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Becker SL, Vague M, Ortega-Loayza AG. Insights into the Pathogenesis of Pyoderma Gangrenosum. J Invest Dermatol 2024:S0022-202X(24)02960-9. [PMID: 39718519 DOI: 10.1016/j.jid.2024.09.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/31/2024] [Accepted: 09/25/2024] [Indexed: 12/25/2024]
Abstract
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unclear etiology. Numerous theories of its underlying pathogenesis have been proposed, including external triggers, neutrophilic dysfunction, complement activation, and autoimmunity, as well as a possible component of underlying genetic susceptibility. This review seeks to synthesize current understanding of the pathogenesis of PG and integrate interactions between the multitude of implicated host immune pathways to guide and inform future directions into the treatment of PG.
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Affiliation(s)
- Sarah L Becker
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Morgan Vague
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Alex G Ortega-Loayza
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA.
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Yadav R, Vague M, Rettig M, Loo CP, Brown K, Samiea A, Moreau JM, Ortega-Loayza AG. IL-12/IL-23 Blockade Reveals Patterns of Asynchronous Inflammation in Pyoderma Gangrenosum. J Invest Dermatol 2024:S0022-202X(24)02181-X. [PMID: 39393505 DOI: 10.1016/j.jid.2024.08.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 10/13/2024]
Affiliation(s)
- Rashi Yadav
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, Oregon, USA
| | - Morgan Vague
- Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA
| | - Malia Rettig
- Division of Oncological Sciences, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA
| | - Christopher P Loo
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, Oregon, USA
| | - Kasidy Brown
- Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA
| | - Abrar Samiea
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, Oregon, USA; Division of Oncological Sciences, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA
| | - Joshua M Moreau
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, Oregon, USA; Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA; Division of Oncological Sciences, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA.
| | - Alex G Ortega-Loayza
- Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA
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Kridin K, Ankary-Khaner M, Kridin M, Cohen AD, Badarny S. Hematological malignancy-associated pyoderma gangrenosum: evaluating the magnitude of the association. Front Med (Lausanne) 2024; 11:1425454. [PMID: 39118665 PMCID: PMC11306151 DOI: 10.3389/fmed.2024.1425454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 07/17/2024] [Indexed: 08/10/2024] Open
Abstract
Background Hematologic malignancies (HMs) are well-known underlying comorbidities of pyoderma gangrenosum (PG). However, studies quantifying the likelihood of PG after HMs are yet to be performed. Objective To investigate the bidirectional association between PG and several HMs, namely acute leukemia, chronic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma. Methods A population-based retrospective cohort study was conducted to study the risk of HMs in patients with PG (n = 302) as compared to age-, sex-and ethnicity-matched control subjects (n = 1,799). A case-control design was used to estimate the likelihood of PG in individuals with a preexisting history of HMs. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively. Results The prevalence of preexisting HM was higher in patients with PG than in controls (6.7% vs. 0.9%, respectively). The likelihood of having PG was significantly greater among patients with a history of HM (adjusted OR, 7.88; 95% CI, 3.85-16.15; p < 0.001), particularly during the first year following the diagnosis. This association was significant for acute leukemia, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma but not for Hodgkin lymphoma. The incidence rate of HM was 3.3 (95% CI, 1.2-7.4) and 1.6 (95% CI, 0.9-2.6)/1,000 person-years among patients with PG and controls, respectively. Relative to controls, patients with PG were not more likely to develop subsequent HM (adjusted HR, 2.22; 95%CI, 0.77-6.45; p = 0.142). Compared to other patients with PG, those with HM-associated PG experienced an increased all-cause mortality rate (adjusted HR, 2.19; 95%CI, 1.09-4.40; p = 0.028). Conclusion HM, particularly acute leukemia and multiple myeloma, are associated with an elevated likelihood of provoking PG.
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Affiliation(s)
- Khalaf Kridin
- Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
| | | | | | - Arnon D. Cohen
- Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
- Clalit Health Services, Tel-Aviv, Israel
| | - Samih Badarny
- Department of Neurology, Galilee Medical Center, Nahariya, Israel
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Yadav R, Vague M, Rettig M, Loo CP, Brown K, Samiea A, Moreau JM, Ortega-Loayza AG. IL-12/IL23 blockade reveals patterns of asynchronous inflammation in pyoderma gangrenosum. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.26.591387. [PMID: 38746177 PMCID: PMC11092430 DOI: 10.1101/2024.04.26.591387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis causing chronic and recalcitrant painful ulcerations. Pathogenic mechanisms are yet poorly understood limiting therapeutic options, however, IL-12/IL-23 inhibition via ustekinumab has previously been associated with positive outcomes. We aimed to elucidate the dysregulated immune landscape of PG and lesional skin changes associated with IL-12/IL-23 blockade. We applied spatial transcriptomics and comparative computation analysis on lesional biopsies from two patients obtained before and after IL-12/IL-23 blockade with ustekinumab. Our data indicate lesional PG skin exhibits complex patterns of inflammation, including a not previously described major infiltration of B cells and establishment of tertiary lymphoid structures. In both patients, IL-12/IL-23 blockade led to marked clinical improvement but was associated with amelioration of contrasting inflammatory pathways. Notably, plasma cell markers and tertiary structures were recalcitrant to the treatment regime suggesting that B cells might play a role in the refractory nature of PG.
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Łyko M, Ryguła A, Kowalski M, Karska J, Jankowska-Konsur A. The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives. Int J Mol Sci 2024; 25:2440. [PMID: 38397117 PMCID: PMC10889749 DOI: 10.3390/ijms25042440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/08/2024] [Accepted: 02/15/2024] [Indexed: 02/25/2024] Open
Abstract
Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs and small molecules administered for coexisting diseases, resulting in ulcer healing. In this review, we summarize the discoveries regarding the pathophysiology of PG and present treatment options to raise awareness and improve the management of this rare entity.
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Affiliation(s)
- Magdalena Łyko
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Anna Ryguła
- Student Research Group of Experimental Dermatology, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.R.); (M.K.); (J.K.)
| | - Michał Kowalski
- Student Research Group of Experimental Dermatology, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.R.); (M.K.); (J.K.)
| | - Julia Karska
- Student Research Group of Experimental Dermatology, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.R.); (M.K.); (J.K.)
- Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland
| | - Alina Jankowska-Konsur
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
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Satoh TK. Genetic mutations in pyoderma gangrenosum, hidradenitis suppurativa, and associated autoinflammatory syndromes: Insights into pathogenic mechanisms and shared pathways. J Dermatol 2024; 51:160-171. [PMID: 38031879 PMCID: PMC11484153 DOI: 10.1111/1346-8138.17028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 10/24/2023] [Indexed: 12/01/2023]
Abstract
Pyoderma gangrenosum (PG), hidradenitis suppurativa (HS), and the associated autoinflammatory syndromes, including pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome, and pyogenic arthritis, pyoderma gangrenosum, acne, and suppurative hidradenitis (PAPASH) syndrome are dermatological conditions characterized by chronic inflammation and tissue damage. Recent advances in genetic research have identified specific mutations associated with these disorders, shedding light on their underlying pathogenic mechanisms. This review aims to summarize the current knowledge of identified mutations and presumed pathophysiology in PG, HS, and the associated autoinflammatory syndromes.
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Affiliation(s)
- Takashi K. Satoh
- Department of Dermatology and AllergyUniversity Hospital, LMUMunichGermany
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7
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Xiong H, Ji L, Yang J, Wan J, Song M, Liu G, Yang L, Dong X. Analysis of CD8 + TCRβ Chain repertoire in peripheral blood of vitiligo via high-throughput sequencing. Mol Immunol 2023; 160:112-120. [PMID: 37421821 DOI: 10.1016/j.molimm.2023.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 06/11/2023] [Accepted: 06/24/2023] [Indexed: 07/10/2023]
Abstract
Vitiligo is an autoimmune depigmentation dermatosis induced by melanocyte destruction, and CD8+ T cells play a pivotal role in melanocyte destruction. However, an accurate profile of the CD8+ T cell receptor (TCR) repertoire in vitiligo patients has not been reported, and the clonotype features of the involved CD8+ T cells remain largely unknown. This study aimed to assess the TCRβ chain repertoire diversity and composition of blood in nine nonsegmental vitiligo patients via high-throughput sequencing. Vitiligo patients manifested a low TCRβ repertoire diversity with highly expanded clones. Differential usage of TRBV, the TRBJ gene, and the TRBV/TRBJ combination were compared between patients with vitiligo and healthy controls. A set of TRBV/TRBJ combinations could differentiate patients with vitiligo from healthy controls (area under the curve = 0.9383, 95% CI: 0.8167-1.00). Our study revealed distinct TCRβ repertoires of CD8+ T cells in patients with vitiligo and will help explore novel immune biomarkers and potential therapeutic targets for vitiligo.
