy Urticarial and hypocomplementic small-vessel with anti-c1q antibodies and common articular, glomerular, ocular and bronchial Recurrent oral and/or genital ulcers with skin, ocular, articular, gastrointestinal, and/or central-nervous-system lesions and possible variable-vessel Vasculitis of small, medium or large arteries occurring in Cogan s syndrome Vasculitis in a single organ and no features indicating a limited form of a systemic Vasculitis secondary to a systemic Vasculitis secondary to a specific cause Each entity is given with its most characteristic features. Adapted from Jennette et al. [7 && ]. to accommodate Behçet s and Cogan s syndrome. Further subclassification occurred for the class of small-vessel divided into immune complex and antineutrophil cytoplasmic antibody (ANCA)-associated [7 && ]. Although appealing in its simplicity, classifying primary systemic by the caliber of involved vessels has practical shortcomings. Despite the acceptability of inferring the size of the affected vessel also by imaging studies or by surrogate markers for small-vessel involvement (e.g. glomerulonephritis, palpable purpura or ANCA), the size of the vessel involved is not always demonstrable in individual patients with. For some of the entities [e.g. Kawasaki, granulomatosis with polyangiitis (GPA; Wegener s), eosinophilic granulomatosis with polyangiitis (EGPA; Churg Strauss), Behçet s ], a subset of patients may lack patent expression of vascular involvement. In addition, the range of vessel sizes affected by the entities grouped in one category commonly overlaps with those from the other categories. In a -positive biopsy, the assignment of an inflamed vessel to the medium or smallsized vessel category is not easy because of changes in the vessel anatomy with the inflammatory 1040-8711 ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-rheumatology.com 3

Vasculitis syndromes process. Consequently, the difficulties in determining the category of based on size of the affected vessel may result in misclassification. Similarly, the use of findings of circulating immune complexes or immune deposits in any tissue sample for reliably discriminating entities can be questioned. ANCA certainly is a dominant classification trait, but is not applicable to the subset of s classified as ANCAassociated with no detectable ANCAs. Secondary vasculitides (with known or probable cause) Secondary encompasses the subgroup of s thought to be caused by an underlying condition or exposure. The main causes are systemic s (e.g., rheumatoid arthritis), cancer, drug exposure, and infection, but the number of factors with a definitely established pathogenic link to remains small. The most prominent known causes of are infection with hepatitis B virus (linked with polyarteritis nodosa) and hepatitis C virus (linked with cryoglobulinemic ), and use of antithyroid compounds and levamisole-contaminated cocaine (both linked to ANCA-associated ). Many other infectious agents and medicinal products have been occasionally found as potential triggers or causes of various entities, but the strength of evidence is low. netheless, discriminating a secondary category is highly relevant because such cases can benefit from a cause-based management. Single-organ Single-organ, previously also called localized, limited, isolated or nonsystemic, denotes restricted to a single organ or organ system, such as cutaneous, peripheral nerve or gastrointestinal single-organ. Further subcategorization of singleorgan into unifocal or diffuse forms has been suggested [7 &&,11] to differentiate the entities involving organs or organ systems covering large areas of the human body from those with limited anatomic extent that could be cured surgically. Single-organ must be differentiated from limited forms of systemic vasculitides, such as localized GPA (Wegener s) or renal-limited ANCA-associated, which may progress to systemic forms. Because apresentingassingle-organmay only be the initial phase of a systemic, single-organ can only be classified retrospectively after a minimal time has elapsed with no progression to systemic. A 6-month period with no progression to systemic has been suggested as a cut-off [12]. Areas of uncertainty and future directions Although classification has become increasingly elaborated, some areas remain illdefined. Individual cases with nonspecific presentations may still be difficult to assign to a specific entity. For example, leucocytoclastic cutaneous with joint involvement could be considered immunoglobulin A (IgA) (with no immune deposits), microscopic polyangiitis (with negative ANCA test results) or polyarteritis nodosa (with no medium-sized vessel seen in tissue). Such cases could also be classified as undifferentiated, but this concept is not widely accepted. A general aspect needing clarification relates to the potentially misleading effect of the vessel-size-based nature of classification, which implies that vessel inflammation must be manifest in any case of. This situation recently led to considering that classification of EGPA should be reserved for the subset of cases with histologically or clinically obvious features of and should no longer include cases with features considered to primarily reflect eosinophilic proliferation [13]. Changes may also occur for the classification of the combined group of GPA and microscopic polyangiitis. Recent data from observational studies [14], genetic studies [15] and cluster analysis [16 & ] support a subclassification of this group by ANCA specificity (i.e. proteinase 3 or myeloperoxidase-anca) than clinical phenotype. A crucial question is how the current classification schemes can be transposed into clinical practice to correctly classify real patients. This problem is, to some extent, hypothetical, because in many cases, presentation immediately suggests a specific entity. However, in other instances, classification guidance may be desirable, but, as previously suggested, the histology-based nature of the current classification systems and the high rank placed on vessel caliber in the categorization is suboptimal for clinical practice. Figure 2 outlines an alternative, clinical-based classification algorithm for. Analogous to a classification algorithm proposed for cutaneous [17], our proposed algorithm ranks testing for ANCA and cryoglobulin as top discriminators for classes of primary systemic entities. Because of its potential practical usefulness and because no attempt has been made to obtain agreement on the ranking of selected features, further efforts may be needed to achieve consensus on such a clinical-based classification tree. 4 www.co-rheumatology.com Volume 27 Number 1 January 2015

Classification of Mahr and de Menthon Vasculitis Singleorgan Systemic Underlying cause Secondary EGPA (Churg Strauss) GPA (Wegener s) ANCA Eosinophilia Granulomatous airway Large vessel Cranial symptoms and age > 50 yr GCA Takayasu arteritis Eosinophilia Granulomatous airway IgA immune deposits Mixed cryoglobulinemia Cryoglobulinemic EGPA GPA IgA (Henoch Schönlein) MPA Undifferentiated Medium-vessel or microaneuryms PAN FIGURE 2. Outline of a practical approach to classification. Some entities, such as Kawasaki, antiglomerular basement membrane, hypocomplementemic urticarial and Cogan s syndrome, are not included for simplification and because of the specific appearance of these entities, so their differential classification from other entities is not relevant. ANCAs, antineutrophil cytoplasmic antibodies; EGPA, eosinophilic granulomatosis with polyangiitis (Churg Strauss); GCA, giant-cell arteritis; GPA, granulomatosis with polyangiitis (Wegener s); IgA, immunoglobulin A; MPA, microscopic polyangiitis, PAN, polyarteritis nodosa. CLASSIFICATION CRITERIA FOR SELECTED VASCULITIS ENTITIES Classification criteria are working tools that serve as inclusion criteria for clinical trials or other research to standardize patient populations and to provide with confidence that the analyzed patients truly have the under investigation. Classification criteria should differentiate a given from its peers, but also from other nonvasculitic conditions that mimic. Even more so than classification, classification criteria must encapsulate the essential elements by which a given is defined. Various methodologies are used to develop classification criteria that range from use of expert opinion to network analyses. Classification criteria also differ as to whether their operating characteristics (e.g. sensitivity and specificity) have been formally assessed. For example, the Lanham criteria for EGPA [18] and the American Heart Association criteria for Kawasaki [19] have never undergone formal evaluation, but are nevertheless widely accepted because they are clinically sound. Some sets, such as the modified American College of Rheumatology (ACR) criteria for GPA [20], consist of slight ad-hoc adjustments to previously published criteria. Confusion derives from the claim of some published criteria that they are diagnostic rather than classification criteria [21 23]. This semantic distinction has no methodological underpinning in terms of the developmental aspects of such diagnostic criteria as compared with those presented as classification criteria. Unlike classification criteria, true diagnostic criteria should be both 100% sensitive and 100% specific [24], which seems out of reach for s whose diagnoses do not rely on a single pathognomonic test. In the context of, the term classification criteria thus seems more appropriate than diagnostic criteria. 1040-8711 ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-rheumatology.com 5

Vasculitis syndromes Well accepted classification criteria are available for most of the entities (Table 2) [7 &&,8,9, 10 &&,18 23,25 34]. Two large collaborative initiatives by the ACR and the European League against Rheumatism/Paediatric Rheumatology International Trial Organization/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) task force [27] have generated classification criteria Table 2. Selected sets of classification criteria for the main entities Vasculitis entity Classification systems (reference) Comments Giant-cell arteritis ACR criteria [25] Should be used in combination with entry criteria Positive temporal artery biopsy (TAB) consensual histological definition for positive TAB. Excludes by definition TAB-negative Takayasu arteritis ACR criteria [26] Should be used in combination with entry criteria Published by Sharma et al. [23] EULAR/PRINTO/PRES [27] Expert-based