In the present study, we examined the clinical characteristics of patients with primary ITP who later developed SLE and identified the factors at the time of ITP diagnosis that were associated with the risk of SLE development. The incidence rate of SLE development in patients with primary ITP was 7.7%, and the development of SLE was significantly associated with young age (< 40 years), organ bleeding, and ANA positivity (≥ 1:160).
Thrombocytopenia of less than 100 × 109/L platelets is one of the hematological criteria for the classification of SLE and is a common clinical manifestation with a prevalence of 7 to 30% in patients with SLE [3,4,5]. It has been reported that thrombocytopenia is associated with poor prognosis including higher mortality in SLE [4, 17]. Although the exact mechanism of immune-mediated thrombocytopenia in SLE is unknown, recent studies have shown that ITP and SLE share commonalities in terms of genes, pathways, and molecular signatures [6,7,8,9]. In a recent study based on the National Database in Taiwan, SLE occurred in 4.7% of patients with idiopathic ITP, and the risk of developing SLE was 26 times higher than that in non-ITP patients . Interestingly, the observed crude rate of SLE development in our study (10/130, 7.7%) is similar to that reported in the previous population-based study on patients with ITP. In addition, our present study provides information on the prognostic factors for the development of SLE in patients with primary ITP.
The incidence of ITP showed a bimodal pattern according to age, with peaks among ages under 5 and over 60 years . ITP has a male predominance in pediatric patients and older patients and a female predominance in reproductive age (18–49 years) populations . Previous studies have shown that younger ITP patients below 40 years of age had different clinical features, including a better response to rituximab treatment than those over 40 years [19,20,21]. On the other hand, SLE is a typical disease that affects women of childbearing age . Interestingly, in our present study, young age (< 40 years) was significantly associated with the development of SLE in ITP patients.
While ANA testing is not essential for the diagnosis of ITP, it can be helpful for differentiating autoimmune diseases such as SLE. In a previous study, the rate of ANA positivity was higher in ITP patients with SLE than in those with primary ITP only . In our present study, the proportion of ANA positivity was also higher in patients who developed SLE than those who did not, and ANA positivity (≥ 1:160) at the time of ITP diagnosis was a significant risk factor for the development of SLE. Notably, most patients who developed SLE showed increases in their ANA titer compared to when it was measured at ITP diagnosis, and half of these patients showed a high ANA titer of 1:1280. Thus, these findings suggested that the test for ANA may be a useful tool in the diagnosis of ITP in particular differentiating SLE; repeated measurement may be required in some instances. The results of our study were different from that of a previous study, in which ANA testing was suggested to be unnecessary for SLE screening in patients with ITP . Although the exact reason for this difference is unclear, differences in the number of study patients and the duration of follow-up may be responsible.
Internal organ bleeding is one of the most serious clinical manifestations in ITP because it may potentially lead to functional impairment in major organs or a life-threatening condition . In our present study, the prevalence of severe thrombocytopenia (< 20 × 109/L) was significantly higher in patients who later developed SLE than those who did not, and organ bleeding was an independent risk factor for the development of SLE. However, platelet count itself was not significantly associated with the occurrence of SLE (Table 4). The bleeding tendency in SLE may be related to various factors including renal function impairment, lupus anticoagulant, and the presence of autoantibodies against coagulation factors other than thrombocytopenia [25,26,27]. Thus, further studies on the mechanisms and risk factors on the bleeding diathesis in SLE will be helpful for providing proper management of bleeding manifestations in SLE.
The present study had some limitations. First, this study may have been affected by a selection bias inherent to its retrospective and single-center design. Specifically, our study included patients who underwent bone marrow examination and ANA test; however, in general, bone marrow examination is not necessary for diagnosing ITP, and the ANA test is not routinely performed for all patients with ITP. Thus, selected patients may have been included in our study. Moreover, very few (n = 9) patients underwent the tests for additional autoantibodies (e.g., antibodies against extractable nuclear antigens) other than ANA at baseline. Second, in order to exclude patients who had SLE at the time of ITP diagnosis, only those who were diagnosed with SLE after the establishment of ITP diagnosis were included. However, it is difficult to completely rule out whether ITP was an initial clinical symptom as one of the systemic manifestations of SLE. Despite these limitations, this is a real-world study investigating the prognostic factors associated with the development of SLE after the diagnosis of ITP.