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1
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Franceschin L, Guidotti A, Mazzetto R, Tartaglia J, Ciolfi C, Alaibac M, Sernicola A. Repurposing Historic Drugs for Neutrophil-Mediated Inflammation in Skin Disorders. Biomolecules 2024; 14:1515. [PMID: 39766222 PMCID: PMC11673839 DOI: 10.3390/biom14121515] [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: 10/01/2024] [Revised: 11/23/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025] Open
Abstract
Neutrophil-mediated inflammation is a key feature of immune-mediated chronic skin disorders, but the mechanistic understanding of neutrophil involvement in these conditions remains incomplete. Dapsone, colchicine, and tetracyclines are established drugs within the dermatologist's therapeutic armamentarium that are credited with potent anti-neutrophilic effects. Anti-neutrophilic drugs have established themselves as versatile agents in the treatment of a wide range of dermatological conditions. Some of these agents are approved for the management of specific dermatologic conditions, but most of their current uses are off-label and only supported by isolated reports or case series. Their anti-inflammatory and immunomodulatory properties make them particularly valuable in managing auto-immune bullous diseases, neutrophilic dermatoses, eosinophilic dermatoses, interface dermatitis, and granulomatous diseases that are the focus of this review. By inhibiting inflammatory pathways, reducing cytokine production, and modulating immune responses, they contribute significantly to the treatment and management of these complex skin conditions. Their use continues to evolve as our understanding of these diseases deepens, and they remain a cornerstone of dermatological therapy.
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Affiliation(s)
| | | | - Roberto Mazzetto
- Dermatology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padova, Italy; (L.F.); (A.G.); (J.T.); (C.C.); (M.A.)
| | | | | | | | - Alvise Sernicola
- Dermatology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padova, Italy; (L.F.); (A.G.); (J.T.); (C.C.); (M.A.)
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2
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Romagnuolo M, Moltrasio C, Iannone C, Gattinara M, Cambiaghi S, Marzano AV. Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report. Front Med (Lausanne) 2023; 10:1197273. [PMID: 37324147 PMCID: PMC10264797 DOI: 10.3389/fmed.2023.1197273] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 05/15/2023] [Indexed: 06/17/2023] Open
Abstract
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed "drug-induced PG." In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.
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Affiliation(s)
- Maurizio Romagnuolo
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Chiara Moltrasio
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Claudia Iannone
- Division of Clinical Rheumatology, ASST Gaetano Pini-CTO Institute, Milan, Italy
| | - Maurizio Gattinara
- Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, University of Milan, Milan, Italy
| | - Stefano Cambiaghi
- Pediatric Dermatology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Angelo Valerio Marzano
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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3
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Ohmura SI, Homma Y, Hanai S, Otsuki Y, Miyamoto T. Successful switching treatment of adalimumab for refractory pyoderma gangrenosum in a patient with rheumatoid arthritis with prior use of tumour necrosis factor inhibitors: A case report and review of the literature. Mod Rheumatol Case Rep 2023; 7:9-13. [PMID: 35285489 DOI: 10.1093/mrcr/rxac023] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/02/2022] [Accepted: 03/10/2022] [Indexed: 01/07/2023]
Abstract
Pyoderma gangrenosum (PG) is a rare chronic skin disease characterised by painful skin ulcers. There are no treatment guidelines for PG, but systemic treatments including biologics are often used. Recently, adalimumab (ADA), a fully human monoclonal antibody against tumour necrosis factor, was approved for refractory PG treatment in Japan. Herein, we report a case of rheumatoid arthritis with refractory PG 2 months after orthopaedic surgery of the foot during treatment with low-dose etanercept and methotrexate. Although adding a moderate dose of glucocorticoid did not improve her PG, the patient showed a remarkable response after switching from etanercept to ADA in a higher dose than that used to treat rheumatoid arthritis. This higher dose of ADA may be effective for the treatment of refractory PG after the failure of other tumour necrosis factor inhibitors.
