British Journal of Clinical Pharmacology

Volume 88, Issue 3 p. 933-941

META-ANALYSIS

Free Access

Antihypertensive drug use and psoriasis: A systematic review, meta- and network meta-analysis

Gonjin Song,

Gonjin Song

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Ha Young Yoon,

Ha Young Yoon

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Jeong Yee,

Jeong Yee

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Myeong Gyu Kim,

Myeong Gyu Kim

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Hye Sun Gwak,

Corresponding Author

Hye Sun Gwak

[email protected]

orcid.org/0000-0003-0278-2563

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

Correspondence

Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.

Email: [email protected]

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Gonjin Song,

Gonjin Song

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Ha Young Yoon,

Ha Young Yoon

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Jeong Yee,

Jeong Yee

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Myeong Gyu Kim,

Myeong Gyu Kim

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

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Hye Sun Gwak,

Corresponding Author

Hye Sun Gwak

[email protected]

orcid.org/0000-0003-0278-2563

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea

Correspondence

Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.

Email: [email protected]

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First published: 05 October 2021

https://doi.org/10.1111/bcp.15060

Citations: 4

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Abstract

Aims

Diverse genetic and/or external factors may induce psoriasis. Drug exposure is 1 such prominent external factor; antihypertensive drugs are reportedly associated with psoriasis, but study results have been inconsistent. In this context, we investigated the associations between antihypertensive drugs and incidence if psoriasis via a systematic literature review and meta-analysis.

Methods

Literature search in databases such as PubMed, Embase and Web of Science was conducted on 8 January 2021, and obtained data were pooled for meta- and network meta-analysis. Fixed- or random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for evaluating the strength of the associations between antihypertensive drugs and psoriasis incidence. In addition to meta-analysis, Bayesian network meta-analysis was performed.

ResultsThirteen eligible studies were included for meta-analysis with 6 378 116 individuals and 8 studies for network meta-analysis with 5 615 918 individuals. All antihypertensive drugs were significantly associated with psoriasis incidence. In a meta-analysis, the pooled ORs were 1.67 (95% CI: 1.31–2.13) for angiotensin-converting enzyme (ACE) inhibitors, 1.40 (95% CI: 1.20–1.63) for β-blockers, 1.53 (95% CI: 1.23–1.89) for calcium-channel blockers (CCBs), and 1.70 (95% CI: 1.40–2.06) for thiazide diuretics. For the comparative risks of psoriasis among antihypertensive drugs in the network meta-analysis, ORs were 2.09 (95% CI: 1.39–3.18) for ACE inhibitors, 1.35 (95% CI: 0.99–1.91) for BBs, 1.53 (95% CI: 1.07–2.24) for CCBs and 1.80 (95% CI: 1.23–2.66) for thiazide diuretics.

Conclusion

This study confirmed the associations between antihypertensive drugs and psoriasis; ACE inhibitors, BBs, CCBs and thiazide diuretics increased the risk of psoriasis. Therefore, antihypertensive drug users should be carefully monitored for psoriasis.

1 INTRODUCTION

Psoriasis is a chronic inflammatory skin disease that, when inflicted, can be detrimental to the individual's overall quality of life.^{1, 2} The prevalence rate of psoriasis is 0.1–11%, more common in Caucasian and Scandinavian populations, and it more frequently occurs in older people and in high-income countries as well.^2-4 Simply put, it is a disease that induces unbearable pain and disfigurement, leading to high burden not only physically but also in a psychosocial standpoint.

Genetic and external factors can cause psoriasis, including sunburn, smoking, mild trauma (scratching, piercings and tattoos), infections, emotional stress, withdrawal of systemic steroids and drugs.⁵ Drug exposure is 1 of the important external factors that can provoke psoriasis; however, how drugs may induce psoriasis has yet to be clarified. One study postulated that some drugs may lead to psoriasis by affecting the autoimmune response, while others may do so via allergic reactions.⁶

Antihypertensive drugs are widely prescribed for patients with not only hypertension but also congestive heart failure, arrhythmias, stroke, migraine and haemangioma.⁷ According to the European Society of Cardiology Guidelines, drugs for hypertension treatment may be classified into the following groups: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), β-blockers (BBs), calcium-channel blockers (CCBs) and thiazide diuretics.⁸ Treatment with these drugs may be associated with various cutaneous adverse effects, such as acute generalized exanthematous pustulosis, annular erythema, bullous eruption, eczematoid photosensitive reactions and psoriasiform eruptions.⁹

Several studies have suggested a possible association between antihypertensive drug use and psoriasis, but consistent results have yet to be obtained.^10-16 In this context, this systematic review, meta- and network meta-analysis aimed to confirm associations between the use of ACE inhibitors, BBs, CCBs and diuretics, and psoriasis incidence.

