Arthritis & Rheumatism Official Journal of the American College of Rheurnatology
THE AMERICAN COLLEGE OF RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF VASCULITIS Introduction GENE G.HUNDER, WILLIAM P. AREND, DANIEL A. BLOCH, LEONARD H. CALABRESE, ANTHONY S. FAUCI, JAMES F. FRIES, RAND1 Y. LEAVITT, J. T. LIE, ROBERT w.LIGHTFOOT, JR., ALFONSE T. MASI, DENNIS J. MCSHANE, BEAT A. MICHEL, JOHN A. MILLS, MARY BETTY STEVENS, STANLEY L. WALLACE, and NATHAN J. ZVAIFLER In the last decade, information about the pathophysiologic mechanisms underlying many rheumatic diseases has increased rapidly. With similar rapidity, many new therapies for these diseases have been developed. In order for this progress to continue and for the laboratory and therapeutic advances to be applied to the proper patient groups, it is imperative that the rheumatic diseases be defined or classified clinically, as clearly as current knowledge permits. Most rheumatic diseases lack pathognomonic features. Because of this, the physician is forced to From the American College of Rheumatology Subcommittee on Classification of Vasculitis (Diagnostic and Therapeutic Criteria Committee of the Council on Research). Gene G. Hunder, MD: Mayo Clinic, Rochester, MN. and Chair, Subcommittee on Classification of Vasculitis; William P. Arend. MD: University of Colorado Health Science Center, Denver, CO; Daniel A. Bloch, PhD: Stanford University, Stanford, CA; Leonard H. Calabrese, DO: Cleveland Clinic Foundation, Cleveland, OH; Anthony S. Fauci. M D NIAID. NIH, Bethesda, MD; James F. Fries, MD: Stanford University, Stanford, CA; Randi Y. Leavitt, MD, PhD: NIAID, NIH, Bethesda, MD; J. T. Lie, MD: Mayo Clinic, Rochester, MN; Robert W. Lightfoot, Jr., MD: University of Kentucky, Lexington, KY; Alfonse T. Masi, MD, DrPH: University of Illinois College of Medicine, Peoria, IL; Dennis J. McShane, MD: Stanford University, Stanford, CA; Beat A. Michel. MD: Rheumaklinik Universitgtsspital, Zurich, Switzerland; John A. Mills, MD: Massachusetts General Hospital, Boston, MA; Mary Betty Stevens, M D Johns Hopkins University, Baltimore, MD; Stanley L. Wallace, MD: SUNY Downstate Medical Center, Brooklyn, NY (Dr. Wallace is deceased); Nathan J. Zvaifler, MD: University of California, San Diego, San Diego, CA. Address reprint requests to the American College of Rheumatology, 17 Executive Park Drive NE, Suite 480, Atlanta. GA 30329.
Submitted for publication October 2, 1989; accepted in revised form April 3, 1990.
rely on the presence of a combination of clinical and laboratory manifestations in order to identify specific rheumatic diseases. To establish uniformity in the definitions of these diseases, classification criteria and diagnostic criteria have been developed. The American College of Rheumatology (ACR) has long had an interest in the classification of rheumatic diseases, and criteria for a number of conditions have been developed under its sponsorship and that of its predecessor, the American Rheumatism Association (1-6). These criteria sets have generally been derived by comparing findings in a group of patients who have the disease in question with findings in a group of control patients. Such classification criteria include manifestations that are characteristic of the disease in question and occur with less frequency or are absent in other conditions. Symptoms or findings that may be typical or common but may also be present in other diseases tend to be excluded. The goal is to identify a set of clinical findings (criteria) that recognize a high proportion of patients with the particular disease (sensitivity) and exclude a high proportion of patients with other diseases (specificity). In other words, classification criteria, as defined in such studies, select those clinical findings which both identify the disease and separate it from others. As a result, classification criteria do not include the full spectrum of manifestations of a disease and are therefore not appropriate to use in the diagnosis of the individual patient. Diagnostic criteria, on the other hand, tend to focus on listing or determining the combinations of findings that need to be present in
1065
HUNDER ET AL
1066 Table 1. Demographic characteristics of 807 patients with vasculitis, according to disease category*
Disease category
n
Age at disease onset (mean 2 SEMI
Polyarteritis nodosa Churg-Strauss syndrome Wegener’s granulomatosis Hypersensitivity vasculitis Henoch-Schonlein purpura Giant cell (temporal) arteritis Takayasu arteritis Other vasculitis, type unspecified
118 20 85 93 85 214 63 129
48.4 f 1.7 49.6 f 3.0 45.2 f 1.8 47.3 f 2.0 17.4 f 2.0 69.3 5 0.5 26.4 f 1.2 44.1 f 1.8
Race % female
% whitehlacklother
38. I 31.0 36.5 53.8 46.4 74.8 85.7 54.7
78/16/6 951510 9Ifll2 7711 1112 6315132 95/411
53/13/34 8211216
