Introduction

Postural orthostatic tachycardia syndrome (POTS) is a disorder of cardiovascular autonomic dysfunction, characterized with heart rate (HR) acceleration and orthostatic intolerance upon standing. Gastrointestinal (GI) symptoms are common in POTS (1).

Aims & Methods

The aim of this study was to explore the prevalence and severity of GI-symptoms in a Swedish POTS-cohort, and to investigate whether previously tested HR acceleration correlates with GI-symptoms.
To this cross-sectional study, we included 43 patients with POTS (93% female, median age 30.6 years) and 74 healthy controls (78% female, median age 35.6 years), who completed a study questionnaire, including prevalence of GI symptoms (2). GI symptom severity was assessed by the IBS severity scoring system (IBS-SSS) (3) and the visual analog scale for IBS (VAS-IBS) (4), both measured in millimetres (0-100). Five items from the IBS-SSS were added, producing a total IBS-SSS (maximum score 500). In addition, extra-intestinal symptoms from the IBS-SSS were assessed. All patients were examined by head up tilt test during 2010-2021, which included monitoring of blood pressure and HR at supine position and after 1, 3 and 10 minutes in upright position (5). Also, the maximum HR was measured. ΔHR was calculated from supine position to each time point of upright position. All continuous variables on the IBS-SSS and VAS-IBS-scale were correlated to ΔHR at each time point and adjustments were made for psychological well-being.

Results

In patients with POTS, all variables on the GI questionnaire were significantly higher than in controls. The most prevalent symptoms were nausea (79,1%), abdominal fullness (69.8%) and bloating (66.7%). The most severe GI symptoms measured on the VAS-IBS scale, were bloating and flatulence and constipation (see table, values presented as median (IQR), measured in millimetres). Total IBS-SSS was 213 (135-319) in POTS. The most common self-reported comorbidities in POTS were IBS (n=12) and hypermobile spectrum disorders (n=12). Seven patients reported organic GI disorder. There was an inverse correlation between ΔHR_max and abdominal pain (r=-0.406, p=0.007). The same tendency was seen at ΔHR_10min (p=0.054). No positive correlations were found between ΔHR and any GI-symptom and no correlations were found between ΔHR and extraintestinal symptoms. When excluding patients with organic GI disorder, we saw significantly inverse correlations between ΔHR_10min and ΔHR_max and abdominal pain, constipation, GI symptom’s influence on daily life, and total-IBS-SSS, respectively. Adjustments for psychological well-being did not affect the results.

Conclusion

This study confirms that GI-symptoms are widespread in POTS, equivalent to moderate IBS. Nausea is the most prevalent symptom, whereas bloating and flatulence, and constipation are the symptoms that are reported as most severe. Higher HR acceleration at diagnosis upon tilt testing seems to be associated with less severe chronic GI-symptoms in POTS. This finding may reflect the heterogeneity and possibly different underlying pathophysiological mechanisms in POTS, but it may also reflect treatment bias.

References

1. DiBaise, J. K., et al. (2018). "Postural Tachycardia Syndrome (POTS) and the GI Tract: A Primer for the Gastroenterologist." Am J Gastroenterol 113(10): 1458-1467.
2. Faraj, J., et al. (2007). "Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus." Diabet Med 24(11): 1235-1239.
3. Francis, C. Y., et al. (1997). "The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress." Aliment Pharmacol Ther 11(2): 395-402.
4. Bengtsson, M., et al. (2007). "Development and psychometric testing of the Visual Analogue Scale for
Irritable Bowel Syndrome (VAS-IBS)." BMC Gastroenterol 7: 16.
5. Brignole, M., et al. (2018). "2018 ESC Guidelines for the diagnosis and management of syncope." Eur Heart J 39(21): 1883-1948.

Introduction

Functional bowel disorders are characterized by the presence of altered bowel habits with or without abdominal pain.¹ Irritable bowel syndrome (IBS) is diagnosed based on recurrent abdominal pain; however, distinctions in the clinical phenotypes of IBS subtypes and other functional bowel disorders (FBDs), such as functional diarrhea (FD) and functional constipation (FC), remain underexplored.^2,3

Aims & Methods

Aims: This study aimed to characterize the clinical presentation of IBS with predominant constipation (IBS-D) and IBS with predominant diarrhea (IBS-C), differentiating them from FD and FC, while recognizing the overlapping symptoms and the continuum between these conditions. Additionally, we examined the prevalence of psychological disorders and extra-intestinal comorbidities and identified potential mediators linking IBS to anxiety and depression.
Methods: Using data from the Rome Foundation Global Epidemiology Study, we analyzed 54,127 participants across 26 countries, including 2,195 patients with IBS. Clinical, dietary and psychological characteristics were assessed using validated questionnaires. Subgroup analyses compared IBS subtypes with FBDs, while mediation analyses (using the PROCESS macro and Baron and Kenny's method⁴) identified mediators of IBS-psychological distress relationship.

