II.1.2 Endoscopy of ulcerative colitis

Dr. Javier Castro Alvariño
Complejo Hospitalario Universitario de Ferrol

 

II.1.2.1. Endoscopy in diagnosing ulcerative colitis

There are multiple indications for performing a colonoscopy in patients with ulcerative colitis (UC), including the initial diagnosis of the disease, differentiating it from Crohn’s Disease (CD), infectious colitis and other causes of colitis, the evaluation of the extension of the colonic involvement, the determination of the activity and severity of the disease, monitoring of the response to medical treatment and the early detection of dysplasia and colorectal cancer.

 

ENDOSCOPIC DIFFERENTIAL DIAGNOSIS OF ULCERATIVE COLITIS

Colonoscopy and ileoscopy enable direct visualisation and biopsy of the rectal mucosa, colon and terminal ileum. Unless there is a contraindication due to very severe colitis or a possible toxic megacolon, a total colonoscopy should be performed with intubation of the distal ileum during the initial assessment of patients with a clinical presentation suggesting inflammatory bowel disease (IBD), including UC cases. Since sodium phosphate-based bowel cleansing preparations and non-steroidal anti-inflammatory drugs (NSAIDs) can cause mucosal abnormalities that simulate IBD, these agents should be avoided before the initial endoscopic assessment1.

Patients with other types of colitis may have clinical presentations and endoscopic findings similar to patients with IBD. Abnormalities may overlap and be unspecified, which is why taking biopsies and determining the clinical course are crucial. These types of colitis include infectious colitis (acute enterocolitis due to cytomegalovirus [CMV], Salmonella, Shigella, Isospora or Yersinia), drug-induced colitis, ischemic colitis and radiation colitis. Furthermore, the prolonged use of laxatives, especially cascara and senna, may lead to the presence of a cathartic colon, which may sometimes be a confusion factor. Other problems must be considered and carefully interpreted along with the symptoms and histopathology, including collagenous colitis and lymphocytic colitis, as well as microscopic colitis, which, despite its name, can be associated with endoscopic changes such as erythema and oedema (which rarely require surgery and have very low risk of malignancy).

Infectious colitis (Video 1) are the entities that most often can be confused with UC during the initial presentation. These often occur with abdominal pain, diarrhoea with blood and even involvement of the distal ileum. In a classic prospective study of patients who had acute haemorrhagic colitis, we found a bacterial or viral infectious cause in 38% of cases2. It is important to collect stool cultures and determine the Clostridium difficile toxin prior to or during the colonoscopy in order to aid in the differential diagnosis (Video 2). Moreover, biopsies in infectious colitis do not show typical signs of chronicity such as distorted crypt architecture, basal plasmacytosis, hyperplasia of the Paneth cells or metaplasia of the pyloric glands3.

Ischemic colitis (Video 3) has a varying segmental involvement distribution, although it is generally located in areas close to the splenic flexure or the right colon, respecting the rectum. Equally, the presence of diverticula and patchy focal impairment confined to the diverticular area must arouse suspicion of the existence of diverticulitis.

Proctitis or actin colitis have typical vascular abnormalities in the mucosa within the context of previous radiation therapy; certain regularly used medications must also be considered, especially NSAIDs, in the initial assessment of patients with unspecified endoscopic lesions (Fig. 1)4.

FIGURA 1. Colitis secundaria a la ingestade AINE.

Cytomegalovirus and ulcerative colitis infections

Colitis due to Cytomegalovirus CMV is rare in immunocompetent patients. It occurs in 2–16% of patients who have received solid organ transplants and in 3–5% of patients with acquired immunodeficiency syndrome (AIDS). Several articles have examined the colonoscopic findings related to CMV infection in these patient subgroups, showing a spectrum of lesions varying from patchy erythema, exudates and microerosions to diffuse oedema, multiple erosions, deep ulcers and pseudo-tumoural lesions.

