Natural history and progression risk factors of ulcerative proctitis: a retrospective study from a single tertiary centre in Poland

Introduction

Ulcerative colitis (UC) is a non-specific inflammatory bowel disease of unknown aetiology characterized by periods of exacerbation and remission. It usually affects young people aged between 20 and 40 years, with equal frequency in men and women. The pathogenesis of ulcerative colitis is still not fully understood, but it is known that immunological, environmental, and genetic factors are involved. Despite new methods of treatment, including innovative biological therapy, ulcerative colitis is still an incurable disease, requiring medication to achieve and maintain remission, often throughout life [1–3]. Ulcerative colitis has negative psychological consequences, and it adversely affects professional and social life of patients, significantly reducing its quality [4]. UC typically starts with the rectum (ulcerative proctitis – UP), being diagnosed at this stage in 25–50% of patients [5]. The natural history of ulcerative proctitis has not been fully understood so far – in some patients the inflammatory lesions progress to the left-sided colitis or pancolitis, while in others the disease has a mild course and the extent of lesions remains limited to the rectum [6, 7]. It is said that patients with inflammatory lesions exceeding the rectum are at greater risk of developing UC complications with the need for glucocorticosteroids, immunosuppressive drugs, and biological and surgical treatment [8–10]. For this reason, it is important to be able to predict the course of ulcerative proctitis at the time of diagnosis [11]. Little research on progression risk factors in ulcerative proctitis has been carried out, the available data are still scarce, and none of the studies have concerned the Polish population. Knowledge of the extent of inflammatory lesions in ulcerative proctitis is necessary to determine the appropriate therapeutic strategy and to estimate the risk of colectomy in the future [2, 8, 11].

Aim

The aim of the study was to identify risk factors for the progression of ulcerative proctitis and investigate the natural history of the disease, taking into account the following parameters: sex, age, body mass index (BMI), type of treatment, endoscopic activity of the disease at diagnosis, smoking, pregnancy, past infections, the patient’s knowledge and awareness of the disease, the number of exacerbations per year, family history of inflammatory bowel diseases (IBD), place of residence, occupation, severity of stress, and personality disorders. Many of these factors have not been studied yet.

Material and methods

This is a retrospective study, which included 116 patients – 75 females and 41 males with ulcerative proctitis, aged between 19 and 84 years, diagnosed in the Gastroenterology Department of Pomeranian Medical University in Szczecin (Poland) from January 2010 to December 2020, who suffered from ulcerative proctitis for at least one year. The average time of follow-up from the diagnosis was 7 years and 6 months. All patients agreed to participate in the study. The study did not require consent from the Bioethics Committee.
The study consisted of the analysis of medical documentation, including endoscopic and histopathological examinations, data collected using the author’s questionnaire, the Perceived Stress Scale (PSS-10), and the Polish adaptation of the Ten-Item Personality Inventory (TIPI-Pl) questionnaire. We also used the Simple Clinical Colitis Activity Index (SCCAI) to assess clinical disease activity and the Mayo Endoscopic Score to assess endoscopic activity of the disease.
The author’s questionnaire comprised 54 questions divided into 3 periods of the patient’s life: before the diagnosis of UP, at the time of the diagnosis of UP, and after the diagnosis of UP. The PSS-10 scale, which consists of 10 questions including subjective feelings related to various events and problems in personal life and methods of coping with them in the last month, was used to assess the intensity of perceived stress. Respondents rated their answers on a scale from 0 to 4, where 0 means never, 1 – almost never, 2 – sometimes, 3 – often, and 4 – very often. The obtained result is the sum of all points collected, which ranges from 0 to 40. A higher result correlates with greater intensity of stress experienced [12, 13]. The TIPI-Pl was used to measure personality disorders in patients with ulcerative proctitis. This is the most popular and the shortest tool for measuring the “Big Five” personality model, which includes 5 basic personality dimensions: extraversion, agreeableness, conscientiousness, emotional stability, and openness to experience. Respondents rated their answers on a scale from 1 to 7, where 1 means strongly disagree, and 7 means strongly agree. The obtained result was the average of 2 items, and one of them was an inverted position [14].

Statistical analysis

The analysis was performed using R software (R Core Team [2022]), version 4.1.3. The obtained results are presented as values of OR parameters with a 95% confidence interval. Kaplan-Meier curves were compared using the log-rank (LR) test. The analysis of the impact of quantitative variables on PFS was performed using the Cox proportional hazards model. The analysis adopted a significance level of 0.05. Thus, all p-values below 0.05 were interpreted as significant associations.

Results

The average duration of the disease was 7.62 years (SD = 4.78) and ranged from 2 to 23 years. The average age at the time of diagnosis was 36.11 years (SD = 15.09) and ranged from 13 to 73 years. Most of the patients were females (65%) (Table I). The time from the first symptoms to the visit to the doctor was on average 2.16 months (SD = 3.69), ranging from 2 days to 24 months, and the time from the presentation to the diagnosis and the start of treatment was on average 3.35 months (SD = 5.27), ranging from 2 days to 36 months. At the time of the diagnosis almost 45% of patients had moderate and 15% of patients had severe endoscopic disease activity. Progression occurred in 65 out of 116 (56%) patients. Left-sided UC developed in 55 (85%) patients, and extensive UC in 10 (15%) patients. The progression of inflammatory lesions most often occurred during the first 5 years of the disease. We detected many factors that affect the extent of inflammatory lesions in ulcerative proctitis. They can be divided into modifiable, non-modifiable, and partially modifiable factors and are presented in Table II. Factors that reduce the risk of progression in UP were also identified and are presented in Table III.

