Is Th17-Targeted Therapy Effective in Systemic Lupus Erythematosus?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical manifestations. The proposed pathophysiological hypotheses of SLE are numerous, involving both innate and adaptive abnormal immune responses. SLE is characterized by the overproduction of different autoantibodies that form immune complexes, which cause damage in different organs. Current therapeutic modalities are anti-inflammatory and immunosuppressive. In the last decade, we have witnessed the development of many biologicals targeting different cytokines and other molecules. One of them is interleukin-17 (IL-17), a central cytokine of a proinflammatory process that is mediated by a group of helper T cells called Th17. Direct inhibitors of IL-17 are used in psoriatic arthritis, spondyloarthritis, and other diseases. Evidence about the therapeutic potential of Th17-targeted therapies in SLE is scarce, and probably the most promising is related to lupus nephritis. As SLE is a complex heterogeneous disease with different cytokines involved in its pathogenesis, it is highly unlikely that inhibition of only one molecule, such as IL-17, will be effective in the treatment of all clinical manifestations. Future studies should identify SLE patients that are eligible for Th17-targeted therapy.

The Levels of Serum Serotonin Can Be Related to Skin and Pulmonary Manifestations of Systemic Sclerosis.

Background and Objective: The most prominent feature of systemic sclerosis (SSc), besides vasculopathy and autoimmune disorders, is excessive fibrosis. Serotonin affects hemostasis and can induce vasoconstriction, which is presumed to be one of the pathophysiological patterns in SSc that leads to fibrosis. Our aim was to explore the possible association of serotonin with some of the clinical features of SSc in our cohort of patients. Materials and Methods: We measured serotonin levels in sera of 29 female SSc patients. Patients were 41-79 years old, their average disease duration was 9 years. Serotonin values were analyzed in correlation with clinical and laboratory parameters, such as modified Rodnan skin score (mRSS), digital ulcers (DU), and spirometry parameters-forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and lung diffusion capacity of carbon monoxide (DLCO). Statistical analyses were performed using statistical software Statistica. Results: We found correlation of serotonin level with mRSS (r = 0.388, p = 0.038). The highest values of serotonin were documented in patients with refractory DU, but this was not statistically significant. We also found a negative correlation between serotonin and FVC (r = -0.397), although it did not reach the level of significance (p = 0.114). Conclusions: Our study suggests that levels of serum serotonin could affect the course of skin fibrosis and partially restrictive pulmonary dysfunction in patients with SSc. We assume that serotonin might have influence on several features of SSc, but more studies are needed to reveal those relations.

[Long-term glucocorticoid therapy and the rapid development of squamous cell carcinoma in systemic sclerosis: Is there a connection?].

Systemic sclerosis (SSC) is an autoimmune disease associated with the risk of malignancies, especially lung cancer, among which adenocarcinoma and squamous cell carcinoma are the most frequent. A 63-year-old female patient with SSC was hospitalized due to blackouts, poor general condition, and changes in her fingers. Because of subsequent epileptic seizures resulting in weakness of the left side of her body, computerized tomography (CT) of the neurocranium was performed which showed metastatic lesions. A CT scan of the thoracic organs displayed pulmonary neoplasia in the right hilum, which were histologically evaluated as grade 2 squamous cell carcinoma. After one month of hospitalization with supportive therapy, the patient's clinical condition improved, and she was discharged into home care with recommendations for further oncological treatment. However, the patient died several days later. In comparison to adenocarcinomas, squamous cell carcinomas of the lungs usually develop through a significantly longer period. We consider that the unusually rapid development of the carcinoma in this patient was stimulated by the immunosuppressive effect of high doses of glucocorticoids that she had been taking for several years on her own initiative.

[Polymyositis and systemic sclerosis overlap - A case report and a review of the literature].