2 METHODS

2.1 Literature search

Two researchers independently searched 3 databases (PubMed, Web of Science and Embase) on 8 January 2021 to identify studies on the associations between antihypertensive drug, including ACE inhibitors, ARBs, BBs, CCBs and diuretics, and psoriasis incidence (Table S1).

Once duplicates had been removed, the researchers identified studies eligible for analysis by examining titles and abstracts of every record, followed by full-text reviews. Disagreement between the researchers was resolved by reaching consensus through discussion. Publication date was not a restricting factor in the literature search.

2.2 Inclusion and exclusion criteria

Studies were eligible for analysis if: (i) they chose psoriasis patients for which specific diagnostic criteria were used and controls without psoriasis; (ii) they used randomized controlled trials, case–control, and cohort study designs; (iii) they presented sufficient information to obtain an odds ratio (OR) or hazard ratio (HR) and 95% confidence intervals (CIs); and (iv) they were published in English. Criteria for exclusion were (i) conference or meeting abstracts, summaries, reviews, comments, letters, news and editorials; (ii) case reports and case series; (iii) studies not having appropriate data; (iv) studies not confirmed whether taking drugs prior to diagnosis of psoriasis; or (v) repeated study populations. If >1 study shared the same population, the study with the largest population was selected.

2.3 Data extraction

From the 13 enrolled studies, the following data were obtained via a standardized method: name of first author; publication year; study design; population characteristics; country; definition of patients with psoriasis; the number of patients with psoriasis (male %); the population size (male %); OR or HR with 95% CIs; and comorbidities when available.

2.4 Quality assessment

Based on the Newcastle–Ottawa Quality Assessment Scale (NOS) for case–control and cohort studies, 2 researches independently assessed the quality of eligible studies.¹⁷ The scoring system of this scale was based on 3 components: subject selection (0–4 points); comparability of study groups (0–2 points); and exposure (case–control study) or outcome (cohort study; 0–3 points). The highest NOS score available for each publication was 9 points.

2.5 Statistical analysis

OR and 95% CIs were measured to estimate the effect size of ACE inhibitors, BBs, CCBs and diuretics for psoriasis incidence. Meta-analysis was performed when >5 studies were included. Heterogeneity was assessed by a χ²–based Q-test and an I² test, where I² > 50% indicates significant heterogeneity.¹⁸ The fixed-effects model (Mantel–Haenszel method) was used when there was no statistical evidence of heterogeneity (I² ≤ 50%), otherwise, the random-effects model (DerSimonian and Laird method) was used to calculate pooled estimates.^{19, 20}

Sensitivity analyses were performed by sequential exclusion in order to assess the liability of study results. Funnel plots, Begg's test and Egger's test were used to analyse publication bias. A P value < .05 was considered statistically significant.

To determine the comparative effects of antihypertensive drugs, Bayesian network meta-analysis was conducted using a Markov chain Monte Carlo method called Gibbs sampling.²¹ The first 50 000 iterations (burn-in) were discarded and 100 000 further iterations were used for the estimations. To rank the treatments based on safety, we calculated the probabilities of the surface under the cumulative ranking curve (SUCRA).²² Review Manager (version 5.3; The Cochrane Collaboration, Copenhagen, Denmark) and R software (version 3.6.0; R Foundation for Statistical Computing, Vienna, Austria) were used to perform all statistical analyses. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.²³