In patients with steroid-refractory UC, CMV infections have been documented in up to 27.3% of cases and in 9.1% of non-refractory colitis5,6. Colonoscopic findings in complicated UC due to a CMV infection have been evaluated and recently typical ulcerative changes have been described (Suzuki, et al.), such as mucosal defects, confluent ulcerations, longitudinal ulcers and irregular, cobblestone-like ulcers7, in which it is important to suspect and perform an early diagnosis of CMV infection in these cases. Although various methods have been developed, such as immunohistochemical histology, serology, CMV cultures, polymerase chain reaction (PCR) of the CMV genome and antigenaemia CMV, it is important to clinically suspect the diagnosis in patients with refractory UC for subsequent confirmation8 (Fig. 2, Fig. 3).

FIGURA 2. Colitis por CMV.

FIGURA 3. Colitis por CMV.

The value of endoscopy solely to differentiate IBD colitis from non-IBD colitis is limited. However, distinguishing between UC and CD is critical for developing a treatment plan. Collecting detailed information from the different colonoscopic parameters for diagnosis is important in order to differentiate CD and UC, because, once treatment is established, differentiating the information between both, such as the segmental or diffuse impairment and the absence of rectal mucosal damage, can be confusing9. At the time of colonosocopy, one must also establish the presence or absence of anal and perianal disease, which is more common within the context of CD.

In addition to the regular exclusions, the World Health Organization guidelines also recommend other considerations in the differential diagnosis of UC and CD10:

Chronic schistosomiasis.

Amebiasis.

Intestinal tuberculosis.

    .

Endoscopic criteria

The most useful endoscopic criteria for diagnosing UC (particularly after the initial endoscopy) are therefore continuous mucosal inflammation and rectal impairment in the absence of ileal or perianal disease, but there are various endoscopic findings that typically suggest UC. However, none of them is specific (Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8).

Erythema.

Oedema/loss of normal vascular pattern.

Granularity of the mucosa.

Spontaneous bleeding/friability.

Pseudo-polyps.

Erosions.

Ulcers.

FIGURA 4. Colitis ulcerosa.

FIGURA 5. CU. Friabilidad.

FIGURA 6. CU. Afec. continua.

FIGURA 7. Colitis ulcerosa.

FIGURA 8. CU. Úlceras confluyentes.

Granular appearance is manifested by changes in luminescence during colonoscopy. Instead of reflecting light in patchy areas, granular mucosa reflects a multitude of small dots of light, giving the appearance of “sandpaper”.

Inflammatory pseudo-polyps can also be seen in patients with severe UC (Video 4), although they are more common in chronic stages (Fig. 9) and occur due to inflammation (Video 5) and regeneration of the mucosa, which surrounds the ulcerations, resulting in the appearance of a cobblestone pattern (Video 6). Pseudo-polyps do not return when treated and tend to persist even in the presence of quiescent disease. They cannot be distinguished from neoplastic polyps solely on the basis of their endoscopic appearance (Video 7) and, therefore, it may be necessary to perform a histopathologic exam of the atypical polyps in order to exclude dysplasia or malignancy11.

FIGURA 9. CU. fases crónicas

Ulcerative colitis versus Crohn’s Disease (Table I)

Macroscopically, CD is typically discontinuous, with interlesional areas of normal mucosa (skip areas). Ulcerations tend to be linear and often lead to the classic cobblestone appearance in the mucosa. CD can affect any segment of the gastrointestinal tract (GIT), while CD basically affects the large intestine, with some aspects that we will analyse.

Microscopically, inflammation in UC and CD can be similar, although non-caseating granulomas are specific in CD, being present in 60% of CD samples. Inflammation in CD is usually transmural, while in UC it is limited to the submucosa and mucosa. Unfortunately, differential diagnosis is not always possible preoperatively. All large series of proctocolectomies include a subgroup of patients (around 10%) who are preoperatively considered to be UC carriers but are later diagnosed with CD.

