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Unsupervised clustering of undifferentiated systemic autoinflammatory diseases (USAID)

Jeanne CHAUFFIER
Oct 18
1 min read
Mieux comprendre et regrouper les maladies auto-inflammatoires systémiques d’origine indéterminée

First author: Jeanne Chauffier

Journal: European Journal of Internal Medicine

Summary author: Jeanne Chauffier


Background:   

Undifferentiated systemic autoinflammatory diseases (USAID) comprise a heterogeneous group of disorders characterized by recurrent systemic inflammation without an identifiable monogenic cause.  


Objective:  

To describe the phenotypic and therapeutic features of adult USAID and identify phenotypic clusters. 


Methods: 

We conducted a retrospective single-center study at the French Reference Center for Autoinflammatory Diseases between 2010 and 2025. USAID was defined as recurrent systemic attacks with ≥3 documented C-reactive protein (CRP) elevations and no pathogenic variant identified. Therapeutic response was classified as complete (CR) or partial (PR). Hierarchical cluster analysis included clinical and biological variables. 


Results:  

Among 150 patients (65.3% women; median age at onset 14 [0–64] years), recurrent attacks occurred in 87.3%. The most frequent manifestations were cutaneous (87.3%), fever (84%), asthenia (80%), musculoskeletal (79.3%), and abdominal involvement (63.3%). Colchicine was prescribed in 56.7% (CR 8.2%, PR 44.7%). Biologic therapies included anti-TNFα (n = 32; CR 21.9%, PR 31.3%), anti-IL-1 (n = 24; CR 25%, PR 16.7%), anti-IL-6 (n = 22; CR 31.8%, PR 31.8%), and JAK inhibitors (n = 16; CR 18.8%, PR 37.5%). 

Four clusters were identified:  

Cluster 1 (15.3%): fever, aphthous ulcers, pharyngitis, abdominal pain and lymphadenopathy.  

Cluster 2 (27.3%): brief attacks, frequent urticaria and abdominal pain.  

Cluster 3 (18.7%): prolonged attacks, prominent arthralgia, arthritis, and myalgia.  

Cluster 4 (38%): predominantly men, higher age at the onset, frequent neutrophilic dermatoses.  

Treatment responses did not differ significantly between clusters.  


Conclusion:  

Adult USAID patients can be subdivided into four clusters. Phenotypic stratification may help structure diagnostic reasoning and guide future therapeutic research. 


 


 
 
 

When to suspect monogenic autoinflammatory diseases in patients with digestive symptoms?

Rim BOURGUIBA
Jun 30
2 min read

Updated: Jul 22

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


When to suspect monogenic autoinflammatory diseases in patients with digestive symptoms?

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.


 
 
 
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