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      老年男性系統(tǒng)性紅斑狼瘡長期誤診分析

      2017-03-06 10:13:24俞傳琪
      臨床誤診誤治 2017年4期
      關(guān)鍵詞:關(guān)節(jié)痛狼瘡藥物性

      俞傳琪,宗 雪,張 翀

      老年男性系統(tǒng)性紅斑狼瘡長期誤診分析

      俞傳琪,宗 雪,張 翀

      目的 探討臨床表現(xiàn)不典型的系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus, SLE)的臨床特點(diǎn)。方法 對我院收治的1例誤診為淋巴結(jié)結(jié)核的SLE患者臨床資料進(jìn)行回顧性分析。結(jié)果 患者為78歲男性,因泡沫尿、夜尿增多伴反復(fù)口腔潰瘍1年入我院。3年前因多發(fā)縱隔淋巴結(jié)增大,行淋巴結(jié)活檢診斷為淋巴結(jié)結(jié)核,轉(zhuǎn)結(jié)核病??漆t(yī)院予抗結(jié)核治療效果不佳。入我院后查抗核抗體和抗雙鏈DNA抗體陽性,外周血三系降低,并結(jié)合關(guān)節(jié)痛、反復(fù)口腔潰瘍等多系統(tǒng)受累表現(xiàn),確診為SLE。予糖皮質(zhì)激素治療,病情明顯改善。結(jié)論 部分SLE患者癥狀不典型,尤以男性為主。對于不明原因的外周血三系下降伴口腔潰瘍、關(guān)節(jié)痛、淋巴結(jié)增大的老年患者,應(yīng)警惕SLE可能,及時(shí)行免疫學(xué)檢查,避免臨床漏誤診。

      系統(tǒng)性紅斑狼瘡;淋巴結(jié)結(jié)核;男性;誤診

      系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus, SLE)是一種累及多臟器、多系統(tǒng)的自身免疫性疾病,癥狀不典型,男性由于發(fā)病率低,誤診率較高[1-2]。我院近期收治1例老年男性SLE,曾在某大型三甲醫(yī)院誤診為淋巴結(jié)結(jié)核,誤診時(shí)間3年余,在我院診斷SLE并給予相應(yīng)治療后癥狀明顯改善,現(xiàn)回顧其診療過程如下。

      1 病例資料

      男,78歲。因泡沫尿、夜尿增多伴反復(fù)口腔潰瘍、脫發(fā)1年,加重1個月入院。1年前患者出現(xiàn)泡沫尿、夜尿增多,未重視。近期夜尿增多加重,每晚7次左右,伴關(guān)節(jié)痛(主要為雙膝關(guān)節(jié)),反復(fù)口腔潰瘍,脫發(fā),病程中無發(fā)熱、咳嗽、咳痰、腹痛、腹瀉、皮疹等表現(xiàn)。來我科門診就診,查血白細(xì)胞5.4×109/L,紅細(xì)胞3.6×1012/L,血紅蛋白112 g/L,血小板69×109/L。以外周血三系減低原因待查收入院。追問病史,患者3年前因2個月內(nèi)體重下降10 kg至某醫(yī)院診治,查外周血三系下降(白細(xì)胞3.45×109/L、紅細(xì)胞3.65×1012/L、血小板84×109/L);骨髓病理檢查示:骨髓增生極度低下,局部網(wǎng)狀纖維輕度增生;骨髓細(xì)胞學(xué)檢查示:紅系偏低,少量幼稚淋巴細(xì)胞(0.004)。該院血液科會診考慮外周血三系輕度下降,暫無需處理,注意隨訪血常規(guī)。進(jìn)一步行正電子發(fā)射型計(jì)算機(jī)斷層掃描(PET-CT)示:縱隔內(nèi)多發(fā)淋巴結(jié)增大,脫氧葡萄糖(FDG)攝取增高,脾臟增大伴FDG攝取輕度增高,考慮淋巴瘤可能。胸腔鏡下行縱隔淋巴結(jié)活檢報(bào)告示:上縱隔淋巴結(jié)呈上皮樣細(xì)胞肉芽腫樣變,可見干酪樣壞死,考慮淋巴結(jié)結(jié)核。轉(zhuǎn)某結(jié)核病專科醫(yī)院給予抗結(jié)核治療(異煙肼、利福賁丁、乙胺丁醇及自制結(jié)核丸),2個月后患者出現(xiàn)皮疹,以四肢為主,伴有瘙癢,考慮藥物過敏,給予抗過敏藥物治療后皮疹有所改善?;颊呖菇Y(jié)核治療后癥狀無明顯改善,復(fù)查血常規(guī)仍呈三系下降,5個月后自行停用抗結(jié)核藥物。