The traditional idea that UC only affects the large intestine has changed over time. Significant gastroduodenal inflammation has been reported in children with UC, although the presence of aphthoid ulcers is considered linked to CD12. In addition, the patchiness of the colonic mucosa with presence of skip areas can be seen endoscopically during the treatment phase in up to 38% of the UC cases, which poses diagnostic concerns. Likewise, uninjured rectum may appear at any time during treatment in up to 44% of the cases (Video 8)13. The presence of proximal disease can be seen after proctocolectomy and capsule endoscopy (CE) tests have shown patchy inflammation in the proximal intestine in patients with chronic pouchitis after proctocolectomy with ileoanal reconstruction.

KEYS TO CONSIDER WHEN DIAGNOSING

 

Activity

There is no specific finding for diagnosing UC. The most relevant facts are the continuous and confluent involvement of the colon with clear delimitation of the inflammation, at times abrupt, and rectal involvement (Video 9)14. Endoscopic severity is better reflected due to the presence of mucosal friability, spontaneous bleeding and deep ulcers.

A wide variability is well known in the interpretation of the endoscopic findings: granularity, abnormal vascular pattern, bleeding-friability and ulceration in varying degrees have been established as predictors of overall endoscopic activity15 (Video 10).

The UC Endoscopic Index of Severity (UCEIS) is the first validated index for the assessment of overall endoscopic activity (Table IV). The final model incorporates the vascular pattern, the presence of bleeding and the presence of ulcerations with accurate definitions and 3 or 4 levels of severity as measurable parameters, which explain almost 90% of variations in determining overall activity16. Recently, the previously developed UC Colonoscopic Index of Severity (UCCIS) has also been validated17.

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Establishing diagnosis

The procedure of choice in patients with suspected UC is colonoscopy with ileoscopy and segmental biopsies that include the rectum. Sigmoidoscopy would be the first-line procedure for confirming the active disease in patients with severe or fulminant symptoms of colitis with risk of perforation, in which the performance of a simple abdominal x-ray must be included. Colonoscopy also helps to establish diagnosis and extension in most cases, often predicting the presence of deep ulcerations, unfavourable progression and the need for subsequent surgery18.

Oesophagogastroscopy with mucosal biopsies is recommended in patients with upper GIT symptoms, and CE represents an advancement in the study of the intestine, but broad prospective studies are necessary to show its relevance in diagnosing UC. CE is a potentially useful tool for classifying patients with indeterminate colitis (IC). Although a normal CE does not exclude CD, it has a very high predictive value19.

Extended analysis

Distribution of the disease

In order to determine the distribution of the disease, the consensus of the Montreal Classification has been adopted, which describes the maximum macroscopic involvement during a colonoscopy and has been classically used as a predictor of the subsequent course (Table II). Percentages according to the initial location vary according to the series, predominantly rectosigmoiditis (40–45%) over left colitis (15–20%) or extensive colitis or pancolitis (35–40%).

Extended analysis is valued as a prognosis factor (it is the primary factor at diagnosis) and as a datum to determine the therapeutic strategy (oral, topical or intensive) or the subsequent assessment of dysplastic risk and the development of colorectal cancer. However, the relevance of the microscopic extension and the macro-microscopic correlation are not well defined20. This is also valid for extension-based classification, considering that it may vary over time, underlying the dynamic nature of the disease21.

Atypical lesion: discontinuous inflammatory pattern

Caecal segmental impairment. Sometimes left colitis and its natural progression are observed to be similar to these when they are isolated.

Appendicular impairment. Can occur in up to 75% of patients with UC. It has been associated with worse progression of the disease and higher risk of pouchitis after ileoanal anastomosis22 (Fig. 10). Histologically confirmed appendectomy due to appendicitis at early ages could have a protective role against the subsequent development of UC or in reducing its severity23.

