Exploring relief for Behçet's disease refractory oral ulcers: a comparison of TNF inhibitors versus apremilast.

OBJECTIVES: Oral and genital ulcers are the hallmark manifestation of Behçet's disease (BD), significantly impacting patients' quality of life. Our study focuses on comparing the effectiveness and safety of TNF inhibitors (TNFis) and apremilast in controlling oral ulcers of BD, aiming to provide evidence-based guidance for physicians in selecting appropriate treatment modalities. METHODS: A retrospective analysis was performed on BD patients treated between December 2016 and December 2021 with TNFis or apremilast for refractory oral ulcers. The study assessed treatment response by the absence of oral ulcers at 3 and 6 months, with additional evaluations for genital ulcers and articular involvement. RESULTS: The study included 78 patients, equally allocated between TNFis and apremilast treatments. Both groups showed significant oral ulcer reduction at 3 (p< 0.001) and 6 months (p= 0.01) with no significant difference between the treatments. Apremilast had a notable corticosteroid-sparing effect by the 3-month follow-up, persisting through 6 months. Both treatments were equally effective in reducing genital ulcers, with TNFis showing greater effectiveness in addressing articular involvement. Apremilast had a higher discontinuation rate due to gastrointestinal side effects. CONCLUSION: TNFis and apremilast are both effective for treating BD refractory oral ulcers. While TNFis may offer broader benefits for other disease manifestations, apremilast is distinguished by its corticosteroid-sparing effect, especially for patients with a milder disease phenotype. Treatment selection should consider individual disease severity and clinical features to ensure a personalized and effective management strategy.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

Investigating cross-orientation inhibition with continuous tracking.

We investigated cross-orientation inhibition with the recently developed continuous tracking technique. We designed an experiment where participants tracked the horizontal motion of a narrow vertical grating. The target was superimposed on one of three different backgrounds, in separate sessions: a uniform gray background or a sinusoidal grating oriented either parallel or orthogonal to the target. Both mask and target where phase reversed. We cross-correlated target and mouse movements and compared the peaks and lags of response with the different masks. Our results are in agreement with previous findings on cross-orientation inhibition: The orthogonal mask had a weak effect on the peaks and lags of correlation as a function of target contrast, consistently with a divisive effect of the mask, while the parallel mask acted subtractively on the response. Interestingly, lags of correlation decreased approximately linearly with contrast, with decrements of the order of 100 ms, even at 10 times the detection threshold, confirming that it is possible to investigate behavioral differences above threshold using the continuous tracking paradigm.

Still's disease continuum from childhood to elderly: data from the international AIDA Network Still's disease registry.

OBJECTIVE: Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease. METHODS: Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease. RESULTS: A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments. CONCLUSIONS: Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages.

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease.

Introduction: The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment. Methods: Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent. Results: No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment. Conclusion: Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment.

Active vision gates ocular dominance plasticity in human adults.

Primary visual cortex (V1) retains a form of plasticity in adult humans: a brief period of monocular deprivation induces an enhanced response to the deprived eye, which can stabilize into a consolidated plastic change1,2 despite unaltered thalamic input3. This form of homeostatic plasticity in adults is thought to act through neuronal competition between the representations of the two eyes, which are still separate in primary visual cortex4,5. During monocular occlusion, neurons of the deprived eye are thought to increase response gain given the absence of visual input, leading to the post-deprivation enhancement. If the decrease of reliability of the monocular response is crucial to establish homeostatic plasticity, this could be induced in several different ways. There is increasing evidence that V1 processing is affected by voluntary action, allowing it to take into account the visual effects of self-motion6, important for efficient active vision7. Here we asked whether ocular dominance homeostatic plasticity could be elicited without degrading the quality of monocular visual images but simply by altering their role in visuomotor control by introducing a visual delay in one eye while participants actively performed a visuomotor task; this causes a discrepancy between what the subject sees and what he/she expects to see. Our results show that homeostatic plasticity is gated by the consistency between the monocular visual inputs and a person's actions, suggesting that action not only shapes visual processing but may also be essential for plasticity in adults.

The role of neural oscillations in visuo-motor communication at the time of saccades.