* Patients with Kawasaki disease, patients whose cases lacked sufficient evidence of vasculitis, and patients with vasculitis and a connective tissue disease were excluded from study (n = 213). order to be certain that a particular disease is present. Manifestations that are not unique to the disease, but are found in related conditions, are likely to be included. The differences between classification criteria and diagnostic criteria are often misunderstood. Classificationcriteria provide a standard way to evaluate and describe groups of patients in therapeutic, epidemiologic, or other studies. A listing of the proportion of patients in a group that fulfills the criteria gives considerable information about the clinical status of the patients that are included. When a tree classification is used, a statement about the numbers of patients in the various subsets adds further insight. These descriptions provide a basis for comparing other patient populations involved in other studies at different times or in different settings. The vasculitides comprise a diverse group of conditions characterized by inflammation and necrosis of blood vessel walls. Arteries, and sometimes veins, of various sizes and in different locations throughout the body may be involved, resulting in a great diversity of symptoms and findings. The causes and the pathogenetic mechanisms that produce inflammatory lesions Table 2. Number of cooperating centers that contributed patients for study, according to disease category*
Disease category Polyarteritis nodosa Churg-Strauss syndrome Wegener’s granulomatosis Hypersensitivity vasculitis Henoch-Schonlein purpura Giant cell (temporal) arteritis Takayasu arteritis Other vasculitis. type unspecified
No. of centers 34 14 27
26 22 31
23 34
* A total of 48 different centers contributed patients to the study. See Table 1 for patients excluded from study.
in the various forms of vasculitis are not completely understood, but it is likely that there are many. This status, added to the marked variability of different cases of the same type of vasculitis, has prevented the development of a universally acceptable classification of vasculitis. Yet, it is apparent that within the group of vasculitis patients, there are several clinical syndromes which appear to be distinct processes. In attempts to define such interrelationships, several investigators have described classifications of vasculitis (7-9).These systems have been empiric and have been based on various aspects of vasculitis, such as the predominant size of the involved vessels, the extent or location of involvement, the suspected pathogenetic processes, and the common symptoms among the most definable groups. In order to improve communication among physicians regarding these syndromes and to permit more direct comparisons of research studies on vasculitis that are performed in different centers, the ACR appointed a subcommittee of the Diagnostic and Therapeutic Criteria Committee to investigate the possibility of developing a standard classificationof vasculitis. After several discussions, the Subcommittee on Classification of Vasculitis decided to formulate criteria through an analytic, rather than empiric, approach add to collect data in a prospective manner, including cases seen consecutively. To limit the scope of the analysis to a manageable size, it was decided that the first step would be to establish criteria that would distinguish individual types of vasculitis from others. Criteria that would differentiate patients with vasculitis from patients without vasculitis would constitute a possible second study to be conducted at a later date. This study was limited to 7 forms of vasculitis that are usually considered clinically distinct syndromes: polyarteritis nodosa, Churg-Strauss syn-
1067
VASCULITIS CRITERIA: INTRODUCTION drome, Wegener’s granulomatosis, hypersensitivity vasculitis, Henoch-Schonlein purpura, giant cell (temporal) arteritis, and Takayasu arteritis. Although some of these syndromes have quite similar clinical or histologic features (e.g., Henoch-Schonlein purpura and hypersensitivity vasculitis), the separate diagnoses were listed to yield a greater initial specificity of classification. Over a 5-year period, rheumatologists from 48 centers in the United States, Canada, and Mexico submitted a total of 1,020 cases, under approximately 37 different diagnostic titles, for this study. After review by the Subcommittee on Classification of Vasculitis, 20 of these cases were eliminated because they appeared to lack sufficient evidence for the presence of vasculitis. In some instances, only 1 case or a few cases were listed under certain uncommon categories, such as urticaria1 vasculitis, cryoglobulinemic vasculitis associated with multiple myeloma, etc. The large number of diagnostic titles that were used reflects some of the problems with both the nomenclature and the understanding of this group of diseases. Table 1 lists the number of patients in each of the 7 vasculitis categories studied, with the remaining patients combined into a single, separate group. Age at disease onset, sex, and ethnic background are also shown. In Table 2, the number of centers that contributed study patients is given, according to the various vasculitis categories. While the relative frequencies of the types of vasculitis do not represent an epidemiologic profile, they do reflect the types of patients rheumatologists examine. This report of the ACR Subcommittee on Classification of Vasculitis is divided into sections describing the patients and methods, the histopathologic features, the criteria for each of the 7 forms of vasculitis studied, a summary, and an overview of statistical approaches to classification. We hope the results of this study will be useful for persons interested in the vasculitides.
