Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Selection Process
2.3. Data Extraction and Synthesis
3. Results
3.1. Quality Assessment
3.2. Lifestyle and Diet
3.2.1. Nutrition and Body Composition
3.2.2. Smoking
3.2.3. Sleep
3.3. Pharmacological Influences
3.4. Psychological Factors
3.4.1. Psychological Health
3.4.2. Quality of Life
3.5. COVID-19
3.5.1. Natural Infection
3.5.2. Vaccination
3.6. Environmental Factors
3.7. Multifactorial Assessments
3.7.1. Clinical Indices
3.7.2. Prediction Models
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
Abbreviations
BMI | Body Mass Index |
CAM | Complementary and Alternative Medicine |
CD | Crohn’s Disease |
CI | Confidence Interval |
COVID-19 | Coronavirus Disease 2019 |
COX | Cyclooxygenase |
DSI | Disease Severity Index |
ECCI | Endoscopic Clinical Correlation Index |
ECCO | European Crohn’s and Colitis Organization |
ESPEN | European Society for Clinical Nutrition and Metabolism |
HR | Hazard Ratio |
IBD | Inflammatory Bowel Disease |
MeSH | Medical Subject Headings |
MMAT | Mixed Methods Appraisal Tool |
NEO-FFI | NEO Five-Factor Inventory |
NSAID | Non-steroidal Anti-inflammatory Drug |
OR | Odds Ratio |
PHQ-8 | Patient Health Questionnaire-8 |
PSQI | Pittsburgh Sleep Quality Index |
QoL | Quality of Life |
RCT | Randomized Controlled Trial |
RR | Relative Risk |
SCCAI | Simple Clinical Colitis Activity Index |
SEO | Seo’s Activity Index |
SNAQ | Short Nutritional Assessment Questionnaire |
TNF | Tumor Necrosis Factor |
UC | Ulcerative Colitis |
UK | United Kingdom |
USA | United States of America |
VAT:SAT | Visceral Adipose Tissue–Subcutaneous Adipose Tissue |
Appendix A. Original Search Terms
Appendix B. Mixed Methods Appraisal Tool Quality Assessment
Study Title | S1. Are There Clear Research Questions? | S2. Do the Collected Data Allow Us to Address the Research Questions? | 2.1. Is Randomization Appropriately Performed? | 2.2. Are the Groups Comparable at Baseline? | 2.3. Are There Complete Outcome Data? | 2.4. Are Outcome Assessors Blinded to the Intervention Provided? | 2.5 Did the Participants Adhere to the Assigned Intervention? |
---|---|---|---|---|---|---|---|
A diet low in red and processed meat does not reduce rate of Crohn’s disease flares [22] | + | + | + | − | + | − | − |
A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity [27] | + | + | + | + | + | + | + |
Optimizing management of Crohn’s disease within a project management framework: results of a pilot study [57] | + | + | +/− | + | +/− | − | + |
Study | S1. Are There Clear Research Questions? | S2. Do the Collected Data Allow Us to Address the Research Questions? | 3.1. Are the Participants Representative of the Target Population? | 3.2. Are Measurements Appropriate Regarding Both the Outcome and Intervention (or Exposure)? | 3.3. Are There Complete Outcome Data? | 3.4. Are the Confounders Accounted for in the Design and Analysis? | 3.5. During the Study Period, is the Intervention Administered (or Exposure Occurred) as Intended? |
---|---|---|---|---|---|---|---|
Influence of diet on the course of inflammatory bowel disease [20] | + | + | − | + | + | +/− | + |
Dietary risk factors for inflammatory bowel disease in Shanghai: A case-control study [21] | + | + | + | + | + | + | + |
High dietary intake of specific fatty acids increases risk of flares in patients with ulcerative colitis in remission during treatment with aminosalicylates [23] | + | + | + | + | + | + | + |
Dietary and metabolomic determinants of relapse in ulcerative colitis patients: a pilot prospective cohort study [24] | + | + | − | + | + | + | + |
Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis [25] | + | + | − | + | + | + | + |
Avoidance of fiber is associated with greater risk of Crohn’s disease flare in a 6-month period [26] | + | + | + | + | + | − | + |
Pro-inflammatory diet is correlated with high veillonella rogosae, gut inflammation and clinical relapse of inflammatory bowel disease [28] | + | + | + | + | + | + | + |
Micronutrient status and prediction of disease outcome in adults with inflammatory bowel disease receiving biologic therapy [29] | + | + | + | + | + | + | + |
Risk of impaired nutritional status and flare occurrence in IBD outpatients [30] | + | + | + | + | + | − | + |
Older age is a risk factor for inadequate energy intake during acute, severe IBD and is associated with shorter time to relapse [31] | + | + | +/− | + | +/− | + | + |
Visceral adiposity independently predicts time to flare in inflammatory bowel disease but body mass index does not [32] | + | + | + | + | + | + | + |
Impact of obesity on disease activity and patient-reported outcomes measurement information system (PROMIS) in inflammatory bowel diseases [33] | + | + | + | +/− | + | + | + |
The impact of smoking and smoking cessation on disease outcomes in ulcerative colitis: a nationwide population-based study [34] | + | + | + | + | + | + | + |
Impact of smoking cessation on the clinical course of Crohn’s disease under current therapeutic algorithms: a multicenter prospective study [35] | + | + | + | + | + | + | + |
Poor sleep quality in Crohn’s disease is associated with disease activity and risk for hospitalization or surgery [37] | + | + | − | + | + | + | + |
Sleep disturbance and risk of active disease in patients with Crohn’s disease and ulcerative colitis [38] | + | + | + | + | + | + | + |
Use of cyclo-oxygenase inhibitors is not associated with clinical relapse in inflammatory bowel disease: a case-control study [39] | + | + | + | + | + | + | + |
Specific Antibiotics Increase the Risk of Flare-Ups in Patients with Inflammatory Bowel Disease: Results from a Danish Nationwide Population-Based Nested Case-Control Study [40] | + | + | + | + | + | + | + |
Factors contributing to flares of ulcerative colitis in North India-a case-control study [41] | + | + | + | + | + | + | + |
β-Blocker use is associated with a higher relapse risk of inflammatory bowel disease: a Dutch retrospective case–control study [42] | + | + | + | +/− | + | +/− | + |
Impact of Opioid Use on the Natural History of Inflammatory Bowel Disease: Prospective Longitudinal Follow-up Study [43] | + | + | + | + | + | + | + |
Hormone therapy for cancer is a risk factor for relapse of inflammatory bowel diseases [44] | + | + | + | + | + | + | + |
Effects of cancer treatment on inflammatory bowel disease remission and reactivation [45] | + | + | +/− | + | + | + | + |
Polypharmacy is a risk factor for disease flare in adult patients with ulcerative colitis: a retrospective cohort study [46] | + | + | +/− | + | + | + | + |
The personality traits activity, self-reproach, and negative affect jointly predict clinical recurrence, depressive symptoms, and low quality of life in inflammatory bowel disease patients [47] | + | + | + | + | + | + | + |
