Early Identification and Management of Ulcerative Colitis: A Narrative Review

1. Undergraduate Student, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research (DU), Nagpur, Maharashtra, India. 2. Professor, Department of Biochemistry, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research (DU), Nagpur, Maharashtra, India. 3. Tutor, Department of Biochemistry, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research (DU), Nagpur, Maharashtra, India. 4. Associate Professor, Department of Medicine, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research (DU), Nagpur, Maharashtra, India. 5. Associate Professor, Department of Microbiology, Jawaharlal Nehru Medical College, Sawangi (Meghe), Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India.

Abstract

Ulcerative Colitis (UC) is a chronic Inflammatory Bowel Disease (IBD) that affects the inner lining of the colon, imposing a significant burden on healthcare systems worldwide. Symptoms include bloody stools and abdominal pain. The prevalence of UC is increasing, particularly among young adults. The pathogenesis involves immune responses, genetics and environmental factors. Diagnostic delays are common, leading to complications and increased costs. Early diagnosis is crucial for preventing complications. Endoscopy is the primary diagnostic tool. Treatment aims to reduce inflammation and achieve remission. Delayed diagnosis can lead to long-term complications such as Colorectal Cancer (CRC) and bowel stenosis. Prompt recognition and management are essential for minimising the disease burden and optimising care. The present study delves into the complex nature of UC, a chronic IBD, revealing its epidemiology, pathogenesis, diagnostic challenges, treatment strategies, prognosis, complications and the impact of delayed diagnosis on patients’ quality of life. The study highlights the evolving understanding of UC pathogenesis, incorporating immune responses, genetics, environmental factors and biomarkers. It also discusses diagnostic delays due to symptom similarities and the need for increased awareness among healthcare providers and the public. The study also discusses advanced diagnostic methods and therapeutic approaches, including novel drug targets and surgical interventions. It also highlights the negative consequences of delayed diagnosis, including increased morbidity, psychological distress and socioeconomic burden. The study emphasises the need for collaborative efforts to ensure timely and appropriate care for UC patients.

Colorectal cancer, Diagnostic delay, Inflammatory bowel disease

The UC is included in the category of chronic IBD because of its lifetime burden and recurrent nature. The innermost portion of the colon is impacted by rectum mucosal inflammation. While the small intestine continues to operate correctly and organically, the large intestine becomes significantly inflamed (1). Although research indicates that overall spending on UC in Europe is approximately €12.5-29.1 billion, with the USA spending about US$8.1-14.9 every twelve months, treatment and therapies attempt to minimise remission and flare-up rates as much as feasible (2). Bloody stools, dysentery, abdominal pain, faecal urgency or tenesmus, cramping in the abdomen, etc., are symptoms of UC. It is now recognised as a dysbiosis illness complication (3).

Concerned adults and children, estimated that 1.2 million people in North America and 2.6 million people in Europe suffer from UC. When it comes to feeling intermittent pain with bowel motions, it typically affects people between the ages of 15 and 25 years (4). In the United States, CRC ranks second in terms of cancer-related mortality. Compared to the general population, individuals with IBD are almost twice as likely to get CRC. Patients with UC had a comparatively lower mean age at which to develop CRC than patients with sporadic CRC. Additionally, there was a statistically significant increase in mortality among the older age group (51-65 years) (5). After continuing for a long period of time, such as over 8 to 10 years, it may result in megacolon (abnormal colon dilation), eye or liver inflammation, joint pain and colonic neoplasia (6). This disease’s rising epidemiologic dawn is brought to light by the heightened incidence and prevalence figures, which also highlight the need to address these covert conditions and put an end to them (7).

