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ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

IntroductionThe 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.MethodsPatients 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.ResultsNo 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.ConclusionCanakinumab has proved to be effective in patients with Still’s disease, regardless of its line of biologic treatment.

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

BeckgroundDespite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment.Materials and methodsPatients’ data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network.ResultsA total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARDs were more useful when combined with biotechnological agents.ConclusionSigns and symptoms referring to axial SpA should be inquired in patients with apparently unexplained recurrent fever episodes. The specific treatment for axial SpA may lead to a remarkable improvement in the severity and/or frequency of fever episodes in patients with unexplained fevers and concomitant axial SpA.

ObjectiveThe present manuscript aims to describe an international, electronic-based, user-friendly and interoperable patient registry for monogenic autoinflammatory diseases (mAIDs), developed in the contest of the Autoinflammatory Diseases Alliance (AIDA) Network.MethodsThis is an electronic platform, based on the Research Electronic Data Capture (REDCap) tool, used for real-world data collection of demographics, clinical, laboratory, instrumental and socioeconomic data of mAIDs patients. The instrument has flexibility, may change over time based on new scientific acquisitions, and communicate potentially with other similar registries; security, data quality and data governance are corner stones of the platform.ResultsAIDA project will share knowledge and expertise on mAIDs. Since its start, 118 centers from 24 countries and 4 continents have joined the AIDA project. Fifty-nine centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 337 users (122 Principal Investigators, 210 Site Investigators, 2 Lead Investigators, and 3 data managers). The Registry collects baseline and follow-up data using 3,748 fields organized into 21 instruments, which include demographics, patient history, symptoms, trigger/risk factors, therapies, and healthcare information for mAIDs patients.ConclusionsThe AIDA mAIDs Registry, acts both as a research tool for future collaborative real-life studies on mAIDs and as a service to connect all the figures called to participate. On this basis, the registry is expected to play a pivotal role in generating new scientific evidence on this group of rare diseases, substantially improving the management of patients, and optimizing the impact on the healthcare system. NCT 05200715 available at https://clinicaltrials.gov.

ObjectiveThe aim of this paper is to present the AutoInflammatory Disease Alliance (AIDA) international Registry dedicated to Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome, describing its design, construction, and modalities of dissemination.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument designed for the retrospective and prospective collection of real-life data. Data gathering is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain real-world evidence for daily patients' management. The Registry may potentially communicate with other on-line tools dedicated to VEXAS syndrome, thus enhancing international collaboration and data sharing for research purposes. The Registry is practical enough to be easily modified to meet future needs regarding VEXAS syndrome.ResultsTo date (April 22nd, 2022), 113 Centers from 23 Countries in 4 continents have been involved; 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) are currently able to access the registry for data entry (or data sharing) and collection. The Registry includes 4,952 fields organized into 18 instruments designed to fully describe patient's details about demographics, clinical manifestations, symptoms, histologic details about skin and bone marrow biopsies and aspirate, laboratory features, complications, comorbidities, therapies, and healthcare access.ConclusionThis international Registry for patients with VEXAS syndrome will allow the achievement of a comprehensive knowledge about this new disease, with the final goal to obtain real-world evidence for daily clinical practice, especially in relation to the comprehension of this disease about the natural history and the possible therapeutic approaches. This Project can be found on https://clinicaltrials.gov NCT05200715.

ObjectiveThis paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs).MethodsThis is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance.ResultsThe focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients.ConclusionsThe development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases. NCT 05200715 available at https://clinicaltrials.gov/.

