Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort

Abstract

Objectives

The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE).

Methods

We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis.

Results

Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20–0.71).

Conclusions

Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.

Keywords

Systemic lupus erythematosus lupus nephritis discoid lupus erythematosus survival analysis GLADEL cohort

Get full access to this article

View all access options for this article.

References

Chong

Werth

Dubois’ Lupus Erythematosus and Related Syndromes. In: Wallace

Hahn

(eds). Skin Disease in Cutaneous Lupus Erythematosus, Philadelphia: Elsevier Saunders, 2013, pp. 319–332.

Obermoser

Sontheimer

Zelger

. Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates. Lupus 2010; 19: 1050–1070.

Tebbe

. Clinical course and prognosis of cutaneous lupus erythematosus. Clin Dermatol 2004; 22: 121–124.

Werth

. Clinical manifestations of cutaneous lupus erythematosus. Autoimmun Rev 2005; 4: 296–302.

Gilliam

Sontheimer

. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981; 4: 471–475.

Hinojosa-Azaloa

Sanchez-Guerrero

Dubois’ Lupus Erythematosus and Related Syndromes. In: Wallace

Hahn

(eds). Overview and Clinical Presentation, Philadelphia: Elsevier Saunders, 2013, pp. 304–309.

Prystowsky

Herndon

Jr Gilliam

. Chronic cutaneous lupus erythematosus (DLE)—a clinical and laboratory investigation of 80 patients. Medicine (Baltimore) 1976; 55: 183–191.

Gronhagen

Gunnarsson

Svenungsson

Nyberg

. Cutaneous manifestations and serological findings in 260 patients with systemic lupus erythematosus. Lupus 2010; 19: 1187–1194.

Watanabe

Tsuchida

. Classification of lupus erythematosus based upon cutaneous manifestations. Dermatological, systemic and laboratory findings in 191 patients. Dermatology 1995; 190: 277–283.

10.

Werth

. Current treatment of cutaneous lupus erythematosus. Dermatol Online J 2001; 7: 2–2.

11.

Vera-Recabarren

Garcia-Carrasco

Ramos-Casals

Herrero

. Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients. Br J Dermatol 2010; 162: 91–101.

12.

Santiago-Casas

Vila

McGwin

Jr . Association of discoid lupus erythematosus with clinical manifestations and damage accrual in a multiethnic lupus cohort. Arthritis Care Res (Hoboken) 2012; 64: 704–712.

13.

Merola

Prystowsky

Iversen

. Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus. J Am Acad Dermatol 2013; 69: 19–24.

14.

Drucker

Mussani

Siddha

Gladman

Urowitz

. Prognostic implications of active discoid lupus erythematosus and malar rash at the time of diagnosis of systemic lupus erythematosus: results from a prospective cohort study. Lupus 2016; 25: 376–381.

15.

Pons-Estel

Catoggio

Cardiel

. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine (Baltimore) 2004; 83: 1–17.

16.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

17.

Tan

Cohen

Fries

. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

18.

Pons-Estel

Alarcon

Burgos

. Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: data from a Latin American cohort. Lupus 2013; 22: 899–907.

19.

Contreras

Pardo

Cely

. Factors associated with poor outcomes in patients with lupus nephritis. Lupus 2005; 14: 890–895.

20.

Mok

. Prognostic factors in lupus nephritis. Lupus 2005; 14: 39–44.

21.

Gladman

Goldsmith

Urowitz

. Crosscultural validation and reliability of 3 disease activity indices in systemic lupus erythematosus. J Rheumatol 1992; 19: 608–611.

22.

Gladman

Ginzler

Goldsmith

. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39: 363–369.

23.

Efron

. Bootstrap methods: another look at the jackknife. Ann Statist 1979; 7: 1–26.

24.

Hosmer

Lemeshow

May

. A Wiley-Interscience Publication. Applied Survival Analysis: Regression Modeling of Time-to-event Data, 2nd edn. New York: John Wiley, 2008, pp. 191–195.

25.

George

Seals

Aban

. Survival analysis and regression models. J Nucl Cardiol 2014; 21: 686–694.

26.

Enders

. Applied Missing Data Analysis, New York, NY: Guilford, 2010.

27.

Bastian

Roseman

McGwin

Jr . Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus 2002; 11: 152–160.

28.

Wallace

Podell

Weiner

. Lupus nephritis. Experience with 230 patients in a private practice from 1950 to 1980. Am J Med 1982; 72: 209–220.

29.

Font

Cervera

Espinosa

. Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis 1998; 57: 456–459.

30.

Alarcon

McGwin

Jr Petri

. Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort. PLoS Med 2006; 3: e396–e396.

31.

Danila

Pons-Estel

Zhang

Vila

Reveille

Alarcon

. Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford) 2009; 48: 542–545.

32.

Bernatsky

Boivin

Joseph

. Mortality in systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2550–2557.

33.

Doria

Amoura

Cervera

. Annual direct medical cost of active systemic lupus erythematosus in five European countries. Ann Rheum Dis 2014; 73: 154–160.

34.

Zhu

Tam

. Cost-of-illness studies in systemic lupus erythematosus: a systematic review. Arthritis Care Res (Hoboken) 2011; 63: 751–760.

35.

Zhu

Tam

Lee

. The impact of flare on disease costs of patients with systemic lupus erythematosus. Arthritis Rheum 2009; 61: 1159–1167.

36.

Merola

Chang

Sanchez

Prystowsky

. Is chronic cutaneous discoid lupus protective against severe renal disease in patients with systemic lupus erythematosus? J Drugs Dermatol 2011; 10: 1413–1420.

37.

Heinlen

McClain

Merrill

. Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms. Arthritis Rheum 2007; 56: 2344–2351.

38.

Wieczorek

Propert

Okawa

Werth

. Systemic symptoms in the progression of cutaneous to systemic lupus erythematosus. JAMA Dermatol 2014; 150: 291–296.

39.

Insawang

Kulthanan

Chularojanamontri

Tuchinda

Pinkaew

. Discoid lupus erythematosus: description of 130 cases and review of their natural history and clinical course. J Clin Immunol Immunopathol Res 2010; 2: 1–8.

40.

Chong

Tseng

Kim

Miller

Yancey

Hosler

. Differential expression of BAFF and its receptors in discoid lupus erythematosus patients. J Dermatol Sci 2014; 73: 216–224.

41.

Kunz

Konig

Schillert

. Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus. Exp Dermatol 2015; 24: 510–515.

42.

Dey-Rao

Smith

Chow

Sinha

. Differential gene expression analysis in CCLE lesions provides new insights regarding the genetics basis of skin vs. systemic disease. Genomics 2014; 104: 144–155.

43.

Millington

. Epigenetics and dermatological disease. Pharmacogenomics 2008; 9: 1835–1850.

44.

Wong

Lee

. Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese. Rheumatology (Oxford) 2013; 52: 337–345.

45.

Callen

. Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus. Clinical and laboratory findings in seventeen patients. J Am Acad Dermatol 1985; 12: 278–288.

46.

Pons-Estel

Alarcon

Hachuel

. Anti-malarials exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a Latin-American cohort. Rheumatology (Oxford) 2012; 51: 1293–1298.

47.

Appel

Cohen

Pirani

Meltzer

Estes

. Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization. Am J Med 1987; 83: 877–885.

48.

Pons-Estel

Alarcon

McGwin

Jr . Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 2009; 61: 830–839.