Because I’m happy–positive affect and its predictive value for future disease activity in patients with inflammatory bowel diseases: a retrospective cohort study [48] | + | + | + | + | + | + | + |
Depressive symptoms predict clinical recurrence of inflammatory bowel disease [49] | + | + | + | + | + | + | + |
Depression is associated with more aggressive inflammatory bowel disease [50] | + | + | + | + | + | + | + |
Characteristics and effect of anxiety and depression trajectories in inflammatory bowel disease [51] | + | + | + | + | + | + | + |
High perceived stress is associated with increased risk of ulcerative colitis clinical flares [52] | + | + | + | + | + | + | + |
Stress as a trigger for relapses in IBD: a case-crossover study [53] | + | + | +/− | + | + | + | + |
Is disease activity associated with social support and psychological distress in Crohn’s disease patients? Results of a cross-sectional study in a Chinese hospital population [54] | + | + | − | − | +/− | + | + |
Bi-directionality of brain–gut interactions in patients with inflammatory bowel disease [55] | + | + | + | + | + | + | + |
Constructing a prediction model of inflammatory bowel disease recurrence based on factors affecting the quality of life [56] | + | + | − | + | + | + | + |
Severe acute respiratory syndrome coronavirus 2 infection does not worsen the course of inflammatory bowel disease in the long term [58] | + | + | + | + | + | + | + |
Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease [59] | + | + | + | + | + | + | + |
SARS-CoV-2 vaccination in inflammatory bowel disease patients is not associated with flares: a retrospective single-centre Swiss study [61] | + | + | +/− | + | + | + | + |
Heat waves, incidence of infectious gastroenteritis, and relapse rates of inflammatory bowel disease: a retrospective controlled observational study [63] | + | + | + | + | + | + | + |
The impact of cold spells on the incidence of infectious gastroenteritis and relapse rates of inflammatory bowel disease: a retrospective controlled observational study [64] | + | + | +/− | +/− | + | + | +/− |
Seasonal variation in onset and relapse of IBD and a model to predict the frequency of onset, relapse, and severity of IBD based on artificial neural network [65] | + | + | +/− | + | − | − | + |
High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients [66] | + | + | + | + | + | + | + |
Clinical factors to predict flare-up in patients with inflammatory bowel disease during international air travel: A prospective study [67] | + | + | +/− | + | + | + | + |
Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic ‘mucosal healing’ and implication for management [68] | + | + | +/− | +/− | + | − | + |
Clinical characteristics and prognostic factors for Crohn’s disease relapses using natural language processing and machine learning: a pilot study [69] | + | + | + | + | +/− | +/− | + |
The disease severity index for inflammatory bowel disease is associated with psychological symptoms and quality of life, and predicts a more complicated disease course [70] | + | + | + | + | + | + | + |
Developing a novel risk-scoring system for predicting relapse in patients with ulcerative colitis: A prospective cohort study [71] | + | + | + | + | + | + | + |
Predictive parameters for the clinical course of Crohn’s disease: development of a simple and reliable risk model [72] | + | + | − | + | + | + | + |
Novel symptom clusters predict disease impact and healthcare utilisation in inflammatory bowel disease: Prospective longitudinal follow-up study [73] | + | + | + | + | + | + | + |
A risk score system to timely manage treatment in Crohn’s disease: a cohort study [74] | + | + | +/− | + | + | + | + |
Evaluating clinical, dietary, and psychological risk factors for relapse of ulcerative colitis in clinical, endoscopic, and histological remission [75] | + | + | − | + | + | + | + |
Young age and short duration of the disease are associated with more frequent relapses in inflammatory bowel disease patients [76] | + | + | + | + | +/− | − | + |
Factors affecting ulcerative colitis flare-ups: associations with smoking habits and other patient characteristics [77] | + | + | + | + | + | + | + |
Study | S1. Are There Clear Research Questions? | S2. Do the Collected Data Allow Us to Address the Research Questions? | 4.1. Is the Sampling Strategy Relevant to Address the Research Question? | 4.2. Is the Sample Representative of the Target Population? | 4.3. Are the Measurements Appropriate? | 4.4. Is the Risk of Non-response Bias Low? | 4.5. Is the Statistical Analysis Appropriate to Answer the Research Question? |
---|---|---|---|---|---|---|---|
Sleep disturbances in Japanese patients with inflammatory bowel disease and their impact on disease flare [36] | + | + | + | + | + | +/− | + |
Adverse events and serological responses after SARS-CoV-2 vaccination in individuals with inflammatory bowel disease [60] | + | + | + | + | + | − | + |
Is vaccination against COVID-19 associated with inflammatory bowel disease flare? self-controlled case series analysis using the UK CPRD [62] | + | + | + | + | + | + | + |
References
- Rubin, D.T.; Torres, J.; Dotan, I.; Xu, L.T.; Modesto, I.; Woolcott, J.C.; Gardiner, S.; Sands, B.E. An insight into patients’ perspectives of ulcerative colitis flares via analysis of online public forum posts. Inflamm. Bowel Dis. 2024, 30, 1748–1758. [Google Scholar]
- Al Khoury, A.; Balram, B.; Bessissow, T.; Afif, W.; Gonczi, L.; Abreu, M.; Lakatos, P.L. Patient perspectives and expectations in inflammatory bowel disease: A systematic review. Dig. Dis. Sci. 2022, 67, 1956–1974. [Google Scholar]
- Abraham, C.; Cho, J.H. Inflammatory bowel disease. New Engl. J. Med. 2009, 361, 2066–2078. [Google Scholar] [CrossRef] [PubMed]
- Singh, N.; Bernstein, C.N. Environmental risk factors for inflammatory bowel disease. United Eur. Gastroenterol. J. 2022, 10, 1047–1053. [Google Scholar]
- Ananthakrishnan, A.N. Epidemiology and risk factors for IBD. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 205–217. [Google Scholar] [PubMed]
- Martin, T.D.; Chan, S.S.; Hart, A.R. Environmental factors in the relapse and recurrence of inflammatory bowel disease: A review of the literature. Dig. Dis. Sci. 2015, 60, 1396–1405. [Google Scholar]
- Black, J.; Sweeney, L.; Yuan, Y.; Singh, H.; Norton, C.; Czuber-Dochan, W. Systematic review: The role of psychological stress in inflammatory bowel disease. Aliment. Pharmacol. Ther. 2022, 56, 1235–1249. [Google Scholar]
- De Sousa, J.F.M.; Paghdar, S.; Khan, T.M.; Patel, N.P.; Chandrasekaran, S.; Tsouklidis, N.; Paghdar, S.; Khan, T.M. Stress and inflammatory bowel disease: Clear mind, happy colon. Cureus 2022, 14, e25006. [Google Scholar]
- Peters, V.; Spooren, C.E.; Pierik, M.J.; Weersma, R.K.; van Dullemen, H.M.; Festen, E.A.; Visschedijk, M.C.; Masclee, A.A.; Hendrix, E.M.; Almeida, R.J.; et al. Dietary intake pattern is associated with occurrence of flares in IBD patients. J. Crohn’s Colitis 2021, 15, 1305–1315. [Google Scholar]