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Affiliation(s)
- Hao Xiong
- Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
| | - Liyan Ji
- Beijing GenePlus Genomics Institute, China
| | - Jin Yang
- Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jianji Wan
- Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
| | | | - Guangren Liu
- Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
| | - Ling Yang
- Beijing GenePlus Genomics Institute, China
| | - Xiuqin Dong
- Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
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Sondermann W, Fischer L, Hadaschik E, Dissemond J. Exacerbated Psoriasis as a Rare Trigger of Multilocular Pyoderma Gangrenosum: A Case Report of a Rare Coincidence. INT J LOW EXTR WOUND 2023; 22:213-215. [PMID: 35220791 PMCID: PMC9902962 DOI: 10.1177/1534734621990297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Wiebke Sondermann
- Department of Dermatology, Venereology and Allergology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Laura Fischer
- Department of Dermatology, Venereology and Allergology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Eva Hadaschik
- Department of Dermatology, Venereology and Allergology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Joachim Dissemond
- Department of Dermatology, Venereology and Allergology, University Hospital Essen, University Duisburg-Essen, Essen, Germany,Joachim Dissemond, Department of Dermatology, Venereology, and Allergology, University Hospital Essen, Hufelandstr 55, Essen 45147, Germany.
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9
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Macleod T, Bridgewood C, McGonagle D. Role of neutrophil interleukin-23 in spondyloarthropathy spectrum disorders. THE LANCET. RHEUMATOLOGY 2023; 5:e47-e57. [PMID: 38251507 DOI: 10.1016/s2665-9913(22)00334-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/17/2022] [Accepted: 10/26/2022] [Indexed: 12/24/2022]
Abstract
Neutrophilic inflammation is a pervasive characteristic common to spondyloarthropathies and related disorders. This inflammation manifests as Munro's microabscesses of the skin and osteoarticular neutrophilic inflammation in patients with psoriatic arthritis, intestinal crypt abscesses in patients with inflammatory bowel disease, ocular hypopyon in anterior uveitis, and neutrophilic macroscopic and microscopic inflammation in patients with Behçet's disease. Strong MHC class I associations are seen in these diseases, which represent so-called MHC-I-opathies, and these associations indicate an involvement of CD8 T-cell immunopathology that is not yet well understood. In this Personal View, we highlight emerging data suggesting that the T-cell-neutrophil axis involves both a T-cell-mediated and interleukin (IL)-17-mediated (type 17) recruitment and activation of neutrophils, and also a sequestration of activated neutrophils at disease sites that might directly amplify type 17 T-cell responses. This amplification likely involves neutrophilic production of IL-23 and proteases as well as other feedback mechanisms that could be regulated by local microbiota, pathogens, or tissue damage. This crosstalk between innate and adaptive immunity offers a novel explanation for how bacterial and fungal microbes at barrier sites could innately control type 17 T-cell development, with the aim of restoring tissue homoeostasis, and could potentially explain features of clinical disease and treatment response, such as the fast-onset action of the IL-23 pathway blockade in certain patients. This axis could be crucial to understanding non-response to IL-23 inhibitors among patients with ankylosing spondylitis, as the axial skeleton is a site rich in neutrophils and a site of haematopoiesis with myelopoiesis in adults.
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Affiliation(s)
- Tom Macleod
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Charles Bridgewood
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Dennis McGonagle
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals, Leeds, UK.
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10
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Owen BS, Pacult MA, Lee BS. Pyoderma Gangrenosum Masquerading as Wound Infection in the Early Postoperative Period After Lumbar Spine Deformity Correction Surgery. Cureus 2022; 14:e25545. [PMID: 35800799 PMCID: PMC9246455 DOI: 10.7759/cureus.25545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/27/2022] [Indexed: 11/05/2022] Open
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Michel D, Dege T, Kneitz H, Stumpf M, Goebeler M, Schmieder A. Pyoderma gangraenosum als diagnostische und therapeutische
interdisziplinäre Herausforderung. AKTUEL RHEUMATOL 2022. [DOI: 10.1055/a-1798-5164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungDas Pyoderma gangraenosum (PG) ist eine neutrophile Dermatose unklarer Genese,
die sowohl in Assoziation zu hämatologischen und neoplastischen
Systemerkrankungen, chronisch-entzündlichen Darmerkrankungen und
autoinflammatorischen Syndromen als auch idiopathisch auftreten kann. Sowohl die
Diagnosestellung wie auch die Therapie des PG stellen aufgrund seiner
Seltenheit, des Fehlens großer randomisierter kontrollierter Studien und
der unzureichend verstandenen Pathogenese eine Herausforderung in der klinischen
Praxis dar. Diese Übersichtsarbeit beschreibt und diskutiert aktuelle
Erkenntnisse, die das PG als autoinflammatorische Erkrankung beschreiben. Durch
eine Dysregulation von T-Lymphozyten und myeloiden Zellen wie den neutrophilen
Granulozyten kommt es zur Entstehung von Pusteln und
großflächigen Ulzera. Klassische Therapieansätze
umfassen eine anti-inflammatorische topische Therapie, eine Analgesie sowie die
systemische Gabe von Immunmodulantien oder -suppressiva. Neuere, bisher nicht
zugelassene Therapieoptionen sind der Einsatz von Biologika und
JAK-Inhibitoren.
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Affiliation(s)
- Daniel Michel
- Klinik für Dermatologie, Venerologie und Allergologie,
Universitätsklinikum Würzburg, Würzburg,
Germany
| | - Tassilo Dege
- Klinik für Dermatologie, Venerologie und Allergologie,
Universitätsklinikum Würzburg, Würzburg,
Germany
| | - Hermann Kneitz
- Klinik für Dermatologie, Venerologie und Allergologie,
Universitätsklinikum Würzburg, Würzburg,
Germany
| | - Marco Stumpf
- Klinik für Dermatologie, Venerologie und Allergologie,
Universitätsklinikum Würzburg, Würzburg,
Germany
| | - Matthias Goebeler
- Dermatologie, Universitätsklinikum Würzburg Klinik und
Poliklinik für Dermatologie Venerologie und Allergologie,
Würzburg, Germany
| | - Astrid Schmieder
- Klinik für Dermatologie, Venerologie und Allergologie,
Universitätsklinikum Würzburg, Würzburg,
Germany
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12
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Ronicke M, Baur A, Kirr M, Erdmann M, Erfurt-Berge C, Ostalecki C. Epidermotropie von Immunzellen unterscheidet Pyoderma gangraenosum vom Ulcus cruris venosum. J Dtsch Dermatol Ges 2022; 20:619-628. [PMID: 35578412 DOI: 10.1111/ddg.14708_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 11/29/2021] [Indexed: 11/30/2022]
Abstract
HINTERGRUND UND ZIELE Pyoderma gangraenosum ist eine ulzerierende, autoinflammatorische Erkrankung. Es gibt keine eindeutigen histopathologischen Merkmale zur Differenzierung von anderen Ursachen chronischer Wunden wie dem Ulcus cruris venosum. Ziel dieser Studie war es, histopathologische Merkmale von Pyoderma gangraenosum und Unterschiede zu venösen Ulzerationen zu detektieren. PATIENTEN UND METHODIK Acht Gewebeproben von Pyoderma gangraenosum, zwölf Proben von Ulcus cruris venosum und sechs Proben von gesunder Haut wurden einer immunhistologischen Multi-Antigen-Analyse unterzogen. Das Immuninfiltrat und seine räumliche Verteilung wurden anhand von Fluoreszenzbildern mit einer Gewebezytometriesoftware analysiert. ERGEBNISSE Die dichte epidermale Präsenz von CD45RO+ -T-Gedächtnis-Zellen und die Rarefizierung von CD1a+ -Langerhans-Zellen in der Epidermis waren Marker für Pyoderma gangraenosum, welche auch auf eine epidermale Immunreaktion schließen lassen. Darüber hinaus konnte dermal eine hohe Anzahl CD11c+ CD68+ pro-inflammatorischer M1-Makrophagen nachgewiesen werden. Diese überstieg die Anzahl der in venösen Ulzerationen beobachteten Makrophagen deutlich. SCHLUSSFOLGERUNGEN Die histopathologischen Unterschiede zwischen Pyoderma gangraenosum und Ulcus cruris venosum können zur Unterscheidung der beiden Erkrankungen herangezogen werden und somit eine wichtige Hilfe zur schnellen Einleitung einer adäquaten Therapie sein. Darüber hinaus deuten unsere Daten auf einen antigengesteuerten Prozess in der Epidermis hin, möglicherweise unter Beteiligung von CD1a+ Langerhans-Zellen.