Earlier, in the 1987, studies and strong beliefs surrounded issues like nicotine’s potential use as a treatment for UC (8). Smoking is a significant environmental risk factor for developing the condition; thus, even if it has been proven to be beneficial, smoking is still prohibited and only permitted in a limited number of circumstances (9). The present study comprehensively investigates UC, focusing on its epidemiology, pathogenesis, diagnostic challenges, treatment strategies, prognosis and impact of delayed diagnosis on patients’ quality of life. It aimed to enhance understanding and management approaches, emphasising the necessity for timely diagnosis and collaborative care efforts.

Pathogenesis/Aetiology

A combination of immune responses, genetic factors, environmental influences and various miscellaneous factors like smoking cigarettes can be held partially responsible for this mysterious disease that is otherwise undetermined. The relapsing-remitting nature of UC is influenced by several gastrointestinal factors, particularly the epithelial barrier, concurrent microbiota, antigen recognition, immune response dysregulation and leukocyte attraction. Tumour Necrosis Factor (TNF), Interleukin (IL)-1, IL-6, IL-9, IL-13 and IL-33, along with antigen-presenting cells (macrophages and dendritic cells), T helper cells, regulatory T cells, natural killer cells and the networks of cytokines are primarily responsible for the most well known tissue damage (10). The IL-1 gene family and the Multidrug Resistance (MDR1) gene have also been recognised to be connected to this phenomenon, as has the Major Histocompatibility Complex (MHC) locus HLA class II alleles, which have always been associated with the development of sickness (11).

A chromosomal or inherited history of the disease does indeed predict a heightened risk of acquiring the disease by about 10%-25% when having a first-degree relationship with a patient with IBD. Additional genetic pathways implicated in UC include the epithelial barrier functions Chromodomain Helicase DNA (deoxyribonucleic acid) binding protein 1 (CHD1) and Laminin Subunit Beta 1 (LAMB1), as well as the inflammatory enzymes TNFRSF15, TNFRSF9, IL1R2, IL8RaIRB and IL7R (12). Other environmental components, namely microRibonucleic Acid (mRNA), have been newly discovered to play a role in inflammatory processes by microarray and Polymerase Chain Reaction (PCR) methods (13).

Causes for Diagnostic Delay

Patients with similar and common symptoms to other ailments have been provided with aid, which has unfortunately led to the deterioration of their health. This delay in an accurate disease diagnosis raises the possibility of disease progression to a later stage. Additionally, alongside increasing healthcare costs and fees, the lack of a conclusive diagnosis or additional prognostic options disturbs the psychological well-being of the patients and those around them (14). So as the delay is common, it may lead to the development of new complications within the patient’s current state, further contributing to deterioration or more failures in treatments and therapies (15).

Based on their use of anti-TNF, Asians who opted out of surgery had their prognosis assessed and it was thought that they might be typical of the Asian community with moderate UC. A 24-month diagnostic delay should be avoided, even in UC patients with mild symptoms, according to research. Remembering to treat UC in teenagers who smoke and have haemorrhoids is imperative. As a consequence, risk variables for the 24-month diagnostic delay in the records included smoking history, age less than 60 at diagnosis and incorrect interpretation of haemorrhoids (16).

Young patients were found to be much more likely to experience a prolonged diagnosis delay through multivariate logistic regression, even though both patients and doctors can contribute to a diagnostic delay. More public and professional expertise is needed to shorten the time it takes for IBD patients to receive a diagnosis (17).

Diagnosis and Advanced Methods for Differential Diagnosis of Ulcerative Colitis (UC)

The most frequent approach to identifying unexpected UC is endoscopy, specifically colonoscopic biopsy. Other procedures include endoscopic ultrasonography, Computed Tomography Enterography (CTE) and Magnetic Resonance Imaging (MRI) (18). Advanced endoscopic imaging methods, such as confocal laser endomicroscopy, endocytoscopy, chromoendoscopy, optical spectroscopy, optical coherence tomography and molecular imaging, are useful for making a differential diagnosis for IBD (which includes UC and Crohn’s disease). It has been discovered that a second ileocolonoscopy is a useful technique for identifying and diagnosing UC (19).