criteria Developed for pediatric populations. Should be used with entry criteria Polyarteritis nodosa (PAN) CHCC definition [7 &&,8] t intended as classification criteria. t validated. Possibly over-restrictive ACR criteria [28] FVSG criteria [22] EMA algorithm [29] EULAR/PRINTO/PRES [27] Should be used in combination with entry criteria. Low sensitivity and specificity Should be used in combination with entry criteria. Moderate sensitivity and specificity Discriminates PAN from GPA, MPA and EGPA Developed for pediatric populations. Should be used in combination with entry criteria Kawasaki American Heart Association [19] May not work well in adult populations Granulomatosis with polyangiitis (GPA) (Wegener s) ACR criteria [30] Modified ACR criteria [20] EMA algorithm [29] EULAR/PRINO/PRES [27] Should be used in combination with entry criteria Alteration of the ACR criteria [30]. Should be used in combination with entry criteria Discriminates GPA from MPA, EGPA and PAN Developed for pediatric populations. Should be used in combination with entry criteria Microscopic polyangiitis (MPA) EMA algorithm [29] Discriminates MPA from GPA, EGPA and PAN Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg Strauss) ACR criteria [18] Published by Lanham et al. [31] EMA algorithm [29] Should be used in combination with entry criteria. Discriminant ability from hypereosinophilic syndrome (HES) unclear Expert-based criteria. Discriminant ability from HES unclear Discriminates EGPA from GPA, MPA and PAN. Discriminant ability from HES unclear IgA (Henoch Schönlein) ACR criteria [26] May not work well in adult populations. Should be used in combination with entry criteria Published by Michel et al. [32] EULAR/PRINTO/PRES [27] Discriminates IgA from hypersensitivity Developed for pediatric populations. Should be used in combination with entry criteria Cryoglobulinemic Published by de Vita et al. [9] Validation study published separately [33] Behçet s ISG [21] More specific than the recently published ICBD criteria [10 && ] ICBD [10 && ] More sensitive than the former ISG criteria [21] 1987 JBDRC criteria [34] Expert-based criteria. Predominantly used in the Asian continent ACR, American College of Rheumatology; CHCC, Chapel Hill Consensus Conference; EMA, European Medicines Agency; EULAR/PRINTO/PRES, European League against Rheumatism/Paediatric Rheumatology International Trial Organization/Paediatric Rheumatology European Society; FVSG, French Vasculitis Study Group; ICBD, International criteria for Behçet s ; ISG, International Study Group; JBDRC, Japanese Behçet s research committee. 6 www.co-rheumatology.com Volume 27 Number 1 January 2015

Classification of Mahr and de Menthon for several entities for adult or children populations, respectively. Another collaborative international effort has led to the publication of the European Medicines Agency (EMA) algorithm [29], and many additional individual efforts have led to the publication of criteria for single entities. ACR criteria The ACR criteria represent the first and still most comprehensive set of classification criteria for several forms of, but they must be understood within the context of their developmental features [35]. The ACR criteria were derived from a dataset with patient data for several entities, and the seven generated sets of criteria therefore essentially differentiate one from the remaining forms. Consequently, the ACR criteria do not allow distinguishing the given from other nonvasculitic conditions and should be used for only illnesses for which a diagnosis has been previously ascertained. Despite these limitations, the ACR criteria have proven very useful for giant-cell arteritis [25], Takayasu arteritis [26], GPA [30] and EGPA [18], but much less for IgA [26], polyarteritis nodosa [28] and hypersensitivity [36]. Pediatric EULAR/PRINTO/PRES classification criteria The EULAR/PRINTO/PRES criteria revisited the classification criteria for four entities that primarily or occasionally occur in childhood, namely IgA, GPA, polyarteritis nodosa and Takayasu arteritis [27], because specific criteria were needed for pediatric cases with these s. Like the ACR criteria, the individual sets of criteria were derived from a large database by comparison with the remaining cases of other diagnoses as controls, which implies that they should be used for only cases with a priori knowledge of. Of note, the criteria for GPA, polyarteritis nodosa and Takayasu arteritis also seem to have face validity for adult cases. European Medicines Agency algorithm The purpose of the EMA algorithm [29], sometimes referred to as Watts criteria, was to harmonize the classification of polyarteritis nodosa and ANCAassociated. The primary scope was for patient populations analyzed in epidemiologic studies, but the tool is applicable to other research areas. The EMA algorithm does not represent an original classification system per se because it was mainly built by using various elements of the CHCC nomenclature [8] and ACR criteria [35]. The major advantage of this system is that it provides a hierarchy of classifying the four vasculitides under consideration. As well, the algorithm provides a detailed definition for the entry criteria clinical, laboratory, histological or imaging characteristics