Recent advances in pathogenesis, diagnosis, and therapeutic approaches for digestive system involvement in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of large amounts of autoantibodies and immune complex formation. Because of their atypical clinical symptoms, SLE patients with digestive system involvement may not be recognized or treated precisely and extensively. Clinicians should pay close attention to SLE with digestive system involvement, as these conditions can easily worsen the condition and possibly endanger the patient’s life. In this review we summarized the pathogenesis, pathological characteristics, clinical manifestations, diagnosis, and therapies for digestive system involvement in SLE.

Keywords

diagnosis / digestive system involvement / etiology / systemic lupus erythematosus / therapy

References

[1] AndersHJ,SaxenaR, ZhaoMH,Parodis I,SalmonJE,MohanC. Lupus nephritis. Nat Rev Dis Primers. 2020; 6(1): 7.

[2] TsokosGC. Systemic lupus erythematosus. N Engl J Med. 2011; 365(22): 2110-2121.

[3] XuD,YangH, LaiCC, et al. Clinical analysis of systemic lupus erythematosus with gastrointestinal manifestations. Lupus. 2010; 19(7): 866-869.

[4] AringerM,Costenbader K,DaikhD, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019; 78(9): 1151-1159.

[5] HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997; 40(9): 1725.

[6] PetriM,OrbaiAM, AlarcónGS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012; 64(8): 2677-2686.

[7] TianXP,ZhangX. Gastrointestinal involvement in systemic lupus erythematosus: insight into pathogenesis, diagnosis and treatment. World J Gastroenterol. 2010; 16(24): 2971-2977.

[8] CrokerJA,Kimberly RP. SLE: challenges and candidates in human disease. Trends Immunol. 2005; 26(11): 580-586.

[9] CarusoR,LoBC, NúñezG. Host–microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020; 20(7): 411-426.

[10] MannER,LamYK, UhligHH. Short-chain fatty acids: linking diet, the microbiome and immunity. Nat Rev Immunol. 2024; 24(8): 577-595.

[11] JohanssonMEV,Phillipson M,PeterssonJ,VelcichA,HolmL, HanssonGC. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008; 105(39): 15064-15069.

[12] OdendahlM,JacobiA, HansenA, et al. Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol. 2000; 165(10): 5970-5979.

[13] NickersonKM,SmitaS, HoehnKB, et al. Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice. J Exp Med. 2023; 220(5): e20221346.

[14] ChanOT,HannumLG, HabermanAM,Madaio MP,ShlomchikMJ. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J Exp Med. 1999; 189(10): 1639-1648.

[15] KamalA,Khamashta M. The efficacy of novel B cell biologics as the future of SLE treatment: a review. Autoimmun Rev. 2014; 13(11): 1094-1101.

[16] WenzelJ. Cutaneous lupus erythematosus: new insights into pathogenesis and therapeutic strategies. Nat Rev Rheumatol. 2019; 15(9): 519-532.

[17] Flores-BorjaF,Kabouridis PS,JuryEC,IsenbergDA,MageedRA. Altered lipid raft-associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus. Arthritis Rheum. 2007; 56(1): 291-302.

[18] Pugh-BernardAE,CambierJC. B cell receptor signaling in human systemic lupus erythematosus. Curr Opin Rheumatol. 2006; 18(5): 451-455.

[19] TsokosGC,WongHK, EnyedyEJ,Nambiar MP. Immune cell signaling in lupus. Curr Opin Rheumatol. 2000; 12(5): 355-363.

[20] KyttarisVC,Krishnan S,TsokosGC. Systems biology in systemic lupus erythematosus: integrating genes, biology and immune function. Autoimmunity. 2006; 39(8): 705-709.

[21] MiharaM,OhsugiY, SaitoK, et al. Immunologic abnormality in NZB/NZW F1 mice. Thymus-independent occurrence of B cell abnormality and requirement for T cells in the development of autoimmune disease, as evidenced by an analysis of the athymic nude individuals. J Immunol. 1988; 141(1): 85-90.

[22] WofsyD. Administration of monoclonal anti-T cell antibodies retards murine lupus in BXSB mice. J Immunol. 1986; 136(12): 4554-4560.