Discussion

This is the first single-centre study for the Polish population that looked for progression risk factors of inflammatory lesions in ulcerative proctitis. Many of them have been detected for the first time and constitute a new discovery in this topic. However, the risk factors such as presence of extraintestinal symptoms, the use of glucocorticoids and immunosuppressants, and moderate and high endoscopic inflammatory activity at onset are consistent with the results obtained in the studies carried out by Farmer, Meucci, Anzai, and Huguet et al. [5, 9, 15, 16]. It is worth adding that progression risk factors in UP, established in the above-mentioned studies, which include young age at diagnosis, BMI, male sex, and smoking cigarettes, were not confirmed in our research, which may be due to population differences; previous studies looked at Italian, Spanish, Belgian, Swedish, American, Korean, and Japanese populations. Our study also confirmed that the use of systemic glucocorticosteroids, both in the first flare of the disease and in exacerbations in mild-to-moderate UP, is a significant risk factor for the progression of ulcerative proctitis [5, 9, 16]. However, no such trend was observed for budesonide. Of the 65 patients who experienced progression, 42 received systemic glucocorticosteroids in the first exacerbation, but only 10 of them had endoscopic disease activity rated at level 3 on the Mayo Endoscopic Score. Our study also showed that the use of oral, not topical, mesalamine increases the risk of progression. The use of suppositories at the time of diagnosis reduces that risk by almost 60%, while the use of oral mesalamine increases the risk of progression 2.5-fold. The exact explanation of this phenomenon is not clear; however, this finding underlines the need to follow the guidelines, which recommend rectal mesalamine as a basic treatment for ulcerative proctitis [1, 2]. It is worth mentioning that the progression of inflammatory lesions in UP occurred more often in patients with endoscopic disease activity at the time of diagnosis defined on the Mayo Endoscopic Score at levels 2 and 3 and is consistent with the results confirmed by Walsh et al. [17]. Based on our study results, a type of patient with ulcerative proctitis, in whom progression of inflammatory lesions should be expected in the future, can be created. This is the patient who delays a visit to the doctor because of symptoms, with late treatment included and constantly active inflammation despite the use of drugs, with endoscopic disease activity assessed on the Mayo Endoscopic Score as 2 or 3 and the extent of inflammatory lesions in the rectum > 5 cm at the time of diagnosis, requiring treatment with systemic glucocorticosteroids and/or immunosuppressive and/or biological drugs, and with more than one exacerbation per year – this is partly consistent with the observations of Meucci et al.; other factors were detected in our study for the first time [5]. Our study also indicates the significant role of patient education in preventing progression of inflammatory lesions in ulcerative proctitis. Some of the results obtained in our research differ from the results of other studies. Farmer et al., Langholz et al., Anzai et al., and Roda et al. found an association between early age at onset of ulcerative colitis and risk of spreading the disease, which was not confirmed in this study [6, 8, 15, 16].
The use of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics in remissions is the next risk factor for the UP progression identified in this study. Several cohort and retrospective studies have confirmed the association of NSAIDs with UC exacerbations [18–20]. The overuse of antibiotics has become quite popular in recent years, and in ulcerative colitis excessive and irrational antibiotic therapy carries a risk of exacerbation as well as proximal extension of the inflammatory lesions [21]. Moreover, the use of antibiotics is known to carry an increased risk of Clostridioides difficile infection, which may also lead to the development of left-sided or extensive UC.
Our study is the first to evaluate personality disorders and stress as potential risk factors for the progression of ulcerative proctitis. It is thought that patients with inflammatory bowel diseases are more likely to develop emotional disorders than the general population [22]. Sajadinejad et al. examined the impact of type D personality and the “Big Five” personality model on the adaptability and quality of life of patients with UC compared to healthy family members. It transpired that type D personality, defined as stress-prone, may adversely affect the quality of life in ulcerative colitis. Patients with this personality type experience more anxiety, have low self-esteem, and are more likely to experience negative emotions. In relation to the “Big Five” personality model, significantly higher scores were observed in neuroticism, indicating emotional instability with overwhelming negative emotions and lower extraversion, which is characterized by assertive, talkative, and sociable people with the ability to develop interpersonal interests and social interactions [13]. In our study we analysed the “Big Five” personality model in the context of the progression of inflammatory lesions in ulcerative proctitis, and statistical significance was obtained in openness to experience, neuroticism, and extroversion. Stress, similarly to personality disorders, has never been considered as a potential risk factor of progression in ulcerative proctitis, and our study is the first in which such an analysis was performed. We showed that a high level of stress increases the risk of UP progression 71-fold compared to the average level. As many as 70 out of 116 patients reached a high level of stress, which is slightly more than 60% of all respondents, indicating that stress is a significant problem for many IBD patients.
The study has some limitations, including the retrospective nature of the study and estimation of disease clinical activity by using SCCAI, a relatively small group of patients, and a lack of randomization and control group. Nevertheless, it was possible to collect and analyse data on many potential risk factors for the progression of inflammatory lesions in UP.

Conclusions

The ability of predicting the course of ulcerative proctitis at the time of diagnosis is relevant for future outcomes. It enables better optimization of treatment, more accurate observation of patients, and prevents disease complications.

Acknowledgments

The project is financed from the program of the Minister of Science and Higher Education under the name "Regional Initiative of Excellence" in 2019-2022 project number 002/RIS/2018/19 amount of financing 12 000 000 PLN. Conflict of interest The authors declare no conflict of interest.

References