Delayed diagnosis in inflammatory bowel disease: Time to consider solutions

Abstract

In this editorial, we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology, with a specific focus on the delayed diagnosis of inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a chronic intestinal disorder. A time lag may exist between the onset of inflammation and the appearance of signs and symptoms, potentially leading to an incorrect or delayed diagnosis, a situation referred to as the delayed diagnosis of IBD. Early diagnosis is crucial for effective patient treatment and prognosis, yet delayed diagnosis remains common. The reasons for delayed diagnosis of IBD are numerous and not yet fully understood. One key factor is the nonspecific nature of IBD symptoms, which can easily be mistaken for other conditions. Additionally, the lack of specific diagnostic methods for IBD contributes to these delays. Delayed diagnosis of IBD can result in numerous adverse consequences, including increased intestinal damage, fibrosis, a higher risk of colorectal cancer, and a decrease in the quality of life of the patient. Therefore, it is essential to diagnose IBD promptly by raising physician awareness, enhancing patient education, and developing new diagnostic methods.

Key Words: Inflammatory bowel disease; Delayed diagnosis; Diagnostic methods; Early diagnosis; Consequences of inflammatory bowel disease

Core Tip: Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, is a chronic intestinal condition. Early diagnosis is vital but often delayed owing to nonspecific symptoms and limited diagnostic tools. Delayed diagnosis exacerbates symptoms, increases risks such as cancer, and reduces quality of life. To improve outcomes, early diagnosis through enhanced physician awareness, patient education, and the development of advanced diagnostic methods is crucial.

INTRODUCTION

Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal disorder that encompasses two distinct forms: Crohn’s disease (CD) and ulcerative colitis (UC). Its prevalence peaks in early adulthood and then stabilizes, but the age-standardized prevalence continues to increase over time. Compared with men, women have a higher prevalence of intestinal diseases, more deaths, and more disability-adjusted life years[1-3]. Over the past half-century, the incidence of IBD has increased in industrialized countries. While it has now stabilized or declined in developed Western countries, the incidence is rising dramatically in newly industrialized developing countries, such as China[4]. Physicians play a crucial role in promoting the early diagnosis of CD to prevent the progression of severe disease and complications. The gap between the onset of IBD and its formal diagnosis, often referred to as delayed diagnosis, can have significant consequences. In CD, delayed diagnosis can result in cumulative intestinal damage, fibrosis, and disability. In UC, early diagnosis and effective treatment can lower the long-term risk of colorectal cancer and reduce the need for surgery[5].

The initial diagnosis of IBD is based on a combination of history, physical examination, laboratory tests, and endoscopic, histologic, and radiologic findings. There is no single definitive test to establish a diagnosis, and current diagnostic methods do not always allow for early detection and treatment[6]. Diagnosing IBD is challenging, and patients often experience significant delays in diagnosis owing to subclinical inflammation, which can lead to poor clinical outcomes[7]. The National Institute for Health and Care Excellence (NICE) guidelines emphasize the importance of early detection and diagnosis of IBD, stating that “delays in assessment and diagnosis can lead to adverse outcomes such as clinical complications and impaired quality of life”[8]. Delays in the diagnosis of IBD are common. A recent systematic review found a median diagnostic delay of 2 to 26 months for adults with CD and 2 to 12 months for those with UC[9]. In a manuscript published in the World Journal of Gastroenterology, Blüthner et al[10] reported that among the first German cohort of adult IBD patients, those with CD exhibited a higher risk of diagnostic delay than those with UC. The study noted that the time to diagnosis largely depended on the physician, with disease-specific symptoms and available diagnostic methods helping to shorten this time.

The reasons for the delay in diagnosing IBD are not fully understood, but one possible explanation is the nonspecific nature of its symptoms, which can easily be mistaken for more common conditions such as irritable bowel syndrome (IBS) or hemorrhoids[11]. The longer delay in diagnosing CD compared with UC may be because UC lesions are confined to the colon and often trigger rectal bleeding, which prompts patients to seek medical attention sooner. In contrast, patients with CD may present with a broader range of nonspecific symptoms, such as abdominal pain or constipation, which are more commonly associated with other conditions that have overlapping symptoms[9]. Early detection of IBD is crucial in primary care. To better manage the impact of delayed diagnosis, it is essential to understand the barriers to diagnosis and develop strategies to overcome them. Early and rapid diagnosis can improve the initial treatment, reduce the duration of illness, and enhance patient satisfaction.

TIPS FOR SUCCESSFULLY IMPROVING DELAYED DIAGNOSIS OF IBD

When chronic inflammation begins in the affected bowel, it may take time before noticeable clinical signs of IBD appear. Consequently, there can be a significant interval between the onset of inflammation and the emergence of symptoms that enable a correct and timely diagnosis. This subclinical inflammation can be difficult to recognize and treat, sometimes leading to intestinal damage even before clinically active inflammation develops[7]. If clinically active inflammation can be diagnosed before complications arise, it may be possible to control and treat the disease within the “window of opportunity,” when interventions are most likely to be successful[12]. While the most common symptoms of IBD are chronic diarrhea, abdominal pain, weight loss, and rectal bleeding, up to 30% of patients with IBD may exhibit no symptoms[13,14]. This makes diagnosing IBD challenging. Additionally, limited knowledge of IBD among the general public, non-specialized gastroenterologists, or general practitioners (GPs) can lead to misinterpretation of potential IBD signs and symptoms, resulting in significant delays in diagnosis and referral[13,14]. Medical diagnostic errors or delays stem from a complex interplay of systemic, organizational, clinical, and patient interaction factors[15].