- Torres, J.; Bonovas, S.; Doherty, G.; Kucharzik, T.; Gisbert, J.P.; Raine, T.; Adamina, M.; Armuzzi, A.; Bachmann, O.; Bager, P.; et al. ECCO guidelines on therapeutics in Crohn’s disease: Medical treatment. J. Crohn’s Colitis 2020, 14, 4–22. [Google Scholar]
- Raine, T.; Bonovas, S.; Burisch, J.; Kucharzik, T.; Adamina, M.; Annese, V.; Bachmann, O.; Bettenworth, D.; Chaparro, M.; Czuber-Dochan, W.; et al. ECCO guidelines on therapeutics in ulcerative colitis: Medical treatment. J. Crohn’s Colitis 2022, 16, 2–17. [Google Scholar]
- Peyrin–Biroulet, L.; Bressenot, A.; Kampman, W. Histologic remission: The ultimate therapeutic goal in ulcerative colitis? Clin. Gastroenterol. Hepatol. 2014, 12, 929–934.e2. [Google Scholar]
- Sandborn, W.J.; Hanauer, S.; Van Assche, G.; Panés, J.; Wilson, S.; Petersson, J.; Panaccione, R. Treating beyond symptoms with a view to improving patient outcomes in inflammatory bowel diseases. J. Crohn’s Colitis 2014, 8, 927–935. [Google Scholar]
- Pariente, B.; Cosnes, J.; Danese, S.; Sandborn, W.J.; Lewin, M.; Fletcher, J.G.; Chowers, Y.; d’Haens, G.; Feagan, B.G.; Hibi, T. Development of the Crohn’s disease digestive damage score, the Lemann score. Inflamm. Bowel Dis. 2011, 17, 1415–1422. [Google Scholar] [PubMed]
- Peyrin-Biroulet, L.; Cieza, A.; Sandborn, W.J.; Coenen, M.; Chowers, Y.; Hibi, T.; Kostanjsek, N.; Stucki, G.; Colombel, J.-F.; the International Programme to Develop New Indexes for Crohn’s Disease (IPNIC) Group. Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health. Gut 2012, 61, 241–247. [Google Scholar]
- Torres, J.; Billioud, V.; Sachar, D.B.; Peyrin-Biroulet, L.; Colombel, J.F. Ulcerative colitis as a progressive disease: The forgotten evidence. Inflamm. Bowel Dis. 2012, 18, 1356–1363. [Google Scholar] [CrossRef] [PubMed]
- Khanna, R.; Bressler, B.; Levesque, B.G.; Zou, G.; Stitt, L.W.; Greenberg, G.R.; Panaccione, R.; Bitton, A.; Paré, P.; Vermeire, S.; et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): A cluster randomised controlled trial. Lancet 2015, 386, 1825–1834. [Google Scholar] [CrossRef]
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar]
- Hong, Q.N.; Fàbregues, S.; Bartlett, G.; Boardman, F.; Cargo, M.; Dagenais, P.; Gagnon, M.-P.; Griffiths, F.; Nicolau, B.; O’Cathain, A.; et al. The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers. Educ. Inf. 2018, 34, 285–291. [Google Scholar]
- Tasson, L.; Canova, C.; Vettorato, M.G.; Savarino, E.; Zanotti, R. Influence of diet on the course of inflammatory bowel disease. Dig. Dis. Sci. 2017, 62, 2087–2094. [Google Scholar]
- Mi, L.; Zhang, C.; Yu, X.-f.; Zou, J.; Yu, Y.; Bao, Z.-J. Dietary risk factors for inflammatory bowel disease in Shanghai: A case-control study. Asia Pac. J. Clin. Nutr. 2022, 31, 405–414. [Google Scholar] [PubMed]
- Albenberg, L.; Brensinger, C.M.; Wu, Q.; Gilroy, E.; Kappelman, M.D.; Sandler, R.S.; Lewis, J.D. A diet low in red and processed meat does not reduce rate of Crohn’s disease flares. Gastroenterology 2019, 157, 128–136.e5. [Google Scholar]
- Barnes, E.L.; Nestor, M.; Onyewadume, L.; de Silva, P.S.; Korzenik, J.R.; Aguilar, H.; Bailen, L.; Berman, A.; Bhaskar, S.K.; Brown, M.; et al. High dietary intake of specific fatty acids increases risk of flares in patients with ulcerative colitis in remission during treatment with aminosalicylates. Clin. Gastroenterol. Hepatol. 2017, 15, 1390–1396.e1. [Google Scholar] [PubMed]
- Keshteli, A.H.; van den Brand, F.F.; Madsen, K.L.; Mandal, R.; Valcheva, R.; Kroeker, K.I.; Han, B.; Bell, R.C.; Cole, J.; Hoevers, T.; et al. Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study. World J. Gastroenterol. 2017, 23, 3890–3899. [Google Scholar]
- Fritsch, J.; Garces, L.; Quintero, M.A.; Pignac-Kobinger, J.; Santander, A.M.; Fernández, I.; Ban, Y.J.; Kwon, D.; Phillips, M.C.; Knight, K.; et al. Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Clin. Gastroenterol. Hepatol. 2021, 19, 1189–1199.e30. [Google Scholar] [CrossRef]
- Brotherton, C.S.; Martin, C.A.; Long, M.D.; Kappelman, M.D.; Sandler, R.S. Avoidance of fiber is associated with greater risk of Crohn’s disease flare in a 6-month period. Clin. Gastroenterol. Hepatol. 2016, 14, 1130–1136. [Google Scholar] [CrossRef]
- Bhattacharyya, S.; Shumard, T.; Xie, H.; Dodda, A.; Varady, K.A.; Feferman, L.; Halline, A.G.; Goldstein, J.L.; Hanauer, S.B.; Tobacman, J.K. A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity. Nutr. Healthy Aging 2017, 4, 181–192. [Google Scholar] [CrossRef] [PubMed]
- Rocha, I.M.G.d.; Torrinhas, R.; Fonseca, D.; Lyra, C.d.O.; de Sousa Alves Neri, J.L.; Balmant, B.D.; Callado, L.; Charlton, K.; Queiroz, N.; Waitzberg, D.L. Pro-inflammatory diet is correlated with high veillonella rogosae, gut inflammation and clinical relapse of inflammatory bowel disease. Nutrients 2023, 15, 4148. [Google Scholar] [CrossRef]
- Brownson, E.; Saunders, J.; Jatkowska, A.; White, B.; Gerasimidis, K.; Seenan, J.P.; Macdonald, J. Micronutrient status and prediction of disease outcome in adults with inflammatory bowel disease receiving biologic therapy. Inflamm. Bowel Dis. 2024, 30, 1233–1240. [Google Scholar] [CrossRef]
- Spooren, C.E.; Wintjens, D.S.; de Jong, M.J.; van der Meulen-de, A.E.; Romberg-Camps, M.J.; Becx, M.C.; Maljaars, J.P.; van Bodegraven, A.A.; Mahmmod, N.; Markus, T.; et al. Risk of impaired nutritional status and flare occurrence in IBD outpatients. Dig. Liver Dis. 2019, 51, 1265–1269. [Google Scholar]
- Kulmala, K.A.; Björk, J.; Andersson, S.; Backman, A.-S.; Eberhardson, M.; Bresso, F.; Hedin, C.R. Older age is a risk factor for inadequate energy intake during acute, severe IBD and is associated with shorter time to relapse. Scand. J. Gastroenterol. 2020, 55, 1185–1192. [Google Scholar] [CrossRef] [PubMed]
- Sehgal, P.; Su, S.; Zech, J.; Nobel, Y.; Luk, L.; Economou, I.; Shen, B.; Lewis, J.D.; Freedberg, D.E. Visceral adiposity independently predicts time to flare in inflammatory bowel disease but body mass index does not. Inflamm. Bowel Dis. 2024, 30, 594–601. [Google Scholar] [CrossRef]
- Jain, A.; Nguyen, N.H.; Proudfoot, J.A.; Martin, C.F.; Sandborn, W.J.; Kappelman, M.D.; Long, M.D.; Singh, S. Impact of obesity on disease activity and patient-reported outcomes measurement information system (PROMIS) in inflammatory bowel diseases. Off. J. Am. Coll. Gastroenterol. 2019, 114, 630–639. [Google Scholar]
- Blackwell, J.; Saxena, S.; Alexakis, C.; Bottle, A.; Cecil, E.; Majeed, A.; Pollok, R.C. The impact of smoking and smoking cessation on disease outcomes in ulcerative colitis: A nationwide population-based study. Aliment. Pharmacol. Ther. 2019, 50, 556–567. [Google Scholar] [CrossRef]
- Nunes, T.; Etchevers, M.J.; García-Sánchez, V.; Ginard, D.; Martí, E.; Barreiro-de Acosta, M.; Gomollón, F.; Arroyo, M.; Bastida, G.; Gonzalez, B.; et al. Impact of smoking cessation on the clinical course of Crohn’s disease under current therapeutic algorithms: A multicenter prospective study. Off. J. Am. Coll. Gastroenterol. 2016, 111, 411–419. [Google Scholar]
