Journal: Clinics and Research in Hepatology and Gastroenterology
First author: Rim Bourguiba
Country of study: France and Tunisia
CEREMAIA Tenon author(s): Marion Delplanque, Catherine Grandpeix-Guyodo, Léa Savey, Sophie Georgin-Lavialle
Reference: Bourguiba R, Delplanque M, Grandpeix-Guyodo C, Boursier G, Savey L, Cuisset L, Georgin-Lavialle S. When to suspect monogenic autoinflammatory diseases in patients with digestive symptoms? Clinics and Research in Hepatology and Gastroenterology. 2026;50:102820.
DOI: https://doi.org/10.1016/j.clinre.2026.102820
5 key points:
Some rare autoinflammatory diseases can cause abdominal pain, diarrhoea, digestive inflammation or symptoms that resemble inflammatory bowel disease.
Familial Mediterranean fever is the most common monogenic autoinflammatory disease and should be considered in people of Mediterranean origin with repeated inflammatory abdominal pain.
Associated signs such as recurrent fever, mouth ulcers, skin rashes, joint pain, macrocytic anaemia or family history should raise suspicion of an autoinflammatory cause.
Diagnosis is based on clinical assessment, inflammation markers, sometimes IL-18 measurement, and appropriate genetic testing.
Earlier diagnosis can reduce diagnostic delay, guide treatment and help prevent complications such as AA amyloidosis.
Introduction
Systemic autoinflammatory diseases are rare conditions caused by abnormal activation of the innate immune system, the body’s first line of defence. They can cause flares of inflammation with fever, pain, skin involvement, joint symptoms or digestive problems. In some patients, digestive symptoms are the main feature and may look like inflammatory bowel disease, such as Crohn’s disease.
Methods
This article is a narrative review of the medical literature. The authors describe the main monogenic autoinflammatory diseases that may cause digestive symptoms and highlight situations in which gastroenterologists should consider these diagnoses.
Results
Several diseases can cause abdominal pain, diarrhoea, colitis, digestive ulcers or inflammation that resembles Crohn’s disease. Familial Mediterranean fever is the most common, especially in people of Mediterranean origin. Other conditions include TRAPS, Mevalonate kinase deficiency, cryopyrin-associated diseases, VEXAS syndrome, A20 haploinsufficiency, and diseases linked to RIPK1, RELA, NFKB1, JAK1, STAT, PSTPIP1, ADA2, LACC1, XIAP or PLCG2. Warning signs include recurrent fever, unexplained inflammation in blood tests, mouth ulcers, skin rashes, joint pain, family history, Mediterranean origin, macrocytic anaemia or poor response to usual treatments for inflammatory digestive diseases.
Discussion
The article emphasizes that not all digestive inflammation should automatically be considered a typical bowel disease. An autoinflammatory disease may mimic inflammatory bowel disease, coexist with it, or be revealed by unusual digestive symptoms. Useful investigations may include inflammation markers, endoscopy, specific biomarkers such as IL-18, and above all appropriate genetic testing, ideally discussed with expert centres.
Conclusion
Rare autoinflammatory diseases should be considered when digestive symptoms are inflammatory, unexplained, recurrent or resistant to usual treatments. Early diagnosis can lead to more appropriate care, often using treatments that target inflammation, and may help prevent complications such as AA amyloidosis.