DERMATOLOGICA SINICA xxx (2016) 1e2 Contents lists available at ScienceDirect Dermatologica Sinica journal homepage: http://www.derm-sinica.com CORRESPONDENCE Paradoxical flare of psoriasis, psoriatic spondyloarthritis, and psoriatic uveitis after switching from infliximab to secukinumab Dear Editor, Numerous therapeutic options are available for the treatment of psoriasis Biologics such as etanercept, adalimumab, infliximab, and ustekinumab are effective for the treatment of moderateesevere psoriasis Switching between biologics is common practice that is used in an effort to achieve these treatment goals While this practice is often safe and effective, a small subset of patients may experience significant worsening of psoriasis signs and symptoms after switching between antitumor necrosis factor (TNF) a drugs.1 We describe a 45-year-old Eurasian man with a long history of chronic plaque psoriasis and psoriatic arthropathy, who experienced paradoxical worsening of his psoriatic arthritis and development of uveitis after switching from infliximab to secukinumab For his treatment history, methotrexate was tried several times but the patient experienced severe nausea even at low doses He received other therapies including phototherapy, acitretin, cyclosporine, etanercept, adalimumab, and ustekinumab but with suboptimal control of his joint pains and with secondary failure after 6e9 months of therapy He had greatest success with infliximab (5 mg/kg), which was able to control his skin and joint pains, but experienced secondary failure with relapse of his skin lesions [Psoriasis Area and Severity Index (PASI) 26.4] after approximately 30 months of therapy Hence, he was switched to secukinumab 300 mg according to the standard regimen After the second dose, his PASI score improved to 10.8 However, after the fourth dose in the induction phase, he developed severe uveitis with red eyes and blurred vision, and a flare of his spondyloarthritis, with severe pain in the neck and spine His skin condition also worsened with a PASI of 14.5 The patient opted to rotate back to infliximab for better joint control Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, showed a downward trend after the patient was switched back to infliximab He was willing to accept poorer control of his skin condition His eye and joint symptoms subsequently subsided Switching biologics may be considered to optimize symptom control, improve quality of life, and minimize adverse effects When switching for safety reasons, a washout period is recommended until the safety parameter is normalized or stabilized.2 If switching due to lack of efficacy, a washout period is not necessary.2 Although the exacerbation of psoriasis in patients treated with TNF antagonists is a known phenomenon, the pathogenesis underlying this mechanism remains elusive Five types of adverse effects induced by biologic agents have been described (a, b, g, d, and 3) based on immunopathogenesis.3 Psoriasiform eruptions, particularly the pustular type, are thought to be due to immune imbalance (g type).3 Increased production of interferon-g after TNF-a blockage, increased T helper 17 function and a reduction of regulatory T cells may have a role to play.4 Adalimumab was one of the first few TNF antagonists and has been shown to be effective in treating moderateesevere psoriasis with arthritic symptoms In a small retrospective cohort study conducted in Taiwan,5 25% of patients achieved a 75% improvement in their PASI 75 and 75% had an improved Psoriatic Arthritis Response Criteria (PsARC) In recent years, however, newer agents, such as ustekinumab, have been proven to be effective for patients who have failed other biologic agents such as etanercept and/or adalimumab.6 Unfortunately, our patient had suboptimal response to etanercept, adalimumab, and ustekinumab Secukinumab is a new human interleukin-17 monoclonal antibody for treating moderateesevere psoriasis To date, there have been no reports of worsening of psoriasis or its associated symptoms after switching to secukinumab However, paradoxical exacerbation of Crohn’s disease in a clinical trial of secukinumab has been described.7 Depending on the local cytokine environment, T helper 17 cells may be primed to be either proinflammatory or regulatory.7 This may explain the paradoxical reactions seen The immunopathogenesis through which adverse and paradoxical reactions may occur with biologic agents is indeed complex Therefore, predicting these reactions might prove a major challenge This case highlights the possibility that anti-interleukin-17 drugs, like anti-TNF agents, may also be associated with paradoxical worsening of symptoms in psoriasis patients While this trend is rare, physicians should exercise vigilance and closer monitoring when switching patients between biologic therapies Peiqi Su*, Jiun Yit Pan National Skin Centre, Mandalay Road, Singapore, Singapore * Corresponding author National Skin Centre, Mandalay Road, Singapore 308205, Singapore E-mail address: peiqi_su@nuhs.edu.sg (P Su) References Conflicts of interest: The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter or materials discussed in this article Bhutani T, Koo J Paradoxical worsening of psoriasis when switching from etanercept to adalimumab: a case series J Dermatolog Treat 2011;22:75e8 http://dx.doi.org/10.1016/j.dsi.2016.10.002 1027-8117/Copyright © 2016, Taiwanese Dermatological Association Published by Elsevier Taiwan LLC This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Su P, Pan JYParadoxical flare of psoriasis, psoriatic spondyloarthritis, and psoriatic uveitis after switching from infliximab to secukinumab, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.002 Correspondence / Dermatologica Sinica xxx (2016) 1e2 Kerdel F, Zaiac M An evolution in switching therapy for psoriasis patients who fail to meet treatment goals Dermatol Ther 2015;28:390e403 Aubin F, Carbonnel F, Wendling D The complexity of adverse side-effects to biological agents J Crohns Colitis 2013;7:257e62 Notley CA, Inglis JJ, Alzabin S, McCann FE, McNamee KE, Williams RO Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells J Exp Med 2008;205:2491e7 Kao PH, Hui RCY, Yang CH, Huang YH Effectiveness and safety of adalimumab in treating moderate to severe psoriasis patients with psoriatic arthritis in Taiwan Dermatol Sinica 2015;33:119e23 Wang TC, Chiu HY, Wang TS, Tsai TF Practical experience of ustekinumab in patients with moderate-to-severe psoriasis who had inadequate therapeutic response to previous tumor necrosis factor blockers Dermatol Sinica 2015;33: 5e10 Marwaha AK, Leung NJ, McMurchy AN, Levings MK TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic? Front Immunol 2012;3:129 Received: May 26, 2016 Revised: Sep 19, 2016 Accepted: Oct 19, 2016 Please cite this article in press as: Su P, Pan JYParadoxical flare of psoriasis, psoriatic spondyloarthritis, and psoriatic uveitis after switching from infliximab to secukinumab, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.002 ... article in press as: Su P, Pan JYParadoxical flare of psoriasis, psoriatic spondyloarthritis, and psoriatic uveitis after switching from infliximab to secukinumab, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.002... immunoregulatory pathway for Th1 and Th17 cells J Exp Med 2008;205:2491e7 Kao PH, Hui RCY, Yang CH, Huang YH Effectiveness and safety of adalimumab in treating moderate to severe psoriasis patients... patients with psoriatic arthritis in Taiwan Dermatol Sinica 2015;33:119e23 Wang TC, Chiu HY, Wang TS, Tsai TF Practical experience of ustekinumab in patients with moderate -to- severe psoriasis who