10.5826/dpc.1301a16
Modern treatments continue to be developed, based on identifying targets within the innate and adaptive immune pathways associated with psoriasis. Whilst there is a sound biologic rationale for increased risk of infection following treatment with immunomodulators, the clinical evidence is confounded by these agents being used in patients affected with several comorbidities. In an era characterized by ever greater and growing risk of infections, it is necessary to always be updated on this risk. In this review, we will discuss recent updates in psoriasis immunopathogenesis as a rationale for systemic therapy, outline the risk of infections linked to the disease itself and systemic therapy as well, and provide an overview about the management of infections.
text/xml
2160-9381
2415
en
Kamran Ghoreschi
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
covid-19
Overview, Management of the Infections in Psoriatic Patients Treated with Systemic Therapies: A lesson from the immunopathogenesis of psoriasis
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Review
2023-01-31
2022-02-23
2023-01-31
2023-02-27
e2023016
Dermatol Pract Concept
Modern treatments continue to be developed, based on identifying targets within the innate and adaptive immune pathways associated with psoriasis. Whilst there is a sound biologic rationale for increased risk of infection following treatment with immunomodulators, the clinical evidence is confounded by these agents being used in patients affected with several comorbidities. In an era characterized by ever greater and growing risk of infections, it is necessary to always be updated on this risk. In this review, we will discuss recent updates in psoriasis immunopathogenesis as a rationale for systemic therapy, outline the risk of infections linked to the disease itself and systemic therapy as well, and provide an overview about the management of infections.
Kamran Ghoreschi
2023/01/31
10.5826/dpc.1301a16
e2023016
Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin, Berlin, Germany
2160-9381
covid-19
en
e2023016
Blauvelt A, Lebwohl MG, Bissonnette R. IL-23/IL-17A Dysfunction Phenotypes Inform Possible Clinical Effects from Anti-IL-17A Therapies. J Invest Dermatol. 2015;135(8):1946-1953. doi:10.1038/jid.2015.144
Overview, Management of the Infections in Psoriatic Patients Treated with Systemic Therapies: A lesson from the immunopathogenesis of psoriasis
https://dpcj.org/index.php/dpc/article/download/2415/1952
   Management of Infections in Psoriatic Patients
 Treated with Systemic Therapies: A Lesson from the
         Immunopathogenesis of Psoriasis
        Anna Balato1, Emanuele Scala2,3, Kilian Eyerich2,3,4, Nicolò Costantino Brembilla5,
                    Andrea Chiricozzi6, Robert Sabat7,8, Kamran Ghoreschi9


1 Dermatology Unit, University of Campania, Naples, Italy
2 Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet,
  Stockholm, Sweden
3 Department of Dermatology and Venereology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg,
  Freiburg, Germany
4 Department of Dermatology and Venereology, Unit of Dermatology, Karolinska University Hospital, Stockholm, Sweden
5 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland
6 Institute of Dermatology, Catholic University, Rome, Italy
7 Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Charité–Universitätsmedizin, Berlin, Germany
8 Psoriasis Research and Treatment Center, Department of Dermatology and Allergy and Institute of Medical Immunology,
  Charité–Universitätsmedizin, Berlin, Germany
9 Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin, Berlin, Germany



Key words: psoriasis, infection, prevention, management, covid-19
Citation: Balato A, Scala E, Eyerich K, et al. Management Of Infections In Psoriatic Patients Treated With Systemic Therapies: A Lesson
From The Immunopathogenesis Of Psoriasis. Dermatol Pract Concept. 2023;13(1):e2023016. DOI: https://doi
.org/10.5826/dpc.1301a16
Accepted: May 30, 2022; Published: January 2023
Copyright: ©2023 Balato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Emanuele Scala, PhD, Division of Dermatology and Venereology, Department of Medicine Solna, and Center for
Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Email: emanuele.scala@ki.se




  ABSTRACT             Modern treatments continue to be developed based on identifying targets within the innate and adap-
                       tive immune pathways associated with psoriasis. Whilst there is a sound biologic rationale for increased
                       risk of infection following treatment with immunomodulators, the clinical evidence is ­confounded by
                       these agents being used in patients affected with several comorbidities. In an era characterized by an
                       ever greater and growing risk of infections, it is necessary to always be updated on this risk. In this
                       mini-review, we will discuss recent updates in psoriasis immunopathogenesis as a rationale for sys-
                       temic therapy, outline the risk of infections linked to the disease itself and systemic therapy as well, and
                       provide an overview of the prevention and management of infections.




