系統(tǒng)性紅斑狼瘡誤診再生障礙性貧血1例

1、系統(tǒng)性紅斑狼瘡誤診再生障礙性貧血1例劉會芳 趙景宏 張靜波（第三軍醫(yī)大學新橋醫(yī)院腎內(nèi)科，重慶 400037）系統(tǒng)性紅斑狼瘡（Systemic Lupus Erythematosus, SLE）一種全身性自身免疫病。活動性SLE常有全血細胞減少；由于免疫功能紊亂及長期免疫抑制劑的應用，易繼發(fā)感染，出現(xiàn)發(fā)熱、腹瀉等癥狀，嚴重時常危及生命 ADDIN EN.CITE Bezalel2012111117Bezalel, S.Asher, I.Elbirt, D.Sthoeger, Z. M.Department of Medicine B, Kaplan Medical Center, Rehovot

2、, affiliated with Hebrew University-Hadassah Medical School, Jerusalem, Israel.Novel biological treatments for systemic lupus erythematosus: current and future modalitiesIsr Med Assoc JIsr Med Assoc J508-141482012/09/18Antibodies, Monoclonal/therapeutic useAntibodies, Monoclonal, Humanized/therapeut

3、ic useAntibodies, Monoclonal, Murine-Derived/therapeutic useB-Cell Activating Factor/bloodB-Lymphocytes/immunologyBiological Therapy/*methodsDrug Delivery SystemsHumansLupus Erythematosus, Systemic/*therapyOligonucleotides/therapeutic useT-Lymphocytes/drug effectsTumor Necrosis Factor Ligand Superfa

4、mily Member 13/metabolism2012Aug1565-1088 (Print)22977972/pubmed/22977972eng HYPERLINK l _ENREF_1 o Bezalel, 2012 #1 1。再生障礙性貧血（Aplastic anemia，AA）是一種獲得性骨髓造血功能衰竭癥，主要表現(xiàn)為骨髓造血功能低下、全血細胞減少和貧血、出血、感染綜合癥 ADDIN EN.CITE 2012222217Aplastic anemia: therapeutic updates in immunosuppression and transplantationHema

5、tology Am Soc Hematol Educ ProgramHematology Am Soc Hematol Educ Program10.1182/asheducation-2012.1.292.2012:292-300.doi0 (Biological Markers)AdultAlgorithmsAnemia, Aplastic/*immunology/*therapyAnimalsBiological Markers/metabolismGraft RejectionGraft vs Host DiseaseHematopoietic Stem Cell Transplant

6、ation/adverse effects/*methodsHistocompatibility TestingHorsesHumansImmunosuppression/*methodsMiddle AgedRabbitsRetrospective StudiesRiskSalvage Therapy/methodsSiblingsTissue DonorsTreatment OutcomeUnrelated Donors20121520-4383 (Electronic)1520-4383 (Linking) HYPERLINK l _ENREF_2 o , 2012 #2 2。在臨床癥狀

7、不典型且合并多系統(tǒng)表現(xiàn)時很難鑒別，易誤診，漏診，現(xiàn)將我科收治的1例SLE誤診AA報告如下。病例報告患者，中年女性，45歲，因“反復頭昏、乏力、水腫2年，腹瀉、發(fā)熱1月”于2013年7月15日入住血液科，2013年7月18日來我科治療?；颊?年前因頭昏、乏力、心慌、雙下肢水腫，入血液科住院治療。經(jīng)查血常規(guī)白細胞計數(shù) 1.1109/L, 紅細胞計數(shù) 2.201012/L,血紅蛋白61g/l,血小板計數(shù) 37109/L；肝功白蛋白15.7g/l；骨髓活檢提示骨髓增生減低，診斷“再生障礙性貧血”。予以復方皂礬丸、十一酸睪丸酮膠囊服用1月，其后自行停藥未隨訪，水腫間斷出現(xiàn)。院外一直按“再生障礙性貧血”進