[23] WofsyD,SeamanWE. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med. 1985; 161(2): 378-391.

[24] DeviBS,Van Noordin S,KrauszT,DaviesKA. Peripheral blood lymphocytes in SLE—hyperexpression of CD154 on T and B lymphocytes and increased number of double negative T cells. J Autoimmun. 1998; 11(5): 471-475.

[25] RajagopalanS,ZordanT, TsokosGC,Datta SK. Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4^-8^- T helper cell lines that express the γδ T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990; 87(18): 7020-7024.

[26] ShivakumarS,TsokosGC, DattaSK. T cell receptor α/β expressing double-negative (CD4^-/CD8^-) and CD4⁺ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis. J Immunol. 1989; 143(1): 103-112.

[27] SielingPA,Porcelli SA,DuongBT, et al. Human double-negative T cells in systemic lupus erythematosus provide help for IgG and are restricted by CD1c. J Immunol. 2000; 165(9): 5338-5344.

[28] SawlaP,HossainA, HahnBH,Singh RP. Regulatory T cells in systemic lupus erythematosus (SLE); role of peptide tolerance. Autoimmun Rev. 2012; 11(9): 611-614.

[29] DongWJ,ZhuP, WangYW,Wang ZG. Follicular helper T cells in systemic lupus erythematosus: a potential therapeutic target. Autoimmun Rev. 2011; 10(6): 299-304.

[30] LiH,Boulougoura A,EndoY,TsokosGC. Abnormalities of T cells in systemic lupus erythematosus: new insights in pathogenesis and therapeutic strategies. J Autoimmun. 2022; 132: 102870.

[31] DengGM,TsokosGC. Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation. J Immunol. 2008; 181(6): 4019-4026.

[32] BanchereauJ,Steinman RM. Dendritic cells and the control of immunity. Nature. 1998; 392(6673): 245-252.

[33] Santiago-RaberML,Baccala R,HaraldssonKM, et al. Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. J Exp Med. 2003; 197(6): 777-788.

[34] RowlandSL,RiggsJM, GilfillanS, et al. Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model. J Exp Med. 2014; 211(10): 1977-1991.

[35] SisirakV,GangulyD, LewisKL, et al. Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. J Exp Med. 2014; 211(10): 1969-1976.

[36] TsokosGC,LoMS, Costa ReisP,Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016; 12(12): 716-730.

[37] KaulA,GordonC, CrowMK, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016; 2: 16039.

[38] WangCM,ChangSW, WuYJJ, et al. Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population. Sci Rep. 2014; 4: 3792.

[39] KelleyJ,JohnsonMR, AlarcónGS,KimberlyRP,EdbergJC. Variation in the relative copy number of the TLR7 gene in patients with systemic lupus erythematosus and healthy control subjects. Arthritis Rheum. 2007; 56(10): 3375-3378.

[40] RobinsonT,KariukiSN, FranekBS, et al. Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-α and serologic autoimmunity in lupus patients. J Immunol. 2011; 187(3): 1298-1303.

[41] FengD,StoneRC, ElorantaML, et al. Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus. Arthritis Rheum. 2010; 62(2): 562-573.

[42] LiD,MattaB, SongS, et al. IRF5 genetic risk variants drive myeloid-specific IRF5 hyperactivation and presymptomatic SLE. JCI Insight. 2020; 5(2): e124020.

[43] DevarapuSK,AndersHJ. Toll-like receptors in lupus nephritis. J Biomed Sci. 2018; 25(1): 35.

[44] HuWP,WuSC, ZhangYL,Sigdel KR,LinY,ZhongHB. Association between toll-like receptor 4 polymorphisms and systemic lupus erythematosus susceptibility: a meta-analysis. Biomed Res Int. 2016; 2016: 7842587.

[45] KatoY,ParkJ, TakamatsuH, et al. Apoptosis-derived membrane vesicles drive the cGAS–STING pathway and enhance type I IFN production in systemic lupus erythematosus. Ann Rheum Dis. 2018; 77(10): 1507-1515.