The occurrence of pseudopolyps detected in endoscopic findings is a sign of recent or ongoing relapses, possibly indicating the risk of bowel stenosis and it signals the need for an increase in immunosuppressive therapy, biological agents, or surgery, clearly demonstrating a powerful surge in disease activity in the patient (20).

The justification for a colectomy has evolved over time. According to a study of Olmsted County, 90% of colectomies performed before 1990 were undertaken to treat disorders that were unresponsive to medical treatment, whereas 5% were conducted to treat fulminant colitis and 5% to treat colorectal neoplasia (21). The bulk (56%) of surgeries carried out after 1990 were for colorectal neoplasia (12%) and fulminant colitis (26%). 54% of patients undergo total protocolectomy with ileal pouch anastomosis; 33% undergo total protocolectomy with end-ileostomy; and 12% undergo subtotal colectomy with ileostomy (22).

Strategies for Early Diagnosis

The measurement of disease activity in IBD has been addressed using numerous measurable laboratory tests. C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), leukocytes, platelets, ferritin, haptoglobin, ceruloplasmin, α-1-antitrypsin, plasminogen, complement factors and fibrinogen are a few examples of frequently used serum laboratory assays. Orosomucoid (α-1-acid glycoprotein), IL-6, sialic acid and serum amyloid A are further experimental serum assays that are not generally offered commercially. Faecal Calprotectin (FC), lactoferrin, polymorphonuclear elastase, myeloperoxidase, metalloproteinase-9 and neopterin are stool assays for identifying inflammation. It has also been demonstrated that specific proteome and microRNA species, only accessible in research settings, can distinguish between active and inactive IBD (23).

The drugs that contain 5-aminosalicylic acid, immunosuppressants and steroids are all used to treat UC. Some patients with medically challenging circumstances or those with colonic neoplasia may require a colectomy. The spectrum of available UC treatments is expanding and in future decades, the number of drugs with fresh objectives will rise significantly. UC is currently treated with 5-aminosalicylates, corticosteroids, immunosuppressants (such as tacrolimus, cyclosporine and purine antimetabolites) and surgery. The goals of treatment for UC management are evolving. Over the past ten years, the evidence for more precise assessments of biological disease activity has increased and now includes biomarkers like CRP, FC and the histological resolution of active inflammation in UC (24),(25). The Platelet to Lymphocyte Ratio (PLR) and IL-8 performed admirably in separating UC from IBS patients. Additionally, increased IL-8 levels showed mucosal inflammation, demonstrating the severity of the condition in UC patients (26).

Treatment and Management

A clinical history should include the disease’s severity, factors and alternative aetiologies. Symptoms include bowel movements, bleeding, urgency, cramps, abdominal pain and weight loss. Hepatobiliary involvement and extraintestinal manifestations should also be evaluated. UC is diagnosed using clinical, laboratory, imaging and endoscopic parameters, including histopathology, which shows constant colonic inflammation (Table/Fig 1),(Table/Fig 2) (27),(28),(29).

Recommended Baseline Assessment in Inflammatory Bowel Diseases (IBD)

The comprehensive assessment of patients with IBD involves various objective measures and evaluations across multiple domains. Clinical symptoms are quantified using scores such as patient-reported outcomes and the Harvey-Bradshaw index. Serum evaluation encompasses markers like haemoglobin, albumin and CRP, alongside liver function tests and electrolyte levels. Faecal calprotectin serves as a stool biomarker, while mucosal assessment is typically done through ileocolonoscopy, with alternative methods like balloon enteroscopy or capsule endoscopy as needed. Psycho-social evaluation includes resilience scales, disease questionnaires and assessments for depression/anxiety and quality of life. Nutritional status is evaluated through anthropometric measures, micronutrient screening and dietary assessments. Immunisation status, including key vaccines, is verified and administered per national guidelines.