Results

As compared to patients with IBS-D, patients with IBS-C reported more severe pain characteristics, including prolonged pain episodes (50.7% vs. 47.0% of the time with pain lasting >30 minutes, p=0.030) and pain episodes that escalated to a sustained severe intensity (44.2% vs. 38.1%, p=0.026), frequently accompanied by back pain (36.7% vs. 30.9%, p<0.001). Regular use of prescribed pain medications was also more frequent in IBS-C (39.3%) than IBS-D (31.8%, p=0.004). In contrast, as compared to IBS-C, patients with IBS-D showed a stronger association of pain with changes in stool consistency (70% vs. 60% of time with pain, p<0.001) and frequency (mean 61.3% vs. 57.8% of time with pain, p=0.008). These associations remained significant in multiple regression models, which confirmed that IBS-C is more strongly linked to prolonged and escalating pain episodes, while IBS-D is more closely linked to pain associated with changes in stool frequency and consistency. As compared to FD, IBS-D patients reported greater dissatisfaction with bowel function (57.3±28.4 vs. 44.2±29.8, p<0.001), and more frequent loose stools (without constipation treatments) (60.0% vs. 50.0% of bowel movements, p<0.001), particularly after meals (60.0% vs. 40.0% of loose stools, p<0.001). IBS-C shows more severe constipation-related symptoms compared to FC (p<0.001). Mediation analyses revealed that concerns about bowel function, embarrassment discussing it, and work-related impairments partially mediated the relationship between IBS and psychological distress.

Conclusion

IBS-C is associated with more severe pain episodes, including prolonged and escalating pain, while in IBS-D pain is more strongly linked to bowel habit changes. These findings highlight the distinct clinical profiles of IBS subtypes and emphasize the need for personalized, multimodal management strategies. Identifying mediators of psychological distress in IBS can guide targeted interventions, improving patient outcomes.

References

1. Lacy, B. E. et al. Bowel Disorders. Gastroenterology (2016) doi:10.1053/j.gastro.2016.02.031.
2. Savarino, E. et al. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J 10, 556–584 (2022).
3. Mearin, F. et al. Clinical Practice Guideline: Irritable bowel syndrome with constipation and functional constipation in the adult. Revista espanola de enfermedades digestivas 108, 332–63 (2016).
4. Baron, R. M. & Kenny, D. A. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51, 1173–82 (1986).

Introduction

Somatization is defined as a tendency to experience and communicate psychological distress in the form of somatic symptoms. Literature suggests that there is a link between somatization and irritable bowel syndrome (IBS). Nevertheless, the association between clinical symptoms of IBS and somatization, especially in children, remains unclear.

Aims & Methods

54 children aged 6-12 with a verified diagnosis of IBS according to Rome criteria IV were included in the study. The control group consisted of 50 healthy children of the same age and gender. The level of somatization was assessed by the Somatoform Symptom Screening test (SOMS-2J by Rief, W., & Hiller, W.), which was modified for children. The intensity of abdominal pain and dyspeptic symptoms were estimated using a 4-point Likert scale. Data were processed using Microsoft Excel 2016 and analyzed with GraphPad (Prism 5.0). Pearson test was used to assess the correlation between SOMS rate and the intensity of somatic complaints.

Results

The level of somatization was significantly higher in children with IBS in comparison to the control group (p<0.0001). There was no difference in somatization rate in patients according to the predominant bowel habit. A direct correlation between the intensity of abdominal pain and the level of somatization (r=+0.37; p=0.005) was established in children with IBS (Fig.1). On the contrary, the intensity of dyspeptic symptoms was less influenced by the rate of somatization (r=+0,18; p=0,20).

Conclusion

To conclude, children with IBS who had higher rates of somatization were revealed to have a higher intensity of somatic complaints, especially abdominal pain. We suggest that somatization plays an important role in the occurrence of somatic symptoms of IBS. It may be one of the reasons for the low effectiveness of pharmacological treatment of IBS in children.

