Fonollosa A, Carreño E, Vitale A, Jindal AK, Ramanan AV , et al.
Frontiers in ophthalmology •
Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still's disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome.
Gómez-Caverzaschi V, Yagüe J, Espinosa G, Mayordomo-Bofill I, Bedón-Galarza R , et al.
Autoimmunity reviews •
Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders. To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations. Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected. Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs. The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options.
La Torre F, Sota J, Insalaco A, Conti G, Del Giudice E , et al.
Frontiers in medicine •
To evaluate the potential role of K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction. The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months. The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [ < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis ( < 0.001), oral aphthae ( < 0.001) and cervical lymphadenopathy ( < 0.001) significantly decreased following SSK12. SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome.