Osteoporotic bone fracture risk assessment in Latvian patients with newly diagnosed sarcoidosis.

BACKGROUND AND AIM: Increased calcitriol synthesis in sarcoid granulomas with subsequent hypercalcaemia and hypercalciuria can affect bone metabolism in patients with sarcoidosis. Multiple factors can increase the fracture risk in patients with sarcoidosis. This study aimed to evaluate a 10-year osteoporotic and a 10-year hip fracture risk and to analyse factors affecting fracture risk for patients with newly diagnosed sarcoidosis compared to an age- and gender-matched control group from a real-world setting. METHODS: The cross-sectional study included 171 patients with a histologically verified diagnosis of sarcoidosis who were hospitalised due to suspected sarcoidosis within two years and an age- and gender-matched control group of 178 hospitalised individuals. QFracture algorithm questions were asked during interviews. RESULTS: A cohort of 349 subjects was analysed. The median age in the patient group was 40 years (IQR:20), and 60.2% were female. 21.6% of patients with sarcoidosis had at least one comorbidity that could potentially influence the osteoporotic fracture risk. Both the median 10-year osteoporotic fracture risk (0.9% (IQR:2) vs 1.3% (IQR:2.3), p=0.005; U=12394) and a 10-year hip fracture risk (0.1% (IQR:0.3) vs 0.2% (IQR:0.5), p=0.003; U=12368.5) was lower in patients with sarcoidosis compared to control group subjects. As compared to the control group, individuals with sarcoidosis exhibited a lower frequency of both osteoporotic (2.4% vs 11.2%, OR=0.189 (95% CI:0.063-0.566), p=0.003) and low-energy trauma fractures (2.9% vs 11.8%, OR=0.225 (95% CI:0.083-0.612), p=0.003) in personal medical history. CONCLUSIONS: This was the first study to investigate osteoporotic fracture risk and related factors in Latvian patients with newly diagnosed sarcoidosis. Our data show a lower risk of a 10-year osteoporotic and a 10-year hip fracture risk in patients with sarcoidosis compared to age- and gender-matched control group subjects from a real-world setting.

COVID-19 Vaccination Coverage and Factors Influencing Vaccine Hesitancy among Patients with Inborn Errors of Immunity in Latvia: A Mixed-Methods Study.

BACKGROUND: The European Society for Immunodeficiencies recommends that all patients with inborn errors of immunity (IEI) without contraindications should receive SARS-CoV-2 vaccination. The aim of this study was to investigate the reasons that discourage IEI patients from receiving the recommended vaccination and to assess vaccination coverage among IEI patients in Latvia. METHODS: In this multicenter mixed-methods study, the vaccination status of all patients with IEI within two tertiary centers in Latvia was reviewed using electronic health records. Semi-structured interviews were conducted with 16 IEI patients who did not undergo vaccination, and a thematic analysis was performed. RESULTS: A total of 341 patients (49.3% female; median age 19.7 years (IQR:17)) were included in the quantitative part. The proportion of fully vaccinated individuals aged ≥ 12 years was 66.8%-70.9% with patients with selective IgA deficiency and 58.8% with other IEI (χ² = 14.12, p < 0.001). The proportion of fully vaccinated individuals aged 5-11 years was 11.1%. Age was associated with vaccination status: younger patients were found to have a significantly lower likelihood of receiving vaccination (U = 8585, p < 0.001). The five main themes identified were as follows: (1) fear and uncertainty; (2) risk and benefit assessment: COVID-19 vaccine-is it worth it? (3) external influences: the dark horse of the decision-making-people around us; (4) individuals against the system; and (5) beliefs about vaccination and COVID-19. Under-representation of certain IEI groups and recall bias are possible limitations of this study. CONCLUSIONS: While most reasons for hesitancy were similar to those previously described in the general population, disease-specific concerns were also identified.

Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies.