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Affiliation(s)
- Shin-Ichiro Ohmura
- Department of Rheumatology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan
| | - Yoichiro Homma
- Department of General Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan
| | - Shiho Hanai
- Department of Dermatology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan
| | - Yoshiro Otsuki
- Department of Pathology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan
| | - Toshiaki Miyamoto
- Department of Rheumatology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan
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Abstract
OBJECTIVE To summarize clinical outcomes of paradoxical pyoderma gangrenosum (PG) onset in patients on biologic therapy. METHODS The authors conducted MEDLINE and EMBASE searches using PRISMA guidelines to include 57 patients (23 reports). RESULTS Of the included patients, 71.9% (n = 41/57) noted PG onset after initiating rituximab, 21.1% (n = 12/57) noted tumor necrosis factor α (TNF-α) inhibitors, 5.3% (n = 3/57) reported interleukin 17A inhibitors, and 1.8% (n = 1/57) reported cytotoxic T-lymphocyte-associated protein 4 antibodies. The majority of patients (94.3%) discontinued biologic use. The most common medications used to resolve rituximab-associated PG were intravenous immunoglobulins, oral corticosteroids, and antibiotics, with an average resolution time of 3.3 months. Complete resolution of PG in TNF-α-associated cases occurred within an average of 2.2 months after switching to another TNF-α inhibitor (n = 1), an interleukin 12/23 inhibitor (n = 2), or treatment with systemic corticosteroids and cyclosporine (n = 3), systemic corticosteroids alone (n = 1), or cyclosporine alone (n = 1). CONCLUSIONS Further investigations are warranted to determine whether PG onset is associated with underlying comorbidities, the use of biologic agents, or a synergistic effect. Nevertheless, PG may develop in patients on rituximab or TNF-α inhibitors, suggesting the need to monitor and treat such adverse effects.
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5
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Gawdzik A, Ponikowska M, Jankowska-Konsur A, Woźniak Z, Maj J, Szepietowski JC. Paradoxical Skin Reaction to Certolizumab, an Overlap of Pyoderma Gangrenosum and Psoriasis in a Young Woman Treated for Ankylosing Spondylitis: Case Report with Literature Review. Dermatol Ther (Heidelb) 2020; 10:869-879. [PMID: 32447747 PMCID: PMC7367980 DOI: 10.1007/s13555-020-00398-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 12/13/2022] Open
Abstract
Introduction Biologic agents form an indispensable part of modern therapeutic regimens for the treatment of severe inflammatory diseases, especially in the fields of rheumatology, dermatology and gastroenterology. They are favoured by both physicians and patients due to their high effectiveness, good patient tolerance and safety. However, interference in the regulation and dynamics of inflammatory cytokines can on occasion lead to an onset of a dermatological condition also known as paradoxical skin reaction. Here, we present a case of paradoxical skin reaction induced by certolizumab. Case Report A young woman with ankylosing spondylitis developed a severe and complex cutaneous reaction after 6 months of otherwise successful treatment with certolizumab. The diagnosis of a rare paradoxical cutaneous reaction post anti-tumour necrosis factor alpha treatment was based on overlapping features of pyoderma gangrenosum and palmoplantar pustular psoriasis. Alopecia developed and there was also nail involvement. Treatment proved to be challenging as the disease did not remit after the patient ceased treatment with certolizumab. The patient was started on a combination of secukinumab and methotrexate to control the symptoms, with a promising outcome. Conclusion Paradoxical skin reactions are an emerging clinical entity that require further research in order to establish risk factors and best personalized treatment.
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Affiliation(s)
- Anna Gawdzik
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland
| | - Małgorzata Ponikowska
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland
| | - Alina Jankowska-Konsur
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland
| | - Zdzisław Woźniak
- Department of Pathomorphology, Wroclaw Medical University, Wrocław, Poland
| | - Joanna Maj
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland
| | - Jacek C Szepietowski
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland.
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Savage KT, Santillan MR, Flood KS, Charrow A, Porter ML, Kimball AB. Tofacitinib shows benefit in conjunction with other therapies in recalcitrant hidradenitis suppurativa patients. JAAD Case Rep 2020; 6:99-102. [PMID: 31993474 PMCID: PMC6974699 DOI: 10.1016/j.jdcr.2019.10.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Kevin T Savage
- Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Monica Rosales Santillan
- Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Kelsey S Flood
- Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Alexandra Charrow
- Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.,Harvard Medical School, Brigham and Women's Hospital Dermatology, Boston, Massachusetts
| | - Martina L Porter
- Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Alexa B Kimball
- Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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7
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Ben Abdallah H, Fogh K, Bech R. Pyoderma gangrenosum and tumour necrosis factor alpha inhibitors: A semi-systematic review. Int Wound J 2019; 16:511-521. [PMID: 30604927 PMCID: PMC7949186 DOI: 10.1111/iwj.13067] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 12/12/2018] [Accepted: 12/18/2018] [Indexed: 12/13/2022] Open
Abstract
Pyoderma gangrenosum (PG) is a rare ulcerative skin disease that presents a therapeutic challenge. Tumour necrosis factor alpha (TNFα) inhibitors have been reported to successfully control PG. Our aim was to systematically evaluate and compare the clinical effectiveness of TNFα inhibitors in adults with PG. A literature search including databases such as PubMed, Embase, Scopus, and Web of Science was conducted, using search terms related to PG and TNFα inhibitors. Studies and case reports were included if patients were diagnosed with PG, over the age of 18 and administered TNFα inhibitor. A total of 3212 unique citations were identified resulting in 222 articles describing 356 patients being included in our study. The study we report found an 87% (95% CI: 83%-90%) response rate and a 67% (95% CI: 62%-72%) complete response rate to TNFα inhibitors. No statistically significant differences in the response rates (P = 0.6159) or complete response rates (P = 0.0773) to infliximab, adalimumab, and etanercept were found. In our study TNFα inhibitors demonstrated significant effectiveness with response and complete response rates supporting the use of TNFα inhibitors to treat PG in adults. Our study suggests that there is no significant difference in effectiveness among infliximab, adalimumab, and etanercept.