FIGURA 10. Colitis ulcerosa. Afectación apendicular

Ileitis due to reflux or backwash and impairment of other segments of the small intestine (SI). Is observed in up to 20% of patients with pancolitis. Erosions in patients without caecal impairment may occur rarely, perhaps simply in pathogenic relationship with the reflux of caecal content to the distal ileum. A more severe course has been suggested in these patients24.

Pouchitis. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients who need colectomy, significantly improving quality of life, although complications are common: other than early post-operative complications, such as abscesses or dehiscences in the pouch, they can appear in the long run as pouchitis, cuffitis, irritable pouch syndrome and CD of the pouch. Pouchitis is the most common, long-term complication, and symptomatic assessment alone is not diagnostic, but endoscopy with biopsies is necessary to confirm it and exclude other causes for the symptoms. It is easier to use a gastroscope to assess the pouch, because of its easy manoeuvrability. Also, endoscopic therapy can be performed as a dilation of the pouch. Endoscopic assessment is also useful in symptomatic patients with ileorectal anastomosis or ileostomy25.

 

UPPER ENDOSCOPY AND ANALYSIS OF THE SMALL INTESTINE IN ULCERATIVE COLITIS

 

Gastroduodenoscopy

In addition, patients with UC can have inflammation in the upper GIT, as diffuse duodenitis. In these cases, endoscopic signs include oedema, erythema, erosion and thickened mucosal folds. A histological exam can show active chronic inflammation with distortion of the mucosal architecture, villous atrophy and intraepithelial lymphocytosis. Other applications of gastroduodenoscopy (OGD) with biopsies of the SD in patients with IBD include the assessment of concomitant coeliac disease, eosinophilic enteritis, common variable immunodeficiency and neoplasm in the SI.

The assessment of the rest of the SI apart from ideocolonoscopy is not recommended on a routine basis for UC, except in atypical cases or with diagnostic difficulty, in which case MR enterography or CE may be necessary to exclude CD. Nevertheless, the assessment of a significant stenosing pathology should exclude the use of CE and propose alternative imaging tests such as computed tomography (CT) enterography or thorough MR enterography11,26.

In patients with symptomatic stenosis, endoscopy is indicated for characterisation and biopsies that enable the exclusion of malignancy, especially in the context of UC, in which a stenosis must be considered malignant until proven otherwise and, if the stenosis exam is not adequate, surgical resection should be considered. Stenosis found within the context of CD is more likely to be benign, although biopsies are necessary whenever possible.

Capsule endoscopy

CE enables the direct and minimally invasive visualisation of the mucosa of the SI. It can help in identifying superficial lesions not detected by conventional radiology or endoscopy and in differentiating CD vs UC or IC. Not all superficial mucosal lesions in the SI are necessarily indicative of IBD, and entities such as infection, ischemia, radiation and drug damage particularly NSAIDS, should be considered, the same as in the colon. Furthermore, it has been reported that up to 14% of healthy individuals present mucosal disruption and other unspecified abnormalities when CE is administered.

Enteroscopy

Single- or double-balloon enteroscopy, often with a higher yield when used orally, have a limited role in the management of patients with IBD, fundamentally in the case of UC. However, in the presence of lesions seen in other imaging tests that are not accessible, push enteroscopy enables endoscopic and histologic assessment, as well as therapeutic interventions. Intraoperative enteroscopy has also been used in selected patients with IC at the time of colectomy and ileoanal pouch anastomosis.

Key points in the endoscopic diagnosis of ulcerative colitis

• Colonoscopy and ileoscopy should be performed in the initial evaluation of IBD and used to differentiate UC from CD (B).

• Mucosal biopsy is important for diagnosing IBD and can help to differentiate UC from CD (B).

• When colonoscopy is contraindicated, flexible sigmoidoscopy can provide an adequate diagnosis (C).

• Upper gastrointestinal endoscopy can help in the diagnosis and characterisation of IBD
when other tests have been negative, and in differential diagnosis in the case of indeterminate colitis (B).

