10.5826/dpc.1401a41
Introduction: Psoriasis is a chronic, inflammatory, and papulo-squamous skin disorder without a radical cure. Although previous observational analyses have discovered a relationship between medication intake and increased risk of psoriasis, they are susceptible to confounders.
Objectives: We intend to ascertain if there is a causal association between specific medication intake and increased risk of psoriasis by utilizing the Mendelian randomization (MR) method.
Methods: We obtained the genome-wide association study (GWAS) data for medication intake (23 types, N = 1809) from UK Biobank samples. And we sourced the GWAS data for psoriasis from the 8th release of the FinnGen database, which included 8,075 psoriasis cases and 330,975 healthy control cases. Then a two-sample MR study was performed to determine their causal association, and inverse-variance-weighted MR (IVW-MR) was applied to calculate the effect estimates.
Results: The IVW-MR analysis uncovered a positive correlation between the intake of HMG CoA reductase inhibitors and the increased risk of psoriasis (odds ratio [OR] = 1.167, 95% confidence interval [CI] = 1.084-1.257). Similarly, the use of thyroid preparations (OR=1.080, 95% CI=1.026-1.138), nonsteroidal anti-inflammatory and antirheumatic products (OR=1.406, 95% CI=1.037-1.908), anilides (OR=1.379, 95% CI=1.004-1.894), antihistamines for systemic use (OR=1.341, 95% CI=1.104-1.630), and antihypertensives (OR=1.099, 95% CI=1.016-1.190) were associated with an increased risk of psoriasis. We did not find evidence from IVW-MR for other associations.
Conclusions: Our study offers a causal testimony that the intake of HMG CoA reductase inhibitors, thyroid preparations, nonsteroidal anti-inflammatory and antirheumatic products, anilides, antihistamines for systemic use, and antihypertensives will potentially increase the risk of psoriasis.
text/xml
2160-9381
3412
en
Huayao Zhang
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
risk factors
The Causal Association Between Medication Intake and Increased Risk of Psoriasis
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-04-10
2024-01-31
2024-02-21
e2024041
Dermatol Pract Concept
Introduction: Psoriasis is a chronic, inflammatory, and papulo-squamous skin disorder without a radical cure. Although previous observational analyses have discovered a relationship between medication intake and increased risk of psoriasis, they are susceptible to confounders.
Objectives: We intend to ascertain if there is a causal association between specific medication intake and increased risk of psoriasis by utilizing the Mendelian randomization (MR) method.
Methods: We obtained the genome-wide association study (GWAS) data for medication intake (23 types, N = 1809) from UK Biobank samples. And we sourced the GWAS data for psoriasis from the 8th release of the FinnGen database, which included 8,075 psoriasis cases and 330,975 healthy control cases. Then a two-sample MR study was performed to determine their causal association, and inverse-variance-weighted MR (IVW-MR) was applied to calculate the effect estimates.
Results: The IVW-MR analysis uncovered a positive correlation between the intake of HMG CoA reductase inhibitors and the increased risk of psoriasis (odds ratio [OR] = 1.167, 95% confidence interval [CI] = 1.084-1.257). Similarly, the use of thyroid preparations (OR=1.080, 95% CI=1.026-1.138), nonsteroidal anti-inflammatory and antirheumatic products (OR=1.406, 95% CI=1.037-1.908), anilides (OR=1.379, 95% CI=1.004-1.894), antihistamines for systemic use (OR=1.341, 95% CI=1.104-1.630), and antihypertensives (OR=1.099, 95% CI=1.016-1.190) were associated with an increased risk of psoriasis. We did not find evidence from IVW-MR for other associations.
Conclusions: Our study offers a causal testimony that the intake of HMG CoA reductase inhibitors, thyroid preparations, nonsteroidal anti-inflammatory and antirheumatic products, anilides, antihistamines for systemic use, and antihypertensives will potentially increase the risk of psoriasis.
Huayao Zhang
2024/01/31
10.5826/dpc.1401a41
e2024041
Department of Breast Surgery, Shaoguan Maternal and Child Health Hospital, Shaoguan, Guangdong, China
2160-9381
risk factors
en
e2024041
Wu S, Han J, Qureshi AA. Use of aspirin, non-steroidal anti-inflammatory drugs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis: a cohort study. Acta Derm Venereol. 2015;95(2):217-223. DOI: 10.2340/00015555-1855. PMID: 24691893. PMCID: PMC4183729.