3 RESULTS

3.1 Identification and characteristics of the included studies

The process by which studies were selected is presented in Figure 1. A total of 3025 records were found across 3 databases, from which 549 duplicates were removed, resulting in 2476 studies remaining. Another 2317 studies were removed after screening for titles and abstracts, and the remaining 159 were subject to full-text reviews, from which 146 were excluded for the following reasons: case report and case series (n = 49); not original research articles (n = 41); not English (n = 6); inappropriate data (n = 38); not being confirmed if drugs were taken before psoriasis diagnosis (n = 2); inappropriate study design (n = 2); and repeated study population (n = 8). Finally, 13 studies^{11-13, 15, 16, 24-31} with 6 378 116 individuals were included for meta-analysis, the characteristics of which are presented in Table 1. Of these, 5 were cohort studies,^{16, 25-27, 29} and 8 were case–control studies.^{11-13, 15, 24, 28, 30, 31} Seven of the studies^{12, 13, 15, 25, 28, 29, 31} were performed in Europe, 2 in the USA^{16, 30} and 4 in Asia.^{11, 24, 26, 27} The quality scores evaluated by NOS ranged from 6–9. The quality of the included studies was high (Table S2).

Details are in the caption following the image — **FIGURE 1**
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Flow diagram of the study selection process

TABLE 1. Characteristics of included studies

First author (y)	Country	Study design	Drugs	Definition of patients with psoriasis	No. of patients with psoriasis (male %)	No. of population (male%)	Age (y) (mean ± SD)	Major comorbidities (% of all patients with psoriasis)	NOS
Cohen et al.¹¹ (2005)	Israel	Case–control study	ACEI, BB, CCB, DU	Patients who were hospitalized for extensive psoriasis	110 (57.3)	625 (58.9)	Case: 49.6 ± 17.2 control: 53.4 ± 17.0	NA	8
Gerdes et al.¹² (2008)	Germany	Case–control study	ACEI, ARB, BB, CCB, DU	Patients with severe psoriasis	1131 (NA)	8230 (NA)	49.7 ± 16.6	Hypertension (25.3%), diabetes mellitus (9.2%), hyperlipoproteinaemia (7.7%)	9
Brauchli et al.¹⁵ (2008)	UK	Case–control study	ACEI, ARB, BB, CCB, DU	Patients with an incident psoriasis diagnosis	36 702 (46.2)	73 404 (46.2)	NA	Hypertension (14.4%), ischaemic heart disease (7.1%), hyperlipidaemia (5.9%)	9
Naldi et al.¹³ (2008)	Italy	Case–control study	BB, CCB, DU	Patients with a first diagnosis of psoriasis made by a dermatologist	560 (56.8)	1250 (53.0)	NA	NA	7
Wolkenstein et al.²⁸ (2009)	France	Case–control study	ACEI, BB, CCB	Psoriasis during the previous 12 months diagnosis confirmed	356 (45.2)	1424 (45.2)	Case: 51.6 ± 17.5 control: 51.6 ± 17.5	Hypertension, diabetes, hypercholesterolaemia	8
Al-Mutairi et al.²⁴ (2010)	Kuwait	Case–control study	ACEI, BB, CCB, DU	Patients with psoriasis vulgaris	1835 (52.5)	3670 (52.5)	Case: 52.3 ± 11.9 control: 52.7 ± 13.5	Diabetes mellitus (39.2%), hypertension (32.6%), metabolic syndrome (16.7%)	7
Wu et al.¹⁶ (2014)	USA	Prospective cohort study	ACEI, BB, CCB, DU	Patients with physician-diagnosed incident psoriasis	817 (0)	77 728 (0)	NA	Cardiovascular disease, type 2 diabetes, hypercholesterolaemia, hypertension	7
Khalid et al.²⁹ (2014)	Denmark	Retrospective cohort study	BB, CCB, DU	Patients with psoriasis ensured by their second prescription	66 389 (48.9)	5 443 231 (49.3)	Case: 43.9 ± 16.3 reference: 40.7 ± 19.6	Hypertension, cardiovascular disease, diabetes mellitus, renal disease, chronic obstructive pulmonary disease	8
Wu JJ et al.³⁰ (2015)	USA	Nested case–control study	BB	Patients with mild psoriasis (those with no systemic therapy or phototherapy) and severe psoriasis (those with any use of systemic therapy or phototherapy)	14 014	84 084	NA	Diabetes, dyslipidaemia hypertension	9
Jacob et al.²⁵ (2016)	Germany	Retrospective cohort study	ACEI, BB	Patients with an incident psoriasis diagnosis	NA	144 296 (48.6)	68.7 ± 12.7	Hyperlipidaemia	7
Kim et al.²⁶ (2018)	Korea	Retrospective cohort study	ACEI, ARB, BB, CCB, DU	Patients with an incident psoriasis diagnosis	9254 (NA)	256 356 (51.4)	NA	Hypertension, diabetes mellitus, dyslipidaemia	8
Liu et al.²⁷ (2018)	Taiwan	Retrospective cohort study	ACEI	Patients with an incident psoriasis diagnosis	89 (100)	10 282 (100)	NA	NA	6
Duvetorp et al.³¹ (2020)	Sweden	Case–control study	BB, CCB, DU	Patients with psoriasis if there was at least 1 visit to a dermatologist with the diagnostic code L40.* and subcodes or at least 2 visits in primary care or any other clinic	4587 (49.7)	273 536 (50.0)	Case: 57.4 ± 17.3 control: 49.7 ± 19.5	Heart disease, metabolic syndrome, depression obstructive lung disease, irritable bowel disease, osteoporosis	9

