Skip to main content
Download PDF

Impact of gastrointestinal and psychological symptoms on disease activity and functional impairment in patients with spondyloarthritis: a cross-sectional study

BMC Rheumatology volume 9, Article number: 28 (2025) Cite this article

Abstract

Introduction

Spondyloarthritis (SpA) exhibits predominantly musculoskeletal symptoms but also significant gastrointestinal (GI) and psychological manifestations. Subclinical gut inflammation is common in SpA, with frequent symptoms such as abdominal pain and diarrhea. Psychological issues like depression and anxiety are also prevalent, with a negative impact on quality of life. This study aimed to evaluate the presence of GI and psychiatric symptoms in SpA patients without inflammatory bowel disease (IBD) and their association with disease characteristics.

Methods

Cross-sectional study, which included SpA patients from two rheumatology outpatient clinics. Patients were assessed for GI, and depressive symptoms (PHQ-9), perceived stress (PSS-10), disease activity (ASDAS, BASDAI) and functionality (BASFI). Laboratory tests included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and Secretory IgA. Statistical analysis involved Spearman correlation, linear regression, and multiple correspondence discriminant analysis (MCDA).

Results

Among 98 SpA patients, 79.6% had axial SpA. High disease activity and functional impairment were common. 65.3% reported ≥ 2 GI symptoms, predominantly abdominal pain and diarrhea. Depression (PHQ-9 ≥ 10) was observed in 46.7% of patients, being moderate to severe in 25.0%. Depression, perceived helplessness, and lack of self-efficacy were associated with high disease activity and GI symptoms. MCDA identified strong correlations between depression, GI symptoms, and disease activity.

Conclusion

This study highlights the association between GI and psychological symptoms with disease activity and functionality in SpA patients. Depression and perceived helplessness are prevalent and closely associated with high disease activity and GI symptoms, suggesting the need for interdisciplinary management from early stages to improve patient outcomes.

Key points

  1. 1.

    65.3% of SpA patients had ≥ 2 gastrointestinal (GI) symptoms, and 46.7% showed depression, highlighting significant psychological and GI involvement.

  2. 2.

    Depression correlated strongly with disease activity (BASDAI and BASFI), impacting SpA severity.

  3. 3.

    Patients with ≥ 2 GI symptoms had a higher risk of depression, indicating a strong GI-psychological link.

  4. 4.

    Findings support the need for interdisciplinary management to address both GI and psychological symptoms in SpA.

Peer Review reports

Introduction

Spondyloarthritis (SpA) is a group of diseases that have common pathophysiological and clinical features despite being phenotypically different [1]. In general, the prevalence varies between 0.1–2.5% [2]. In Latin America, it has been reported between 0.3–0.9% [3]. Subclinical gut inflammation has been reported in 50% of patients with axial spondyloarthritis (axSpA) [4], and a variable degree of patients report gastrointestinal (GI) symptoms such as abdominal distension, abdominal pain, diarrhea, presence of blood in stool, and weight loss in the absence of inflammatory bowel disease (IBD) [5]. With a prevalence as high as 15%, factors such as female sex, unemployment, higher disease activity, and mood symptoms are associated with the presentation of GI symptoms. This correlates with the higher risk of SpA patients having GI symptoms (OR = 1.59; 95% CI [1.05 to 2.40]) [6].

The relationship between the joint and mental health can be explained by the gradual reduction of mobility, stiffness, and fatigue in SpA, which can lead to psychological consequences, including depression and anxiety, which negatively affect quality of life (QoL) [7]. Approximately 30% of patients with axSpA [8] and 17% of patients with psoriatic arthritis (PsA) had depressive symptoms, and about 30% had anxiety symptoms [9]. The incidence of affective and anxiety symptoms increases both in the year before and the year after the diagnosis of inflammatory arthritis [10].

The relationship between the immune system and the GI and mental systems is evidenced by how different stressors affect its functioning [11]. On the other hand, the activation of immune cells and proinflammatory cytokines production has been associated with mood disorders changes, depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction, and sleep disturbances [12]; being possible biomarkers for depression [13].

A link between GI and mood symptoms in relation to the microbiome-gut-brain axis has been observed through the effect of disease activity on QoL in patients with SpA. In this context, psychosocial impairment independent of age, sex, body mass index (BMI), and smoking was reported in a cohort of rheumatoid arthritis (RA) and SpA patients. These patients exhibited abdominal pain, diarrhea, bloating, and reflux, along with anxiety and depression symptoms, fatigue, and sleep disturbances. Conversely, GI symptoms were less frequent in patients whose routine lives were less impacted [14]. Thus, there is a need for comprehensive assessment of SpA patients that extends beyond disease activity to include interventions aimed at improving overall functioning. This could involve nutritional interventions, given the role of microbiota in GI and mood symptoms.

Few studies have evaluated psychological symptoms and GI symptoms simultaneously in SpA patients without IBD. Thus, the present study aimed to evaluate the presence of GI and psychological symptoms in patients with SpA and their association with disease characteristics.

