10.5826/dpc.1301a27
Introduction: Psoriasis and its treatments may predispose patients to various infections. This is considered one of the most significant complications in patients with psoriasis. 
Objectives: In the present study, we aimed to determine the prevalence of infection in hospitalized psoriasis patients and its relationship with systemic and biologic treatments.
Methods: All hospitalized patients with psoriasis from 2018 to 2020 in Razi Hospital in Tehran, Iran, were studied and cases of infection were recorded.
Results: Overall, 516 patients were studied and 25 types of infection in 111 patients were found. The most common types of infection were pharyngitis and cellulitis, followed by oral candida, urinary tract infections, common cold, fever of unknown origin, and pneumonia. Female sex and pustular psoriasis were significantly associated with infection in psoriatic patients. Those patients who received prednisolone had a higher risk of infection, and those under treatment with methotrexate or infliximab had a lower risk of infection.
Conclusion: Overall, 21.5% of psoriasis patients in our study had at least one episode of infection. This demonstrates that the prevalence of infection in these patients is not low. Using systemic steroids was associated with a higher risk of infection, while using methotrexate or infliximab was concomitant with a lower risk of infection.
text/xml
2160-9381
2385
en
Maryam Daneshpazhooh
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
methotrexate
Infections In Hospitalized Patients With Psoriasis In A Skin Referral Hospital
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-01-31
2022-02-11
2023-01-31
2023-02-27
e2023027
Dermatol Pract Concept
Introduction: Psoriasis and its treatments may predispose patients to various infections. This is considered one of the most significant complications in patients with psoriasis. 
Objectives: In the present study, we aimed to determine the prevalence of infection in hospitalized psoriasis patients and its relationship with systemic and biologic treatments.
Methods: All hospitalized patients with psoriasis from 2018 to 2020 in Razi Hospital in Tehran, Iran, were studied and cases of infection were recorded.
Results: Overall, 516 patients were studied and 25 types of infection in 111 patients were found. The most common types of infection were pharyngitis and cellulitis, followed by oral candida, urinary tract infections, common cold, fever of unknown origin, and pneumonia. Female sex and pustular psoriasis were significantly associated with infection in psoriatic patients. Those patients who received prednisolone had a higher risk of infection, and those under treatment with methotrexate or infliximab had a lower risk of infection.
Conclusion: Overall, 21.5% of psoriasis patients in our study had at least one episode of infection. This demonstrates that the prevalence of infection in these patients is not low. Using systemic steroids was associated with a higher risk of infection, while using methotrexate or infliximab was concomitant with a lower risk of infection.
Maryam Daneshpazhooh
2023/01/31
10.5826/dpc.1301a27
e2023027
Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
2160-9381
methotrexate
en
e2023027
Haddad A, Li S, Thavaneswaran A, Cook RJ, Chandran V, Gladman DD. The Incidence and Predictors of Infection in Psoriasis and Psoriatic Arthritis: Results from Longitudinal Observational Cohorts. The Journal of rheumatology. 2016;43(2):362-6.
Infections In Hospitalized Patients With Psoriasis In A Skin Referral Hospital
https://dpcj.org/index.php/dpc/article/download/2385/1975
    Infections in Hospitalized Patients with Psoriasis
                in a Skin Referral Hospital
         Nafise Zaredar1, Hamidreza Mahmoudi1,2, Tahereh Soori1,3, Amir Teimourpour1,
                Kamran Balighi1,2, Ali Salehi Farid1,2, Maryam Daneshpazhooh1,2


1 Department of Dermatology, Tehran University of Medical Sciences, Tehran, Iran
2 Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Infectious Diseases, Tehran University of Medical Sciences, Tehran, Iran