Introduction

Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell proliferation in one or more organs that induces cutaneous and/or systemic symptoms. While gastrointestinal (GI) symptoms are frequently reported (prevalence ~60%), no surrogate markers have been investigated yet.

Aims & Methods

This study aimed to explore disease-specific markers and their link to gastrointestinal symptoms in mastocytosis. Plasma samples were collected from patients with mastocytosis, including patients with cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), and Advanced SM (AdvSM). The presence of GI symptoms was registered. Patients with polycythemia vera (PCV), a stem cell disorder characterized by sludging of blood, were included as controls. In total, 276 systemic proteins were analyzed by Proximity Extension Assay using the OLINK Target 96 Cardiovascular II and III, and Immune response panels. Relative protein concentrations, expressed in NPX (log₂ Normalized Protein eXpression), were analyzed using Principal Component Analysis (PCA), linear regression of protein adjusted values (for age and sex) and the Boruta algorithm (based on random forest) in R. Mann-Whitney U test, false discovery rate and Spearman correlation were applied for univariate analyses (GraphPad Prism 9).

Results

A PCA based on the systemic proteomic profile (SProtP, n=275 detected proteins) of mastocytosis patients revealed 1 cluster of CM (n=15) and ISM (n=81) patients that separated away from AdvSM (n=12) patients. A separate PCA confirmed the ISM and AdvSM centroid distance (p<0.001). Feature selection with boruta confirmed 29 markers to be relevant for the outcome ISM (vs AdvSM), the majority found in low levels such as the Interleukin 1 Receptor Type 1 (IL-1RT1) (FDR-adjusted p value (q)<0.001), and inhibitory receptor Lymphocyte Activating 3 (LAG3) (q<0.01). Both ISM and AdvSM groups showed a distinct SProtP against PCV patients, respectively, in separate PCAs (p<0.001). For the outcome ISM (vs PCV), high levels of the mast cell mediator Tryptase α/β 1 (TPSAB1) (q<0.0001) and Mast Cell Immunoglobulin Like Receptor 1 (MILR1) (q<0.0001) and low levels of Fibroblast Growth Factor 2 (FGF2) (q<0.0001) were confirmed among the 27 relevant markers. For the outcome AdvSM (vs PCV), 25 relevant markers were found in high levels, including MILR1 (q<0.001), IL-1RT1 (q<0.0001), and Granulin Precursor (GRN) (q<0.0001).
Upper and/or lower GI manifestations were often reported within the mastocytosis group: 53.3% (n=8) CM, 73.1% (n=57) ISM, and 58.3% (n=7) AdvSM. ISM patients that reported GI manifestations (/GI+) showed higher levels of MILR1 (4.3 (3.9-5.0) vs 4.07 (3.4-4.3), p<0.01) and Transferrin Receptor protein 1 (TR) (4.9 (4.3-5.3) vs 4.36 (4.0-4.9), p<0.05) than patients without GI symptoms (GR-). In contrast, AdvSM/GI+ patients weakly tended to show higher NPX values than patients GI- manifestations (p>0.05). In addition, plasma TPSAB1 levels of ISM/GI+ patients correlated with MILR1 levels (r=0.45; 95%CI (0.2-0.6), p<0.001), while in patients with ISM/GI- TPSAB1 correlated moderately with FGF2 (r=0.6; 95%CI (0.2-0.8), p<0.01). No correlations were found between the top confirmed markers and TPSAB1 in AdvSM, regardless of the presence of GI symptoms.

Conclusion

Distinct systemic proteomic profiles, and specific plasma markers, of ISM and AdvSM patients support different disease mechanisms. While some of these markers might be associated with the presence of GI symptoms, further investigations are needed.

