The present study aimed to determine the frequency and identify factors associated with systemic lupus flares in patients with lupus nephritis in a Guyanese cohort, including 62 patients, of whom 72.58% had lupus nephritis and 27.42% did not (Fig. 1). The two groups were comparable in terms of their clinical, biological, and therapeutic characteristics (Tables 1 and 2). Fifty-three percent of the population experienced at least one lupus relapse. Lupus relapse was observed in 62.22% of patients in the lupus nephritis subgroup versus 29.41% in the subgroup without lupus nephritis. The following clinical and laboratory parameters were significantly higher in patients with lupus nephritis: anti-native Dna and antinuclear factor antibody positivity, low haptoglobin levels, polyarthralgia, discoid rash, verspetillo, and oral ulceration. High levels of anti-Dna and anti-Smith antibodies, fever, pleurisy, discoid rash, verspetillo, oral ulceration, and a high Sledai score were found more frequently and significantly in patients with relapse. According to the multivariate logistic regression analysis adjusted for anti-DNase and anti-Smith antibody levels, lupus nephritis and anti-DNase antibody levels were significantly associated with systemic flares. In terms of evolution, there was a significantly higher frequency of infection and progression to chronic kidney disease.
The frequency of lupus nephropathy in our study was 72.58%, which was higher than that reported in the literature. Indeed, in an international cohort study published in February 2016 that included 1827 patients, the frequency was 38.3%, among whom 80.9% had a diagnosis at inclusion, with an average follow-up time of six months before inclusion [7]. This difference can be explained by the size of our sample, the monocentric and historical nature of the cohort, and the difficult access to care in French Guiana, which often leads patients to consult late. However, a more recent study published in 2020 in the U.S. suggested a slightly greater and more heterogeneous incidence depending on the population, compared to the international cohort [8]. These underscore the geographical disparities in the incidence and complications of lupus.
Of the total population, 53% had at least one history of lupus relapse (Fig. 2). The development of lupus was punctuated by episodes of remission and relapse (Table 3). According to an Indian study published in 2015, 71.69% of patients experienced at least one relapse over a 6-month period [11]. Despite current therapeutic advances, relapse remains inherent to the natural history of lupus and can be of variable severity [10, 13, 14, 15,16]. Compared to those in our two groups, lupus flares were more frequent (62.22%) in patients with renal involvement (Fig. 3). These results corroborate other findings reported in the literature, notably in the 20-year Spanish cohort, in which the incidence of flares was 38%, 58.6% of which were present in patients with lupus nephritis at the time of diagnosis [9]. Another study also revealed that 30–40% of relapses involve at least two organs, with the kidney being the most frequent [10].
The clinical and laboratory parameters that were significantly more frequent in the lupus nephritis group were native anti-DNase and antinuclear factor antibody positivity, low haptoglobin levels, polyarthralgia, discoid rash, verspetillo, and oral ulceration (Table 4). These findings are consistent with other observations described in the literature, in which anti-dna antibody positivity was associated with renal involvement and overall disease activity. [14, 17,18]
The factors with significantly higher frequencies in patients with lupus flares in the present study were high levels of anti-Dna and anti-Smith antibodies, fever, pleurisy, discoid rash, verspetillo, oral ulceration, and high Sledai score. These factors have also been found to vary in other studies worldwide [12]. A South Korean study published in 2023, which assessed the risk of relapse in relation to antibody positivity, revealed that double positivity for anti-DNase and anti-Smith antibodies at diagnosis was associated with an increased risk of relapse [14].
Our logistic regression model investigating the association between lupus nephritis and lupus flares by adjusting for anti-DNase and anti-Smith antibody levels revealed a significant correlation between lupus nephritis and lupus flares, as well as between flares and anti-DNase antibody levels (Table 5). Indeed, as discussed above, the frequency of flare-up is greater in patients with lupus nephritis, depending on the initial degree of organ damage [10,8]. This finding is in line with numerous studies on the role of the kidney in the biological and clinical treatment of this disease. Although several studies have demonstrated that disease activity and relapse episodes persist in patients with end-stage chronic renal failure undergoing dialysis according to certain risk factors [20], several other studies have reported clinical and hematological remission of lupus, or at least a significant reduction in disease activity and relapse in patients with chronic kidney disease on dialysis, even after therapeutic minimization [19, 20].
Finally, from an evolutionary point of view, the study noted a significantly greater frequency of infection and progression to chronic kidney disease in patients who had experienced relapses. Indeed, it has been widely demonstrated that a high frequency of relapse is associated with organ damage and progression to end-stage renal disease in patients with lupus nephritis [21]. Moreover, the high frequency of infection is explained by immunosuppression induced by the intensification of immunosuppressive therapy instituted at each relapse episode [22].
Study strengths and weaknesses:
Similar to all retrospective studies, our study suffered from missing data, which, combined with the monocentric nature of our study, led to a reduction in sample size. Given that the diagnosis of lupus relapse has been documented, it was not possible to compare our findings with the current criteria for defining lupus relapse. Despite these limitations, our study is the first to assess the impact of initial renal involvement on systemic lupus relapse in French Guiana, a territory with a high prevalence of lupus.