Cutaneous lupus erythematosus (CLE) patients are at risk of developing systemic lupus erythematosus (SLE). Most studies have used the 1982 American College of Rheumatology (ACR) criteria to identify CLE patients who progress to SLE, reporting progression rates of 12–17%.1,2 We found a lower progression rate with the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria versus ACR criteria in our patient cohort.2 Since the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria has yet to be utilized in studying CLE to SLE progression, we sought to compare progression rates, baseline risk factors and criteria gained amongst all three criteria.
This was a retrospective, single-center study of CLE patients treated in the outpatient dermatology clinics at University of Texas Southwestern Medical Center and Parkland Health between November 2008 and July 2021. Patients had a minimum of 3 months follow-up and be at least 18 years of age. Exclusion criteria included drug-induced CLE or diagnosis with SLE within 3 months of their first visit. Baseline categorical variables were compared by Fisher’s exact tests and continuous variables by Mann-Whitney rank sum tests between patients with CLE and CLE developing to SLE. Rates of progression were compared using McNemar’s Test. A two-sided p-value ≤0.05 was considered statistically significant. SAS v. 9.4 and GraphPad Prism v. 9.3 were used for statistical analyses.
Of the 107 CLE patients, three (2.8%) patients progressed to SLE by the EULAR/ACR criteria over a median time of 3.5 years (Table 1). The progression rate under the EULAR/ACR criteria was significantly less than that of the SLICC (n=9, 8.4%, p=0.034) and ACR (n=14, 13.1%, p=0.0016) criteria. All three patients developing SLE under EULAR/ACR criteria reached SLE diagnosis under SLICC and/or ACR criteria (Figure 1). Baseline risk factors for disease progression under EULAR/ACR criteria included positive anti-nuclear antibody (ANA) (100% vs. 35.2%, p=0.049) and low C3 levels (33.3% vs. 0%, p=0.03). All three patients who progressed under EULAR/ACR criteria developed joint involvement after initial visit.
Table 1.
Baseline demographic and clinical information in CLE patients who did or did not progress to SLE using ACR, SLICC, and EULAR/ACR criteria.
| Demographic/clinical variable | All (n=107) | CLE only (n=91) | CLE to SLE, EULAR/ACR (n=3) | p-valuea | CLE to SLE, ACR (n=14) | p-valuea | CLE to SLE, SLICC (n=9) | p-valuea |
|---|---|---|---|---|---|---|---|---|
| Sex, no. (%) | ||||||||
| Men | 26 (24.3) | 21 (23.1) | 0 (0) | >0.99 | 4 (28.6) | 0.74 | 4 (44.4) | 0.22 |
| Women | 81 (75.7) | 70 (76.9) | 3 (100) | 10 (71.4) | 5 (55.6) | |||
| Race/ethnicity, no (%) | ||||||||
| Black | 54 (50.5) | 45 (49.5) | 2 (66.7) | 0.26 | 9 (64.3) | 0.25 | 4 (44.4) | 0.85 |
| White, non-Hispanic | 38 (35.5) | 34 (37.4) | 0 (0) | 2 (14.3) | 4 (44.4) | |||
| White, Hispanic | 10 (9.3) | 8 (8.8) | 1 (33.3) | 2 (14.3) | 1 (11.1) | |||
| Asian | 5 (4.7) | 4 (4.4) | 0 (0) | 1 (7.1) | 0 (0) | |||
| Smoking Status, no. (%) | ||||||||
| Ever | 57 (53.3) | 49 (53.8) | 1 (33.3) | 0.60 | 8 (57.1) | 0.82 | 3 (33.3) | 0.31 |
| Never | 50 (46.7) | 42 (46.2) | 2 (66.7) | 6 (42.9) | 6 (66.7) | |||
| Age at presentation, median (IQR), y | 47.5 (38.6–57) | 47.1 (38.6–56.3) | 46 (37.1–51.6) | 0.70 | 54.2 (45.9–57.7) | 0.29 | 58.2 (46–59.8) | 0.33 |
| CLE onset to diagnosis (IQR), y | 1 (0.1–3.2) | 1 (0–3) | 0.3 (0.1–1.8) | 0.66 | 2 (0.6–4) | 0.23 | 0.6 (0.6–1.5) | 0.63 |
| CLE Subtype, no (%) | ||||||||
| DLE | 75 (70.1) | 62 (68.1) | 3 (100) | 0.84 | 12 (85.7) | 0.84 | 6 (66.7) | 0.87 |
| SCLE | 12 (11.2) | 11 (12.1) | 0 (0) | 1 (7.1) | 1 (11.1) | |||
