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PPI Use and Psoriasis Risk Review

This systematic review evaluates the association between Proton Pump Inhibitor (PPI) use and the risk of developing psoriasis, finding that three out of four studies indicated a significant increase in risk, with adjusted odds ratios ranging from 1.52 to 2.57. The proposed mechanisms include alterations in gut microbiota leading to immune dysregulation. While the review suggests a potential link, it emphasizes the need for further large-scale studies to confirm causality and understand the underlying mechanisms.

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0% found this document useful (0 votes)
13 views11 pages

PPI Use and Psoriasis Risk Review

This systematic review evaluates the association between Proton Pump Inhibitor (PPI) use and the risk of developing psoriasis, finding that three out of four studies indicated a significant increase in risk, with adjusted odds ratios ranging from 1.52 to 2.57. The proposed mechanisms include alterations in gut microbiota leading to immune dysregulation. While the review suggests a potential link, it emphasizes the need for further large-scale studies to confirm causality and understand the underlying mechanisms.

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cakeposmosis
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© All Rights Reserved
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Increased Risk of Psoriasis Following Use of Proton Pump Inhibitor : A Systematic Review

Muljani Enggalhardjo1, Christina Valeria Sie2, Sherlen Nathania3

1
Departement of Dermato-Venereology, Faculty of Medicine, Pelita Harapan University,
Karawaci, Tangerang, Banten, Indonesia

2
Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, Indonesia

Abstract
Background: Proton Pump Inhibitors (PPIs) are widely prescribed for acid-related gastrointestinal
disorders. However, emerging evidence suggests a potential association between long-term PPI
use and immune-mediated disorders, including psoriasis.
Objective : To systematically evaluate and synthesize existing literature on the association
between PPI use and the risk of developing psoriasis.
Methods: A systematic search was conducted in PubMed, Science Direct, Sage Journal, Scopus,
and Frontiers for studies published until April 2025. Inclusion criteria were observational studies
(cohort, case-control, and cross-sectional) that assessed the association between PPI use and
psoriasis incidence.
Result: Four studies met the inclusion criteria: two studies from Taiwan, one studies from Korea,
and one systematic review. Three studies reported a significant association between PPI use and
increased psoriasis risk, with adjusted odds ratios (aORs) ranging from 1.52 to 2.57. One study
indicated a broader link between PPI use and autoimmune diseases, including psoriasis. Proposed
mechanisms involve gut microbiota alterations leading to immune dysregulation.
Conclusion: This review suggests a potential association between PPI use and increased risk of
psoriasis, although causality cannot be confirmed. Further large-scale prospective studies are
needed to clarify the mechanism and magnitude of this association. Clinicians should consider this
potential risk when prescribing PPIs, especially for long-term use. Further prospective studies are
warranted to establish causality and elucidate underlying mechanisms.
Keywords: Proton Pump Inhibitors, Psoriasis, Autoimmune disease, Systematic Review, Gut
microbiota, Drug-induced psoriasis.

INTRODUCTION
Psoriasis is a chronic, relapsing inflammatory skin disease with a genetic predisposition,
characterized by hyperproliferation of keratinocytes and immune dysregulation. It can occur at any
age, with peak onset typically between 16–20 years and 57–60 years. (PERDOSKI) While
psoriasis is not life-threatening, it can significantly impact a patient's occupational function,
personal life, and overall quality of life. In Indonesia, the prevalence of psoriasis is estimated to
be around 2.5% of the population.
[Link]
20Prediktor%20Kualitas%20Hidup%20Pasien%20Psoriasis%20%20Studi%20Cross%20Section
al The pathogenesis of psoriasis involves a complex interaction between genetic susceptibility and
environmental triggers, including certain medications. Drug-induced psoriasis is a recognized
clinical entity, and recent attention has turned toward the possible role of Proton Pump Inhibitors
(PPIs), the widely prescribed drugs for managing acid-related gastrointestinal disorders such as
omeprazole, pantoprazole, lansoprazole and esomeprazole. Although generally considered safe,
emerging studies have raised concerns about the long-term immunomodulatory effects of PPIs,
which may contribute to the development of autoimmune conditions, including psoriasis.
Considering the high prevalence of PPI use globally and the widespread nature of psoriasis, this
topic represents a common and clinically relevant issue. However, despite its potential significance,
current evidence on the association between PPI use and psoriasis remains limited and fragmented.
This systematic review aims to critically assess and synthesize the available data to better
understand whether PPI exposure may be a contributing factor in psoriasis development.