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Affiliation(s)
- Moritz Ronicke
- Hautklinik, Universitätsklinikum Erlangen.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nürnberg, Erlangen.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen
| | - Andreas Baur
- Hautklinik, Universitätsklinikum Erlangen.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nürnberg, Erlangen.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen
| | | | - Michael Erdmann
- Hautklinik, Universitätsklinikum Erlangen.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nürnberg, Erlangen.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen
| | - Cornelia Erfurt-Berge
- Hautklinik, Universitätsklinikum Erlangen.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nürnberg, Erlangen.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen
| | - Christian Ostalecki
- Hautklinik, Universitätsklinikum Erlangen.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen
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13
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Ronicke M, Baur A, Kirr M, Erdmann M, Erfurt-Berge C, Ostalecki C. Epidermotropism of inflammatory cells differentiates pyoderma gangrenosum from venous leg ulcers. J Dtsch Dermatol Ges 2022; 20:619-627. [PMID: 35487858 DOI: 10.1111/ddg.14708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 11/29/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND OBJECTIVES Pyoderma gangrenosum is an ulcerative autoinflammatory disease, lacking distinct histopathological characteristics to differentiate from other ulcerating conditions, like venous leg ulcers. The objective of this study was therefore to find histopathological characteristics of pyoderma gangrenosum in a head-to-head comparison to venous leg ulcers. PATIENTS AND METHODS Eight tissue samples of pyoderma gangrenosum, twelve samples of venous leg ulcers and six samples of healthy skin were stained using an immunohistological multi antigen staining technology. The immune infiltrate and its spatial distribution were analyzed with contextual tissue cytometry software using fluorescence images. RESULTS The dense epidermal presence of CD45RO+ memory T cells and the rarefication of CD1a+ Langerhans cells in the epidermis were defining markers for pyoderma gangrenosum, implicating an epidermal immune reaction. In addition, high numbers of CD11c+ CD68+ pro-inflammatory M1 macrophages were detected in the dermis, significantly extending the numbers seen in venous leg ulcers. CONCLUSIONS The histopathological differences found between pyoderma gangrenosum and venous leg ulcer can be used to distinguish between the two diseases and thus provide an important aid for the rapid initiation of adequate therapy. In addition, our data hint at an antigen-driven process in the epidermis, possibly involving CD1a+ Langerhans cells.
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Affiliation(s)
- Moritz Ronicke
- University Hospital Erlangen, Dermatological Department, Ulmenweg 18, Erlangen, 91054, Germany.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nuremberg, Ulmenweg 18, Erlangen, 91054, Germany.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
| | - Andreas Baur
- University Hospital Erlangen, Dermatological Department, Ulmenweg 18, Erlangen, 91054, Germany.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nuremberg, Ulmenweg 18, Erlangen, 91054, Germany.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
| | | | - Michael Erdmann
- University Hospital Erlangen, Dermatological Department, Ulmenweg 18, Erlangen, 91054, Germany.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nuremberg, Ulmenweg 18, Erlangen, 91054, Germany.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
| | - Cornelia Erfurt-Berge
- University Hospital Erlangen, Dermatological Department, Ulmenweg 18, Erlangen, 91054, Germany.,Deutsches Zentrum für Immuntherapie (DZI), FAU Erlangen-Nuremberg, Ulmenweg 18, Erlangen, 91054, Germany.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
| | - Christian Ostalecki
- University Hospital Erlangen, Dermatological Department, Ulmenweg 18, Erlangen, 91054, Germany.,Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
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14
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Flora A, Kozera E, Frew JW. Pyoderma Gangrenosum: A Systematic Review of the Molecular Characteristics of Disease. Exp Dermatol 2022; 31:498-515. [PMID: 35114021 DOI: 10.1111/exd.14534] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 01/18/2022] [Accepted: 01/30/2022] [Indexed: 11/30/2022]
Abstract
Pyoderma Gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can present in numerous heterogeneous clinical presentations and be associated with multiple inflammatory conditions including Rheumatoid Arthritis, inflammatory bowel disease and hidradenitis suppurativa. However, no critical evaluation of the observed molecular characteristics in PG studies in association with their clinical findings has been assessed. Additionally, emerging evidence suggests a potential role for other cell types and immune pathways including B cells, macrophages, autoantibodies, and the complement system in PG although these have not yet been integrated into the pathogenesis of disease. This systematic review aims to critically evaluate the current molecular observations regarding the pathogenesis of PG and discuss associations with clinical characteristics as well as the evidence supporting novel cell types and immune pathways in PG.
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Affiliation(s)
- Akshay Flora
- Ingham Institute for Applied Medical Research.,Department of Dermatology, Liverpool Hospital.,University of New South Wales
| | - Emily Kozera
- Ingham Institute for Applied Medical Research.,Department of Dermatology, Liverpool Hospital
| | - John W Frew
- Ingham Institute for Applied Medical Research.,Department of Dermatology, Liverpool Hospital.,University of New South Wales
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15
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Raghavan SS, Wang JY, Gru AA, Marqueling AL, Teng JMC, Brown RA, Novoa RA, Kim Y, Zehnder J, Zhang BM, Rieger KE. Next-generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides. J Cutan Pathol 2021; 49:252-260. [PMID: 34614220 DOI: 10.1111/cup.14143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 08/10/2021] [Accepted: 09/28/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population. METHODS We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T-cell receptor beta (TRB) and gamma (TRG) genes. RESULTS Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow-up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites. CONCLUSIONS T-cell clonality is a common finding in PL, probably representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma.
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Affiliation(s)
- Shyam S Raghavan
- Department of Pathology, University of Virginia Medical Center, Charlottesville, Virginia, USA
| | - Jennifer Y Wang
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA
| | - Alejandro A Gru
- Department of Pathology, University of Virginia Medical Center, Charlottesville, Virginia, USA
| | - Ann L Marqueling
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA
| | - Joyce M C Teng
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA
| | - Ryanne A Brown
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA.,Department of Pathology, Stanford University Medical Center, Stanford, California, USA
| | - Roberto A Novoa
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA.,Department of Pathology, Stanford University Medical Center, Stanford, California, USA
| | - Youn Kim
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA
| | - James Zehnder
- Department of Pathology, Stanford University Medical Center, Stanford, California, USA
| | - Bing Melody Zhang
- Department of Pathology, Stanford University Medical Center, Stanford, California, USA
| | - Kerri E Rieger
- Department of Dermatology, Stanford University Medical Center, Stanford, California, USA.,Department of Pathology, Stanford University Medical Center, Stanford, California, USA
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16
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Kridin K, Damiani G, Ludwig RJ, Tzur Bitan D, Cohen AD. Estimating the Odds of Ulcerative Colitis-Associated Pyoderma Gangrenosum: A Population-Based Case-Control Study. Dermatology 2021; 237:323-329. [PMID: 33647909 DOI: 10.1159/000512931] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 08/04/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a well-known underlying comorbidity of pyoderma gangrenosum (PG). However, the risk conferred by UC for the subsequent development of PG is yet to be elucidated. We aimed to estimate the magnitude of the association between UC and the subsequent occurrence of PG, which would enable us to assess the odds of PG developing in individuals with a history of UC. METHODS A population-based case-control study was conducted to compare PG patients (n = 302) and age-, sex- and ethnicity-matched control subjects (n = 1,497) regarding the presence of UC. Logistic regression models were utilized for univariate and multivariate analyses. RESULTS The prevalence of preexisting UC was greater in patients with PG than in controls (7.3 vs. 0.5%; p < 0.001). A 15-fold increase in the odds of PG in individuals with preexisting UC was observed (OR 14.62, 95% CI 6.45-33.18). The greatest risk of developing PG occurred in the first years following the diagnosis of UC (OR 35.50, 95% CI 4.35-289.60), and decreased thereafter to 10.03 (95% CI 1.83-55.03), 6.69 (95% CI 1.49-30.02), and 10.03 (95% CI 1.83-55.03) at 1-5, 5-10, and 10-15 years after the diagnosis of UC, respectively. This association retained its statistical significance following the adjustment for confounding factors (adjusted OR 10.78, 95% CI 4.55-25.52). Patients with both PG and UC were younger and had a lower prevalence of smoking than the remaining patients with PG. CONCLUSIONS UC increases the odds of developing PG by 15-fold, with the highest probability of developing PG occurring within the first year after the diagnosis of UC. Patients with UC may be advised to avoid additional precipitating factors for the development of PG.
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Affiliation(s)
- Khalaf Kridin
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany, .,Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel,
| | - Giovanni Damiani
- Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.,Young Dermatologists Italian Network, GISED, Bergamo, Italy.,Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Ralf J Ludwig
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
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17
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Treatment of Pyoderma Gangrenosum in Pediatric Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2020; 1:e008. [DOI: 10.1097/pg9.0000000000000008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 08/03/2020] [Indexed: 11/26/2022]
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18
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Abstract
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG is often associated with a variety of other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis. The cause of PG is not well understood, but PG is generally considered an autoinflammatory disorder. Studies have focused on the role of T cells, especially at the wound margin; these cells may support the destructive autoinflammatory response by the innate immune system. PG is difficult to diagnose as several differential diagnoses are possible; in addition to clinical examination, laboratory tests of biopsied wound tissue are required for an accurate diagnosis, and new validated diagnostic criteria will facilitate the process. Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) to reduce inflammation followed by the addition of more slowly acting immunosuppressive drugs with superior adverse event profiles, including biologics (in particular, anti-tumour necrosis factor (TNF) agents). Appropriate wound care is also essential. Future research should focus on PG-specific outcome measures and PG quality-of-life studies.
