Overcoming difficulty in diagnosis and differential diagnosis of Crohn’s disease: the potential role of serological and genetic tests

Abstract

Crohn’s disease (CD) represents a heterogeneous group of chronic inflammatory disorders with various phenotypes. Establishing a definite diagnosis of CD should be based upon a combined assessment of clinical, endoscopic, radiological and pathological features. Although segmental disease distribution, transmural inflammation and non-caseating epithelioid granulomas have been considered as a ‘hallmarks’ for CD, clear diagnosis of CD in some patients has been challenging, due to overlapping endoscopic, radiographic and histologic features with other inflammatory bowel disease-like conditions. Laboratory markers (serological and genetic tests) may provide additional clues for the diagnosis and differential diagnosis of CD. This review focuses on the application of the currently available serological and genomic markers and in diagnosis and differential diagnosis of CD.

Keywords:

• biomarkers
• Crohn’s disease
• diagnosis
• differential diagnosis
• genetic testing
• inflammatory bowel disease
• serology

Financial & competing interests disclosure

B Shen is supported by the Ed and Joey Story Endowed Chair. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Crohn’s disease (CD) represents a spectrum of disease process with various locations, phenotypes and prognoses.

• The complete exclusion of chronic infectious enteritis/colitis, particularly intestinal tuberculosis, can be challenging.

• Laboratory testing plays a complimentary role in the diagnosis, differential diagnosis and prognosis, and routine clinical, endoscopic, histologic and radiographic evaluations.

• Bacteria-based serology may provide some clues for the pathogenesis of inflammatory bowel disease, especially in gut microbiome and interaction between microbiome and gut and systemic immunity.

• Bacteria-antigen-based serological tests are valuable for the diagnosis and differential diagnosis of CD, in the setting of known pre-test probability.

• A combined assay of various serology tests provide a more powerful diagnostic value than a single individual tests.

• Serology tests may be more valuable when prognostic markers, rather than diagnostic modalities are used.

• NOD2/CARD15 mutations, with the best-so-far delineated pathogenic pathway in ID, have been shown to have the strongest association with disease location, disease behavior and prognosis, among all currently reported inflammatory bowel disease-related single nucleotide polymorphism mutations. However, NOD2/CARD15 has not been a part of routine clinical evaluation for diagnosis, differential diagnosis and disease monitoring in CD.