The Causal Association Between Medication Intake and Increased Risk of Psoriasis
https://dpcj.org/index.php/dpc/article/download/3412/2422
 The Causal Association Between Medication Intake
          and Increased Risk of Psoriasis
      Zhichen Li1 , Haobin Zhou2 , Chuxian Hu3, Zechao Lu4, Zechu Lu1, Huayao Zhang5


1 The Second Clinical College of Guangzhou Medical University, Guangzhou, Guangdong, China
2 The First Clinical College of Guangzhou Medical University, Guangzhou, Guangdong, China
3 The Sixth Clinical Medical School of Guangzhou Medical University, Guangzhou, Guangdong, China
4 Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
5 Department of Breast Surgery, Shaoguan Maternal and Child Health Hospital, Shaoguan, Guangdong, China



Key words: psoriasis, medicine intake, Mendelian randomization, risk factors
Citation: Li Z, Zhou H, Hu C, Lu Z, Lu Z, Zhang H. The Causal Association Between Medication Intake and Increased Risk of Psoriasis.
Dermatol Pract Concept. 2024;14(1):e2024041. DOI: https://doi.org/10.5826/dpc.1401a41
Accepted: August 29, 2023; Published: January 2024
Copyright: ©2024 Li 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: Zhichen Li and Haobin Zhou contributed equally to this work.
Corresponding Author: Huayao Zhang, Department of Breast Surgery, Shaoguan Maternal and Child Health Hospital, No.1, Yucai Road,
Shaoguan, Guangdong, 512026, China. E-mail: hyzhang1988@163.com




  ABSTRACT             Introduction: Psoriasis is a chronic, inflammatory, and papulo-squamous skin disorder without a
                       radical cure. Although previous observational analyses have discovered a relationship between medi-
                       cation intake and increased risk of psoriasis, they are susceptible to confounders.
                       Objectives: We intend to ascertain if there is a causal association between specific medication intake
                       and increased risk of psoriasis by utilizing the Mendelian randomization (MR) method.
                       Methods: We obtained the genome-wide association study (GWAS) data for medication intake (23
                       types, N = 1809) from UK Biobank samples. And we sourced the GWAS data for psoriasis from the
                       8th release of the FinnGen database, which included 8,075 psoriasis cases and 330,975 healthy con-
                       trol cases. Then a two-sample MR study was performed to determine their causal association, and
                       inverse-variance-weighted MR (IVW-MR) was applied to calculate the effect estimates.
                       Results: The IVW-MR analysis uncovered a positive correlation between the intake of HMG CoA re-
                       ductase inhibitors and the increased risk of psoriasis (odds ratio [OR] = 1.167, 95% confidence inter-
                       val [CI] = 1.084-1.257). Similarly, the use of thyroid preparations (OR=1.080, 95% CI=1.026-1.138),
                       nonsteroidal anti-inflammatory and antirheumatic products (OR=1.406, 95% CI=1.037-1.908),
                       anilides (OR=1.379, 95% CI=1.004-1.894), antihistamines for systemic use (OR=1.341, 95%
                       CI=1.104-1.630), and antihypertensives (OR=1.099, 95% CI=1.016-1.190) were associated with an
                       increased risk of psoriasis. We did not find evidence from IVW-MR for other associations.




Original Article | Dermatol Pract Concept. 2024;14(1):e2024041                                                                       1
                      Conclusions: Our study offers a causal testimony that the intake of HMG CoA reductase inhibitors,
                      thyroid preparations, nonsteroidal anti-inflammatory and antirheumatic products, anilides, antihista-
                      mines for systemic use, and antihypertensives will potentially increase the risk of psoriasis.




Introduction                                                        Objectives
Psoriasis is a chronic, inflammatory, and p
                                          ­ apulo-squamous          It is widely accepted that genetic variants are randomly dis-
skin disorder. Psoriasis vulgaris is the most common                tributed during meiosis and scarcely influenced by environ-
­subtype, accounting for approximately 90% of cases [1].            mental factors. Unlike traditional observational analyses,
Clinically, it is characterized by sharply demarcated               the Mendelian randomization (MR) study leverages this ad-
­salmon-pink plaques in individuals with white skin but             vantage of genetic variants by utilizing them as instrumental
gray plaques in those with black skin, both covered by              variables, thereby mitigating limitations such as potential
silvery scales [2]. According to a systematic review [3],           confounders, information biases, and reverse causality to
the prevalence of psoriasis varied widely across different          the greatest extent [17]. Accordingly, we conducted an MR
regions, ranging from 0.09% in Tanzania to 5.1% in the              study and explored the causal association between medica-
USA. The distribution of psoriasis patients was also un-            tion intake and increased risk of psoriasis in this article.
