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Table of Contents
CORRESPONDENCE
Year : 2020  |  Volume : 38  |  Issue : 2  |  Page : 113-114

Reactivation of Epstein–Barr virus and cytomegalovirus in patients with psoriasis after ustekinumab treatment


1 Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
3 Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Date of Submission13-Oct-2018
Date of Decision25-Dec-2018
Date of Acceptance02-Aug-2019
Date of Web Publication27-Dec-2019

Correspondence Address:
Dr. Tsen-Fang Tsai
Department of Dermatology, National Taiwan University Hospital and National Taiwan, University College of Medicine, No. 7, Zhongshan South Rodd, Zhongzheng District, Taipei City 100
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_20_19

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How to cite this article:
Hsieh CY, Chiu HY, Hua TC, Tsai TF. Reactivation of Epstein–Barr virus and cytomegalovirus in patients with psoriasis after ustekinumab treatment. Dermatol Sin 2020;38:113-4

How to cite this URL:
Hsieh CY, Chiu HY, Hua TC, Tsai TF. Reactivation of Epstein–Barr virus and cytomegalovirus in patients with psoriasis after ustekinumab treatment. Dermatol Sin [serial online] 2020 [cited 2020 Sep 25];38:113-4. Available from: http://www.dermsinica.org/text.asp?2020/38/2/113/274169



Dear Editor,

Ustekinumab, a human monoclonal antibody targeting shared p40 subunit of interleukin-12 (IL-12) and IL-23, is a well-established therapy for moderate-to-severe psoriasis with efficacy and safety proved in a double-blind, placebo-controlled trial. Studies have suggested that IL-12 could play a vital role in defense of viral and bacterial infections and cancers. A recent registry data suggested a higher hazard ratio of zoster in patients using ustekinumab compared to those using tumor necrosis factor inhibitor.[1] Furthermore, a subgroup analysis of Asian patients in the CLEAR study revealed a higher percentage of zoster in a patient receiving ustekinumab compared to secukinumab.[2] However, the risk of other herpesviruses reactivation is not well studied in patients receiving biologics.

In this study, we investigated whether ustekinumab could affect Epstein–Barr virus (EBV) and cytomegalovirus (CMV) viral loads in patients with psoriasis. A prospective, observational study which included 18 consecutive patients treated with ustekinumab was performed in our clinics after institutional bureau approval between July 2011 and January 2015. Ustekinumab 45 mg was given at weeks 0, 4, and 16. Samples of both plasma and peripheral blood mononuclear cells (PBMCs) were obtained at baseline (week 0) and after treatment (week 28), and viral loads were quantified by the real-time polymerase chain reaction.

The patient profiles before and after ustekinumab use are shown in [Table 1]. Seventeen (94.4%) patients had positive CMV IgG at baseline, indicating past infection. However, no patients had detectable CMV DNA in PBMCs or serum. After treatment, CMV DNA remained undetectable in all 18 patients.
Table 1: Patient demographics, diseases characteristics, viral and antibody status before and after ustekinumab treatment

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All patients had positive EBV IgG at baseline, which is compatible with remote infection. The EBV viral loads remained undetectable in serum before and after the treatment. Two (11.1%) patients had baseline detectable EBV DNA in PBMCs. One (5.55%) patient with baseline detectable EBV DNA reverted to undetectable; one (5.55%) patient with baseline detectable EBV DNA sustained positivity and increased in viral loads. Two (11.1%) patients with baseline undetectable EBV DNA converted to detectable in PBMCs. These changes, nonetheless, were not statistically significant, and no clinical symptoms of EBV infection occurred. Compared with baseline, although the mean EBV loads of eighteen patients increased from 52.2 ± 191.6 to 268.3 ± 897 copies/μg DNA (mean ± standard deviation), which was higher than the result of our previous study performed in patients treated with secukinumab (46.6 ± 129.1–70.9 ± 223.5),[3] both trends were not statistically significant [Table 2]. Besides, no specific features in PASI score at baseline, PASI improvement, age, and the duration of psoriasis were observed in patients with EBV viral load changes.
Table 2: Changes in Epstein–Barr virus viral loads in peripheral blood mononuclear cells before and after ustekinumab treatment in psoriasis patients

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Both EBV and CMV are ubiquitous viruses present in the most normal population. However, severe and fatal cases can occur after immunosuppression. The primary infection of EBV and CMV usually occurs in childhood and persisted lifelong in infected individuals. Virus-specific CD8+ cytotoxic T lymphocytes and virus-specific CD4+ T-cells are indispensable in preventing reactivation.[4] Certain immunosuppressive agents such as anti-thymoglobulin, alemtuzumab, tofacitinib, cyclosporine, and methotrexate may induce EBV and CMV reactivation.[5],[6] However, the human IL-12/IL-23-interferon-γ axis seems to play a relatively redundant role in immunity to most viruses compared to its mice counterpart.[7] It may possibly explain the rare occurrence of clinically significant viral reactivation, especially EBV and CMV, seen in psoriasis patients treated with biologics, including ustekinumab.

The limitations of this study are small sample size and lack of control group. However, a similar study was reported in patients treated with secukinumab.[3] Although no significant change in EBV and CMV viral loads was detected, we noticed a numerical increment in the proportion of EBV positivity and mean EBV viral load in PBMCs. Thus, clinical vigilance is still needed in psoriasis patients presenting with the symptoms of EBV infection during ustekinumab treatment. Further studies which include more patients with longer duration of follow-up are needed to better address the effect of biologics on CMV, EBV, and other viral reactivation and its clinical implications.

Financial support and sponsorship

This study was financially supported by the National Taiwan University Hospital, Hsin-Chu Branch (107-HCH009).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Shalom G, Naldi L, Lebwohl M, Nikkels A, de Jong EM, Fakharzadeh S, et al. Biological treatment for psoriasis and the risk of herpes zoster: results from the psoriasis longitudinal assessment and registry (PSOLAR). J Dermatolog Treat 2019;30:534-9.  Back to cited text no. 1
    
2.
Tsai TF, Huang YH, Lee JH, Lee JC, Kim TG, Aw DC, et al. Secukinumab demonstrates superior efficacy and faster response in clearing skin of Asian patients with moderate-to-severe plaque psoriasis compared to ustekinumab: A subgroup analysis of the CLEAR study. 27th European Academy of Dermatology and Venereology, Annual Meeting. Poster 1930. Paris, France; 12-16 September, 2018.  Back to cited text no. 2
    
3.
Chiu HY, Chan CC, Tsai TF. The impact of long-term secukinumab treatment on Epstein–Barr virus and cytomegalovirus loads in patients with psoriasis. Int J Dermatol 2016;55:e600-02.  Back to cited text no. 3
    
4.
Khanna R, Burrows SR. Role of cytotoxic T lymphocytes in Epstein-Barr virus-associated diseases. Annu Rev Microbiol 2000;54:19-48.  Back to cited text no. 4
    
5.
Valenzuela F, Papp KA, Pariser D, Tyring SK, Wolk R, Buonanno M. Effects of tofacitinib on lymphocyte sub-populations, CMV and EBV viral load in patients with plaque psoriasis. BMC Dermatol 2015;15:8.  Back to cited text no. 5
    
6.
Scheinberg P, Fischer SH, Li L, Nunez O, Wu CO, Sloand EM, et al. Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 2007;109:3219-24.  Back to cited text no. 6
    
7.
Novelli F, Casanova JL. The role of IL-12, IL-23 and IFN-gamma in immunity to viruses. Cytokine Growth Factor Rev 2004;15:367-77.  Back to cited text no. 7
    



 
 
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