Trial of Cardiovascular Risk Factor Assessment and Transthoracic Echocardiography Results in Patients with Primary Antibody Deficiency.

The life expectancy and the risk of developing cardiovascular diseases in patients with inborn errors of immunity are systematically increasing. The aim of the study was to assess cardiovascular risk factors and to evaluate the heart in echocardiography in patients with primary antibody deficiency (PAD). Cardiac echography and selected cardiovascular risk factors, including body mass index, sedentary lifestyle, nicotine, glucose, C-reactive protein, lipid profile, uric acid level, certain chronic diseases, and glucocorticoid use, were analyzed in 94 patients >18 years of age with PAD. Of the patients,25.5% had a cardiovascular disease (mostly hypertension, 18%), 10.5% smoked, 17% were overweight, 14% were obese, and 15% were underweight. Abnormal blood pressure was found in 6.5% of the patients. Lipid metabolism disorders were found in 72.5% of in the studied cohort, increased total cholesterol (45.5%), non-high-density lipoprotein (HDL) (51%), low-density lipoprotein (LDL) (47%), and triglycerides (32%) were observed. Furthermore, 28.5% had a decrease in HDL and 9.5% had a history of hyperuricemia. The average number of risk factors was 5 ± 3 for the entire population and 4 ± 2 for those under 40 years of age. Elevated uric acid levels were found de novo in 4% of participants. In particular, 74.5% of the patients had never undergone an echocardiogram with a successful completion rate of 87% among those tested. Among them, 30% showed parameters within normal limits, primarily regurgitation (92.5%). New pathologies were identified in 28% of patients. Prevention in patients with PAD, aimed at reducing cardiovascular risk, should be a priority.

Anxiety in Polish adult patients with inborn errors of immunity: a cross-sectional study.

Background: Patients 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. Methods: Data 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. Results: Thirty-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. Discussion: Anxiety 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.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Case report: VEXAS as an example of autoinflammatory syndrome in pulmonology clinical practice.

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.

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.

The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements.

BACKGROUND: Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. METHODS: Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. FINDINGS: Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. INTERPRETATION: Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. FUNDING: An unrestricted grant from Boehringer Ingelheim International.