equal regarding race, age, and geography. For instance, it
occurred more commonly in Caucasians, adults, and indi-
                                                                    Methods
viduals from wealthy countries [2-4]. Furthermore, psori-
asis patients often experienced poor self-esteem, anxiety,          Source of Genome-wide Association Study (GWAS)
depression, insomnia, and even suicidality because of their         Data and Harmonization
unsightly external appearance [5-8], which placed a heavy           Our MR study included 23 types of medications in the ex-
burden on individuals and society.                                  posure group, derived from the GWAS data and used to
    A previous study indicated that the intake of certain           quantify the future risk associated with medication use. The
medications might induce psoriatic lesions on normal skin in        study samples were drawn from the UK Biobank (UKB) and
psoriasis patients or trigger psoriasis in predisposed individ-     consisted of 502,616 participants with medication records
uals, even in those without a family history of this disease [9].   during their first visit to the UKB evaluation [18]. Out of
These medications included nonsteroidal anti-inflammatory           the 6,745 types of medications recorded in the UKB, 1,809
drugs (NSAIDs), penicillins, antimalarial drugs, psycho-            were reported by at least ten individuals and subsequently
tropic drugs, and others [10]. Psoriasis is closely associ-         included in the GWAS. These medications were integrated
ated with various comorbidities. For example, studies have          into 23 categories and underwent a series of quality control
demonstrated that psoriasis patients had a risk of developing       measures to form the aggregated GWAS data. We obtained
metabolic syndromes such as type II diabetes, hypertension,         these GWAS data and used the “format_data” function of the
atherogenic dyslipidemia, and nonalcoholic fatty liver, that        TwoSampleMR package to transform them into a recogniz-
was at least twice as high as that of healthy individuals [11].     able format. To select instrumental variables for each med-
Besides, psoriasis patients were susceptible to coronary            ication GWAS, we applied the following thresholds: 1) The
atherosclerosis and even coronary artery disease [12,13].           P -value was less than 5e-08; 2) We conducted clump analysis
Moreover, a meta-analysis indicated that psoriasis patients         with an r2 = 0.001 and kb=10000 setting; 3) We calculated
had a tremendously increased risk of asthma, inflammatory           the F statistic for each instrumental variable, and those with
bowel disease, chronic kidney disease, and end-stage renal          an F value less than ten were eliminated [19]. The calculation
disease [14-16]. In such cases, they should treat not only the      formula was as follows [20] where N is the sample size and
primary illness but also the associated complications. How-         r2 the variance explained by IVs:
ever, medications used for treating its complications may, in
turn, exacerbate psoriasis. Consequently, regardless of the
                                                                                               r 2 (N – 2)
patient’s disease control status, clinicians need to evaluate
the potential effects of medication intake on the occurrence,                                   (1 – r 2 )
recurrence, or aggravation of psoriasis.




2                                                                       Original Article | Dermatol Pract Concept. 2024;14(1):e2024041
    Since we required at least four single nucleotide poly-      Results
morphisms (SNPs) as instrumental variables for subsequent
analysis, we set a P -value threshold of P < 5e-07 in case the   Causality of Medicine Intake on Psoriasis
medications GWAS yielded insufficient instrumental vari-         Occurrence
ables after screening and normalization. If still inadequate,    After conducting IVW on 23 different types of medications,
we would adjust the cutoff point to P < 5e-06.                   we identified six of them as significant risk factors for psori-
    The study focused on psoriasis as the primary out-           asis (P < 0.05). Supplementary Table 1 provided all the drug
come of interest. We obtained the GWAS data for psoriasis        IDs and their corresponding detailed names. As depicted
from the 8th release of the FinnGen database [21], where         in Figure 1, the intake of HMG-CoA reductase inhibitors
the PhenoCode for psoriasis was L12_PSORIASIS (https://          (OR=1.167, 95% CI: 1.084-1.257, P < 0.001) substantially
finngen.gitbook.io/documentation/). The dataset included         increased the risk of developing psoriasis. Thyroid prepa-
8,075 cases and 330,975 controls, with a total sample size       rations (OR=1.080, 95% CI: 1.026-1.138, P = 0.004) and
of 339,050. FinnGen conducted a series of quality control        antihistamines for systemic use (OR=1.341, 95% CI: 1.104-
measures on the GWAS data (DOI: https://doi.org/10.1101/         1.630, P = 0.003) also showed significant associations. Ad-
2022.03.03.22271360). And we used National registries to         ditionally, NSAIDs and antirheumatic products (OR=1.406,
define psoriasis cases.                                          95% CI: 1.037-1.908, P = 0.028), antihypertensives
    We harmonized the exposure and outcome groups data           (OR=1.099, 95% CI: 1.016-1.190, P = 0.019), and anilides
to ensure that the effect allele was consistently related to     (OR=1.379, 95% CI: 1.004-1.894, P = 0.047) contributed
the same allele. This was achieved using the effect allele       to the occurrence or aggravation of psoriasis. Supplementary
frequency (EAF) to deduce the orientation of all SNPs on         Table 2 provided detailed outcomes of the other four MR
the forward strand. SNPs with incorrect effects or reference     methods.