Saccadic eye-movements are fundamental for active vision, allowing observers to purposefully scan the environment with the high-resolution fovea. In this brief perspective we outline a series of experiments from our laboratories investigating the role of eye-movements and their consequences to active perception. We show that saccades lead to suppression of visual sensitivity at saccadic onset, and that this suppression is accompanied by endogenous neural oscillations in the delta range. Similar oscillations are initiated by purposeful hand movements, which lead to measurable changes in responsivity in area V1, and in the connectivity with motor area M1. Saccades also lead to clear distortions in apparent position, but only for verbal reports, not when participants respond with rapid pointing, consistent with the action of two separate visual systems in neurotypical adults. At the time of saccades, serial dependence, the positive influence on perception of previous stimulus attributes (such as orientation) is particularly strong. Again, these processes are accompanied by neural oscillations, in the alpha and low beta range. In general, oscillations seem to be tightly linked to serial dependence in perception, both in auditory judgments (around 10 Hz), and for visual judgements of face gender (14 Hz for female, 17 Hz for male). Taken together, the studies show that neural oscillations play a fundamental role in dynamic, active vision.

Harnessing brain plasticity to improve binocular vision in amblyopia: An evidence-based update.

Amblyopia is a developmental visual disorder resulting from atypical binocular experience in early childhood that leads to abnormal visual cortex development and vision impairment. Recovery from amblyopia requires significant visual cortex neuroplasticity, i.e. the ability of the central nervous system and its synaptic connections to adapt their structure and function. There is a high level of neuroplasticity in early development and, historically, neuroplastic responses to changes in visual experience were thought to be restricted to a "critical period" in early life. However, as our review now shows, the evidence is growing that plasticity of the adult visual system can also be harnessed to improve vision in amblyopia. Amblyopia treatment involves correcting refractive error to ensure clear and equal retinal image formation in both eyes, then, if necessary, promoting the use of the amblyopic eye by hindering or reducing visual input from the better eye through patching or pharmacologic therapy. Early treatment in children can lead to visual acuity gains and the development of binocular vision in some cases; however, many children do not respond to treatment, and many adults with amblyopia have historically been untreated or undertreated. Here we review the current evidence on how dichoptic training can be used as a novel binocular therapeutic approach to facilitate visual processing of input from the amblyopic eye and can simultaneously engage both eyes in a training task that requires binocular integration. It is a novel and promising treatment for amblyopia in both children and adults.

Serial dependence in orientation judgments at the time of saccades.

We actively seek information from the environment through saccadic eye movements, necessitating continual integration of presaccadic and postsaccadic signals, which are displaced on the retina by each saccade. We tested whether trans-saccadic integration may be related to serial dependence (a measure of how perceptual history influences current perception) by measuring how viewing a presaccadic stimulus affects the perceived orientation of a subsequent test stimulus presented around the time of a saccade. Participants reproduced the position, and orientation of a test stimulus presented around a 16° saccade. The reproduced position was mislocalized toward the saccadic target, agreeing with previous work. The reproduced orientation was attracted toward the prior stimulus and regressed to the mean orientation. These results suggest that both short- and long-term past information affects trans-saccadic perception, most strongly when the test stimulus is presented perisaccadically. This study unites the fields of serial dependence and trans-saccadic perception, leading to potential new insights of how information is transferred and accumulated across saccades.

The administration of methotrexate in patients with Still's disease, "real-life" findings from AIDA Network Still Disease Registry.

OBJECTIVES: To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect. METHODS: Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry. RESULTS: In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy. CONCLUSIONS: Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent.

The duration effect of short-term monocular deprivation measured by binocular rivalry and binocular combination.

The ocular dominance shift observed after short-term monocular deprivation is a widely used measure of visual homeostatic plasticity in adult humans. Binocular rivalry and binocular combination techniques are used interchangeably to characterize homeostatic plasticity, sometimes leading to contradictory results. Here we directly compare the effect of short-term monocular deprivation on ocular dominance measured by either binocular rivalry or binocular combination and its dependence on the duration of deprivation (15 or 120 min) in the same group of participants. Our results show that both binocular rivalry and binocular combination provide reliable estimates of ocular dominance, which are strongly correlated across techniques both before and after deprivation. Moreover, while 15 min of monocular deprivation induce a larger shift of ocular dominance when measured using binocular combination compared to binocular rivalry, for both techniques, the shift in ocular dominance exhibits a strong dependence on the duration of monocular deprivation, with longer deprivation inducing a larger and longer-lasting shift in ocular dominance. Taken together, our results indicate that both binocular rivalry and binocular combination offer very consistent and reliable measurements of both ocular dominance and the effect short-term monocular deprivation.