Methods

Patients

The study was designed as a cross-sectional study, conducted in adult patients from two rheumatology outpatient clinics between 2019–2022. The patient must have a clinical SpA diagnosis and fulfill the International Spondyloarthritis Assessment Society (ASAS) classification criteria [15]. The medical record was retrieved to find information about GI symptoms. Those with two or more GI symptoms in the last six months were referred to the gastroenterology clinic. Individuals with concomitant IBD, pregnancy, comorbidities such as malignancies, autoinflammatory or autoimmune diseases, immunodeficiency, acute or chronic pancreatitis, liver disease, or treatment with antibiotics or antiparasitics in the last 3 months were excluded. The study was approved by the Hospital Militar Central Research Ethics Committee (HMC-2017-023, Memo No. 9, May 5, 2017, and Memo No. 19, November 1, 2019). Additionally, the patients provided written informed consent.

Assessment of clinical and laboratory characteristics

A rheumatology specialist collected data related to disease activity, extra-articular manifestations, and treatment at the time of inclusion. Disease activity was assessed using the Axial Spondyloarthritis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and functionality with the Bath Ankylosing Spondylitis Functional Index (BASFI) [15, 16].

High-sensitivity C-reactive protein (CRP) was measured using the LKCRP1 chemiluminescence kit (Immulite 1000, Siemens®) according to the manufacturer’s instructions, and the reference values were 0–3 mg/dL. The erythrocyte sedimentation rate (ESR) was determined using the Wintrobe quantitative method (mm/hour), according to the manufacturer’s instructions. Values above 20 mm/hour were considered high. HLA*B27 allele measurement was performed using DNA Next-Generation Sequencing (NGS): Illumina/PacBio Sequencing with analysis of the second and third exons. The names of the repository/repositories and accession number(s) can be found below:

https://www.ncbi.nlm.nih.gov/, PRJNA843059.

Fecal calprotectin was quantified using the Enzyme-Linked Immunosorbent Assay (ELISA) kit, following the manufacturer’s guidelines: DiaSource-Quantitative Fecal Calprotectin KAPEPKT849®, with a suggested cut-off point for levels considered high at > 120 ng/mL, manufactured in Louvain La Neuve, Belgium.

Total serum secretory immunoglobulin A (SIgA) antibody quantitation was performed in an ELISA in-house sandwich assay described in previous studies [17], and total serum IgA levels were determined with system kinetic nephelometry IMMAGE Immunochemistry (Kit IMMAGE® IgA Ref. 446460) according to manufacturer’s specifications. SIgA values greater than 45 mg/mL and 82 to 453 mg/dL reference values for adults were considered positive respectively for total IgA.

Assessment of gastrointestinal symptoms

A survey was conducted to identify the presence of GI symptoms and diagnosis of SpA, and information was confirmed from medical records: diarrhea (defined as watery and loose stools three or more times in one day), stools with mucus, hematochezia, number of stools per day, abdominal pain, abdominal swelling, food intolerance, and weight loss. Patients with two or more GI symptoms were referred to the gastroenterology clinic. Under gastroenterologist criteria colonoscopy with digital chromoendoscopy with histological analysis was performed to rule-out IBD [18,19,20,21].

Assessment of depressive symptoms

The Patient Health Questionnaire-9 (PHQ-9) is a self-administered tool used for screening, diagnosing, monitoring, and measuring the severity of depression [22]. The score is assigned according to the frequency with which symptoms occur, and their severity can be organized into four categories according to this score: 0–4 (none), 5–9 (mild), 10–14 (moderate), 15–19 (moderately-severe), 20–27 (severe). The PHQ-9 has been validated in Colombia in patients using primary care services and in a group of healthy subjects [23].

Assessment of perceived helplessness and lack of self-efficacy

The Perceived Stress Scale (PSS-10) is a self-administered diagnostic tool used to evaluate the perception of stress. It measures how individuals perceive their life as stressful, focusing on the degree to which situations in their life are perceived as unpredictable, uncontrollable, and overwhelming [24] was applied. Questions 1,2,3,6,9,10 refer to perceived helplessness (measuring an individual’s feelings of a lack of control over their circumstances or their own emotions or reactions), and questions 4,5,7,8 to lack of self-efficacy (measuring an individual’s perceived inability to handle problems). The questions were answered on a Likert frequency scale with scores from 0 to 4, where the higher the score, the higher the perceived helplessness and the lower the lack of self-efficacy. In this study, the subscales of the PSS-10 were reported according to the results of the validation conducted in Colombia [25]. The results were grouped into categories if the participants responded with the following options: never, almost never, and occasionally.

Statistical analysis

Descriptive analyses were performed according to the variable characteristics and distributions. Spearman correlation analysis was performed to assess the strength and direction of associations between continuous variables. Then, linear regression models and multiple correspondence discriminant analysis (MCDA) were used to explore the relationship between GI and psychological symptoms with overall disease activity. Finally, from the MCDA, the significant variables that showed a significant correlation with PQH9 were included in a multinomial logistic regression analysis. Statistical significance was set at p-value < 0.05. The analyses were performed using IBM SPSS version 26 statistical program. Selection bias was addressed by evaluating patients based on ASAS criteria and excluding those with IBD through clinical and paraclinical assessments. Measurements were taken using standardized tools and validated measures. Statistical analyses were conducted to identify associations between relevant variables.

Results

A total of 98 patients with SpA without concurrent IBD were included, with 58.2% male gender and a mean age of 42.3 ± 10.4. The most frequently identified clinical subtype was axSpA (79.6%), followed by PsA, ReA, and undifferentiated SpA. Axial involvement was identified in 77.6% of patients. The HLA*B27 allele was present in 32.7% of the patients. The clinimetric results showed high disease activity above 50% according to the BASDAI and ASDAS scores, with a similar result in terms of impaired functionality according to the BASFI.