alleles, and those with ambiguous palindromic sequences
that EAF could not resolve, were excluded from further           Sensitivity Analyses
analysis.                                                        For the IVW-MR analysis, the Cochran Q test indicated no
                                                                 heterogeneity among the reported results (P > 0.05). More-
Mendelian Randomization and Sensitivity Test                     over, the MR‒Egger regression analysis demonstrated that
To validate the primary MR analysis method, we per-              overall horizontal pleiotropy did not significantly affect the
formed MR-PRESSO analysis [22] with an element set to            results obtained through IVW-MR (P > 0.05). Supplementary
10,000 to identify and remove outliers. We simultaneously        Table 2 provided the integrated outcomes of MR PRESSO
conducted MR analysis and computed p values. The data            and detailed sensitivity analyses. Based on these findings, we
with outliers removed were the corrected data for subse-         could assert their causal relationship’s credibility.
quent studies. Inverse-variance-weighted (IVW) was cho-
sen as the primary MR method due to its robustness and
                                                                 Conclusions
reliability [23]. The results obtained through IVW were
considered the main MR results. At the same time, we con-        Psoriasis is an immune-mediated chronic inflammatory skin
ducted four additional MR methods (MR‒Egger, simple              disease mainly affecting the knees, elbow, trunk, and scalps,
mode, weighted median, and weighted mode) to comple-             which presents with well-demarcated erythematous plaques
ment IVW and to observe if their results were consistent         covered by silvery-white scales. Medication-provoked pso-
with those of IVW.                                               riasis can be classified into two types. Medication-induced
    To ensure the reliability of the MR results, we performed    psoriasis often occurs in patients with no family or personal
sensitivity analyses after obtaining them. We employed the       history of psoriasis, whose lesions typically subsided after
MR‒Egger intercept method to test whether they were af-          ceasing medication use [25]. Medication-aggravated psori-
fected by horizontal pleiotropy [24]. A P value less than 0.05   asis usually affects patients with a history of psoriasis or a
was considered evidence of horizontal pleiotropy, indicat-       genetic predisposition, generally exacerbating their existing
ing unreliable results. We evaluated heterogeneity using the     lesions or developing new ones [25]. However, identifying
Cochrane Q test with IVW and MR‒Egger. A p-value less            medication-related triggers for psoriasis flares in clinical
than 0.05 indicated the presence of heterogeneity among          practice can be challenging for various reasons. For example,
the instrumental variables. Since IVW can effectively handle     variations in the absorption rate and half-time period among
heterogeneity, we should regard its results as the main MR       different medications may lead to an inconspicuous tempo-
results [23].                                                    ral relationship [26]. As mentioned earlier, MR analysis can




Original Article | Dermatol Pract Concept. 2024;14(1):e2024041                                                                 3
    Figure 1. The forest plot displayed the results of a two-sample Mendelian randomization analysis, investigating the relationship
    ­between the intake of 23 different types of medications and the risk of psoriasis. The effect estimates were presented as odds ratios.
     CI = confidence interval; OR = odds ratio.