Review | Dermatol Pract Concept. 2023;13(1):e2023016                                                                                      1
Introduction                                                      the current IL-23/IL-17-targeted therapies, possibly helping
                                                                  to explain unwanted effects or secondary loss of efficacy.
In the last decade, our understanding of psoriasis pathogen-
esis made significant steps forwards leading to the develop-      Psoriasis and Skin Infection
ment of multiple game-changer therapies [1]. Although we          Psoriatic lesions show a disturbed skin barrier function, sim-
can confidently say that the horizon is now a little brighter,    ilar to the affected skin of patients with atopic dermatitis
we cannot argue that “the whole job” has been done. The           (AD) [23-24]. This altered epidermal barrier facilitates the
advent of therapies targeting specific components of the im-      penetration of bacteria and viruses into the skin and should
mune response has highlighted the possible association of         lead to an increased incidence of cutaneous infections. How-
infections with psoriasis. Whilst there is a sound biologic       ever, the frequency of skin infections is impressively under-
rationale for increased risk of infection following treatment     represented in patients with psoriasis [25, 26]. The main
with immunomodulators, the clinical evidence is confounded        reason for this clinical observation is the specific increase
by these agents being used in moderate-to-severe psoriasis        in the levels of antimicrobial peptides (AMPs) and antivi-
in association with several comorbidities. In this article, we    ral peptides (AVPs) within the epidermis of psoriatic lesions
summarize the available information on the risk of infec-         [14, 27-29]. Correspondingly, the enhancement of AMPs
tions, including the respiratory ones, linked to psoriasis and    and AVPs in the affected skin of AD patients is only mini-
immunomodulators as well. Lastly, we provide an overview          mal and these patients often suffer from bacterial and viral
of the prevention and management of infections in psoriatic       skin infections. The mostly up-regulated AMPs in psoriatic
patients on immunomodulatory therapies.                           skin are human β-defensin (HBD)-2, S100A7 (psoriasin) and
                                                                  to a lesser extent HBD-3, S100A8 (calgranulin A), S100A9
Immunopathogenesis of Psoriasis: An Update                        (calgranulin B), and lipocalin (LCN)-2 [27, 30-32]. The spec-
Psoriasis has been primarily defined as an autoimmune,            trum of affected microbes differs among the diverse AMPs.
T-cell-mediated disease with dysregulated inflammatory            For example, S100A7 is primarily an E. coli-killing antimi-
response that is composed of both innate and adaptive im-         crobial peptide, whereas HBD-3 exhibits a broad spectrum
munity [1-4]. Other factors such as environmental ones and        of antimicrobial activity against various Gram‐negative and
genetic susceptibility are also involved [4,5]. Several gene      Gram‐positive bacteria as well as fungi [33]. AMPs inhibit
loci are associated with psoriasis, such as HLA-Cw6 and           propagation and kill microbes through various mechanisms
PSORS1-9, providing initial evidence of a possibly (auto)         such as destabilization of their membrane or sequestrating
immune component [6,7]. However, ~ 60 loci identified             metal ions [33, 34]. Most of the AMPs are constitutively ex-
contain genes involved in the immune system at large and          pressed at low levels in keratinocytes and might be strongly
the interleukin (IL)-23/T helper (Th)17 pathway in partic-        up-regulated by cytokines under inflammatory conditions.
ular [8,9]. IL-17A is the most studied cytokine of the pso-       The powerful inducers of AMPs in epithelial cells are IL-17
riatic IL-23/Th17 cell pathogenic axis and is claimed to be       and IL-22 [31, 35]. However, the synergistic action of both
directly responsible for the development of the psoriatic le-     cytokines is essential for the strong induction of AMPs in
sion [10,11]. It does not act as a single cytokine but exerts     keratinocytes [36, 37]. In psoriatic lesions, this effect might
its function in a complex cytokine network which includes         be amplified by TNF-α, interferon (IFN)-γ, IL-19, and IL-36s
IL-19, IL-22, IL-23, tumor necrosis factor (TNF)-α and sev-       [15, 37-39]. Interestingly, the joint action of IL-22 and
eral IL-1 family members [12-15]. IL-17A is not exclusively       TNF-α seems to be relevant for the maintenance of epider-
produced by Th17 cells in the lesion, but possibly also by        mal integrity during infection with Candida albicans [38].
several other cells: such as γδ T cells, type 3 innate lymphoid   The up-regulated AVPs in psoriatic lesions comprise OAS2,
cells (ILC3s) and invariant natural killer (iNK)T cells, and      BST2 (tetherin), MX1, and ISG15 [29]. The main driver
other thymus-independent cells, including mast cells and          for this increase is IL-29, a member of the IL-10-IFN fam-
neutrophils [16-19]. Besides IL-17A, the immune-derived IL-       ily of cytokines [40]. In psoriatic lesions, IL-29 is produced
17F, the epithelial-derived IL-17C and IL-17E, have all been      by Th17 cells [29]. It directly acts on keratinocytes via the
shown to independently participate in psoriasiform inflam-        transmembrane receptor complex composed of IL-28R1
mation in murine models [20-22]. Interestingly, the inhibi-       and IL-10R2 and activates intracellular JAK-STAT signal-
tion of the IL-17A/IL-23 axis might potentially lead to the       ing. Interestingly, IL-10R2 is also a part of the IL-22 recep-
enhancement of other IL-17 cytokine members, particularly         tor complex [41]. The AVP-inducing effect of IL-29 can be
the epithelial-derived cytokines. A better assessment of the      only minimally amplified by IFN-γ in keratinocytes [40]. An
different sources and the possible IL-17 substitute cytokines     overview of the main psoriasis signature cytokines and their
is critical to better understand the mechanism of action of       effects on infections is shown in Table 1.