Facilitated subcutaneous immunoglobulin (fSCIG) replacement therapy is the latest method of IgG administration; however, real-life data are limited. We retrospectively analyzed the everyday experience of fSCIG administration, particularly, the method used to switch from intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) to fSCIG and the dosing modifications required. Of the 39 adult patients with primary immunodeficiency (PID) who received fSCIG, 34 remained on the therapy at the end of the study. The median observation time was 18 (range, 3–24) months. Two patients were IgG-treatment-naïve; 23 had previously received IVIG and 14 had received SCIG. In 25 cases, a non-ramp-up dosing mode was used to switch to fSCIG (including two half-monthly doses given biweekly in 14 cases, and full monthly doses given in 11 cases), a ramp-up mode was used in six cases; other methods were used in eight cases. The median IgG trough level at baseline was 7.9 g/L (n = 38), 7.9 g/L (n = 32) at Month 6, 9.0 g/L (n = 30) at Month 12, 8.6 g/L (n = 22) at Month 18, and 9.0 g/L (n = 11) at Month 24. No serious bacterial infections or hospitalizations due to PID complications occurred. At the end of the study, 24 patients (71%) received fSCIG every 4 weeks, six (18%) received fSCIG every 3 weeks, and four (12%) received fSCIG biweekly. In conclusion, our study provides real-life evidence of clinical efficacy of personalized fSCIG treatment when switching from prior immunoglobulin replacement using various switching modes and dosing frequencies.

BackgroundPatients with inborn errors of immunity (IEI) experience recurrent infections, autoimmunity, and malignancies. Owing to repeated medical procedures, the need for constant treatment and surveillance, and the unpredictable course of the disease, patients with IEI are prone to develop mental health disorders, including anxiety. In this study, we aimed to assess the prevalence and level of anxiety symptoms in adult Polish patients with IEI and explore the determinants of anxiety in this group of patients.MethodsData from 105 Polish patients with IEI were collected via the hospital anxiety and depression scale (HADS), brief illness perception questionnaire (B-IPQ), illness cognition questionnaire (ICQ), Pittsburgh sleep quality index (PSQI), and a questionnaire on general health and demographic data. For statistical analyses of data, the normality of distribution of quantitative data was assessed, and internal consistency of tests was investigated using Cronbach’s alpha coefficient; moreover, we performed the analysis of correlations and between-group differences, and path analysis to explore causal relationships. Significance was considered at p < 0.050.ResultsThirty-eight (36.2%) patients had anxiety symptoms (HADS-A ≥ 8); 14 (13.3%) patients had severe anxiety (score ≥ 11), and 24 (22.9%) had moderate anxiety (score of 8–10). Patients with poor sleep quality, higher pain frequency, younger age, and no fixed income had higher anxiety scores than others. Emotional and cognitive representations of illness were positively correlated with anxiety levels. Intense anxiety was related to more negative illness perception, higher helplessness, lower illness acceptance, and lower perceived benefits.DiscussionAnxiety is common in patients with IEI. However, results indicate that it is not related to a more severe course of IEI or several comorbidities, whereas, pain frequency and poor sleep quality were identified to be important clinical factors for anxiety. Because anxiety was related to negative illness perception, psychological therapy may apply to this group of patients.

Lung involvement is not widely recognized as a complication of auto-inflammatory diseases. We present a broad approach to diagnose a severe form of autoinflammatory syndrome in an adult male patient. A 63-year-old Caucasian male presented with recurrent episodes of high fever, interstitial lung infiltration, and pleural effusion. Laboratory tests performed during the flares revealed lymphopenia and increased levels of C-reactive protein and ferritin. Broad diagnostic research on infections, connective tissue diseases, and malignancies yielded negative results. The patient’s symptoms promptly resolved upon the administration of glucocorticoids; however, they reappeared when the prednisone dose was reduced. All attempts to administer immunomodulatory and immunosuppressive medications were ineffective. During follow-up, autoinflammatory syndrome was suspected; however, no pathological variants of monogenic autoinflammatory diseases were identified by genome-exome sequencing. The patient did not respond to interleukin 1 blockade with anakinra. He died due to multi-organ failure, and his condition remained unresolved until the first reported description of vacuole, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome (VEXAS). We describe the diagnostic traps and reasoning process involved in establishing that the patient’s symptoms were autoinflammatory in nature based on clinical symptoms, in addition to the proof of concept gained from genetic reevaluation and identification of pathogenic variants in the UBA1 gene. The aim of this review is to increase the awareness of VEXAS among pulmonologists. Genetic screening for UBA1 should be considered in patients with recurrent pneumonitis of unknown origin with elevated inflammatory markers and signs of cytopenia, especially if they require chronic steroids to control the disease. Respiratory manifestations are part of VEXAS; these may be dominant in the course of the disease and severe at presentation.

