坏疽性脓皮病的临床特征和治疗情况分析

赵景峰; 郝岱峰; 李涛; 冯光

doi:10.3760/cma.j.cn501225-20220317-00068

坏疽性脓皮病的临床特征和治疗情况分析

doi: 10.3760/cma.j.cn501225-20220317-00068

北京阜诚医院创面修复重建中心，北京　　100143

详细信息

通讯作者:
冯光，Email：fengguang_304@aliyun.com

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出版历程
- 收稿日期: 2022-03-17
- 网络出版日期: 2022-08-12
- 刊出日期: 2022-06-20

Analysis of clinical features and treatment of pyoderma gangrenosum

Wound Repair and Reconstruction Center, Beijing Fucheng Hospital, Beijing 100143, China

More Information

Corresponding author: Feng Guang, Email: fengguang_304@aliyun.com

摘要

摘要:
目的探讨坏疽性脓皮病（PG）的临床特征和治疗情况。
方法采用回顾性观察性研究方法。2012年1月—2021年7月，北京阜诚医院收治25例符合入选标准的PG患者，其中男16例、女9例，发病年龄14~75岁，PG分型为溃疡型者17例、脓疱型者6例、增殖型者1例、大疱型者1例，6例患者合并系统性疾病、19例患者未合并系统性疾病。应用糖皮质激素等进行系统治疗的同时，行创面换药或手术植皮处理。统计患者实验室检查及组织病理学检查结果，总体疗效及随访情况，创面分泌物标本微生物培养结果阳性和阴性患者的创面愈合时间，合并和未合并系统性疾病患者的疗效。
结果 19例患者血常规检查结果出现异常，全部患者各项免疫学指标均未见异常；14例患者创面分泌物标本微生物培养结果为阳性；15例创面进展快的患者溃疡边界组织病理学检查结果主要为局部组织炎症改变。17例患者创面治愈、7例患者创面大部分愈合、1例患者创面未愈合。经1年随访，3例患者因出院后自行停药导致PG复发，后调整用药后创面逐渐愈合；其余患者未复发。14例创面分泌物标本微生物培养结果阳性患者创面愈合天数为21~55 d，11例创面分泌物标本微生物培养结果阴性患者创面愈合天数为20~54 d。6例合并系统性疾病患者中3例患者创面治愈、3例患者创面大部分愈合，19例未合并系统性疾病患者中14例患者创面治愈、4例患者创面大部分愈合、1例患者创面未愈合。
结论 PG患者的实验室检查和病理表现无特征性、临床表现丰富多样，因而易被误诊。应用糖皮质激素加免疫抑制剂治疗PG的效果较好，对其创面可进行外科干预，具体为急性期不建议过度清创、收缩期可植皮。
- 坏疽性脓皮病 /
- 伤口愈合 /
- 皮肤
Abstract:
Objective To explore the clinical features and treatment of pyoderma gangrenosum (PG).
Methods A retrospective observational study was conducted. From January 2012 to July 2021, 25 patients with PG who met the inclusion criteria were admitted to Beijing Fucheng Hospital, including 16 males and 9 females, with the age of onset of disease being 14 to 75 years. Among them, the classification of PG identified 17 cases of ulcerative type, 6 cases of pustular type, 1 case of proliferative type, and 1 case of bullous type. Six patients were accompanied with systemic diseases, while 19 patients were not accompanied with systemic diseases. At the same time of systemic treatment with glucocorticoids, dressing changes or surgical skin grafting was performed on the wounds. The results of laboratory and histopathological examinations, the overall curative effects and follow-up of patients, the wound healing time of patients with negative and positive microbial culture results of wound secretion specimens, and the curative effects of patients with and without systemic diseases were analyzed.
Results The results of blood routine examination of 19 patients were abnormal, and all the immunological indexes were normal in all the patients; the microbial culture results of wound secretion specimens were positive in 14 patients; and the histopathological examination results of ulcer boundary tissue in 15 patients with rapid wound progress were mainly local tissue inflammatory changes. The wounds were cured in 17 patients, mostly healed in 7 patients, and not healed in 1 patient. After one-year's follow-up, the PG in 3 patients relapsed due to self-discontinuation of medication after discharge, and the wounds were healed gradually after adjustment of medication, while the remaining patients had no relapse. The days of wound healing in 14 patients with positive microbial culture results of wound secretion specimens were 21-55 days, and the days of wound healing in 11 patients with negative microbial culture results in wound secretion specimens were 20-54 days. In the 6 patients with systemic diseases, the wounds of 3 patients were cured, and the wounds of the other 3 patients were mostly healed. In the 19 patients without systemic diseases, the wounds of 14 patients were cured, the wounds of 4 patients were mostly healed, and the wound of 1 patient was not healed.
Conclusions The laboratory examination and pathological manifestations of patients with PG lacks characteristics, and their clinical manifestations are rich and diverse, thus PG can be easily misdiagnosed. The glucocorticoids combined with immunosuppressive therapy have good effects on PG. Surgical intervention can be performed on the wounds. Specifically, excessive debridement is not recommended in the acute phase, but skin grafting can be performed in the contraction phase.
- Pyoderma gangrenosum /
- Wound healing /
- Skin
赵景峰：数据采集、论文撰写；郝岱峰、冯光：撰写指导、论文修改；李涛：数据整理、统计分析

