坏疽性脓皮病发病机制与诊断的研究进展

杨岚; 杨青文; 付妍婕

doi:10.3760/cma.j.cn501225-20220331-00117

坏疽性脓皮病发病机制与诊断的研究进展

doi: 10.3760/cma.j.cn501225-20220331-00117

1.
滨州医学院第二临床医学院，烟台　　264003
2.
潍坊医学院临床医学院，潍坊　　261053
3.
临沂市人民医院烧伤整形外科，临沂　　276002

基金项目:

山东省自然科学基金面上项目 ZR2021MH338

详细信息

通讯作者:
付妍婕，Email：zcfyjzzy@163.com

计量
- 文章访问数: 845
- HTML全文浏览量: 52
- PDF下载量: 49
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-31

Research advances on the pathogenesis and diagnosis of pyoderma gangrenosum

1.
The Second Clinical Medical College, Binzhou Medical University, Yantai 264003, China
2.
The Clinical Medical College, Weifang Medical University, Weifang 261053, China
3.
Department of Burns and Plastic Surgery, Linyi People's Hospital, Linyi 276002, China

Funds:

General Program of Natural Science Foundation of Shandong Province of China ZR2021MH338

More Information

Corresponding author: Fu Yanjie, Email: zcfyjzzy@163.com

摘要

摘要: 坏疽性脓皮病（PG）是一种罕见的嗜中性皮肤病，与免疫系统密切相关，其发病机制目前并不明确。PG的临床表现及组织病理学变化缺乏特异性，导致其临床诊断周期较长甚至可能被误诊，容易因此延误治疗或促使溃疡创面恶化。目前该病的诊断仍十分困难，给创面修复医师带来了极大的挑战。该文综述了近年来有关PG的病理生理、临床特征、诊断等方面的研究进展，以期为相关临床工作者提供参考。
- 坏疽性脓皮病 /
- 诊断 /
- 病理学，临床 /
- 临床分型
Abstract: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis, closely associated with the immune system. Its pathogenesis is currently not clear. The lack of specificity in the clinical manifestations and histopathological changes of PG leads to a long clinical diagnosis cycle and even misdiagnosis, which is easy to delay treatment or promote the deterioration of ulcer wound. The diagnosis of this disease is still very difficult, which poses a great challenge to wound repair practitioners. This article reviews the research advances on the pathophysiology, clinical features, and diagnosis of PG in recent years, with the aim of providing reference for relevant clinical practitioners.
- Pyoderma gangrenosum /
- Diagnosis /
- Pathology, clinical /
- Clinical typing
所有作者均声明不存在利益冲突

HTML全文

参考文献(45)