[46] KirbyJM,JhaveriKS, MaizlinZV,Midia M,HaiderE,KhaliliK. Abdominal manifestations of systemic lupus erythematosus: spectrum of imaging findings. Can Assoc Radiol J. 2009; 60(3): 121-132.

[47] Lyn-CookBD,XieC, OatesJ, et al. Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol. 2014; 61(1): 38-43.

[48] SharmaS,Fitzgerald KA,CancroMP,Marshak-RothsteinA. Nucleic acid-sensing receptors: rheostats of autoimmunity and autoinflammation. J Immunol. 2015; 195(8): 3507-3512.

[49] ChenY,LinW, YangHX, et al. Aberrant expansion and function of follicular helper T cell subsets in IgG4-related disease. Arthritis Rheumatol. 2018; 70(11): 1853-1865.

[50] CaielliS,AthaleS, DomicB, et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J Exp Med. 2016; 213(5): 697-713.

[51] DiekerJ,TelJ, PieterseE, et al. Circulating apoptotic microparticles in systemic lupus erythematosus patients drive the activation of dendritic cell subsets and prime neutrophils for NETosis. Arthritis Rheumatol. 2016; 68(2): 462-472.

[52] SalviV,Gianello V,BusattoS, et al. Exosome-delivered microRNAs promote IFN-α secretion by human plasmacytoid DCs via TLR7. JCI Insight. 2018; 3(10): e98204.

[53] SisirakV,SallyB, D’AgatiV, et al. Digestion of chromatin in apoptotic cell microparticles prevents autoimmunity. Cell. 2016; 166(1): 88-101.

[54] BanchereauR,HongS, CantarelB, et al. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell. 2016; 165(3): 551-565.

[55] BallestarE,Esteller M,RichardsonBC. The epigenetic face of systemic lupus erythematosus. J Immunol. 2006; 176(12): 7143-7147.

[56] CooperGS,DooleyMA, TreadwellEL,St Clair EW,ParksCG,GilkesonGS. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. Arthritis Rheum. 1998; 41(10): 1714-1724.

[57] GrossAJ,Hochberg D,RandWM,Thorley-LawsonDA. EBV and systemic lupus erythematosus: a new perspective. J Immunol. 2005; 174(11): 6599-6607.

[58] KangI,QuanT, NolascoH, et al. Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus. J Immunol. 2004; 172(2): 1287-1294.

[59] WangH,Nicholas MW,ConwayKL, et al. EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity. J Immunol. 2006; 177(5): 2793-2802.

[60] ZengQ,WangSY, LiMY, et al. Spleen fibroblastic reticular cell-derived acetylcholine promotes lipid metabolism to drive autoreactive B cell responses. Cell Metab. 2023; 35(5): 837-854.e8.

[61] HondaK,LittmanDR. The microbiome in infectious disease and inflammation. Annu Rev Immunol. 2012; 30: 759-795.

[62] AzzouzD,Omarbekova A,HeguyA, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis. 2019; 78(7): 947-956.

[63] RosserEC,MauriC. A clinical update on the significance of the gut microbiota in systemic autoimmunity. J Autoimmun. 2016; 74: 85-93.

[64] Cerf-BensussanN,Gaboriau-Routhiau V. The immune system and the gut microbiota: friends or foes? Nat Rev Immunol. 2010; 10(10): 735-744.

[65] CrabbéPA,BazinH, EyssenH,Heremans JF. The normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing IgA in the gut. The germ-free intestinal tract. Int Arch Allergy Appl Immunol. 1968; 34(4): 362-375.

[66] IvanovII,Atarashi K,ManelN, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009; 139(3): 485-498.

[67] AtarashiK,TanoueT, ShimaT, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011; 331(6015): 337-341.

[68] HooijkaasH,BennerR, PleasantsJR,Wostmann BS. Isotypes and specificities of immunoglobulins produced by germ-free mice fed chemically defined ultrafiltered "antigen-free" diet. Eur J Immunol. 1984; 14(12): 1127-1130.

[69] BauerH,Horowitz RE,LevensonSM,PopperH. The response of the lymphatic tissue to the microbial flora. Studies on germfree mice. Am J Pathol. 1963; 42(4): 471-483.