Abstract Introduction Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. Methods This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. Results Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. Conclusions ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

Abstract To present the utility of dual-energy computed tomography (DECT) in the assessment of angiogenesis of focal lesions as an example of a solitary pulmonary nodule (SPN). This prospective study comprised 28 patients with SPN who underwent DECT and perfusion computed tomography (CTP), according to a proprietary protocol. Two radiologists independently analyzed four perfusion parameters, namely blood flow (BF), blood volume (BV), the time to maximum of the tissue residue function (Tmax), permeability surface area product (PS) from CTP, in addition to the iodine concentration (IC) and normalized iodine concentration (NIC) of the SPN from DECT. We used the Pearson R correlation and interclass correlation coefficients (ICCs). Statistical significance was assumed at p

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p

ObjectiveTo evaluate the potential role of Streptococcus salivarius 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.Patients and methodsThe 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.ResultsThe 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), p < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p < 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), p < 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, p < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p < 0.001), oral aphthae (p < 0.001) and cervical lymphadenopathy (p < 0.001) significantly decreased following SSK12.ConclusionSSK12 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.

IntroductionPrimary immunodeficiencies (PIDs) are clinically heterogeneous disorders caused by abnormalities in the immune system. However, PIDs are genetically determined and may occur at any age from early childhood to elderly age. Due to chronic patterns, the risk of malignancy and organ damage in patients with PIDs may affect any aspect of life, including sleep patterns. To our knowledge, the prevalence of insomnia and subjective sleep quality have not been investigated in patients with PIDs. Therefore, this pilot study was conducted to investigate sleep quality, the prevalence of sleep disturbances, and fatigue in adult patients with PIDs in Poland.MethodsAll participants were surveyed using the Athens Insomnia Scale, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, and a questionnaire concerning general health and demographic data. We included 92 participants: 48 women (52.2%) and 44 men (47.8%).ResultsParticipants’ mean age was 41.9 ± 13.9 years. The mean sleep duration was 7.0 ± 1.5 hours, and the mean sleep latency was 41.2 ± 53.1 minutes. Additionally, 44.6% of patients (n=41) had symptoms of insomnia and 44.6% (n=42) had poor sleep quality. Less than one-fourth (n=22; 23.9%) of the patients reported the use of sleeping pills; moreover, clinically significant fatigue was reported in 52.2% (n=48).DiscussionOur investigation provides insight into the problem of sleep disturbances in patients with PIDs. Data have demonstrated that sleeping disorders with concomitant fatigue are common in patients with PID. Further studies are needed to determine the determinants of poor sleep quality in this specific group of patients.