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19
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Eisendle K, Thuile T, Deluca J, Pichler M. Surgical Treatment of Pyoderma Gangrenosum with Negative Pressure Wound Therapy and Skin Grafting, Including Xenografts: Personal Experience and Comprehensive Review on 161 Cases. Adv Wound Care (New Rochelle) 2020; 9:405-425. [PMID: 32320362 DOI: 10.1089/wound.2020.1160] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Significance: Pyoderma gangrenosum (PG) is a rare debilitating autoinflammatory ulcerative skin disease. No gold standard has been established for the treatment of PG. The role of surgical interventions and negative pressure wound therapy (NPWT) was discussed controversially until recently as these procedures might pose a trigger to further aggravate the condition. Recent Advances: Recent advances confirm the paradigm change that a surgical approach of PG with split thickness skin grafting (STSG) secured by NPWT is a safe and valuable treatment if performed under adequate immunosuppression. We elaborate this on the hand of a broad literature search retrieving 101 relevant articles describing 138 patients complemented with our personal experience on 23 patients, including 2 patients treated with a porcine xenodressing. Critical Issues: A wide range of surgical approaches have been reported, including xenografts. Treatment was finally successful in 86%, including the xenotransplant cases. Ten percent improved and failures were mainly reported without immunosuppression. Despite halting the inflammatory process, NPWT alone, without skin grafting, does not much accelerate healing time. The best surgical approach appears to be STSG fixed with NPWT as this leads to higher skin graft take. There remains the problem of the chronic nature of PG and the recurrence after tapering of immunosuppression or trauma; therefore, a sustained immunosuppressive treatment is suggested. Future Directions: While surgical treatment is supported by the published data, the exact immunosuppression is still evolving. Due to deeper insights into pathogenesis and growing clinical reports, a broader utilization of biologic treatments and a shift from tumor necrosis factor (TNF)-alpha to interleukin (IL)-12/23 or IL-23 antibodies alone are predictable, as IL-12/23 antibodies show good clinical responses with fewer side effects. The positive results with porcine xenodressings might be due to immunological effects of the xenomaterial; they appear promising, but are preliminary and should be confirmed in a larger patient collective.
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Affiliation(s)
- Klaus Eisendle
- Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Teaching Hospital Bolzano/Bozen, Bolzano/Bozen, Italy
- IMREST Interdisciplinary Medical Research Center South Tyrol, Claudiana, College of Health-Care Professions, Bolzano/Bozen, Italy
| | - Tobias Thuile
- Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Teaching Hospital Bolzano/Bozen, Bolzano/Bozen, Italy
| | - Jenny Deluca
- Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Teaching Hospital Bolzano/Bozen, Bolzano/Bozen, Italy
| | - Maria Pichler
- Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Teaching Hospital Bolzano/Bozen, Bolzano/Bozen, Italy
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20
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Snyder MH, Ampie L, Forrester VJ, Wilson JC, Nguyen JH, Shaffrey CI, Buchholz AL. Postoperative pyoderma gangrenosum after spinal fusion with instrumentation: case report. J Neurosurg Spine 2020; 32:285-291. [PMID: 31653821 DOI: 10.3171/2019.7.spine19708] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 07/31/2019] [Indexed: 11/06/2022]
Abstract
Pyoderma gangrenosum (PG) is a rare inflammatory dermatosis that is most often associated with inflammatory bowel disease, but which can occur as a pathergic reaction around surgical incisions. The authors report the case of a patient who developed postoperative PG over the course of several months after undergoing extensive spinal instrumentation between the T4 and iliac levels. This is only the second such case occurring after spine surgery to be reported. The authors additionally review the literature to characterize treatment approaches and outcomes for this condition. The case highlights a potentially severe adverse effect of surgery that can be difficult to recognize and causes delays in effective treatment. It also demonstrates the importance of multidisciplinary collaboration in the effective care of patients.
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Affiliation(s)
| | | | - Vernon J Forrester
- 2Dermatology, University of Virginia Health System, Charlottesville, Virginia; and
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21
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Herberger K, Dissemond J, Brüggestrat S, Sorbe C, Augustin M. Biologika und Immunglobuline für die Therapie des Pyoderma gangraenosum - Analyse von 52 Patienten. J Dtsch Dermatol Ges 2019; 17:32-42. [PMID: 30615279 DOI: 10.1111/ddg.13741_g] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 06/27/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Katharina Herberger
- Competenzzentrum Versorgungsforschung in der Dermatologie (CVderm), Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg
| | | | - Sarah Brüggestrat
- Competenzzentrum Versorgungsforschung in der Dermatologie (CVderm), Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg
| | - Christina Sorbe
- Competenzzentrum Versorgungsforschung in der Dermatologie (CVderm), Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg
| | - Matthias Augustin
- Competenzzentrum Versorgungsforschung in der Dermatologie (CVderm), Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg
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22
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Abstract
Pyoderma gangrenosum (PG) is a reactive non-infectious inflammatory dermatosis falling under the spectrum of the neutrophilic dermatoses. There are several subtypes, with 'classical PG' as the most common form in approximately 85% cases. This presents as an extremely painful erythematous lesion which rapidly progresses to a blistered or necrotic ulcer. There is often a ragged undermined edge with a violaceous/erythematous border. The lower legs are most frequently affected although PG can present at any body site. Other subtypes include bullous, vegetative, pustular, peristomal and superficial granulomatous variants. The differential diagnosis includes all other causes of cutaneous ulceration as there are no definitive laboratory or histopathological criteria for PG. Underlying systemic conditions are found in up to 50% of cases and thus clinicians should investigate thoroughly for such conditions once a diagnosis of PG has been made. Treatment of PG remains largely anecdotal, with no national or international guidelines, and is selected according to severity and rate of progression. Despite being a well-recognised condition, there is often a failure to make an early diagnosis of PG. This diagnosis should be actively considered when assessing ulcers, as prompt treatment may avoid the complications of prolonged systemic therapy, delayed wound healing and scarring.
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23
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24
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Xiong H, Wang L, Jiang M, Chen S, Yang F, Zhu H, Zhu Q, Tang C, Qin S, Xing Q, Luo X. Comprehensive assessment of T cell receptor β repertoire in Stevens-Johnson syndrome/toxic epidermal necrolysis patients using high-throughput sequencing. Mol Immunol 2019; 106:170-177. [PMID: 30623817 DOI: 10.1016/j.molimm.2019.01.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Revised: 12/01/2018] [Accepted: 01/02/2019] [Indexed: 12/17/2022]
Abstract
Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse drug reactions characterized by widespread epidermal necrosis. Recent studies have indicated that SJS/TEN is a specific immune reaction regulated by T cells. Certain drug serves as foreign antigens that are presented by major histocompatibility complex (MHC) and recognized by T cell receptors (TCRs), inducing adaptive immune responses. However, few studies have performed detailed characterization of TCR repertoire in SJS/TEN, and it remains unclear whether the particular types of TCRs expanded clonally are drug-specific, which would provide a potential underlying mechanism of SJS/TEN. In this study, using high-throughput sequencing, we comprehensively assessed the diversity, composition and molecular characteristics of the TCRβ repertoires in 17 SJS/TEN patients associated with three different causative drugs including methazolamide (MZ), carbamazepine (CBZ) and allopurinol (ALP). Systematic analysis of the TCRβ sequences revealed that SJS/TEN patients had more highly expanded clones and less TCR repertoire diversity, and the TCR repertoire diversity of these patients showed certain associations with the clinical severity of disease. Similar predominant clonotypes, shared-usage TRBV/TRBJ subtypes and combinations thereof were observed among different subjects with the same causative agent. Our observations provide enhanced understanding of the role of T lymphocytes in the pathogenesis of SJS/TEN and enumerate potential therapeutic targets.
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Affiliation(s)
- Hao Xiong
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Lanting Wang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Menglin Jiang
- Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Shengan Chen
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Fanping Yang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Huizhong Zhu
- Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Qinyuan Zhu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Chenling Tang
- BGI-Shenzhen, Shenzhen, 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China
| | - Shengying Qin
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Qinghe Xing
- Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
| | - Xiaoqun Luo
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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25
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Herberger K, Dissemond J, Brüggestrat S, Sorbe C, Augustin M. Biologics and immunoglobulins in the treatment of pyoderma gangrenosum - analysis of 52 patients. J Dtsch Dermatol Ges 2018; 17:32-41. [PMID: 30592563 DOI: 10.1111/ddg.13741] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 06/27/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND OBJECTIVES Corticosteroids and cyclosporine A are frequently ineffective as first-line therapies in the treatment of pyoderma gangrenosum (PG) and associated with a number of adverse effects. The objective of the present study was to analyze the effectiveness and safety of biologics and intravenous immunoglobulins (IVIGs). PATIENTS AND METHODS Retrospective, dual-center cohort study analyzing the treatment outcome in patients with PG who received biologics and IVIGs. RESULTS Fifty-two patients (mean age: 58.4 years) with 75 wound episodes (mean wound size: 53.2 cm²) were included in the study. Overall, 92.3 % of patients initially received corticosteroids (CSs; 48/52); 51.9 % cyclosporine A (CSA; 27/52). In 275 therapeutic attempts, complete remission or improvement were achieved in 63.6 % (21/33) of patients on infliximab; 57.1 % (16/28) on adalimumab; 71.4 % (5/7) on etanercept; 66.6 % (6/9) on ustekinumab and 66.7 % (10/15) of patients who were given IVIGs. That figure was 48.8 % (38/78) for those treated with CSs and 20.0 % (7/35) for individuals on CSA. On average, adverse events occurred in 18.5 % (15/81) of cases treated with biologics in 20 % (3/15) of patients receiving IVIGs, in 40 % (14/35) of individuals on CSA and in 10.4 % of those treated with CSs (5/48). CONCLUSIONS The present retrospective analysis suggests that both biologics - especially TNFα antagonists - and IVIGs are well-tolerated and safe options in the treatment of PG. Data from prospective comparative studies would be highly desirable.