[70] PanF,TangW, ZhouZ,Gilkeson G,LangR,JiangW. Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease. Lupus. 2018; 27(12): 1898-1902.

[71] Johansson-LindbomB,Svensson M,PabstO, et al. Functional specialization of gut CD103⁺ dendritic cells in the regulation of tissue-selective T cell homing. J Exp Med. 2005; 202(8): 1063-1073.

[72] VarolC,ZigmondE, JungS. Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria. Nat Rev Immunol. 2010; 10(6): 415-426.

[73] QiuJ,GuoXH, ChenZME, et al. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity. 2013; 39(2): 386-399.

[74] HouMH,LiuSY. Innate lymphoid cells are increased in systemic lupus erythematosus. Clin Exp Rheumatol. 2019; 37(4): 676-679.

[75] LeeGR. The balance of Th17 versus Treg cells in autoimmunity. Int J Mol Sci. 2018; 19(3): 730.

[76] O’MahonyC,ScullyP, O’MahonyD, et al. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation. PLoS Pathog. 2008; 4(8): e1000112.

[77] AnsaldoE,SlaydenLC, ChingKL, et al. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science. 2019; 364(6446): 1179-1184.

[78] ChenYF,LinJ, XiaoLL, et al. Gut microbiota in systemic lupus erythematosus: a fuse and a solution. J Autoimmun. 2022; 132: 102867.

[79] YuanSW,LianF, ChenDY, et al. Clinical features and associated factors of abdominal pain in systemic lupus erythematosus. J Rheumatol. 2013; 40(12): 2015-2022.

[80] JuJH,MinJK, JungCK, et al. Lupus mesenteric vasculitis can cause acute abdominal pain in patients with SLE. Nat Rev Rheumatol. 2009; 5(5): 273-281. PMID: 19412194.

[81] BeukRJ,Tangelder GJ,MaassenRLJG,QuaedackersJSLT,Heineman E,Oude EgbrinkMGA. Leucocyte and platelet adhesion in different layers of the small bowel during experimental total warm ischaemia and reperfusion. Br J Surg. 2008; 95(10): 1294-1304.

[82] HamelinL. Mesenteric vascular insufficiency. J Can Assoc Radiol. 1966; 17(2): 107-115. [in French].

[83] SchwartzS,BoleySJ, RobinsonK,Krieger H,SchultzL,AllenAC. Roentgenologic features of vascular disorders of the intestines. Radiol Clin North Am. 1964; 2: 71-87.

[84] CerveraR,Espinosa G,CorderoA, et al. Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical and immunologic characteristics of 97 patients: comparison of classic and catastrophic APS. Semin Arthritis Rheum. 2007; 36(5): 287-296.

[85] Del PapaN,GuidaliL, SalaA, et al. Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-β₂-glycoprotein I antibodies react in vitro with endothelial cells through adherent β₂-glycoprotein I and induce endothelial activation. Arthritis Rheum. 1997; 40(3): 551-561.

[86] SimantovR,LaSalaJM, LoSK, et al. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest. 1995; 96(5): 2211-2219.

[87] GoldenBD,BelmontHM. The role of microvasculopathy in the catastrophic antiphospholipid syndrome: comment on the article by Neuwelt et al. Arthritis Rheum. 1998; 41(4): 751-753.

[88] CockwellP,TseWY, SavageCO. Activation of endothelial cells in thrombosis and vasculitis. Scand J Rheumatol. 1997; 26(3): 145-150.

[89] TomizawaK,Sato-Matsumura KC. Kajii N. The coexistence of cutaneous vasculitis and thrombosis in childhood-onset systemic lupus erythematosus with antiphospholipid antibodies. Br J Dermatol. 2003; 149(2): 439-441.

[90] HaHK,LeeSH, RhaSE, et al. Radiologic features of vasculitis involving the gastrointestinal tract. Radiographics. 2000; 20(3): 779-794.

[91] MedinaF,AyalaA, JaraLJ,Becerra M,MirandaJM,FragaA. Acute abdomen in systemic lupus erythematosus: the importance of early laparotomy. Am J Med. 1997; 103(2): 100-105.