Key words: psoriasis, infection, biologic treatment, anti-TNFa, methotrexate
Citation: Zaredar N, Mhamoudi H, Soori T, et al. Infections In Hospitalized Patients With Psoriasis In A Skin Referral Hospital. Dermatol
Pract Concept. 2023;13(1):e2023027. DOI: https://doi.org/10.5826/dpc.1301a27
Accepted: July 15, 2022; Published: January 2023
Copyright: ©2023 Zaredar 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: Maryam Daneshpazhooh, Razi Hospital, Vahdate-Eslami Sq, Tehran 11996 Iran; ORCID 0000-0003-1020-8895
Phone number and fax: +98-21-55618989; Email: maryamdanesh.pj@gmail.com




  ABSTRACT             Introduction: Psoriasis and its treatments may predispose patients to various infections. This is
                       ­considered one of the most significant complications in patients with psoriasis.
                       Objectives: In the present study, we aimed to determine the prevalence of infection in hospitalized
                       psoriasis patients and its relationship with systemic and biologic treatments.
                       Methods: All hospitalized patients with psoriasis from 2018 to 2020 in Razi Hospital in Tehran, Iran,
                       were studied and cases of infection were recorded.
                       Results: Overall, 516 patients were studied and 25 types of infection in 111 patients were found. The
                       most common types of infection were pharyngitis and cellulitis, followed by oral candida, urinary tract
                       infections, common cold, fever of unknown origin, and pneumonia. Female sex and pustular psoriasis
                       were significantly associated with infection in psoriatic patients. Those patients who received prednis-
                       olone had a higher risk of infection, and those under treatment with methotrexate or infliximab had
                       a lower risk of infection.
                       Conclusion: Overall, 21.5% of psoriasis patients in our study had at least one episode of infection.
                       This demonstrates that the prevalence of infection in these patients is not low. Using systemic steroids
                       was associated with a higher risk of infection, while using methotrexate or infliximab was c­ oncomitant
                       with a lower risk of infection.