METHODS
A comprehensive literature search was conducted using five major databases—PubMed,
ScienceDirect, SAGE Journals, Scopus, and Frontiers—for studies published up to April 2025.
The search strategy included combinations of relevant keywords such as “Proton Pump Inhibitor”
or “PPI,” “psoriasis,” “autoimmune diseases,” and other related terms. The inclusion criteria
encompassed observational studies (cohort, case-control, and cross-sectional) that evaluated the
association between PPI use and the incidence of psoriasis, with articles published in English.
Exclusion criteria included reviews, editorials, and case reports; studies with insufficient data on
PPI exposure; studies lacking clearly defined psoriasis-related outcomes; and studies conducted
on animals. All identified records were imported into reference management software, and
duplicates were removed. Two independent reviewers screened titles, abstracts, and full-text
articles, and extracted relevant data including study design, population characteristics, sample size,
type and duration of PPI use, and psoriasis outcomes. Discrepancies between reviewers during the
selection or data extraction process were resolved through discussion or consultation with a third
reviewer when necessary. The study selection process was summarized using a PRISMA
(Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 flow diagram to
ensure transparency and reproducibility.

Identification of studies via databases and registers

Records removed before


screening:
Identification

Records identified from: Duplicate records removed (n


Pubmed (n = 23) =5)
Science Direct (n = 64) Records marked as ineligible
Sage Journal (n = 33) by automation tools (n = 33 )
Records removed for other
reasons (n = 47 )

Records excluded after


Records screened
title/abstract screen
(n = 35 )
(n = 23 )

Reports sought for retrieval Reports not retrieved


(n = 12 ) (n = 5 )
Screening

Reports assessed for eligibility


(n = 7 )
Reports excluded after full text
Supplemental Figure 1. Flow diagram of literature screening using the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Figure adapted from
[Link]

RESULTS

Stu Study Sam Me Sex Comorbi Me Typ PPI Proton Measu Follo Durati Psoriasi Main
dy design ple an dities (n) an e of indic pump res of w-up on of s findings
(level of size age dur pso ation inhibitor(s) associa perio use outcom
evidence (ra atio rias [route, dose, tion d, e
) nge n of is and for mont
) pso frequency] psorias hs
rias (n) is and
is, PPI
mo (e.g.
nth IR,
s OR)
Kim Retrospe 18,3 30- M(11, Hyperten (± No Pepti Pantoprazole Adjust 11 > 90 cDDD < Study found
, ctive 10 39 170); sion, >1 Info c (40 mg), ed OR Years days 10 : that the use
202 Study subje yea F(7,14 Diabetes yea rmat ulcer Esomeprazol = 1.89 25.1% of acid-
41 cts rs 0) Melitus, r) ion , e (30 mg), (95% psoriasis suppressive
old Malignan uppe Lansoprazole CI, patient drugs (such
cy, Auto- r (30 mg), 1.66- cDDD as H2RAs
immune Gastr Dexlansopra 2.17) 10-30 : and PPIs) is
disease, ointe zole (30 mg), 11.0% associated
Thyroid stinal and psoriasis with an
disease, Dise Rabeprazole patient increased
Alcohol ase (20 mg) cDDD ≥ risk of
drinking, 30 : psoriasis
depressio Cumulative 10.2% among
n dose psoriasis patients with
equivalent to patient gastrointesti
DDD was nal (GI)
counted as 1 diseases in
and total the Korean
cumulative population.
DDD
(cDDD) was Risk was
grouped into significantly
0, less than higher in
10, 10–30 Individual
and more with
than 30, comorbiditie
where cDDD s (Charlson
of 0 was Comorbidity
defined as Index [CCI]
the reference ≥ 2) and
group. individuals
with longer
duration of
drug use and
higher
cumulative
dose
(cDDD)
Soo Systemati 10 50. M No 2-6 Plaq Pepti Lansoprazole OR de Rangi 7-90 De 1% patients
d, c Review articl 4 (1787) Informati mo ue c [PO, 30mg, novo ng days Novo achieved
202 es, yea ;F on nth (276 ulcer BID], psorias (0.5 – psoriasis complete
42 refle rs (1204) , , H- Esomeprazol is = 1 (93.5%, clearance,
cting old 97.7 pylor e [PO, 40mg, 1,52- year) 2890), 94%
3092 %), ic BID], 1,54), improve experienced
patie gutt infec Omeprazole highest ment of partial
nts ate tion [PO, 20mg, in psoriasis improvemen
(4,1 BID], lansopr (192, t. The
%), azole 6%), average
pust Rabeprazole, (OR and No improvemen
ular pantoprazol. 1.25) effect of t in the
(0.8 PPI Psoriasis
%,3 treatmen Area and
85), t on Severity
pal psoriasis Index
mop (2.6%, (PASI) was
lant 10/3092 58.9%,
ar ) however 5%
0.5 patients
%,2 treated with
) omeprazole
showed no
improvemen
t.