Gastrointestinal symptoms account for approximately 10% of all primary care visits. However, in high-income countries, the prevalence of IBD is only 0.3%[4]. Blüthner et al[10] demonstrated that the delay in diagnosing CD is significantly longer and largely dependent on the physician compared with UC in the German population. Physician awareness plays a crucial role, and since more than one-third of primary care physicians struggle to confidently recognize the major symptoms of IBD, we recommend developing a strategy to train primary care physicians and raise awareness of IBD within medical school curricula[5]. One medical school in New York has integrated IBD patient panels into its curriculum as a supplement to traditional lectures-an initiative that could enhance theoretical knowledge and understanding of IBD in later medical careers[16]. At the same time, data on the prevalence of IBD are limited, which may be attributed to differences in healthcare systems, data collection methods, and definitions of time to diagnosis (including symptom onset and the initial visit)[15]. Collecting more detailed health-related data and categorizing meaningful outcomes, such as health-related complications, could provide a more consistent framework for addressing these systemic challenges.

To reduce the delay in diagnosing IBD, it is crucial not only to enhance the diagnostic skills of primary care physicians and other clinicians but also to develop more innovative and accurate diagnostic methods. Clinically available diagnostic approaches may include fecal examination, colonoscopy, radiology, and capsule endoscopy[17]. These tests can be uncomfortable, painful, and sometimes even dangerous for patients. Additionally, genetic and serologic tests are not sufficiently specific or sensitive to be useful for diagnosing IBD[18,19]. Non-invasive alternatives can assist in diagnosing IBD, with fecal markers showing promise. Fecal lactoferrin and calprotectin can help differentiate between IBD and non-inflammatory diseases. Additionally, fecal calprotectin has proven to be a cost-effective screening tool for identifying patients with subclinical symptoms of IBD[19,20]. These screening modalities are now commonly used and are supported by NICE. Gastrointestinal ultrasound also demonstrates high sensitivity and specificity for diagnosing CD and for the initial evaluation of patients with suspected UC. Additionally, it is inexpensive, safe, and does not require bowel preparation[21].

Recent studies have explored advances in diagnostic modalities for IBD by focusing on volatile organic compounds released in body fluids, including feces, urine, and breath[22,23]. Apical space gases in feces or urine can be analyzed via gas chromatography/mass spectrometry[24,25]. Modeling based on these compounds could help distinguish CD and UC from IBS and healthy populations[26]. Similar studies have found that headspace gases in urine can be used to diagnose IBS[22]. While fecal samples are relatively easy to obtain, patients often dislike or resist collecting them, making urine testing an attractive alternative. Early data from breath samples also show promise[27]. Non-invasive diagnosis of IBD is becoming a reality, helping to avoid patient discomfort and embarrassment while reducing associated risks. This approach can also lead to significant savings in both money and resources for healthcare providers. Additionally, advancements in artificial intelligence (AI) are making substantial progress in improving IBD diagnosis. AI is increasingly used to enhance the interpretation of endoscopic images and assess disease severity. For example, a convolutional neural network model can automatically detect the degree of erosions and ulcers in small bowel mucosa from capsule endoscopy images with an accuracy of 95.6%, sensitivity of 90.8%, and specificity of 97.1%. This capability can help determine the risk of bleeding in IBD mucosal lesions[28]. AI technology is expected to significantly impact clinical practice and trials, as it will aid clinicians and help patients manage their diseases more effectively[28].

CONCLUSION

IBD is a common chronic intestinal disease that includes CD and UC, both of which can present with a wide range of clinical manifestations[1]. Early diagnosis of IBD is crucial for effective patient care and prognosis, yet delays in diagnosis remain common. Such delays can result in intestinal damage, fibrosis, and dysfunction, and may increase the likelihood of requiring surgical intervention[5]. The reasons for delayed diagnosis of IBD are not fully understood, but they may be related to the nonspecific nature of clinical symptoms, the limited number of diagnostic modalities available, and the need to enhance the diagnostic skills of GPs and some clinicians[9,11]. Improving the personal competence of GPs and clinicians could also be a significant factor in addressing these delays[5]. Existing tests, such as endoscopy, may cause embarrassment and pose risks for patients, whereas fecal calprotectin has shown promise as an effective diagnostic method[20]. Recent studies have explored the use of volatile organic compounds released in body fluids, including feces, urine, and breath[22,23,27]. Given the current limitations in improving the diagnosis of IBD, it is important to consider additional solutions to address and reduce delays in diagnosis.