Original Article | Dermatol Pract Concept. 2023;13(1):e2023027                                                                          1
Introduction                                                         to the probability that the result will occur in the absence of
                                                                     that exposure.
Psoriasis is a common, chronic, inflammatory cutaneous dis-
ease, causing morbidity and mortality in severe cases. The
                                                                     Results
approximate prevalence rate is 0.14-5.32% of the general
population. [1, 2]                                                   Among 516 patients, 172 (33%) women and 344 (67%)
    The characteristic of psoriasis is sustained inflammation        men, with a mean age of 43.85 +/- 15.95 (range: 8 to 89).
which causes uncontrolled proliferation of keratinocytes and         The mean age of men was greater than women (44.97 +/-
dysfunctional differentiation that activates through TNF-α,          15.40 vs 41.62 +/- 16.83) (P- value: 0.024).
IL-17, and IFN-γ.                                                       380 (73.6%), 106 (20.5%), 25 (4.8%), 4 (0.8%) and
    The psoriatic plaque’s histology shows acanthosis, which         1(0.2%) were plaque-type, pustular, erythrodermic, inverse
covers inflammatory infiltrates consisting of dermal den-            and guttate, respectively.
dritic cells, macrophages, T cells, and neutrophils as well as          Furthermore, from 248 available data, 144 (58.06%)
neovascularization [3].                                              patients had arthropathy. Meanwhile, 111 (21.5%) patients
    Infections are among the most concerning complications           had at least one episode of infection; overall, 166 cases were
of psoriasis per se and its treatments. Two types of conven-         detected.
tional and biological treatments are used to treat this disease.        Considering the low number of patients with inverse and
Biologic treatments are mostly used in more severe psoriasis         guttate psoriasis, only plaque-type, pustular and erythroder-
patients; however, infections are the most crucial side effect       mic psoriasis were analyzed.
of these drugs. Recent studies have found conflicting results           The most common types of infection were pharyngitis,
regarding the prevalence of infection in this disease and its        cellulitis followed by oral candidiasis, urinary tract infec-
relationship with various systemic treatments. This study            tions (UTI), common cold, fever of unknown origin (FUO),
evaluated the prevalence of infection in psoriasis hospital-         and pneumonia (Table 1).
ized patients in a skin referral hospital and its relationship          There was a significant correlation between age and oral
with variables such as biologic treatments in hospitalized           candidiasis, UTI, and herpes simplex virus (HSV) infection
patients with psoriasis.                                             (P-values: 0.023, 0.012, 0.001, respectively), while no signif-
                                                                     icant relationship was found between age and other types of
                                                                     infections (P-value<0.05 for all).
Methods
                                                                        Infections were 2 times more frequent in women (30.2%)
In this retrospective cross-sectional study, all hospitalized pso-   than men (17.2%) (OR: 2.09, 95%CI: 1.36-3.21, P-value:
riasis patients from 2018 to 2020 in Razi Hospital in Tehran,        0.001). Additionally, oral candidiasis, flexural candidiasis,
Iran were examined for any documented infection. Demo-               and erythrasma were significantly more common in women
graphic data, psoriasis subtypes, the existence of arthropathy,      (P-values: 0.011, 0.044, 0.001, respectively).
and present treatments (methotrexate, prednisolone, cyclo-              Regarding psoriasis subtypes, there was a significant
sporine, acitretin, phototherapy, topical treatment, and bio-        ­relation between plaque-type and pustular psoriasis with in-
logical treatment) were extracted. Furthermore, the wound,           fection (P-values: <0.001, OR: 0.282; P-value <0.001, OR:
blood, and urine culture results were recorded. All hospital         3.845, respectively). In other words, patients with pustular
records over the course of the study were reviewed and cases         and plaque-type psoriasis had a 3.8 and 2.8 times higher risk
of diagnosed psoriasis were included in the study. Cases of          of infection in comparison with other subtypes, respectively.
comorbid psoriasis with other skin disease were excluded.            Furthermore, cellulitis, pharyngitis, FUO, oral candidiasis,
    These data were analyzed with SPSS software (IBM                 UTI, vaginal candidiasis, and bacterial blepharitis were sig-
Corp. Released 2017. IBM SPSS Statistics for Windows, Ver-           nificantly more common in the pustular subtype (Table 2).
sion 25.0. Armonk, NY: IBM Corp). Associations between                  Concerning the relationship between medications and
infections and other variables were examined using the Chi-          infection, patients treated with prednisolone (OR: 2.93,
Square test. The frequency has been calculated for quantita-         95%CI: 1.82-4.73, P-value< 0.001) had a higher risk of
tive data, mean and standard deviation, for qualitative data.        infection. From a total of 99 cases on prednisolone, 38
The significance level was considered a P-value < 0.05. Con-         (38.4%) had at least one episode of infection, while the in-
fidence interval (CI) is the range of values between which           fection was seen in 73 (17.5%) out of 417 cases who were
you expect your estimate to be if you repeat your test, at a         not receiving prednisolone (P-value: <0.001, OR: 2.93).
certain level of confidence.                                         On the other hand, those under treatment of methotrexate
    An odds ratio (OR) is a measure of how an exposure re-           (OR: 2.1, 95%CI: 0.29-0.76, P-value: 0.002) or infliximab
lates to a result. The OR represents the probability that a re-      (OR: 5.12, 95%CI: 0.10-0.35, P-value< 0.001) had a lower
sult will occur as a result of a particular exposure compared        risk of infection (Table 3).