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Affiliation(s)
- Hakim Ben Abdallah
- Institute of Clinical Medicine, Aarhus Faculty of Health SciencesAarhus UniversityAarhusDenmark
| | - Karsten Fogh
- Department of DermatologyAarhus University HospitalAarhusDenmark
| | - Rikke Bech
- Department of DermatologyAarhus University HospitalAarhusDenmark
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8
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Garcovich S, De Simone C, Genovese G, Berti E, Cugno M, Marzano AV. Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders. Front Pharmacol 2019; 10:282. [PMID: 30971924 PMCID: PMC6443901 DOI: 10.3389/fphar.2019.00282] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 03/06/2019] [Indexed: 12/13/2022] Open
Abstract
Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet’s syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.
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Affiliation(s)
- Simone Garcovich
- Institute of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Clara De Simone
- Institute of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Genovese
- UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy
| | - Emilio Berti
- UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy
| | - Massimo Cugno
- Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.,Medicina Interna, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Angelo Valerio Marzano
- UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy
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9
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McKenzie F, Cash D, Gupta A, Cummings LW, Ortega-Loayza AG. Biologic and small-molecule medications in the management of pyoderma gangrenosum. J DERMATOL TREAT 2018; 30:264-276. [PMID: 30051737 DOI: 10.1080/09546634.2018.1506083] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disorder characterized by neutrophil dysfunction. There are currently no FDA-approved drugs for the treatment of this disease, and treatment has typically relied on traditional immunosuppressive medications such as prednisone or cyclosporine. The efficacy of biologics in the treatment of other pro-inflammatory conditions such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease is well-documented in the literature. Therefore, the use of biologic medications for the treatment of rarer inflammatory skin conditions, such as PG, is a compelling topic for investigation. Biologic and small-molecule therapies allow physicians to target specific pro-inflammatory mediators that underlie PG pathogenesis. This review provides an update on the use of biologic and small-molecule medications for the treatment of PG and summarizes the latest data on the clinical efficacy and pharmacology of these treatments.
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Affiliation(s)
- Fatima McKenzie
- a Department of Dermatology , Oregon Health & Science University , Portland , OR , USA
| | - Devin Cash
- b School of Medicine , Virginia Commonwealth University , Richmond , VA , USA
| | - Angela Gupta
- b School of Medicine , Virginia Commonwealth University , Richmond , VA , USA
| | - Laurel W Cummings
- b School of Medicine , Virginia Commonwealth University , Richmond , VA , USA
| | - Alex G Ortega-Loayza
- a Department of Dermatology , Oregon Health & Science University , Portland , OR , USA
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10
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Sehgal R, Stratman EJ, Cutlan JE. Biologic Agent-Associated Cutaneous Adverse Events: A Single Center Experience. Clin Med Res 2018; 16:41-46. [PMID: 29610119 PMCID: PMC6108513 DOI: 10.3121/cmr.2017.1364] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 11/12/2017] [Accepted: 12/15/2017] [Indexed: 01/16/2023]
Abstract
Biologic agents are regarded as an effective treatment for a variety of autoimmune diseases. These drugs have an acceptable safety and tolerability profile, although an increasing number of autoimmune conditions have been reported with their use. Additionally, a variety of cutaneous diseases have been associated with their use. Here we report our experience of adverse cutaneous events with the use of biologic agents. An alternative explanation for patients presenting with adverse cutaneous events including drug interactions must be carefully investigated.
