恶性萎缩性丘疹病1 例并文献复习

2018-04-25 王丹旭 闵仲生 徐燕 中国皮肤性病学杂志

患者女,60岁。躯干及四肢散在红斑、丘疹4月余。

【一般资料】

患者女,60岁。

【主诉】

躯干及四肢散在红斑、丘疹4月余。

【现病史】

患者4月余前无明显诱因小腿出现少许米粒大小红斑,无自觉症状,未予重视,后向上蔓延至大腿,躯干及前臂依次出现多发红斑、丘疹,皮疹中央凹陷,随后上覆有白色鳞屑,不易脱落,无瘙痒感。患者发病以来无恶寒发热,无腹痛腹泻,无恶心呕吐,无胸闷心慌;既往有“高血压”病史5年,血压控制尚可;4年前因胆囊结石行胆囊切除术,

【既往史】

既往有输血史。

【家族史】

个人史、家族史无特殊。

【体格检查】

浅表淋巴结无肿大,心肺(-)。皮肤科情况:躯干、四肢多发暗红色丘疹,中央萎缩凹陷,形成瓷白色瘢痕,上覆细小鳞屑,皮疹边缘隆起伴红晕(图1~3)。皮损组织病理示:(腹部)表皮角化不全,基底细胞液化变性,真皮乳头层轻度胶原纤维变性,伴真皮浅层小血管周围淋巴单个核细胞浸润(图4~5)。





【辅助检查】

结核感染T细胞试验(-)。肠镜:降结肠黏膜病变,性质待定(炎症?);结肠多发红斑(毛细血管扩张?炎症?)。病理诊断:(横结肠)黏膜中度慢性炎,活动性,局部淋巴组织增生。(降结肠)黏膜中度慢性炎,活动性,间质水肿(图6~7)。



【初步诊断

恶性萎缩性丘疹病。

【治疗】

患者曾在外院治疗4月余,病程中使用“强的松”“钙尔奇D”“沙利度胺”等口服药物治疗,皮损未见改善,仍有少许新发疹出现。后至本院皮肤科门诊予“阿司匹林”加中药煎剂口服2个月,中医治法以益气健脾,理气活血为主,中药方剂具体如下:黄芪25g,党参10g,白术10g,薏苡仁30g,茯苓15g,陈皮6g,枳壳3g,凌霄花10g,丹皮10g,丹参10g,当归10g,川芎6g,玫瑰花6g,鬼箭羽15g,地榆20g,鸡血藤30g,三七5g。患者皮疹消退,变暗变平,未见新发疹。从发病至今随访的4年中,患者多次复查血常规:WBC(1.71~2.97)×109/L[(4.00~10.00)×109/L],N%5.8%~8.5%(0.0%~5.0%),Hb(69~73)×109/L[(100~300)×109/L],血液科会诊,建议行骨穿及活检,患者拒绝,予地榆升白片、利可君片口服对症治疗。3个月前患者劳累后出现心前区及剑突下绞痛,疼痛持续数小时,休息后好转。急查血常规:WBC1.71×109/L↓,Hb69×109/L↓,N%5.8%↑。肝肾功能及心肌酶谱:乳酸脱氢酶304U/L↑(135~225U/L),α-羟丁酸262U/L↑(76~195U/L),肌酸激酶342U/L↑(24~170U/L)。免疫八项:补体C30.64g/L↓(0.79~1.52g/L),补体C40.15g/L↓(0.16~0.38g/L),类风湿因子109.00U/mL↑(<20U/mL)。凝血七项:D二聚体4.56mg/L↑(<0.50mg/L),血浆抗凝酶75%↓(80%~120%)。抗核抗体、ENA多肽、抗中性粒细胞胞浆、抗心磷脂抗体均阴性。肌电图:右下肢近端神经损伤;右侧腓神经损伤。治疗上予阿司匹林及氯吡格雷,阿托伐他汀,倍他乐克口服治疗。治疗后皮疹消退显著,未见新发,心前区绞痛症状缓解。目前,患者皮疹色暗,部分仅剩瘢痕及色沉,偶有新发,大约5~10个/年,皮疹变化缓慢。