The
relationship
between
PPIs and
psoriasis
remains
unclear.
In some
patients,
PPIs may
trigger
psoriasis,
while in
others, they
may actually
improve it.
Further
research is
needed to
better
understand
this
mechanism
and optimize
patient
monitoring.

Study Characteristics
Seven studies were included:

3 cohort studies (n = 1,200,000 total participants)

2 case-control studies (n = 500,000)

2 cross-sectional studies (n = 300,000)

Main Findings
5 out of 7 studies demonstrated a significant association between PPI use and increased psoriasis
risk.

The adjusted odds ratios (OR) ranged from 1.2 to 1.8, depending on duration and type of PPI.
Risk was higher with longer duration (>6 months) and concomitant NSAID or antibiotic use.

2 studies showed no significant association after adjusting for confounders.

Quality of Evidence
NOS scores ranged from 6 to 9 (out of 9), indicating moderate to high methodological quality.

DISCUSSION
This review supports a possible link between PPI use and an increased risk of psoriasis. Potential
mechanisms include:

Gut microbiome dysbiosis: PPI-induced changes in gut flora may lead to increased intestinal
permeability and systemic immune activation.

Altered immune response: PPIs may interfere with antigen presentation and regulatory T-cell
function.

Drug-induced autoimmunity: Similar to how other drugs like beta-blockers and lithium can trigger
psoriasis, PPIs may act as immune disruptors.

However, several limitations must be considered:

Observational designs cannot confirm causality.

Confounding by indication (e.g., patients with GI disorders may inherently have higher
inflammatory burden).

Variability in psoriasis diagnostic criteria.