      本次入院查體:體溫37℃,脈搏80/min,呼吸20/min,血壓120/80 mmHg。全身皮膚無皮疹,口腔可見散在潰瘍,雙側(cè)頸部、頜下、鎖骨上、腋下未觸及增大淋巴結(jié)。兩肺呼吸音清,未聞及明顯干濕啰音;心臟聽診未見異常。腹平軟,無壓痛,肝脾肋下未觸及。雙下肢無水腫。查血白細(xì)胞3.9×109/L,紅細(xì)胞3.55×1012/L,血紅蛋白103 g/L,血小板55×109/L,紅細(xì)胞沉降率26 mm/h;白蛋白41.2 g/L,球蛋白35.1 g/L;血肌酐74 μmol/L;抗核抗體(ANA)效價(jià)1∶160,抗雙鏈DNA抗體及抗著絲點(diǎn)抗體均陽性;免疫球蛋白(Ig)G 21.1 g/L,補(bǔ)體C3 0.64 g/L,補(bǔ)體C4 0.24 g/L;核周型抗中性粒細(xì)胞胞質(zhì)抗體陽性,胞漿型抗中性粒細(xì)胞胞質(zhì)抗體陰性,蛋白酶 3抗中性粒細(xì)胞胞質(zhì)抗體102.94 RU/ml,髓過氧化物酶抗中性粒細(xì)胞胞質(zhì)抗體115.22 RU/ml,抗GBM抗體48.42 RU/ml;24 h尿量1200 ml,24 h尿蛋白定量156.12 mg;尿蛋白電泳:球蛋白0.079,微球蛋白0.178,白蛋白0.743,提示混合型蛋白尿。胸部CT增強(qiáng)掃描示:右肺下葉輕度炎性變,右側(cè)胸膜點(diǎn)狀鈣化,兩肺多枚小結(jié)節(jié),炎性病灶可能。腹部超聲檢查示:肝稍大,脾大。根據(jù)患者ANA、抗雙鏈DNA抗體陽性,外周血三系降低,以及關(guān)節(jié)痛、反復(fù)口腔潰瘍等臨床表現(xiàn),經(jīng)風(fēng)濕免疫科會診,確診SLE。予潑尼松25 mg/d、羥氯喹100 mg每日2次口服,癥狀逐步緩解,出院后繼續(xù)用藥。2個月后復(fù)查,患者關(guān)節(jié)痛、口腔潰瘍、脫發(fā)減輕,免疫學(xué)指標(biāo)及血常規(guī)較前改善:ANA效價(jià)1∶80,IgG 15.4 g/L,補(bǔ)體C3 0.71 g/L,補(bǔ)體C4 0.25 g/L;血白細(xì)胞7.1×109/L,紅細(xì)胞4.16×1012/L,血紅蛋白127 g/L,血小板87×109/L,紅細(xì)胞沉降率17 mm/h。4個月后復(fù)查24 h尿蛋白陰性。