to ensure that the algorithm is used for cases only with some evidence of, and it includes a subgroup of undifferentiated. The main strength of the algorithm appears to be its good ability to unequivocally classify the s within the subcategory of ANCA-associated [37]. Other classification criteria Numerous other classification criteria, focusing on single entities, are available and are regularly used (Table 2). The recently added classification criteria for cryoglobulinemic [9] and the international criteria for Behçet s [10 && ] stem from international collaborations and were evaluated on the basis of real patient data. The international criteria for Behçet s were found more sensitive than the previous International Study Group criteria [21], although at the expense of specificity. The classification of giant-cell arteritis based on the sole criterion of positive temporal artery biopsy findings likely represents the most simple classification system and highlights the close link of diagnosis and classification. In clinical practice, a positive temporal artery biopsy is considered a stringent diagnostic criterion, although false-negative cases exist, and it can sporadically be observed in other entities. Because a positive temporal artery biopsy is not 100% specific to giant-cell arteritis, it is not a definite and stand-alone criterion to diagnose giant cell arteritis in a given patient but it still can be considered as an acceptable classification criterion to be applied to patient populations. This being said, a limitation of temporal artery biopsy for classifying giant-cell arteritis is the lack of a consensus on the microscopic findings required to comply with a histological diagnosis of giant-cell arteritis. Limitations and future directions A number of unresolved or new matters remain to be addressed. Polyarteritis nodosa, microscopic polyangiitis and adult IgA (Henoch Schönlein) are likely the most challenging s in terms of generally accepted classification criteria. The ACR criteria for IgA are poorly specific, and although enhanced criteria are now available for pediatric cases [27], similarly improved criteria need to be devised for adults. Microscopic polyangiitis has no proper classification system, but can be classified by using the EMA algorithm [29]. 1040-8711 ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-rheumatology.com 7

Vasculitis syndromes Polyarteritis nodosa is problematic as well, and we lack confidence in the value of the ACR criteria [28]. For EGPA, the major difficulty is distinguishing it from hypereosinophlic syndrome [38]. Adjustments will have to be made for other entities to account for shifting diagnostic paradigms. For example, with giant-cell arteritis, imaging techniques are increasingly being used to document vessel inflammation instead of temporal artery biopsy. The changing practices currently result in an inadequacy of the ACR criteria for discriminating giant-cell arteritis and the need for updated criteria incorporating imaging findings. In general, classification criteria developed by using only cases as controls should be applied for only cases also satisfying a minimal set of entry characteristics to ensure that they are used in the correct setting. CONCLUSION Undoubtedly, progress has been made in the classification of, which reflects the increasing knowledge about the natural history of this group of s and refined diagnostic skills. The list of illnesses categorized as has become more extensive, and the incorporation of secondary and single-organ in the classification spectrum of the 2012 CHCC nomenclature has been important. Several international efforts have been undertaken to produce widely acceptable classification criteria for virtually all entities and now offer a solid basis to homogenize patient populations enrolled in research studies. The classification of, however, remains a challenge, and further evolution is expected. The most important challenge is the current disconnect of the classification systems from clinical practice, which may indicate that the current general classification scheme of, although conceptually accurate, is of limited use in clinical practice. With respect to the unmet needs in the area of classification criteria, further progress in the near future is being anticipated to come from the diagnostic and classification criteria for (DCVAS) study [39 & ] currently underway. Acknowledgements ne. Financial support and sponsorship ne. Conflicts of interest ne. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Alarcon-Segovia D. The necrotizing vasculitides. A new pathogenetic classification. Med Clin rth Am 1977; 61:241 260. 2. deshazo RD. The spectrum of systemic : a classification to aid diagnosis. Postgrad Med 1975; 58:78 82. 3. Fauci AS, Haynes B, Katz P. The spectrum of : clinical, pathologic, immunologic and therapeutic considerations. Ann Intern Med 1978; 89:660 676. 4. Lie JT. menclature and classification of : plus ca change, plus c est la meme chose. Arthritis Rheum 1994; 37:181 186. 5. Zeek PM. Periarteritis nodosa: a critical review. Am J Clin Pathol 1952; 22:777 790. 6. Watts RA, Suppiah R, Merkel PA, Luqmani R. Systemic : is it time to reclassify? Rheumatology (Oxford) 2011; 50:643 645. 7. && Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference menclature of Vasculitides. Arthritis Rheum 2013; 65:1 11. This international revision of the consensus conference for the nomenclature of represents a significant update on the labeling, definition and categorization of entities. 8. Jennette JC, Falk RJ, Andrassy K, et al. menclature of systemic vasculitides: proposal of an international consensus conference. Arthritis Rheum 1994; 37:187 192. 9. De Vita S, Soldano F, Isola M, et al. Preliminary classification criteria for the cryoglobulinaemic. Ann Rheum Dis 2011; 70:1183 1190. 10. && International Team for the Revision of the International Criteria for Behcet s Disease. The International Criteria for Behcet s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014; 28:338 347. This large multinational effort resulted in the establishment and validation of a set of classification criteria for Behçet s that represents an evolution of the previous widely used International Study Group criteria. 11. Atisha-Fregoso Y, Hinojosa-Azaola A, Alcocer-Varela J. Localized, singleorgan : clinical presentation and management. Clin Rheumatol 2013; 32:1 6. 12. Hernandez-Rodriguez J, Hoffman GS. Updating single-organ. Curr Opin Rheumatol 2012; 24:38 45. 13. Cordier JF, Cottin V, Guillevin L, et al. L5. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Presse Med 2013; 42:507 510. 14. Lionaki S, Blyth ER, Hogan SL, et al. Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in recognition and prognosis. Arthritis Rheum 2012; 64:3452 3462. 15. Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated. N Engl J Med 2012; 367:214 223. 16. & Mahr A, Katsahian S, Varet H, et al. Revisiting the classification of clinical phenotypes of antineutrophil cytoplasmic antibody-associated : a cluster analysis. Ann Rheum Dis 2013; 72:1003 1010. This cluster analysis supports classifying ANCA-associated better by specific ANCA type and renal involvement than by the traditional phenotypes of GPA and microscopic polyangiitis. 17. Kawakami T. New algorithm (KAWAKAMI algorithm) to diagnose primary cutaneous. J Dermatol 2010; 37:113 124. 18. Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33:1094 1100. 19. Dajani AS, Taubert KA, Gerber MA, et al. Diagnosis and therapy of Kawasaki in children. Circulation 1993; 87:1776 1780. 20. WGET Research Group. Design of the Wegener s Granulomatosis Etanercept Trial (WGET). Control Clin Trials 2002; 23:450 468. 21. Criteria for diagnosis of Behcet s. International Study Group for Behcet s. Lancet 1990; 335:1078 1080. 22. Henegar C, Pagnoux C, Puechal X, et al. A paradigm of diagnostic criteria for polyarteritis nodosa: analysis of a series of 949 patients with vasculitides. Arthritis Rheum 2008; 58:1528 1538. 23. Sharma BK, Jain S, Suri S, Numano F. Diagnostic criteria for Takayasu arteritis. Int J Cardiol 1996; 54 (Suppl):S141 S147. 24. Doria A, Mosca M, Gambari PF, Bombardieri S. Defining unclassifiable connective tissue s: incomplete, undifferentiated, or both? J Rheumatol 2005; 32:213 215. 25. Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122 1128. 8 www.co-rheumatology.com Volume 27 Number 1 January 2015

Classification of Mahr and de Menthon 26. Mills JA, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum 1990; 33:1114 1121. 27. Ozen S, Ruperto N, Dillon MJ, et al. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 2006; 65:936 941. 28. Lightfoot RW Jr, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990; 33:1088 1093. 29. Watts R, Lane S, Hanslik T, et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007; 66:222 227. 30. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener s granulomatosis. Arthritis Rheum 1990; 33:1101 1107. 31. Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic with asthma and eosinophilia: a clinical approach to the Churg Strauss syndrome. Medicine (Baltimore) 1984; 63:65 81. 32. Michel BA, Hunder GG, Bloch DA, Calabrese LH. Hypersensitivity and Henoch-Schönlein purpura: a comparison between the 2 disorders. J Rheumatol 1992; 19:721 728. 33. Quartuccio L, Isola M, Corazza L, et al. Validation of the classification criteria for cryoglobulinaemic. Rheumatology (Oxford) 2014; Jul 3. pii: keu271. [Epub ahead of print] 34. Mizushima Y. Recent research into Behçet s in Japan. Int J Tissue React 1988; 10:59 65. 35. Hunder GG, Arend WP, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of. Introduction. Arthritis Rheum 1990; 33:1065 1067. 36. Calabrese LH, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of hypersensitivity. Arthritis Rheum 1990; 33:1108 1113. 37. Liu LJ, Chen M, Yu F, et al. Evaluation of a new algorithm in classification of systemic. Rheumatology (Oxford) 2008; 47:708 712. 38. Mahr A, Moosig F, Neumann T, et al. Eosinophilic granulomatosis with polyangiitis (Churg Strauss): evolutions in classification, etiopathogenesis, assessment and management. Curr Opin Rheumatol 2014; 26:16 23. 39. & Craven A, Robson J, Ponte C, et al. ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS). Clin Exp Nephrol 2013; 17:619 621. This article outlines the aims, methods and current state of a large ongoing study to develop revised classification criteria for several entities. 1040-8711 ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-rheumatology.com 9