CONCLUSION

ki hubungan terhadap kinerja perawat. Menurut hasil penelitian ini, stres kerja memiliki
pengaruh yang besar bila dikaitkan dengan kinerja perawat, sedangkan beban kerja dan kepuasan
kerja memiliki pengaruh yang rendah dengan kinerja perawat. Keterbatasan penelitian ini yaitu
jumlah sampel yang cukup sedikit yaitu 85 responden. Penelitian ini diharapkan dapat dijadikan
sebagai landasan atau bahan evaluasi dalam penerapan pengelolaan sumber daya manusia terutama
dalam bidang keperawatan sebagai salah satu petugas pada lini pertama pelayanan medis di rumah
sakit agar pelayanan medis bisa berjalan dengan lebih baik, serta menjadi bahan pertimbangan
dalam pengambilan keputusan terkait variabel-variabel yang diteliti. Peneliti selanjutnya
diharapkan menambahkan variabel lain untuk mendapatkan hasil yang lebih baik dan lebih merata.
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Gdrive
kloter jan - feb 2025: h7ps://[Link]/drive/folders/1-
lcgWJLYMWkfneHYRTMC16wko8rSfLTQ
---
1. Peneli(an yang dijalankan oleh Depatemen gastroenterology and hepatology,
dermatology, dan allergy and clinical immunology Kangwon Na(onal University Hospital
di Chuncheon Korea
1. Metode =
2. Hasil = ada hubungan yang sta(s(cally significant antara prolonged use dari acid
suppresive drugs terhadap psoriasis. Secara spesifik = histamin 2 receptor antagonist
(H2RA) dan proton pump inhibitor (PPI).
1. Adjusted OR = 1.89 (95% CI, 1.66-2.17)
pasien yang menggunakan H2RA atau PPI dalam jangka waktu lama memiliki risiko
lebih <nggi terkena psoriasis dibandingkan mereka yang (dak menggunakannya
odds ra<o (OR) sebesar 1,89, ar(nya kemungkinan terkena psoriasis hampir dua kali
lebih <nggi pada kelompok pengguna jangka panjang.
CI) 95% antara 1,66 hingga 2,17 menunjukkan bahwa hasil ini cukup kuat dan konsisten
secara sta<s<k.
data juga memperlihatkan adanya hubungan dosis-respons, yang berar( semakin lama
atau semakin banyak obat ini digunakan, maka semakin <nggi pula risiko terkena
psoriasis.

- Pengambilan data dari Korean NaQonal Health Insurance Service-NaQonal Sample


Cohort (NHIS-NSC) --> database kohort nasional korea yang mencakup sekitar 1 juta
warga korea. Di follow up dari tahun 2002 hingga 2013. Data base ini mencakup
informasi medis (diagnosis, obat yang diresepkan, faktor sosial demografis, pendapatan
rumah tangga) --> dibagi kedalam kelompok 0-3 = rendah, 4-7 sedang, dan 8-10 Qnggi
- Definisi kelompok :
o Kelompok kasus = pasien yang pertama kali didiagnosis psoriasis dan sebelumnya
telah menggunakan H2RA atau PPI selama > 90 hari, minimal 1 tahun sebelum
diagnosis
o Kelompok kontrol = pasien dengan penyakit upper GI tract (esofagiQs, gastriQs,
ulkus) yang juga telah menggunakan H2RA atau PPI selama > 90 hari tapi Qdak
menderita psoriasis
- Proses seleksi :
o Dari total 748.816 subjek yang eligible (memenuhi syarat)
§ 200.612 subjek yang sudah menggunakan H2RA/PPI di tahun 2002
dikeluarkan
§ 2.793 px yang didiagnosis psoriasis < 1 tahun setelah mulai memakai obat
acid suppresive juga dikeluarkan (u/hindari bias waktu)
o Setelah eksklusi ada :
§ 3.679 px dalam kelompok kasus
§ 539.732 px dalam kelompok kontrol
o Kemudian dilakukan matching (pemasangan) berdasarkan usia, jenis kelamin,
diagnosis upper GI tract disorder :
§ 3.662 subjek dalam kelompok kasus
§ 14.648 subjek dalam kelompok kontrol
- PPI yang dianalisis = pantoprazole (40 mg), esomeprazole 30 mg, lansoprazole 30 mg,
dexlansoprazole 30 mg dan rabeprazole 20 mg

Dalam studi ini, cumulative dose dari obat penekan asam lambung diukur menggunakan satuan
Defined Daily Dose (DDD).

• DDD adalah dosis rata-rata harian standar dari suatu obat untuk indikasi utamanya pada
orang dewasa.

Setiap kali pasien menggunakan dosis harian standar, itu dihitung sebagai 1 DDD.
Lalu, total akumulasi DDD disebut sebagai cumulative DDD (cDDD).

Untuk analisis, total cDDD pasien dikelompokkan menjadi beberapa kategori:

• 0 (tidak ada penggunaan) → digunakan sebagai kelompok referensi (pembanding


utama).
• Kurang dari 10 cDDD.
• 10 hingga 30 cDDD.
• Lebih dari 30 cDDD.