• Capsule endoscopy (CE) is a less invassive evaluation technique of the small intestine, and it has been observed
to be more sensitive than conventional endoscopy and radiologic techniques in detecting small mucosal lesions (B).

• In patients with IBD and confirmed or suspected high-grade stenosis, CE should not be used, being replaced by alternative imaging tests such as CT enterography or MR enterography by using diluted contrast (C).

• A colonic stenosis within the context of UC must be considered malignant until proven otherwise. If an adequate assessment cannot be performed, colectomy may
be indicated (C).

 

ENDOSCOPIC ACTIVITY INDICES IN ULCERATIVE COLITIS

Several activity indices have been used to establish the severity of endoscopic lesions, primarily in therapeutic analyses27. The instrument most used in practice during the last few decades is the Mayo Index, which combines clinical and endoscopic signs, empirically including scores dependent upon the assessment of the patient, such as the frequency of bleeding and the number of stools, along with an overall activity assessment by the physician28. The Mayo Index establishes a range of 0–12, with the maximum values corresponding to a more severe disease. The endoscopic subindex ranges vary between 0–3.

Previously, in the beginning of the 1950s, Truelove had already recognised the need for a measurement that was more objective than symptoms in determining therapeutic effectiveness in UC, in which an inaccurate correlation is observed between clinical remission and the appearance of sigmoidoscopic findings for the purpose of hydrocortisone treatment29. Subsequently, Baron et al. critically evaluated endoscopically available items in order to measure activity, and they detected significant differences in its reproducibility between expert observers30.

In recent years, an activity index review process has been carried out, as well as primary objectives with regards to pharmacological efficacy in clinical trials, in view of the differences between investigators and drug evaluation agencies in the assessment of the response to treatment. Generally, populations enrolled in clinical trials are heterogeneous and the difficulty to determine concepts such as refractibility in UC is problematic due to the variability of progression. The consensus process is complex and must set the foundation for determining the optimal instruments for assessing UC, in such a way that they can be validated and applied in medical practice30.

The gold standard for establishing the activity of the disease in UC should be a diagnostic test that could reliably predict the course of the disease by increasing the value of the clinical assessment. Endoscopy is a final, but expensive and invasive, endpoint, for which it is important to establish endoscopic indices that correlate well and are better predictors of progression than symptoms or biomarkers such as PCR, calprotectin or lactoferrin. The burden of proof to show superiority must lie on endosocopy, given that it is expensive and invasive.

Some classic activity indexes

Tools based solely on endoscopic activity:

Mayo Subindex: flexible rectosigmoidoscopic assessment.

Baron Index: assessment of the rectal mucosa by using a rigid rectoscope in patients with UC and establishing a 4-point scale (0–3), primarily based on the severity of bleeding. Oddly, the presence of ulcers is not considered. Interobserver variations have been contemplated for all variables30.

Modified Baron Index: Fegan et al. performed serial endoscopic assessments during an a4b7-integrin-controlled clinical trial for active UC and described a 5-point scale (0–4), modifying the Baron Index and defining endoscopic remission as 0 and endoscopic response as a 2 degree drop in basal activity32.

Endoscopic Rachmilewitz Index: utilised during a comparative controlled clinical trial of mesalazine with an enteric coating and sulfasalazine for the treatment of active UC. 4 items were described: granulations, vascular pattern, vulnerability of the mucosa and mucosal damage (mucus, exudate, fibrin erosions and ulcers). The score ranges between 0–12 points and endoscopic remission is determined by an endoscopic index between 0–4 points33.

Tools combining clinical and endoscopic signs:

Mayo Activity Index (Table III).

Sutherland Index: established during a controlled clinical trial with mesalazine enemas. It measures 4 variables (frequency of stools, rectorrhagia, mucosal appearance and assessment of severity of symptoms) ranging 0–12. Although a score <2.5 has not been formally validated, it correlates well with patient-defined remission34,35.

