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Dai D, He C, Wang S, Wang M, Guo N, Song P. Toward Personalized Interventions for Psoriasis Vulgaris: Molecular Subtyping of Patients by Using a Metabolomics Approach. Front Mol Biosci 2022; 9:945917. [PMID: 35928224 PMCID: PMC9343857 DOI: 10.3389/fmolb.2022.945917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/15/2022] [Indexed: 11/29/2022] Open
Abstract
Aim: Psoriasis vulgaris (PV) is a complicated autoimmune disease characterized by erythema of the skin and a lack of available cures. PV is associated with an increased risk of metabolic syndrome and cardiovascular disease, which are both mediated by the interaction between systemic inflammation and aberrant metabolism. However, whether there are differences in the lipid metabolism between different levels of severity of PV remains elusive. Hence, we explored the molecular evidence for the subtyping of PV according to alterations in lipid metabolism using serum metabolomics, with the idea that such subtyping may contribute to the development of personalized treatment. Methods: Patients with PV were recruited at a dermatology clinic and classified based on the presence of metabolic comorbidities and their Psoriasis Area and Severity Index (PASI) from January 2019 to November 2019. Age- and sex-matched healthy controls were recruited from the preventive health department of the same institution for comparison. We performed targeted metabolomic analyses of serum samples and determined the correlation between metabolite composition and PASI scores. Results: A total of 123 participants, 88 patients with PV and 35 healthy subjects, were enrolled in this study. The patients with PV were assigned to a “PVM group” (PV with metabolic comorbidities) or a “PV group” (PV without metabolic comorbidities) and further subdivided into a “mild PV” (MP, PASI <10) and a “severe PV” (SP, PASI ≥10) groups. Compared with the matched healthy controls, levels of 27 metabolites in the MP subgroup and 28 metabolites in the SP subgroup were found to be altered. Among these, SM (d16:0/17:1) and SM (d19:1/20:0) were positively correlated with the PASI in the MP subgroup, while Cer (d18:1/18:0), PC (18:0/22:4), and PC (20:0/22:4) were positively correlated with the PASI in the SP subgroup. In the PVM group, levels of 17 metabolites were increased, especially ceramides and phosphatidylcholine, compared with matched patients from the PV group. In addition, the correlation analysis indicated that Cer (d18:1/18:0) and SM (d16:1/16:1) were not only correlated with PASI but also has strongly positive correlations with biochemical indicators. Conclusion: The results of this study indicate that patients with PV at different severity levels have distinct metabolic profiles, and that metabolic disorders complicate the disease development. These findings will help us understand the pathological progression and establish strategies for the precision treatment of PV.
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Affiliation(s)
- Dan Dai
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chunyan He
- Department of Dermatology, Hubei Provincial Hospital of TCM, Wuhan, China
| | - Shuo Wang
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Mei Wang
- Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology Leiden, Leiden University, Leiden, Netherlands
- SU BioMedicine, BioPartner Center 3, Leiden, Netherlands
- *Correspondence: Mei Wang, ; Na Guo, ; Ping Song,
| | - Na Guo
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Mei Wang, ; Na Guo, ; Ping Song,
| | - Ping Song
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Mei Wang, ; Na Guo, ; Ping Song,
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Townsend CM, Lovegrove F, Khanna R, Wilson AS. Review article: paradoxical psoriasis as a consequence of tumour necrosis factor antagonists in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2022; 55:1379-1388. [PMID: 35312094 DOI: 10.1111/apt.16883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/12/2022] [Accepted: 02/28/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Tumour necrosis factor (TNF) antagonists are an efficacious therapy used in the management of several immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD) and psoriasis. However, since being prescribed more widely, reports of new-onset psoriatic lesions have began to emerge in the literature and are known as paradoxical psoriasis. AIM To review the evidence available in both the dermatology and gastroenterology literature pertaining to the entity known as paradoxical psoriasis as it relates to IBD and to create a comprehensive guide to assist clinicians who treat this challenging patient population. METHODS A literature search was conducted in PubMed to identify manuscripts that presented, discussed or summarised data pertaining to paradoxical psoriasis presenting in individuals with IBD. RESULTS Paradoxical psoriasis is now thought to be a contradictory effect of TNF antagonist therapy leading to psoriatic lesions often within the first year of treatment. The underlying pathogenesis, although not completely understood, is likely related to an imbalance of inflammatory cytokines. The histological appearance, while similar to classical psoriasis, does have unique features. The clinical presentation can vary among patients but often presents during maintenance therapy for inflammatory bowel disease. Treatment options should be determined based upon the severity of the skin lesion, activity of the underlying inflammatory bowel disease and the patient's unique clinical history. CONCLUSIONS The approach to paradoxical psoriasis in IBD should be discussed with a multidisciplinary team to optimise and preserve intestinal disease remission and to ensure the resolution of debilitating skin lesions.