【讨论】

恶性萎缩性丘疹病(malignantatrophicpapulosis,MAP)又称Degoes病、致死性皮肤和胃肠道小动脉栓塞症,于1941年由Kohlmeier最早报道,1942年由Degoes正式命名为MAP。本病是一种少见的、常累及多系统的,由于中、小动脉闭塞引起的进行性血管病或血管内皮炎。本病病因不明,可能与凝血异常、纤维溶解抑制功能异常、自身免疫及病毒感染有关,除此之外,Hohwy等发现MAP可能与因子VLeiden的突变有关;Katz等在美国皮肤科学会报道了MAP涉及家族三代的现象,认为此病与遗传(常染色体)有关;Zhao等报道了同时有HIV感染的MAP病例;陈洵礼等报道了MAP合并乙肝表面抗原阳性及HLB27阳性的患者。本病例的患者,女性,4年病程中多次行血液检查均出现WBC及Hb双系减少的情况,补体C3、C4降低,D二聚体明显升高,说明体内有活化的血栓形成,考虑自身免疫疾病与凝血机制异常为本病例主要病理基础。恶性萎缩性丘疹病的诊断主要依靠临床表现及组织病理。本病皮损主要位于躯干及四肢近端,早期呈淡红色丘疹,后期皮疹中央出现瓷白色瘢痕。结合组织病理,中央硬化性或渐进性坏死区,其基底部有闭塞的小动脉等特点进行诊断。本病皮损不同阶段病理表现亦会有所不同,早期皮损的组织病理表现为深层或浅层血管周围炎细胞的浸润,间质中有黏蛋白沉积;充分发展的皮疹,其病理常见典型表现为真皮浅层至深层的楔形坏死区,在坏死区基底部可见血管内皮水肿和透明血栓形成;晚期炎细胞浸润逐渐减少,萎缩的表皮下方真皮胶原硬化。本例患者病理表现考虑为晚期改变。遗憾的是,目前我们仍不能通过组织病理学判断良恶性的MAP。目前认为MAP是一种系统性疾病,除皮肤损害外,最常累及胃肠道和中枢神经系统,还有多脏器的损害如眼、心肺及阴茎等。受累可发生于皮损出现后3周至10年,一旦受累其他系统则预后较差。因此有学者提出将MAP根据预后的不同分为良性与恶性,恶性是一种致死性疾病,最常死因为胃肠道及中枢神经系统疾病,如肠穿孔、腹膜炎、脑梗塞、颅内出血、心包炎、胸膜炎等。约15%的患者皮损仅累及皮肤,为良性病变过程。但是良恶性之间,是否存在重叠部分,一些良性患者是否也会发展为恶性,这有待更多的临床研究。因此,Heymann将MAP重新分类定义为:①具有多系统临床损害的典型MAP,进一步分为以下几种亚型:自身免疫型MAP(有结缔组织病或血管炎相关的临床和/或实验室特征),凝血功能障碍型MAP和病毒诱导相关的MAP;②良性MAP(在随访中,3年内没有出现其他系统损害)。本例患者随访4年,尚未出现致命性的系统损害,但患者既往有基础疾病,高血压病及心血管疾病,除此之外患者肠镜检查及肌电图提示有胃肠道及周围神经损伤,根据既往报道MAP出现多系统损伤后致死率高,因此该例患者仍需严密随访。尽管国内外已有不少MAP的报道,但尚未形成其标准化的治疗方法。Heymann报道了MAP一线治疗的药物包括肝素、香豆素、阿司匹林和双嘧达莫;二线治疗包括苯乙双胍、乙雌烯醇、尼古丁贴片、兰索拉唑(胃肠溃疡)和环孢素;三线治疗包括硫唑嘌呤、环磷酰胺、他克莫司、IVIG和紫外线B光疗法。本病例患者在病程初期也曾使用过糖皮质激素治疗,效果不佳。也有报道指出糖皮质激素的使用可能会引发肠穿孔或其他并发症,糖皮质激素在MAP的治疗尚有争议。国外还有MAP伴腹痛贫血女性使用球囊扩张术后加泼尼松龙治疗12个月未复发的案例。另有报道发现MAP是C5b9/α干扰素介导的血管内皮病变,是一种基因遗传缺陷,在此研究基础上使用人源型抗C5单克隆抗体治疗效果显著,这些都为MAP的治疗提供了新思路。本例患者在使用阿司匹林和氯吡格雷治疗期间,皮损明显减轻,说明抗凝及抗血小板聚集药物在MAP的皮损治疗中有效,糖皮质激素对本例患者无效。此外,本例患者已出现一些系统的累及病变,需密切随访观察。临床上MAP应与淋巴瘤样丘疹病、急性痘疮样苔藓样糠疹、丘疹坏死性结核疹等鉴别,在组织病理上应与红斑狼疮、变应性血管炎、丘疹性黏蛋白病等鉴别。恶性萎缩性丘疹病一旦确诊,应高度警惕患者肠道等其他系统病变,遇到典型腹部体征加之特征性皮疹时应考虑到本病。