[1]	Smith-PliegoM,Contreras-RuizJ,RyanS,et al.Cutaneous malakoplakia masquerading as pyoderma gangrenosum[J].Int Wound J,2017,14(4):658-660.DOI: 10.1111/iwj.12661.
[2]	LanganSM,GrovesRW,CardTR,et al.Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: a retrospective cohort study[J].J Invest Dermatol,2012,132(9):2166-2170.DOI: 10.1038/jid.2012.130.
[3]	AlaviA,FrenchLE,DavisMD,et al.Pyoderma gangrenosum: an update on pathophysiology, diagnosis and treatment[J].Am J Clin Dermatol,2017,18(3):355-372.DOI: 10.1007/s40257-017-0251-7.
[4]	Greenlee-WackerMC.Clearance of apoptotic neutrophils and resolution of inflammation[J].Immunol Rev,2016,273(1):357-370.DOI: 10.1111/imr.12453.
[5]	SatohTK,MellettM,ContassotE,et al.Are neutrophilic dermatoses autoinflammatory disorders?[J].Br J Dermatol,2018,178(3):603-613.DOI: 10.1111/bjd.15105.
[6]	Vignon-PennamenMD,WallachD.Cutaneous manifestations of neutrophilic disease. A study of seven cases[J].Dermatologica,1991,183(4):255-264.DOI: 10.1159/000247696.
[7]	MistryP,Carmona-RiveraC,OmbrelloAK,et al.Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome[J].Ann Rheum Dis,2018,77(12):1825-1833.DOI: 10.1136/annrheumdis-2018-213746.
[8]	WangY,LiM,StadlerS,et al.Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation[J].J Cell Biol,2009,184(2):205-213.DOI: 10.1083/jcb.200806072.
[9]	SørensenOE,BorregaardN.Neutrophil extracellular traps - the dark side of neutrophils[J].J Clin Invest,2016,126(5):1612-1620.DOI: 10.1172/JCI84538.
[10]	PapayannopoulosV.Neutrophil extracellular traps in immunity and disease[J].Nat Rev Immunol,2018,18(2):134-147.DOI: 10.1038/nri.2017.105.
[11]	AdachiY,KindzelskiiAL,CookinghamG,et al.Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma gangrenosum[J].J Invest Dermatol,1998,111(2):259-268.DOI: 10.1046/j.1523-1747.1998.00311.x.
[12]	McKenzieF,ArthurM,Ortega-LoayzaAG. Pyoderma gangrenosum: what do we know now?[J]. Current Dermatology Reports,2018,7(4):147-157.DOI: 10.1007/s13671-018-0224-y.
[13]	AntonelliE,BassottiG,TramontanaM,et al.Dermatological manifestations in inflammatory bowel diseases[J].J Clin Med,2021,10(2):364.DOI: 10.3390/jcm10020364.
[14]	CugnoM,BorghiA,MarzanoAV.PAPA, PASH and PAPASH syndromes: pathophysiology, presentation and treatment[J].Am J Clin Dermatol,2017,18(4):555-562.DOI: 10.1007/s40257-017-0265-1.
[15]	PlumptreI,KnabelD,TomeckiK.Pyoderma gangrenosum: a review for the gastroenterologist[J].Inflamm Bowel Dis,2018,24(12):2510-2517.DOI: 10.1093/ibd/izy174.
[16]	HobbsMM,Ortega-LoayzaAG.Pyoderma gangrenosum: from historical perspectives to emerging investigations[J].Int Wound J,2020,17(5):1255-1265.DOI: 10.1111/iwj.13389.
[17]	MaverakisE,MarzanoAV,LeST,et al.Pyoderma gangrenosum[J].Nat Rev Dis Primers,2020,6(1):81.DOI: 10.1038/s41572-020-0213-x.
[18]	WangEA,SteelA,LuxardiG,et al.Classic ulcerative pyoderma gangrenosum is a T cell-mediated disease targeting follicular adnexal structures: a hypothesis based on molecular and clinicopathologic studies[J].Front Immunol,2018,8:1980.DOI: 10.3389/fimmu.2017.01980.
[19]	CaproniM,AntigaE,VolpiW,et al.The Treg/Th17 cell ratio is reduced in the skin lesions of patients with pyoderma gangrenosum[J].Br J Dermatol,2015,173(1):275-278.DOI: 10.1111/bjd.13670.
[20]	QuaglinoP,FavaP,CaproniM,et al.Phenotypical characterization of circulating cell subsets in pyoderma gangrenosum patients: the experience of the Italian immuno-pathology group[J].J Eur Acad Dermatol Venereol,2016,30(4):655-658.DOI: 10.1111/jdv.13100.
[21]	NesterovitchAB,GyorfyZ,HoffmanMD,et al.Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses[J].Am J Pathol,2011,178(4):1434-1441.DOI: 10.1016/j.ajpath.2010.12.035.
[22]	NesterovitchAB,SzantoS,GondaA,et al.Spontaneous insertion of a b2 element in the Ptpn6 gene drives a systemic autoinflammatory disease in mice resembling neutrophilic dermatosis in humans[J].Am J Pathol,2011,178(4):1701-1714.DOI: 10.1016/j.ajpath.2010.12.053.
[23]	NesterovitchAB,ArbievaZ,TothDM,et al.A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice[J].J Dermatol Sci,2016,83(1):17-25.DOI: 10.1016/j.jdermsci.2016.03.005.