8、行治療，效果不明顯。貧血及血小板低下一直未糾正。1月前，無明顯誘因出現(xiàn)全身水腫、腹瀉、發(fā)熱，最高體溫39，無畏寒、咳嗽、胸痛，無腹痛、惡心、嘔吐；到當?shù)蒯t(yī)院查血常規(guī)白細胞計數(shù) 3.52109/L、 紅細胞計數(shù) 1.981012/L、血紅蛋白50g/l、血小板計數(shù) 36109/L；給予對癥處理，未再發(fā)熱、腹瀉，但自覺癥狀及水腫無好轉(zhuǎn)，入住血液科；查體：慢性病容，貧血貌，顏面眼瞼重度水腫，面色蒼白，心肺陰性，腹軟，肝脾未捫及，移動性濁音陽性，四肢重度水腫；實驗室檢查：白細胞計數(shù) 1.27109/L, 紅細胞計數(shù) 2.101012/L,血紅蛋白61g/l,血小板計數(shù) 27109/L；尿常規(guī)蛋白+，潛

9、血+，白細胞+；白蛋白12.1g/l，總蛋白38.4g/l。結(jié)合既往病史，診斷AA。給予輸注紅細胞懸液，水腫進一步加重；血漿白蛋白12.1g/l，24小時尿蛋白定量5.14g，于2013年7月18日來我科治療。入院后查補體C3 0.11 （參考值0.9-2.1）；尿蛋白+；抗核抗體譜SS-A陽性、Ro-52陽性、抗核抗體核型核均質(zhì)型、核小體陽性、組蛋白陽性、抗核抗體滴度1:1000；腎功能正常；腹部超聲：腹盆腔積液；腎活檢病理結(jié)果：狼瘡性腎炎III型。結(jié)合既往病史，診斷“系統(tǒng)性紅斑狼瘡 狼瘡性腎炎”；予以激素免疫抑制（住院期間暫未用環(huán)磷酰胺，因其白細胞低，一般情況較差；告知門診隨訪據(jù)情況加此藥

10、）、降尿蛋白、保腎、改善循環(huán)。7月30日復查血常規(guī)白細胞計數(shù) 10.23109/L, 紅細胞計數(shù) 2.351012/L,血紅蛋白65g/l,血小板計數(shù) 80109/L；肝功白蛋白21g/l，總蛋白46.9g/l?；颊呔駹顟B(tài)明顯好轉(zhuǎn)，頭昏、乏力癥狀明顯減輕，全身水腫明顯消退，體重較入院時減輕10公斤，于8月7日出院，院外繼續(xù)治療，效果良好。討論該患者表現(xiàn)為貧血、白細胞減少及血小板減少，按AA進行治療了2年，效果不好。經(jīng)腎活檢及抗核抗體譜結(jié)果診斷為“系統(tǒng)性紅斑狼瘡、狼瘡性腎炎”明確，給予激素治療后效果明顯。狼瘡患者三系減少常見，主要因狼瘡活動細胞毒型變態(tài)引起細胞溶解所致 ADDIN EN.CIT

11、E 2013535517Mechanisms of disease for the clinician: systemic lupus erythematosusAnn Allergy Asthma ImmunolAnn Allergy Asthma Immunol228-32. doi: 10.1016/j.anai.2012.12.010. Epub 2013 Jan 5.11040 (Antibodies, Monoclonal)AdolescentAdultAntibodies, Monoclonal/immunologyB-Lymphocytes/immunologyFemaleHu

12、mansImmune ToleranceImmunosuppressionLupus Erythematosus, Systemic/epidemiology/*immunology/*physiopathology/therapyMaleMiddle AgedYoung Adult2013Apr1534-4436 (Electronic)1081-1206 (Linking) HYPERLINK l _ENREF_3 o , 2013 #5 3；少數(shù)系統(tǒng)性紅斑狼瘡患者中存在有針對造血干細胞的高效價自身抗體也可致三系減少 ADDIN EN.CITE 2013343317Belimumab fo