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Affiliation(s)
- Cassandra Marie Townsend
- Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Fiona Lovegrove
- Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada.,Lovegrove Dermatology, London, Ontario, Canada
| | - Reena Khanna
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Aze Suzanne Wilson
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada.,Division of Clinical Pharmacology, Department of Medicine, Western University, London, Ontario, Canada.,Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
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Mazloom SE, Yan D, Hu JZ, Ya J, Husni ME, Warren CB, Fernandez AP. TNF-α inhibitor–induced psoriasis: A decade of experience at the Cleveland Clinic. J Am Acad Dermatol 2020; 83:1590-1598. [DOI: 10.1016/j.jaad.2018.12.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 12/08/2018] [Accepted: 12/10/2018] [Indexed: 02/08/2023]
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Ustekinumab for the Treatment of Refractory Crohn's Disease: The Spanish Experience in a Large Multicentre Open-label Cohort. Inflamm Bowel Dis 2016; 22:1662-9. [PMID: 27306072 DOI: 10.1097/mib.0000000000000842] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. METHODS Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. RESULTS One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. CONCLUSIONS Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.
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Guerra I, Pérez-Jeldres T, Iborra M, Algaba A, Monfort D, Calvet X, Chaparro M, Mañosa M, Hinojosa E, Minguez M, Ortiz de Zarate J, Márquez L, Prieto V, García-Sánchez V, Guardiola J, Rodriguez GE, Martín-Arranz MD, García-Tercero I, Sicilia B, Masedo Á, Lorente R, Rivero M, Fernández-Salazar L, Gutiérrez A, Van Domselaar M, López-SanRomán A, Ber Y, García-Sepulcre M, Ramos L, Bermejo F, Gisbert JP. Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study. Inflamm Bowel Dis 2016; 22:894-901. [PMID: 26933750 DOI: 10.1097/mib.0000000000000757] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect. AIM To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. METHODS Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. RESULTS Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. CONCLUSIONS The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.
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Affiliation(s)
- Iván Guerra
- 1Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain; 2Department of Gastroenterology, Hospital Clinic, Barcelona, Spain; 3Department of Gastroenterology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD); 4Department of Gastroenterology, Hospital Universitario La Fe, Valencia, Spain; 5Department of Gastroenterology, Consorci Sanitari de Terrassa, Barcelona, Spain; 6Department of Gastroenterology, Corporació Sanitaria Parc Taulí, Sabadell, Spain; 7Department of Gastroenterology, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain; 8Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 9Department of Gastroenterology, Hospital de Manises, Valencia, Spain; 10Department of Gastroenterology, Hospital Clínico de Valencia, Universitat de València, Valencia, Spain; 11Department of Gastroenterology, Hospital de Basurto, Bilbao, Spain; 12Department of Gastroenterology, Hospital del Mar, Barcelona, Spain; 13Department of Gastroenterology, Hospital Universitario de Salamanca, Salamanca, Spain; 14Department of Gastroenterology, Hospital Reina Sofía, IMIBIC, Universidad de Córdoba, Córdoba, Spain; 15Department of Gastroenterology, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain; 16Department of Gastroenterology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; 17Department of Gastroenterology, Hospital Universitario La Paz, Madrid, Spain; 18Department of Gastroenterology, Hospital Universitario Santa Lucía, Cartagena, Spain; 19Department of Gastroenterology, Hospital Universitario de Burgos, Burgos, Spain; 20Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain; 21Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain; 22Department of Gastroenterology, Hospital Universitario Marqué
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Her M, Kavanaugh A. Alterations in immune function with biologic therapies for autoimmune disease. J Allergy Clin Immunol 2016; 137:19-27. [DOI: 10.1016/j.jaci.2015.10.023] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 10/21/2015] [Accepted: 10/28/2015] [Indexed: 02/08/2023]
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Mihály E, Székely H, Herszényi L, Wikonkál N, Tulassay Z. Letter: dermatological complications with therapy for inflammatory bowel disease. Aliment Pharmacol Ther 2014; 39:232-3. [PMID: 24330244 DOI: 10.1111/apt.12566] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2013] [Accepted: 08/11/2013] [Indexed: 12/16/2022]
Affiliation(s)
- E Mihály
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
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Biswas S, Myszor M, De Silva A. Management of psoriasis in patients treated with anti-TNF-α therapy for inflammatory bowel disease. J Crohns Colitis 2013; 7:e708-9. [PMID: 23972498 DOI: 10.1016/j.crohns.2013.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Accepted: 08/02/2013] [Indexed: 02/08/2023]
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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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