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Affiliation(s)
- Katharina Herberger
- Center of Competence for Health Care Research in Dermatology (CVderm), Institute for Health Care Research in Dermatology and Nursing (IVDP), Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | - Joachim Dissemond
- Department of Dermatology, Essen University Medical Center, Essen, Germany
| | - Sarah Brüggestrat
- Center of Competence for Health Care Research in Dermatology (CVderm), Institute for Health Care Research in Dermatology and Nursing (IVDP), Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | - Christina Sorbe
- Center of Competence for Health Care Research in Dermatology (CVderm), Institute for Health Care Research in Dermatology and Nursing (IVDP), Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | - Matthias Augustin
- Center of Competence for Health Care Research in Dermatology (CVderm), Institute for Health Care Research in Dermatology and Nursing (IVDP), Hamburg-Eppendorf University Medical Center, Hamburg, Germany
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26
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Satake M, Sakuraba H, Hiraga H, Tarakita N, Akemoto Y, Ota S, Hasui K, Nishiya D, Hayamizu S, Kikuchi H, Sawaya M, Chinda D, Mikami T, Shimoyama T, Fukuda S. Successful treatment with tacrolimus of refractory pyoderma gangrenosum with pouchitis after restorative proctocolectomy for ulcerative colitis. Immunol Med 2018; 41:142-146. [PMID: 30618342 DOI: 10.1080/25785826.2018.1531194] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
We describe herein a case of severe relapsed pyoderma gangrenosum (PG) concomitantly with severe pouchitis treated by tacrolimus. A 25-year-old woman had undergone proctocolectomy with construction of ileo-anal pouch surgery for refractory ulcerative colitis (UC). She first developed PG with refractory pouchitis, and infliximab (IFX) was administered to induce remission due to resistance to glucocorticoid therapy. After achieving remission, IFX was stopped. Five years later, severe skin ulcers concomitantly with severe pouchitis recurred and treatment with 30 mg oral prednisolone (PSL) combined with topical tacrolimus showed partial improvement. When PSL was tapered to 15 mg, the skin ulcers and diarrhea aggravated. Endoscopy revealed multiple ulcers in the ileal pouch. Treatment with oral tacrolimus was initiated for severe pouchitis and refractory PG. Forty days later, all skin ulcers became scars and multiple ulcers in the ileal pouch were also improved. Our case suggests that oral tacrolimus treatment could be a valuable treatment option for UC patients with refractory PG and pouchitis.
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Affiliation(s)
- Miwa Satake
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Hirotake Sakuraba
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan.,b Department of Community Medicine , Hirosaki University Graduate School of Medicine , Hirosaki , Japan
| | - Hiroto Hiraga
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan.,c Department of Community Healthcare Development in Odate and North Akita , Hirosaki University Graduate School of Medicine , Hirosaki , Japan
| | - Natsumi Tarakita
- d Department of Neuropsychiatry , Hirosaki University Graduate School of Medicine , Hirosaki , Japan
| | - Yui Akemoto
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Shinji Ota
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Keisuke Hasui
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Daisuke Nishiya
- e Department of Gastroenterology , Aomori Rosai Hospital , Hachinohe , Japan
| | - Shiro Hayamizu
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Hidezumi Kikuchi
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Manabu Sawaya
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Daisuke Chinda
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Tatsuya Mikami
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan.,f Division of endoscopy , Hirosaki University Hospital , Hirosaki , Japan
| | - Tadashi Shimoyama
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan
| | - Shinsaku Fukuda
- a Department of Gastroenterology and Hematology , Hirosaki University Graduate school of medicine , Hirosaki , Japan.,b Department of Community Medicine , Hirosaki University Graduate School of Medicine , Hirosaki , Japan
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27
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Maloney C, Blickenstaff N, Kugasia A, Buford LB, Hoffman MD. Vulvovaginal pyoderma gangrenosum in association with rituximab. JAAD Case Rep 2018; 4:907-909. [PMID: 30302361 PMCID: PMC6176040 DOI: 10.1016/j.jdcr.2018.09.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Affiliation(s)
- Catherine Maloney
- Rush University College of Medicine, Chicago, Illinois.,Department of Dermatology, Rush University Medical Center, Chicago, Illinois
| | | | - Aman Kugasia
- Department of Rheumatology, Rush University Medical Center, Chicago, Illinois
| | | | - Mark D Hoffman
- Department of Dermatology, Rush University Medical Center, Chicago, Illinois
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28
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Abstract
INTRODUCTION Pyoderma gangrenosum (PG) is a complex neutrophilic dermatosis that can occur as an idiopathic disease, in association with systemic conditions such as inflammatory bowel disease, as part of an inherited inflammatory syndrome. It can be challenging to treat, as it occurs in a wide variety of clinical settings and there is a lack of a standardized treatment approach. The main limitations to treatment have been an incomplete understanding of the pathogenesis. However, recent advances have been made in understanding the pathogenesis of this condition, and PG is now considered an autoinflammatory disease process. Areas covered: This review discusses the newest studies that further define our understanding of this disease and the relevant literature on treatment options for pyoderma gangrenosum. Expert commentary: The presence of abnormal neutrophils and T-cells lead to immune dysregulation, leading to lesions of PG. Increased levels of inflammatory mediators including IL-1β, IL-8, IL-17, and TNF-α contribute to the development of the disease but there are still several unknown factors, including the trigger for immune dysregulation and additional contributory components of the immune system. We provide our approach to the management of PG lesions, which involves a multi-faceted approach including wound care, topical therapy, and systemic medications in most cases.
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Affiliation(s)
- Christine Ahn
- a Department of Dermatology , Wake Forest School of Medicine , Winston Salem , North Carolina , USA
| | - Deborah Negus
- a Department of Dermatology , Wake Forest School of Medicine , Winston Salem , North Carolina , USA
| | - William Huang
- a Department of Dermatology , Wake Forest School of Medicine , Winston Salem , North Carolina , USA
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Jockenhöfer F, Herberger K, Schaller J, Hohaus KC, Stoffels-Weindorf M, Ghazal PA, Augustin M, Dissemond J. Trizentrische Analyse von Kofaktoren und Komorbidität des Pyoderma gangraenosum. J Dtsch Dermatol Ges 2018; 14:1023-1031. [PMID: 27767262 DOI: 10.1111/ddg.12791_g] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
EINLEITUNG Das Pyoderma gangraenosum (PG) ist eine seltene, inflammatorische destruktiv-ulzerierende neutrophile Erkrankung mit weitgehend unklarer Pathophysiologie. MATERIAL UND METHODIK In dieser Studie wurden die potenziell relevanten Kofaktoren und Begleiterkrankungen von Patienten mit PG aus drei dermatologischen Wundzentren in Deutschland differenziert ausgewertet. ERGEBNISSE Von den insgesamt 121 analysierten Patienten waren Frauen (66,9 %) häufiger betroffen als Männer. Das Alter der Patienten war 18-96 Jahre (Mittelwert [MW]: 59,8); die Wunden hatten eine Größe von 1-600 cm² (MW: 65,6 cm²) und waren überwiegend sehr schmerzhaft (VAS 1-10, MW: 7). Die Unterschenkel waren am häufigsten (71,9 %) betroffen. Bei 12 (9,9 %) Patienten bestanden chronisch entzündliche Darmerkrankungen (5,8 % Colitis ulcerosa; 4,1 % Morbus Crohn), bei 14,1 % der Patienten wurde eine Begleiterkrankung aus dem rheumatischen Formenkreis beschrieben. Neoplasien bestanden bei 20,6 % der Patienten, von denen 6,6 % als hämatologische und 14,1 % als solide Neoplasien klassifiziert wurden. Aus dem Kreis des metabolischen Syndroms wurde bei 69,4 % Patienten eine Adipositas, bei 57,9 % eine arterielle Hypertonie und bei 33,9 % ein Diabetes mellitus diagnostiziert. SCHLUSSFOLGERUNGEN Diese Datenanalyse bestätigt Assoziationen des PG mit dem metabolischen Syndrom und mit Neoplasien, die zukünftig frühzeitig bei einer zielgerichteten Diagnostik der Patienten beachtet und behandelt werden sollten.
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Affiliation(s)
- Finja Jockenhöfer
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Essen
| | - Katharina Herberger
- Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen/Universitäres Wundzentrum (CWC), Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Jörg Schaller
- Klinik für Dermatologie, Allergologie und Phlebologie, Helios Kliniken Duisburg
| | - Katja Christina Hohaus
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Essen
| | - Maren Stoffels-Weindorf
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Essen
| | - Philipp Al Ghazal
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Göttingen
| | - Matthias Augustin
- Klinik für Dermatologie, Allergologie und Phlebologie, Helios Kliniken Duisburg
| | - Joachim Dissemond
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Essen.