GI symptoms and 65.3% of the patients reported ≥ 2 GI symptoms in the previous month. Other clinical and demographic characteristics are presented in Table 1. The most frequently reported symptoms were abdominal pain and bloating, food intolerance, and diarrhea, lasting for more than four weeks, in addition, fatigue was present at 59.2% and weight loss in 20.4% (Supplementary Table 1). The macroscopic and histological analyses revealed notable GI abnormalities, varying by anatomical region. Macroscopically, rectal involvement was characterized by mucosal alterations and vascular pattern loss, each observed in 21.2% of cases, along with inflammation in 18.2% of patients. In the sigmoid colon, mucosal abnormalities were present in 18.2% of cases, with vascular pattern loss identified in 12.1%. The ileum exhibited the highest prevalence of abnormalities, including mucosal alterations in 51.5% of cases, intestinal villi atrophy in 42.4%, and vascular pattern loss in 33.3%.

Table 1 Patient characteristics according to presence of gastrointestinal symptoms
Full size table

Histologically, 72.7% of patients demonstrated abnormalities, predominantly in the ileum, where inflammatory patterns (36.4%), architectural alterations (39.4%), and chronic inflammation (33.3%) were prominent. Cryptitis or atrophy was identified in 30.3% of ileal samples. In contrast, inflammatory patterns were noted in 24.2% of colonic samples and 27.3% of rectal samples.

Furthermore, patients with ≥ 2 GI symptoms exhibited a higher frequency of disease activity (BASDAI, BASDAI > 4, ASDAS-CRP, ASDAS-CRP > 2.1; p < 0.05) and greater functional impairment (BASFI and BASFI > 4; p < 0.05). These findings underscore significant region-specific GI involvement in SpA, highlighting the need for further investigation into its pathological mechanisms and clinical implications.

The PHQ-9 was administered to 91 patients. 46.7% had depression (≥10), and depression severity was moderate to severe in 25% of patients. The PSS-10 was administered to 90 patients, the perceived helplessness was present more than often for question 1 in 56.7%, question 2 in 71.1%, question 3 in 70.0%, question 6 in 54.4%, question 9 in 62.2%, and question 10 52.2%. Meanwhile, lack of self-efficacy was present more frequently than sometimes for question 4 (65.6 %), question 5 (68.9 %), question 7 (72.2 %), and question 8 (85.6 %).

A higher frequency of depressive symptoms was found in male 34.7%; (p = 0.015), patients with BMI ≥ 25 (p = 0.028), and those with ASDAS-CRP ≥ 3.5 (p = 0.013). Regarding GI symptoms there was a tendence to higher frequency of depressive symptoms compared with absence of GI symptoms (53.2% vs 33.3% respectively, p = 0.073), additionally, a higher frequency of depressive symptoms was found in those with blood in stool (p = 0.028) and weight loss (p = 0.001).

A higher frequency of lack of self-efficacy was found in SpA patients with ASDAS-CRP ≥ 3.5 (p = 0.001) and non-high educational level (p = 0.032). Regarding GI symptoms, a higher frequency of a lack of self-efficacy was found with food intolerance (p = 0.031). There were no significant differences between individual GI symptoms perceived helplessness. Other disease specific variables including HLA or SpA subtype were not significant.

Disease activity and functional indexes and emotional scales

There was a strong positive correlation between the PHQ-9 score (depression severity) and the BASDAI (r = 0.74) and BASFI (r = 0.70) scores, and a moderate positive correlation for ASDAS-CRP (r = 0.59). PSS-10 scores had a moderate positive correlation between helplessness and BASDAI (r = 0.31) and BASFI (r = 0.32). However, there was a weak positive correlation with ASDAS-CRP. For lack of self-efficacy, there was a weak positive correlation, although it was significant with BASDAI and BASFI.

Additionally, patients with high moderate or severe depression more frequently had high disease activity (BASDAI ≥ 4, ASDAS-CRP ≥ 2.1 or ≥ 3.5, p = 0.001) and functional impairment (BASFI ≥ 4, p = 0.001). Helplessness was more frequently associated with high disease activity (BASDAI ≥ 4, ASDAS-CRP ≥ 2.1 or ≥ 3.5, p = 0.047, 0.003, and 0.013, respectively), as well as functional impairment (BASFI ≥ 4, p = 0.004). Lack of self-efficacy was also associated with high disease activity (ASDAS-CRP score ≥ 2.1, p = 0.042) and functional impairment (BASFI score ≥ 4, p = 0.028).

Regression model and multiple correspondence discriminant analysis

As a result of the logistic regression analysis, after controlling for demographic and clinical SpA variables the severity of depression measured by PQH-9 showed associations for mild depression with male gender with an OR 3.9 (95%CI 1.1–15.1). Additionally, there was a positive association for ≥ 2 GI symptoms and depression severity, increasing from mild depression OR 3.7 (95%CI 1.0–15.1) to severe depression OR 23.3 (95%CI, 3.4–160.3) (Table 2).

Table 2 Logistic regression model for factors associated with depression by PHQ-9 clinical and demographic variables in patients with SpA
Full size table

The PHQ-9 multiple correspondence discriminant model demonstrated good internal consistency (α = 0.803), generating two dimensions. Dimension 1 included the presence of ≥ 2 GI symptoms [correlation coefficient (CC) = 0.700)], abdominal pain (CC = 0.703), and fatigue (CC = 0.621). Dimension 2 consisted of depression assessed by the PHQ-9 (CC = 0.723), and high disease activity assessed by the BASDAI > 4 (CC = 0.381) (Fig. 1).