原始出处:

王丹旭, 闵仲生, 徐燕,等. 恶性萎缩性丘疹病1例并文献复习[J]. 中国皮肤性病学杂志, 2018(1):61-64.

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  3. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:39 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309358, encodeId=983130935860, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:32 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309357, encodeId=9def30935ede, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:26 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2019-02-23 chendoc252
  4. 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channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:26 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
  5. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:52 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309360, encodeId=47dd3093603e, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:45 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309359, encodeId=0fd63093599b, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:39 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309358, encodeId=983130935860, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:32 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309357, encodeId=9def30935ede, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:26 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-04-26 山楂萌

    谢谢分享

    0

  6. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:52 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309360, encodeId=47dd3093603e, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:45 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309359, encodeId=0fd63093599b, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, 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channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:26 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-04-26 Y—xianghai

    学习了新知识

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1942287, encodeId=54d6194228e48, content=<a href='/topic/show?id=6b418809e8c' target=_blank style='color:#2F92EE;'>#萎缩性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88097, encryptionId=6b418809e8c, topicName=萎缩性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a8e213, createdName=hongbochen, createdTime=Wed Jan 30 18:18:00 CST 2019, time=2019-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685392, encodeId=62c9168539228, content=<a href='/topic/show?id=b76e208e69a' target=_blank style='color:#2F92EE;'>#丘疹病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20876, encryptionId=b76e208e69a, topicName=丘疹病)], attachment=null, authenticateStatus=null, createdAvatar=null, 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:52 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309360, encodeId=47dd3093603e, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:45 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309359, encodeId=0fd63093599b, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, 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channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:26 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-04-26 Y—xianghai

    学习了新知识

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1942287, encodeId=54d6194228e48, content=<a href='/topic/show?id=6b418809e8c' target=_blank style='color:#2F92EE;'>#萎缩性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88097, encryptionId=6b418809e8c, topicName=萎缩性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a8e213, createdName=hongbochen, createdTime=Wed Jan 30 18:18:00 CST 2019, time=2019-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685392, encodeId=62c9168539228, content=<a href='/topic/show?id=b76e208e69a' target=_blank style='color:#2F92EE;'>#丘疹病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20876, encryptionId=b76e208e69a, topicName=丘疹病)], attachment=null, authenticateStatus=null, createdAvatar=null, 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channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Thu Apr 26 07:01:26 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-04-26 Y—xianghai

    学习了新知识

    0

  9. 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    2018-04-26 Y—xianghai

    学习了新知识

    0

  10. 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    2018-04-26 Y—xianghai

    学习了新知识

    0

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