ObjectiveInterleukin (IL)-1 inhibitors are largely employed in patients with Still’s disease; in cases with refractory arthritis, IL-6 inhibitors have shown to be effective on articular inflammatory involvement. The aim of the present study is to assess any difference in the effectiveness of the IL-1β antagonist canakinumab prescribed as first-line biologic agent between the systemic and the chronic-articular Still’s disease.MethodsData were drawn from the retrospective phase of the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to Still’s disease. Patients with Still’s disease classified according to internationally accepted criteria (Yamaguchi criteria and/or Fautrel criteria) and treated with canakinumab as first-line biologic agent were enrolled.ResultsA total of 26 patients (17 females, 9 males; 18 patients developing Still’s disease after the age of 16 years) were enrolled; 16 (61.5%) patients suffered from the systemic pattern of the disease; 10 (38.5%) patients suffered from the chronic-articular type. No differences were observed between the systemic and the chronic-articular Still’s disease in the frequency of complete response, of flares after the start of canakinumab (p = 0.701) and in the persistence in therapy (p = 0.62). No statistical differences were observed between the two groups after 3 months, 12 months and at the last assessment in the decrease of: the systemic activity score (p = 0.06, p = 0.17, p = 0.17, respectively); the disease activity score on 28 joints (p = 0.54, p = 0.77, p = 0.98, respectively); the glucocorticoid dosage (p = 0.15, p = 0.50, and p = 0.50, respectively); the use of concomitant disease modifying anti-rheumatic drugs (p = 0.10, p = 1.00, and p = 1.00, respectively). No statistically significant differences were observed in the decrease of erythrocyte sedimentation rate (p = 0.34), C reactive protein (p = 0.48), and serum ferritin levels (p = 0.34) after the start of canakinumab.ConclusionCanakinumab used for Still’s disease has been effective in controlling both clinical and laboratory manifestations disregarding the type of disease course when used as first-line biotechnological agent. These excellent results might have been further enhanced by the early start of IL-1 inhibition.

The mechanisms underlying the immune response to coronavirus disease 2019 (COVID-19) and the recovery process have not been fully elucidated. The aim of the study was to analyze leukocyte subpopulations in patients at significant time points (at diagnosis, and 3 and 6 months after infection) selected according to the analysis of changes in the lungs by the CT classification system, considering the severity of the disease. The study groups consisted of severe and non-severe COVID-19 patients. There was a significant decrease in CD8+ T cells, NK and eosinophils, with an increasing percentage of neutrophils during hospitalization. We noticed lower levels of CD4 and CD8 T lymphocytes, eosinophils, basophils, and CD16+ monocytes and elevated neutrophil levels in severe patients relative to non-severe patients. Three months after infection, we observed higher levels of basophils, and after 6 months, higher CD4/CD8 ratios and T cell levels in the severe compared to non-severe group. Non-severe patients showed significant changes in the leukocyte populations studied at time of hospitalization and both within 3 months and 6 months of onset. The CT CSS classification with parameters of the flow cytometry method used for COVID-19 patients determined changes that proved useful in the initial evaluation of patients.

Pulmonary involvement is the most common complication in patients with predominantly antibody deficiencies (PADs). Therefore, patients require repeated imaging tests. Unlike high-resolution computed tomography (HRCT), lung ultrasonography (LUS) does not expose patients to X-rays or contrast agents, and can be performed even at the bedside. This study aimed to evaluate lung lesions using simultaneous LUS and HRCT in a group of patients with PADs. Twenty-nine adult patients (13 women and 16 men) diagnosed with PADs according to the ESID criteria (23 Common variable immunodeficiency, 2 X-linked agammaglobulinemia, 2 IgG subclass deficiencies, and 2 Unspecified hypogammaglobulinemia) were included in the study. The mean age was 39.0 ± 11.9 years. The mean time elapsed between the first symptoms of PADs and the examination was 15.4 ± 10.1 years. Lung ultrasonography and high-resolution computed tomography were performed simultaneously according to a defined protocol during the clinic visits. In both examinations, lesions were compared in the same 12 regions: for each lung in the upper, middle, and lower parts, separately, front and back. A total of 435 lesions were described on LUS, whereas 209 lesions were described on HRCT. The frequencies of lesions in the lung regions were similar between LUS and HRCT. In both examinations, lesions in the lower parts of the lungs were most often reported (LUS 60.9% vs. HRCT 55.5%) and least often in the upper parts of the lungs (LUS 12.7% vs. HRCT 12.0%). The most frequently described lesions were LUS consolidations (99; 22.8%) and HRCT fibrosis (74; 16.5%). A statistically significant relationship was found in the detection of fibrosis in 11 of the 12 regions (phi = 0.4−1.0). Maximum values of the phi coefficient for the upper part of the left lung were recorded. Compared with HRCT, LUS is an effective alternative for evaluating and monitoring pulmonary lesions in adult patients with PADs, especially for pulmonary fibrosis.

