Journal of Autoimmunity xxx (2014) 1e4
Contents lists available at ScienceDirect
Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm
Review
Diagnostic criteria for systemic lupus erythematosus: A critical review Cong Yu a, M. Eric Gershwin b, Christopher Chang c, * a
Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing, China Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA c Division of Allergy and Immunology, Thomas Jefferson University, 1600 Rockland Road, Wilmington, DE 19803, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 October 2013 Accepted 13 November 2013
Systemic lupus erythematosus is a multi-organ system autoimmune disease with clinical and serological heterogeneity. The formulation of initial criteria for SLE was first proposed by the American College of Rheumatology and appeared in 1971. Although the original purpose of the criteria was to classify the disease, it became widely used as a diagnostic criteria in clinical situations. Since then the ACR criteria have undergone at least two changes (in 1982 and 1997). Clinical manifestations that can differentiate SLE patients from healthy people such as skin lesions, arthritis, renal disorder, neurologic disorder, hematologic changes and others are included in these criteria. Serum anti-nuclear antibody, anti-ds-DNA antibody and anti-Sm antibody are important biomarkers of SLE patients. In 2012, the Systemic Lupus Collaborating Clinics proposed the SLICC criteria for SLE in view of new knowledge of autoantibodies and the importance of low complement. Future biomarkers may be useful in distinguishing SLE from other diseases and in monitoring of disease activity. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Systemic lupus erythematosus Criteria Autoantibodies Biomarkers Anti-Ro Anti-nucleosome antibodies
1. Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of clinical manifestations and a wide profile of autoantibodies. The clinical and serological heterogeneity makes it a great challenge for diagnosis, especially at the very early stage, when an inadequate number of features required to meet the criteria may be present. The most widely used classification criteria for SLE are those proposed by the American College of Rheumatology (ACR). The first version of the criteria was published in 1971 and revised in 1982 and 1997. 2. The preliminary criteria for classification of SLE The preliminary criteria including 14 items (Table 1) were effective in excluding normal patients in the population from which it was derived. However, it performed less well in patients during the early stage of their disease. Moreover, LE-cell test were often unavailable for these patients, thus high titers of anti-nuclear antibodies were also utilized as a criteria for validation [1]. Wolf et al. examined 100 healthy women for any of the preliminary criteria of SLE. They found that no patient had more than three of the criteria and half of them had none. Twenty patients had a positive ANA, but
* Corresponding author. Tel.: þ1 302 651 4321; fax: þ1 302 651 6558. E-mail address: [email protected] (C. Chang).
none of the patients with positive ANA had clinical evidence of SLE. This false positive serum ANA may be associated with oral contraceptives, which may make the ANA item by itself less specific for the diagnosis of SLE [2]. 3. The 1982 revision of classification criteria for SLE A number of suggestions were proposed after the publication of 1971 classification. Too many criteria for cutaneous manifestations and too few for major organ involvement reduced the specificity of ACR 1971. In 1982, a set of revised criteria was published (Table 1) [3]. Compared with the 1971 criteria, this revision excluded certain cutaneous items such as Raynaud’s phenomenon and alopecia, and the ANA test was separated out as a new item. In addition, the criterion for proteinuria was reduced from >3.5g/day to >0.5g/day and two renal items were consolidated into one. The arthritis criterion had an additional description of non-erosive arthritis involving two or more joints. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity [3]. The 1982 ACR criteria have been validated. Passas et al. tested 207 patients and found that the specificity of the revised criteria was slightly higher than the preliminary criteria (99% vs. 98%) [4]. Levin et al. tested 159 SLE patients and found the ANA test accounted for the increased sensitivity of the revised criteria [5]. In contrast,
0896-8411/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jaut.2014.01.004
Please cite this article in press as: Yu C, et al., Diagnostic criteria for systemic lupus erythematosus: A critical review, Journal of Autoimmunity (2014), http://dx.doi.org/10.1016/j.jaut.2014.01.004
2
C. Yu et al. / Journal of Autoimmunity xxx (2014) 1e4
Table 1 Diagnostic criteria over the years.