NA: not applicable; ACEI: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor blockers; BB: β-blockers; CCB: calcium channel blockers; DU: diuretics; NOS: Newcastle–Ottawa Quality Assessment Scale.

3.2 Meta-analysis of the associations between antihypertensive drugs and psoriasis

Of the 13 studies including 6 378 116 individuals which focused on the associations between antihypertensive drugs and psoriasis incidence, nine studies included ACE inhibitors,^{11, 12, 15, 16, 24-28} 12 studies included BBs,^{11-13, 15, 16, 24-26, 28-31} 10 studies included CCBs,^{11-13, 15, 16, 24, 26, 28, 29, 31} and nine studies included diuretics.^{11-13, 15, 16, 24, 26, 29, 31} ARBs were excluded from the analysis because there was only 3 studies on the association with psoriasis^{12, 15, 26} (Table 1).

Patients that used ACE inhibitors demonstrated a higher association with psoriasis incidence compared to nonusers (OR 1.67, 95% CI: 1.31–2.13). Heterogeneity was observed between these studies (I² = 96%; P < .0001); hence, effect size was calculated via the random-effects model (Figure 2A). BB, CCB and diuretics use was also associated with higher risk of psoriasis incidence (OR 1.40, 95% CI: 1.20–1.63; OR 1.53, 95% CI: 1.23–1.89; OR 1.70, 95% CI: 1.40–2.06) and effect sizes were calculated in a similar fashion (I² = 97%, P < .0001; I² = 96%; P = .0001, I² = 98%; P < .00001; Figure 2B–D). Neither Begg's test nor Egger's test provided any evident indication of publication bias (Table S3, P > .05). Funnel plots suggested no evidence of publication bias among the studies (Figure S1).

We conducted sensitivity analyses by sequential exclusion of each study to assess their effects on the overall meta-analysis estimate. Similar results were obtained before and after the exclusion; the OR ranges were 1.50–1.85 for ACE inhibitors, 1.32–1.45 for BBs, 1.35–1.63 for CCBs, and 1.56–1.82 for diuretics. All results showed statistical significance (Table S4).

Subgroup analyses using hypertensive patients showed consistent results except for CCBs; ORs were 1.44 (95% CI: 1.33–1.56) for ACE inhibitors, 1.46 (95% CI: 1.37–1.55) for BBs, 1.27 (95% CI: 0.97–1.68) and 1.47 (95% CI: 1.40–1.56) for diuretics (Figure S2).

3.3 Bayesian network meta-analysis of comparative risks among antihypertensive drugs on psoriasis

For the network meta-analysis, 8 studies with a total of 5 615 918 individuals were included^{11–13,15,16,24,28,29}; 5 studies included ACE inhibitors,^{11, 12, 15, 24, 28} 8 studies included BBs,^{11–13,15,16,24,28,29} 7 studies included CCBs^{11-13, 15, 24, 28, 29} and 6 studies included diuretics.^{11-13, 15, 24, 29} Table 2 shows that ACE inhibitors, CCBs and diuretics were associated with an increased risk of psoriasis compared with nonuse (OR for ACE inhibitors, 2.09; 95% CI: 1.39–3.18, OR for CCBs, 1.53; 95% CI: 1.07–2.24, OR for diuretics, 1.80; 95% CI: 1.23–2.66, respectively). As for BBs, there was no statistical significance (OR for BBs, 1.35; 95% CI: 0.99–1.91).