Imaging modalities like CT enterography and small-bowel MRI aid in disease assessment. Virus screening methods cover blood-borne serology and tests for latent tuberculosis. Pharmacogenetic evaluation, if available, informs therapeutic medication monitoring plans utilising genotyping for human leukocyte antigen and thiopurine S-methyltransferase (29).

Intravenous steroids are routinely suggested for those with toxic megacolon due to UC. On the other hand, steroid use is associated with refractoriness, which can result in cytomegalovirus reactivation and mask the presence of intra-abdominal sepsis. Thus, in a study conducted by Narabayashi K et al., two unique examples of megacolon linked with pan-colonic severe UC were reported, one of which involved a patient who had never used steroids. It was suggested to reduce the need for steroids and enhance the long-term prognosis in cases of UC with megacolon, oral tacrolimus therapy is recommended (30). An urgent colectomy should be considered when UC patients are admitted and fail to respond to intravenous corticosteroids. Salvage therapy options include infliximab or cyclosporine (31).

When treating individuals with toxic megacolon, exsanguinating haemorrhage, or intestinal perforation who have Acute Severe Ulcerative Colitis (ASUC), colectomy should be considered early in the process. In the absence of improvement after seven days following the start of rescue medication, a colectomy should be considered in patients with steroid-refractory illness who have been hospitalised for three days and are judged unsuitable for second-line therapy. When compared to urgent colectomy, planned colectomy is associated with much lower rates of morbidity and death. This emphasises how crucial it is to identify individuals who are likely to need surgery as soon as possible. The recommended first procedure is a colectomy combined with an ileostomy. A follow-up complete proctectomy with a pouch might be scheduled if the patient’s physical and dietary status has improved (32).

Prognosis and Complications

The prevalence of UC, which has impacted around five million individuals globally, is on the rise. Therefore, a diagnosis and forecast are now crucial (33). The prognosis for patients with UC has shown significant variation in terms of phenotypic presentation, along with several clinical and demographic factors (34).

The prognosis is severely hampered by the widespread misdiagnosis of the entire ulcerative population. There are many controversies that have an effect, such as Appendiceal Orifice Inflammation (AOI), which is frequently disregarded and deemed unimportant during diagnosis and treatment. However, studies have shown therapeutic effects in a variety of patients, both with and without AOI (35),(36),(37),(38). In particular, for patients who have never received a type of biologic therapy before, several professional gastroenterologists have shown that a short duration of illness is independently associated with a higher probability of treatment failure and a smaller chance of achieving endoscopic remission. This shows that patients with UC taking biologic drugs may have an early requirement, which would encourage early identification and robust therapy (39),(40).

Extra-intestinal Manifestations (EIMs) are other UC-related disorders that include pancreatitis, thromboembolism, renal disease, pulmonary illness and other conditions. These conditions include musculoskeletal EIMs, cutaneous EIMs, ophthalmic EIMs, hepatobiliary EIMs and more. These illnesses frequently co-exist with arthropathies and often induce inflammation in the eyes, skin, joints and liver (41).

Potential negative effects of postponing treatment for UC include an increased risk of CRC, intestinal stenosis, bowel blockages, toxic megacolon, colonic perforation, anaemia, nutritional inadequacy and psychological problems (42).

Another short-term diagnostic delay complication that frequently occurs is emotional and behavioural distress, such as aggressiveness, overthinking, fear, depression, or anxiety, caused by the patient’s inability to meet their own needs due to bowel urgency or bowel incontinence, which serves as a major stressor and also makes them irritable (43). Non curable sickness is linked to a societal difficulty, such as spending a lot of money over the course of a lifetime (44).