A MCDA was conducted to explore multinomial correlations and identify significant variables associated with PQH9. The model demonstrated strong internal consistency, with a Cronbach’s alpha of 0.803. Two distinct dimensions were identified: Dimension 1, which grouped > 2 GI symptoms (CC = 0.700), abdominal pain (CC = 0.703), and fatigue (CC = 0.621); and Dimension 2, which included PQH9 (CC = 0.723) and BASDAI > 4 (CC = 0.381) (Fig. 1).

Figure 1 presents a graphical representation of the interconnections among the variables in the model, depicted on a vector map within a Cartesian coordinate system. In this representation, the angle between each pair of variables conveys the strength of their correlation: smaller angles indicate a strong positive correlation, angles nearing 90° suggest no correlation, and angles approaching 180° reflect a strong negative or inverse correlation.

Fig. 1
figure 1

Multiple correspondence discriminant analysis. Discriminant analysis of multiple correspondence between depression (PHQ9) and disease activity (BASDAI), gastrointestinal symptoms, abdominal pain, and fatigue

Full size image

Discussion

The present study investigated non-inflammatory GI and psychological symptoms in SpA patients without concurrent IBD, identifying depression in half of the population. The findings revealed significant correlations between depression, helplessness, and lack of self-efficacy with SpA outcomes, such as disease activity and functional impairment. Specifically, mild depression was predominantly observed in male patients with ≥ 2 GI symptoms. Additionally, there was a statistically significant association between moderate depression and SpA patients with ≥ 2 GI symptoms, regardless of gender. These results suggest a relationship between GI and mental health symptoms in individuals with SpA.

Rheumatologic diseases are associated with a higher risk of psychological disorders. The standardized incidence ratios for rheumatoid arthritis (RA), systemic lupus erythematosus, and axSpA were 1.5, 2.4, and 1.7, respectively [26]. Depression is the second most frequent comorbidity in axSpA [27], with a meta-analysis indicating a prevalence of about 15% [28]. In a multinational cohort from Europe, Asia, and South America the prevalence is 32.3% [29], while in Colombia, 22% [30]. Interestingly, most studies used the Hospital Anxiety and Depression Scale (HADS) or the Zung Self-Rating Depression Scale (SDS) for depression diagnosis. Focusing on the PHQ-9 depression prevalence had been reported as high as 36% in India [31], similar to findings from Turkey [32] and China [33]. Meanwhile our results are higher than those reported, suggesting variability across regions.

The coexistence of SpA and IBD is not rare, leading to the development of screening tools for gastroenterology referrals [19]. In our center, diarrhea and abdominal pain were the most prevalent major and minor screening criteria associated with higher disease activity scores [21]. Consistent with previous reports, a higher frequency of GI symptoms, particularly abdominal pain, bloating, and diarrhea, was observed in active disease [34].

A recent study evaluated in RA and SpA European population the association between depression and GI symptoms such as abdominal pain, diarrhea, distension, and reflux. Additionally, there was an association between anxiety and abdominal pain, diarrhea, swallowing disorders, flatulence, and reflux [14]. When other GI diseases are evaluated, such as irritable bowel syndrome (IBS) patients exhibit elevated frequency of psychological symptoms [35, 36]. Meanwhile in IBD patients, the new onset GI symptoms were associated with anxiety [36]. Differentiating GI symptoms and the presence of IBS is challenging due to symptom overlap [37], which could be also challenging in other conditions such as SpA. Interestingly, in axSpA, those patients with depression, anxiety and fibromyalgia associated with IBS reported worse quality of life, global health, fatigue, disease activity, pain, and functional impairment [27]. This aligns with our findings highlighting the significance of the “gut-brain axis”, with the interplay between GI symptoms and mental illnesses. Up to 70% of SpA patients exhibit subclinical gut inflammation, and 5–10% of those with more severe intestinal inflammation progress to clinically defined IBD, which is the most common extra-articular manifestation of AS. This association leads to local inflammation through mechanisms such as molecular mimicry, increased intestinal permeability, IgA immune response, and the overexpression of inflammatory factors. These physiological processes underlying SpA also contribute to the development of depressive symptoms. This is primarily due to the activation of the immune system, resulting in the production and release of cytokines such as interferon-alpha (IFN-α), interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) [38].

Our study results demonstrate a correlation between high disease activity (BASDAI and ASDAS), functional limitation (BASFI), and psychological symptoms. Durmus et al. also found high disease activity associated with depression, anxiety, and other psychological symptoms, which were also related to functional capacity and fatigue [39]. Additionally, in SpA patients with high BASDAI scores, had increased SIgA levels [40], although the initial results showed evidence of differences in SIgA levels with GI symptoms, no further significant differences were evident in the subsequent analysis.

The male gender was the most affected by moderate depression, consistent with other studies showing higher incidence rates of psychological disorders in males with rheumatic diseases [41]. However, other publications observed an association between females and psychological symptoms with disease activity, sleep disturbances, fatigue, and quality of life [31]. A multinational study an association with female gender and psychological disorders was present, but in further analysis was not significant [42].