TABLE 2. Network meta-analysis of the association between different kinds of antihypertensive drugs and the risk of psoriasis

	Nonuse	ACE inhibitor	BB	CCB	Diuretics
Nonuse		0.48 (0.31–0.72)	0.74 (0.52–1.01)	0.65 (0.45–0.93)	0.55 (0.38–0.82)
ACE inhibitor	2.09 (1.39–3.18)		1.54 (0.91–2.59)	1.37 (0.78–2.36)	1.16 (0.66–2.05)
BB	1.35 (0.99–1.91)	0.65 (0.39–1.10)		0.89 (0.54–1.44)	0.75 (0.46–1.27)
CCB	1.53 (1.07–2.24)	0.73 (0.43–1.28)	1.13 (0.69–1.84)		0.85 (0.50–1.46)
Thiazide diuretics	1.80 (1.23–2.66)	0.86 (0.49–1.51)	1.33 (0.79–2.19)	1.18 (0.69–1.99)

Odds ratio (95% confidence interval). Drug in the first line was the comparison group. Statistically significant values are given in bold.
ACEI: angiotensin-converting enzyme inhibitors; BB: β-blockers; CCB: calcium channel blockers

Figure 3 presents an overall comparison of the effect of each antihypertensive drug on psoriasis risk in the network using ranking probabilities. ACE inhibitors was the strongest factor with the highest probability (SUCRA 65.3%), followed by diuretics (SUCRA 45.8%), CCBs (SUCRA 44.2%) and BBs (SUCRA 59.9%).

4 DISCUSSION

This meta-analysis suggests significant associations between psoriasis incidence and various drugs including antihypertensive drugs, including ACE inhibitors, BBs, CCBs and diuretics. Sensitivity analyses supported the robustness of the results. These associations were maintained in the subgroup analyses using hypertensive patients except for CCBs. There was no significant difference among ACE inhibitors, BBs, CCBs, and diuretics in terms of comparative risks of psoriasis.

It has been suggested that the use of ACE inhibitors and the consequent elevation of bradykinin concentrations may affect the kinin-kallikrein arachidonic acid system.³² By inhibiting bradykinin degradation, ACE inhibitors may induce an increase in kinin concentration, activation of the arachidonic acid cascade, and release of relevant inflammatory cytokines.^{33, 34} Among the increased cytokines, interleukins (ILs), the hallmark of psoriasis, are known to be responsible for the presence of abnormal keratinocyte proliferation.³⁵ In addition, the tachykinin substance P was postulated to increase due to ACE inhibitor use,³⁶ which may have triggered keratinocyte proliferation and upregulation of cytokines such as IL-1, IL-8 and tumour necrosis factor-α.³⁷

The pathogenesis of the association between BBs and psoriasis is related with a decrease in intraepidermal cyclic adenosine monophosphate (cAMP) with a consequent increase of epidermal cell proliferation^38-40 and immunological mechanisms, including impaired lymphocyte transformation.^41-43 The blockade of epidermal β2 receptors, found on the surface of keratinocytes, decreases intraepidermal cAMP, resulting in decreased intracellular calcium concentrations. This in turn causes keratinocyte hyperproliferation and granulocyte hyperfunctions, both of which may induce psoriasis.^38-40 These cAMP pathways and cascades are the most frequent hypothesis for the association between BB use and psoriasis.

A hypothesis for the association between CCB use and psoriasis is related to intracellular calcium.^44-46 Dysregulations of epidermal barrier formation and hyperproliferation of keratinocytes are mainly responsible for the pathophysiology of psoriasis.^47-49 Calcium has been proposed to be the major factor in keratinocyte differentiation regulation.^50-52 A calcium gradient that exists across the epidermis promotes the sequential differentiation of keratinocytes to form the permeability barrier of the stratum corneum.^{47, 50} Denda et al. revealed that L-type voltage gated calcium channels, which are blocked by CCBs, were expressed in keratinocytes.⁵³ As a result, blockage of intracellular calcium influx may lead to a disturbance in calcium metabolism and ultimately psoriasis.⁵⁰ In a previous study, nifedipine inhibited calcium influx, which is needed in the processing of final steps in the cornification of epidermal cells.⁴⁸

