BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

Early discoid lupus onset protective against nephritis