[92] ZizicTM,ClassenJN, StevensMB. Acute abdominal complications of systemic lupus erythematosus and polyarteritis nodosa. Am J Med. 1982; 73(4): 525-531.

[93] EndoH,KondoY, KawagoeK, et al. Lupus enteritis detected by capsule endoscopy. Intern Med. 2007; 46(18): 1621-1622.

[94] KanekoY,Hirakata M,SuwaA, et al. Systemic lupus erythematosus associated with recurrent lupus enteritis and peritonitis. Clin Rheumatol. 2004; 23(4): 351-354.

[95] LinWY,LanJL, WangSJ. Lupus mesenteric vasculitis detected by Ga-67 scan. Clin Nucl Med. 2001; 26(8): 726.

[96] TsuchiyaM,OkazakiI, AsakuraH,Okubo T. Radiographic and endoscopic features of colonic ulcers in systemic lupus erythematosus. Am J Gastroenterol. 1975; 64(4): 277-285.

[97] YuanSW,YeYJ, ChenDY, et al. Lupus mesenteric vasculitis: clinical features and associated factors for the recurrence and prognosis of disease. Semin Arthritis Rheum. 2014; 43(6): 759-766.

[98] ByunJY,HaHK, YuSY, et al. CT features of systemic lupus erythematosus in patients with acute abdominal pain: emphasis on ischemic bowel disease. Radiology. 1999; 211(1): 203-209.

[99] KoSF,LeeTY, ChengTT, et al. CT findings at lupus mesenteric vasculitis. Acta Radiol. 1997; 38(1): 115-120.

[100] Si-HoeCK,ThngCH, CheeSG,Teo EK,ChngHH. Abdominal computed tomography in systemic lupus erythematosus. Clin Radiol. 1997; 52(4): 284-289.

[101] GrimbacherB,HuberM, von KempisJ, et al. Successful treatment of gastrointestinal vasculitis due to systemic lupus erythematosus with intravenous pulse cyclophosphamide: a clinical case report and review of the literature. Br J Rheumatol. 1998; 37(9): 1023-1028.

[102] BreuerGS,BaerA, DahanD,Nesher G. Lupus-associated pancreatitis. Autoimmun Rev. 2006; 5(5): 314-318.

[103] NesherG,BreuerGS, TempranoK, et al. Lupus-associated pancreatitis. Semin Arthritis Rheum. 2006; 35(4): 260-267.

[104] WangF,WangNS, ZhaoBH,Tang LQ. Acute pancreatitis as an initial symptom of systemic lupus erythematosus: a case report and review of the literature. World J Gastroenterol. 2005; 11(30): 4766-4768.

[105] Lariño NoiaJ,Macías GarcíaF,Seijo Ríos S,Iglesias GarcíaJ, Domínguez MuñozJE. Pancreatitis and systemic lupus erythematosus. Rev Esp Enferm Dig. 2009; 101(8): 571-579.

[106] JohnsonCD,Besselink MG,CarterR. Acute pancreatitis. BMJ. 2014; 349: g4859.

[107] MuhammedH,JainA, IrfanM, et al. Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus. Rheumatol Int. 2022; 42(8): 1363-1371.

[108] LiZ,XuD, WangZ, et al. Gastrointestinal system involvement in systemic lupus erythematosus. Lupus. 2017; 26(11): 1127-1138.

[109] ZhangLL,XuD, YangH, et al. Clinical features, morbidity, and risk factors of intestinal pseudo-obstruction in systemic lupus erythematosus: a retrospective case-control study. J Rheumatol. 2016; 43(3): 559-564.

[110] BanksPA,ConwellDL, ToskesPP. The management of acute and chronic pancreatitis. Gastroenterol Hepatol (N Y). 2010; 6(2 Suppl 3): 1-16.

[111] PigaM,VaccaA, PorruG,Cauli A,MathieuA. Liver involvement in systemic lupus erythematosus: incidence, clinical course and outcome of lupus hepatitis. Clin Exp Rheumatol. 2010; 28(4): 504-510.