Data regarding the willingness of patients affected by inborn errors of immunity to accept vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Therefore, this study assessed SARS-CoV-2 vaccination coverage and hesitancy in immunodeficient patients by surveying adults with primary immune deficiencies and autoinflammatory and rheumatic diseases on biologic therapy. The study was conducted from September 20, 2021, to January 22, 2022, when the primary coronavirus disease 2019 (COVID-19) vaccinations were available to all adults in Poland. We included 207 participants consecutively recruited from five referral centers (57% female; median age: 42.6 [range: 18–76, standard deviation ± 14.70] years). Overall, 55% (n = 114), 17% (n = 36), and 28% (n = 57) of the patients had primary immune deficiencies, autoinflammatory diseases, and rheumatic diseases, respectively. Among the entire cohort, 168 patients (81%) were vaccinated, and 82% were willing to receive a booster dose. Patients with autoinflammatory diseases had the highest vaccination rate (94.4%). A strong conviction that it was the correct decision (72%), fear of getting COVID-19 (38%), and expert opinions (34%) influenced the decision to vaccinate. Among the unvaccinated patients, 33.3% had primary or vocational education (p

At the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, patients with inborn errors of immunity (IEI) appeared to be particularly vulnerable to a severe course of the disease. It quickly turned out that only some IEI groups are associated with a high risk of severe infection. However, data on the course of Coronavirus Disease 2019 (COVID-19) in patients with IEI are still insufficient, especially in children; hence, further analyses are required. The retrospective study included 155 unvaccinated people with IEI: 105 children and 50 adults (67.7% and 32.3%, respectively). Male patients dominated in the study group (94 people, 60.6%). At least two comorbidities were found in 50 patients (32.3%), significantly more often in adults (56% vs. 21%). Adult patients presented significantly more COVID-19 symptoms. Asymptomatic and mildly symptomatic course of COVID-19 was demonstrated in 74.8% of the entire group, significantly more often in children (88.6% vs. 46%). Moderate and severe courses dominated in adults (54% vs. 11.4%). Systemic antibiotic therapy was used the most frequently, especially in adults (60% vs. 14.3%). COVID-19-specific therapy was used almost exclusively in adults. In the whole group, complications occurred in 14.2% of patients, significantly more often in adults (30% vs. 6.7%). In the pediatric group, there were two cases (1.9%) of multisystem inflammatory syndrome in children. Deaths were reported only in the adult population and accounted for 3.9% of the entire study group. The death rate for all adults was 12%, 15.4% for adults diagnosed with common variable immunodeficiency, 12.5% for those with X-linked agammaglobulinemia, and 21.4% for patients with comorbidity. The results of our study imply that vaccinations against COVID-19 should be recommended both for children and adults with IEI. Postexposure prophylaxis and early antiviral and anti-SARS-CoV-2 antibody-based therapies should be considered in adults with IEI, especially in those with severe humoral immune deficiencies and comorbidity.

The majority of primary immunodeficiencies (PIDs) are antibody deficiencies (PADs), and not all of them are rare diseases; As an example, Caucasian individuals suffer from selective IgA deficiency at a frequency of 1:500. In addition to infections, symptomatic patients with PAD are more likely to develop neoplastic, autoimmune, and allergic diseases. In the event that PAD is neglected or delayed for more than ten years, complications develop, eventually resulting in death. No studies have been conducted to devise and report detailed ready-to-use protocols for managing PAD to date. This study aimed to propose protocols and guidelines for the adult PAD patients’ standard care. Preparing the protocol, we considered the frequency and type of laboratory tests, imaging, endoscopic examinations, specialist consultations, and standardized recommendations for further care in the place of residence. As a result of the proposed monitoring scheme, patients can be provided with complete care in terms of their underlying conditions and comorbidities, as well as early detection of complications. This protocol will serve as a guide for physicians dealing with these patients and enable comparisons of patient groups across a variety of treatment centers, even far away from each other. A national consultant in the field of clinical immunology verified the protocol mainly developed by Polish experts from reference immunology centres for adults.