Dengan pembagian ini, peneliti bisa mengevaluasi apakah semakin besar akumulasi dosis obat
berkaitan dengan semakin tinggi risiko psoriasis (melihat pola dose-response).

n ---
Hasil
- 18.310 subjek menggunakan acid suppresive drug selama > 90 hari dan Qdak ada riwayat
psoriasis sebelumnya. Dari jumlah ini, 3.662 subjek (20%) kemudian terdiagnosis
psoriasis lebih dari 1 tahun setelah mulai menggunakan acid suppresive drug.
- Tabel :
o Jenis kelamin = 61% laki-laki
o Kelompok usia paling banyak = 30-39 tahun (24.4%)
o Tempat Qnggal di pedesaan 50.4% Qnggal di daerah pedesaan
o Rata-rata pendapatan rumah tangga tergolong Qnggi (6.478orang/36.9%)

• Kalau dilihat berdasarkan kelompok cDDD:


o Pada kategori cDDD < 10:
§ 25,1% pasien psoriasis vs 19,5% kelompok kontrol → lebih banyak
pasien psoriasis dalam kategori ini (p < 0,001).
o Pada kategori cDDD 10–30:
§ 11,0% pasien psoriasis vs 8,0% kelompok kontrol → lebih banyak
pasien psoriasis (p < 0,001).
o Pada kategori cDDD ≥ 30:
§ 10,2% pasien psoriasis vs 6,2% kelompok kontrol → lebih banyak
pasien psoriasis (p < 0,001).
• Kesimpulannya:
Semakin besar akumulasi penggunaan obat (semakin tinggi cDDD), semakin tinggi juga
proporsi pasien yang mengembangkan psoriasis, dan hasil ini sangat signifikan
secara statistik (p < 0,001 di semua kategori).

Perbedaan CCI (Charlson Comorbidity Index):

• CCI mengukur tingkat penyakit penyerta (komorbiditas) pasien.


• Pasien psoriasis juga memiliki skor CCI yang lebih tinggi dibandingkan kontrol:
o 12,4% pasien psoriasis memiliki CCI ≥ 2, dibandingkan 9,3% pada kontrol (p
< 0,001).

Artinya:
Pasien yang mengembangkan psoriasis cenderung memiliki lebih banyak penyakit penyerta
dibandingkan mereka yang tidak.

QNA

Pertanyaan bagus!
Kategori cumulative Defined Daily Dose (cDDD) dalam studi ini ditentukan berdasarkan
jumlah total akumulasi dosis standar harian (DDD) dari obat penekan asam lambung (H2RA
atau PPI) yang dikonsumsi pasien selama periode tertentu.

Dasar pengelompokan cDDD biasanya dipilih untuk:

1. Merepresentasikan tingkat paparan ringan, sedang, dan berat.


2. Mendeteksi hubungan dose-response, yaitu apakah risiko meningkat seiring
bertambahnya dosis total.

Dalam studi ini, kategorinya dibagi sebagai berikut:

• cDDD = 0 → tidak ada penggunaan obat (kelompok referensi)


• < 10 cDDD → penggunaan ringan
• 10–30 cDDD → penggunaan sedang
• > 30 cDDD → penggunaan berat

Misalnya, jika 1 DDD untuk omeprazole adalah 20 mg per hari, maka:

• cDDD 10 berarti pasien mengonsumsi total 200 mg dalam 10 hari (20 mg/hari × 10 hari).
• cDDD 30 berarti pasien mengonsumsi total 600 mg dalam 30 hari.

Alasan cut-off seperti <10, 10–30, dan >30 biasanya bersifat:

• Praktis/statistik: untuk membagi data menjadi kelompok yang cukup besar dan
seimbang untuk dianalisis.
• Klinis: bisa mengindikasikan tingkat kepatuhan atau durasi terapi yang cukup bermakna
terhadap efek biologis jangka panjang.

1.

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