Helplessness, resulting from pain catastrophizing, significantly impacts quality of life [43], and it correlates with depression, anxiety, and disease activity in RA and axSpA [44,45,46]. This factor is rarely explored in conjunction with GI symptoms but are shown in our study to significantly correlate with SpA outcomes, such as disease activity and functional impairment. Penhoat et al. [47], reported persistent catastrophizing scores in patients under bDMARD, similar to our study, where no impact of therapy was evident in these scores. Additionally, lack of self-efficacy was associated with a low educational level. In agreement with another study that identified low education in SpA patients associated with depression and anxiety [32].

In a population-based survey, the presence of anxiety and depression was shown to be associated with non-inflammatory GI symptoms [48]. Similarly, a primary care study demonstrated that the number of GI symptoms increased the risk for anxiety [49]. This relationship appears to be bidirectional, as GI problems have been shown to increase the probability of developing depression by 7% and anxiety by 8.8% [50]. Although the design of our study does not establish causality, our findings contribute important insights into this relationship, specifically within the SpA population these findings suggest that GI symptoms may exacerbate depression in SpA patients [51]. However, it is also possible that baseline depression rates are inherently higher in those with GI symptoms [14, 52], as supported by existing evidence of the gut-brain axis influencing mental health [4]. We observed that GI symptoms were significantly associated with higher rates of depression, including moderate depression. These results suggest that GI symptoms may act as a factor that exacerbates depression in SpA patients, potentially amplifying disease activity and impairing overall quality of life.

Our study has several limitations. First, cross-sectional design restricts our ability to infer causality; while we identified associations between psychological symptoms and disease activity, we cannot determine the directionality of these relationships. Second, the generalizability of our findings is hindered by the relatively small sample size, which may not adequately represent the broader SpA population. Third, variations in reported levels of depression, perceived helplessness, and self-efficacy may arise from the specific cutoff values used for each scale and questionnaire. Despite this, our findings align with those reported in other populations, suggesting some degree of consistency.

Fourth is the exclusive use of self-report measures. While these tools provide valuable insights, they lack the diagnostic rigor of structured clinical interviews, and future studies employing such methods are necessary to validate our findings. Furthermore, we conducted a thorough evaluation of GI symptoms to exclude other underlying conditions that could confound our results. This distinction allows us to explore the relationship between GI symptoms and depression within a subset of patients where inflammation is not the primary driver of GI complaints. However, reliance on self-reporting may introduce bias, as patients’ perceptions of their symptoms could be influenced by various factors, including their psychological state.

In summary, the significance of our findings lies in their implications for the clinical management of SpA patients. Addressing GI symptoms as part of a comprehensive treatment approach may not only improve GI health but also reduce the psychological burden of depression and its negative impact on disease outcomes. Further longitudinal studies are essential to better understand the directionality of this relationship and to develop targeted interventions that address both GI and psychological symptoms in SpA patients.

Hence, underscore the importance of interdisciplinary management from early stages, addressing both GI and psychological symptoms as plausible targets for improving both psychological well-being and disease outcomes, which has important implications for the comprehensive care of SpA patients.

Data availability

The HLA datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, PRJNA843059.

Abbreviations

ASDAS:

Ankylosing Spondylitis Disease Activity Score

axSpA:

Axial Spondyloarthritis

BASDAI:

Bath Ankylosing Spondylitis Disease Activity Index

BASFI:

Bath Ankylosing Spondylitis Functional Index

bDMARDs:

Biologic Disease-Modifying Antirheumatic Drugs

BMI:

Body Mass Index

CRP:

C-Reactive Protein

csDMARDs:

Conventional Synthetic Disease-Modifying Antirheumatic Drugs

ESR:

Erythrocyte Sedimentation Rate

GI:

Gastrointestinal

HLA-B27:

Human Leukocyte Antigen B27

IBD:

Inflammatory Bowel Disease

IFN-α:

Interferon-alpha

IL-1, IL-6:

Interleukin-1, Interleukin-6

MCDA:

Multiple Correspondence Discriminant Analysis

NSAID:

Non-Steroidal Anti-Inflammatory Drugs

PHQ-9:

Patient Health Questionnaire-9

PsA:

Psoriatic Arthritis

PSS-10:

Perceived Stress Scale-10

QoL:

Quality of Life

RA:

Rheumatoid Arthritis

ReA:

Reactive Arthritis

SIgA:

Secretory Immunoglobulin A

SpA:

Spondyloarthritis

TNF-α:

Tumor Necrosis Factor-alpha

References

  1. Stolwijk C, Boonen A, van Tubergen A, Reveille JD. Epidemiology of Spondyloarthritis. Rheum Dis Clin North Am. 2012;38:441–76. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.rdc.2012.09.003.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Muñoz-Fernández S, de Miguel E, Cobo-Ibáñez T, et al. Early spondyloarthritis: results from the pilot registry ESPIDEP. Clin Exp Rheumatol. 2010;28:498–503.

    PubMed  Google Scholar 

  3. Citera G, Bautista-Molano W, Peláez-Ballestas I, et al. Prevalence, demographics, and clinical characteristics of Latin American patients with spondyloarthritis. Adv Rheumatol. 2021;61:2.

    Article  PubMed  Google Scholar 

  4. Gracey E, Vereecke L, McGovern D, et al. Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis. Nat Rev Rheumatol. 2020;16:415–33.

    Article  PubMed  Google Scholar 

  5. Caplan L, Kuhn KA. Gastrointestinal and hepatic disease in spondyloarthritis. Rheum Dis Clin North Am. 2018;44:153–64. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.rdc.2017.09.004.