2                                                                            Review | Dermatol Pract Concept. 2023;13(1):e2023016
                      Table 1. Psoriasis signature cytokines and their effects on infections.
     Cytokines                          Cellular sources                                              Findings
 IL-12                DCs, monocytes, macrophages, neutrophils, B             Enhances HBD-2 production in KCs, and the
                      cells and KCs                                           antimicrobial activity of macrophages
 IL-17A               Th17 cells, ILC3s, mast cells, neutrophils,             Induces the production of AMPs (HBD-2, LL-37,
                      CD8+ T cells, γδ T cells, NK cells, iNKT cells,         LCN-2, and S100A7-9) in KCs, neutrophil
                      and LTi cells                                           recruitment, and immunity to extracellular
                                                                              pathogens
 IL-17C               Prostate and fetal kidney cells, KCs, colonic           Enhances epithelial host defense (HBD-2/-3, and
                      epithelial cells, and lung epithelial cells             S100A7-9) in an autocrine/paracrine manner
 IL-17E               Intraepithelial lymphocytes, lung epithelial cells, Promotes innate cell recruitment and activation.
                      alveolar macrophages, eosinophils, basophils,       Provides immunity to extracellular pathogens
                      NKT cells, Th2 cells, mast cells, and cells of the
                      gastrointestinal tract and uterus
 IL-17F               Th17 cells, mast cells, neutrophils, CD8+ T             Synergistically cooperates with IL-17A and IL-22
                      cells, γδ T cells, NK cells, NKT cells, and LTi         for the induction of AMPs in KCs. Provides
                      cells                                                   immunity to extracellular pathogens and is involved
                                                                              in neutrophil recruitment
 IL-19                Monocytes, DCs and KCs                                  Increases the production of AMPs (S100A7-9) in
                                                                              KCs and amplifies IL-17A activity.
 IL-21                Th17 cells, Th1* cells, Th2 cells, CD8+ T cells,        Enhances the antimicrobial activity of
                      and NKT cells                                           macrophages, and maintains the CD8+ T cell
                                                                              effector activity during the infection
 IL-22                Th22 cells, Th17 cells, Th1 cells, CD8+ T cells,        Increases the expression of HBD-2/-3, and
                      γδ T cells, ILC3s, NKT cells, LTi cells, alveolar       S100A7-9 in KCs, and reinforces TNF-α activity
                      macrophages*, and neutrophils*
 IL-23                DCs, macrophages, and psoriatic KCs                     Induces HBD-2 expression in KCs, and optimizes
                                                                              the antimicrobial activity of macrophages
 IL-26                Th17 cells, Th1 cells, epithelial cells, NK cells,      Exerts antiviral and antimicrobial actions, as well
                      alveolar macrophages, and macrophage-like               as regulates the expression of HBD-2/-3
                      synoviocytes
 IL-29 (alternative Th17 cells, DCs, macrophages, mast cells, and             Induces the production of antiviral proteins (MX1,
 name INFλ)         alveolar cells                                            BST2, ISG15, and OAS2) in KCs
 IL-36s               KCs, macrophages, monocytes, DCs, and                   Promote viral resistance, and the production of
                      lymphocytes                                             AMPs in KCs
 TNF-α                Macrophages, monocytes, DCs, NK cells, T                Induces the production of S100A7 and HBD-2/-3,
                      cells, B cells, and KCs                                 as well as antimicrobial chemokines CXCL-9/-10/-
                                                                              11 in KCs