2                                                                        Original Article | Dermatol Pract Concept. 2023;13(1):e2023027
              Table 1. Types of infections and frequency of each occurrence in psoriatic patients.
                                              Number of infections
         Type of infection                   1            2           3          Total/Person                Total/Infection
 Cellulitis                                 20            1           -                21                     22 (13.25%)
 Pharyngitis                                26             -          1                27                     29 (17.47%)
 Common cold                                11             -          -                11                      11 (6.62%)
 Pneumonia                                    7            -          -                  7                      7 (4.21%)
 Paronychia                                   3            -          -                  3                      3 (1.8%)
 FUO                                          5            -          1                  6                      8 (4.82%)
 Oral Candida                               17            1           -                18                     19 (11.44%)
 Conjunctivitis                               5           1           -                  6                      7 (4.21%)
 UTI                                        12            1           1                14                     17 (10.24%)
 HBV                                          3            -          -                  3                      3 (1.8%)
 HCV                                          4            -          -                  4                      4 (2.41%)
 HIV                                          3            -          -                  3                      3 (1.8%)
 HSV                                          3            -          -                  3                      3 (1.8%)
 Erythrasma                                   6            -          -                  6                      6 (3.61%)
 Gastroenteritis                              4            -          -                  4                      4 (2.41%)
 Otitis externa                               2            -          -                  2                      2 (1.2%)
 Tuberculosis                                 1            -          -                  1                      1 (0.6%)
 Epididymitis                                 1            -          -                  1                      1 (0.6%)
 Axillary abscess                             1            -          -                  1                      1 (0.6%)
 Septic arthritis                             2            -          -                  2                      2 (1.2%)
 Impetigo                                     1            -          -                  1                      1 (0.6%)
 Flexural candidiasis                         7            -          -                  7                      7 (4.21%)
 Folliculitis                                 1            -          -                  1                      1 (0.6%)
 Vaginal Candidiasis                          2            -          -                  2                      2 (1.2%)
 Blepharitis                                  2            -          -                  2                      2 (1.2%)
 Total                                                                                                              166

FUO: fever of unknown origin, UTI: urinary tract infection, HBV: hepatitis B virus, HCV: hepatitis C virus, HIV: human immunodeficiency
virus, HSV: herpes simplex virus



       Table 2. The relationship between psoriasis subtypes and the most prevalent infection types.
                                                  Non- plaque                                         Non- pustular
                              Plaque type            type           P-value      Pustular type            type              P-value
 Cellulitis                     8 (2.1%)           13 (9.6%)         0.000         11 (10.4%)            10 (2.4%)           0.001
 Pharyngitis                   15 (3.9%)           12 (8.8%)         0.028         11 (10.4%)            16 (3.9%)           0.008
 FUO                            1 (0.3%)            5 (3.7%)         0.006          4 (3.8%)              2 (0.5%)           0.018
 Oral Candidiasis               7 (1.8%)           11 (8.1%)         0.002          9 (8.5%)              9 (2.2%)           0.004
 UTI                            7 (1.8%)            7 (5.1%)         0.061          6 (5.7%)               8 (2%)            0.047
 HSV                             0 (0%)             3 (2.2%)         0.018          2 (1.9%)              1 (0.2%)           0.109
 Vaginal Candidiasis             0 (0%)             2 (1.5%)         0.069          2 (1.9%)               0 (0%)            0.042
 Blepharitis                     0 (0%)             2 (1.5%)         0.069          2 (1.9%)               0 (0%)            0.042



    In patients on prednisolone, the risk of cellulitis, pharyn-          Regarding the anti-TNFα group, infliximab was associ-
gitis, common cold, FUO, UTI, and blepharitis was higher.            ated with a lower risk of cellulitis (OR:0.04, P-value: 0.001)
Additionally, cyclosporine was associated with a higher risk         (Table 4), while adalimumab and etanercept were not linked
of FUO and patients receiving methotrexate had a lower               to any type of infection (all p-values>0.05). It is worth noting
chance of pharyngitis (Table 4).                                     that although no case of active tuberculosis was recognized,

Original Article | Dermatol Pract Concept. 2023;13(1):e2023027                                                                        3
                   Table 3. The relationship between infections and current treatments.
                                                    Infection
                                               No               Yes             Total         P-value         OR         95%CI
 Methotrexate        No     Count             237               83               320           0.002         0.47      0.29-0.76
                            %               74.10%           25.90%           100.00%
                     Yes    Count             168               28               196
                            %               85.70%           14.30%           100.00%
 Prednisolone        No     Count             344               73               417           0.000         2.93      1.82-4.73
                            %               82.50%           17.50%           100.00%
                     Yes    Count              61               38                99
                            %               61.60%           38.40%           100.00%
 Cyclosporine        No     Count             386               103              489            0.29         1.57       0.67-3.7
                            %               78.90%           21.10%           100.00%
                     Yes    Count              19                8                27
                            %               70.40%           29.60%           100.00%
 Acitretin           No     Count             249               54               303           0.075         1.68      0.81-1.57
                            %               82.20%           17.80%           100.00%
                     Yes    Count             186               27               213
                            %               87.32%           12.68%           100.00%
 Phototherapy        No     Count             375               100              475            0.38         1.37      0.66-2.84
                            %               78.90%           21.10%           100.00%
                     Yes    Count              30               11                41
                            %               73.20%           26.80%           100.00%
 Topical             No     Count              92               22               114            0.51         1.18         0.7-2
                            %               80.70%           19.30%           100.00%
                     Yes    Count             313               89               402
                            %               77.90%           22.10%           100.00%
 Infliximab          No     Count             241               98               339           0.000         0.19      0.10-0.35
                            %               71.10%           28.90%           100.00%
                     Yes    Count             164               13               177
                            %               92.70%           7.30%            100.00%
 Adalimumab          No     Count             401               110              511              1          0.91       0.1-8.23
                            %               78.50%           21.50%           100.00%
                     Yes    Count              4                 1                5
                            %               80.00%           20.00%           100.00%
 Etanercept          No     Count             401               110              511              1          0.91       0.1-8.23
                            %               78.50%           21.50%           100.00%
                     Yes    Count              4                 1                5
                            %               80.00%           20.00%           100.00%
 Total                      Count             405               111              516
                            %               78.50%           21.50%           100.00%



63 (12.2%) patients received isoniazid due to positive PPD      detected micro-organisms in blood cultures. In urine cul-
and use of immunosuppressive therapy.                           tures, E-coli (18.51%) followed by Pseudomonas (11.11%),
    Culture results were available in 82 cases; 45 (54.8%)      and in wound cultures, Staph epidermidis (29.76%) fol-
were negative. Staphylococcus epidermidis (36.36%) fol-         lowed by Staphylococcus aureus (28.57%) were the most
lowed by Enterobacter (9.09%) were the most commonly            common pathogens.




4                                                                     Original Article | Dermatol Pract Concept. 2023;13(1):e2023027
              Table 4. The relationship between treatments and the most prevalent infection types.
                             Methotrexate                 Prednisolone              Cyclosporine                  Infliximab
                          P-value          OR          P-value      OR          P-value         OR         P-value         OR
 Cellulitis                0.172          0.497         0.042       2.73          0.302         1.97       0.001*         0.04
 Pharyngitis              0.032*          0.355         0.016       2.64          0.645         1.48        0.346         0.65
 Common cold              0.755           1.37          0.009       5.31            1           0.75        0.108         0.18
 FUO                      0.088           0.12          0.001     22.12           0.035         9.7         0.669         0.38
 UTI                      0.703           1.23          0.034       3.29          0.533         1.408       0.154         0.31
 Blepharitis              0.528           0.32          0.037     21.41           0.102        18.77          1           1.92