ObjectiveAim 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.MethodsThis 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.ResultsA 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.ConclusionsThe 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 NCT 05200715.

ObjectiveThe present paper describes the design, development, and implementation of the AutoInflammatory Disease Alliance (AIDA) International Registry specifically dedicated to patients with Schnitzler's syndrome.MethodsThis is a clinical physician-driven, population- and electronic-based registry implemented for the retrospective and prospective collection of real-life data from patients with Schnitzler's syndrome; the registry is based on the Research Electronic Data Capture (REDCap) tool, which is designed to collect standardized information for clinical research, and has been realized to change over time according to future scientific acquisitions and potentially communicate with other existing or future similar registries.ResultsSince its launch, 113 centers from 23 countries in 4 continents have been involved. Fifty-seven have already obtained the approval from their local Ethics Committees. The platform counts 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) at current (April 28th, 2022). The registry collects baseline and follow-up data using 3,924 fields organized into 25 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, laboratory, instrumental exams, therapies, socioeconomic information, and healthcare access.ConclusionsThis International Registry for patients with Schnitzler's syndrome facilitates standardized data collection, enabling international collaborative projects through data sharing and dissemination of knowledge; in turn, it will shed light into many blind spots characterizing this complex autoinflammatory disorder.

The NLRP3 gene mutations are the cause of autosomal dominant autoinflammatory disorders (NLRP3-AID). Recently, hearing loss (HL) has been found to be the sole or major manifestation of NLRP3-AID. Here, we tested 110 autosomal dominant HL families with a custom panel of 237 HL genes and found one family carrying the NLRP3 c.1872C>G, p.Ser624Arg mutation. Functional studies revealed that this novel variant is a gain of function mutation, leading to increased activity of caspase-1 and subsequent oversecretion of proinflammatory interleukin-1β. Clinical reanalysis of the affected individuals, together with serological evidence of inflammation and pathological cochlear enhancement on FLAIR-MRI images, guided our diagnosis to atypical NLRP3-AID. The study highlights the role of genetic analysis in patients with progressive postlingual HL. This can help to identify individuals with hereditary HL as a consequence of NLRP3-AID and allow timely and effective treatment with interleukin-1-receptor antagonist.

ObjectiveAim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions.ResultsStarting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access.ConclusionsThis international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from “real-life” data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT 05200715 available at https://clinicaltrials.gov/.

Monogenic autoinflammatory diseases (AIDs, formerly known as hereditary periodic fever syndromes) cover a spectrum of diseases which lead to chronic or recurrent inflammation caused by activation of the innate immune system. The most common monogenic AID is familial Mediterranean fever. Monogenic autoinflammatory diseases are generally considered intracellular signalling defects. Some stereotypical knowledge may be misleading; e.g. monogenic AIDs are not exclusively found in children, family history is often negative, fever frequently is not a leading manifestation and frequency of attacks in adults is usually variable. Lack of genetic confirmation should not stop anti-inflammatory ex juvantibus therapy. The pattern of tissue injury in AIDs is basically different from that observed in autoimmunity. There is no autoaggression against organ-specific antigens, but substantial damage (amyloidosis, cachexia, premature cardiovascular disease) is secondary to long-lasting inflammation. The Polish national programme of anti-interleukin 1 treatment opens new possibilities for the treatment. However, monogenic AIDs are frequently misdiagnosed and more awareness is needed.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most common cause of periodic fever in childhood. Reports of adult patients are sparse. In adults the clinical picture is more heterogeneous than in children, so PFAPA can be a real diagnostic challenge. Data regarding treatment efficacy and disease outcome are available mainly for children, whereas for adult patients they are limited and conflicting. Our aim is to increase the awareness about PFAPA among clinical practitioners. We present a case of PFAPA beginning in childhood and without resolution of symptoms in maturity. In our case the diagnostic delay was 15 years. We treated the patient with a prophylactic dose of colchicine. Colchicine helped to control flares and significantly improved the patient’s quality of life. Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis in adults is a rare disease, but it should be included in the differential diagnosis of fever of unknown origin in adults.