*Controversial among researchers. AMPs antimicrobial peptides, DCs dendritic cells, ILC3s type 3 innate lymphoid cells, KCs keratino-
cytes, LTi lymphoid tissue inducer, iNKT invariant natural killer T cells, Th T helper. Data from multiple sources [12-15, 20-22, 29, 31,
35-41, 81-98]


                                                                      hypertension, are smokers, and have elevated body mass in-
Psoriasis and Respiratory Infections
                                                                      dex (BMI), which can make them vulnerable to infectious
Lower respiratory tract infections including pneumonia are            diseases [25,46].
the most frequent types of serious infections among psoria-
sis patients as documented by numerous registries [42, 43].           Systemic Therapies and Infection Risk, Including
The incidence of pneumonia seems to be even increased                 SARS-CoV-2
among psoriasis patients compared to those without psoria-            The conventional systemic therapies for plaque psoriasis
sis [44,45]. However, it is not definitely clear to what extent       include cyclosporine, methotrexate, and oral retinoids [47].
this increase is related, either to psoriasis itself, its concomi-    Cyclosporine is a calcineurin inhibitor broadly suppressing
tant disorders, or its treatment [44]. In fact, psoriasis patients    T cells; methotrexate, and retinoids have multiple effects on
frequently suffer from diabetes mellitus, hyperlipidemia, and         several immune cells. More recently, 2 small-molecule drugs




