Diagnostic delay in inflammatory bowel disease: Current situation and problems

Abstract

In this article, we comment on the article by Blüthner et al published recently. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic relapsing and remitting condition primarily as a consequence of intestinal inflammation. It is important about adopting early and effective treatment to control clinical symptoms of IBD patients. Diagnostic delay can lead to adverse clinical outcomes and increase disease burden. Diagnostic delay is multifactorial. There are some factors related to diagnostic delay, such as patient factors and healthcare factors. We focus on the diagnostic tools for IBD, the outcomes and factors of diagnostic delay of IBD.

Key Words: Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Diagnostic delay; Clinical outcome

Core Tip: Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is a chronic relapsing and remitting condition primarily as a consequence of intestinal inflammation. It is important about adopting early and effective treatment to control clinical symptoms of inflammatory bowel disease patients. Diagnostic delay can lead to adverse clinical outcomes and increase disease burden. Diagnostic delay is multifactorial. There are some factors related to diagnostic delay, such as patient factors and healthcare factors.

TO THE EDITOR

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic relapsing and remitting condition primarily as a consequence of intestinal inflammation. In the past few years, the global incidence rate of IBD has steadily increased[1]. However, there are significant differences in the prevalence of IBD among different countries[2]. This difference is mainly attributed to the consultation time of primary medical care, such as 15 minutes in Australia, 10 minutes in United Kingdom, and only 3-5 minutes in China. Therefore, it is very difficult to diagnose IBD in China. IBD is a multifactorial disease that develops as a result of immune disorders. Immune balance affects the clinical, laboratory, endoscopic and pathological effects of the disease. When the immune balance loses its protective effect, IBD reflects more pathognomic findings. If the immune balance protective feature is dominant, the clinician can see non-specific findings. Non-steroidal anti-inflammatory drugs and antibiotic use can cause ulcers in the terminal ileum. The pathologist can sometimes present a result such as IBD to the clinician. In this case, the clinician is forced to stop the drug used and try to decide by following the patient. Is it the protective effect of the immune balance? Are CD/IBD faint findings? These issues naturally cause a delay in diagnosis. On the other hand, due to their well-being, the patients’ not coming to follow-up also causes a delay in diagnosis. 10% of the IBD patients present with gastrointestinal symptoms in primary care. However, more than one-third of primary care physicians are unable to accurately identify symptoms of IBD and make timely diagnoses. Therefore, training for primary care physicians and promotion of IBD characteristics are required[3]. Diagnostic delay is common in IBD and is affected by various factors, such as medical related factors and patient specific factors. Among them, the cognition of clinical physicians plays an important role in the diagnostic delay of IBD, but there is currently limited research in this area.

Comment

Blüthner et al[4] gathered data on 430 IBD patients from Germany between 2012 and 2022. In this study, the total diagnostic time was 12 months for CD and 4 months for UC specifically. There was no difference in the patient waiting time between the group of UC, which is 1.0 months [interquartile range (IQR): 0.5-4.0], and the group of CD, which is 2.0 months (IQR: 0.5-6.0). However, the physician diagnostic time was longer in CD patients, which is 5.5 months (IQR: 0.75-23.5), compared to the physician diagnostic time in UC patients, which is 1.0 month (IQR: 0-5.0). Blüthner et al[4] analyzed some clinical factors related to diagnosis time. In univariate analysis, a longer physician diagnostic time was found in CD patients with diarrhea (P = 0.012) and skin lesions (P = 0.028), and UC patients with fatigue (P = 0.011) and positive family history (P = 0.046). But the shorter physician diagnostic time was found in UC patients with fever (P = 0.020). What is more, the authors concluded that age and gender were not related factors. According to previous studies, longer diagnostic time was found in IBD patients with younger age.