Antibody determination is routinely used in everyday rheumatological practice. Its result repeatedly determines the diagnosis or exclusion of a particular disease. Antibodies are immunoglobulins, i.e. some of the most important proteins in the immune system, and have specific properties that we should know. In addition, there are a number of factors that can affect their concentration, including drugs commonly used in the treatment of rheumatic diseases. There are definite indications, when the total concentrations of individual classes of immunoglobulins should be initially determined and it should be evaluated whether the patient produces them at all or their production is impaired. In some cases, we should evaluate the levels of specific antibodies along with the total protein concentration and the -globulin fraction, in which the antibodies are contained. The article presents information on the most common mistakes made when performing these tests.

Background: This study aims at describing the therapeutic outcome of patients carrying the R92Q variant in the TNFRSF1A gene treated with anakinra (ANA) or canakinumab (CAN) and identifying any factors predictive of complete response to IL-1 inhibition. Methods: Clinical data of patients treated with ANA or CAN for recurrent inflammatory attacks due to the presence of the R92Q variant were retrospectively collected and analysed. Results: Data about 20 treatment courses with IL-1 inhibitors (16 with ANA and 4 with CAN) from 19 patients were collected. Mean age at disease onset was 20.2 ± 14.8 years. In 5 cases (26%) the R92Q variant was found in a family member affected by recurrent fever. The therapeutic response was complete in 13(68%) and partial in 2 patients (11%); treatment failure was observed in 4 cases (21%). Median AIDAI decreased from 10 (interquartile range [IQR] = 28) to 0 (IQR = 1) at the 12-month follow-up visit ( p

Common variable immunodeficiency (CVID) is the most clinically significant primary antibody immunodeficiency recognized in adulthood. Previously published data have shown an average diagnostic delay of 10 years for Polish adult patients with CVID. In the current study, we aimed to analyze the current diagnostic delay of adult patients with CVID in Poland. To this end, we identified patients from four immunological centers specialized in the care of adult patients with primary immunodeficiencies (PID). Demographic and clinical data of patients were collected using an internet database. We identified 103 adult patients (F:M 44.7%:55.3%) in Poland with CVID. The median age at onset of symptoms was 24 (0–66), 33 (4–70) at diagnosis, and 37 (18–73) years at the time of analysis. The median diagnostic delay for the entire study population was 6 (0–57) years. However, this delay was higher in patients with symptom onset before the year 2000 than after the year 1999 [15 (0–57) vs. 3 (0–19) years; p < 0.001]. Comparing patients (median ≤ 6 years, N = 53) with short diagnostic delay (SDD) and those (median > 6 years, N = 50) with long diagnostic delay (LDD), the LDD group had a statistically significant higher incidence of infections of the lower respiratory tract before diagnosis (90.0 vs. 71.70%). During the entire observation period, cytopenias (44.00 vs. 22.64%), granulomatous lesions (28.00 vs. 11.32%), and solid tumors (14.00 vs. 1.89%) were significantly more frequent in the LDD group. In conclusion, we found a significant reduction in the median diagnostic delay in Polish CVID patients with disease onset in the last two decades.