- Uemura, R.; Fujiwara, Y.; Iwakura, N.; Shiba, M.; Watanabe, K.; Kamata, N.; Yamagami, H.; Tanigawa, T.; Watanabe, T.; Tominaga, K.; et al. Sleep disturbances in Japanese patients with inflammatory bowel disease and their impact on disease flare. SpringerPlus 2016, 5, 1792. [Google Scholar]
- Sofia, M.A.; Lipowska, A.M.; Zmeter, N.; Perez, E.; Kavitt, R.; Rubin, D.T. Poor sleep quality in Crohn’s disease is associated with disease activity and risk for hospitalization or surgery. Inflamm. Bowel Dis. 2020, 26, 1251–1259. [Google Scholar] [CrossRef]
- Ananthakrishnan, A.N.; Long, M.D.; Martin, C.F.; Sandler, R.S.; Kappelman, M.D. Sleep disturbance and risk of active disease in patients with Crohn’s disease and ulcerative colitis. Clin. Gastroenterol. Hepatol. 2013, 11, 965–971. [Google Scholar]
- Hensley, A.; Beales, I.L. Use of cyclo-oxygenase inhibitors is not associated with clinical relapse in inflammatory bowel disease: A case-control study. Pharmaceuticals 2015, 8, 512–524. [Google Scholar] [CrossRef]
- Lo, B.; Biederman, L.; Rogler, G.; Dora, B.; Kreienbühl, A.; Vind, I.; Bendtsen, F.; Burisch, J. Specific Antibiotics Increase the Risk of Flare-Ups in Patients with Inflammatory Bowel Disease: Results from a Danish Nationwide Population-Based Nested Case-Control Study. J. Crohn’s Colitis 2024, 18, 1232–1240. [Google Scholar]
- Rana, V.S.; Mahajan, G.; Patil, A.N.; Singh, A.K.; Jearth, V.; Sekar, A.; Singh, H.; Saroch, A.; Dutta, U.; Sharma, V. Factors contributing to flares of ulcerative colitis in North India-a case-control study. BMC Gastroenterol. 2023, 23, 336. [Google Scholar]
- Willemze, R.A.; Bakker, T.; Pippias, M.; Ponsioen, C.Y.; de Jonge, W.J. β-Blocker use is associated with a higher relapse risk of inflammatory bowel disease: A Dutch retrospective case–control study. Eur. J. Gastroenterol. Hepatol. 2018, 30, 161–166. [Google Scholar]
- Riggott, C.; Fairbrass, K.M.; Selinger, C.P.; Gracie, D.J.; Ford, A.C. Impact of Opioid Use on the Natural History of Inflammatory Bowel Disease: Prospective Longitudinal Follow-up Study. Inflamm. Bowel Dis. 2024, 30, 1724–1731. [Google Scholar] [PubMed]
- Axelrad, J.E.; Bazarbashi, A.; Zhou, J.; Castañeda, D.; Gujral, A.; Sperling, D.; Glass, J.; Agrawal, M.; Hong, S.; Lawlor, G.; et al. Hormone therapy for cancer is a risk factor for relapse of inflammatory bowel diseases. Clin. Gastroenterol. Hepatol. 2020, 18, 872–880.e1. [Google Scholar] [PubMed]
- Axelrad, J.E.; Fowler, S.A.; Friedman, S.; Ananthakrishnan, A.N.; Yajnik, V. Effects of cancer treatment on inflammatory bowel disease remission and reactivation. Clin. Gastroenterol. Hepatol. 2012, 10, 1021–1027.e1. [Google Scholar]
- Wang, J.; Nakamura, T.I.; Tuskey, A.G.; Behm, B.W. Polypharmacy is a risk factor for disease flare in adult patients with ulcerative colitis: A retrospective cohort study. Intest. Res. 2019, 17, 496–503. [Google Scholar]
- Jordi, S.B.U.; Lang, B.M.; Wyss, J.; Auschra, B.; Yilmaz, B.; Krupka, N.; Greuter, T.; Schreiner, P.; Biedermann, L.; Preisig, M.; et al. The personality traits activity, self-reproach, and negative affect jointly predict clinical recurrence, depressive symptoms, and low quality of life in inflammatory bowel disease patients. J. Gastroenterol. 2022, 57, 848–866. [Google Scholar]
- Lang, B.M.; Ledergerber, M.; Jordi, S.B.U.; Krupka, N.; Biedermann, L.; Schreiner, P.; Juillerat, P.; Wyss, J.; Vavricka, S.R.; Zeitz, J.; et al. Because I’m happy–positive affect and its predictive value for future disease activity in patients with inflammatory bowel diseases: A retrospective cohort study. Ther. Adv. Gastroenterol. 2023, 16, 17562848231179335. [Google Scholar]
- Jordi, S.B.U.; Lang, B.M.; Auschra, B.; von Känel, R.; Biedermann, L.; Greuter, T.; Schreiner, P.; Rogler, G.; Krupka, N.; Sulz, M.C.; et al. Depressive symptoms predict clinical recurrence of inflammatory bowel disease. Inflamm. Bowel Dis. 2022, 28, 560–571. [Google Scholar]
- Kochar, B.; Barnes, E.L.; Long, M.D.; Cushing, K.C.; Galanko, J.; Martin, C.F.; Raffals, L.E.; Sandler, R.S. Depression is associated with more aggressive inflammatory bowel disease. Off. J. Am. Coll. Gastroenterol. 2018, 113, 80–85. [Google Scholar]
- Fairbrass, K.M.; Guthrie, E.A.; Black, C.J.; Selinger, C.P.; Gracie, D.J.; Ford, A.C. Characteristics and effect of anxiety and depression trajectories in inflammatory bowel disease. Off. J. Am. Coll. Gastroenterol. 2023, 118, 304–316. [Google Scholar] [CrossRef] [PubMed]
- Sauk, J.S.; Ryu, H.J.; Labus, J.S.; Khandadash, A.; Ahdoot, A.I.; Lagishetty, V.; Katzka, W.; Wang, H.; Naliboff, B.; Jacobs, J.P.; et al. High perceived stress is associated with increased risk of ulcerative colitis clinical flares. Clin. Gastroenterol. Hepatol. 2023, 21, 741–749.e3. [Google Scholar] [CrossRef] [PubMed]
- Jaghult, S.; Saboonchi, F.; Moller, J.; Johansson, U.-B.; Wredling, R.; Kapraali, M. Stress as a trigger for relapses in IBD: A case-crossover study. Gastroenterol. Res. 2013, 6, 10–16. [Google Scholar] [CrossRef] [PubMed]
- Huang, M.; Tu, L.; Wu, L.; Zou, Y.; Li, X.; Yue, X.; Huang, C.; Lei, P.; Li, Q.; Han, P.; et al. Is disease activity associated with social support and psychological distress in Crohn’s disease patients? Results of a cross-sectional study in a Chinese hospital population. BMJ Open 2023, 13, e076219. [Google Scholar] [CrossRef]
- Gracie, D.J.; Guthrie, E.A.; Hamlin, P.J.; Ford, A.C. Bi-directionality of brain–gut interactions in patients with inflammatory bowel disease. Gastroenterology 2018, 154, 1635–1646.e3. [Google Scholar] [CrossRef]
- Li, M.; Tao, Y.; Sun, Y.; Wu, J.; Zhang, F.; Wen, Y.; Gong, M.; Yan, J.; Liang, H.; Bai, X.; et al. Constructing a prediction model of inflammatory bowel disease recurrence based on factors affecting the quality of life. Front. Med. 2023, 10, 1041505. [Google Scholar] [CrossRef]
- Keefer, L.; Doerfler, B.; Artz, C. Optimizing management of Crohn’s disease within a project management framework: Results of a pilot study. Inflamm. Bowel Dis. 2012, 18, 254–260. [Google Scholar] [CrossRef]
- Neri, B.; D’Agostini, G.; Salvatori, S.; Mossa, M.; Bettin, F.; Mancone, R.; Marafini, I.; Lolli, E.; Calabrese, E.; Monteleone, G.; et al. Severe acute respiratory syndrome coronavirus 2 infection does not worsen the course of inflammatory bowel disease in the long term. Eur. J. Gastroenterol. Hepatol. 2023, 35, 948–954. [Google Scholar] [CrossRef]
- Wetwittayakhlang, P.; Albader, F.; Golovics, P.A.; Hahn, G.D.; Bessissow, T.; Bitton, A.; Afif, W.; Wild, G.; Lakatos, P.L. Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease. Can. J. Gastroenterol. Hepatol. 2021, 2021, 7591141. [Google Scholar] [CrossRef]