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Affiliation(s)
- Rahul Sehgal
- Mayo Clinic Health System, Department of Rheumatology, Eau Claire, WI 54702 USA
| | - Erik J Stratman
- Marshfield Clinic Health System, Department of Dermatology, Marshfield, WI 54449 USA
| | - Jonathan E Cutlan
- Marshfield Clinic Health System, Department of Pathology, Marshfield, WI 54449 USA
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11
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Abstract
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be caused by an adverse drug reaction. We discuss the clinical presentation and outcomes of 52 cases of drug-induced PG reported to date in the literature. We conducted our literature search for case reports of drug-induced PG using keywords on PubMed and Medical Subject Heading (MeSH) terms on MEDLINE and EMBASE. To assess the probability that each case of PG was related to drug therapy, we used the Naranjo criteria. We identified 44 studies in the literature, with a total of 52 cases of drug-induced PG. The mean Naranjo score for cocaine-induced PG (n = 13) was 9.4, indicating a definite adverse drug reaction, while the mean Naranjo scores for isotretinoin (n = 5), propylthiouracil (n = 5), and sunitinib (n = 5) were 6.2, 6.8, and 7.4, respectively, indicating probable adverse drug reactions. Drugs should be considered as a possible triggering event whenever PG is diagnosed, and clinicians should particularly consider this in patients taking isotretinoin, propylthiouracil, or sunitinib, as well as in patients with a history of cocaine use.
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Affiliation(s)
- Jane Y Wang
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Lars E French
- Department of Dermatology, Zürich University Hospital, Zurich, Switzerland
| | - Neil H Shear
- Division of Dermatology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Division of Dermatology, Women's College Hospital, University of Toronto, 76 Grenville St, 5th Floor, Toronto, ON, M5S 1B2, Canada
| | | | - Afsaneh Alavi
- York Dermatology Centre, Toronto, ON, Canada.
- Division of Dermatology, Women's College Hospital, University of Toronto, 76 Grenville St, 5th Floor, Toronto, ON, M5S 1B2, Canada.
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12
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Fudman DI, Flier SN. Anti-TNF Therapy for Treatment of Extraintestinal Manifestations of Inflammatory Bowel Disease. TREATMENT OF INFLAMMATORY BOWEL DISEASE WITH BIOLOGICS 2018:49-57. [DOI: 10.1007/978-3-319-60276-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Skalkou A, Manoli SM, Sachinidis A, Ntouros V, Petidis K, Pagkopoulou E, Vakirlis E, Pyrpasopoulou A, Dimitroulas T. Pyoderma gangrenosum and pyogenic arthritis presenting as severe sepsis in a rheumatoid arthritis patient treated with golimumab. Rheumatol Int 2017; 38:161-167. [PMID: 29075910 DOI: 10.1007/s00296-017-3861-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 10/19/2017] [Indexed: 01/27/2023]
Abstract
Rheumatoid arthritis is a systemic autoimmune disease resulting in joint destruction and deformities, but also associated with extraarticular and systemic manifestations. The later devastating conditions, such as the development of rheumatoid vasculitis, are more frequently encountered in seropositive patients and their incidence has been attenuated after the introduction of biologic disease modifying drugs, such as anti-tumor necrosis factor alpha (TNFa) agents, which generally have considerably contributed to the better control and long-term outcomes of the disease. Interestingly, autoimmune syndromes may, rarely, present in patients without a positive history after the initiation of treatment. We present a rare case of a woman with seronegative rheumatoid arthritis who developed pyoderma gangrenosum whistle on treatment with golimumab, a fully humanized anti TNFa antibody. The recording of this as well as analogous paradoxical autoimmune syndromes in association with the individual patient characteristics will render treating physicians aware of potential adverse reactions and assist in the understanding of the cytokine driven pathophysiological mechanisms underlying these disorders.
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Affiliation(s)
- Anastasia Skalkou
- 2nd Propedeutic Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Sofia-Magdalini Manoli
- 1st Department of Dermatology, Hospital for Skin and Venereal Diseases, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alexandros Sachinidis
- 2nd Propedeutic Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vasilios Ntouros
- 2nd Propedeutic Department of Surgery, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantinos Petidis
- 2nd Propedeutic Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Pagkopoulou
- 4th Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Str, 54642, Thessaloniki, Greece
| | - Efstratios Vakirlis
- 1st Department of Dermatology, Hospital for Skin and Venereal Diseases, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athina Pyrpasopoulou
- 2nd Propedeutic Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodoros Dimitroulas
- 4th Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Str, 54642, Thessaloniki, Greece.