Review | Dermatol Pract Concept. 2023;13(1):e2023016                                                                                   3
have been approved for the treatment of plaque psoriasis:          such as IL-1β and IL-6, which may play a pathogenic role
apremilast, an oral phosphodiesterase (PDE)-4 inhibitor,           in the ­
                                                                          severe/fatal course of Covid-19 infection are only
and dimethyl fumarate [48,49]. Both molecules impact the           moderately expressed in psoriatic lesions and do not play an
NF-kB complex and have broad functions on the immune               important role in psoriasis pathogenesis compared to other
system. Modern biological therapies, such as anti-TNF-α,           inflammatory skin diseases [57,58]. Importantly, the inci-
anti-IL-12/23, anti-IL-17, and anti-IL-23 antibodies, are          dence of Covid-19 infection, Covid-19-related hospitaliza-
designed to block specific molecular steps important in the        tion, and Covid-19-related death do not seem to be elevated
pathogenesis of psoriasis. Namely, anti-TNF-α agents neu-          among psoriasis patients treated with biologics [60,61]. The
tralize TNF-α which has a dual role as an upstream media-          disease course in most patients with biological treatment was
tor of T cell differentiation into Th1, Th17 and Th22 cells,       even milder, indicating that the anti-cytokine therapy may be
as well as a pro-inflammatory mediator synergistic with            beneficial in preventing a severe cytokine storm [59,62]. A
IL-17A, IL-17F, and IL-22 [50]. The anti-IL-12/23 agent tar-       schematization of the risks and benefits of cytokine-blocking
gets the P40 subunit shared by IL-12 and IL-23 preventing          therapies in psoriasis is displayed in Figure 1.
their interaction with the receptor and thereby blocking Th1/
Th17 immunity [1,50]. This was further developed into bi-          Prevention and Management of Infections in
ologics neutralizing only IL-23 via the p19 subunit, thereby       Psoriatic Patients Treated With Systemic Therapies
only blocking Th17 immunity [1]. Finally, direct interaction       As any patient with moderate to severe psoriasis may prog-
with IL-17A and/or other members of the IL-17 family is            ress to immunomodulatory therapies, it is important that
a successful strategy realized through IL-17A, IL-7RA, or          their immunizations are up to date. Two general strategies
bispecific IL-17A/F targeting.                                     have been suggested: screening for infection prior to therapy
    However, analysis of the population-based electronic           initiation as well as providing protection through vaccina-
medical record database from the UK on approximately               tion. As for the first strategy, guidelines suggest tuberculo-
200,000 patients with psoriasis indicates that patients with       sis screening before starting all biological therapies [63,64].
moderate-to-severe disease that receive immunosuppressive          However, data from clinical trials and post-marketing sur-
therapies do have an increased risk for opportunistic infec-       veillance with IL-23 and IL-17 inhibitors suggest that they
tions and reactivation of varicella-zoster virus [51]. Further-    are not crucial to tuberculosis reactivation [65]. Further-
more, analyzing data from psoriasis patients treated with          more, screening for Candida infections, hepatitis, human
biologic (n=2258) or non-biologic systemic agents (n=3631)         immunodeficiency virus (HIV), and other chronic infections
demonstrated that systemic therapies with biologics signifi-       is generally recommended. As for the latter, vaccination is a
cantly increase the overall risk for serious infection [52]. The   proven strategy to reduce infections. In view of this, derma-
extent of impairment and the type of infection are related to      tologists can play an important role in educating patients
the mode of action of individual drugs or drug groups [1].         about immunizations. To prevent severe infections, it is
For instance, TNF-α antagonists can lead to the reactivation       suggested that psoriatic patients receive their complete rec-
of latent tuberculosis and IL-17 neutralization may result in      ommended vaccinations (especially live vaccines) before ini-
mucocutaneous candidiasis [1]. However, it should be noted,        tiating biological therapy [66]. In short, the medical board of
there is no signal for increased risk of invasive fungal disease   the National Psoriasis Foundation recommends that all pa-
due to anti-IL-17 therapy [53]. Cases of opportunistic in-         tients with moderate-to-severe psoriasis have an assessment
fections like atypical histoplasmosis or toxoplasmosis have        of their immunization status, including immunization or
been mainly reported in connection with blocking TNF-α             disease history for varicella zoster, Haemophilus influenzae,
or IL-12/IL-23 p40 [53,54]. Accordingly, the evaluation of         tetanus, pertussis, hepatitis A and B, human papillomavirus
registry data primarily notes the association of the use of        (HPV), influenza, Neisseria meningitides, and Streptococcus
infliximab, a chimeric monoclonal anti-TNF-α antibody,             pneumoniae during initial workup [67]. Notably, vaccines
with increased incidence of pneumonia [44,45]. Further-            such as Mycobacterium vaccae, live attenuated varicella zos-
more, while neutralizing TNF-α or IL-17 has been associated        ter virus and Leishmania amastigotes have been reported to
with such a risk, there is no evidence that blocking IL-23         be effective during psoriasis treatment [68-70] even though
increases the risk of respiratory tract infections [55]. Despite   these data need to be confirmed in larger and controlled
the relevant concomitant disorders such as obesity, hyper-         clinical trials. Lastly, vaccination against SARS-CoV-2 is rec-
tension, and diabetes, recent data accumulated during the          ommended in patients with psoriasis, even in those under
Covid-19 pandemic indicate that patients with psoriasis with       biological therapy [71].
or without systemic treatment are neither at higher risk for          Hence, it is clear now that immune pathways involved in
infection with SARS-CoV-2 nor show more severe symp-               psoriasis pathogenesis contribute to host defense against cer-
toms [56]. This might be caused by the fact that cytokines,        tain pathogens, thus a possible consequence is represented



