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(huì)芳 趙景宏 張靜波（第三軍醫(yī)大學(xué)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?；顒?dòng)性SLE常有全血細(xì)胞減少；由于免疫功能紊亂及長(zhǎng)期免疫抑制劑的應(yīng)用，易繼發(fā)感染，出現(xiàn)發(fā)熱、腹瀉等癥狀，嚴(yán)重時(shí)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(xì)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(shí)很難鑒別，易誤診，漏診，現(xiàn)將我科收治的1例SLE誤診AA報(bào)告如下。病例報(bào)告患者，中年女性，45歲，因“反復(fù)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(lái)我科治療。患者2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(xì)胞計(jì)數(shù) 1.1109/L, 紅細(xì)胞計(jì)數(shù) 2.201012/L,血紅蛋白61g/l,血小板計(jì)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(fù)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(jìn)

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(wú)明顯誘因出現(xiàn)全身水腫、腹瀉、發(fā)熱，最高體溫39，無(wú)畏寒、咳嗽、胸痛，無(wú)腹痛、惡心、嘔吐；到當(dāng)?shù)蒯t(yī)院查血常規(guī)白細(xì)胞計(jì)數(shù) 3.52109/L、 紅細(xì)胞計(jì)數(shù) 1.981012/L、血紅蛋白50g/l、血小板計(jì)數(shù) 36109/L；給予對(duì)癥處理，未再發(fā)熱、腹瀉，但自覺(jué)癥狀及水腫無(wú)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(dòng)性濁音陽(yáng)性，四肢重度水腫；實(shí)驗(yàn)室檢查：白細(xì)胞計(jì)數(shù) 1.27109/L, 紅細(xì)胞計(jì)數(shù) 2.101012/L,血紅蛋白61g/l,血小板計(jì)數(shù) 27109/L；尿常規(guī)蛋白+，潛

9、血+，白細(xì)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(xì)胞懸液，水腫進(jìn)一步加重；血漿白蛋白12.1g/l，24小時(shí)尿蛋白定量5.14g，于2013年7月18日來(lái)我科治療。入院后查補(bǔ)體C3 0.11 （參考值0.9-2.1）；尿蛋白+；抗核抗體譜SS-A陽(yáng)性、Ro-52陽(yáng)性、抗核抗體核型核均質(zhì)型、核小體陽(yáng)性、組蛋白陽(yáng)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(xì)胞低，一般情況較差；告知門(mén)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(fù)查血常規(guī)白細(xì)胞計(jì)數(shù) 10.23109/L, 紅細(xì)胞計(jì)數(shù) 2.351012/L,血紅蛋白65g/l,血小板計(jì)數(shù) 80109/L；肝功白蛋白21g/l，總蛋白46.9g/l。患者精神狀態(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(shí)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(xì)胞減少及血小板減少，按AA進(jìn)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(jiàn)，主要因狼瘡活動(dòng)細(xì)胞毒型變態(tài)引起細(xì)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(duì)造血干細(xì)胞的高效價(jià)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(diǎn)：多為增生性骨髓象，骨髓紅系及巨核細(xì)胞數(shù)量增生良好，Ret/Nc不降低；而AA的骨髓象特點(diǎn)表現(xiàn)為：多部位增生減低，三系造血細(xì)胞減少，淋巴及非造血細(xì)胞相對(duì)增多，Ret/Nc降低。系統(tǒng)性紅斑狼瘡是一種復(fù)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(méi)有特異性特征，可以僅僅表現(xiàn)為1-2個(gè)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(xì)病史詢問(wèn)、仔細(xì)的體格檢查及實(shí)驗(yàn)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(yīng)加強(qiáng)業(yè)務(wù)學(xué)習(xí)，提高對(duì)本病的警惕性，要對(duì)臨床治療進(jìn)行全面仔

20、細(xì)的綜合分析，尤其遇到治療效果不好的患者，要深究原因，應(yīng)考慮系統(tǒng)性疾病的可能。希望通過(guò)本例報(bào)告引起廣大臨床醫(yī)師對(duì)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(xué)改變，有助于臨床診斷，減少誤診及漏診。參考文獻(xiàn)： 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(jìn)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