所有作者均声明不存在利益冲突

获得性大疱性类天疱疮样表皮松解症（EBA）是一种自身抗体驱动的、粒细胞介导的皮肤病。既往研究证据表明，免疫细胞的分化、功能、代谢相互影响，这是免疫反应的先决条件。例如，Th1和M1型巨噬细胞即使在有氧条件下也要依赖于糖酵解，而M2型巨噬细胞、调节性T细胞（Treg）和静止记忆T细胞则主要依赖于氧化磷酸化（OxPhos）。但细胞代谢的作用及其作为EBA治疗靶点的潜力尚不清楚。为此作者研究了2-脱氧-D-葡萄糖和二甲双胍在EBA抗体转移C57BL/6J野生型小鼠中的作用。研究结果显示二甲双胍和2-脱氧-D-葡萄糖均能够在该模型中减轻EBA症状。而后，该项研究证明了免疫复合物对中性粒细胞的刺激增加了有氧糖酵解的速率，并且这种增加是诱导对EBA至关重要的白三烯B4和活性氧的释放所必需的。因此，2-脱氧-D-葡萄糖作为糖酵解酶己糖激酶和磷酸葡萄糖异构酶的抑制剂，庚酸作为GAPDH的抑制剂，减弱了这种中性粒细胞的反应。在超药理学剂量时，二甲双胍能够降低氧化磷酸化水平，也能抑制这种中性粒细胞反应，而在体内二甲双胍却不大可能对中性粒细胞产生直接影响。氧化磷酸化抑制剂寡霉素同样能够抑制这种中性粒细胞反应，且免疫复合物刺激不会改变氧化磷酸化的速率，这意味着中性粒细胞完整线粒体反应是抑制糖代谢反应的基础。总的来说，该研究强调2-脱氧-D-葡萄糖和二甲双胍是治疗EBA的潜在药物，而中性粒细胞的糖酵解和氧化磷酸化都是EBA颇具前景的治疗靶点。

张修航,编译自《J Invest Dermatol》,2021,141(7):1646-1655.e3;于家傲,审校

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1 例1坏疽性脓皮病（脓疱型）患者背部创面的治疗情况。1A.入院时背部创面红肿明显，可探及皮下多方向窦道；1B.入院后7 d背部清创后；1C.入院后7 d于背部行自体头部刃厚皮邮票状皮片移植术后即刻；1D.植皮术后10 d皮片存活不良；1E.入院后20 d右侧髋部新发病灶红肿明显；1F.入院后50 d，2次植皮后创面治愈

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2 例2坏疽性脓皮病（溃疡型）患者胸部创面治疗情况；2A.入院时右胸壁见浅紫色溃疡；2B.入院后7 d肛周新发溃疡；2C.入院后45 d，创面治愈

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参考文献(40)

