Cutaneous lupus erythematosus (CLE) is an autoimmune skin condition with increased risk for development of systemic lupus erythematosus (SLE). SLE diagnosis occurs by accrual of criteria, of which multiple sets exist. CLE to SLE progression studies primarily utilize the 1982 American College of Rheumatology (ACR) criteria for diagnosis of SLE.1,2 ACR criteria limitations include potential SLE diagnosis by mucocutaneous manifestations without end-organ involvement.3 The 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria was developed, in part, to address this limitation. However, few studies have evaluated CLE to SLE progression by the SLICC. Our study aimed to characterize CLE to SLE progression using the SLICC criteria by determining frequency, baseline risk factors, and criteria gained in a CLE patient cohort. We secondarily aimed to compare SLE diagnosis frequency by the SLICC versus the ACR criteria.
This was a single-center, retrospective chart review study of CLE patients seen in the outpatient dermatology clinics at the University of Texas Southwestern and Parkland Memorial Hospital between 2008 and 2020. Adult CLE patients with a minimum of 6 months follow-up were included, while patients with other autoimmune conditions or SLE diagnosis within 6 months of initial visit were excluded. We collected demographic and clinical information by chart review at baseline and follow-up visits. Baseline categorical variables were compared by Fisher’s exact tests between CLE only and CLE to SLE patients under the SLICC. Analysis was performed using SAS 9.4 (Cary, NC).
93 patients were included in our study, of which 10 progressed from CLE to SLE (10.8%) under the SLICC criteria at a median time of 7.8 years, while 83 remained CLE only (89.2%) (Table 1). Baseline risk factors included positive ANA (p=0.02), SLICC immunologic criteria (p=0.002), and SLICC total criteria (p=0.007). CLE to SLE patients frequently gained the following criteria: leukopenia, thrombocytopenia, chronic CLE, and ANA (Table 2). Fewer patients progressed from CLE to SLE under the SLICC (n=10, 10.8%) than the ACR (n=15, 16.1%). 7 of 15 patients met ACR SLE diagnosis but not SLICC, and 2 of 10 met SLICC SLE diagnosis but not ACR.
Table 1.
Demographic and clinical patient information at baseline comparing CLE-only to CLE to SLE using the SLICC
| All, (n=93) | CLE-only (n=83) | CLE to SLE (n=10) | p-valuea | |
|---|---|---|---|---|
| Sex, n (%) | ||||
| Male | 23 (24.7%) | 19 (22.9%) | 4 (40%) | 0.26 |
| Female | 70 (75.3%) | 64 (77.1%) | 6 (60%) | |
| Race/ Ethnicity, n (%) | ||||
| Caucasian | 33 (35.5%) | 28 (33.7%) | 5 (50%) | 0.69 |
| African American | 49 (52.7%) | 45 (54.2%) | 4 (40%) | |
| Hispanic | 9 (9.7%) | 8 (9.6%) | 1 (10%) | |
| Asian | 2 (2.2%) | 2 (2.4%) | 0 (0%) | |
| Age at presentation, y, median (IQR) | 48.1 (38.8-58) | 48.5 (39.8-57.6) | 46.5 (33.7-57.6) | 0.58 |
| Time from CLE onset to diagnosis, y, median (IQR) | 0.53 (0-2.1) | 0.56 (0-2.1) | 0.42 (0-1.24) | 0.78 |
| Smoking Statusb n (%) | ||||
| Ever Smoker | 44 (56.4%) | 40 (56.3%) | 4 (57.1%) | >0.99 |
| Never Smoker | 34 (43.6%) | 31 (43.7%) | 3 (42.9%) | |
| SLICC Criteria n (%) | ||||
| Acute cutaneous Lupusc | 15 (16.1%) | 12 (14.5%) | 3 (30%) | 0.20 |
| Chronic cutaneous Lupusd | 79 (85.0%) | 71 (85.5%) | 8 (80%) | 0.64 |
| Oral/Nasal Ulcers | 6 (6.5%) | 4 (4.8%) | 2 (20%) | 0.12 |
| Synovitis | 2 (2.2%) | 2 (2.4%) | 0 (0%) | >0.99 |
| Leukopenia | 11 (11.8%) | 10 (12.1%) | 1 (10%) | >0.99 |
| Lymphopenia | 4 (4.3%) | 3 (3.6%) | 1 (10%) | 0.37 |
| Thrombocytopenia | 7 (7.5%) | 6 (7.2%) | 1 (10%) | 0.56 |
| Anti-dsDNA | 2 (2.2%) | 1 (1.2%) | 1 (10%) | 0.20 |
| Anti-Sm | 2 (2.2%) | 1 (1.2%) | 1 (10%) | 0.20 |
| ANA | 41 (44.1%) | 33 (39.8%) | 8 (80%) | 0.02 |
| Low Complement | 7 (7.5%) | 5 (6.0%) | 2 (20%) | 0.16 |
| DLE Subtype, n (%) | ||||
| Localized DLE | 44 (67.7%) | 40 (67.8%) | 4 (66.7%) | >0.99 |
| Generalized DLE | 21 (32.3%) | 19 (32.2%) | 2 (33.3%) | |
| SLICC Immunologic Criteria, median (IQR) | 1 (1-2) | 0 (0-1) | 1 (1-2) | 0.002 |
| SLICC Clinical Criteria, median (IQR) | 0 (0-1) | 1 (1-2) | 1.5 (1-2) | 0.12 |
| SLICC Total Criteria, median (IQR) | 2 (1-3) | 2 (1-2) | 3 (3-3) | 0.007 |
| CLASI Activity Score, median (IQR)e | 4 (2-8.5) | 3 (2-8) | 6.5 (2-10) | 0.50 |
| CLASI Damage Score, median (IQR)e | 4 (0-10) | 4 (0-10) | 2.5 (0-8) | 0.61 |
| Physician Skin Score Overall, median (IQR)f | 8 (6.5-9) | 8 (7-9) | 7 (6-8) | 0.37 |
| Physician Activity Score, median (IQR)f | 8 (7-9) | 8 (7-9) | 7 (6-8) | 0.27 |
| Physician Damage Score, median (IQR)f | 9 (7-10) | 8.5 (7-10) | 9.5 (7-10) | 0.46 |
p-values for all categorical variables were obtained by Fisher’s exact tests. p-values for continuous variables were obtained by Wilcoxon Rank Sum tests.
