Rheumatology (Bulgaria)

Tenascin-C and Interleukin-17 Up-regulation in Axial Spondyloarthritis Patients

Mohammed S. Al-Hindawi — 2023-03-06

Background: Axial spondyloarthritis (axSpA) is an inflammatory, systemic rheumatic condition that mostly affects the axial skeleton. Tenascin-C (TN-C) is a hexameric glycoprotein of considerable size, upregulated in many inflammatory conditions, while Interleukin-17 (IL-17) a cytokine that plays an important role in SpA symptoms. Objective: to investigate the upregulation between the serum levels of TN-C and IL-17 in Iraqi axSpA patients and the disease characteristics. Patients and Methods: Seventy-four axSpA patients and 28 matched controls were studied. Fifty-four patients received a tumor necrosis factor inhibitor (TNFi) and 20 did not. Serum TN-C and IL-17 concentrations were determined using the ELISA technique. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was assessed. For statistical tests, Chi Square, Mann Whitney, Independent Samples T, and Pearson's correlation tests are used. Results: Patients mean age was 35.6±0.9 years, 65 males and 9 females, and disease duration was 5.18±0.6 years. 47.4% were smokers, 47% had inflammatory low back pain, and HLA-B27 was present in 91%. BASDAI mean was 6.1±0.4 in non-TNFi and 2.6±0.3 in those on TNFi. The serum TN-C concentration was significantly increased in patients, especially those on non-TNFi (79±9.6 pg/mL) compared to those on TNFi (69.1±3.2 pg/mL) and control (53±3.9 pg/mL) (p=0.003). Serum IL-17 was significantly elevated in those receiving TNFi (877.9±257 pg/mL) compared to non-TNFi (487.2±234 pg/mL) and control (182.4±36.6 pg/mL) (p=0.033). The TN-C significantly correlated with erythrocyte sedimentation rate (r=0.27, p=0.02) and with hemoglobin (Hb) concentration (r=0.26, p=0.02). TN-C and IL-17 were non-significantly related (r=0.14, p=0.2). Conclusions: axSpA Patients demonstrated high levels of serum TN-C, particularly in those not receiving TNFi, and high IL-17 levels in those receiving TNFi, suggesting that there is an association with tissue injury from the disease and stimulation of immunological and resident tissue cells. Patients who had not received TNFi showed significantly higher disease activity than others.

Biomarkers in Systemic Lupus Erythematodes

Valentina Simeonova Reshkova — 2023-03-06

A biomarker is defined as a genetic, biological, biochemical or molecular event, whose alterations correlate with the pathogenesis and/or manifestations of a disease and can be evaluated qualitatively and/or quantitatively in laboratories. Biomarkers are used for diagnosis, assessment of activity and better understanding of the pathogenesis of SLE (systemic lupus erythematodes). Biomarkers in SLE are conditionally subdivided into markers of genetic susceptibility, markers of diagnosis and markers of disease activity. Recent genetic studies of SLE have focused on correlating SLE (susceptibility, disease spectrum and severity) with polymorphisms of hypothetical candidate genes. These include genes coding for mannose-binding lectin (MBL), cytokines (IL-6, IL-10, IL-21, TNF-α and osteopontin), chemokines (MCP-1), cytokine receptors/antagonists (type II TNF-α receptor and IL-1 receptor antagonist), Fcγ receptors (FcγRIIa, FcγRIIb, FcγRIIIa, and FcγRIIIb), IFNα, programmed death protein-1 (PD-1; also known as PDCD-1) and other cell surface receptors (cytotoxic T lymphocyte antigen-4 (CTLA-4) involved in the pathogenesis of SLE. Biomarkers for diagnostic are anti-dsDNA, erythrocyte-bound C4d/Erythrocyte-CR1 and platelet-bound C4d. Markers of disease activity are complement components, cytokines, soluble cytokine receptors IL-2R, TNFR, IL-1Ra, soluble molecules expressed on the cell surface − BLyS (BAFF), CD27, CD154, endothelial dysfunction markers − sICAM, sVCAM, thrombomodulin, circulating endothelial cells, acute-phase proteins − CRP, ferritin. Genetic testing for biomarkers in SLE patients is currently being introduced in the Rheumatology Clinic to “Sv. Ivan Rilski” Multiprofile University Hospital for Active Treatment, Sofia, Bulgaria. Its performance is expected to help solve multiple unmet needs in SLE patients – precise diagnosis, identification and prediction of the timing of disease flares, clinical assessment and adequate treatment approach.

Pain in COVID-19 and features of pathogenetic molecular mechanisms

Simona Bogdanova — 2023-03-06

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.

