Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes.

Although it has been almost three years since the World Health Organization (WHO) declared a pandemic, COVID-19 is still an unsolved problem, thereby attracting great scientific interest. The disease has a heterogeneous clinical picture with multiple manifestations from different organs and systems. Currently, COVID-19 is perceived as a polysyndromic inflammatory disease involving not only the respiratory system, but also the musculoskeletal system, the cardiovascular system, the skin, the excretory and the nervous system, and is accompanied by a number of hematological, gastrohepatoenterological and endocrine disorders. Various pain phenomena also appear in the clinical presentation of the disease, often as a single manifestation or in combination with symptoms from different organs and systems. The pathogenesis of pain is complex and there is still no consensus on the exact driving mechanisms. Several different signaling pathways play an important role in the generation of pain impulses and perception. They are different for different types of pain. At this stage, the role of angiotensin-converting enzyme 2 (ACE), the renin-angiotensin system (RAC), angiotensin 2 receptors (AT2R), direct neuronal invasion of the virus, the involvement of pro-inflammatory cytokines, hypoxia, the involvement of macrophages, is discussed. as well as the role of overactivity of the immune system, causing the so-called "cytokine storm". Pain is the result of complex biochemical processes influenced to varying degrees by biological, physiological and social factors. Our knowledge at this stage remains scarce and is the subject of many studies on the key pathogenic mechanisms. Therefore, the purpose of this review is to describe the known mechanisms for the occurrence and persistence of pain in patients with COVID-19, as well as to classify the pain phenomena and present its most common localizations. The diagnosis and treatment of COVID-19 and associated pain should be carried out by a multidisciplinary team of specialists, given the heterogeneous clinical presentation of the disease.

Introduction: Periarthritis humeroscapularis is one of the most common causes of pain in the shoulder joint. The most applied treatment is conservative. Physical therapy and therapeutic modalities are effective, but there is uncertainty about their optimal combination. Objective: To examine whether the addition of either extracorporeal shock wave therapy or interferential electrotherapy to physical therapy of shoulder would be more effective in the management of periarthritis humeroscapularis. Materials and Methods: A total of 35 subjects with periarthritis humeroscapularis were divided into Group-A and Group-B. Both groups received 10 sessions of shoulder exercises and either extracorporeal shock wave therapy (Group-A) or interferential electrotherapy (Group-B). The outcome measures represent the American Shoulder and Elbow Surgeons Shoulder Score - the patient self-evaluation section (pain and activities of daily living) and the clinical assessment section (active and passive range of motion, strength, and stability). Results: Subjects showed statistically significant differences in reducing pain, improving range of motion and functional disability in the pre and post values of both the extracorporeal shock wave therapy and interferential electrotherapy groups. Group A was superior in improving external rotation ROM from abduction and flexion and Group B in alleviating pain. Conclusion: Either extracorporeal shock wave therapy or interferential electrotherapy in combination with physical therapy seemed to be significantly effective in the management of patients of periarthritis humeroscapularis. However, the group who received interferential electrotherapy showed higher improvement in pain, and the group with extracorporeal shock wave therapy demonstrated higher improvement in range of motion.