- Markovinović, A.; Quan, J.; Herauf, M.; Hracs, L.; Windsor, J.W.; Sharifi, N.; Coward, S.; Caplan, L.; Gorospe, J.; Ernest-Suarez, K.; et al. Adverse events and serological responses after SARS-CoV-2 vaccination in individuals with inflammatory bowel disease. Off. J. Am. Coll. Gastroenterol. 2023, 118, 1693–1697. [Google Scholar] [CrossRef]
- Rossier, L.N.; Décosterd, N.P.; Matter, C.B.; Staudenmann, D.A.; Moser, A.; Egger, B.; Seibold, F.W. SARS-CoV-2 vaccination in inflammatory bowel disease patients is not associated with flares: A retrospective single-centre Swiss study. Ann. Med. 2024, 56, 2295979. [Google Scholar] [CrossRef]
- Card, T.R.; Nakafero, G.; Grainge, M.J.; Mallen, C.D.; Van-Tam, J.S.N.; Williams, H.C.; Abhishek, A. Is vaccination against COVID-19 associated with inflammatory bowel disease flare? self-controlled case series analysis using the UK CPRD. Off. J. Am. Coll. Gastroenterol. 2023, 118, 1388–1394. [Google Scholar] [CrossRef] [PubMed]
- Manser, C.N.; Paul, M.; Rogler, G.; Held, L.; Frei, T. Heat waves, incidence of infectious gastroenteritis, and relapse rates of inflammatory bowel disease: A retrospective controlled observational study. Off. J. Am. Coll. Gastroenterol. 2013, 108, 1480–1485. [Google Scholar] [CrossRef]
- Manser, C.N.; Kraus, A.; Frei, T.; Rogler, G.; Held, L. The impact of cold spells on the incidence of infectious gastroenteritis and relapse rates of inflammatory bowel disease: A retrospective controlled observational study. Inflamm. Intest. Dis. 2017, 2, 124–130. [Google Scholar] [CrossRef] [PubMed]
- Peng, J.C.; Ran, Z.H.; Shen, J. Seasonal variation in onset and relapse of IBD and a model to predict the frequency of onset, relapse, and severity of IBD based on artificial neural network. Int. J. Color. Dis. 2015, 30, 1267–1273. [Google Scholar] [CrossRef]
- Vavricka, S.R.; Rogler, G.; Maetzler, S.; Misselwitz, B.; Safroneeva, E.; Frei, P.; Manser, C.N.; Biedermann, L.; Fried, M.; Higgins, P.; et al. High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients. J. Crohn’s Colitis 2014, 8, 191–199. [Google Scholar] [CrossRef] [PubMed]
- Park, J.; Yoon, H.; Shin, C.M.; Park, Y.S.; Kim, N.; Lee, D.H. Clinical factors to predict flare-up in patients with inflammatory bowel disease during international air travel: A prospective study. PLoS ONE 2022, 17, e0262571. [Google Scholar] [CrossRef]
- Pagnini, C.; Menasci, F.; Festa, S.; Rizzatti, G.; Corleto, V.D.; Delle Fave, M.; D’Ambra, G.; Di Giulio, E.; Delle Fave, G. Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic’mucosal healing’and implication for management. Eur. Rev. Med. Pharmacol. Sci. 2015, 19, 3674–3681. [Google Scholar]
- Gomollón, F.; Gisbert, J.P.; Guerra, I.; Plaza, R.; Villarroya, R.P.; Almazán, L.M.; Martín, M.C.L.; Antonaya, M.D.; Mendoza, M.I.V.; Aparicio, J.; et al. Clinical characteristics and prognostic factors for Crohn’s disease relapses using natural language processing and machine learning: A pilot study. Eur. J. Gastroenterol. Hepatol. 2022, 34, 389–397. [Google Scholar] [CrossRef]
- Swaminathan, A.; Fan, D.; Borichevsky, G.M.; Mules, T.C.; Hirschfeld, E.; Frampton, C.M.; Day, A.S.; Siegel, C.A.; Gearry, R.B. The disease severity index for inflammatory bowel disease is associated with psychological symptoms and quality of life, and predicts a more complicated disease course. Aliment. Pharmacol. Ther. 2022, 56, 664–674. [Google Scholar] [CrossRef]
- Hosseini, S.V.; Safarpour, A.R.; Taghavi, S.A. Developing a novel risk-scoring system for predicting relapse in patients with ulcerative colitis: A prospective cohort study. Pak. J. Med. Sci. 2015, 31, 1511–1516. [Google Scholar] [PubMed]
- Stallmach, A.; Bokemeyer, B.; Helwig, U.; Lügering, A.; Teich, N.; Fischer, I.; Rath, S.; Lang, D.; Schmidt, C.; EPIC Study Group. Predictive parameters for the clinical course of Crohn’s disease: Development of a simple and reliable risk model. Int. J. Color. Dis. 2019, 34, 1653–1660. [Google Scholar]
- Riggott, C.; Fairbrass, K.M.; Black, C.J.; Gracie, D.J.; Ford, A.C. Novel symptom clusters predict disease impact and healthcare utilisation in inflammatory bowel disease: Prospective longitudinal follow-up study. Aliment. Pharmacol. Ther. 2023, 58, 1163–1174. [Google Scholar] [CrossRef] [PubMed]
- Pallotta, N.; Vincoli, G.; Pezzotti, P.; Giovannone, M.; Gigliozzi, A.; Badiali, D.; Vernia, P.; Corazziari, E.S. A risk score system to timely manage treatment in Crohn’s disease: A cohort study. BMC Gastroenterol. 2018, 18, 164. [Google Scholar]
- Dhingra, R.; Kedia, S.; Mouli, V.P.; Garg, S.K.; Singh, N.; Bopanna, S.; Singla, V.; Choudhury, B.N.; Verma, P.; Tiwari, V.; et al. Evaluating clinical, dietary, and psychological risk factors for relapse of ulcerative colitis in clinical, endoscopic, and histological remission. J. Gastroenterol. Hepatol. 2017, 32, 1698–1705. [Google Scholar]
- Nakov, R.; Nakov, V. Young age and short duration of the disease are associated with more frequent relapses in inflammatory bowel disease patients. Med. Pharm. Rep. 2021, 94, 43–47. [Google Scholar]
- Malibary, N.H.; Ezzat, M.A.; Mogharbel, A.M.; Kouzaba, K.A.; Alkadi, A.A.; Malki, U.H.; Gharib, S.M.; Altowairqi, F.M.; Saadah, O.I.; Mosli, M.H. Factors affecting ulcerative colitis flare-ups: Associations with smoking habits and other patient characteristics. Cureus 2021, 13, e19834. [Google Scholar]
- Bischoff, S.C.; Escher, J.; Hébuterne, X.; Kłęk, S.; Krznaric, Z.; Schneider, S.; Shamir, R.; Stardelova, K.; Wierdsma, N.; Wiskin, A.E.; et al. ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease. Clin. Nutr. 2020, 39, 632–653. [Google Scholar] [CrossRef]
- Laing, B.B.; Lim, A.G.; Ferguson, L.R. A Personalised Dietary Approach—A Way Forward to Manage Nutrient Deficiency, Effects of the Western Diet, and Food Intolerances in Inflammatory Bowel Disease. Nutrients 2019, 11, 1532. [Google Scholar] [CrossRef]
- Guerreiro, C.S.; Ferreira, P.; Tavares, L.; Santos, P.M.; Neves, M.; Brito, M.; Cravo, M. Fatty acids, IL6, and TNFα polymorphisms: An example of nutrigenetics in Crohn’s disease. Off. J. Am. Coll. Gastroenterol. 2009, 104, 2241–2249. [Google Scholar] [CrossRef]
- Armstrong, H.K.; Bording-Jorgensen, M.; Santer, D.M.; Zhang, Z.; Valcheva, R.; Rieger, A.M.; Kim, J.S.-H.; Dijk, S.I.; Mahmood, R.; Ogungbola, O.; et al. Unfermented β-fructan fibers fuel inflammation in select inflammatory bowel disease patients. Gastroenterology 2023, 164, 228–240. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, M.; Iwao, Y.; Sasaki, S.; Okamoto, S.; Ogata, H.; Hibi, T.; Kazuma, K. Moderate dietary temperance effectively prevents relapse of Crohn disease: A prospective study of patients in remission. Gastroenterol. Nurs. 2007, 30, 202–210. [Google Scholar] [PubMed]
- World Health Organization. Regional Office for the Eastern Mediterranean. Healthy Diet; World Health Organization. Regional Office for the Eastern Mediterranean: Geneva, Switzerland, 2019.
