Diagnosis traps for patients with acquired NLRP3 mutation (CAPS)

First author: M. DELPLANQUE et al,

Journal: European Journal of Internal Medicine

Reference: https://doi.org/10.1016/j.ejim.2024.01.028

Summary:

The article highlights the diagnostic challenges of cryopyrin-associated periodic syndromes CAPS, caused by NLRP3 gene mutations. These autoinflammatory diseases include three main forms: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome.

The study presents two cases of patients with acquired somatic NLRP3 mutations, illustrating the difficulty of diagnosis due to atypical phenotypes:

• Patient 1 (P1): A 46-year-old woman with neuroinflammatory symptoms (persistent headaches, aseptic meningitis, hearing loss), initially misdiagnosed. A somatic M406I mutation was identified after 10 years of diagnostic wandering, explaining her atypical presentation. Treatment with anti-IL-1 drastically improved her condition.

• Patient 2 (P2): A male patient with severe CINCA syndrome since infancy, presenting with urticaria, arthritis, and growth delay. His genetic diagnosis was challenging, and the M406V mutation was only detected at the age of 15 using deep sequencing techniques.

The authors emphasize that somatic mutations in the NACHT domain of NLRP3 lead to constitutive activation of the inflammasome, resulting in excessive IL-1β production and severe chronic inflammation. The study underscores the importance of advanced genetic sequencing to detect these mutations, particularly in atypical cases.

Conclusion

Identifying somatic mutations in NLRP3 is crucial to avoid misdiagnosis and ensure effective treatment. Diagnostic delays can be prolonged in the absence of classic clinical signs (such as urticaria), and next-generation sequencing is essential for detecting low-percentage mosaicism.

Nouvelles mutations CAPS.

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