13、r systemic lupus erythematosusN Engl J MedN Engl J Med1528-35. doi: 10.1056/NEJMct1207259.368160 (Antibodies, Monoclonal)73B0K5S26A (belimumab)Antibodies, Monoclonal/adverse effects/*therapeutic useFemaleHumansLupus Erythematosus, Systemic/*drug therapyYoung Adult2013Apr 181533-4406 (Electronic)0028

14、-4793 (Linking) HYPERLINK l _ENREF_4 o , 2013 #3 4；SLE的骨髓象特點：多為增生性骨髓象，骨髓紅系及巨核細胞數(shù)量增生良好，Ret/Nc不降低；而AA的骨髓象特點表現(xiàn)為：多部位增生減低，三系造血細胞減少，淋巴及非造血細胞相對增多，Ret/Nc降低。系統(tǒng)性紅斑狼瘡是一種復雜的自身免疫性疾病，以出現(xiàn)多種自身抗體為特征 ADDIN EN.CITE 2013656617B-cell-targeted therapies in systemic lupus erythematosusCell Mol ImmunolCell Mol Immunol133-4

15、2. doi: 10.1038/cmi.2012.64. Epub 2013 Jan 28.1020 (Cytokines)0 (Growth Inhibitors)AnimalsAntigen-Presenting Cells/immunology/metabolism/pathologyB-Lymphocyte Subsets/*immunology/*metabolism/pathologyCell Death/immunologyCytokines/metabolismDisease Models, AnimalGrowth Inhibitors/metabolismHumansLup

16、us Erythematosus, Systemic/*immunology/pathology/*therapyMolecular Targeted Therapy/*methods2013Mar2042-0226 (Electronic)1672-7681 (Linking) HYPERLINK l _ENREF_5 o , 2013 #6 5，臨床表現(xiàn)多樣化，尤其在早期沒有特異性特征，可以僅僅表現(xiàn)為1-2個系統(tǒng)受損 ADDIN EN.CITE 2013767717Biologic therapy for autoimmune diseases: an updateBMC MedBMC M

17、ed10.1186/1741-7015-11-88.11:88.doi0 (Immunosuppressive Agents)Autoimmune Diseases/*therapyBiological Therapy/adverse effects/*methodsHumansImmunosuppressive Agents/administration & dosage/adverse effectsImmunotherapy/adverse effects/*methods2013Apr 41741-7015 (Electronic)1741-7015 (Linking) HYPERLI

18、NK l _ENREF_6 o , 2013 #7 6，故極容易誤診。很多病人早期表現(xiàn)不典型，自身抗體僅表現(xiàn)為未分化型結(jié)締組織病 ADDIN EN.CITE 2013878817Renal involvement in autoimmune connective tissue diseasesBMC MedBMC Med10.1186/1741-7015-11-95.11:95.doi0 (Immunologic Factors)Autoimmune Diseases/*complications/drug therapy/*pathologyConnective Tissue Disease

19、s/*complications/drug therapy/*pathologyHumansImmunologic Factors/adverse effects/*therapeutic useKidney Diseases/*etiology/*pathology2013Apr 41741-7015 (Electronic)1741-7015 (Linking) HYPERLINK l _ENREF_7 o , 2013 #8 7。診斷主要依據(jù)詳細病史詢問、仔細的體格檢查及實驗室檢查，其中自身抗體譜的篩查及追蹤尤為重要。因此臨床醫(yī)師應加強業(yè)務學習，提高對本病的警惕性，要對臨床治療進行全面仔

20、細的綜合分析，尤其遇到治療效果不好的患者，要深究原因，應考慮系統(tǒng)性疾病的可能。希望通過本例報告引起廣大臨床醫(yī)師對三系減少鑒別診斷的重視。特別是我們血液科醫(yī)師了解SLE的血液學改變，有助于臨床診斷，減少誤診及漏診。參考文獻： ADDIN EN.CITE 2013535517Mechanisms of disease for the clinician: systemic lupus erythematosusAnn Allergy Asthma ImmunolAnn Allergy Asthma Immunol228-32. doi: 10.1016/j.anai.2012.12.010. Ep

