How Did the Two Years of the COVID-19 Pandemic Affect the Outcomes of the Patients with Inflammatory Rheumatic Diseases in Lithuania?

Background and objectives: the COVID-19 pandemic globally caused more than 18 million deaths over the period of 2020-2021. Although inflammatory rheumatic diseases (RD) are generally associated with premature mortality, it is not yet clear whether RD patients are at a greater risk for COVID-19-related mortality. The aim of our study was to evaluate mortality and causes of death in a retrospective inflammatory RD patient cohort during the COVID-19 pandemic years. Methods: We identified patients with a first-time diagnosis of inflammatory RD and followed them up during the pandemic years of 2020-2021. Death rates, and sex- and age-standardized mortality ratios (SMRs) were calculated for the prepandemic and pandemic periods. Results: We obtained data from 11,636 patients that had been newly diagnosed with inflammatory RD and followed up until the end of 2021 or their death. The mean duration of the follow-up was 5.5 years. In total, 1531 deaths occurred between 2013 and 2021. The prevailing causes of death in the prepandemic period were cardiovascular diseases, neoplasms, and diseases of the respiratory system. In the pandemic years, cardiovascular diseases and neoplasms remained the two most common causes of death, with COVID-19 in third place. The SMR of the total RD cohort was 0.83. This trend was observed in rheumatoid arthritis and spondyloarthropathy patients. The SMR in the group of connective-tissue diseases and vasculitis was higher at 0.93, but did not differ from that of the general population. The excess of deaths in the RD cohort during the pandemic period was negative (-27.2%), meaning that RD patients endured the pandemic period better than the general population did. Conclusions: The COVID-19 pandemic did not influence the mortality of RD patients. Strict lockdown measures, social distancing, and early vaccination were the main factors that resulted in reduced mortality in this cohort during the pandemic years.

Association between Androgen Deprivation Therapy and the Risk of Inflammatory Rheumatic Diseases in Men with Prostate Cancer: Nationwide Cohort Study in Lithuania.

Background: The aim of this study was to assess the association between androgen deprivation therapy (ADT) and the risk of inflammatory rheumatic diseases in men with prostate cancer. Methods: Patients with prostate cancer between 2012 and 2016 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database, on the basis of rheumatic diseases diagnoses and information on prescriptions for androgen deprivation therapy. Cox proportional hazard models were used to estimate hazard ratios (HR) to compare the risks of rheumatic diseases caused by androgen deprivation therapy exposure in groups of prostate cancer patients. Results: A total of 12,505 prostate cancer patients were included in this study, out of whom 3070 were ADT users and 9390 were ADT non-users. We observed a higher risk of rheumatic diseases in the cohort of prostate cancer patients treated with ADT compared with ADT non-users (HR 1.55, 95% confidence interval (CI) 1.01−2.28). Detailed risk by cumulative use of ADT was performed for rheumatoid arthritis, and a statistically significant higher risk was found in the group with longest cumulative ADT exposure (>105 weeks) (HR 3.18, 95% CI 1.39−7.29). Conclusions: Our study suggests that ADT usage could be associated with increased risk of rheumatoid arthritis, adding to the many known side effects of ADT.

The manifestation of myositis in tick-borne encephalitis as a prophet of severe disease course: a rare case report.

Tick-borne encephalitis (TBE) is one of the most serious neurological tick-transmitted diseases. The initial phase usually occurs with non-specific symptoms such as fever, headache, and muscular pain. The clinical spectrum of the second phase of the disease typically ranges from mild meningitis to severe meningoencephalitis. Our case demonstrates a rare clinical case of acute myositis as manifestation of TBE virus infection. A 33-year-old female was admitted to the Rheumatology centre with a fever followed by proximal muscle pain and weakness. Despite the tick bite history and marginally positive anti-TBE virus IgM titre, the patient did not present any neurological symptoms. Laboratory test results showed elevated creatine kinase (CK) and myoglobin. Other infections, idiopathic inflammatory myopathies, were excluded. TBE virus infection was confirmed by rapid seroconversion of specific IgG class antibodies in serum. The second phase of the disease was followed by neurological symptoms and a repeated increase of CK and myoglobin. We suggest that in the case of acute myositis of unknown cause and the history of thick bite, TBE virus infection should be considered and creatine kinase might be considered as a laboratory marker of disease activity that correlates with the severity of the disease.

Mortality in Inflammatory Rheumatic Diseases: Lithuanian National Registry Data and Systematic Review.