Tools that measure activity based on biological clinical signs:

Truelove-Witts Index: is a ground-breaking instrument, despite numerous limitations that do not enable validation, since the index does not adequately define the concepts of remission, improvement or worsening. It can be used to establish inclusion criteria in clinical trials, but it is not discriminative in measuring changes in activity29.

Rachmilewitz Clinical Index.

UC Clinical Index (Feagan).

Patient-Defined remission Index: defined by Higgins et al. in 200536, based on a survey of 56 patients on the question: “Is your UC in remission (inactive)?” Only “Yes” and “No” answers were accepted. The questions was asked again 1–14 months later by using a subjective 7-point activity scale. The Patient-Defined remission Index showed good sensitivity (86%) and specificity (76%) for defining remission based on the modified Baron score (0–2).

Tools that measure quality of life.

Tools that measure histologic activity:
the correlation with clinical indices is varied and even poor, and there is currently no single optimal histologic index, although it is recommended that they be include as a secondary objective in the evaluation of therapeutic efficacy37.

 

Recently validated endoscopic indices

UCEIS: A 2-phase analysis that used a video library of 670 video sigmoidoscopies of patients with Mayo scores between 0–11, supplemented with 10 videos of 5 people without UC and five hospitalised patients with severe acute UC. In phase 1, the study evaluated the variability in endoscopic interpretation among specialists in IBD and established definitions for endoscopic descriptive terms. Phase 2 determined the inter- and intraobserver variations to construct a model to assess the global severity of the disease. The final model incorporates the vascular pattern (3 grades), bleeding (4 grades) and the presence of ulcers (4 grades) with accurate definitions that explain almost 90% of variations in determining overall activity. Friability is excluded from the endoscopic description of severity14,16 (Table IV).

UCCIS: Samuel et al.16 have gone one step forward by assessing the entire colon, unlike the sigmoidoscopic assessment of most of the previous indices. The potential value of UCCIS was established by 8 experts that examined videos of 4 colonic segments (rectum, sigmoid, descending, transverse and ascending/caecum) in 50 patients with UC during the withdrawal phase. Every segment was punctuated according to the vascular pattern, granularity, friability, ulceration and severity of the overall damage. Generally, there was coincidence in ratings between experts with the exception of friability. A good degree of correlation with the biologic activity parameters (PCR, hemoglobin [Hb], albumin) was also determined, which provided support for its validation.

 

SEVERE ULCERATIVE COLITIS

The first attempt to identify patients with severe UC and poor a prognosis was made by Truelove and Witts in 1955, who defined the situation as:

6 bloody stools/day.

• Temperature 37.8º.

• Peripheral pulse 90 bpm.

• Haemoglobin 10.5 g/100 ml

• Erythrocyte sedimentation rate (ESR) 30 mm per hour28.

These criteria continue to be used due to their simplicity, objectivity and ease of application in practice. There are many more key predicting factors or acceptable prognostic criteria primarily based on variations of the criteria established by Lennard Jones et al. in 197538 (Table V).

Tabla_SEC2_01_02_01_T05

It is generally accepted that approximately 15% of patients with UC develop a severe acute or “fulminant” attack and at least 30% require a colectomy39,40. The prognosis for UC has changed significantly in the past few decades and most epidemiological studies now indicate that life expectancy in patients is similar to that of the general population, although some show a minimum increase in mortality41. In the beginning of the 20th century, it was considered a fatal disease with death rates close to 75%, but as of 1950 it reduced to 25% in the first year after diagnosis42.

Although corticoids remain a pivotal medical treatment for severe UC, new treatment options appeared for steroid refractory patients to avoid colectomies such as ciclosporin43,44 or more recently, intensive treatment with biological drugs45. A risk assessment index (Table VI) that helps to identify non-corticoid IV-responding patients could be useful to provide a second line of treatment or surgery. Ho et al.46 propose an assessment index developed from a cohort of patients after a statistical analysis on multiple regression, with the objective of establishing the probability of response to initial steroidal treatment. However, with the improvement of available medical treatments in severe UC, the objective can be geared towards identifying patients who would benefit from a second line of treatment by selecting subjects for early surgery. Consensus and stratification of patients according to risks in future therapeutic trials is basic for improving treatment in the most severe cases.