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14
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Inflammatory Joint Disorders and Neutrophilic Dermatoses: a Comprehensive Review. Clin Rev Allergy Immunol 2017; 54:269-281. [DOI: 10.1007/s12016-017-8629-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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15
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Wu BC, Patel ED, Ortega-Loayza AG. Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum. Br J Dermatol 2017; 177:72-83. [PMID: 27864925 DOI: 10.1111/bjd.15193] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/30/2016] [Indexed: 12/14/2022]
Abstract
Pyoderma gangrenosum (PG) is a rare autoinflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the aetiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum. In total, we found 43 cases of drug-induced PG. Most of them were caused by colony-stimulating factors and small-molecule tyrosine kinase inhibitors. We propose that drugs induce PG through various mechanisms such as dysfunctional neutrophil migration and function, dysregulated inflammatory response, promotion of keratinocyte apoptosis and alteration of epigenetic mechanisms. PG is a rare condition with complex pathophysiology and drug-induced cases are even more scarce; this is the main limitation of this review. Understanding the possible mechanisms of drug-induced PG, via abnormal neutrophil migration and function, abnormal inflammation, keratinocyte apoptosis and alteration of epigenetic mechanisms would help to better understand the pathogenesis of PG and ultimately to optimize targeted therapy.
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Affiliation(s)
- B C Wu
- Department of Medicine, Drexel University College of Medicine/Hahnemann University Hospital, Philadelphia, PA, U.S.A
| | - E D Patel
- Virginia Commonwealth University School of Medicine, Richmond, VA, U.S.A
| | - A G Ortega-Loayza
- Center for Wound and Healing, Department of Dermatology, Oregon Health & Science University, 3303 SW Bond Avenue, CHD 16D, Portland, OR, 97034, U.S.A
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Alavi A, French LE, Davis MD, Brassard A, Kirsner RS. Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment. Am J Clin Dermatol 2017; 18:355-372. [PMID: 28224502 DOI: 10.1007/s40257-017-0251-7] [Citation(s) in RCA: 185] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the genetic basis of PG and the role of auto-inflammation provides a better understanding of the disease and new therapeutic targets. PG equally affects patients of both sexes and of any age. Uncontrolled cutaneous neutrophilic inflammation is the cornerstone in a genetically predisposed individual. Multimodality management is often required to reduce inflammation, optimize wound healing, and treat underlying disease. A gold standard for the management of PG does not exist and high-level evidence is limited. Multiple factors must be taken into account when deciding on the optimum treatment for individual patients: location, number and size of lesion/ulceration(s), extracutaneous involvement, presence of associated disease, cost, and side effects of treatment, as well as patient comorbidities and preferences. Refractory and rapidly progressive cases require early initiation of systemic therapy. Newer targeted therapies represent a promising pathway for the management of PG, and the main focus of this review is the management and evidence supporting the role of new targeted therapies in PG.
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17
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DeFilippis E, Feldman S, Huang W. The genetics of pyoderma gangrenosum and implications for treatment: a systematic review. Br J Dermatol 2015; 172:1487-1497. [PMID: 25350484 DOI: 10.1111/bjd.13493] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2014] [Indexed: 12/22/2022]
Affiliation(s)
- E.M. DeFilippis
- Center for Dermatology Research; Department of Dermatology; Wake Forest School of Medicine, Medical Center Boulevard; Winston-Salem NC 27157 U.S.A
| | - S.R. Feldman
- Center for Dermatology Research; Department of Dermatology; Wake Forest School of Medicine, Medical Center Boulevard; Winston-Salem NC 27157 U.S.A
- Department of Pathology; Wake Forest School of Medicine, Medical Center Boulevard; Winston-Salem NC 27157 U.S.A
- Department of Public Health Sciences; Wake Forest School of Medicine, Medical Center Boulevard; Winston-Salem NC 27157 U.S.A
| | - W.W. Huang
- Center for Dermatology Research; Department of Dermatology; Wake Forest School of Medicine, Medical Center Boulevard; Winston-Salem NC 27157 U.S.A
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Tada M, Nakanishi T, Hirata C, Okano T, Sugioka Y, Wakitani S, Nakamura H, Koike T. Use of infliximab in a patient with pyoderma gangrenosum and rheumatoid arthritis. Mod Rheumatol 2014. [DOI: 10.3109/s10165-010-0336-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Wendling D, Prati C. Paradoxical effects of anti-TNF-α agents in inflammatory diseases. Expert Rev Clin Immunol 2013; 10:159-69. [DOI: 10.1586/1744666x.2014.866038] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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20
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Sánchez-Cano D, Callejas-Rubio JL, Ruiz-Villaverde R, Ríos-Fernández R, Ortego-Centeno N. Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoidosis, and noninfectious uveitis. Mediators Inflamm 2013; 2013:286857. [PMID: 23983404 PMCID: PMC3747407 DOI: 10.1155/2013/286857] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Revised: 07/09/2013] [Accepted: 07/15/2013] [Indexed: 12/11/2022] Open
Abstract
Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.