Despite significant improvement in survival, rheumatic diseases (RD) are associated with premature mortality rates comparable to cardiovascular and neoplastic disorders. The aim of our study was to assess mortality, causes of death, and life expectancy in an inflammatory RD retrospective cohort and compare those with the general population as well as with the results of previously published studies in a systematic literature review. Patients with the first-time diagnosis of inflammatory RD during 2012-2019 were identified and cross-checked for their vital status and the date of death. Sex- and age-standardized mortality ratios (SMR) as well as life expectancy for patients with inflammatory RDs were calculated. The results of a systematic literature review were included in meta-standardized mortality ratio calculations. 11,636 patients with newly diagnosed RD were identified. During a total of 43,064.34 person-years of follow-up, 950 death cases occurred. The prevailing causes of death for the total cohort were cardiovascular diseases and neoplasms. The age- and sex-adjusted SMR for the total cohort was calculated to be 1.32 (1.23; 1.40). Patients with rheumatoid arthritis if diagnosed at age 18-19 tend to live for 1.63 years less than the general population, patients with spondyloarthritis-for 2.7 years less, patients with connective tissue diseases-for almost nine years less than the general population. The findings of our study support the hypothesis that patients with RD have a higher risk of mortality and lower life expectancy than the general population.

Incidence of Tuberculosis in Inflammatory Rheumatic Diseases: Results from a Lithuanian Retrospective Cohort Study.

Background and objective: With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients' population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population. Methods: Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website. Results: Overall, 8779 patients with newly diagnosed RD were identified during the 2013-2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18-97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41-1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk. Conclusions: Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.

Clinical characteristics and long-term survival differences of the ANCA-associated vasculitis group: a cross-sectional study of 27 patients.

OBJECTIVE: The goal of this study was to describe long-term patient survival and possible prognostic factors of a group of patients diagnosed with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) hospitalized at the tertiary Rheumatology Centre in Vilnius. MATERIAL AND METHODS: A cross-sectional study of 27 patients hospitalized at the Rheumatology Centre of Santaros klinikos of Vilnius University Hospital from 1 January 2001 to 31 December 2015 with diagnoses of GPA and MPA were carried out. Data on demographics, clinical characteristics, laboratory data, and the Birmingham Vasculitis Activity Score were collected. RESULTS: Seven (25.9%) patients during the onset of the disease received only oral glucocorticoids and 20 (74.1%) patients took additional medication. The BVAS median was 7 (minimum [min] - 2; maximum [max] - 23). The age median was 52 years (min - 12; max - 75). The overall mortality rate was 18.5%. Mean survival time was 126.6 months (95% confidence interval [CI] = 104.5 to 148.6) limited to 154.6 months for the longest-surviving patient. CONCLUSIONS: Life expectancy during past 15 years for AAV patients increased from 99.4 to 126.6 months. A high BVAS score at the onset of the disease is a bad prognostic factor related to shorter life expectancy. The growth of Staphylococcus aureus from nasopharynx might be associated with higher mortality rates and relapses in AAV patients.

The fact not to ignore: Mean blood pressure is the main predictor of increased arterial stiffness in patients with systemic rheumatic diseases.

PURPOSE: We aimed to evaluate the association between carotid-radial pulse wave velocity (PWV), augmentation index (AIx), and flow-mediated dilatation (FMD) of the brachial artery and factors potentially influencing them in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). MATERIAL AND METHODS: 316 patients diagnosed with RA (32%), SLE (20%), SSc (16%) and 156 controls (32%) were included in the study. Parameters of arterial stiffness AIx and PWV were obtained using applanation tonometry. FMD reflecting endothelial function was measured by ultrasound. RESULTS: AIx was increased in all three diseases (p<0.0001), but no differences were found between rheumatic diseases. In most of the RA cases PWV values were abnormal (on average by 0.52m/sec higher than in controls), while in SSc patients FMD values were diminished (p=0.006). Mean blood pressure (MBP) was the most consistent predictive factor in all three diseases, influencing both PWV and AIx, although patient age was also important in variation of AIx. The disease activity score (DAS28) was relevant only in RA patients. Furthermore, SLE disease activity index in SLE or Rodnan skin thickness score had no statistical significance in SSc and inflammatory markers. CONCLUSIONS: Both, PWV and AIx are dependent on MBP and age DAS28 may affect AIx in RA patients, while other disease or inflammatory markers are unlikely to have any effect. MBP is one of the main cardiovascular risk factors affecting the arterial stiffness in RA, SLE and SSc patients therefore controlling MBP in systemic rheumatic disease patients is mandatory.

Tumour-induced osteomalacia: a literature review and a case report.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report.