Continuous inflammation over an extended period of time damages the mucosal layer and destroys the epithelial barrier, affecting the production of epithelial cells and their susceptibility to apoptosis or the development of immune resistance. As a result, there are eventually fewer goblet cells in the mucus layer, which may lead to the recurrence of UC (45). Malnutrition, specifically malabsorption, is one of the additional consequences that chronic inflammation may cause. Due to a reduction in epithelial transport and integrity, the function of nutrient absorption is reduced or halted. Other causes of malnutrition resulting from UC include decreased oral food intake, which may be related to pharmaceutical side-effects such as anorexia, nausea, cramping, or stomach soreness, or post-surgical complications like diarrhoea (46).

Long-term effects of diagnostic delays can stem from chronic inflammation, malnutrition, an increased risk of surgery, toxic megacolon, colon perforation and an increased risk of CRC. Specifically, cases of pancolitis appear to have a higher surgery risk due to colorectal neoplasia or poorly controlled inflammation (47). Public anxiety about surgical procedures is significant as they often accompany comorbid conditions, accounting for approximately 40% of cases. Infectious co-morbidities may include small intestine blockages, dehydration and conditions related to the urinary tract such as ischuria and wound infections, with postoperative ileus being the most common (48). Toxic megacolon is a similar side-effect of inflammatory colitis (49), characterised by small and insignificant colon perforations (50).

A recent study highlighted an unexplained sigmoid perforation and concurrent colovesicular and colocutaneous fistula diseases in a 43-year-old man with a history of UC that required ongoing surgical care. Further investigation revealed severe diverticulitis with UC as the underlying cause. There are few documented cases of perforated diverticulitis layered on UC in the literature, exacerbating the diagnostic challenges (51). Additionally, research indicates that individuals with IBD are more prone to developing cardiovascular disorders [52-55]. Postoperative complications were more prevalent in elderly individuals and those with multiple existing illnesses (56).

Impact of Delayed Diagnosis on Quality of Life

According to a multicentered European study, individuals experiencing intermediate to severe UC have higher rates of disease incidence, poorer health-related quality of life and more severe impairment of social and professional activities compared to the average person. They also have higher percentages of both sick leave and unemployment (57). Patients often experience body image and weight issues, which have been linked to long-term steroid use and disease activity (58). Consistent with previous studies (59),(60), individuals reported a delay between the onset of UC symptoms and diagnosis, with 42% of patients experiencing a delay of more than a year. Patients may become frustrated and anxious if the diagnosis of UC is delayed, potentially leading to strain in the patient-physician relationship (61).

The UC narrative survey included inquiries about how UC impacted daily activities, how to manage the condition, how to set goals and how to communicate with doctors. Responses from physicians and patients were gathered regarding dialogue during UC therapy. The idea behind the present survey is that by identifying gaps, strategies can be developed to enhance patient-physician interactions and communication, ultimately empowering patients to better manage their symptoms and adhere to their treatment plan. Improving patient-physician communication allows patients to make more informed decisions about available medications and procedures, enabling them to play a more active role in their healthcare (61).

Conclusion

In conclusion, a delay in the diagnosis of UC may result in serious short- and long-term consequences, such as increased morbidity and mortality. To avoid these problems and enhance patient outcomes, early UC diagnosis is crucial. Increasing public awareness, educating healthcare professionals, utilising diagnostic equipment, developing screening programs and enhancing access to healthcare are all strategies for the early identification of UC. To avoid potential consequences linked to diagnostic delay, it is crucial to collaborate to guarantee timely and appropriate care for people with UC. We can improve the lives of patients and minimise the burden that this chronic disease places on people and society by promoting the early identification and management of UC.

DOI and Others

DOI: 10.7860/JCDR/2024/67203.19800

Date of Submission: Aug 25, 2023
Date of Peer Review: Jan 31, 2024
Date of Acceptance: May 17, 2024
Date of Publishing: Aug 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Aug 29, 2023
• Manual Googling: Feb 02, 2024
• iThenticate Software: May 15, 2024 (8%)

ETYMOLOGY: Author Origin

EMENDATIONS: 8