While Blüthner et al[4] do not discuss fecal calprotectin, it is a rapid screening tool to minimize diagnostic delay for IBD. A major challenge of fecal calprotectin for screening IBD would be the cut-off value. The cut-off value can affect the specificity and sensitivity of fecal calprotectin. For example, if the value of fecal calprotectin is greater than 50, the likelihood of having a diagnosis of IBD is 62%. But if the value of fecal calprotectin is greater than 800, the likelihood of having a diagnosis of IBD will increase to 93%. Therefore, a consensus fecal calprotectin value is needed for screening IBD. Abdominal pain, diarrhea, blood in stools, and weight loss are the common symptoms of IBD. Some IBD patients may experience extra-intestinal manifestations such as arthritis and pyoderma gangrenosum. An important problem of diagnostic delay is that gastrointestinal symptoms are common presentations in IBD and other gastrointestinal diseases. The awareness of ‘red flags’ can be helpful in deciding which patient should be diagnosis with IBD. The red flags include: (1) Symptoms: Diarrhea or loose stools for > 14 days, bloody stool or rectal bleeding, weight loss, and abdominal pain > 14 days; (2) Signs: Perianal disease including anal fistula or perianal abscess, frequent oral ulcers, and extra-intestinal manifestations including uveitis, arthropathy and erythema nodosum; (3) Positive family history of IBD; (4) High inflammatory markers including C-reactive protein and erythrocyte sedimentation rate; (5) Low albumin; and (6) Low hemoglobin.

CD diagnosis usually takes longer than UC. UC starts from the rectum and causes diffuse mucosal involvement, bloody mucous stools, and tenesmus. It does not have both endoscopic and pathological difficulties in diagnosis as much as CD. However, CD leads the doctor to be a bit more suspicious. Non-specific ulcers in the terminal ileum, tuberculosis ileitis, rheumatological involvements (such as Behcet’s disease) in the differential diagnosis are important factors that make the disease diagnosis difficult.

Diagnostic tools of IBD

Endoscopy is an important tool in the diagnosis of IBD. Now use of non-invasive alternatives to endoscopy including fecal calprotectin and gastrointestinal ultrasound plays an important role in the diagnosis of IBD. Fecal calprotectin is a protein produced by inflammatory cells in intestinal tissue and has high sensitivity in the diagnosis of IBD[5]. It raised in intestinal inflammatory diseases and other gastrointestinal disease. Calprotectin can remain stable in feces for more than one week. Therefore, it is widely used in IBD screening in primary care. Some studies and guidelines have indicated that fecal calprotectin is a screening tool for IBD. The major drawbacks are the relatively poor specificity, uncertainty cut-off value, and the high cost per sample[6]. For example, calprotectin can be affected by other diseases such as tuberculosis ileitis and rheumatological involvements. Intestinal ultrasound is an important tool that can effectively diagnose CD and evaluate the disease activity of UC. It has some advantages such as safety, convenience, and inexpensive. The combination of these tools warrants further investigation for its utility in the diagnosis of IBD. Public media should be used to improve awareness of IBD symptoms and encourage symptomatic patients to seek medical attention promptly. Some clinical tools such as the red flags index, fecal calprotectin, intestinal ultrasound, and endoscopy have been proven to be effective methods for identifying IBD and avoiding diagnostic delay.

The outcomes of diagnostic delay

Delayed diagnosis can lead to adverse clinical outcomes and severe disease burden, including stricture development, fistula formation, and intestinal dysplasia[7]. Undetected and untreated patients with IBD can also lead to a significant burden to society and healthcare expenditure. Therefore, earlier recognition and treatment are key measures to improve clinical outcomes and disease burden of IBD.

The factors of diagnostic delay

Diagnostic delay is multifactorial, including patient and healthcare related factors. Poor public awareness of IBD, low physician confidence in identifying the early symptoms of IBD, and difficulty distinguishing clinical symptoms of IBD from other gastrointestinal disorders can lead to diagnostic delay[8]. Some studies showed that the average diagnosis time of IBD is significantly longer in low-middle income countries than in high income countries. It suggests that accessibility of specialist medical services for patients with IBD remains an important issue for diagnostic delay.