Certolizumab pegol, a pegylated anti‐TNF‐α antagonist, caused de novo<i>‐</i>onset palmoplantar pustulosis followed by generalized pustular psoriasis in a patient with rheumatoid arthritis

Generalized pustular psoriasis (GPP) is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances-while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP. Classifying GPP is challenging since clinical criteria for description and diagnosis are not consistent between expert centres. We therefore defined diagnostic feasibility of the reviewed cases by assessing four criteria: compatible clinical history, typical dermatological features and/or diagnostic histopathology, consistent clinical pictures and the DITRA status. Pathogenesis of GPP is mediated by pathways that partly overlap plaque type psoriasis, with a more pronounced activity of the innate immune system. Both IL-1 and IL-36 but also IL-17 play a major role in disease formation. We ascertained a total of 101 published cases according to our predefined criteria and identified TNF-α, IL-12/23, IL-17 and IL-1β as targets for immunotherapy for the treatment of GPP. Of those cases, 61% showed complete response and 27% partial response to targeted immunotherapy. Only 12% experienced weak or no response. These data indicate that specific immunotherapy can be used to effectively treat GPP, with most evidence existing for anti-IL-17 agents.

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“…On the other hand, several reports suggest that TNF‐a inhibitors can also trigger GPP flares as a paradoxical reaction …”

Section: Resultsmentioning

confidence: 99%

Generalized pustular psoriasis – a model disease for specific targeted immunotherapy, systematic review

Boehner

Navarini

Eyerich

2018

Experimental Dermatology

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“…In RA, the synovium is highly infiltrated with polarized macrophages that can produce TNF‐α, interleukin‐1 beta (IL‐1β), and other proinflammatory cytokines. As TNF‐α can induce the generation of various cytokines that will drive other proinflammatory mediators, it has become a critical therapeutic target in RA, and numerous anti‐TNF‐α drugs have been successfully applied for the treatment of arthritis . Recently, Bao et al .…”

Section: Introductionmentioning

confidence: 99%

“…In RA, the synovium is highly infiltrated with polarized macrophages that can produce TNF-a, interleukin-1 beta (IL-1b), and other proinflammatory cytokines. As TNF-a can induce the generation of various cytokines that will drive other proinflammatory mediators, it has become a critical therapeutic target in RA, and numerous anti-TNF-a drugs have been successfully applied for the treatment of arthritis [8][9][10]. Recently, Bao et al [11] reported that after the failure of treatment with IL-1 receptor antagonist, switching from IL-1Ra to infliximab, the TNF-a inhibitor, is effective in improving disease activity and maintaining joint function for patients with RA.…”

Section: Introductionmentioning

confidence: 99%

IL‐35 ameliorates collagen‐induced arthritis by promoting TNF‐α‐induced apoptosis of synovial fibroblasts and stimulating M2 macrophages polarization

Peng

Qiang

et al. 2019

The FEBS Journal

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Synovitis, the chronic inflammation of the synovial membranes, is a hallmark of rheumatoid arthritis, a chronic disease with profound impact on human health. Recently, interleukin‐35 (IL‐35), a new member of the IL‐12 family, was identified as an anti‐inflammatory and immunosuppressive cytokine and was shown to ameliorate collagen‐induced arthritis (CIA) in mice. However, the mechanism by which IL‐35 alleviates CIA remains unknown. In this study, we investigated the effect of IL‐35 on the CIA microenvironment and, specifically, the tumor necrosis factor alpha (TNF‐α)‐induced macrophage inflammatory response and apoptosis of fibroblast‐like synoviocytes (FLSs). Firstly, using RT‐PCR, western blot, and flow cytometry, we found that IL‐35 suppressed TNF‐α‐induced inflammatory responses by down‐regulating iNOS and COX‐2 in peripheral blood monocyte‐derived macrophages. IL‐35 also activated alternative M2 macrophage polarization, as determined by evaluation of CCR7 and CD206 expression. Moreover, we showed that IL‐35 enhanced TNF‐α‐induced FLS apoptosis. Using a panel of immunohistochemical and immunofluorescence analyses in a CIA model established in 18 DBA/1J mice, we demonstrated that IL‐35 promotes synoviocyte apoptosis and alternative activation of macrophages to alleviate arthritis in vivo. Taken together, our results show that IL‐35 promotes TNF‐α‐induced FLS apoptosis and modulates M2 macrophage polarization to ameliorate CIA inflammation both in vitro and in vivo.

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“…In the literature, there are only five published case reports of certolizumab-pegol-induced psoriatic lesions in which the demographic and clinical findings of the patients were documented in detail (Mocciaro, Renna, Orlando, & Cottone, 2009;Klein, Spivack, & Choate, 2010;Shelling et al, 2012;Koizumi et al, 2017;Fischer, DaCunha, & Rajpara, 2017). None of these cases had AS, as the underlying disease like ours.…”

Section: Discussionmentioning

confidence: 99%

Psoriasiform skin eruption in a patient receiving certolizumab-pegol for ankylosing spondylitis: Report of a case and review of the literature

Kobaner

Ekinci

Yılmaz

et al. 2018

Dermatologic Therapy

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Certolizumab-pegol is the first and only pegylated TNF-α antagonist approved in the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. We herein present a case of certolizumab-pegol induced generalized psoriasiform eruption in a patient with ankylosing spondylitis. The diagnosis was based on typical clinical and histopathological findings and further confirmed with Naranjo Adverse Drug Reaction Probability Scale which revealed a total score of nine supporting a definite causal relationship between the drug and skin eruption. As an important finding, a significant improvement of the generalized plaque lesions was achieved upon a therapy including high-potency topical corticosteroid and oral antihistamine without discontinuation of certolizumab-pegol. Moreover, we also present a literature review of the previously published cases with certolizumab-pegol induced psoriasiform eruption. Since all of these cases had Crohn's disease or rheumatoid arthritis as the underlying disease, this is the first case report of certolizumab-pegol induced psoriasiform eruption in a patient with ankylosing spondylitis, to the best of our knowledge.

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Certolizumab pegol, a pegylated anti‐TNF‐α antagonist, caused de novo‐onset palmoplantar pustulosis followed by generalized pustular psoriasis in a patient with rheumatoid arthritis

Cited by 18 publications

References 4 publications

Generalized pustular psoriasis – a model disease for specific targeted immunotherapy, systematic review

Generalized pustular psoriasis – a model disease for specific targeted immunotherapy, systematic review

IL‐35 ameliorates collagen‐induced arthritis by promoting TNF‐α‐induced apoptosis of synovial fibroblasts and stimulating M2 macrophages polarization

Psoriasiform skin eruption in a patient receiving certolizumab-pegol for ankylosing spondylitis: Report of a case and review of the literature

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