Cell response to novel coronavirus disease 19 (COVID-19) is currently a widely researched topic. The assessment of leukocytes population and the maturation of both B and T lymphocytes may be important in characterizing the immunological profile of COVID-19 patients. The aim of the present study was to evaluate maturation of B and T cells in COVID-19 patients with interstitial lesions on chest X-ray (COVID-19 X-ray (+)), without changes on X-ray (COVID-19 X-ray (−)) and in healthy control. The study group consisted of 23 patients divided on two groups: COVID-19 X-ray (+) n = 14 and COVID-19 X-ray (−) n = 9 and control n = 20. The flow cytometry method was performed. We observed a significantly higher percentage of plasmablasts and lower CD4+ lymphocytes in COVID-19 X-ray (+) patients than in COVID-19 X-ray (−) and control. In the COVID-19 X-ray (+) patients, there was a lower proportion of effector CD4+ T cells, naïve CD8+ T cells and higher central memory CD4+ cells and effector CD8+ T cells than control. The above results showed that the assessment of selected cells of B and T lymphocytes by flow cytometry can distinguish patients with COVID-19 and differentiate patients with and without changes on chest X-ray.

Powikłania sercowo-naczyniowe są przyczyną 20–30% zgonówchorych na toczeń rumieniowaty układowy (TRU). Występują onew tej grupie chorych częściej i w młodszym wieku niż w populacjiogólnej (tab. I). Przyczyny tego zjawiska nie zostały wyjaśnione. Naprzyspieszony rozwój miażdżycy wpływają zaburzenia lipidowe,współistniejące zapalenie oraz być może stosowanie glikokortykosteroidów.W pracy przedstawiono tradycyjne i swoiste dla TRU czynnikiwpływające na rozwój miażdżycy (tab. II). Zwrócono uwagę nakorzyści wynikające z kontroli aktywności choroby i stosowanialeków antymalarycznych. Omówiono miejsce badań obrazowychw diagnostyce miażdżycy, w tym badania ultrasonograficznegotętnic szyjnych z oceną grubości kompleksu błony wewnętrzneji środkowej (intima-media thickness – IMT). Obecnie nie ma jednoznacznychzaleceń dotyczących profilaktyki pierwotnej i wtórnejwśród chorych na TRU. Zaproponowano strategię postępowania,której wprowadzenie może zmniejszyć ryzyko rozwojupowikłań sercowo-naczyniowych (tab. III).

Tętnicze nadciśnienie płucne (TNP) to przewlekle postępująca choroba,która jest główną przyczyną zgonów w przebiegu twardzinyukładowej. W innych układowych chorobach tkanki łącznej TNPwystępuje rzadziej. W ostatnim dziesięcioleciu daje się zauważyćpostęp w zrozumieniu patogenezy tętniczego nadciśnienia płucnego,który zaowocował wprowadzeniem nowych leków. Warunkiemskutecznej terapii jest wczesne ustalenie rozpoznania. W artykuleomówiono strategię wykrywania TNP u chorych na twardzinę układową.Optymalne narzędzia badań przesiewowych wciąż nie sąokreślone. Zaleca się coroczną echokardiografię dopplerowską. Ważnymkrokiem jest diagnostyka różnicowa przyczyn nadciśnienia płucnego,które mogą wynikać także z uszkodzenia lewej komory serca,choroby śródmiąższowej płuc, zmian zatorowo-zakrzepowych czyzapalenia mięśnia sercowego. Wciąż wymagają określenia, szczególniew grupie chorych z łagodnym nadciśnieniem płucnym, optymalneprogi wartości nieprawidłowych w badaniu echokardiograficznym.Echokardiografia wiąże się z ryzykiem wyników zarówno fałszywiedodatnich, jak i fałszywie ujemnych. We wszystkich przypadkach,w których podejrzenie TNP okazuje się uzasadnione, konieczne jestpotwierdzenie rozpoznania za pomocą cewnikowania serca.