[1]	GoldustM,HagstromEL,RathodD, et al.Diagnosis and novel clinical treatment strategies for pyoderma gangrenosum[J].Expert Rev Clin Pharmacol,2020,13(2):157-161.DOI: 10.1080/17512433.2020.1709825.
[2]	Santa LuciaG, DeMaioA, KarlinS, et al. A case of extracutaneous pyoderma gangrenosum in a patient with persistent cutaneous and systemic symptoms: implications for differential diagnosis and treatment[J].JAAD Case Rep,2021,15:85-87.DOI: 10.1016/j.jdcr.2021.07.019.
[3]	JinSY, ChenM, WangFY, et al. Applying intravenous immunoglobulin and negative-pressure wound therapy to treat refractory pyoderma gangrenosum: a case report[J].Int J Low Extrem Wounds,2021,20(2):158-161.DOI: 10.1177/1534734620940459.
[4]	GeorgeC,DeroideF,RustinM.Pyoderma gangrenosum - a guide to diagnosis and management[J].Clin Med (Lond),2019,19(3):224-228.DOI: 10.7861/clinmedicine.19-3-224.
[5]	SasorSE,SoleimaniT,ChuMW,et al.Pyoderma gangrenosum demographics, treatments, and outcomes: an analysis of 2,273 cases[J].J Wound Care,2018,27(Suppl 1):S4-8.DOI: 10.12968/jowc.2018.27.Sup1.S4.
[6]	PlatzerKD,KostnerL,VujicI,et al.Clinical characteristics and treatment outcomes of 36 pyoderma gangrenosum patients - a retrospective, single institution observation[J].J Eur Acad Dermatol Venereol,2019,33(12):e474-e475.DOI: 10.1111/jdv.15803.
[7]	IlterN,KeskinN,AdisenE,et al.Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma mimicking pyoderma gangrenosum[J].Australas J Dermatol,2021,62(4):e605-e607.DOI: 10.1111/ajd.13708.
[8]	PinardJ, ChiangDY, MostaghimiA, et al. Wounds that would not heal: pyoderma gangrenosum[J].Am J Med,2018,131(4):377-379.DOI: 10.1016/j.amjmed.2017.12.009.
[9]	BordaLJ, WongLL, MarzanoAV, et al.Extracutaneous involvement of pyoderma gangrenosum[J].Arch Dermatol Res,2019,311(6):425-434.DOI: 10.1007/s00403-019-01912-1.
[10]	ZhangXH, JiaoY. Takayasu arteritis with pyoderma gangrenosum: case reports and literature review[J].BMC Rheumatol,2019,3:45.DOI: 10.1186/s41927-019-0098-z.
[11]	ChakiriR,BaybayH,HatimiAE,et al.Clinical and histological patterns and treatment of pyoderma gangrenosum[J].Pan Afr Med J,2020,36:59.DOI: 10.11604/pamj.2020.36.59.12329.
[12]	冯尘尘,杨转花,李高洁,等. 坏疽性脓皮病诊疗研究进展[J]. 中国麻风皮肤病杂志,2022,38(6):414-418. DOI: 10.12144/zgmfskin202206414.
[13]	AbdelmaksoudA.Pyoderma gangrenosum: a clinical conundrum[J]. J Eur Acad Dermatol Venereol,2018,32(10):e381-e382.DOI: 10.1111/jdv.14977.
[14]	KimYJ,YangHJ,LeeMW,et al.Cutaneous indicator of myelodysplastic syndrome: sudden bullous pyoderma gangrenosum[J].Jpn J Clin Oncol,2020,50(8):958-959.DOI: 10.1093/jjco/hyz207.
[15]	傅汝倩, 康志娟, 李志辉. 化脓性关节炎、坏疽性脓皮病和痤疮综合征孪生兄弟报道[J]. 中华实用儿科临床杂志, 2021, 36(5): 382-384. DOI: 10.3760/cma.j.cn101070-20191015-00985.
[16]	Martinez-RiosC, JariwalaMP, HighmoreK, et al. Imaging findings of sterile pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome: differential diagnosis and review of the literature[J].Pediatr Radiol,2019,49(1):23-36.DOI: 10.1007/s00247-018-4246-1.
[17]	FeldmanSR, LacyFA, HuangWW. The safety of treatments used in pyoderma gangrenosum[J]. Expert Opin Drug Saf,2018,17(1):55-61.DOI: 10.1080/14740338.2018.1396316.
[18]	HrinML,BashyamAM,HuangWW,et al.Mycophenolate mofetil as adjunctive therapy to corticosteroids for the treatment of pyoderma gangrenosum: a case series and literature review[J].Int J Dermatol,2021,60(12):e486-e492.DOI: 10.1111/ijd.15539.