- Lichtenstein, G.R.; Loftus, E.V.; Isaacs, K.L.; Regueiro, M.D.; Gerson, L.B.; Sands, B.E. ACG clinical guideline: Management of Crohn’s disease in adults. Off. J. Am. Coll. Gastroenterol. 2018, 113, 481–517. [Google Scholar]
- To, N.; Ford, A.C.; Gracie, D.J. Systematic review with meta-analysis: The effect of tobacco smoking on the natural history of ulcerative colitis. Aliment. Pharmacol. Ther. 2016, 44, 117–126. [Google Scholar] [PubMed]
- Lamers, C.R.; De Roos, N.M.; Heerink, H.H.; Van de Worp-Kalter, L.A.; Witteman, B.J. Lower impact of disease on daily life and less fatigue in patients with inflammatory bowel disease following a lifestyle intervention. Inflamm. Bowel Dis. 2022, 28, 1791–1799. [Google Scholar]
- Singh, S.; Graff, L.A.; Bernstein, C.N. Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Off. J. Am. Coll. Gastroenterol. 2009, 104, 1298–1313. [Google Scholar]
- Govani, S.M.; Wiitala, W.L.; Stidham, R.W.; Saini, S.D.; Hou, J.K.; Feagins, L.A.; Sussman, J.B.; Higgins, P.D.; Waljee, A.K. Age disparities in the use of steroid-sparing therapy for inflammatory bowel disease. Inflamm. Bowel Dis. 2016, 22, 1923–1928. [Google Scholar] [CrossRef]
- Asscher, V.E.; Waars, S.N.; van der Meulen-de, A.E.; Stuyt, R.J.; Baven-Pronk, A.M.C.; van Der Marel, S.; Jacobs, R.J.; Haans, J.J.; Meijer, L.J.; Klijnsma-Slagboom, J.D.; et al. Deficits in geriatric assessment associate with disease activity and burden in older patients with inflammatory bowel disease. Clin. Gastroenterol. Hepatol. 2022, 20, e1006–e1021. [Google Scholar]
- European Crohn’s and Colitis Organisation. Phychosocial Issues. Interventions 2024; Overview of Psychosocial Issues Related to Crohn’s Disease & Ulcerative Colitis. Available online: https://www.e-guide.ecco-ibd.eu/interventions-investigational/psychosocial-issues (accessed on 7 January 2025).
- Olivera, P.; Danese, S.; Jay, N.; Natoli, G.; Peyrin-Biroulet, L. Big data in IBD: A look into the future. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 312–321. [Google Scholar] [CrossRef]
- Borg-Bartolo, S.P.; Boyapati, R.K.; Satsangi, J.; Kalla, R. Precision medicine in inflammatory bowel disease: Concept, progress and challenges. F1000Research 2020, 9, 54. [Google Scholar]
- La Rosa, G.R.M.; Lorenzo-Pouso, A.I.; Caponio, V.C.A.; Puci, M.V. Apical periodontitis in inflammatory bowel disease: A meta-analysis at patient and tooth level. Front. Dent. Med. 2025, 6, 1553914. [Google Scholar]
- Wang, Q.; Chen, S.; Zhou, J.; Zhao, L. Bidirectional associations between periodontitis and inflammatory bowel disease: A systematic review of longitudinal studies with meta-analysis and trial sequential analysis. J. Periodontal Res. 2024, 59, 1083–1094. [Google Scholar] [PubMed]
- Kumar, A.; Teslova, T.; Taub, E.; Miller, J.D.; Lukin, D.J. Comorbid diabetes in inflammatory bowel disease predicts adverse disease-related outcomes and infectious complications. Dig. Dis. Sci. 2021, 66, 2005–2013. [Google Scholar] [CrossRef] [PubMed]
Author | Study Design | Population | Intervention | Outcome Measure | Key Results |
---|---|---|---|---|---|
Nutrition | |||||
[20] | Cross-sectional Study | Diagnosis: IBD n = 103 (Italy) | N.A. | Disease activity (FCP > 150) | ↓ Consumption of legumes and potatoes linked to lower relapse risk ↑ Meat consumption linked to higher relapse risk |
[21] | Case–Control Study | Diagnosis: IBD n = 50 (Shanghai) | N.A. | Association between dietary components and recurrent IBD | ↑ Consumption of chilis, fish, milk, nuts, eggs, and fruit linked to higher relapse risk |
[22] | Randomized Controlled Trial | Diagnosis: CD n= 213 | Low-meat vs. high-meat diet | Time to relapse (sCDAI score or treatment changes) | ↑ Pro-inflammatory diet associated with higher gut inflammation and relapse risk |
[23] | Prospective Observational Study | Diagnosis: UC n = 412 (USA) | N.A. | UC relapse within 12 months | ↑ Higher intake of fatty acids associated with increased risk of UC relapse and no significant association with processed meats or alcohol |
[24] | Prospective Cohort Study (pilot) | Diagnosis: UC n = 20 (USA) | N.A. | Clinical UC relapse (partial Mayo score ≥ 3) | ↑ Normal weight increases the risk of relapse vs. overweight/obese ↓ Poultry intake linked to lower risk of relapse |
[25] | Parallel-group, Cross-over Study | Diagnosis: UC n = 17 (USA) | Low-fat diet (LFD) vs. improved standard American diet | Clinical disease activity, inflammatory markers, and microbiome | ↑ Low-fat diet reduced inflammation and dysbiosis |
[26] | Prospective Cohort | Diagnosis: IBD n = 1619 (USA) | N.A. | Disease flare (CDAI or SCCAI) | ↓ High fiber intake associated with reduced CD relapses ~ No link with UC relapses |
[27] | Randomized Controlled Trial | Diagnosis: UC n = 12 (USA) | Carrageenan vs. placebo | UC relapse (SCCAI ≥ 2, treatment escalation) | ↑ Carrageenan may aggravate UC and shorten the time to relapse |
[28] | Prospective Cohort | Diagnosis: IBD n= 40 (Brazil) | N.A. | Biochemical inflammation (FCP, CRP, and fecal zonulin) | ↑ Pro-inflammatory diet associated with higher gut inflammation and relapse risk |
[29] | Retrospective Cohort | Diagnosis: IBD n= 216 (UK) | N.A. | Adverse clinical outcomes (e.g., surgery and steroids) | ↑ Zinc and selenium deficiencies predicted adverse outcomes in CD and UC |
[30] | Longitudinal Observational Study | Diagnosis: IBD n = 417 (The Netherlands) | N.A. | Disease flares (symptom increase combined with biomarkers or imaging) | ↑ Nutritional deficiencies increased the likelihood of disease relapses ↑ Low BMI increased the likelihood of disease relapses |
[31] | Retrospective Cohort Study | Diagnosis: IBD n = 91 (Sweden) | N.A. | Steroid use, readmissions, and highest calprotectin | ↓ Low energy intake associated with shorter time to steroid use and relapse |
[32] | Retrospective Cohort Study | Diagnosis: IBD n = 200 (USA) | N.A. | Time to flare (treatment escalation) | ↑ High SAT associated with shorter time to relapse |
[33] | Cohort Study | Diagnosis: IBD (USA) | N.A. | Disease activity (sCDAI, SCCAI) | ↑ Obesity linked to worsening disease activity |
Smoking | |||||
[34] | Cohort Study | Diagnosis: UC n = 6754 (UK) | N.A. | Corticosteroid use, thiopurine use, hospitalization, and colectomy | ~ Smoking and non-smoking patients had similar outcomes for relapses and treatments. Smoking cessation did not worsen disease |
[35] | Multicenter Prospective Cohort Study | Diagnosis: CD n = 573 (Spain) | N.A. | Clinical relapse, time to relapse, surgery, hospitalization, and medication use | ↑ Smokers had higher relapse rates |
Sleep | |||||