[112] ZhengRH,WangJH, WangSB,Chen J,GuanWM,ChenMH. Clinical and immunopathological features of patients with lupus hepatitis. Chin Med J (Engl). 2013; 126(2): 260-266.

[113] TakahashiA,AbeK, SaitoR, et al. Liver dysfunction in patients with systemic lupus erythematosus. Intern Med. 2013; 52(13): 1461-1465.

[114] AlanaziT,Alqahtani M,Al DuraihimH, et al. Hepatic vasculitis mimicking liver abscesses in a patient with systemic lupus erythematosus. Ann Saudi Med. 2009; 29(6): 474-477.

[115] ChowdharyVR,CrowsonCS, PoteruchaJJ,Moder KG. Liver involvement in systemic lupus erythematosus: case review of 40 patients. J Rheumatol. 2008; 35(11): 2159-2164.

[116] RunyonBA,LaBrecque DR,AnurasS. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med. 1980; 69(2): 187-194.

[117] ArnettFC,Reichlin M. Lupus hepatitis: an under-recognized disease feature associated with autoantibodies to ribosomal P. Am J Med. 1995; 99(5): 465-472.

[118] OhiraH,Takiguchi J,RaiT, et al. High frequency of anti-ribosomal P antibody in patients with systemic lupus erythematosus-associated hepatitis. Hepatol Res. 2004; 28(3): 137-139.

[119] AfzalW,HaghiM, HasniSA,Newman KA. Lupus hepatitis, more than just elevated liver enzymes. Scand J Rheumatol. 2020; 49(6): 427-433.

[120] LacroixI,Lapeyre-Mestre M. BagheriH,PathakA,Montastruc JL. Nonsteroidal anti-inflammatory drug-induced liver injury: a case–control study in primary care. Fundam Clin Pharmacol. 2004; 18(2): 201-206.

[121] SchmeltzerPA,Kosinski AS,KleinerDE, et al. Liver injury from nonsteroidal anti-inflammatory drugs in the United States. Liver Int. 2016; 36(4): 603-609.

[122] HosseiniN,ShorJ, SzaboG. Alcoholic hepatitis: a review. Alcohol Alcohol. 2019; 54(4): 408-416.

[123] BellH,Tallaksen CM,TryK,HaugE. Carbohydrate-deficient transferrin and other markers of high alcohol consumption: a study of 502 patients admitted consecutively to a medical department. Alcohol Clin Exp Res. 1994; 18(5): 1103-1108.

[124] SorbiD,BoyntonJ, LindorKD. The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol. 1999; 94(4): 1018-1022.

[125] AdigaA,NugentK. Lupus hepatitis and autoimmune hepatitis (lupoid hepatitis). Am J Med Sci. 2017; 353(4): 329-335.

[126] GromAA,MellinsED. Macrophage activation syndrome: advances towards understanding pathogenesis. Curr Opin Rheumatol. 2010; 22(5): 561-566.

[127] SimonettoDA,LiuM, KamathPS. Portal hypertension and related complications: diagnosis and management. Mayo Clin Proc. 2019; 94(4): 714-726.

[128] MokCC,YingKY, MakA,ToCH, SzetoML. Outcome of protein-losing gastroenteropathy in systemic lupus erythematosus treated with prednisolone and azathioprine. Rheumatology (Oxford). 2006; 45(4): 425-429.

[129] KimYG,LeeCK, ByeonJS, et al. Serum cholesterol in idiopathic and lupus-related protein-losing enteropathy. Lupus. 2008; 17(6): 575-579.

[130] HungJ,WoodCA, WoronikV,Vieira JM Jr,BarrosRT. Protein-losing gastroenteropathy in a patient with systemic lupus erythematosus and antiphospholipid antibody syndrome simulating nephrotic syndrome. Nephrol Dial Transplant. 2006; 21(7): 2027-2028.

[131] ZhengWJ,TianXP, LiL, et al. Protein-losing enteropathy in systemic lupus erythematosus: analysis of the clinical features of fifteen patients. J Clin Rheumatol. 2007; 13(6): 313-316.