      2 討論

      2.1 疾病特點(diǎn) SLE以多系統(tǒng)損害為特征,好發(fā)于年輕女性,男女發(fā)病比例為1︰5~1︰9,男性SLE出現(xiàn)癥狀及確診年齡均較女性晚,誤診率、病死率較女性高[3-6]。男性SLE特征性表現(xiàn)如面部盤狀或蝶形紅斑、皮疹、雷諾現(xiàn)象、口腔潰瘍、關(guān)節(jié)炎等,較女性少見[7-9],血液系統(tǒng)損害[10-12]、腎臟損害、中樞神經(jīng)系統(tǒng)損害等較女性多見且程度重[13-16],ANA、抗雙鏈DNA抗體、抗SM抗體、抗心磷脂抗體等指標(biāo)陽性率高[17]。本例以血液系統(tǒng)損害為主要表現(xiàn),伴淋巴結(jié)增大,ANA、抗雙鏈DNA抗體陽性,IgG升高,補(bǔ)體降低,臨床特點(diǎn)與前述文獻(xiàn)報(bào)道相符。

      2.2 診斷分析 該患者3年前初診于一三甲醫(yī)院,當(dāng)時(shí)即發(fā)現(xiàn)外周血三系減低、皮疹等表現(xiàn),但未受到重視,疏忽了對病情的綜合分析,亦未行免疫學(xué)檢查。盡管患者在該院作為疑難病例多次會診討論,最終僅根據(jù)淋巴結(jié)活檢結(jié)果診斷為淋巴結(jié)結(jié)核,但系統(tǒng)抗結(jié)核治療并無確切效果?;颊弑敬我蚺菽?、夜尿增多1年收治我科,結(jié)合患者伴關(guān)節(jié)痛、反復(fù)口腔潰瘍、脫發(fā)、外周血三系減低等多系統(tǒng)損害表現(xiàn),查ANA和抗雙鏈DNA抗體陽性,根據(jù)1997年美國風(fēng)濕病學(xué)會制定的SLE診斷標(biāo)準(zhǔn),本例滿足11項(xiàng)診斷要點(diǎn)中的5項(xiàng)(關(guān)節(jié)痛、反復(fù)口腔潰瘍、血液系統(tǒng)疾病、免疫學(xué)異常、ANA陽性),可確診SLE。因SLE亦可出現(xiàn)多發(fā)淋巴結(jié)增大,該患者3年前出現(xiàn)的淋巴結(jié)增大與其他SLE癥狀同時(shí)存在,還是SLE造成的淋巴結(jié)增大?由于干酪樣壞死是結(jié)核病特征性表現(xiàn),只有推翻淋巴結(jié)結(jié)核病理診斷,才能考慮淋巴結(jié)增大是SLE癥狀的一部分。但由于時(shí)間久遠(yuǎn),無法獲得當(dāng)初淋巴結(jié)病理片重新閱片,所以該患者為單純SLE或SLE合并結(jié)核,我們不能定論。

      2.3 腎損害原因分析 該患者腎損害較輕,腎小球?yàn)V過率正常,但腎小管損傷表現(xiàn)較突出,包括尿濃縮稀釋功能減退、小分子蛋白尿等,而腎小球損傷相對較輕,也正因?yàn)榇?,我們未行腎活檢。根據(jù)SLE診斷標(biāo)準(zhǔn),24 h尿蛋白達(dá)0.5 g以上才能作為SLE的診斷依據(jù),且患者以腎小管功能障礙為主,故未將腎臟病變列入該患者的診斷依據(jù)。如前所述,該患者腎小管損傷可能為SLE腎小管損傷或藥物性腎小管損傷。SLE腎損害雖以腎小球病變?yōu)橹?,但腎小管病變并非罕見?;颊哂杼瞧べ|(zhì)激素等藥物治療4個月后24 h尿蛋白轉(zhuǎn)陰,但夜尿增多癥狀未見明顯改善,且患者夜尿增多癥狀出現(xiàn)于抗結(jié)核治療中后期,考慮患者腎小管損傷為抗結(jié)核藥物引起的藥物性損傷可能性大。

