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Periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a relatively common autoinflammatory condition that primarily affects children. Although tendencies were reported for this syndrome, genetic variations influencing risk and disease progression are poorly understood. In this study, we performed next-generation sequencing for 82 unrelated PFAPA patients and identified a frameshift variant in the CARD8 gene (CARD8-FS). Subsequently, we compared the frequency of CARD8-FS carriers in our PFAPA cohort (13.9%) with a healthy local population group (3.2%) and found a significant association between the CARD8-FS polymorphism and risk for PFAPA syndrome (p = 0.012; odds ratio: 4.96 [95% confidence interval, 1.33-18.47]). Moreover, CARD8-FS carriers display a distinct PFAPA phenotype that is characterized by a higher prevalence of symptoms out of flares and oral aphthosis (both p = 0.02 compared with PFAPA patients without the frameshift variant). CARD8 encodes a protein component of the NLRP3 inflammasome, which plays an important role in inflammation and contributes to the pathology of various autoinflammatory diseases. We found that the CARD8-FS variant led to a truncated CARD8 protein lacking the FIIND and CARD domains. As a result, the mutant CARD8 protein lost the ability to interact with the NOD domain of NLRP3. In summary, these results identify a new CARD8 variant associated with PFAPA and further suggest that disruption of the interaction between CARD8 and NLRP3 can regulate autoinflammation in patients. [ABSTRACT FROM AUTHOR]

Background: The aim of our study is to describe clinical features, therapy, and outcome of children with inflammatory choroidal neovascularization (CNV)., Methods: Retrospective case series of children seen at the Jules-Gonin Eye Hospital between 2000 and 2024 with macular choroidal neovascularisation secondary to ocular inflammation., Results: Four children (one male, three females) developed a retro-foveolar neovascular membrane after a median time of 2.5 months (range 1 - 16 months) following uveitis onset. The median age at presentation was 12 years (range 5 - 12 years). The CNV presentation was unilateral in all four cases, with three patients having posterior uveitis and one panuveitis. Two patients had idiopathic bilateral granulomatous uveitis while the other two had suspected toxoplasmosis chorioretinitis. Idiopathic cases were treated with oral steroids, with one patient being additionally treated with adalimumab. Toxoplasmosis cases were managed with antibiotics and oral steroids. CNV treatment involved a single anti-VEGF injection in two cases, six injections in one case, and no injection in one case due to CNV inactivity. Median follow-up period was 4.25 years (range 0.75 to 11 years) and the median final best-corrected visual acuity was 0.9 (range 0.6 - 1.25). No recurrence of CNV was observed, despite uveitis reactivation in two cases., Conclusion: Anti-VEGF therapy is safe even in young children with minimal injections required to control the disease. Treating the underlying cause of uveitis with appropriate therapy is also crucial., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Adenosine deaminase 2 deficiency (DADA2) is a genetic auto- inflammatory disease that most often presents in childhood, but that can also have a late onset in adulthood. It is characterized by vasculitis, mainly of the skin and nervous system most often in the form of a stroke, associated to immunodeficiency and cytopenias. The diagnosis is made by measuring adenosine deaminase 2 (ADA2) enzymatic activity and confirming the presence of mutations in the ADA2 gene by genetic testing. The treatment of choice for the inflammatory phenotype is the early administration of anti-TNFa to avoid the risk of major neurological disabilities. In the case of severe hematological involvement, hematopoietic stem cell transplantation is the only curative treatment currently available., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Severe Combined Immunodeficiency (SCID) is one of the most severe forms of Primary Immunodeficiencies (PID) and leads to a potentially fatal course of disease without early and definitive treatment. Adequate management, from the first days of life, can improve the survival and outcome of patients with SCID. This can be achieved through newborn screening (NBS) based on the measurement of T-cell receptor excision circles (TREC). Already present in many countries, this NBS test was introduced in Switzerland in January 2019 on a pilot phase. In addition to the assessment of TRECs, the measurement of kappa recombinant excision circles (KREC) has also been introduced at the same time and allows the identification of severe forms of PID characterized by profound B cell lymphopenia., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Still's disease is a rare multifactorial disease associated with systemic inflammation. Systemic-onset juvenile idiopathic arthritis and adult-onset Still's disease are both pediatric and respectively adult forms of the disease with a cut-off age of 16 years. The disease is characterized by the following features : hectic fever > 39° C, arthralgia or arthritis, rash, neutrophilia and systemic inflammation. The prognosis of the disease is functional and vital. The evolution over time is variable : regression, evolution by relapses with regression at term and chronic joint evolution. This focus describes the two forms of the disease, their complications and the therapeutic options., Competing Interests: Sophie Georgin Lavialle est consultante occasionnelle pour Novartis et SOBI ; elle a été invitée à des congrès par SOBI.