REFERENCES 1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Tala1 N, Winchester RJ: The
1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271-1277, 1982 2. Pinals RS, Masi AT, Larsen RA, Subcommittee for
Criteria of Remission in Rheumatoid Arthritis of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 24:13011315, 1981 3. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and TherapeuticCriteria Committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23: 581-590, 1980 4. Arnett FC, Edworthy SM,Bloch DA, McShane DJ, Fries
5.
6.
7.
8. 9.
JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315-324, 1988 Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ Jr, Fink CW, Hanson V, Jacobs JC, Masi AT, Schaller JG, Fries JF, McShane D, Young D: A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum 29:274-281, 1986 Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D, Kaplan D. Koopman W, Longley S 111, Mankin H, McShane DJ, Medsger T Jr, Meenan R, Mikkelsen W, Moskowitz R, Murphy W, Rothschild B, Segal M, Sokoloff L, Wolfe F Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 29:1039-1049, 1986 Fauci AS, Haynes BF, Katz P: The spectrum of vasculitis: clinical, pathologic, immunologic, and therapeutic considerations. Ann Intern Med 89:660-676, 1978 Alarc6n-Segovia D: Classification of necrotizing vasculitides in man. CIin Rheum Dis 6:223-231, 1980 Hunder GG, Lie JT: The vasculitides. Clin Cardiovasc Dis 12:261-291, 1983
THE AMERICAN COLLEGE OF RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF VASCULITIS Introduction GENE G.HUNDER, WILLIAM P. AREND, DANIEL A. BLOCH, LEONARD H. CALABRESE, ANTHONY S. FAUCI, JAMES F. FRIES, RAND1 Y. LEAVITT, J. T. LIE, ROBERT w.LIGHTFOOT, JR., ALFONSE T. MASI, DENNIS J. MCSHANE, BEAT A. MICHEL, JOHN A. MILLS, MARY BETTY STEVENS, STANLEY L. WALLACE, and NATHAN J. ZVAIFLER In the last decade, information about the pathophysiologic mechanisms underlying many rheumatic diseases has increased rapidly. With similar rapidity, many new therapies for these diseases have been developed. In order for this progress to continue and for the laboratory and therapeutic advances to be applied to the proper patient groups, it is imperative that the rheumatic diseases be defined or classified clinically, as clearly as current knowledge permits. Most rheumatic diseases lack pathognomonic features. Because of this, the physician is forced to From the American College of Rheumatology Subcommittee on Classification of Vasculitis (Diagnostic and Therapeutic Criteria Committee of the Council on Research). Gene G. Hunder, MD: Mayo Clinic, Rochester, MN. and Chair, Subcommittee on Classification of Vasculitis; William P. Arend. MD: University of Colorado Health Science Center, Denver, CO; Daniel A. Bloch, PhD: Stanford University, Stanford, CA; Leonard H. Calabrese, DO: Cleveland Clinic Foundation, Cleveland, OH; Anthony S. Fauci. M D NIAID. NIH, Bethesda, MD; James F. Fries, MD: Stanford University, Stanford, CA; Randi Y. Leavitt, MD, PhD: NIAID, NIH, Bethesda, MD; J. T. Lie, MD: Mayo Clinic, Rochester, MN; Robert W. Lightfoot, Jr., MD: University of Kentucky, Lexington, KY; Alfonse T. Masi, MD, DrPH: University of Illinois College of Medicine, Peoria, IL; Dennis J. McShane, MD: Stanford University, Stanford, CA; Beat A. Michel. MD: Rheumaklinik Universitgtsspital, Zurich, Switzerland; John A. Mills, MD: Massachusetts General Hospital, Boston, MA; Mary Betty Stevens, M D Johns Hopkins University, Baltimore, MD; Stanley L. Wallace, MD: SUNY Downstate Medical Center, Brooklyn, NY (Dr. Wallace is deceased); Nathan J. Zvaifler, MD: University of California, San Diego, San Diego, CA. Address reprint requests to the American College of Rheumatology, 17 Executive Park Drive NE, Suite 480, Atlanta. GA 30329.