      2.4 SLE病因鑒別 患者在服用異煙肼等抗結(jié)核藥物后出現(xiàn)SLE相關(guān)癥狀,是否可能為異煙肼所誘導(dǎo)的藥物性狼瘡?藥物性狼瘡是指由于服用藥物后出現(xiàn)發(fā)熱、皮疹、關(guān)節(jié)痛、漿膜炎、ANA及抗組蛋白抗體陽性等類似狼瘡樣表現(xiàn)的一種臨床綜合征,好發(fā)于老年患者。異煙肼被明確認(rèn)為是可以誘導(dǎo)藥物性狼瘡的藥物。與普通SLE相比,藥物性狼瘡引起腎臟和中樞神經(jīng)系統(tǒng)損害較少,較多表現(xiàn)為亞急性皮膚紅斑狼瘡型,可有發(fā)熱、體重下降等全身癥狀,多數(shù)患者可有非炎癥性對稱性關(guān)節(jié)疼痛,但口腔潰瘍、脫發(fā)、雷諾現(xiàn)象較SLE少見。而且95%的藥物性狼瘡患者出現(xiàn)抗組蛋白抗體、抗單鏈DNA抗體陽性率較高,但抗SM抗體和抗雙鏈DNA抗體多為陰性,補(bǔ)體C3、C4水平多正常[18-19]。以上藥物性狼瘡的臨床特征與該患者基本不符,且患者病初未服用抗結(jié)核藥物時(shí)即出現(xiàn)外周血三系下降,雖當(dāng)時(shí)未行免疫學(xué)檢查,但該患者為異煙肼誘發(fā)的藥物性狼瘡可能性不大。

      綜上,SLE患者部分癥狀不典型,男性患者尤為明顯,皮疹、關(guān)節(jié)痛等典型癥狀出現(xiàn)率低,較易漏誤診[20-24]。故對于不明原因的外周血三系下降伴口腔潰瘍、關(guān)節(jié)痛、淋巴結(jié)增大的老年男性患者應(yīng)警惕SLE的可能,及時(shí)行免疫學(xué)檢查,避免漏誤診。

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      Misdiagnosis Analysis of One Elderly Patient with Systemic Lupus Erythematosus

      YU Chuan-qi, ZONG Xue, ZHANG Chong

      (Department of Nephrology, Xinhua Hospital Affiliated to School of Medicine of Shanghai Jiao Tong University, Shanghai 200092, China)

      Objective To discuss diagnosis and treatment of atypical systemic lupus erythematosus (SLE). Methods Clinical data of one SLE patient misdiagnosed as having lymph node tuberculosis was retrospectively analyzed. Results A 78-years-old male was admitted for foamy urine, increasing nocturia and repeat oral ulcer for one year. The patient was misdiagnosed as having lymph node tuberculosis for multiple mediastinal lymph nodes enlargement 3 years ago by result of lymph node biopsy, but symptoms failed to alleviate by anti-tuberculosis therapy after transferring to tuberculosis hospital. After admission in our hospital, results of antinuclear antibodies and anti-double-stranded DNA antibody were positive, and leukocytes, erythrocytes and hemoglobin levels in peripheral blood were decreased, and he had multiple organ injuries such as joint pain and repeat mouth ulcers, and then SLE was confirmed. Symptoms were relieved, and immunological indexes and leukocytes, erythrocytes and hemoglobin levels in peripheral blood were significantly improved after glucocorticoids treatment. Conclusion Part of SLE patients have atypical symptoms, especially in male patients, and therefore it is easily misdiagnosed. Clinicians should consider a diagnosis of SLE for elderly patients with unexplained decline in leukocytes, erythrocytes and hemoglobin levels in peripheral blood associated by oral ulcers, joint pain and lymph nodes enlargement, and immunological test should be performed as early as possible to avoid misdiagnosis and missed diagnosis.

      Systemic lupus erythematosus; lymph node tuberculosis; Male; Misdiagnosis

      200092 上海,上海交通大學(xué)醫(yī)學(xué)院附屬新華醫(yī)院腎臟科

      張翀,E-mail:zhangchongzc@gmail.com

      R593.241

      A

      1002-3429(2017)04-0028-04

      10.3969/j.issn.1002-3429.2017.04.010

      2016-08-23 修回時(shí)間:2017-01-25)

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