Although there is no study on the association between diuretics and psoriasis risk, thiazide diuretics, such as hydrochlorothiazide, has been known to produce skin photosensitivity reaction. Recent studies proposed a possible association between hydrochlorothiazide use and higher risk of keratinocyte cancer.^{54, 55} Exposure to UV light may activate hydrochlorothiazide to highly reactive metabolites, which allow the absorption of ultraviolet radiation. These photosensitizing reactions may lead to a dose dependent inflammatory reaction (phototoxicity) or to a T-cell mediated, nondose-dependent, immunological reaction (photoallergy).^{56, 57} Photosensitive psoriasis, which is especially excruciating in the areas with exposure to the sun (face, neck, hands and forearms), is rare. The prevalence among this type of psoriasis is up 5.5%.⁵⁸ Ramdial et al. showed that chronic phototoxic reactions demonstrated variable epidermal disorganisation, dyskeratosis, atrophy, hypergranulosis, acanthosis, hyperkeratosis, melanocyte hyperplasia and increased melanin pigment.⁵⁹

Another possible mechanism between thiazide diuretics and psoriasis is related with hyperuricaemia.^60-62 In most of these adverse effects, disturbances in fluid and electrolyte balance are relevant.⁶³ Thiazides decrease acid excretion and thus increase serum uric acid. The insoluble uric acid then deposits in the joint, possibly inducing an inflammatory disease. It was reported that asymptomatic hyperuricaemia was nearly 3 times as common among psoriasis patients as it was amongst the control patients.⁶⁰

Several studies have investigated the association between hypertension and psoriasis.^{26, 64, 65} A meta-analysis by Duan et al. showed that psoriasis was associated with an increased risk of hypertension (OR: 1.43, 95% CI: 1.25–1.64).⁶⁵ Conversely, hypertension also increased the risk of psoriasis.²⁶ However, our result showed that, except for CCBs, the significances of association between antihypertensive medications and psoriasis persisted in subgroup analyses of hypertensive patients. It supported that medication themselves affected the psoriasis risk, regardless of hypertensive state.

The results of this meta- and network meta-analysis must be interpreted with consideration of its limitations. First, due to the lack of information from individual studies, it was not possible to calculate or adjust for the confounders, such as the latency period between the start of medication and the onset of psoriasis, drug dosage and antihypertensive combination therapy. Second, considerable heterogeneity was observed. Third, there were small numbers of studies included in the subgroup analysis for hypertensive group.

Nevertheless, this is the first meta- and network meta-analysis to confirm the associations between antihypertensive drugs and psoriasis incidence, including over 6 million people. The results of this study show the significant associations between antihypertensive drugs and psoriasis incidence. Therefore, antihypertensive drug users should be carefully monitored for psoriasis.

5 CONCLUSION

In conclusion, the present results propose a possible association between antihypertensive drug use and incidence of psoriasis. ACE inhibitors, BBs, CCBs, and diuretics increased the risk of psoriasis, although BB failed to achieve statistical significance in Bayesian network meta-analysis. Further studies must be conducted to strengthen such results. However, to our knowledge, this is the first systematic review, meta-analysis to evaluate the associations between ACE inhibitors, BBs, CCBs and thiazide diuretics, and psoriasis incidence. In addition, this study unravelled significant possible associations between antihypertensive drugs and psoriasis by combining the results of numerous studies, even if the results failed to show statistical significance in their respective papers. Based on our results, careful monitoring of cutaneous adverse events during antihypertensive drug use is recommended, with a particular focus on possible psoriasis incidence.

5.1 Nomenclature of targets and ligands

Key protein targets and ligands in this article are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, and are permanently archived in the Concise Guide to PHARMACOLOGY 2019/20 (Alexander et al., 2019a,b).

ACKNOWLEDGEMENT

We did not receive any funding.

COMPETING INTERESTS

The authors declare that they do not have any conflict of interest.

CONTRIBUTORS

All the authors have made substantial contributions to the conception of the study. G.S. and H.S.G. contributed to designing the study. G.S. and H.Y.Y. and M.G.K. contributed to acquisition and analysis of data. G.S., J.Y., M.G.K. and H.S.G. contributed to interpretation of data. G.S., H.Y.Y., and J.Y. contributed to drafting of the manuscript. H.S.G. contributed to critical revision of the manuscript. All authors approved the final manuscript.

Supporting Information

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Citing Literature

Volume88, Issue3

March 2022

Pages 933-941

Antihypertensive drug use and psoriasis: A systematic review, meta- and network meta-analysis

Abstract