effectively dispose of this drawback, making it a more credi-                Pruritus is a common symptom experienced by most pso-
ble tool for causal estimation between medication intake and             riasis patients and can significantly impact their quality of
the increased risk of psoriasis.                                         life. Itching often leads to the scratching of psoriatic lesions,
      Psoriasis patients are susceptible to developing cardio-           further intensifying the itch and creating a vicious cycle of
vascular episodes [12,13]. Statins, also known as HMG-CoA                “itching-scratching,” ultimately worsening skin inflamma-
reductase inhibitors, are commonly prescribed to lower cho-              tion. In clinical practice, dermatologists use antihistamines
lesterol levels and decrease the incidence of cardiovascular dis-        to alleviate itch in skin disorders. Few large-scale, random-
eases. However, there is an ongoing debate among researchers             ized, controlled trials have examined whether antihistamines
regarding the relationship between statin use and psoriasis.             use increases the risk of psoriasis. Some case reports have
Some studies suggested that statins had beneficial effects on            suggested that fexofenadine and terfenadine may exacerbate
plaque psoriasis and could reduce its severity [27,28]. Con-             psoriasis [33,34]. Our research provided theoretical evidence
versely, others argued that there was insufficient evidence that         that antihistamines use may be a risk factor for psoriasis,
using oral statins as an auxiliary treatment could reduce the            but the underlying reason for this remained unclear. Further
severity of psoriasis [29]. Psoriasis patients with hypercholes-         pharmacological studies are required to elucidate the mech-
terolemia may even worsen their pre-existing psoriasis after             anism of this adverse reaction.
using statins due to the activation of signal transducer and                 Recent studies have shed light on the relationship be-
activator of transcription 3 (STAT3) [30]. These studies also            tween psoriasis and thyroid disease. For instance, hypo-
stated that statins could result in the deterioration of psoriasis       thyroidism was highly prevalent in psoriasis patients [35].
lesions [31,32]. Our study found that statin intake increased            Hashimoto’s thyroiditis was also more prevalent in pso-
the risk of triggering or exacerbating psoriasis, providing ge-          riasis patients (especially in females) than in healthy
netic evidence for exploring the concrete pharmacological                people [35-37]. Levothyroxine is usually used to treat hypo-
mechanism of statins in psoriasis patients.                              thyroidism and Hashimoto’s thyroiditis. To date, few studies



4                                                                             Original Article | Dermatol Pract Concept. 2024;14(1):e2024041
have investigated the effect of thyroid preparations on pso-      instrumental variable assumptions cannot be empirically
riasis lesions. Our results suggested, for the first time, that   verified, but we have conducted sensitivity analyses to ensure
thyroid preparations may contribute to the onset of psori-        no heterogeneity or horizontal pleiotropy.
asis, which can guide future research in exploring the role             Our study offers a causal testimony that the intake of
of thyroid preparations in the occurrence, recurrence, and        HMG CoA reductase inhibitors, thyroid preparations, non-
exacerbation of psoriasis.                                        steroidal anti-inflammatory and antirheumatic products,
    Hypertension was reported to have a higher risk of psori-     anilides, antihistamines for systemic use, and antihyperten-
asis incidence (HR: 1.54, 95% CI: 1.47-1.61, P < 0.001) and       sives are substantially associated with the increased risk of
was also known to be more challenging to control in psori-        psoriasis.
asis patients [38,39]. Antihypertensives are mainly divided
into five categories: diuretics, β-receptor blockers, calcium
channel blockers, angiotensin-converting enzyme inhibitors,       References
and angiotensin receptor blockers. Our study did not find a
                                                                   1. Griffiths CE, Barker JN. Pathogenesis and clinical features of
correlation between these medicines and an increased risk of          psoriasis. Lancet. 2007;370(9583):263-271. DOI: 10.1016
psoriasis. In contrast, the remaining minorities, such as sym-        /S0140-6736(07)61128-3. PMID: 17658397.
patholytic agents (reserpine, clonidine), direct vasodilators      2. Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN.
(hydrazine), and α1-receptor blockers (prazosin, terazosin),          Psoriasis. Lancet. 2021;397(10281):1301-1315. DOI: 10.1016
                                                                      /S0140-6736(20)32549-6. PMID: 33812489.
were implicated. For example, a large population-based,
                                                                   3. Michalek IM, Loring B, John SM. A systematic review of world-
case-control study found no connection between the use of
                                                                      wide epidemiology of psoriasis. J Eur Acad Dermatol Vene-
β-blockers and an increased risk of psoriasis [40]. However,            reol. 2017;31(2):205-212. DOI: 10.1111/jdv.13854. PMID:
clonidine may increase the risk of psoriasiform eruption by             27573025.
decreasing intracellular cyclic AMP and promoting the pro-         4.   Parisi R, Iskandar IYK, Kontopantelis E, Augustin M, Griffiths
liferation of epidermal cells [41]. Taking urapidil resulted in         CEM, Ashcroft DM; Global Psoriasis Atlas. National, regional,
                                                                        and worldwide epidemiology of psoriasis: systematic analysis
the observation of a similar lesion [42]. These findings were
                                                                        and modelling study. BMJ. 2020;369:m1590. DOI: 10.1136
consistent with the results of our study, which instructed
                                                                        /bmj.m1590. PMID: 32467098. PMCID: PMC7254147.