Data was only available for 59 patients.
Acute cutaneous lupus consisted of 13 with SCLE, 3 malar rash, and 1 patient with both SCLE and malar rash
Chronic cutaneous lupus consisted of 2 lupus panniculitis, 13 tumid lupus, and 65 discoid lupus, and 1 patient with both discoid lupus and lupus panniculitis.
Data was only available for 78 patients.
Data was only available for 50 patients.
Abbreviations: ANA, anti-nuclear antibody, dsDNA, double-stranded DNA antibody, Anti-Sm, Anti-smith antibody SLICC, Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus
Table 2.
Frequency of and change in SLICC criteria in CLE to SLE patients at baseline visit and visit of SLE diagnosis
| SLICC Criteriaa | Initial Visit n, (%) | Visit of SLE diagnosis n, (%) | Increase between visits n, (%) |
|---|---|---|---|
| Leukopenia | 1 (10%) | 4 (40%) | 3 (30%) |
| Thrombocytopenia | 1 (10%) | 4 (40%) | 3 (30%) |
| Synovitis | 0 (0%) | 2 (20%) | 2 (20%) |
| Chronic cutaneous lupus | 8 (80%) | 10 (100%) | 2 (20%) |
| Oral/Nasal ulcers | 2 (20%) | 3 (30%) | 1 (10%) |
| Low Complement | 2 (20%) | 3 (30%) | 1 (10%) |
| Antiphospholipid | 0 (0%) | 1 (10%) | 1 (10%) |
| Lymphopenia | 1 (10%) | 2 (20%) | 1 (10%) |
| Anti-dsDNA | 1 (10%) | 2 (20%) | 1 (10%) |
| ANA | 8 (80%) | 9 (90%) | 1 (10%) |
| Acute cutaneous lupus | 3 (30%) | 3 (30%) | 0 (0%) |
| Anti-Sm | 1 (10%) | 1 (10%) | 0 (0%) |
SLICC criteria not listed were not present in patients who progressed from CLE to SLE.
Abbreviations: ANA, anti-nuclear antibody, anti-Sm, anti-Smith antibody, CLE, cutaneous lupus erythematosus, dsDNA, double-stranded DNA antibody, SLE, systemic lupus erythematosus, SLICC, Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus,
In our cohort, the 10.8% SLE diagnosis rate under the SLICC was lower than the 16.1% using the ACR, similar to prior studies.4,5 This discrepancy was attributable to absence of the vague photosensitivity criterion from the SLICC. Also, the two patients diagnosed with SLE under SLICC but not ACR criteria acquired hematologic abnormalities defined by SLICC but not ACR. All patients who progressed from CLE to SLE under the SLICC lacked serious end-organ damage, confirming prior reports of CLE patients developing mild SLE phenotype under the ACR criteria.4 Our study was limited by retrospective nature, small sample size, short follow-up time, and lack of CLE patients developing moderate to severe SLE. As more providers are using the SLICC for SLE diagnosis, it is important to recognize these criteria differences. Patients should receive close monitoring for development of autoantibodies and hematologic disorders as SLE manifestations under the SLICC. We encourage larger, multi-center studies to confirm our findings.
Acknowledgements:
The authors would like to thank participants of the UTSW Cutaneous Lupus Erythematosus Registry for their contributions to lupus research.
Funding Sources: This study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number K23AR061441. The content is solely the responsibility of the authors and does not necessarily represent the official views of the University of Texas Southwestern Medical Center at Dallas and its affiliated academic and health care centers, the National Center for Research Resources, and the National Institutes of Health.
Footnotes
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Conflict of Interest Disclosure: Dr. Chong is an investigator for Daavlin Corporation and Biogen Incorporated and Pfizer Incorporated. He is a consultant for Viela Bio, Beacon Bioscience, Bristol Meyers Squibb, and Principia Biopharma. The other authors have no conflicts of interest.
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