| LE tumidus | 15 (14) | 13 (14.3) | 0 (0) | 1 (7.1) | 2 (22.2) | |||
| LE panniculitis | 4 (3.7) | 4 (4.4) | 0 (0) | 0 (0) | 0 (0) | |||
| Chilblains LE | 1 (0.9) | 1 (1.1) | 0 (0) | 0 (0) | 0 (0) | |||
| CLASI Activity score, median (IQR)b | 4 (2–7) | 4 (2–7) | 9 (5.5–12.5) | 0.68 | 5 (4–7) | 0.21 | 5.5 (4–10.8) | 0.14 |
| CLASI Damage score, median (IQR)b | 4 (1–12) | 3 (0.3–10.8) | 7.5 (4.8–10.3) | 0.63 | 6.5 (4.5–12.8) | 0.11 | 6.5 (4.5–10.8) | 0.52 |
Abbreviations: ACR, American College of Rheumatology; ANA, Antinuclear antibody; Anti-Sm, anti-Smith antibody; CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; CLE, cutaneous lupus erythematosus; DLE, discoid lupus erythematosus; EULAR/ACR, European League Against Rheumatism/America College of Rheumatology; IQR, interquartile range; LE, lupus erythematosus; SCLE, subacute cutaneous lupus erythematosus; SLE, systemic lupus erythematosus; SLICC, Systemic Lupus International Collaborating Clinics.
P-values listed for baseline variables represent a comparison between CLE only patients and those that progress from CLE to SLE under each classification criteria set, respectively.
Data only available for 64 patients
Figure 1. CLE patients progressing to SLE under ACR, SLICC, and EULAR/ACR criteria.
The Venn diagram showed CLE patients who progressed to SLE using one or more SLE classification criteria. Six patients met ACR criteria alone. Two patients met SLICC criteria alone. No patients met EULAR/ACR criteria alone. Two patients met all three criteria. One patient met ACR and EULAR/ACR criteria. Five patients met ACR and SLICC criteria together.
Abbreviations: ACR, American College of Rheumatology; European League Against Rheumatism/America College of Rheumatology; SLICC, Systemic Lupus International Collaborating Clinics;
We found that fewer patients progressed from CLE to SLE under EULAR/ACR criteria versus ACR and SLICC criteria. The EULAR/ACR criteria has a hierarchical design, which counts the most heavily weighted criterion, instead of all criteria, within each domain, and positive ANA does not count toward total point accumulation.4 Most patients developed SLE under ACR and SLICC criteria by having positive ANA, lymphopenia, and photosensitivity, none of which count toward SLE progression under EULAR/ACR criteria. None of the patients who progressed to SLE under any three criteria had severe end-organ damage, supporting previous findings that CLE to SLE patients have mild disease severity.5 Limitations include small sample size and retrospective study design. Larger prospective studies are needed to confirm our findings. We suggest that providers using EULAR/ACR criteria monitor for the development of new joint aches. Our study highlights important differences between criteria sets that may potentially influence prognosis for CLE patients developing SLE.
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.
Abbreviations:
- ACR
American College of Rheumatology
- ANA
anti-nuclear antibody
- CLE
cutaneous lupus erythematosus
- EULAR/ACR
European League Against Rheumatism/America College of Rheumatology
- SLE
systemic lupus erythematosus
- SLICC
Systemic Lupus International Collaborating Clinics
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 Bristol Meyers Squibb, EMD Serono, Biogen Incorporated, and Horizon Therapeutics. The other authors have no conflicts of interest.
This manuscript is not simultaneously being submitted elsewhere, and no portion of the data has or will be published in proceedings or transactions of meetings or symposium volumes.
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