Development of BOLD Response to Motion in Human Infants.

Behavioral studies suggest that motion perception is rudimentary at birth and matures steadily over the first few years. We demonstrated previously that the major cortical associative areas serving motion processing, like middle temporal complex (MT+), visual cortex area 6 (V6), and PIVC in adults, show selective responses to coherent flow in 8-week-old infants. Here, we study the BOLD response to the same motion stimuli in 5-week-old infants (four females and four males) and compare the maturation between these two ages. The results show that MT+ and PIVC areas show a similar motion response at 5 and 8 weeks, whereas response in the V6 shows a reduced BOLD response to motion at 5 weeks, and cuneus associative areas are not identifiable at this young age. In infants and in adults, primary visual cortex (V1) does not show a selectivity for coherent motion but shows very fast development between 5 and 8 weeks of age in response to the appearance of motion stimuli. Resting-state correlations demonstrate adult-like functional connectivity between the motion-selective associative areas but not between primary cortex and temporo-occipital and posterior-insular cortices. The results are consistent with a differential developmental trajectory of motion area respect to other occipital regions, probably reflecting also a different development trajectory of the central and peripheral visual field.SIGNIFICANCE STATEMENT How the cortical visual areas attain the specialization that we observed in human adults in the first few months of life is unknown. However, this knowledge is crucial to understanding the consequence of perinatal brain damage and its outcome. Here, we show that motion selective areas are already functioning well in 5-week-old infants with greater responses for detecting coherent motion over random motion, suggesting that very little experience is needed to attain motion selectivity.

Quantum spin models for numerosity perception.

Humans share with animals, both vertebrates and invertebrates, the capacity to sense the number of items in their environment already at birth. The pervasiveness of this skill across the animal kingdom suggests that it should emerge in very simple populations of neurons. Current modelling literature, however, has struggled to provide a simple architecture carrying out this task, with most proposals suggesting the emergence of number sense in multi-layered complex neural networks, and typically requiring supervised learning; while simple accumulator models fail to predict Weber's Law, a common trait of human and animal numerosity processing. We present a simple quantum spin model with all-to-all connectivity, where numerosity is encoded in the spectrum after stimulation with a number of transient signals occurring in a random or orderly temporal sequence. We use a paradigmatic simulational approach borrowed from the theory and methods of open quantum systems out of equilibrium, as a possible way to describe information processing in neural systems. Our method is able to capture many of the perceptual characteristics of numerosity in such systems. The frequency components of the magnetization spectra at harmonics of the system's tunneling frequency increase with the number of stimuli presented. The amplitude decoding of each spectrum, performed with an ideal-observer model, reveals that the system follows Weber's law. This contrasts with the well-known failure to reproduce Weber's law with linear system or accumulators models.

Using Cone Beam Computed Tomography for Radiological Assessment Beyond Dento-maxillofacial Imaging: A Review of the Clinical Applications in other Anatomical Districts.

BACKGROUND: Cone Beam Computed Tomography (CBCT) represents the optimal imaging solution for the evaluation of the maxillofacial and dental area when quantitative geometric and volumetric accuracy is necessary (e.g., in implantology and orthodontics). Moreover, in recent years, this technique has given excellent results for the imaging of lower and upper extremities. Therefore, significant interest has been increased in using CBCT to investigate larger and non-traditional anatomical districts. OBJECTIVE: The purpose of this work is to review the scientific literature in Pubmed and Scopus on CBCT application beyond head districts by paying attention to image quality and radiological doses. METHODS: The search for keywords was conducted in Pubmed and Scopus databases with no back-date restriction. Papers on applications of CBCT to head were excluded from the present work. From each considered paper, parameters related to image quality and radiological dose were extracted. An overall qualitative evaluation of the results extracted from each issue was done by comparing the conclusive remarks of each author regarding doses and image quality. PRISMA statements were followed during this process. RESULTS: The review retrieved 97 issues from 83 extracted papers; 46 issues presented a comparison between CBCT and Multi-Detector Computed Tomography (MDCT), and 51 reviewed only CBCT. The radiological doses given to the patient with CBCT were considered acceptable in 91% of cases, and the final image quality was found in 99%. CONCLUSION: CBCT represents a promising technology not only for imaging of the head and upper and lower extremities but for all the orthopedic districts. Moreover, the application of CBCT derived from C-arms (without the possibility of a 360 ° rotation range) during invasive investigations demonstrates the feasibility of this technique for non-standard anatomical areas, from soft tissues to vascular beds, despite the limits due to the incomplete rotation of the tube.