us to choose appropriate antihypertensives medications for         5.   Fleming P, Bai JW, Pratt M, Sibbald C, Lynde C, Gulliver WP. The
psoriasis patients.                                                     prevalence of anxiety in patients with psoriasis: a systematic re-
    Acetaminophen and aspirin are two of the most widely                view of observational studies and clinical trials. J Eur Acad Der-
used NSAIDs. Shaowei Wu et al. reported that regular acet-              matol Venereol. 2017;31(5):798-807. DOI: 10.1111/jdv.13891
                                                                        . PMID: 27620704.
aminophen users may increase the risk of developing psori-
                                                                   6.   Gonzalez J, Cunningham K, Perlmutter J, Gottlieb A. System-
asis and psoriatic arthritis [43]. This phenomenon may be
                                                                        atic Review of Health-Related Quality of Life in Adolescents
attributed to its inhibition of arachidonic acid metabolism             with Psoriasis. Dermatology. 2016;232(5):541-549. DOI:
via the cyclo-oxygenase pathway, resulting in the accumula-             10.1159/000450826. PMID: 27811471.
tion of leukotrienes and aggravating psoriasis [10]. Notably,     7.    Soliman MM. Depressive, anxiety, stress, and insomnia
acetaminophen belongs to both NSAIDs and anilides. This                 symptoms in patients with psoriasis: a cross-sectional study.
                                                                        ­Postepy Dermatol Alergol. 2021;38(3):510-519. DOI: 10.5114
finding aligned with our study outcomes, which indicated
                                                                         /ada.2020.98726. PMID: 34377136. PMCID: PMC8330873.
NSAIDs and anilides were associated with a greater risk of
                                                                   8.    Liang SE, Cohen JM, Ho RS. Psoriasis and suicidality: A re-
psoriasis. These results reminded clinicians that aspirin may            view of the literature. Dermatol Ther. 2019;32(1):e12771. DOI:
be a safer alternative to acetaminophen when prescribing                 10.1111/dth.12771. PMID: 30315629.
NSAIDs to psoriasis patients in the short term. However,           9.    Basavaraj KH, Ashok NM, Rashmi R, Praveen TK. The role
clinicians should still pay attention to psoriasis occurrence            of drugs in the induction and/or exacerbation of psoriasis. Int
                                                                         J Dermatol. 2010;49(12):1351-1361. DOI: 10.1111/j.1365
when patients use NSAIDs for a long time [43].
                                                                         -4632.2010.04570.x. PMID: 21091671.
    This reliable evidence emphasizes the importance of ra-
                                                                  10.    Fry L, Baker BS. Triggering psoriasis: the role of infections
tional medication administration, which is crucial in pre-               and medications. Clin Dermatol. 2007;25(6):606-615. DOI:
venting and managing psoriasis. However, we acknowledge                  10.1016/j.clindermatol.2007.08.015. PMID: 18021899.
that our research has some limitations. Firstly, the study sam-   11.    Gisondi P, Fostini AC, Fossà I, Girolomoni G, Targher G. Psoriasis
ples were predominantly of European populations, so the re-              and the metabolic syndrome. Clin Dermatol. 2018;36(1):21-28.
                                                                         DOI: 10.1016/j.clindermatol.2017.09.005. PMID: 29241748.
sults may not be generalizable to other racial populations.
                                                                  12.    Zhang L, Wang Y, Qiu L, Wu J. Psoriasis and cardiovascu-
Moreover, the risk factors for disease onset may not align
                                                                         lar disease risk in European and East Asian populations: ev-
with its prognosis or severity. In other words, the value of             idence from meta-analysis and Mendelian randomization
our research findings lies in the prevention instead of treat-           analysis. BMC Med. 2022;20(1):421. DOI: 10.1186/s12916-022
ment for psoriasis. Finally, like any other MR research, the             -02617-5. PMID: 36320003. PMCID: PMC9628092.



