Patients with fibromyalgia syndrome (FMS) are 1.40 times more likely to develop peptic ulcer disease (PUD) compared with those without FMS, according to a study recently published in PLOS One.1 Older patients with FMS were especially vulnerable, with those aged 50 to 64 years and ≥65 years having a 1.58- and 1.96-fold higher risk for PUD, respectively.
“This is the first study that showed the long-term risk for PUD in FMS patients by using a population-based database,” the researchers wrote. They used the Longitudinal Health Insurance Database 2000 (LHID2000), which enables encrypted patient data to be pulled from Taiwan’s single-payer universal health insurance program.
Using LHID2000, the researchers identified 26,068 patients aged >20 years who received an FMS diagnosis between 2000 and 2011. They then randomly pulled data for another 104,269 people without FMS to serve as controls. The control cohort was matched to the FMS cohort by index year, sex, and age. Both cohorts had average follow-up durations between 5 and 6 years, and neither had PUD at baseline.
The researchers reported a PUD incidence density rate of 29.8 per 1000 person-years in the FMS cohort vs 19.4 per 1000 person-years in the control cohort. Patients with other comorbidities, including hyperlipidemia, liver cirrhosis, hypertension, depression, anxiety, sleep disorders, and gastroesophageal reflux disease were also found to be at increased risk for PUD, but these comorbidities were also more prevalent in the FMS cohort. Unlike in other studies, use of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other antidepressants were not found to increase the risk for PUD,2-6 but those taking nonsteroidal anti-inflammatory drugs (NSAIDs) had a 1.28-fold higher risk for PUD than those not taking NSAIDs (95% confidence interval, 1.24-1.33). Regardless of how the cohorts were stratified (ie, age, sex, comorbidities, medication use), the risk for PUD was consistently elevated in those with FMS.
“The mechanisms underlying the association of FMS with an increased risk for PUD are unclear,” the researchers wrote. “However, many patients reported an intestinal infection as the initial symptom of FMS; therefore, current and past infection with common intestinal pathogens (ie, H pylori) might induce PUD development in FMS patients,” they indicated. They also suggested that factors such as stress, trauma, or use of certain medications could cause PUD and subsequent development of leaky gut syndrome, resulting in an immune response secondary to systemic inflammation, triggering FMS and other diseases. Additional studies in more diverse cohorts are needed to better determine the link between FMS and PUD and define their underlying mechanisms.
Summary and Clinical Applicability
Patients with FMS are known to have a variety of comorbidities, with gastrointestinal problems being common.1 The current study provides epidemiological evidence that these patients might also be at increased risk for PUD. Although more definitive studies are needed, it might be prudent to inform patients with FMS of this risk, particularly if they are older (≥49 years) and/or taking NSAIDs.
Limitations and Disclosures
The researchers reported several study limitations, including limited data in the LHID2000 database (eg, no information on certain potentially confounding factors, such as diet, smoking, alcohol use); lack of assessment of severity of FMS and PUD, making it unclear how FMS severity might affect PUD risk; and use of a homogenous study population.
Several sources of government and medical foundation funding were reported, but the funders were reported to have “no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.”
- Wang KA, Wang JC, Lin CL, Tseng CH. Association between fibromyalgia syndrome and peptic ulcer disease development. PLOS One. 2017;12(4): e0175370. doi: 10.1371/journal.pone.0175370
- de Jong JC, van den Berg PB, Tobi H, de Jong-van den Berg LT. Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse effects. Br J Clin Pharmacol. 2003;55(6):591-595. doi: 10.1046/j.0306-5251.2002.01770.x
- Calandre EP, Rico-Villademoros F, Slim M. An update on pharmacotherapy for the treatment of fibromyalgia. Expert Opin Pharmacother. 2015;16(9):1347-1368. doi: 10.1517/14656566.2015.1047343
- Liao CH, Chang CS, Chang SN, et al. The association of peptic ulcer and schizophrenia: a population-based study. J Psychosom Res. 2014;77(6):541-546. doi: 10.1517/14656566.2015.1047343
- Dall M, Schaffalitzky de Muckadell OB, et al. Helicobacter pylori and risk of upper gastrointestinal bleeding among users of selective serotonin reuptake inhibitors. Scand J Gastroenterol. 2011;46(9):1039-1044. doi: 10.3109/00365521.2011.580100
- Itatsu T, Nagahara A, Hojo M, et al. Use of selective serotonin reuptake inhibitors and upper gastrointestinal disease. Intern Med. 2011;50(7):713-717. doi: 10.2169/internalmedicine.50.4644