21、ub 2013 Jan 5.11040 (Antibodies, Monoclonal)AdolescentAdultAntibodies, Monoclonal/immunologyB-Lymphocytes/immunologyFemaleHumansImmune ToleranceImmunosuppressionLupus Erythematosus, Systemic/epidemiology/*immunology/*physiopathology/therapyMaleMiddle AgedYoung Adult2013Apr1534-4436 (Electronic)1081-

22、1206 (Linking)1 ADDIN EN.REFLIST Bezalel S, Asher I, Elbirt D, Sthoeger ZM. Novel biological treatments for systemic lupus erythematosus: Current and future modalities. Isr Med Assoc J. 2012 14: 508-514. ADDIN EN.CITE 2013535517Mechanisms of disease for the clinician: systemic lupus erythematosusAnn

23、 Allergy Asthma ImmunolAnn Allergy Asthma Immunol228-32. doi: 10.1016/j.anai.2012.12.010. Epub 2013 Jan 5.11040 (Antibodies, Monoclonal)AdolescentAdultAntibodies, Monoclonal/immunologyB-Lymphocytes/immunologyFemaleHumansImmune ToleranceImmunosuppressionLupus Erythematosus, Systemic/epidemiology/*imm

24、unology/*physiopathology/therapyMaleMiddle AgedYoung Adult2013Apr1534-4436 (Electronic)1081-1206 (Linking)2Aplastic anemia: therapeutic updates in immunosuppression and transplantation. Hematology Am Soc Hematol Educ Program, 2012. 2012:292-300.(doi): p. 10.1182/asheducation-2012.1.292.3 李圣楠, 黃慈波. 系

25、統(tǒng)性紅斑狼瘡的診斷治療進展. 臨床藥物治療雜志. 2010 8: 6-10. ADDIN EN.CITE 2013535517Mechanisms of disease for the clinician: systemic lupus erythematosusAnn Allergy Asthma ImmunolAnn Allergy Asthma Immunol228-32. doi: 10.1016/j.anai.2012.12.010. Epub 2013 Jan 5.11040 (Antibodies, Monoclonal)AdolescentAdultAntibodies, Mo

26、noclonal/immunologyB-Lymphocytes/immunologyFemaleHumansImmune ToleranceImmunosuppressionLupus Erythematosus, Systemic/epidemiology/*immunology/*physiopathology/therapyMaleMiddle AgedYoung Adult2013Apr1534-4436 (Electronic)1081-1206 (Linking)4Belimumab for systemic lupus erythematosus. N Engl J Med,

27、2013. 368(16): p. 1528-35. doi: 10.1056/NEJMct1207259. ADDIN EN.CITE 2013535517Mechanisms of disease for the clinician: systemic lupus erythematosusAnn Allergy Asthma ImmunolAnn Allergy Asthma Immunol228-32. doi: 10.1016/j.anai.2012.12.010. Epub 2013 Jan 5.11040 (Antibodies, Monoclonal)AdolescentAdu

28、ltAntibodies, Monoclonal/immunologyB-Lymphocytes/immunologyFemaleHumansImmune ToleranceImmunosuppressionLupus Erythematosus, Systemic/epidemiology/*immunology/*physiopathology/therapyMaleMiddle AgedYoung Adult2013Apr1534-4436 (Electronic)1081-1206 (Linking)5B-cell-targeted therapies in systemic lupu

29、s erythematosus. Cell Mol Immunol, 2013. 10(2): p. 133-42. doi: 10.1038/cmi.2012.64. Epub 2013 Jan 28. ADDIN EN.CITE 2013535517Mechanisms of disease for the clinician: systemic lupus erythematosusAnn Allergy Asthma ImmunolAnn Allergy Asthma Immunol228-32. doi: 10.1016/j.anai.2012.12.010. Epub 2013 Jan 5.11040 (Antibodies, Monoclonal)AdolescentAdultAntibodies, Monoclonal/immunologyB-Lymphocy