[36] | Cross-sectional Study | Diagnosis: UC or CD n= 136 (Japan) | N.A. | IBD flare ((1) more than a 2-point increase in HBI or pMayo, (2) therapy initiation, escalation, or switch, (4) surgery, or (5) hospitalization) | ↑ Sleep disturbances increase relapse risk |
[37] | Prospective Cohort Study | Diagnosis: CD (tertiary care) n= 92 (Controls: n = 82) (USA) | N.A. | Hospitalization or surgery | ↑ Lower sleep quality scores correlate with increased incidence of active disease |
[38] | Prospective Cohort Study | Diagnosis: IBDn = 3173 (USA) | N.A. | Clinical disease activity (CDAI or SCCAI scores) | ↑ Lower sleep quality associated with increased risk for relapse in CD ↔ No association found in UC patients |
Pharmacological influences | |||||
[39] | Case–Control Study | Diagnosis: IBD n = 158 (UK) | N.A. | Primary outcome: Association between COX inhibitor use and IBD relapse. Separate analyses for UC and CD. | ↑ COX-2 inhibitor use associated with reduced relapse in UC but no association for CD |
[40] | Nested Case–Control Study | Diagnosis: IBD n = 15,636 (Denmark) | N.A. | IBD flares defined as IBD-related hospitalizations | ↑ Antibiotics (quinolones and antimycotics) associated with increased relapse risk |
[41] | Prospective Case–Control Study | Diagnosis: UC n = 84 (India) | N.A. | Flares: SCCAI scores > 5 and evidence of endoscopic activity. Remission: SCCAI scores < 4 and normal fecal calprotectin. | ↑ Antibiotic use associated with increased relapse risk. ↑ CAM use associated with increased relapse risk |
[42] | Retrospective Case–Control Study | Diagnosis: IBD n = 470 (European population) | N.A. | IBD relapse risk identified through IBD medication prescriptions as a proxy relapse rate reported per 1000 person-years HR | ↑ β-blocker use linked to higher relapse risk |
[43] | Prospective Longitudinal Follow-up Study | Diagnosis: IBD n = 1029 (116 Opioid users) (UK) | N.A. | Occurrence of flare, prescription of corticosteroids, treatment escalation, hospitalization, or intestinal resection during 12 months of follow-up | ↑ Opioid use linked to psychological comorbidity and higher risk of intestinal resection |
[44] | Retrospective Cohort Study | Diagnosis: IBD n = 447 (USA) | N.A. | Clinical or endoscopic + histological disease activity after cancer treatment | ↑ Hormone therapy linked to increased risk of relapse |
[45] | Retrospective Cohort Study | Diagnosis: IBD n = 84 (USA) | N.A. | Clinical or endoscopic + histological disease activity after cancer treatment | ↑ Hormone therapy, alone or in combination with cytotoxic chemotherapy, increases the risk of IBD reactivation |
[46] | Retrospective Cohort Study | Diagnosis: UC n = 265 (USA) | N.A. | Disease flare (defined by attending gastroenterologist’s documentation and changes in treatment), therapy escalation, UC-related hospitalization, and surgery within 5 years | ↑ Polypharmacy linked to increased risk of relapse |
Psychological health | |||||
[47] | Prospective Cohort Study | Diagnosis: IBD n = 1154 (Switzerland) | Disease flare (clinical disease activity (CDAI or MTWAI), physician-reported flare, new fistula, stenosis, surgery, systemic steroids, therapy start, escalation or switch, new complication, or new EIM | ↑ Higher activity, self-reproach, and negative emotions linked to increased disease activity | |
[48] | Retrospective Cohort Study | Diagnosis: IBD n= 702 (Switzerland) | N.A. | Disease flare (clinical disease activity (CDAI or MTWAI), physician-reported flare, new fistula, stenosis, surgery, systemic steroids, therapy start, escalation or switch, new complication, or new EIM | ↑ High positive affect scores (Marburg questionnaire >3.5) associated with longer flare-free survival periods |
[49] | Prospective Cohort Study | Diagnosis: IBD n = 1154 (Switzerland) | N.A. | Disease flare (clinical disease activity (CDAI or MTWAI), physician-reported flare, new fistula, stenosis, surgery, systemic steroids, therapy start, escalation or switch, new complication, or new EIM | ↑ Depressive symptoms are associated with increased relapse risk |
[50] | Longitudinal Cohort Study | Diagnosis: IBD n = 2789 (CD), n = 1516 (UC) (USA) | N.A. | Clinical relapse (HBI or SCCAI) | ↑ Baseline depression associated with relapse risk |
[51] | Longitudinal Cohort Study | Diagnosis: IBD n = 1031 (UK) | N.A. | Healthcare utilization and clinical outcomes (number of flares, corticosteroid prescriptions, therapy escalations, hospitalizations, and intestinal resections) | ↑ Persistently abnormal or worsening anxiety or depression scores linked to flare risk and more healthcare utilization |
[52] | Prospective Longitudinal Study | Diagnosis: UC n = 110 (USA) | N.A. | Clinical flares (SCCAI) and biochemical flares (SCCAI ≥5 with fecal calprotectin ≥250 μg/g) | ↑ High perceived stress linked to 3.6× higher odds of clinical flare ↔ No difference in biochemical flares between high- and low-stress groups |
[53] | Prospective Case-Crossover Study | Diagnosis: IBD n = 60 (Sweden) | N.A. | Relapse occurrence (Truelove and Witt criteria: blood in stools, diarrhea, and abdominal pain) | ↑ High perceived stress linked to higher risk of relapse |
[54] | Cross-sectional Study | Diagnosis: CD n = 162 (China) | N.A. | Clinical relapse (CDAI) | ↑ Psychological distress and lower social support were significant predictors of disease activity |
[55] | Longitudinal Cohort Study | Diagnosis: IBD n= 405 (UK) | N.A. | Disease flare (HBI or SCCAI, corticosteroid prescription, therapy escalation, hospitalization, or surgery | ↔ Bidirectional effect; abnormal anxiety associated with increased flares. Baseline disease activity associated with increased risk for anxiety |
Quality of Life | |||||
[56] | Prospective Cohort Study | Diagnosis: IBD n = 191 (China) | N.A. | Clinical disease activity (pMayo or CDAI), therapy change, or escalation | ↑ Low income, high stress, and poor quality of life predicted disease flares |
[57] | Randomized Controlled Trial | Diagnosis: CD n = 28 (USA) | Project Management vs. Treatment as Usual | Quality of life (IBDQ), self-efficacy (IBD-SES), stress (PSQ), and medication adherence (MAS) | ↓ Project management improved quality of life, self-efficacy, and reduced stress ↓ Project management has the potential to reduce flare risk |
COVID-19 | |||||
[58] | Prospective Cohort Study | Diagnosis: IBD n = 118 (Italy) | N.A. | Frequency of IBD relapse within 12 months (clinical relapse, medication change, hospitalization, or need for surgery) | ↔ Recent COVID-19 infection did not increase the risk of relapse |