Original Article | Dermatol Pract Concept. 2024;14(1):e2024041                                                                          5
13. Karbach S, Hobohm L, Wild J, et al. Impact of Psoriasis on Mor-         28. Socha M, Pietrzak A, Grywalska E, Pietrzak D, et al. The effect
    tality Rate and Outcome in Myocardial Infarction. J Am Heart                of statins on psoriasis severity: a meta-analysis of randomized
    Assoc. 2020;9(18):e016956. DOI: 10.1161/JAHA.120.016956.                    clinical trials. Arch Med Sci. 2019;16(1):1-7. DOI: 10.5114
    PMID: 32914667. PMCID: PMC7726965.                                          /aoms.2019.90343. PMID: 32051699. PMCID: PMC6963135.
14. Wang J, Ke R, Shi W, Yan X, et al. Association between pso-             29. Ramessur R, Gill D. The effect of statins on severity of psori-
    riasis and asthma risk: A meta-analysis. Allergy Asthma Proc.               asis: A systematic review. Indian J Dermatol Venereol Leprol.
    2018;39(2):103-109. DOI: 10.2500/aap.2018.39.4109. PMID:                    2017;83(2):154-161. DOI: 10.4103/0378-6323.188655. PMID:
    29490768. PMCID: PMC5827153.                                                27549870.
15. Fu Y, Lee CH, Chi CC. Association of Psoriasis With Inflamma-           30. Ibrahim AM, Attwa EM, Benjuma HH. The exacerbating effect
    tory Bowel Disease: A Systematic Review and Meta-analysis.                  of atorvastatin on psoriasis. Dermatol Ther. 2022;35(8):e15603.
    JAMA Dermatol. 2018 Dec 1;154(12):1417-1423. DOI:                           DOI: 10.1111/dth.15603. PMID: 35644872.
    10.1001/jamadermatol.2018.3631. PMID: 30422277. PMCID:                  31. Cozzani E, Scaparro M, Parodi A. A case of psoriasis wors-
    PMC6583370.                                                                 ened by atorvastatin. J Dermatol Case Rep. 2009;3(4):60-1.
16. Ungprasert P, Raksasuk S. Psoriasis and risk of incident chronic            DOI: 10.3315/jdcr.2009.1037. PMID: 21886735. PMCID:
    kidney disease and end-stage renal disease: a systematic review             PMC3163346.
    and meta-analysis. Int Urol Nephrol. 2018;50(7):1277-1283.              32. Jacobi TC, Highet A. A clinical dilemma while treating hyper-
    DOI: 10.1007/s11255-018-1868-z. PMID: 29644523.                             cholesterolaemia in psoriasis. Br J Dermatol. 2003;149(6):
17. Burgess S, Small DS, Thompson SG. A review of instrumental vari-            1305-1306. DOI: 10.1111/j.1365-2133.2003.05675.x. PMID:
    able estimators for Mendelian randomization. Stat Methods Med               14674922.
    Res. 2017;26(5):2333-2355. DOI: 10.1177/0962280215597579.               33. Saraswat A, Saraswat M. Pustular exacerbation of psoriasis due
    PMID: 26282889. PMCID: PMC5642006.                                          to fexofenadine. Clin Exp Dermatol. 2006;31(3):477-478. DOI:
18. Wu Y, Byrne EM, Zheng Z, et al. Genome-wide association study               10.1111/j.1365-2230.2006.02104.x. PMID: 16681618.
    of medication-use and associated disease in the UK Biobank. Nat         34. Navaratnam AE, Gebauer KA. Terfenadine-induced exacer-
      Commun. 2019;10(1):1891. DOI: 10.1038/s41467-019-09572-5.                   bation of psoriasis. Clin Exp Dermatol. 1990;15(1):78. DOI:
      PMID: 31015401. PMCID: PMC6478889.                                          10.1111/j.1365-2230.1990.tb02035.x. PMID: 1968794.
19.   Burgess S, Butterworth A, Thompson SG. Mendelian random-              35.   Cira CI, Carsote M, Nistor C, Petca A, Petca RC, Sandru F.
      ization analysis with multiple genetic variants using summarized            Conundrum for Psoriasis and Thyroid Involvement. Int J Mol
      data. Genet Epidemiol. 2013;37(7):658-665. DOI: 10.1002                     Sci. 2023;24(5):4894. DOI: 10.3390/ijms24054894. PMID:
      /gepi.21758. PMID: 24114802. PMCID: PMC4377079.                             36902323. PMCID: PMC10003398.
20.   Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-            36.   Valduga JAG, Rebeiko LB, Skare TL. Prevalence of Hashimo-
      scale association analyses identify host factors influencing                to’s thyroiditis in psoriasis patients. Rev Assoc Med Bras (1992).
      human gut microbiome composition. Nat Genet. 2021;53(2):                    2021;67(1):52-57. DOI: 10.1590/1806-9282.67.01.20200274.