Submitted for publication October 2, 1989; accepted in revised form April 3, 1990.
rely on the presence of a combination of clinical and laboratory manifestations in order to identify specific rheumatic diseases. To establish uniformity in the definitions of these diseases, classification criteria and diagnostic criteria have been developed. The American College of Rheumatology (ACR) has long had an interest in the classification of rheumatic diseases, and criteria for a number of conditions have been developed under its sponsorship and that of its predecessor, the American Rheumatism Association (1-6). These criteria sets have generally been derived by comparing findings in a group of patients who have the disease in question with findings in a group of control patients. Such classification criteria include manifestations that are characteristic of the disease in question and occur with less frequency or are absent in other conditions. Symptoms or findings that may be typical or common but may also be present in other diseases tend to be excluded. The goal is to identify a set of clinical findings (criteria) that recognize a high proportion of patients with the particular disease (sensitivity) and exclude a high proportion of patients with other diseases (specificity). In other words, classification criteria, as defined in such studies, select those clinical findings which both identify the disease and separate it from others. As a result, classification criteria do not include the full spectrum of manifestations of a disease and are therefore not appropriate to use in the diagnosis of the individual patient. Diagnostic criteria, on the other hand, tend to focus on listing or determining the combinations of findings that need to be present in
1065
HUNDER ET AL
1066 Table 1. Demographic characteristics of 807 patients with vasculitis, according to disease category*
Disease category
n
Age at disease onset (mean 2 SEMI
Polyarteritis nodosa Churg-Strauss syndrome Wegener’s granulomatosis Hypersensitivity vasculitis Henoch-Schonlein purpura Giant cell (temporal) arteritis Takayasu arteritis Other vasculitis, type unspecified
118 20 85 93 85 214 63 129
48.4 f 1.7 49.6 f 3.0 45.2 f 1.8 47.3 f 2.0 17.4 f 2.0 69.3 5 0.5 26.4 f 1.2 44.1 f 1.8
Race % female
% whitehlacklother
38. I 31.0 36.5 53.8 46.4 74.8 85.7 54.7
78/16/6 951510 9Ifll2 7711 1112 6315132 95/411
53/13/34 8211216
* Patients with Kawasaki disease, patients whose cases lacked sufficient evidence of vasculitis, and patients with vasculitis and a connective tissue disease were excluded from study (n = 213). order to be certain that a particular disease is present. Manifestations that are not unique to the disease, but are found in related conditions, are likely to be included. The differences between classification criteria and diagnostic criteria are often misunderstood. Classificationcriteria provide a standard way to evaluate and describe groups of patients in therapeutic, epidemiologic, or other studies. A listing of the proportion of patients in a group that fulfills the criteria gives considerable information about the clinical status of the patients that are included. When a tree classification is used, a statement about the numbers of patients in the various subsets adds further insight. These descriptions provide a basis for comparing other patient populations involved in other studies at different times or in different settings. The vasculitides comprise a diverse group of conditions characterized by inflammation and necrosis of blood vessel walls. Arteries, and sometimes veins, of various sizes and in different locations throughout the body may be involved, resulting in a great diversity of symptoms and findings. The causes and the pathogenetic mechanisms that produce inflammatory lesions Table 2. Number of cooperating centers that contributed patients for study, according to disease category*
Disease category Polyarteritis nodosa Churg-Strauss syndrome Wegener’s granulomatosis Hypersensitivity vasculitis Henoch-Schonlein purpura Giant cell (temporal) arteritis Takayasu arteritis Other vasculitis. type unspecified
No. of centers 34 14 27
26 22 31
23 34
* A total of 48 different centers contributed patients to the study. See Table 1 for patients excluded from study.