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Jockenhöfer F, Herberger K, Schaller J, Hohaus KC, Stoffels-Weindorf M, Ghazal PA, Augustin M, Dissemond J. Tricenter analysis of cofactors and comorbidity in patients with pyoderma gangrenosum. J Dtsch Dermatol Ges 2018; 14:1023-1030. [PMID: 27767288 DOI: 10.1111/ddg.12791] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Pyoderma gangrenosum (PG) is a rare neutrophilic, ulcerative skin disease of largely unknown pathophysiology. MATERIAL AND METHODS In this study, potentially relevant cofactors and comorbidities in patients with PG from three dermatological wound care centers in Germany were evaluated. RESULTS Of the 121 patients assessed, women (66.9 %) were more frequently affected than men. Patient age ranged from 18 to 96 years (mean 59.8). Wound size varied from 1-600 cm² (mean 65.6 cm²), and the pain intensity was predominantly very high (VAS 1-10, mean 7). The lower legs were most commonly (71.9 %) affected. Overall, 12 (9.9 %) patients had inflammatory bowel disease (ulcerative colitis, 5.8 %; Crohn's disease, 4.1 %), 14.1 % exhibited rheumatic comorbidities. Neoplasms were found in 20.6 % of patients, with 6.6 % classified as hematological and 14.0 % as solid neoplasms. With respect to criteria for the metabolic syndrome, obesity was found in 69.4 %, arterial hypertension in 57.9 %, and diabetes mellitus in 33.9 % of patients. CONCLUSIONS The present data analysis confirms the association of PG with metabolic syndrome and neoplasms. In the future, these aspects should be included in the targeted diagnostic workup of patients with PG and subsequently treated in a timely fashion.
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Affiliation(s)
- Finja Jockenhöfer
- Department of Dermatology, Venereology, and Allergology, University Hospital Essen, Essen, Germany
| | - Katharina Herberger
- Institute for Health Services Research in Dermatology and Nursing/Comprehensive Wound Center (CWC), University Medical Center Hamburg Eppendorf, Hamburg, Germany
| | - Jörg Schaller
- Department of Dermatology, Allergology, and Phlebology, Helios Hospitals Duisburg, Duisburg, Germany
| | - Katja Christina Hohaus
- Department of Dermatology, Venereology, and Allergology, University Hospital Essen, Essen, Germany
| | - Maren Stoffels-Weindorf
- Department of Dermatology, Venereology, and Allergology, University Hospital Essen, Essen, Germany
| | - Philipp Al Ghazal
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
| | - Matthias Augustin
- Department of Dermatology, Allergology, and Phlebology, Helios Hospitals Duisburg, Duisburg, Germany
| | - Joachim Dissemond
- Department of Dermatology, Venereology, and Allergology, University Hospital Essen, Essen, Germany.
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Wang EA, Steel A, Luxardi G, Mitra A, Patel F, Cheng MY, Wilken R, Kao J, de Ga K, Sultani H, Merleev AA, Marusina AI, Brassard A, Fung MA, Konia T, Shimoda M, Maverakis E. Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies. Front Immunol 2018; 8:1980. [PMID: 29379508 PMCID: PMC5775228 DOI: 10.3389/fimmu.2017.01980] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 12/20/2017] [Indexed: 12/12/2022] Open
Abstract
Background Pyoderma 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. Objective Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Methods Ten 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. Results All 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. Limitations Small sample size was the main limitation. Conclusion We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.
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Affiliation(s)
- Elizabeth A Wang
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Andrea Steel
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Guillaume Luxardi
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Anupam Mitra
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Forum Patel
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Michelle Y Cheng
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Reason Wilken
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Jason Kao
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Kristopher de Ga
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Hawa Sultani
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Alexander A Merleev
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Alina I Marusina
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Alain Brassard
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Maxwell A Fung
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States.,Department of Pathology, University of California, Davis, Sacramento, CA, United States
| | - Thomas Konia
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States.,Department of Pathology, University of California, Davis, Sacramento, CA, United States
| | - Michiko Shimoda
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
| | - Emanual Maverakis
- Department of Dermatology, University of California, Davis, Sacramento, CA, United States
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32
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Feygina VM, Hahn TF, Muchant DG. Refractory skin lesion, hypertension, and acute kidney injury in a young boy: Answers. Pediatr Nephrol 2017; 32:2053-2056. [PMID: 28101638 DOI: 10.1007/s00467-016-3567-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 12/02/2016] [Accepted: 12/06/2016] [Indexed: 11/28/2022]
Affiliation(s)
- Valeriya M Feygina
- Department of Pediatrics, Division of Pediatric Nephrology, Geisinger Medical Center, 100 Academy Avenue, Danville, PA, 17822, USA.
| | - Thomas F Hahn
- Department of Pediatrics, Division of Pediatric Rheumatology, Geisinger Medical Center, 100 Academy Avenue, Danville, PA, 17822, USA
| | - Dianne G Muchant
- Department of Pediatrics, Division of Pediatric Nephrology, Geisinger Medical Center, 100 Academy Avenue, Danville, PA, 17822, USA
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Antiga E, Maglie R, Volpi W, Bianchi B, Berti E, Marzano AV, Caproni M. T helper type 1-related molecules as well as interleukin-15 are hyperexpressed in the skin lesions of patients with pyoderma gangrenosum. Clin Exp Immunol 2017; 189:383-391. [PMID: 28518224 DOI: 10.1111/cei.12989] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2017] [Indexed: 01/03/2023] Open
Abstract
Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Although a number of studies confirmed the central role of innate immunity, only few studies have investigated the possible contributing role of acquired immunity. In particular, no reports concerning T helper type 1 (Th1) and Th2 cells are available as yet. Therefore, 15 patients with PG, five with Sweet's syndrome (SS) and nine skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers interleukin (IL)-12, interferon (IFN)-γ, C-X-C motif chemokine receptor 3 (CXCR3) and C-C motif chemokine receptor 5 (CCR5), of the Th2-related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40 ligand, of IL-15 and the natural killer (NK) cell marker CD56 in skin lesions by immunohistochemistry. Patients with PG and SS showed a higher expression of Th1 markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous in PG skin lesions compared to SS (P = 0·0157 and < 0·0001, respectively). Both CD40 and CD40L were expressed more in PG than in SS and HC (P < 0·0001 for both). Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients with PG than in those of SS and HC (P < 0·0001 for both). Our results suggest that Th2 cells are down-regulated in PG. At the same time, over-expression of the co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance. Both these findings might explain the most aggressive behaviour of PG in comparison to SS. Moreover, over-expression of IL-15+ and CD56+ cells may suggest a possible role of NK cells in the pathogenesis of the disease.
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Affiliation(s)
- E Antiga
- Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy
| | - R Maglie
- Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy
| | - W Volpi
- Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy
| | - B Bianchi
- Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy
| | - E Berti
- Dermatology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - A V Marzano
- Dermatology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - M Caproni
- Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy
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34
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Abstract
Pyoderma gangrenosum (PG) is an ulcerating, neutrophilic dermatosis of unknown etiology. Clinical appearance is characterized by sudden onset of sterile pustules that rapidly develop into very painful ulcerations with violaceous, undermined borders. Due to the lack of specific diagnostic and therapeutic markers, PG is a diagnosis of exclusion. An association with further diseases such as chronic inflammatory bowel disease, rheumatoid arthritis, diabetes, neoplasms, or metabolic syndrome exists in over 50 % of cases. Treatment of PG consists of suppression of inflammatory disease activity, treatment of associated morbidities, promotion of wound healing, and pain relief. Recommended first-line treatment consists of systemic glucocorticosteroids and additional or alternatively cyclosporine. A controlled trial on infliximab in PG points to efficacy of TNF-alpha antagonists. Due to chronicity, frequent recurrences, and often complicated courses, treatment with good tolerability is important.
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Affiliation(s)
- K Herberger
- Comprehensive Wound Center (CWC), Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland.
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35
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Shi X, Cui ZG, Hou F, Xu H, Wang H, Su Z, Zhao HG. [Acute lymphoblastic leukemia complicated with pyoderma gangrenosum: a case report and literatures review]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2017; 38:333-336. [PMID: 28468097 PMCID: PMC7342720 DOI: 10.3760/cma.j.issn.0253-2727.2017.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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36
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Loetscher J, Fistarol S, Walker UA. Pyoderma Gangrenosum and Erythema Nodosum Revealing Takayasu's Arteritis. Case Rep Dermatol 2016; 8:354-357. [PMID: 28101023 PMCID: PMC5216248 DOI: 10.1159/000452829] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2016] [Indexed: 11/19/2022] Open
Abstract
We report a Caucasian female who presented with simultaneous erythema nodosum and pyoderma gangrenosum due to underlying Takayasu's arteritis. Takayasu's arteritis is a chronic large vessel vasculitis of unknown cause. The disease has a worldwide distribution but is most commonly seen in Asian populations. There is a strong predilection for young females. The clinical presentation is variable, but mostly derives from stenosis or occlusion of affected arteries, resulting in claudication and ischemia. Skin manifestations are observed in up to 28% of patients with Takayasu's arteritis, with erythema nodosum reported more frequently in Caucasians. Pyoderma gangrenosum is more common in Asian patients. This report demonstrates the importance to exclude Takayasu's arteritis in patients with such skin lesions.