Clinical Case Summary

We describe a case of an 80-year-old woman with a history of bronchiectasis, nasal polyps, and chronic sinusitis who presented to the emergency department with diarrhea(>10 bowel movements/day),abdominal pain and estimated weight loss of 6 kg over one month. She was previously treated with antiparasitics without clinical improvement. Laboratory tests showed peripheral eosinophilia(10,400/mm3 eosinophils, 51.4% of total leukocytes). Viral serologies and autoimmune study were negative. Microbiological and parasitological analyses of stool samples were negative too. Immunoglobulin E levels were elevated. Abdominal computed tomography(CT) revealed thickening of the rectal ampulla and sigmoid colon. Upper gastrointestinal endoscopy did not show any abnormalities, but rectosigmoidoscopy revealed colorectal mucosa with millimetric whitish dots, some scattered erosions, and a 20 mm ulcer in the distal rectum that was biopsied. Histological evaluation showed inflammatory changes with predominance of eosinophilic polymorphonuclear cells(>50/field). Bone marrow study showed eosinophilic myeloid hyperplasia without blasts. No cytogenetic abnormalities were identified on chromosomal analysis. During hospitalization, she developed pruritic erythematous macules on the sacral region and inner thighs that gradually improved with topical steroids. Idiopathic hypereosinophilic syndrome with gastrointestinal involvement and possible cutaneous and pulmonar, was assumed. Prednisolone 40 mg/day was started with clinical and laboratory improvement, with complete resolution of peripheral eosinophilia. The diagnosis of idiopathic hypereosinophilic syndrome is a challenge because it is a diagnosis of exclusion and manifests in various ways depending on the affected system, with gastrointestinal involvement being possible, as in the case presented here. Recognition and early initiation of appropriate treatment can improve the survival and quality of life of these patients.

Introduction

Irritable bowel syndrome (IBS) is the most common disorder of gut-brain interaction (DGBI) and associated with other pain syndromes, lifetime stress, and psychological disorders. During the last years, associations have also been described between IBS and overweight and the metabolic syndrome. Low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) and a starch- and sucrose-reduced diet (SSRD) reduce IBS symptoms (1,2). However, concerns have been raised whether a diet may lead to malnutrition when adhered to for a longer time.

Aims & Methods

The aim of the study was to randomize IBS patients according to Rome IV with a total score of IBS-SSS > 175 to either SSRD or low FODMAP and measure nutritional status over time. 155 patients, 131 women (84.5%), age 42 (32-55) years, weight 69.2 (63.0-82.9) kg, BMI 25 (23-28) kg/m² were included. 77 received SSRD (5 dropouts) and 78 low FODMAP (6 dropouts) for 4 weeks, with a second follow-up at week 24. Rome IV, IBS-severity scoring system (IBS-SSS) and visual analog scale-IBS were completed at baseline, and after 4 and 24 weeks. Nutritional status, lipid profile, and glycosylated hemoglobin A1c (HbA1c) were analyzed in blood according to clinical routines at the laboratory. Differences were calculated by Wilxon Signed Ranks with values at week 4 and 24 in comparison with baseline. P<0.05 was considered statistically significant.

Results

There were no differences in baseline values between the groups. All gastrointestinal and extraintestinal symptoms were improved by both diets (p<0.001 in most variables). The weight reduction was most pronounced in SSRD. At week 4, folate was increased (p=0.003), and iron decreased (p=0.001), in the SSRD group, whereas vitamin D was increased in both groups (p=0.004 vs. p=0.017) and HbA1c was decreased (p=0.010 vs. p=0.009). The only negative nutritional measurement at week 24 was lower cobalamin levels in both groups (p=0.009 vs. p=0.002) and lower ferritin in the low FODMAP group (p=0.007). Cholesterol, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol were decreased throughout the study in the SSRD group, but only after 4 weeks in the low FODMAP group (Table).

Conclusion

Both SSRD and low FODMAP decrease gastrointestinal and extraintestinal symptoms. Although some nutritional analyses showed lower values after the intervention, other showed improved values. Metabolic risk factors such as weight, lipid values and HbA1c were improved by the diets, especially SSRD. Thus, dietary interventions in IBS do not only improve symptoms but also improve lipid and glycemic profiles without any major impact on nutritional status when the IBS patients are followed for 6 months. Reducing carbohydrate intake appears to positively impact bowel symptoms and metabolism in IBS patients, irrespective of the specific carbohydrates targeted by the corresponding diet. Future studies are warranted to identify the individual saccharides most likely to exert therapeutic effects, eventually in relation to their breakdown capacity in individual patients.

References

Mitchell H, Porter J, Gibson PR, Barrett J, Garg M. Review article: implementation of a diet low in FODMAPs for patients with irritable bowel syndrome-directions for future research. Aliment Pharmacol Ther. 2019 Jan;49(2):124-139.
Nilholm C, Roth B, Ohlsson B. A Dietary Intervention with Reduction of Starch and Sucrose Leads to Reduced Gastrointestinal and Extra-Intestinal Symptoms in IBS Patients. Nutrients. 2019 Jul 20;11(7):1662.