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Zippi M, Pica R, De Nitto D, Paoluzi P. Biological therapy for dermatological manifestations of inflammatory bowel disease. World J Clin Cases 2013; 1:74-78. [PMID: 24303470 PMCID: PMC3845939 DOI: 10.12998/wjcc.v1.i2.74] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Revised: 02/18/2013] [Accepted: 03/29/2013] [Indexed: 02/05/2023] Open
Abstract
Ulcerative colitis and Crohn’s disease are the two forms of inflammatory bowel disease (IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions (immune-mediated extraintestinal manifestations), erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor (TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab (a fusion protein dimer of the human TNF-α receptor) and adalimumab (a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD (EN, PG and psoriasis).
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Abstract
Neutrophilic dermatoses, including Sweet's syndrome, pyoderma gangrenosum, and rheumatoid neutrophilic dermatitis, are inflammatory conditions of the skin often associated with underlying systemic disease. These are characterized by the accumulation of neutrophils in the skin. The associated conditions, potential for systemic neutrophilic infiltration, and therapeutic management of these disorders can be similar. Sweet's syndrome can often be effectively treated with a brief course of systemic corticosteroids. Pyoderma gangrenosum, however, can be recurrent, and early initiation of a steroid-sparing agent is prudent. Second-line treatment for both of these conditions includes medications affecting neutrophil function, in addition to immunosuppressant medications.
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Affiliation(s)
- Courtney R Schadt
- Division of Dermatology, University of Louisville, 310 East Broadway, Louisville, KY 40202, USA.
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23
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Freeman HJ. Colitis associated with biological agents. World J Gastroenterol 2012; 18:1871-4. [PMID: 22563166 PMCID: PMC3337561 DOI: 10.3748/wjg.v18.i16.1871] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2011] [Revised: 02/09/2012] [Accepted: 02/16/2012] [Indexed: 02/06/2023] Open
Abstract
In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohn’s disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody), bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept.
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Kerr GS, Aggarwal A, McDonald-Pinkett S. A woman with rheumatoid arthritis, Sjögren's syndrome, leg ulcer, and significant weight loss. Arthritis Care Res (Hoboken) 2012; 64:785-92. [PMID: 22290720 DOI: 10.1002/acr.21628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Gail S Kerr
- Veterans Affairs Medical Center, 50 Irving Street, Washington, DC 20422, USA.
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Lee HY, Pelivani N, Beltraminelli H, Hegyi I, Yawalkar N, Borradori L. Amicrobial Pustulosis-Like Rash in a Patient with Crohn’s Disease under Anti-TNF-Alpha Blocker. Dermatology 2011; 222:304-10. [DOI: 10.1159/000329428] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2011] [Accepted: 04/16/2011] [Indexed: 11/19/2022] Open
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Tada M, Nakanishi T, Hirata C, Okano T, Sugioka Y, Wakitani S, Nakamura H, Koike T. Use of infliximab in a patient with pyoderma gangrenosum and rheumatoid arthritis. Mod Rheumatol 2010; 20:598-601. [PMID: 20680379 DOI: 10.1007/s10165-010-0336-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2010] [Accepted: 06/25/2010] [Indexed: 11/26/2022]
Abstract
Pyoderma gangrenosum (PG) is characterized by ulcerative skin lesions. Infliximab (IFX) may promote PG healing in patients with inflammatory bowel disease, but whether IFX is effective for treating PG in patients with rheumatoid arthritis (RA) has not reported. We report the case of a 53-year-old woman with PG complicated by RA who was treated using IFX therapy. This case suggests that IFX therapy might offer effective treatment for such patients.
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Affiliation(s)
- Masahiro Tada
- Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2008. [PMID: 18533281 PMCID: PMC7167700 DOI: 10.1002/pds.1487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 20 sections: 1 Reviews; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Teratogens/fetal exposure; 20 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.
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