4                                                                             Review | Dermatol Pract Concept. 2023;13(1):e2023016
                                                                                                                              -TNF
                                                                                                                                   

                                                                                                                              -IL-12/23
                                                                                                                              -IL-23
                                                                                                                              -IL-17A
                                                                                                                              -IL17RA
                                                                                      TN
                                      D                                                  F




                                                            ine blocking
                                                   of cytok              the
                                                ts                          rap
                                              fi                               ies
                                           ene                                     in
                                          b
                                      d




                                                                                       ps
                                 an




                                                                                         or
                              KS




                                                                                           ias
                           RIS




                                 UPPER AND LOWER




                                                                                              is
                                RESPIRATORY INFECTIONS
                                                                        KEY PSORIATIC
                                                                       INFLAMMATORY
                                 VARICELLA ZOSTER INFECTIONS
IL-23




                                                                       MEDIATORS
                                 REACTIVATION OF LATENT                NEUTROPHIL AND
                                  TUBERCULOSIS                         T-CELL IMMUNE                           K          K
                                                                       RESPONSE
                                  MUCOCUTANEOUS                       NO HIGHER RISK OF
                                 CANDIDIASIS                           COVID-19 INFECTION




                                                                                                    7F
                                TH17
                                                                                                IL-1
                                                                                              ,
                                                                                            7A
                                                                                        IL-1


Figure 1. Schematization of risks and benefits of cytokine blocking therapies in psoriasis. D dendritic cell, IL interleukin, K keratinocyte,
Th T helper, TNF tumor necrosis factor.




by the fact that a selective inhibition might predispose to spe-        antibiotic, antiviral, or antifungal therapy. Evaluating the
cific infections. Nevertheless, some biologic agents and novel          risk-benefit ratio for recurrent serious infections, therapy
small molecule drugs (i.e., apremilast) appeared to be safer            can be restarted once infection has been fully resolved, em-
or at least not associated with significant increases in the risk       pirically after 2-4 weeks from the resolution of the infectious
of serious infections, compared to conventional nonbiologic             event [73]. Analogous therapeutic management during the
systemic compounds [72]. Mild to moderate infections (i.e.,             SARS-CoV-2 pandemic has been suggested [74,75]. In the
upper respiratory tract infections) or minor surgery (i.e., skin        event of SARS-CoV-2 infection, psoriasis treatments should
surgery, dental procedures) do not usually cause treatment              be suspended and resumed after complete resolution of
discontinuation where it would otherwise be continued. De-              COVID-19 symptoms and SARS-CoV-2 negativization. On
layed starting or interruption of immunomodulatory thera-               the contrary, in those asymptomatic SARS-CoV-2+ patients
pies is recommended in case of clinically meaningful active             with high-need-to-treat psoriasis, as well as in psoriasis
infection (severe signs and symptoms requiring systemic oral            patients who have had a severe hospital course or the per-
or intramuscular antibiotic, antiviral, or antifungal therapy)          sistence of 1 or more symptoms of COVID-19, beyond the
or serious infection requiring hospitalization or intravenous           acute phase of the illness, the decision to restart treatment



Review | Dermatol Pract Concept. 2023;13(1):e2023016                                                                                       5
    Table 2. Infectious diseases to consider for selecting biological and new small-molecule therapies.
 Class of agents          Drug              HCV                HBV                     HIV               Latent TB            CMCC
 Anti-TNF-α         Etanercept          Preferred      Not preferred          Preferred                Not                Preferred
                    Adalimumab                                                                         preferred
                    Infliximab
                    Certolizumab
                    Golimumab
 Anti-IL-12/23      Ustekinumab         Preferred      Preferred              Preferred                Preferred          Preferred
 Anti-IL-17A        Secukinumab         Preferred      Likely safe/Not        Likely safe/Not          Preferred          Not preferred
                    Ixekizumab                         enough data            enough data
 Anti-IL-17RA       Brodalumab          Preferred      Likely safe/Not        Likely safe/Not          Preferred          Not preferred
                                                       enough data            enough data
 Anti-IL-23         Guselkumab          Preferred      Not enough data        Not enough data          Preferred          Preferred
                    Tildrakizumab
                    Risankizumab
 Oral novel         Apremilast          Preferred      Not enough data        Not enough data          Preferred          Preferred
 small molecule