Predominantly antibody deficiencies (PADs) are inborn disorders characterized by immune dysregulation and increased susceptibility to infections. Response to vaccination, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be impaired in these patients, and studies on responsiveness correlates, including cytokine signatures to antigen stimulation, are sparse. In this study, we aimed to describe the spike-specific cytokine response following whole-blood stimulation with SARS-CoV-2 spike peptides in patients with PAD (n = 16 with common variable immunodeficiency and n = 15 with selective IgA deficiency) and its relationship with the occurrence of coronavirus disease 2019 (COVID-19) during up to 10-month follow-up period. Spike-induced antibody and cytokine production was measured using ELISA (anti-spike IgG, IFN-γ) and xMAP technology (interleukin-1ß (IL-1ß), IL-4, IL-6, IL-10, IL-15, IL-17A, IL-21, TNF-α, TGF-ß1). No difference was found in the production of cytokines between patients with PAD and controls. Anti-spike IgG and cytokine levels did not predict contraction of COVID-19. The only cytokine that distinguished between vaccinated and naturally infected unvaccinated PAD patients was IFN-γ (median 0.64 (IQR = 1.08) in vaccinated vs. 0.10 (IQR = 0.28) in unvaccinated). This study describes the spike-specific cytokine response to SARS-CoV-2 antigens, which is not predictive of contracting COVID-19 during the follow-up.

Long-Term Immunological Memory of SARS-CoV-2 Is Present in Patients with Primary Antibody Deficiencies for up to a Year after Vaccination.

Some studies have found increased coronavirus disease-19 (COVID-19)-related morbidity and mortality in patients with primary antibody deficiencies. Immunization against COVID-19 may, therefore, be particularly important in these patients. However, the durability of the immune response remains unclear in such patients. In this study, we evaluated the cellular and humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in a cross-sectional study of 32 patients with primary antibody deficiency (n = 17 with common variable immunodeficiency (CVID) and n = 15 with selective IgA deficiency) and 15 healthy controls. Serological and cellular responses were determined using enzyme-linked immunosorbent assay and interferon-gamma release assays. The subsets of B and T lymphocytes were measured using flow cytometry. Of the 32 patients, 28 had completed the vaccination regimen with a median time after vaccination of 173 days (IQR = 142): 27 patients showed a positive spike-peptide-specific antibody response, and 26 patients showed a positive spike-peptide-specific T-cell response. The median level of antibody response in CVID patients (5.47 ratio (IQR = 4.08)) was lower compared to healthy controls (9.43 ratio (IQR = 2.13)). No difference in anti-spike T-cell response was found between the groups. The results of this study indicate that markers of the sustained SARS-CoV-2 spike-specific immune response are detectable several months after vaccination in patients with primary antibody deficiencies comparable to controls.

Inborn error of immunity as the cause of recurrent pericarditis.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by a pyrin dysfunction, leading to uncontrolled interleukin-1 production that triggers the attacks. Here we report a case of a 36-year-old female patient repeatedly admitted to the cardiology ward with recurrent episodes of pericarditis, with intervals of 1 and 2 months between the episodes. During the attacks, chest pain and fever were the only symptoms. Following the administration of steroids and non-steroidal anti-inflammatory drugs, the patient became afebrile. She also had lymphoma and thyroid carcinoma in anamnesis essential for differential diagnosis. Laboratory tests for infection and autoimmune disease were all negative, and the positron emission tomography-CT scan did not reveal lymphoma relapse. Genetic testing revealed a mutation in the MEFV gene. It is very rare for pericarditis to be the first and only manifestation of FMF.

Serum and urinary calcium level in Latvian patients with sarcoidosis.

OBJECTIVES: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that in 90% of cases affects the lungs. Calcium metabolism testing can be useful in diagnostics. The aim of the study was to assess the correlation between calcium metabolism and sarcoidosis form of manifestation/demographic indicators. MATERIAL AND METHODS: In a retrospective study medical records of all patients (n = 699) who had been hospitalized with suspected sarcoidosis in a specialized clinic of Riga Eastern Clinical University Hospital during the period from January 1st, 2013 until December 31st, 2014 were analyzed. Further analysis included only patients with histologically and/or clinically confirmed sarcoidosis (n = 281). RESULTS: Patients' average age at the time of diagnosis was 39 ±13 years. Elevated serum calcium was observed in 9.9% of cases. A statistically significant correlation was found between serum calcium and age (p < 0.01). There was an association between serum calcium and gender (p < 0.05) - levels were higher in men (2.43 mmol/l) than in women (2.40 mmol/l). Elevated calcium in 24-hour urine was observed in 22.7% of patients. The mean value was 232.3 mg/24 h, levels were higher in men (258.7 mg/24 h) than in women (202.3 mg/24 h), and the association with gender was statistically significant (p < 0.01). CONCLUSIONS: We can conclude that in Latvia sarcoidosis affects mostly young and middle-aged people. Both serum calcium and calcium in 24-hour urine are important parameters for sarcoidosis diagnostics. Hypercalcemia was found in 9.9% of patients, hypercalciuria in 22.7% of patients, and both were statistically significantly higher in men, regardless of age.