This is a multicentre clinical study of cSLE-associated pancreatitis in China. Given the disease’s low incidence in children [5] and previous domestic reports of it were all on isolated cases, this study represents the largest number of cases included in the case group of its kind in China. First, the study results reveal that the SLEDAI-2K score at the onset of disease in the case group was 18, higher than that of the control group (P < 0.05), indicating that cSLE-associated pancreatitis is a critical complication of cSLE. The fatality rate in the case group was as high as 33.3%, similar to the reported rate of 37.04% in the literature [6]. Secondly, this study found that cSLE-associated pancreatitis is more likely to present with Raynaud's phenomenon (RP), splenic infarction, pleural effusion, and concurrent MAS (P < 0.05). Thirdly, abdominal pain of varying levels was observed in all cases of the case group (100%), significantly more than in the control group (P < 0.05), indicating that the occurrence of pancreatitis should be considered in cSLE patients presenting with acute abdominal pain. Fourthly, this study also found higher levels of 24-hour urine protein, SF, ALT, AST, LDH, and amylase in the case group. Therefore, clinicians should closely monitor abdominal symptoms in cSLE cases. When lupus pancreatitis is suspected, renal function, SF, liver enzymes, and amylase should be assessed more attentively to monitor the disease progression. Lastly, during induction, the case group received methylprednisolone pulse therapy, cyclophosphamide pulse therapy, and therapeutic plasma exchange more frequently than the control group (P < 0.05). This suggests that for early detection of pancreatitis, high-intensity treatment regimen should be chosen as mentioned above. In the presence of surgical indications, active surgical intervention should be administered to gain more time for remission of the primary disease of SLE.
The pathogenesis of SLE-associated pancreatitis remains unclear, but vascular trauma is one of the main causes [7–13]. Vascular trauma includes necrotising vasculitis, arterial thromboembolism caused by severe hypertension and antiphospholipid syndrome, vascular endothelial injury, immune complex deposition, and complement activation in pancreatic arterial walls, among others. The mechanism by which RP occurs with SLE is not entirely clear, but endothelial dysfunction might underlie its pathophysiology. It is currently believed to be caused by increased endothelin, decreased calcitonin gene-related peptide, the presence of anti-fibrin-binding tissue-type plasminogen activator (t-PA) in circulating blood, decreased fibrinolytic activity in the organism, and coagulation in small blood vessels. In addition, increased protein tyrosine kinase (PTK) activity in vascular endothelial cells might be associated with RP development [14], suggesting that vascular endothelial injury could be a mechanism leading to RP in SLE-associated pancreatitis. Literature reports suggest that splenic infarction in SLE is associated with the deposition of circulating immune complexes on vascular walls and the activation of the complement pathway by the circulating immune complexes; both the deposition and the activation stimulate vascular endothelial injury [15–16], potentially explaining the higher proportion of splenic infarction cases in the study's case group compared to the control group. Lupus anticoagulant and antiphospholipid antibodies are risk factors for arteriovenous thrombosis or embolism in SLE, and these mechanisms are also considered to be the pathogenesis of SLE-associated pancreatitis [17].
Risk factors for cSLE-associated pancreatitis remain unclear. In this study, one child in the case group exhibited fever, neurological damage, intravascular haemolytic anaemia, thrombocytopenia, and renal failure, combined with pancreatitis and heart failure. The patient tested positive for ADAMTS-13 antibodies and was diagnosed with thrombotic thrombocytopenic purpura (TTP). Thus, TTP may be a high-risk factor for cSLE-associated pancreatitis. Among the four deceased cases in the case group, three (25%) had MAS, a severe, acute and lethal syndrome. In 2009, Parod et al. proposed preliminary diagnostic guidelines for childhood SLE-MAS through statistical analysis of laboratory indicators of SLE-MAS [18]. In this study, the proportion of MAS cases in the case group was higher than in the control group (P < 0.05). Therefore, in cSLE cases presenting clinical features that are difficult to be explained by the primary disease activity, such as fever, bleeding, hepatosplenomegaly, lymphadenectasis, neurological dysfunction, heart and renal failure, the diagnosis of SLE-associated MAS is considered, particularly when SF, AST, LDH are consistently elevated, and dynamic erythrocyte sedimentation rate decreases. Further attention should be given to the occurrence of pancreatitis.
Literature search did not reveal any correlation between pleural effusion and the occurrence of pancreatitis in SLE patients. In this study, 24-hour urine protein levels were significantly higher in the case group than in the control group. Thus, whether the occurrence of pleural effusion is caused by renal protein loss requires further research. Currently, there is limited research on cSLE-associated pancreatitis at home and abroad, and there is a lack of large-sample data. Although this study is the multicentre study with the biggest number of cases in China at present, limitations still exist due to the small sample size.