Histologic measurement tools for evaluation of disease activity in Crohn’s disease

What is Crohn's disease?

Crohn’s disease is a life-long (chronic), inflammatory disease of the gastrointestinal tract characterized by abdominal pain (cramping), rectal bleeding, diarrhoea, weight loss, and tiredness. The disease has a changing course with periods of symptoms (called 'active' disease or relapse) and periods without symptoms (called 'remission').

What is a histological scoring index?

A histological scoring index measures disease activity based on the examination of biopsy specimens from the bowel (small pieces of tissue removed from the bowel) under a microscope. Biopsy specimens are removed from the bowel during colonoscopy (a non-surgical procedure used to view the digestive tract using a camera) with biopsy forceps (instruments to grasp and remove pieces of tissue). Biopsies are then processed and assessed under microscope by a pathologist (a physician who interprets and diagnoses the changes caused by disease in tissues) who then rates disease activity using the index.

What did the researchers investigate?

It is important that histological scoring indices measure what they are supposed to measure (validity); that they detect change after treatment (responsiveness); that the scores are consistently reproducible (reliability); and that they can be easily utilized (feasibility). The researchers investigated whether studies have assessed the validity, responsiveness, reliability and feasibility of histological scoring indices.

What did the researcher find?

The researchers found that none of the existing histological scoring indices have been fully validated.

Authors' conclusions: 

Currently there is no fully validated histological scoring index for evaluation of Crohn's disease activity. Development of a validated histological scoring index for Crohn’s disease is a clinical and research priority.

Read the full abstract...

Histologic assessment of mucosal disease activity has been increasingly used in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently existing histologic scoring indices remain unclear.


A systematic review was undertaken to evaluate the development and operating characteristics of available histologic disease activity indices in Crohn's disease.

Search strategy: 

Electronic searches of MEDLINE, EMBASE, PubMed, and the Cochrane Library (CENTRAL) databases from inception to 20 July 2016 were supplemented by manual reviews of bibliographies and abstracts submitted to major gastroenterology meetings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organisation).

Selection criteria: 

Any study design (e.g. randomised controlled trial, cohort study, case series) that evaluated a histologic disease activity index in patients with Crohn’s disease was considered for inclusion. Study participants included adult patients (> 16 years), diagnosed with Crohn’s disease using conventional clinical, radiographic or endoscopic criteria.

Data collection and analysis: 

Two authors independently reviewed the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations were reviewed for inclusion and the study investigators were contacted as needed for clarification. Any disagreements regarding study eligibility were resolved by discussion and consensus with a third author.

Two authors independently extracted and recorded data using a standard form. The following data were recorded from each eligible study: number of patients enrolled; number of patients per treatment arm; patient characteristics: age and gender distribution; description of histologic disease activity index utilized; and outcomes such as content validity, construct validity, criterion validity, responsiveness, intra-rater reliability, inter-rater reliability, and feasibility.

Main results: 

Sixteen reports of 14 studies describing 14 different numerical histological indices fulfilled the inclusion criteria.

Inter-rater reliability was assessed in one study. For the Naini and Cortina Score, estimates of correlation were 'almost perfect', ranging from r = 0.94 to 0.96. The methodological quality of this study with respect to reliability was 'good'.

With respect to validity, correlation estimates between various histological scoring systems and Crohn's disease activity as measured by objective markers of inflammation (including C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and fecal lactoferrin); endoscopic disease activity scores; clinical disease activity scores; and quality of life questionnaires were reported. Comparisons between histologic scoring indices and endoscopic scoring indices ranged from no correlation to 'substantial' (r = 0.779). The methodological quality of the studies that explored validity ranged form 'poor' to 'good'.

Responsiveness data were available in seven studies. After subjects were administered a treatment of known efficacy, statistically significant change in the index score was demonstrated in five studies with respect to six indices. Two studies failed to indicate whether there was statistically significant change in the index score post-treatment. With regard to methodological quality, six of the studies were rated as 'poor' and one of the studies was rated as 'fair'.

Feasibility was assessed by one study. The Naini and Cortina Score was shown to be simple to use and feasible for every given case.