[59] | Retrospective Observational Study | Diagnosis: IBD n = 3516 (Canada) | N.A. | COVID outcomes (severe/mild), IBD flares (symptoms, HBI, pMayo, an post-COVID infection biomarkers), prevalence of COVID infection in the IBD population vs. the general population | ↔ COVID-19 infection did not increase the risk of relapse |
[60] | Prospective Cohort Study | Diagnosis: IBD n = 316 (Canada) | N.A. | Adverse events, severe adverse events, injection site reactions, and IBD flare | ↔ No association found between COVID-19 vaccination and relapses |
[61] | Retrospective Cohort Study | Diagnosis: IBD n = 396 (Switzerland) | N.A. | Incidence of IBD flares post-vaccination (1-month post-vaccination and after 1 month) and adverse events (self-reported surveys) | ↔ No association found between COVID-19 vaccination and relapses |
[62] | Self-Controlled Case Series | Diagnosis: IBD n = 1911 (UK) | N.A. | IBD flare (defined by primary care consultation with diagnostic coding for IBD, diarrhea, abdominal pain, or rectal bleeding, and corticosteroid prescription) | ↔ No association found between COVID-19 vaccination and relapses |
Altitude, Climate, and Seasons | |||||
[63] | Retrospective Observational Study | Diagnosis: IBD n = 2030 (IBD: 736, Infectious gastroenteritis: 786, and Control: 506) (Switzerland) | N.A. | Hospital admission | ↑ Heat waves increase the risk of IBD-related hospital admission |
[64] | Retrospective Observational Study | Diagnosis: IBD, n = 2030 (IBD: 736, Infectious gastroenteritis: 786, and Control: 506) (Switzerland) | N.A. | Hospital admission | ↔ No association found between cold spells and IBD flares |
[65] | Retrospective Cohort Study and Model Assessment | Diagnosis: IBD n = 901 (Shanghai) | N.A. | Monthly patterns of onset and relapse and predictive accuracy of the model | ↑ Relapse peaks in from July to August in CD patients ↔ No seasonal patterns observed for UC |
[66] | Retrospective Observational Study | Diagnosis: IBD n = 103 (Switzerland) | N.A. | Clinical IBD flare (HBI or the Rachmilewitz Index) | ↑ Exposure to high altitudes increases the risk of disease flares |
[67] | Prospective Observational Study | Diagnosis: IBD n = 38 (Seoul) | N.A. | Worsening symptoms or medication prescribed during air travel, with assessment at the first outpatient visit after travel | ↑ Flight travel increases the risk of disease flares in patients with IBD comorbidities ↑ Flight travel increases the risk of disease flares in patients with a history of more frequent ER visits |
Clinical Index | |||||
[68] | Retrospective Cohort Study | Diagnosis: UC n= 75 (Italie) | N.A. | Onset or exacerbation of symptoms (abdominal pain, increased bowel movements, blood in stools, and urgency) requiring prompt medical consultation. | ↑Higher scores (ECCI, Seo’s Activity Index, SCCAI, and Partial Mayo Score) are associated with a higher risk of disease flares |
Prediction Models | |||||
[69] | Retrospective Cohort Study | Diagnosis: CD n = 5938 (Spain) | N.A. | Clinical relapse and hospitalization | ↑ Cumulative past flare, age, past admissions, proton pump inhibitors, smoking, acetic acid derivatives and related substances, and belladonna and derivatives in combination with analgesics |
[70] | Prospective Cohort Study | Diagnosis: IBD n = 172 (New Zealand) | N.A. | IBD relapse (medication escalation, hospitalization, and surgery) | ↑ High Disease Severity Index (DSI) predicted impaired quality of life, moderate-to-severe psychological distress, and increased flare risk |
[71] | Prospective Cohort Study | Diagnosis: UC n = 157 (Iran) | N.A. | IBD relapse (based on symptoms like bowel movements, bleeding, abdominal pain, and diarrhea) | ↑ Fecal calprotectin levels, age, Seo’s Activity Index, and number of previous relapses predicted relapse. Risk-scoring formula developed to predict relapse risk |
[72] | Prospective Observational Study | Diagnosis: CD n = 341 (Germany) | N.A. | Complicated disease course (need for immunosuppressants, anti-TNF agents, and hospitalization) | ↑ Age at onset <40 years, anemia, and treatment with systemic corticosteroids at first flare predicted a complicated disease course |
[73] | Longitudinal Follow-up Study | Diagnosis: IBD n = 692 (UK) | N.A. | Disease flare (global assessment or corticosteroid use) | ↑ Patients with severe gastrointestinal and psychological symptoms had an increased risk of flare or corticosteroid use |
[74] | Prospective Cohort Study | Diagnosis: CD n = 160 (Italy) | N.A. | Risk of disease progression and need for intensive treatment (steroids, azathioprine, anti-TNF-α drugs, and surgery); flare risk based on clinical and imaging findings | ↑ CD complications, small bowel CD lesion >20 cm, absence of colonic–ileal reflux, age <40 years, structuring behavior, and specific intestinal symptoms predicted higher corticosteroid use predictive of intensifying treatment |
Multiple factors | |||||
[75] | Prospective Cohort Study | Diagnosis: UC n = 79 (India) | N.A. | Clinical relapse (all also demonstrated endoscopic relapse) | ↑ NSAID use associated with clinical relapse ↑ Higher vitamin A intake associated with clinical relapse |
[76] | Prospective Cohort Study | Diagnosis: IBD n = 289 (Bulgaria) | N.A. | Frequency of relapses | ↑ Younger age increases relapse risk ↑ Shorter disease duration increases relapse risk ↔ No effect of sex ↔ No effect of smoking |
[77] | Retrospective Cohort Study | Diagnosis: UC n = 89 (Saudi Arabia) | N.A. | Recurrent UC flares | ↑ Family history of UC increases the risk of recurrent relapse ↑ Fecal incontinence increases the risk of recurrent relapse ↔ No association with smoking |
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Koppelman, L.J.M.; Oyugi, A.A.; Maljaars, P.W.J.; van der Meulen-de Jong, A.E. Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factors. J. Clin. Med. 2025, 14, 2296. https://doi.org/10.3390/jcm14072296
Koppelman LJM, Oyugi AA, Maljaars PWJ, van der Meulen-de Jong AE. Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factors. Journal of Clinical Medicine. 2025; 14(7):2296. https://doi.org/10.3390/jcm14072296
Chicago/Turabian StyleKoppelman, Lola J. M., Aroha A. Oyugi, P. W. Jeroen Maljaars, and Andrea E. van der Meulen-de Jong. 2025. "Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factors" Journal of Clinical Medicine 14, no. 7: 2296. https://doi.org/10.3390/jcm14072296
APA StyleKoppelman, L. J. M., Oyugi, A. A., Maljaars, P. W. J., & van der Meulen-de Jong, A. E. (2025). Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factors. Journal of Clinical Medicine, 14(7), 2296. https://doi.org/10.3390/jcm14072296