    Article  PubMed  Google Scholar 

  6. Bernard J, Barnetche T, Amory C, et al. Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis. RMD Open. 2024;10:e003836.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Gupta L, Ahmed S, Choudhury G, et al. Poor quality of life in indian ankylosing spondylitis patients. Indian J Rheumatol. 2018;13:101.

    Article  Google Scholar 

  8. Karmacharya P, Crowson CS, Lennon RJ, et al. Multimorbidity phenotypes in ankylosing spondylitis and their association with disease activity and functional impairment: data from the prospective study of outcomes in ankylosing spondylitis cohort. Semin Arthritis Rheum. 2024;64:152282.

    Article  CAS  PubMed  Google Scholar 

  9. Freire M, Rodríguez J, Möller I, et al. Prevalencia de síntomas de ansiedad y de depresión en pacientes con artritis psoriásica en consultas de reumatología. Reumatol Clin. 2011;7:20–26.

    Article  PubMed  Google Scholar 

  10. Vestergaard SB, Esbensen BA, Klausen JM, et al. Prevalence of anxiety and depression and the association with self-management behaviour in >12 000 patients with inflammatory rheumatic disease: a cross-sectional nationwide study. RMD Open. 2024;10(e003412). doi:https://doiorg.publicaciones.saludcastillayleon.es/10.1136/rmdopen-2023-003412

  11. Söderholm JD, Perdue MH. II. Stress and intestinal barrier function. Am J Physiol Gastrointest Liver Physiol. 2001;280:G7–G13. https://doiorg.publicaciones.saludcastillayleon.es/10.1152/ajpgi.2001.280.1.G7.

    Article  PubMed  Google Scholar 

  12. Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011;130:226–38. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.pharmthera.2011.01.014.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Poletti S, Mazza MG, Benedetti F. Inflammatory mediators in major depression and bipolar disorder. Transl Psychiatry. 2024;14:247. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41398-024-02921-z.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Iaquinta F, Mauro D, Pantano I, et al. Gastrointestinal symptoms impact psychosocial function and quality of life in patients with rheumatoid arthritis and spondyloarthritis: a cross-sectional study. J Clin Med. 2023;12:3248.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Rudwaleit M, van der Heijde D, Landewe R, et al. The development of assessment of spondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68:777–83.

    Article  CAS  PubMed  Google Scholar 

  16. Machado PMMC, Landewé RBM, Van Der Heijde DM. Endorsement of definitions of disease activity states and improvement scores for the ankylosing spondylitis disease activity score: results from OMERACT 10. J Rheumatol. 2011;38:1502–06. https://doiorg.publicaciones.saludcastillayleon.es/10.3899/JRHEUM.110279.

    Article  PubMed  Google Scholar 

  17. Arias I, Herrera D, Bautista-Molano W, et al. Increasing of SIgA serum levels may reflect subclinical intestinal involvement in non-radiographic axial and peripheral spondyloarthritis. Clin Rheumatol. 2021;40:1343–51.

    Article  PubMed  Google Scholar 

  18. Felice C, Leccese P, Scudeller L, et al. Red flags for appropriate referral to the gastroenterologist and the rheumatologist of patients with inflammatory bowel disease and spondyloarthritis. Clin Exp Immunol. 2019;196:123–38.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Sanz Sanz J, Juanola Roura X, Seoane-Mato D, et al. Criterios de cribado de enfermedad inflamatoria intestinal y espondiloartritis para derivación de pacientes entre Reumatología y Gastroenterología. Gastroenterol Hepatol. 2018;41:54–62.

    Article  PubMed  Google Scholar 

  20. Viviana PI, Jaiber G, Cristian F, et al. P060 screening criteria of inflammatory bowel disease: application in Colombian patients with spondyloarthritis. Am J Gastroenterol. 2021;116:S16.

    Article  Google Scholar 

  21. Gutiérrez-Sánchez J, Parra-Izquierdo V, Flórez-Sarmiento C, et al. Implementation of screening criteria for inflammatory bowel disease in patients with spondyloarthritis and its association with disease and endoscopic activity. Clin Rheumatol. 2023;42:415–22.

    Article  PubMed  Google Scholar 

  22. Walker EA, Roy-Byrne PP, Katon WJ, et al. Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease. Am J Psychiatry. 1990;147:1656–61.

    Article  CAS  PubMed  Google Scholar 

  23. Berrío N, Sánchez JP, Mora S, et al. Validación del cuestionario sobre depresión PHQ-9 en una muestra colombiana no clínica. Revista de Psicopatología Y Psicología Clínica. 2024;29:59–69.

    Article  Google Scholar 

  24. Cohen S. Perceived stress in a probability sample of the United States. In: Spacapan S, Oskamp S, editors. The Social Psychology of Health. Sage Publications; 1988. p. 31–67.

    Google Scholar 

  25. Campo-Arias A, Oviedo HC, Herazo E. Escala de Estrés Percibido-10: desempeño psicométrico en estudiantes de medicina de Bucaramanga, Colombia. Revista de la Facultad de Medicina. 2015;62:407–13. https://doiorg.publicaciones.saludcastillayleon.es/10.15446/revfacmed.v62n3.43735.