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Affiliation(s)
- Jonas Loetscher
- University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland
| | | | - Ulrich A Walker
- University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland
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37
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Gupta AS, Ortega-Loayza AG. Ocular pyoderma gangrenosum: A systematic review. J Am Acad Dermatol 2016; 76:512-518. [PMID: 27836332 DOI: 10.1016/j.jaad.2016.08.049] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 08/22/2016] [Accepted: 08/23/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Pyoderma gangrenosum (PG) is a rare, ulcerative cutaneous disorder. Ophthalmic involvement in PG is atypical, but can have devastating consequences. OBJECTIVE We sought to characterize ocular PG to allow for earlier diagnosis and therapy. To our knowledge, this is the first systematic review summarizing this clinical variant. METHODS A systematic review was conducted using PubMed and Web of Science. Data were extracted and studies were qualitatively assessed and analyzed. RESULTS We identified all 34 cases of PG involving the eye and periorbital area, and categorized them into 4 different subtypes. Common presenting signs include ulceration, peripheral ulcerative keratitis, and decreased visual acuity. Although it is often difficult to biopsy ocular PG, histologic features are nonspecific. Combined therapy using corticosteroids and further surgical reconstruction as needed is the mainstay of treatment. Cases of the eye/orbit in particular should be treated aggressively, as these are more likely to relapse compared with cases of the periorbital area. LIMITATIONS Use of case reports, paucity of ocular PG cases, and heterogeneity of studies are limitations. CONCLUSION PG should be considered in the differential diagnosis of ulceration of ocular/periocular tissues. An aggressive, early, multimodal treatment strategy should be used to prevent relapse, especially in cases of the eye/orbit.
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Affiliation(s)
- Angela S Gupta
- School of Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Alex G Ortega-Loayza
- Department of Dermatology, Oregon Health and Sciences University, Portland, Oregon.
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38
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Fozza C, Barraqueddu F, Corda G, Contini S, Virdis P, Dore F, Bonfigli S, Longinotti M. Study of the T-cell receptor repertoire by CDR3 spectratyping. J Immunol Methods 2016; 440:1-11. [PMID: 27823906 DOI: 10.1016/j.jim.2016.11.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 09/26/2016] [Accepted: 11/02/2016] [Indexed: 11/28/2022]
Abstract
The T-cell receptor (TCR) is the key player within the so called immunological synapse and the analysis of its repertoire offers a picture of both versatility and wideness of the whole immune T-cell compartment. Among the different approaches applied to its study the so-called spectratyping identifies the pattern of the third complementarity determining region (CDR3) length distribution in each one of the beta variable (TRBV) subfamilies encoded by the corresponding genes. This technique consists in a CDR3 fragment analysis through capillary electrophoresis, performed after cell separation, RNA extraction and reverse transcriptase PCR. This review will run through the most relevant studies which have tried to dissect the TCR repertoire usage in patients with different immune-mediated and infective diseases as well as solid or haematologic malignancies.
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Affiliation(s)
- Claudio Fozza
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
| | - Francesca Barraqueddu
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
| | - Giovanna Corda
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
| | - Salvatore Contini
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
| | - Patrizia Virdis
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
| | - Fausto Dore
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
| | - Silvana Bonfigli
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
| | - Maurizio Longinotti
- Hematology, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy
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Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol 2015; 73:691-8. [PMID: 26253362 DOI: 10.1016/j.jaad.2015.06.021] [Citation(s) in RCA: 158] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 06/05/2015] [Accepted: 06/10/2015] [Indexed: 12/11/2022]
Abstract
Pyoderma gangrenosum is a challenging skin condition to identify and treat because of its multifactorial pathogenesis. It is a rare cutaneous manifestation diagnosed clinically by exclusion of infection, neoplasia, thrombophilia, and other inflammatory conditions. Pathogenetic and treatment studies are scarce. Abnormalities in the function of inflammatory cytokines, the immune system, and neutrophils combined with specific genetic mutations predispose patients to develop this complex disease process. Early recognition of patients at risk for pyoderma gangrenosum, the necessity to improve its early diagnosis, and the future outlook of targeted and personalized therapies relies on the improved comprehension of the complex pathogenesis of pyoderma gangrenosum.
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Affiliation(s)
- Sara F Braswell
- Department of Dermatology, Virginia Commonwealth University, Richmond, Virginia
| | | | - Alex G Ortega-Loayza
- Department of Dermatology, Virginia Commonwealth University, Richmond, Virginia.
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40
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Yamamoto T. Pyoderma gangrenosum: An important dermatologic condition occasionally associated with rheumatic diseases. World J Rheumatol 2015; 5:101-107. [DOI: 10.5499/wjr.v5.i2.101] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 04/29/2015] [Indexed: 02/06/2023] Open
Abstract
Pyoderma gangrenosum (PG) presents with refractory, sterile, deep ulcers most often on the lower legs. Clinically, PG exhibits four types, i.e., ulcerative, bullous, pustular, and vegetative types. PG may be triggered by surgical operation or even by minor iatrogenic procedures such as needle prick or catheter insertion, which is well-known as pathergy. PG is sometimes seen in association with several systemic diseases including rheumatoid arthritis (RA), inflammatory bowel disease, hematologic malignancy, and Takayasu’s arteritis. In particular, various cutaneous manifestations are induced in association with RA by virtue of the activation of inflammatory cells (neutrophils, lymphocytes, macrophages), vasculopathy, vasculitis, drugs, and so on. Clinical appearances of ulcerative PG mimic rheumatoid vasculitis or leg ulcers due to impaired circulation in patients with RA. In addition, patients with PG sometimes develop joint manifestations as well. Therefore, it is necessary for not only dermatologists but also rheumatologists to understand PG.
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Quaglino P, Fava P, Caproni M, Antiga E, De Simone C, Papini M, Parodi A, Novelli M, Osella-Abate S, Ribero S, Sanlorenzo M, Ponti R, Fierro M, Marzano A, Savoia P. Phenotypical characterization of circulating cell subsets in pyoderma gangrenosum patients: the experience of the Italian immuno-pathology group. J Eur Acad Dermatol Venereol 2015; 30:655-8. [DOI: 10.1111/jdv.13100] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Accepted: 02/17/2015] [Indexed: 12/18/2022]
Affiliation(s)
- P. Quaglino
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - P. Fava
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - M. Caproni
- Section of Dermatology; Department of Surgery and Translational Medicine; University of Florence; Florence Italy
| | - E. Antiga
- Section of Dermatology; Department of Surgery and Translational Medicine; University of Florence; Florence Italy
| | - C. De Simone
- Dermatologic Clinic; Catholic University of the Sacred Heart; Rome Italy
| | - M. Papini
- Dermatologic Clinic; Department of Surgical and Biomedical Sciences; University of Terni; Terni Italy
| | - A. Parodi
- Section of Dermatology; DISSAL; IRCCS San Martino- IST; Genoa Italy
| | - M. Novelli
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - S. Osella-Abate
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - S. Ribero
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - M. Sanlorenzo
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - R. Ponti
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - M.T. Fierro
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
| | - A.V. Marzano
- Dermatologic Clinic; Department of Medical and Surgical Physiopathology and Transplants; IRCCS Cà Granda Foundation; University of Milan Policlinic; Milan Italy
| | - P. Savoia
- Dermatologic Clinic; Department of Medical Sciences; University of Turin; Turin Italy
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Ohashi T, Miura T, Yamamoto T. Auricular pyoderma gangrenosum with penetration in a patient with rheumatoid arthritis. Int J Rheum Dis 2014; 21:563-565. [PMID: 24916772 DOI: 10.1111/1756-185x.12411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Takenobu Ohashi
- Department of Dermatology, Fukushima Medical University, Fukushima, Japan
| | - Takako Miura
- Department of Dermatology, Fukushima Medical University, Fukushima, Japan
| | - Toshiyuki Yamamoto
- Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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Al Ghazal P, Herberger K, Schaller J, Strölin A, Hoff NP, Goerge T, Roth H, Rabe E, Karrer S, Renner R, Maschke J, Horn T, Hepp J, Eming S, Wollina U, Zutt M, Sick I, Splieth B, Dill D, Klode J, Dissemond J. Associated factors and comorbidities in patients with pyoderma gangrenosum in Germany: a retrospective multicentric analysis in 259 patients. Orphanet J Rare Dis 2013; 8:136. [PMID: 24010984 PMCID: PMC3844435 DOI: 10.1186/1750-1172-8-136] [Citation(s) in RCA: 102] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 08/30/2013] [Indexed: 12/16/2022] Open
Abstract
Background Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG. Methods Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany. Results We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8%) patients were female, 117 (45.2%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6% with anemia, 44.8% with endocrine diseases, 12.4% with internal malignancies, 9.3% with chronic inflammatory bowel diseases and 4.3% with elevated creatinine levels. Moreover 25.5% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome. Conclusions Our study describes one of the world’s largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients’ characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients.