Cutaneous manifestation
Joints
1971 ACR
1982 ACR
1997 ACR
2012 SLICC
6 items Facial erythema (butterfly rash) Discoid rash Raynaud’s phenomenon Alopecia Photosensitivity Oral or nasopharyngeal ulceration 1 item Arthritis without deformity one peripheral joint, characterized by pain, tenderness or swelling
4 items Malar rash DLE lesion Photosensitivity Oral ulcers
4 items Malar rash Discoid rash Photosensitivity Oral ulcers
4 items ACLE/SCLE CCLE Oral ulcers Nonscarring alopecia
1 item Nonerosive arthritis 2 peripheral joints, characterized by pain, tenderness or swelling 1 item Serositis (any of the following): pleuritis, pericarditis
1 item Nonerosive arthritis 2 peripheral joints, characterized by pain, tenderness or swelling
1 item Synovitis 2 peripheral joints, characterized by pain, tenderness, swelling or morning stiffness 30min
1 item Serositis (any of the following): pleuritis rub, evidence of pleural effusion, pericarditis, EKG
1 item Serositis (any of the following): pleuritis, typical pleurisy > 1day, history, rub, evidence of pleural effusion, pericarditis, typical pericardial pain >1day, EKG evidence of pericardial fusion 1 item Renal disorder (Any of the following): urine protein/creatinine ratio or urinary protein concentration of 0.5 g of protein/24 h, Red blood cell casts 3 items Hemolytic anemia Leukopenia or lymphopenia (
Contents lists available at ScienceDirect
Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm
Review
Diagnostic criteria for systemic lupus erythematosus: A critical review Cong Yu a, M. Eric Gershwin b, Christopher Chang c, * a
Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing, China Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA c Division of Allergy and Immunology, Thomas Jefferson University, 1600 Rockland Road, Wilmington, DE 19803, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 October 2013 Accepted 13 November 2013
Systemic lupus erythematosus is a multi-organ system autoimmune disease with clinical and serological heterogeneity. The formulation of initial criteria for SLE was first proposed by the American College of Rheumatology and appeared in 1971. Although the original purpose of the criteria was to classify the disease, it became widely used as a diagnostic criteria in clinical situations. Since then the ACR criteria have undergone at least two changes (in 1982 and 1997). Clinical manifestations that can differentiate SLE patients from healthy people such as skin lesions, arthritis, renal disorder, neurologic disorder, hematologic changes and others are included in these criteria. Serum anti-nuclear antibody, anti-ds-DNA antibody and anti-Sm antibody are important biomarkers of SLE patients. In 2012, the Systemic Lupus Collaborating Clinics proposed the SLICC criteria for SLE in view of new knowledge of autoantibodies and the importance of low complement. Future biomarkers may be useful in distinguishing SLE from other diseases and in monitoring of disease activity. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Systemic lupus erythematosus Criteria Autoantibodies Biomarkers Anti-Ro Anti-nucleosome antibodies
1. Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of clinical manifestations and a wide profile of autoantibodies. The clinical and serological heterogeneity makes it a great challenge for diagnosis, especially at the very early stage, when an inadequate number of features required to meet the criteria may be present. The most widely used classification criteria for SLE are those proposed by the American College of Rheumatology (ACR). The first version of the criteria was published in 1971 and revised in 1982 and 1997. 2. The preliminary criteria for classification of SLE The preliminary criteria including 14 items (Table 1) were effective in excluding normal patients in the population from which it was derived. However, it performed less well in patients during the early stage of their disease. Moreover, LE-cell test were often unavailable for these patients, thus high titers of anti-nuclear antibodies were also utilized as a criteria for validation [1]. Wolf et al. examined 100 healthy women for any of the preliminary criteria of SLE. They found that no patient had more than three of the criteria and half of them had none. Twenty patients had a positive ANA, but
* Corresponding author. Tel.: þ1 302 651 4321; fax: þ1 302 651 6558. E-mail address: [email protected] (C. Chang).
none of the patients with positive ANA had clinical evidence of SLE. This false positive serum ANA may be associated with oral contraceptives, which may make the ANA item by itself less specific for the diagnosis of SLE [2]. 3. The 1982 revision of classification criteria for SLE A number of suggestions were proposed after the publication of 1971 classification. Too many criteria for cutaneous manifestations and too few for major organ involvement reduced the specificity of ACR 1971. In 1982, a set of revised criteria was published (Table 1) [3]. Compared with the 1971 criteria, this revision excluded certain cutaneous items such as Raynaud’s phenomenon and alopecia, and the ANA test was separated out as a new item. In addition, the criterion for proteinuria was reduced from >3.5g/day to >0.5g/day and two renal items were consolidated into one. The arthritis criterion had an additional description of non-erosive arthritis involving two or more joints. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity [3]. The 1982 ACR criteria have been validated. Passas et al. tested 207 patients and found that the specificity of the revised criteria was slightly higher than the preliminary criteria (99% vs. 98%) [4]. Levin et al. tested 159 SLE patients and found the ANA test accounted for the increased sensitivity of the revised criteria [5]. In contrast,
0896-8411/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jaut.2014.01.004
Please cite this article in press as: Yu C, et al., Diagnostic criteria for systemic lupus erythematosus: A critical review, Journal of Autoimmunity (2014), http://dx.doi.org/10.1016/j.jaut.2014.01.004
2
C. Yu et al. / Journal of Autoimmunity xxx (2014) 1e4
Table 1 Diagnostic criteria over the years.
Cutaneous manifestation
Joints
1971 ACR
1982 ACR
1997 ACR
2012 SLICC
6 items Facial erythema (butterfly rash) Discoid rash Raynaud’s phenomenon Alopecia Photosensitivity Oral or nasopharyngeal ulceration 1 item Arthritis without deformity one peripheral joint, characterized by pain, tenderness or swelling
4 items Malar rash DLE lesion Photosensitivity Oral ulcers
4 items Malar rash Discoid rash Photosensitivity Oral ulcers
4 items ACLE/SCLE CCLE Oral ulcers Nonscarring alopecia
1 item Nonerosive arthritis 2 peripheral joints, characterized by pain, tenderness or swelling 1 item Serositis (any of the following): pleuritis, pericarditis
1 item Nonerosive arthritis 2 peripheral joints, characterized by pain, tenderness or swelling
1 item Synovitis 2 peripheral joints, characterized by pain, tenderness, swelling or morning stiffness 30min
1 item Serositis (any of the following): pleuritis rub, evidence of pleural effusion, pericarditis, EKG
1 item Serositis (any of the following): pleuritis, typical pleurisy > 1day, history, rub, evidence of pleural effusion, pericarditis, typical pericardial pain >1day, EKG evidence of pericardial fusion 1 item Renal disorder (Any of the following): urine protein/creatinine ratio or urinary protein concentration of 0.5 g of protein/24 h, Red blood cell casts 3 items Hemolytic anemia Leukopenia or lymphopenia (
