Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

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Abstract

Objectives

To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality.

Methods

This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared.

Results

Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons).

Conclusions

In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

Introduction

Systemic lupus erythematosus (SLE) is a complex systemic rheumatic disease in which several domains should be assessed: disease activity, organ damage and health-related quality of life [1]. As survival in SLE patients has improved over the past decades 2, 3, evaluation of organ damage has become more relevant.

Damage in SLE is defined as an irreversible change, unrelated to active inflammation, that occurs after diagnosis of the disease, and which is present for at least 6 months [4]. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) has been shown to be a valid and reliable measure for damage in SLE [4, 5, 6–].

Several studies have shown that organ damage predicts future mortality in SLE patients, usually by using the global SDI score to analyze the association between damage and mortality [7, 8, 9, 10, 11, 12, 13, 14, 15–]. Very few studies have assessed damage clustering and the impact of the different SDI domains on survival [16–18]. Recently, our RELESSER Study Group has detected three clusters associated with different mortality rates in our entire SLE cohort, mainly based on the proportion of patients with musculoskeletal and cardiovascular damage [18]. Our group also compared juvenile-onset SLE (jSLE) and adult-onset SLE (aSLE) patients within RELESSER without finding significant differences in the mortality rate between the two subgroups [19]. However, cluster analysis of damage manifestations and their potential association with mortality in jSLE patients has not been carried out.

Therefore, the primary objective of our study was to identify patterns (clusters) of damage manifestation within a large cohort of jSLE patients. In addition, we sought to evaluate the potential association of these clusters with the risk of mortality in jSLE.

Section snippets

Research study network

The Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology (RELESSER) is a hospital-based registry that consists of two stages. The first one is a cross-sectional stage whose main objective is to describe the characteristics and comorbidities of the patients diagnosed with SLE in Spain. This is followed by a longitudinal follow-up stage over time with repeated yearly visits. The RELESSER Registry was conducted by the Systemic Autoimmune Diseases Study Group of

Results

We collected data from 345 jSLE patients who fulfilled the inclusion criteria. Baseline demographics, mortality data and specific damage domain involvement from these jSLE patients are summarized in Table 1a.

Discussion

In a large national jSLE cohort we observed several clinical patterns of damage manifestation and their association with different risks of mortality. To the best of our knowledge, this is the first study to perform such an analysis in jSLE. We found significant differences among clusters not only in the proportion of patients with some kind of damage, but also in the level of damage, both in terms of the number of SDI domains affected and in the mean SDI score.

Similarly, as we previously

Conclusions

In conclusion, this is the first study to analyze and identify different patterns (clusters) of damage manifestations within a large cohort of jSLE patients. Renal and musculoskeletal damage were the two dominant forms of damage used to sort these patients into clinically meaningful clusters. Our study suggests that musculoskeletal, and particularly renal damage, manifestations are significantly associated with an increased risk of mortality. Therefore, physicians should pay special attention

Disclosure statement

Dr. Pego-Reigosa is supported by grant 316265 (BIOCAPS) from the European Union 7th Framework Program (FP7/REGPOT-2012-2013.1). The FIS Grant PI11/02857 (Instituto Carlos III, Fondos FEDER) has supported this work.

Francisco Javier López-Longo has received speaker fees from Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, MSD, Actelion. Francisco Javier López Longo has received research funding from Abbvie and GSK.

The RELESSER Registry was funded by grants from GSK, Roche, UCB and

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