CMCC chronic mucocutaneous candidiasis, HBV hepatitis B virus, HCV hepatitis C virus, HIV human immunodeficiency virus, IL
­interleukin, RA receptor A, TB tuberculosis, TNF tumor necrosis factor. Data from several sources [99-101].




should be taken on a case-by-case basis [76,77]. Similar to         2. Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-
active serious infections, in case of major surgery (i.e., un-         994. doi:10.1016/S0140-6736(14)61909-7
                                                                    3. Nickoloff BJ, Qin JZ, Nestle FO. Immunopathogenesis of psoria-
der general anesthesia with exposure of large body areas,
                                                                       sis. Clin Rev Allergy Immunol. 2007;33(1-2):45-56. doi:10.1007/
internal organ surgery), guidelines recommend treatment
                                                                       s12016-007-0039-2
interruption, evaluating case-by-case patient characteris-          4. Cai Y, Fleming C, Yan J. New insights of T cells in the patho-
tics, the risk of infection, the risk of psoriasis worsening and       genesis of psoriasis. Cell Mol Immunol. 2012;9(4):302-309.
consultation with the surgeon [78]. Therapy restart can be             doi:10.1038/cmi.2012.15
considered after full recovery. Nevertheless, real-life data on     5. Harden JL, Krueger JG, Bowcock AM. The immunogenetics of
                                                                       Psoriasis: A comprehensive review. J Autoimmun. 2015;64:66-73.
perioperative management are limited and do not provide
                                                                       doi:10.1016/j.jaut.2015.07.008
strong evidence of peri- or post-operative complications due
                                                                    6. Elder JT. Genome-wide association scan yields new insights
to continuous treatment with biologic agents or apremilast             into the immunopathogenesis of psoriasis. Genes Immun.
[78-80]. Infectious diseases to consider for selecting biolog-         2009;10(3):201-209. doi:10.1038/gene.2009.11
ical and new small-molecule therapies are listed in Table 2.        7. Capon F. The Genetic Basis of Psoriasis. Int J Mol Sci.
                                                                       2017;18(12):2526. Published 2017 Nov 25. doi:10.3390/ijms
                                                                       18122526
Conclusion                                                          8. Bianchi E, Rogge L. The IL-23/IL-17 pathway in human chronic
                                                                       inflammatory diseases-new insight from genetics and targeted
In an era characterized by an ever greater and growing risk            therapies. Genes Immun. 2019;20(5):415-425. doi:10.1038
of infections, but at the same time by increasingly specific           /s41435-019-0067-y
and advanced immune-mediated therapies, it is necessary to          9. Ray-Jones H, Eyre S, Barton A, Warren RB. One SNP at a
                                                                       Time: Moving beyond GWAS in Psoriasis. J Invest Dermatol.
always be updated on the risk of such infections and on the
                                                                       2016;136(3):567-573. doi:10.1016/j.jid.2015.11.025
ability to manage them. Currently, we are witnessing a revo-
                                                                   10. Li B, Huang L, Lv P, et al. The role of Th17 cells in psoriasis. Immu-
lution in the treatment of psoriasis where the starting point          nol Res. 2020;68(5):296-309. doi:10.1007/s12026-020-09149-1
is the translational approach, and we firmly believe that by       11. Martin DA, Towne JE, Kricorian G, et al. The emerging role of
following this path we can reach a wider knowledge that                IL-17 in the pathogenesis of psoriasis: preclinical and clinical
will help us in preventing and treating properly infections            findings. J Invest Dermatol. 2013;133(1):17-26. doi:10.1038/
                                                                       jid.2012.194
associated with psoriasis.
                                                                   12. Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M, et al. Inte-
                                                                       grative responses to IL-17 and TNF-α in human keratinocytes
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Review | Dermatol Pract Concept. 2023;13(1):e2023016                                                                                           9