Rheumatological aspects of IgG4-related disease (IgG4-RD)

Detelin Dimov — 2023-03-06

Abstract. Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory disorder, characterized by a tissue IgG4(+)plasma cells infiltration, leading to fibrosis and destruction of the involved organs. The IgG4-RD scope includes all organs and systems but within the review only the actual diagnostic and therapeutic data concerning disease localisations in the lacrimal and salivary glands, kidneys, retroperitoneum, lungs and aorta and arteries are included because they are also a terrain of a rheumatological pathology – vasculitides, Sjogren’s syndrome, SLE, systemic sclerosis and so on.

Patient with Systemic Lupus Erythematodes, high pANCA antibodies and end-stage renal failure

Rada Gancheva — 2023-03-06

A 47-year-old female patient with active Systemic lupus erythematosus (SLE) - skin, joint, hematological, and renal involvement was admitted for rapidly progressive renal failure at the background of very high anti-dsDNA and pANCA antibodies. Active pathogenetic treatment was started pulse therapy with methylprednisolone, intravenous immunoglobulins (IVIG) and cyclophosphamide, blood transfusions were performed, symptomatic treatment with infusions ad diuretic was initiated. Due to progression of renal failure with volume overload and increase in urea and creatinine levels renal-replacement therapy was initiated. The patient developed E. faecalis and E. durans sepsis with disseminated intravascular coagulation and ground-glass-type lung changes and the condition further deteriorated to fatal multiorgan failure. The authors discuss the role of pANCA antibodies in SLE with renal and lung involvement.

Clinical case of a patient with Thoracic outlet syndrome

Zhaklin Rumenova Dimova — 2023-03-06

Thoracic outlet syndrome (TOS) is a group of conditions that result in compression of the brachial plexus, causing symptoms of pain, muscle weakness, and numbness in the shoulders and upper extremities. The classification of TOS is based on pathophysiological symptoms and is mainly divided into neurogenic (nTOS), venous (vTOS) and arterial (aTOS). Depending on the etiology, TOC can be classified as congenital, traumatic, or functionally acquired.

We present a clinical case of a 34-year-old man who was admitted to the Rheumatology Clinic, UMBAL "St. Ivan Rilski" in July 2022. The patient reports complaints of numbness in the fingers, weakness of the upper extremities when the arms are raised, and periungual bruising. The patient underwent phlebography in 2021, with the conclusion of compression of v.subclavia dextra et sinistra during abduction and ipsilateral rotation of the head. From the performed CT-angiography, compression of the right common iliac artery on the left common iliac vein was found, which was dilated, corresponding to the highest degree with May-Turner syndrome. In the rheumatology clinic, capillaroscopy was performed, which visualized peripheral vascular spasm and nonspecific changes. Laboratory and immunological tests did not reveal any abnormalities.

Early diagnosis of Takayasu arteritis

Soner Emin — 2023-03-06

Systemic vasculitis is a group of heterogeneous diseases characterized by inflammation of the vascular wall. They can be primary or arise in the context of another disease. Blood vessels of different sizes are affected, being mainly divided into small, medium and large vessels. Takayasu's arteritis is a vasculitis of the large blood vessels, most often affecting the aorta and its branches, subclavian arteries, iliac, femoral arteries and others. The presented clinical case concerns a woman with non-specific symptoms - low fever, sweating, weight loss, easy fatigue. After excluding an infectious genesis of the complaints, a diagnosis of Takayasu's Arteritis was made in the early phase of the disease as a result of Positron emission tomography. Corticosteroid and immunosuppressive therapy was started. When conducting a control PET, 20 months after the start of the therapy, a significant regression to absence of the findings from the imaging study was observed.

Case report of a patient with Ewing’s sarcoma.

Nikolay Stoilov — 2023-03-06

Ewing's sarcoma is the second most common bone tumor in childhood and adolescence. Its incidence varies significantly among races, but is relatively rare among black children and the Chinese population. Patients with Ewing sarcoma exhibit local symptoms characterized by tumor mass formation, pain, swelling, venous dilatation, and hyperemia. Pathological fractures due to bone metastases with progressive neurological deficit to paralysis may occur. In cases where Ewing's sarcoma originates in the chest wall, pleural infiltration combined with carcinomatous pleuritis is often presented .

We present the case of a 40-year-old patient initially diagnosed with a Baker's cyst in the left popliteal fossa. After consultation with an orthopedic surgeon, the patient was referred for surgical removal of the formation. An extirpation was performed, but the histological result did not confirm the diagnosis and characterized the finding as "cystic lobular capillary hemangioma ". A re-excision was performed in November 2018 due to recurrence of the formation. Immunohistochemical tests performed subsequently found that immunophenotypically and morphologically the finding correlated most highly with Ewing's extraskeletal sarcoma. Two months after excision, PT/CT was performed, which showed no recurrence and no secondary dissemination. One year later, due to arthralgias in the right shoulder joint, the patient underwent MRI and CT. The result of imaging studies revealed tumor recurrence in the diaphysis of the right humerus with secondary intrapulmonary dissemination. The patient was started on chemotherapy with good clinical response.