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Affiliation(s)
- Philipp Al Ghazal
- Department of Dermatology, Venereology and Allergology, University School of Medicine Essen-Duisburg, Hufelandstrasse 55, Essen 45122, Germany.
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Goodarzi H, Sivamani RK, Garcia MS, Wehrli LN, Craven H, Ono Y, Maverakis E. Effective Strategies for the Management of Pyoderma Gangrenosum. Adv Wound Care (New Rochelle) 2012; 1:194-199. [PMID: 24527305 DOI: 10.1089/wound.2011.0339] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Pyoderma gangrenosum (PG) is an inflammatory disease characterized by painful ulcerations. It is often associated with other systemic inflammatory diseases, especially inflammatory bowel disease (IBD) and autoimmune arthritis. THE PROBLEM PG does not have characteristic serologic or histologic features. Therefore, other potential causes such as malignancy, vasculitis, infection, and coagulation disorders should be ruled out. In addition, patients often have aggressive disease that is refractory to immunosuppressive therapy, but there is only a paucity of clinical data to help direct therapy. BASIC/CLINICAL SCIENCE ADVANCES There are several lines of evidence to support an immunologic etiology of PG. Although the pathogenesis is still not well understood, it is clear that PG is associated with the upregulation of several cytokines including interleukin 8 (IL-8), tumor necrosis factor (TNF), IL-1β, IL-6, and interferon gamma, among many others. TNF and IL-1β are of particular interest, because some biologic medications that target these cytokines have been effective in treating PG. CLINICAL CARE RELEVANCE Multiple drugs are available to help control PG. Biologics, intravenous immunoglobulin (IVIG), and conventional immunosuppressive drugs have been reported to be effective. Multidrug therapies should be considered for refractory cases. CONCLUSION PG is a complex inflammatory disease with multiple involved pathways. Anti-TNF agents and IVIG represent a significant advancement in treatment options. Since some biologic therapies are relatively new, their unknown long-term side effects should be taken into consideration.
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Affiliation(s)
- Heidi Goodarzi
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
| | - Raja K. Sivamani
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
| | - Miki Shirakawa Garcia
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
| | - Lisa N. Wehrli
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
- Veterans Affairs Northern California Health Care System, Sacramento, California
| | - Hilary Craven
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
| | - Yoko Ono
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
- Veterans Affairs Northern California Health Care System, Sacramento, California
| | - Emanual Maverakis
- Department of Dermatology, University of California Davis School of Medicine Sacramento, California
- Veterans Affairs Northern California Health Care System, Sacramento, California
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Maverakis E, Goodarzi H, Wehrli LN, Ono Y, Garcia MS. The etiology of paraneoplastic autoimmunity. Clin Rev Allergy Immunol 2012; 42:135-44. [PMID: 21246308 DOI: 10.1007/s12016-010-8248-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Although they may sometimes appear similar, paraneoplastic autoimmunity has a unique pathogenesis, different from the classical autoimmune diseases not associated with cancer. When distinguished clinically, paraneoplastic autoimmunity is more severe and often presents with a broader range of clinical signs and symptoms. Management of these patients is difficult and is usually centered in part on treatment of the underlying malignancy. Self-antigens recognized in the setting of paraneoplastic autoimmunity can be diverse, and the number of determinants recognized within a single antigen can be numerous. This review uses prototypic examples of paraneoplastic immune-mediated diseases and their associated malignancies to describe the mechanisms by which immune dysregulation can occur in the setting of cancer. Specific diseases covered include paraneoplastic pemphigus, Sweet's syndrome, pyoderma gangrenosum, thymoma-associated multiorgan autoimmunity, myasthenia gravis, autoimmune hemolytic anemia, immune thrombocytopenia, and the paraneoplastic neurological syndromes. The malignancies discussed include thymoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia, among others. The mechanisms by which cancers induce autoimmunity are broken down into the following categories: disruption of central tolerance, peripheral immune dysregulation, and alteration of self-antigens. For each category, examples of paraneoplastic autoimmune diseases and their associated malignancies are discussed. Finally, mechanisms by which cancer treatment can lead to autoimmunity and examples of polymorphisms that are linked to both cancer and autoimmunity are discussed.
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Affiliation(s)
- Emanual Maverakis
- Department of Dermatology, School of Medicine, University of California-Davis, 3301 C Street, Sacramento, CA, 95816, USA.
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Wall LB, Stern PJ. Pyoderma gangrenosum. J Hand Surg Am 2012; 37:1083-5. [PMID: 22365821 DOI: 10.1016/j.jhsa.2011.12.044] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2011] [Revised: 12/15/2011] [Accepted: 12/27/2011] [Indexed: 02/02/2023]
Affiliation(s)
- Lindley B Wall
- Mary S. Stern Hand Surgery Fellowship, Cincinnati, OH, USA
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Dua J, Elliot E, Bright P, Grigoriadou S, Bull R, Millar M, Wijesuriya N, Longhurst HJ. Pyoderma gangrenosum-like ulcer caused by Helicobacter cinaedi in a patient with x-linked agammaglobulinaemia. Clin Exp Dermatol 2012; 37:642-5. [DOI: 10.1111/j.1365-2230.2011.04293.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Bonamigo RR, Razera F, Olm GS. Dermatoses neutrofílicas: parte I. An Bras Dermatol 2011; 86:11-25; quiz 26-7. [DOI: 10.1590/s0365-05962011000100002] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2010] [Indexed: 12/16/2022] Open
Abstract
Os autores apresentam uma revisão das dermatoses neutrofílicas que possuem grande repercussão à saúde dos pacientes: síndrome de Sweet, pioderma gangrenoso, doença de Behçet e urticária neutrofílica. São discutidos, baseados nos resultados e conclusões de estudos relevantes publicados recentemente e na experiência dos autores, os principais aspectos clínicos, as importantes alterações histopatológicas e as opções para o manejo.
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Abstract
Skin ulceration is a major source of morbidity and is often difficult to manage. Ulcers caused by an inflammatory cause or microvascular occlusion are particularly challenging in terms of diagnosis and treatment. The management of such ulcers requires careful assessment of associated systemic conditions and a thorough analysis of the ulcer's clinical and histologic findings. In this article, the authors discuss several examples of inflammatory ulcers and the approach to the diagnosis and treatment of these ulcers.
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Affiliation(s)
- Jaymie Panuncialman
- Department of Dermatology, Roger Williams Medical Center, 50 Maude Street, Providence, RI 02908, USA
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Ficarra G, Baroni G, Massi D. Pyostomatitis vegetans: cellular immune profile and expression of IL-6, IL-8 and TNF-alpha. Head Neck Pathol 2009; 4:1-9. [PMID: 20237982 PMCID: PMC2825530 DOI: 10.1007/s12105-009-0149-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2009] [Accepted: 10/28/2009] [Indexed: 10/20/2022]
Abstract
The aim of this study was to investigate the cellular immune profile and the expression of IL-6, IL-8 and TNF-alpha in tissue biopsies of pyostomatitis vegetans (PV). Working hypothesis was that knowledge of the cellular immune profile and role of mediators such as IL-6, IL-8 AND TNF-alpha may contribute to a better understanding of the pathogenesis of this rare entity. Archival tissues from three patients with clinically and histologically confirmed PV were studied. Analysis of the immune profile of the cellular infiltrate and expression of IL-6 and IL-8 were evaluated by immunohistochemistry. ISH was performed to evaluate the expression of TNF-alpha. Biopsy tissues from erythema multiforme, recurrent aphthous stomatitis, lichen planus and normal buccal mucosa were analyzed as controls. All patients were affected by multiple mucosal ulcerations and yellow pustules mainly located in the vestibular, gingival and palatal mucosa. Histopathologically, all specimens showed ulcerated epithelium with characteristic intraepithelial and/or subepithelial microabscesses containing abundant eosinophils plus a mixed infiltrate composed of lymphocytes and neutrophils. Cellular immune profile of the inflammatory infiltrate revealed a predominance of T-lymphocytes, mainly of cytotoxic (CD3+/CD8+) phenotype, over B-cells. CD20+ B-lymphocytes were also identified to a lesser degree among the lymphoid cells present in the lamina propria. Overexpression of IL-6 and TNF-alpha was found in both epithelial and inflammatory mononuclear cells. IL-8 expression was shown in the mononuclear cells scattered among the inflammatory infiltrate. Similar findings of overexpression of IL-6, IL-8 and TNF-alpha were, however, found in control tissues. In PV lesions, the inflammatory infiltrate shows a predominance of cytotoxic lymphocytes. Expression of IL-6, IL-8 and TNF-alpha, although not specific to PV, appears up-regulated thus these cytokines would represent a suitable therapeutic target. However, the complexity of the cytokine network and their numerous functions require further studies in order to confirm our findings.
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Affiliation(s)
- Giuseppe Ficarra
- Reference Center for the Study of Oral Diseases, Florence, Italy ,Department of Odonto-Stomatology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy
| | - Gianna Baroni
- Department of Human Pathology and Oncology, University Hospital of Careggi, Florence, Italy
| | - Daniela Massi
- Department of Human Pathology and Oncology, University Hospital of Careggi, Florence, Italy
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