[132] GornisiewiczM,Rodriguez M,SmithJK,SaagK,Alarcón GS. Protein-losing enteropathy in a young African-American woman with abdominal pain, diarrhea and hydronephrosis. Lupus. 2001; 10(12): 835-840.

[133] Pardos-GeaJ,Ordi-Ros J,SelvaA,Perez-LopezJ,BaladaE, VilardellM. Chronic intestinal pseudo-obstruction associated with biliary tract dilatation in a patient with systemic lupus erythematosus. Lupus. 2005; 14(4): 328-330.

[134] AlexopoulouA,Andrianakos A,DourakisSP. Intestinal pseudo-obstruction and ureterohydronephrosis as the presenting manifestations of relapse in a lupus patient. Lupus. 2004; 13(12): 954-956.

[135] ParkFD,LeeJK, MadduriGD,Ghosh P. Generalized megaviscera of lupus: refractory intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus. World J Gastroenterol. 2009; 15(28): 3555-3559.

[136] CeccatoF,SalasA, GóngoraV, et al. Chronic intestinal pseudo-obstruction in patients with systemic lupus erythematosus: report of four cases. Clin Rheumatol. 2008; 27(3): 399-402.

[137] MokMY,WongRW, LauCS. Intestinal pseudo-obstruction in systemic lupus erythematosus: an uncommon but important clinical manifestation. Lupus. 2000; 9(1): 11-18.

[138] NojimaY,MimuraT, HamasakiK, et al. Chronic intestinal pseudoobstruction associated with autoantibodies against proliferating cell nuclear antigen. Arthritis Rheum. 1996; 39(5): 877-879.

[139] KnowlesCH,Lindberg G,PanzaE,GiorgioRD. New perspectives in the diagnosis and management of enteric neuropathies. Nat Rev Gastroenterol Hepatol. 2013; 10(4): 206-218.

[140] EtminanM,Lévesque L,FitzgeraldJM,BrophyJM. Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control study. Aliment Pharmacol Ther. 2009; 29(11): 1188-1192.

[141] GuZC,WeiAH, ZhangC, et al. Risk of major gastrointestinal bleeding with new vs conventional oral anticoagulants: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2020; 18(4): 792-799.e61.

[142] IwamuroM,Takahashi T,OtaY, et al. Intestinal diffuse large B-cell lymphoma in a patient with systemic lupus erythematosus. Case Rep Gastrointest Med. 2020; 2020: 7947540.

[143] WuMC,LeongPY, ChiouJY,Chen HH,HuangJY,WeiJC. Increased isk of systemic lupus erythematosus in patients with Helicobacter pylori Infection: a nationwide population-based cohort study. Front Med (Lausanne) 2020; 3: 330.doi:10.3389/fmed.2019.00330

[144] WangLR,BarberCE, JohnsonAS,Barnabe C. Invasive fungal disease in systemic lupus erythematosus: a systematic review of disease characteristics, risk factors, and prognosis. Semin Arthritis Rheum. 2014; 44(3): 325-330.

[145] SciasciaS,Cuadrado MJ,KarimMY. Management of infection in systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2013; 27(3): 377-389.

[146] ChenHS,TsaiWP, LeuHS,Ho HH,LiouLB. Invasive fungal infection in systemic lupus erythematosus: an analysis of 15 cases and a literature review. Rheumatology (Oxford). 2007; 46(3): 539-544.

[147] ZhouA,WangY, ChenY,Zhong H,ChenB,TanC. A case report of systemic lupus erythematosus and intestinal tuberculosis with lower gastrointestinal bleeding: a treatment approach utilizing parenteral nutrition. Medicine (Baltimore). 2023; 102(41): e35374.

[148] WuP,ZengJ, YangL. Case report: vesicorectal fistula caused by intestinal tuberculosis complicated with systemic lupus erythematosus. Infect Drug Resist. 2022; 15: 6237-6243.

[149] XiaoX,DaG, XieX, et al. Tuberculosis in patients with systemic lupus erythematosus-a 37-year longitudinal survey-based study. J Intern Med. 2021; 290(1): 101-115.

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2024 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.