    Article  Google Scholar 

  26. Branco JC, Rodrigues AM, Gouveia N, et al. Prevalence of rheumatic and musculoskeletal diseases and their impact on health-related quality of life, physical function and mental health in Portugal: results from EpiReumaPt– a national health survey. RMD Open. 2016;2(e000166). https://doiorg.publicaciones.saludcastillayleon.es/10.1136/rmdopen-2015-000166

  27. Zhao SS, Radner H, Siebert S, et al. Comorbidity burden in axial spondyloarthritis: a cluster analysis. Rheumatology. 2019;58:1746–54.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Zhao S, Thong D, Miller N, et al. The prevalence of depression in axial spondyloarthritis and its association with disease activity: a systematic review and meta-analysis. Arthritis Res Ther. 2018;20. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/S13075-018-1644-6.

  29. Dougados M, Logeart I, Szumski A, et al. Evaluation of whether extremely high enthesitis or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores suggest fibromyalgia and confound the anti-TNF response in early non-radiographic axial spondyloarthritis. Clin Exp Rheumatol. 2017;35:50–53.

    PubMed  Google Scholar 

  30. Moreno Ramos MJ, Linares Ferrando LF, Moreno Martínez MJ. Ansiedad y depresión en la espondilitis anquilosante: una visión histórica. Revista Colombiana de Reumatología. 2015;22:201–09. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.rcreu.2015.10.003.

    Article  Google Scholar 

  31. Narendra Reddy K, Sabu N, Pandey N, et al. Anxiety and depression among patients with axial spondyloarthritis. Eur J Rheumatol. 2022;9:8–13.

    Article  Google Scholar 

  32. Kilic G, Kilic E, Ozgocmen S. Relationship between psychiatric status, self-reported outcome measures, and clinical parameters in axial spondyloarthritis. Medicine. 2014;93:e337. https://doiorg.publicaciones.saludcastillayleon.es/10.1097/MD.0000000000000337.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Xu X, Shen B, Zhang A, et al. Anxiety and depression correlate with disease and quality-of-life parameters in Chinese patients with ankylosing spondylitis. Patient Prefer Adherence. 2016;10:879–85.

    PubMed Central  PubMed  Google Scholar 

  34. Romero-Sánchez C, Bautista-Molano W, Parra V, et al. Gastrointestinal symptoms and elevated levels of Anti- Saccharomyces cerevisiae antibodies are associated with higher disease activity in Colombian patients with spondyloarthritis. Int J Rheumatol. 2017;2017:1–8.

    Article  Google Scholar 

  35. Dean B, Tawadros N, Scarr E, Gibbons AS. Regionally-specific changes in levels of tumour necrosis factor in the dorsolateral prefrontal cortex obtained postmortem from subjects with major depressive disorder. J Affect Disord. 2010;120:245–48. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jad.2009.04.027.

    Article  CAS  PubMed  Google Scholar 

  36. Koloski NA, Jones M, Talley NJ. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study. Aliment Pharmacol Ther. 2016;44:592–600. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/apt.13738.

    Article  CAS  PubMed  Google Scholar 

  37. Pérez de Arce E, Quera R, Beltrán CJ, et al. Irritable bowel syndrome in inflammatory bowel disease. Synergy in alterations of the gut-brain axis? Gastroenterol Hepatol. 2022;45:66–76.

    Article  Google Scholar 

  38. Zhang L, Hu Y, Xu Y, et al. The correlation between intestinal dysbiosis and the development of ankylosing spondylitis. Microb Pathog. 2019;132:188–92.

    Article  PubMed  Google Scholar 

  39. Durmus D, Sarisoy G, Alayli G, et al. Psychiatric symptoms in ankylosing spondylitis: their relationship with disease activity, functional capacity, pain and fatigue. Compr Psychiatry. 2015;62:170–77.

    Article  PubMed  Google Scholar 

  40. Salas-Cuestas F, Bautista-Molano W, Bello-Gualtero JMM, et al. Higher levels of secretory IgA are associated with low disease activity index in patients with reactive Arthritis and undifferentiated Spondyloarthritis. Front Immunol. 2017;8:476.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Sundquist K, Li X, Hemminki K, Sundquist J. Subsequent risk of hospitalization for Neuropsychiatric disorders in patients with rheumatic diseases. Arch Gen Psychiatry. 2008;65:501. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/archpsyc.65.5.501.

    Article  PubMed  Google Scholar 

  42. Garrido-Cumbrera M, Gálvez-Ruiz D, Delgado-Domínguez CJ, et al. Impact of axial spondyloarthritis on mental health in Europe: results from the EMAS study. RMD Open. 2021;7:e001769.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Wilk M, Łosińska K, Pripp AH, et al. Pain catastrophizing in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: biopsychosocial perspective and impact on health-related quality of life. Rheumatol Int. 2022;42:669–82.

    Article  PubMed  Google Scholar 

  44. Gossec L, Chauvin P, Saraux A, et al. Development and psychometric validation of a patient-reported outcome measure to assess fears in rheumatoid arthritis and axial spondyloarthritis: the Fear Assessment in Inflammatory Rheumatic diseases (FAIR) questionnaire. Ann Rheum Dis. 2018;77:258–63.

    Article  PubMed  Google Scholar 

  45. Jang JH, Green CE, Assassi S, et al. The contribution of disease activity on functional limitations over time through psychological mediators: a 12-month longitudinal study in patients with ankylosing spondylitis. Rheumatology. 2011;50:2087–92.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Currado D, Biaggi A, Pilato A, et al. The negative impact of pain catastrophising on disease activity: analyses of data derived from patient-reported outcomes in psoriatic arthritis and axial spondyloarthritis. Clin Exp Rheumatol. 2023;41:1856–61.