After assessing the progression and prognostic factors following steroid IV treatment in severe outbreaks after the failure of oral steroids, a Korean group concluded that, in addition, a considerable number of patients remained cortico-dependent or oral steroid refractory, with the duration of steroid treatment and haemoglobin levels being the factors most strongly associated with poor progression. Prospective studies will be needed to determine the optimal time for steroid withdrawal and confirm the results47.

Key points: prognosis for severe ulcerative colitis

• Acute breakout of severe UC must be considered a medical emergency.

• Early detection of prognostic factors significantly reduces mortality in these cases.

• The finding of a distended small intestine in simple abdominal x-rays identifies patients with a high risk of developing toxic megacolon.

• Ciclosporin or infliximab can be used in patients with severe UC when there is no clear and quick response to an intensive treatment with steroid IV.

• A particularly aggressive treatment plan is appropriate in patients with multi-organ dysfunction.

• The time of colectomy is without a doubt the most difficult and significant key clinical decision, and it must be agreed upon by the gastroenterologist and surgeon.

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INDETERMINATE COLITIS: IS IT IMPORTANT TO CLARIFY THE DIAGNOSIS?

 

Clinical relevance and concept

The term IC is disputed and has been used to describe IBD cases that cannot be classified as UC or CD. However, this concept has been applied variably, which, along with the intrinsic difficulties of the IBD diagnosis, has led to great confusion. Strictly speaking, the term indeterminate colitis should be utilised only in cases in which a colectomy has been performed and the histological findings do not allow for a final diagnosis. Throughout the progress, most patients remain diagnosed with unclassifiable colitis or show symptoms that suggest UC. Ileoanal pouch anastomosis can be performed in these cases with an expected functional progression similar to patients with UC but with increased post-operative pouch complications48.

Originally used by pathologists to describe colectomy specimens in which a diagnosis could not be determined, this term has been adopted by physicians to describe patients who, after standard medical assessment (colonoscopy, imaging tests, laboratory test and biopsies), could not be diagnosed as CD or UC (IBD unclassifiable), however, the original term of indeterminate colitis remained in the new ICD-10 codification, which will be implemented shortly. Its frequency is approximately 10% and has not changed in the past 30 years despite the introduction of new diagnostic models. Although there certainly are patients with a long-standing diagnosis of indeterminate colitis, suggesting that there may be a third entity, there is no appropriate method for determining this49,50.

Clarifying the diagnosis of indeterminate colitis is more significant in patients who have failed medical treatment and face radical surgery. The surgical gold standard for treating UC is total ileal pouch-anal anastomosis (IPAA). Traditionally, this surgery is not used in CD due to the high risk of complications. In retrospective series, in indeterminate colitis, post-surgical progress is not as favourable as in UC, but the risk of complications for the patients is less than if they had CD, which is relevant for the decision when proposing the surgical treatment of CD51.

Diagnosis

In addition to the usual diagnostic tools (colonoscopy, biopsy and radiologic imaging tests), the most reliable technique for assessing these patients is serology. The serological markers that have proven most useful for indeterminate colitis (although unspecified) are anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti-neutrophil cytoplasmatic antibodies (pANCA), also known as nuclear-specific antigens. Most patients with indeterminate colitis are negative for both52,53, meanwhile 80% of patients with CD are positive for ASCA50.

Therapeutic Management

Patients with IC are often treated the same as those who have UC from a medial treatment and surgical approach standpoint; it is important to consider that some patients with UC may have backwash ileitis, and that those who have CD may have ileal involvement, which can complicate things further when personalising the cases. Almost half of patients with IC will progress to be diagnosed with CD of the colon or UC, while the other half will maintain a long-term diagnosis54.

 

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