Effect of fasting on short-term visual plasticity in adult humans.

Brain plasticity and function is impaired in conditions of metabolic dysregulation, such as obesity. Less is known on whether brain function is also affected by transient and physiological metabolic changes, such as the alternation between fasting and fed state. Here we asked whether these changes affect the transient shift of ocular dominance that follows short-term monocular deprivation, a form of homeostatic plasticity. We further asked whether variations in three of the main metabolic and hormonal pathways affected in obesity (glucose metabolism, leptin signalling and fatty acid metabolism) correlate with plasticity changes. We measured the effects of 2 h monocular deprivation in three conditions: post-absorptive state (fasting), after ingestion of a standardised meal and during infusion of glucagon-like peptide-1 (GLP-1), an incretin physiologically released upon meal ingestion that plays a key role in glucose metabolism. We found that short-term plasticity was less manifest in fasting than in fed state, whereas GLP-1 infusion did not elicit reliable changes compared to fasting. Although we confirmed a positive association between plasticity and supraphysiological GLP-1 levels, achieved by GLP-1 infusion, we found that none of the parameters linked to glucose metabolism could predict the plasticity reduction in the fasting versus fed state. Instead, this was selectively associated with the increase in plasma beta-hydroxybutyrate (B-OH) levels during fasting, which suggests a link between neural function and energy substrates alternative to glucose. These results reveal a previously unexplored link between homeostatic brain plasticity and the physiological changes associated with the daily fast-fed cycle.

Vision: Neuronal mechanisms enabling stable perception.

Eye movements cause rapid motion of the retinal image, potentially confusable with external motion. A recent study shows that neurons in mouse primary visual cortex distinguish self-generated from external motion by combining sensory input with saccade-related signals from the thalamic pulvinar nucleus.

The Readiness Potential Correlates with Action-Linked Modulation of Visual Accuracy.

Visual accuracy is consistently shown to be modulated around the time of the action execution. The neural underpinning of this motor-induced modulation of visual perception is still unclear. Here, we investigate with EEG whether it is related to the readiness potential, an event-related potential (ERP) linked to motor preparation. Across 18 human participants, the magnitude of visual modulation following a voluntary button press was found to correlate with the readiness potential amplitude measured during visual discrimination. Participants' amplitude of the readiness potential in a purely motor-task was also found to correlate with the extent of the motor-induced modulation of visual perception in the visuomotor task. These results provide strong evidence that perceptual changes close to action execution are associated with motor preparation processes and that this mechanism is independent of task contingencies. Further, our findings suggest that the readiness potential provides a fingerprint of individual visuomotor interaction.

Evidence of Serial Dependence from Decoding of Visual Evoked Potentials.

It is well known that recent sensory experience influences perception, recently demonstrated by a phenomenon termed "serial dependence." However, its underlying neural mechanisms are poorly understood. We measured ERP responses to pairs of stimuli presented randomly to the left or right hemifield. Seventeen male and female adults judged whether the upper or lower half of the grating had higher spatial frequency, independent of the horizontal position of the grating. This design allowed us to trace the memory signal modulating task performance and also the implicit memory signal associated with hemispheric position. Using classification techniques, we decoded the position of the current and previous stimuli and the response from voltage scalp distributions of the current trial. Classification of previous responses reached full significance only 700 ms after presentation of the current stimulus, consistent with retrieval of an activity-silent memory trace. Cross-condition classification accuracy of past responses (trained on current responses) correlated with the strength of serial dependence effects of individual participants. Overall, our data provide evidence for a silent memory signal that can be decoded from the EEG potential, which interacts with the neural processing of the current stimulus. This silent memory signal could be the physiological substrate subserving at least one type of serial dependence.SIGNIFICANCE STATEMENT The neurophysiological underpinnings of how past perceptual experience affects current perception are poorly understood. Here, we show that recent experience is reactivated when a new stimulus is presented and that the strength of this reactivation correlates with serial biases in individual participants, suggesting that serial dependence is established on the basis of a silent memory signal.

Long Covid: where we stand and challenges ahead.

Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome.

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT05200715.