*Negative correlation




Discussion                                                         disease-based registry (PSOLAR) reported that the most
                                                                   common types of serious infections were pneumonia and cel-
In the present study, we found that 21.5% of hospitalized          lulitis. [9] Likewise, in the present study, the most common
psoriasis patients had at least one episode of infection; a to-    infections were respiratory tract infections followed by skin
tal of 25 types were recorded in 111 patients. Men outnum-         infections and UTIs.
bered women in this study, which may reflect more severe                 In terms of the psoriasis subtypes, 50% of inverse,
disease needing hospitalization in men. However, psoriatic         42.5% of pustular, 24% of erythrodermic, and 15.3% of
women were more prone to infections.                               plaque-type psoriasis had a history of infection. In the pres-
    In our study, the most common types of infection were          ent study, the chance of infection in patients with pustu-
pharyngitis (n=29), cellulitis (n=22), oral candidiasis (n=19),    lar psoriasis was 3.8 times higher than with other types;
UTI (n=17), common cold (n=11), FUO (n=8) and pneumo-              however, because of the low frequency of inverse psoriasis,
nia (n=7).                                                         the high frequency of infections in this group cannot be
    There was a significant correlation between age and            inferred.
oral candidiasis, UTI, and HSV. Previous studies have                    Patients with psoriasis may be more susceptible to infec-
shown a higher prevalence of oral and cutaneous candida            tions due to both the disease per se and the immunosuppres-
colonization and infection in psoriasis. [4, 5] Similarly, in      sive medications. Previous studies have shown conflicting
the present study, oral candidiasis was the third most com-        results about the correlation between different treatments
mon infection, especially seen in the elderly; this may be         and the risk of infection. The essential difference between
partly attributed to dentures. Meanwhile, the older age of         the biologic and conventional treatments, using combina-
prevalence of UTI could be due to more common genitouri-           tion therapies, could be considered possible reasons for this
nary problems in the elderly and lack of personal hygiene          discrepancy.
in this group.                                                           In our study, cyclosporine was significantly associated
    We did not have precise details regarding the reason for       with FUO, although the overall risk of infection was not
the patients’ hospitalization, although it was primarily due       higher in contrast to Sejio et al., who reported a higher
to the psoriasis flare-up and not the infections per se. The       risk of overall and serious infections. [10] Likewise, pred-
most serious infections that led to hospitalization in this        nisolone was associated with 2.93 times more frequent
study were probably cellulitis followed by UTI.                    infections. Furthermore, we did not find any relationship
    In a Prospective Cohort Study from the British Associ-         between acitretin and infections, while Seijo et al. reported a
ation of Dermatologists Biologic and Immunomodulators              lower risk of infection with acitretin. [10] These controver-
Register, the most common types of infection in psoriatic          sial results could be due to the predominant use of acitretin
patients were lower respiratory tract infections, followed         as a combination therapy with other drugs in the present
by skin and soft tissue infections, and urinary tract infec-       study. Another controversial finding of our study was the
tions. [6] While in a cohort study in the United Kingdom,          lower risk of infection among patients treated with metho-
upper and lower respiratory tract infections were the most         trexate, which is not in concordance with its immunosup-
prevalent. [7] In addition, a population-based cohort in the       pressive nature.
Netherlands showed that respiratory tract, abdominal, and                These controversies also exist in the prevalence of infec-
skin infections occurred most frequently in patients with          tions in psoriasis patients using biologic drugs. Hsu et al.
psoriasis. [8] Another study in a multicenter, longitudinal,       stated that biologic treatments might increase the risk of




Original Article | Dermatol Pract Concept. 2023;13(1):e2023027                                                                   5
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the relationship between the risk of COVID-19 infection
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and the variables mentioned above.                                 12. Carneiro C, Bloom R, Ibler E, Majewski S, Sable KA, Guido NJ,
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                                                                   13. Yiu ZZ, Exton LS, Jabbar-Lopez Z, Mustapa MFM,
Overall, 21.5% of psoriasis patients in the present study had          ­Samarasekera EJ, Burden AD, et al. Risk of serious infections in
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risk of infection in patients receiving prednisolone, while             and meta-analysis. 2016;136(8):1584-91.
                                                                   14. Garcia-Doval I, Cohen AD, Cazzaniga S, Feldhamer I, Addis A,
there was no increase in infection risk in patients treated
                                                                        Carretero G, et al. Risk of serious infections, cutaneous bacte-
with biologic drugs and even a relatively reduced risk in
                                                                        rial infections, and granulomatous infections in patients with
MTX-treated patients.                                                   psoriasis treated with anti–tumor necrosis factor agents versus




6                                                                       Original Article | Dermatol Pract Concept. 2023;13(1):e2023027
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    2017;76(2):299-308. e16.                                                  flammation index for predicting the disease activation in pa-
15. Yiu ZZN, Ashcroft DM, Evans I, McElhone K, Lunt M, Smith                  tients with psoriasis. International Journal of Clinical Practice.
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Original Article | Dermatol Pract Concept. 2023;13(1):e2023027                                                                                7