in the various forms of vasculitis are not completely understood, but it is likely that there are many. This status, added to the marked variability of different cases of the same type of vasculitis, has prevented the development of a universally acceptable classification of vasculitis. Yet, it is apparent that within the group of vasculitis patients, there are several clinical syndromes which appear to be distinct processes. In attempts to define such interrelationships, several investigators have described classifications of vasculitis (7-9).These systems have been empiric and have been based on various aspects of vasculitis, such as the predominant size of the involved vessels, the extent or location of involvement, the suspected pathogenetic processes, and the common symptoms among the most definable groups. In order to improve communication among physicians regarding these syndromes and to permit more direct comparisons of research studies on vasculitis that are performed in different centers, the ACR appointed a subcommittee of the Diagnostic and Therapeutic Criteria Committee to investigate the possibility of developing a standard classificationof vasculitis. After several discussions, the Subcommittee on Classification of Vasculitis decided to formulate criteria through an analytic, rather than empiric, approach add to collect data in a prospective manner, including cases seen consecutively. To limit the scope of the analysis to a manageable size, it was decided that the first step would be to establish criteria that would distinguish individual types of vasculitis from others. Criteria that would differentiate patients with vasculitis from patients without vasculitis would constitute a possible second study to be conducted at a later date. This study was limited to 7 forms of vasculitis that are usually considered clinically distinct syndromes: polyarteritis nodosa, Churg-Strauss syn-
1067
VASCULITIS CRITERIA: INTRODUCTION drome, Wegener’s granulomatosis, hypersensitivity vasculitis, Henoch-Schonlein purpura, giant cell (temporal) arteritis, and Takayasu arteritis. Although some of these syndromes have quite similar clinical or histologic features (e.g., Henoch-Schonlein purpura and hypersensitivity vasculitis), the separate diagnoses were listed to yield a greater initial specificity of classification. Over a 5-year period, rheumatologists from 48 centers in the United States, Canada, and Mexico submitted a total of 1,020 cases, under approximately 37 different diagnostic titles, for this study. After review by the Subcommittee on Classification of Vasculitis, 20 of these cases were eliminated because they appeared to lack sufficient evidence for the presence of vasculitis. In some instances, only 1 case or a few cases were listed under certain uncommon categories, such as urticaria1 vasculitis, cryoglobulinemic vasculitis associated with multiple myeloma, etc. The large number of diagnostic titles that were used reflects some of the problems with both the nomenclature and the understanding of this group of diseases. Table 1 lists the number of patients in each of the 7 vasculitis categories studied, with the remaining patients combined into a single, separate group. Age at disease onset, sex, and ethnic background are also shown. In Table 2, the number of centers that contributed study patients is given, according to the various vasculitis categories. While the relative frequencies of the types of vasculitis do not represent an epidemiologic profile, they do reflect the types of patients rheumatologists examine. This report of the ACR Subcommittee on Classification of Vasculitis is divided into sections describing the patients and methods, the histopathologic features, the criteria for each of the 7 forms of vasculitis studied, a summary, and an overview of statistical approaches to classification. We hope the results of this study will be useful for persons interested in the vasculitides.
REFERENCES 1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Tala1 N, Winchester RJ: The
1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271-1277, 1982 2. Pinals RS, Masi AT, Larsen RA, Subcommittee for
Criteria of Remission in Rheumatoid Arthritis of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 24:13011315, 1981 3. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and TherapeuticCriteria Committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23: 581-590, 1980 4. Arnett FC, Edworthy SM,Bloch DA, McShane DJ, Fries
5.
6.
7.
8. 9.
JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315-324, 1988 Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ Jr, Fink CW, Hanson V, Jacobs JC, Masi AT, Schaller JG, Fries JF, McShane D, Young D: A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum 29:274-281, 1986 Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D, Kaplan D. Koopman W, Longley S 111, Mankin H, McShane DJ, Medsger T Jr, Meenan R, Mikkelsen W, Moskowitz R, Murphy W, Rothschild B, Segal M, Sokoloff L, Wolfe F Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 29:1039-1049, 1986 Fauci AS, Haynes BF, Katz P: The spectrum of vasculitis: clinical, pathologic, immunologic, and therapeutic considerations. Ann Intern Med 89:660-676, 1978 Alarc6n-Segovia D: Classification of necrotizing vasculitides in man. CIin Rheum Dis 6:223-231, 1980 Hunder GG, Lie JT: The vasculitides. Clin Cardiovasc Dis 12:261-291, 1983
