Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies
BackgroundPyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood...
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-01-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01980/full |
id |
doaj-fe3ea2b9197646ba9e0c3fd94e1b89c6 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elizabeth A. Wang Andrea Steel Guillaume Luxardi Anupam Mitra Forum Patel Michelle Y. Cheng Reason Wilken Jason Kao Kristopher de Ga Hawa Sultani Alexander A. Merleev Alina I. Marusina Alain Brassard Maxwell A. Fung Maxwell A. Fung Thomas Konia Thomas Konia Michiko Shimoda Emanual Maverakis |
spellingShingle |
Elizabeth A. Wang Andrea Steel Guillaume Luxardi Anupam Mitra Forum Patel Michelle Y. Cheng Reason Wilken Jason Kao Kristopher de Ga Hawa Sultani Alexander A. Merleev Alina I. Marusina Alain Brassard Maxwell A. Fung Maxwell A. Fung Thomas Konia Thomas Konia Michiko Shimoda Emanual Maverakis Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies Frontiers in Immunology pyoderma gangrenosum CD4 T cell autoimmune cytokine pilosebaceous unit |
author_facet |
Elizabeth A. Wang Andrea Steel Guillaume Luxardi Anupam Mitra Forum Patel Michelle Y. Cheng Reason Wilken Jason Kao Kristopher de Ga Hawa Sultani Alexander A. Merleev Alina I. Marusina Alain Brassard Maxwell A. Fung Maxwell A. Fung Thomas Konia Thomas Konia Michiko Shimoda Emanual Maverakis |
author_sort |
Elizabeth A. Wang |
title |
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies |
title_short |
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies |
title_full |
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies |
title_fullStr |
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies |
title_full_unstemmed |
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies |
title_sort |
classic ulcerative pyoderma gangrenosum is a t cell-mediated disease targeting follicular adnexal structures: a hypothesis based on molecular and clinicopathologic studies |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-01-01 |
description |
BackgroundPyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood.ObjectiveUse data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology.MethodsTen PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR.ResultsAll PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype.LimitationsSmall sample size was the main limitation.ConclusionWe put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units. |
topic |
pyoderma gangrenosum CD4 T cell autoimmune cytokine pilosebaceous unit |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01980/full |
work_keys_str_mv |
AT elizabethawang classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT andreasteel classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT guillaumeluxardi classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT anupammitra classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT forumpatel classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT michelleycheng classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT reasonwilken classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT jasonkao classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT kristopherdega classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT hawasultani classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT alexanderamerleev classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT alinaimarusina classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT alainbrassard classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT maxwellafung classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT maxwellafung classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT thomaskonia classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT thomaskonia classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT michikoshimoda classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies AT emanualmaverakis classiculcerativepyodermagangrenosumisatcellmediateddiseasetargetingfollicularadnexalstructuresahypothesisbasedonmolecularandclinicopathologicstudies |
_version_ |
1725654204870033408 |
spelling |
doaj-fe3ea2b9197646ba9e0c3fd94e1b89c62020-11-24T22:56:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.01980316327Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic StudiesElizabeth A. Wang0Andrea Steel1Guillaume Luxardi2Anupam Mitra3Forum Patel4Michelle Y. Cheng5Reason Wilken6Jason Kao7Kristopher de Ga8Hawa Sultani9Alexander A. Merleev10Alina I. Marusina11Alain Brassard12Maxwell A. Fung13Maxwell A. Fung14Thomas Konia15Thomas Konia16Michiko Shimoda17Emanual Maverakis18Department of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Pathology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Pathology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesDepartment of Dermatology, University of California, Davis, Sacramento, CA, United StatesBackgroundPyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood.ObjectiveUse data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology.MethodsTen PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR.ResultsAll PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype.LimitationsSmall sample size was the main limitation.ConclusionWe put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01980/fullpyoderma gangrenosumCD4T cellautoimmunecytokinepilosebaceous unit |