      156-165. DOI: 10.1038/s41588-020-00763-1. PMID: 33462485.                   PMID: 34161490.
      PMCID: PMC8515199.                                                    37.   Alidrisi HA, Al Hamdi K, Mansour AA. Is There Any
21.   Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic           ­Association Between Psoriasis and Hashimoto’s Thyroiditis?
      insights from a well-phenotyped isolated population. Nature.                 ­Cureus. 2019;11(3):e4269. DOI: 10.7759/cureus.4269. PMID:
      2023;613(7944):508-518. DOI: 10.1038/s41586-022-05473-8.                      31157131. PMCID: PMC6529052.
      PMID: 36653562. PMCID: PMC9849126.                                    38.     Kim HN, Han K, Song SW, Lee JH. Hypertension and risk of pso-
22.   Verbanck M, Chen CY, Neale B, Do R. Detection of widespread                   riasis incidence: An 11-year nationwide population-based cohort
      horizontal pleiotropy in causal relationships inferred from Men-              study. PLoS One. 2018;13(8):e0202854. DOI: 10.1371/journal.
      delian randomization between complex traits and diseases. Nat                 pone.0202854. PMID: 30142208. PMCID: PMC6108501.
      Genet. 2018;50(5):693-698. DOI: 10.1038/s41588-018-0099-7.            39.     Armstrong AW, Lin SW, Chambers CJ, Sockolov ME, Chin DL.
      PMID: 29686387. PMCID: PMC6083837.                                            Psoriasis and hypertension severity: results from a case-control
23.   Burgess S, Davey Smith G, Davies NM, et al. Guidelines for perform-           study. PLoS One. 2011;6(3):e18227. DOI: 10.1371/journal.
      ing Mendelian randomization investigations: update for summer                 pone.0018227. PMID: 21479272. PMCID: PMC3066207.
      2023. Wellcome Open Res. 2023;4:186. DOI: 10.12688/wellco-            40.     Brauchli YB, Jick SS, Curtin F, Meier CR. Association be-
      meopenres.15555.3. PMID: 32760811. PMCID: PMC7384151.                         tween beta-blockers, other antihypertensive drugs and pso-
24.   Burgess S, Thompson SG. Interpreting findings from Mendelian                  riasis: population-based case-control study. Br J Dermatol.
      randomization using the MR-Egger method. Eur J Epidemiol.                     2008;158(6):1299-1307. DOI: 10.1111/j.1365-2133.2008
      2017;32(5):377-389. DOI: 10.1007/s10654-017-0255-x. PMID:                     .08563.x. PMID: 18410416.
      28527048. PMCID: PMC5506233.                                          41.     Wilkin J. Exacerbation of psoriasis during clonidine therapy.
25.   Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug in-                 Arch Dermatol. 1981;117(1):4. PMID: 7458381.
      duced or drug aggravated?: understanding pathophysiology and          42.     Takehara Y, Igawa K, Satoh T, Yokozeki H. Psoriasiform erup-
      clinical relevance. J Clin Aesthet Dermatol. 2010;3(1):32-38.                 tion induced by alpha1-adrenergic blocker, urapidil. J Eur Acad
      PMID: 20725536. PMCID: PMC2921739.                                            Dermatol Venereol. 2007;21(4):577-578. DOI: 10.1111/j.1468
26.   Balak DM, Hajdarbegovic E. Drug-induced psoriasis: clinical                   -3083.2006.01977.x. PMID: 17374017.
      perspectives. Psoriasis (Auckl). 2017;7:87-94. DOI: 10.2147           43.     Wu S, Han J, Qureshi AA. Use of aspirin, non-steroidal
      /PTT.S126727. PMID: 29387611. PMCID: PMC5774610.                              anti-inflammatory drugs, and acetaminophen (paracetamol),
27.   Shirinsky IV, Shirinsky VS. Efficacy of simvastatin in plaque pso-            and risk of psoriasis and psoriatic arthritis: a cohort study. Acta
      riasis: A pilot study. J Am Acad Dermatol. 2007;57(3):529-531.                Derm Venereol. 2015;95(2):217-223. DOI: 10.2340/00015555
      DOI: 10.1016/j.jaad.2007.05.040. PMID: 17707157.                              -1855. PMID: 24691893. PMCID: PMC4183729.



6                                                                                 Original Article | Dermatol Pract Concept. 2024;14(1):e2024041