[19]	McKenzieF, CashD, GuptaA, et al.Biologic and small molecule medications in the management of pyoderma gangrenosum[J].J Dermatolog Treat,2019,30(3):264-276.DOI: 10.1080/09546634.2018.1506083.
[20]	信跃文,柴艳芬,姚咏明.皮肤调节性T细胞与创面愈合及免疫疾病的关系研究进展[J].中华烧伤杂志,2020,36(2):156-160.DOI: 10.3760/cma.j.issn.1009-2587.2020.02.015.
[21]	HoffmanKP, ShearerS, ChungC, et al.Clinical and therapeutic overlap of pyoderma gangrenosum, cutaneous small vessel vasculitis, and immunoglobulin A[J].Int J Dermatol,2020,59(8):e286-e288. DOI: 10.1111/ijd.14841.
[22]	王克甲,王耘川,计鹏,等.手术治疗坏疽性脓皮病一例[J].中华烧伤杂志,2016,32(3):187-188.DOI: 10.3760/cma.j.issn.1009-2587.2016.03.014.
[23]	OuazzaniA, BertheJV, de FontaineS.Post-surgical pyoderma gangrenosum: a clinical entity[J]. Acta Chir Belg, 2007,107(4):424-428. DOI: 10.1080/00015458.2007.11680088.
[24]	陈宾,李叶扬,梁岷,等.坏疽性脓皮病误诊为皮肤感染性溃疡一例[J].中华烧伤杂志,2015,31(3):230-231.DOI: 10.3760/cma.j.issn.1009-2587.2015.03.020.
[25]	WangJY, FrenchLE, ShearNH, et al.Drug-induced pyoderma gangrenosum: a review[J]. Am J Clin Dermatol,2018,19(1):67-77. DOI: 10.1007/s40257-017-0308-7.
[26]	曾琳茜,姚越,黄欣,等.生物制剂在坏疽性脓皮病治疗中的研究进展[J/OL].中国皮肤性病学杂志,2022(2022-03-17)[2022-04-22]. https://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13735/j.cjdv.1001-7089.202110142. [网络预发表]. https://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13735/j.cjdv.1001-7089.202110142
[27]	SongH,LahoodN,MostaghimiA.Intravenous immunoglobulin as adjunct therapy for refractory pyoderma gangrenosum: systematic review of cases and case series[J].Br J Dermatol, 2018, 178(2):363-368.DOI: 10.1111/bjd.15850.
[28]	吴超,晋红中.坏疽性脓皮病的辅助检查及治疗[J].中华临床免疫和变态反应杂志,2019,13(4):301-305.DOI: 10.3969/j.issn.1673-8705.2019.04.010.
[29]	刘崔.坏疽性脓皮病的临床特点及治疗分析[J/CD].临床检验杂志:电子版,2017,6(2):290-291.
[30]	Di GuidaA, FabbrociniG, ScalvenziM, et al.Coexistence of bullous pemphigoid and pyoderma gangrenosum[J].J Clin Aesthet Dermatol,2022,15(1):16-17.
[31]	HaJW, HahmJE, KimKS, et al. A case of pyoderma gangrenosum with myelodysplastic syndrome[J].Ann Dermatol,2018,30(3):392-393.DOI: 10.5021/ad.2018.30.3.392.
[32]	HaagC, HansenT, HajarT, et al. Comparison of three diagnostic frameworks for pyoderma gangrenosum[J].J Invest Dermatol,2021,141(1):59-63.DOI: 10.1016/j.jid.2020.04.019.
[33]	吴超,方凯,晋红中.泼尼松联合依那西普治疗并发坏疽性脓皮病的关节病性银屑病[J].临床皮肤科杂志,2016,45(3):197-199.DOI: 10.16761/j.cnki.1000-4963.2016.03.014.
[34]	BaltazarD, HaagC, GuptaAS, et al.A comprehensive review of local pharmacologic therapy for pyoderma gangrenosum[J].Wounds,2019,31(6):151-157.
[35]	褚万立,郝岱峰,赵景峰,等. 慢性创面外露内置物的保全和创面修复临床策略[J]. 中华烧伤杂志,2020,36(6):484-487. DOI: 10.3760/cma.j.cn501120-20190215-00027.
[36]	QureshiA,PersaudK,ZulfiqarS, et al.Atypical pyoderma gangrenosum: a case of delayed recognition[J].J Community Hosp Intern Med Perspect,2021,11(2):242-248. DOI: 10.1080/20009666.2020.1866250.
[37]	Penalba-TorresM,Zarco-OlivoC,Calleja-AlgarraA.Postsurgical pyoderma gangrenosum: a diagnosis we cannot miss[J].Med Clin (Barc),2021,157(12):597.DOI: 10.1016/j.medcli.2021.02.019.
[38]	高琼,薛晓东.创面床准备的研究进展[J].临床医学研究与实践,2017,2(28):194-196.DOI: 10.19347/j.cnki.2096-1413.201728096.
[39]	吴新果,黄茜,周小勇.糖皮质激素联合环孢素A治疗溃疡型坏疽性脓皮病1例[J].中国皮肤性病学杂志,2015,29(11):1203,1207.DOI: 10.13735/j.cjdv.1001-7089.201411011.
[40]	吴志华,郭红卫.糖皮质激素作用机制进展及在皮肤科中的应用[J].皮肤病与性病,2011,33(6):321-324,339.DOI: 10.3969/j.issn.1002-1310.2011.06.004.