    PubMed  Google Scholar 

  47. Penhoat M, Saraux A, Le Goff B, et al. High pain catastrophizing scores in one-fourth of patients on biotherapy for spondylarthritis or rheumatoid arthritis. Joint Bone Spine. 2014;81:235–39.

    Article  PubMed  Google Scholar 

  48. Haug TT, Mykletun A, Dahl AA. Are anxiety and depression related to gastrointestinal symptoms in the general population? Scand J Gastroenterol. 2002;37:294–98. https://doiorg.publicaciones.saludcastillayleon.es/10.1080/003655202317284192.

    Article  PubMed  Google Scholar 

  49. Mussell M, Kroenke K, Spitzer RL, et al Gastrointestinal symptoms in primary care: prevalence and association with depression and anxiety. J Psychosom Res. 2008;64:605–12.

    Article  PubMed  Google Scholar 

  50. Cantarero-Prieto D, Moreno-Mencia P. The effects of gastrointestinal disturbances on the onset of depression and anxiety. PLoS One. 2022;17:e0262712. https://doiorg.publicaciones.saludcastillayleon.es/10.1371/journal.pone.0262712.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Zou Q, Jiang Y, Mu F, et al. Correlation of Axial Spondyloarthritis with Anxiety and Depression. Med Sci Monit. 2016;22:3202–08.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Walter S, Jones MP, Sjödahl J, et al. Measuring the impact of gastrointestinal inconvenience and symptoms on perceived health in the general population– validation of the Short Health Scale for gastrointestinal symptoms (SHS-GI). Scand J Gastroenterol. 2021;56:1406–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank to the patients who participated in this study, and made it possible.

Funding

This study was supported by The Ministry of Science, Technology, and Innovation - MinCiencias (Grant No. 130877757442.). Universidad El Bosque, Hospital Militar Central (Grant 2017-023), Clínicos IPS, Gastroadvanced IPS, Fundación Instituto de Reumatología Fernando Chalem, in Bogotá, Colombia and Biomedicina de Chihuahua, México.

Author information

Authors and Affiliations

  1. Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia

    Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Juan Manuel Bello-Gualtero & Consuelo Romero-Sánchez

  2. Clinical Immunology Group, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia

    Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Juan Manuel Bello-Gualtero, Wilson Bautista-Molano & Consuelo Romero-Sánchez

  3. Hospital Universitario Nacional, School of Medicine, Bogotá, Universidad Nacional de Colombia, Bogotá, Colombia

    Julián Andrés Sucerquia-Quintero

  4. Cellular and Molecular Immunology Group, Universidad El Bosque, Bogotá, Colombia

    Omar-Javier Calixto, Juliette De Ávila, Cristian Flórez-Sarmiento, Wilson Bautista-Molano & Consuelo Romero-Sánchez

  5. Psychiatry and Mental Health Department, Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia

    Oscar Gómez

  6. Gastroadvanced IPS, Bogotá, Colombia

    Cristian Flórez-Sarmiento

Authors
  1. Ángelo Arzuaga-Hernández
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Omar-Javier Calixto
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Oscar Gómez
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Juliette De Ávila
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Julián Andrés Sucerquia-Quintero
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Juan Manuel Bello-Gualtero
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Cristian Flórez-Sarmiento
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Wilson Bautista-Molano
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Consuelo Romero-Sánchez
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

The authors certify that they have participated sufficiently in the work to take public responsibility for the appropriateness of the design and method of review, as well as the reviewing of the manuscript and approve it for publication: Conceptualization: Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Oscar Gómez, Julián Andrés Sucerquia-Quintero, Wilson Bautista-Molano, Consuelo Romero-Sánchez. Methodology: Ángelo Arzuaga-Hernández, Julián Andrés Sucerquia-Quintero, Consuelo Romero-Sánchez. Formal analysis and investigation: Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Oscar Gómez, Juliette De Ávila, Consuelo Romero-Sánchez. Writing - original draft preparation: Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Oscar Gómez, Wilson Bautista-Molano, Consuelo Romero-Sánchez. Writing - review and editing: Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Oscar Gómez, Juliette De Ávila, Julián Andrés Sucerquia-Quintero, Juan Manuel Bello-Gualtero, Cristian Flórez-Sarmiento, Wilson Bautista-Molano, Consuelo Romero-Sánchez. Funding acquisition: Consuelo Romero-Sánchez. Resources: Consuelo Romero-Sánchez. Supervision: Ángelo Arzuaga-Hernández, Omar-Javier Calixto, Oscar Gómez, Juliette De Ávila, Julián Andrés Sucerquia-Quintero, Juan Manuel Bello-Gualtero, Cristian Flórez-Sarmiento, Wilson Bautista-Molano, Consuelo Romero-Sánchez

Corresponding author

Correspondence to Consuelo Romero-Sánchez.

Ethics declarations

Ethics approval and consent to participate

The study was designed in compliance with the Helsinki Declaration, and approved by Hospital Militar Central Institutional Ethics Committee (HMC-2017-023). The patients provided written informed consent form.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arzuaga-Hernández, Á., Calixto, OJ., Gómez, O. et al. Impact of gastrointestinal and psychological symptoms on disease activity and functional impairment in patients with spondyloarthritis: a cross-sectional study. BMC Rheumatol 9, 28 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41927-025-00478-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41927-025-00478-y

Keywords

BMC Rheumatology

ISSN: 2520-1026

Contact us