Introduction: The end of 2019 marked the beginning of a new disease for the mankind, which changed the lives of people all over the world. Almost 3 years have passed from the declaration of a global pandemic till today, but despite this, our knowledge of the disease COVID-19 caused by SARS CoV-2 is still the object of many researches. This is because the heterogeneous manifestation of the disease and the involvement of many organs and systems in the clinical presentation. The spectrum of rheumatological manifestations that directly concern the rheumatologist is also very miscellaneus. Most common are musculoskeletal pain phenomena as a rheumatic manifestation of the disease. Objectives: The purpose of the study is to assess the frequency and intensity of pain of musculoskeletal origin - joint (arthralgia) and muscle (myalgia) and its relationship with anxiety and depressive attitudes in hospitalized patients with COVID-19 in the Rheumatology Clinic - Varna. Material and methods: In a single-center, observational study, were included patients with diagnosed COVID-19, hospitalized in the Rheumatology Clinic, UMBAL "St. Marina" - Varna. The etiological diagnosis was accepted with a positive result of polymerase chain reaction (PCR) test or rapid antigen test for SARS-CoV-2. An inclusion criterion was new-onset musculoskeletal pain during the acute phase of COVID-19. Visual analogue scales (VAS) were used to assess pain intensity (muscular and joint) and Tsung self-report scales for depression (SDS) and anxiety (SAS). Laboratory acute inflammatory indicators and thrombotic biomarkers were investigated, chest imaging was performed in all patients. Descriptive statistics, Spearman Rho correlation analysis and SPSS linear regression analysis were used. A significance level of p<0.05 was accepted. Results: 226 patients (aged 26-91 years) with musculoskeletal pain were included. 46.5% (n=105) were women and 53.5% (n=121) were men. The mean age of the study population was 65.5 years (65.57 ± SD). A significant correlation (p=0.001) and predictive value was found between the score for depression and anxiety and the intensity of pain (for the two studied pain phenomena - arthralgias and myalgias). No correlation was found between pain intensity and inflammatory markers, nor with thrombogenic markers in patients with SARS-CoV-2. Of all examined patients with musculoskeletal pain, 46.5% (n=105) were women and 53.5% (n=121) were men. The average age of the study population was 65.5 years (65.57). After the correlation and regression analysis, a significant correlation (0.001) and predictive value was found between the score for depression and anxiety and the strength of pain (for the two studied pain phenomena - arthralgias and myalgias). On the other hand, in the studied patients, we found no correlation with either inflammation indicators or thrombogenic markers in the SARS-CoV-2 patients.mong all 226 COVID-19 patients with musculoskeletal pain, 46.5% (n =105) were women and 53.5% (n =121), were men. Mean age was 65 and a half years (65.57). After correlation and regression (ANOVA) analysis made we found strongly significant correlation (correlation is significant et the 0.001 level) and predictive value between depression and anxiety scales score from one side and pain intensity from other (both arthralgia and myalgia). On the other hand, musculoskeletal pain does not correlate with any of inflammation and thrombotic biomarkers assessed in SARS-CoV-2 patients. mong all 226 COVID-19 patients with musculoskeletal pain, 46.5% (n =105) were women and 53.5% (n =121), were men. Mean age was 65 and a half years (65.57). After correlation and regression (ANOVA) analysis made we found strongly significant correlation (correlation is significant et the 0.001 level) and predictive value between depression and anxiety scales score from one side and pain intensity from other (both arthralgia and myalgia). On the other hand, musculoskeletal pain does not correlate with any of inflammation and thrombotic biomarkers assessed in SARS-CoV-2 patients. Conclusion: Musculoskeletal pain is one of the most common clinical presentations of COVID-19. The intensity of the pain correlates with anxiety and depressive symptoms in these patients and does not correlate with the levels of inflammation and thrombotic biomarkers.

Objectives: Aim of the study was to assess the therapeutic efficacy and safety of upadacitinib in Rheumatoid arthritis patients with moderate to high disease activity in real-world clinical practice and to identify predictors of therapeutic success. Materials and methods: A retrospective single-center study was performed in RA patients treated with upadacitinib 15 mg daily. Demographic and clinical indicators were analyzed. The effectiveness and safety of the medication were evaluated over a six-month period. Disease activity was assessed with index-based scores. The primary endpoint was defined as low disease activity over a six-month treatment period with upadacitinib 15 mg/day (DAS28CRP ≤ 3.2, CDAI ≤ 10 and SDAI ≤ 11). Results: 41 patients were included, mean age 56.56 years (± 13.4), with long-standing RA (8 years ± 5.8), mostly female (80.5%). 19.5% of them were obese (BMI ≥ 30 kg/m2), 80.5% had osteoarthritis and 58.5% - hypertensive disease. Erosive arthritis was observed in 41.5% of patients  and 61% had functional class III motor deficit. "Bio-naïve" were 58.5%, the rest had previous experience with biologic therapy. Upadacitinib was used as monotherapy in 90% of patients and in combination with Methotrexate in 10%. There was a significant reduction in the painful and swollen joint counts, VAS and CRP six months after starting treatment with upadacitinib. Low disease activity was achieved by a significant proportion of patients (DAS28CRP-70.7%, CDAI-60.5% and SDAI 63.2%).  Therapeutic outcome was not determined by demographics, clinical factors, comorbidities, or prior biologic treatment. Increase in liver enzymes (n=3), decrease in hemoglobin levels (n=2), and urinary tract infection (n=2) were the adverse events recorded over the six-month treatment period. One patient died from COVID-19. Conclusion: A significant proportion of RA patients on treatment with upadacitinib 15 mg was able to achieve the therapeutic target in real clinical settings. No predictors of therapeutic efficacy were found. The registered side effects do not differ from the safety profile of the medication.