[24]	SoodAK,McShaneDB,GoogePB,et al.Successful treatment of PAPA syndrome with dual adalimumab and tacrolimus therapy[J].J Clin Immunol,2019,39(8):832-835.DOI: 10.1007/s10875-019-00685-6.
[25]	WangY,WuN,YuK,et al.Case report: pyogenic arthritis, pyoderma gangrenosum, and acne: a single-center experience and literature review[J].Front Immunol,2021,12:735851.DOI: 10.3389/fimmu.2021.735851.
[26]	MaitrepierreF,MarzanoAV,LipskerD.A unified concept of acne in the PAPA spectrum disorders[J].Dermatology,2021,237(5):827-834.DOI: 10.1159/000509874.
[27]	AhnC,NegusD,HuangW.Pyoderma gangrenosum: a review of pathogenesis and treatment[J].Expert Rev Clin Immunol,2018,14(3):225-233.DOI: 10.1080/1744666X.2018.1438269.
[28]	Alonso-LeónT,Hernández-RamírezHH,Fonte-AvalosV,et al.The great imitator with no diagnostic test: pyoderma gangrenosum[J].Int Wound J,2020,17(6):1774-1782.DOI: 10.1111/iwj.13466.
[29]	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.
[30]	SullivanSN.Bullous pyoderma gangrenosum and inflammatory bowel disease[J].Inflamm Bowel Dis,2018,24(5):e16-e17.DOI: 10.1093/ibd/izy018.
[31]	ShavitE,CecchiniM,LimacherJJ,et al.Superficial granulomatous pyoderma gangrenosum involving the face: a case series of five patients and a review of the literature [formula: see text][J].J Cutan Med Surg,2021,25(4):371-376.DOI: 10.1177/1203475420988864.
[32]	AfifiL,SanchezIM,WallaceMM,et al.Diagnosis and management of peristomal pyoderma gangrenosum: a systematic review[J].J Am Acad Dermatol,2018,78(6):1195-1204.e1.DOI: 10.1016/j.jaad.2017.12.049.
[33]	PearsonWA,PrenticeDA,SinclairDL,et al.A novel topical therapy for resistant and early peristomal pyoderma gangrenosum[J].Int Wound J,2019,16(5):1136-1143.DOI: 10.1111/iwj.13164.
[34]	XuA,BalgobindA,StrunkA,et al.Prevalence estimates for pyoderma gangrenosum in the United States: an age- and sex-adjusted population analysis[J].J Am Acad Dermatol,2020,83(2):425-429.DOI: 10.1016/j.jaad.2019.08.001.
[35]	GuptaAS,Ortega-LoayzaAG.Ocular pyoderma gangrenosum: a systematic review[J].J Am Acad Dermatol,2017,76(3):512-518.DOI: 10.1016/j.jaad.2016.08.049.
[36]	ScherlingerM,GuilletS,DoutreMS,et al.Pyoderma gangrenosum with extensive pulmonary involvement[J].J Eur Acad Dermatol Venereol,2017,31(4):e214-e216.DOI: 10.1111/jdv.13976.
[37]	KridinK,CohenAD,AmberKT.Underlying systemic diseases in pyoderma gangrenosum: a systematic review and meta-analysis[J].Am J Clin Dermatol,2018,19(4):479-487.DOI: 10.1007/s40257-018-0356-7.
[38]	WallachD,Vignon-PennamenMD.Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses[J].Br J Dermatol,2018,178(3):595-602.DOI: 10.1111/bjd.13955.
[39]	FloraA,KozeraE,FrewJW.Pyoderma gangrenosum: a systematic review of the molecular characteristics of disease[J].Exp Dermatol,2022,31(4):498-515.DOI: 10.1111/exd.14534.
[40]	MarzanoAV,BorghiA,WallachD,et al.A comprehensive review of neutrophilic diseases[J].Clin Rev Allergy Immunol,2018,54(1):114-130.DOI: 10.1007/s12016-017-8621-8.
[41]	LandisET,TaheriA,JorizzoJL.Gulliver's sign: a recognizable transition from inflammatory to healing stages of pyoderma gangrenosum[J].J Dermatolog Treat,2015,26(2):171-172.DOI: 10.3109/09546634.2014.883061.
[42]	SkopisM,ElghawyAA,PociurkoB,et al.Pyoderma gangrenosum associated with limited cutaneous systemic sclerosis: a rare case with literature review[J].Clin Rheumatol,2021,40(3):1141-1145.DOI: 10.1007/s10067-020-05285-z.
[43]	JockenhöferF,WollinaU,SalvaKA,et al.The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum[J].Br J Dermatol,2019,180(3):615-620.DOI: 10.1111/bjd.16401.
[44]	MaverakisE,MaC,ShinkaiK,et al.Diagnostic criteria of ulcerative pyoderma gangrenosum: a Delphi consensus of international experts[J].JAMA Dermatol,2018,154(4):461-466.DOI: 10.1001/jamadermatol.2017.5980.
[45]	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.

表1 诊断坏疽性脓皮病的PARACELSUS评分量表

诊断标准内容	标准等级	标准评分（分）
病程进展迅速	主要标准	3
相关鉴别诊断的评估	主要标准	3
紫红色溃疡边缘	主要标准	3
对免疫抑制剂反应良好	次要标准	2
典型的不规则形状溃疡	次要标准	2
极度疼痛，VAS评分>4分	次要标准	2
病灶位于创伤部位	次要标准	2
组织病理学证实化脓性炎症	附加标准	1
边缘潜行的溃疡	附加标准	1
与系统性疾病相关	附加标准	1
注：该表引自文献[43];PARACELSUS中各字母为各诊断标准（从上到下依次排列）英文首字母，VAS为视觉模拟评分法