Polymyositis (PM) is an autoimmune disease which affects skeletal muscles. In young age, it usually occurs as an idiopathic disorder associated with specific autoantibodies (anti-Jo), while in older age it is often associated with neoplasms. It can present with symptoms of other autoimmune diseases, such as systemic sclerosis (SSc), a rare progressive disease characterized by collagen deposits in various tissues and organs. A 65-year-old patient, long-time smoker, came to the ER because of painful edema in the distal parts of his limbs and proximal muscle weakness of his arms and legs. Although his muscle enzymes were not increased, PM was confirmed by the characteristic pathohistological finding. The patient had sclerodermal skin lesions on his back, but he did not have other typical SSc symptoms, and the specific autoantibodies were negative. He received glucocorticoid therapy (GC) after we had finished screening for malignant tumors. He felt better, his muscle strength returned, and the limb edema disappeared. Four weeks later, he developed symptoms which are more typical of SSc, such as dysphagia, Raynaud's phenomenon, and skin thickening of the limbs that had been swollen. PM is often associated with SSc. It is not clear if the exacerbation of latent SSc was stimulated by GC, or if it was just a simple overlap of the two diseases with different onsets. There are no therapy guidelines for the treatment of this combination of diseases. Careful use of GC is necessary even if SSc symptoms are discreet, because of the well-known effects of GC in SSc.

Adropin Serum Levels in Patients with Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) patients have higher prevalence of endothelial dysfunction and premature atherosclerosis. Recent studies investigated adropin, a secretory protein that can regulate lipid metabolism and insulin resistance and protect endothelial cells' function and that has an anti-inflammatory effect. The aim of this study was to determine adropin levels in pSS patients compared to healthy controls. Additional goals were exploring the correlation between adropin and several metabolic and immunological parameters in pSS, including disease specific antibodies, EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), and Sjögren's Syndrome Disease Damage Index (SSDDI). This research included 52 pSS patients and 52 healthy controls. pSS patients have significantly higher adropin levels compared to the control group (3.76 ± 0.68 vs. 3.14 ± 0.69 ng/mL, p < 0.001). Correlation analysis showed that adropin levels in pSS patients have positive correlation with high-density lipoprotein (HDL) (r = 0.290, p = 0.036) and anti SSA/Ro52 antibodies (r = 0.307, p = 0.026) and negative correlation with SSDDI (r = -0.401, p = 0.003). Multivariant linear regression showed that adropin levels are independently associated with HDL (ß ± SE, 0.903 ± 0.283, p = 0.002) and SSDDI (ß ± SE, -0.202 ± 0.073, p = 0.008). Our findings imply that adropin could be involved in the pathophysiology of pSS, yet it remains to be elucidated in future studies whether adropin has a protective or detrimental role in this setting.

Low dose intravenous immunoglobulin in addition to cyclophosphamide in systemic sclerosis : Single centre experience.

AIM: Systemic sclerosis (SSc) is a rare chronic disease characterized by pathologic collagen deposits in the skin and internal organs. Although it is considered to be an autoimmune disease, immunosuppressants have a limited effect on severe SSc. Intravenous immunoglobulins (IVIG) have shown favorable effects in patients with SSc by suppressing the action of profibrotic cytokines, so they could have additional effect on standard treatment such as cyclophosphamide (CYC). This article presents the immunomodulatory effect of low-dose IVIG in addition to CYC in the treatment of severe SSc in this center during the last 9 years. METHODS: This retrospective observational study analyzed the medical documentation of nine patients with SSc treated with low-dose IVIG (0.4 g/kg and month) together with intravenous CYC (600 mg/m2 and month). The therapeutic effect on lung and skin manifestations was assessed. RESULTS: Of the patients one had interstitial lung diseases (ILD), two had progressive skin diseases, and six had a combination of skin and lung involvement. The best results were achieved in skin changes, where complete healing of digital ulcers (DU) was recorded in every reported case. A decrease in the modified Rodnan skin score (mRSS) was noted in three patients and increased diffusion capacity of the lungs for carbon monoxide in another three patients. CONCLUSION: The results of the study suggest that IVIG may be an additional treatment option together with CYC for patients for whom other therapies have failed, but further studies on the exact role of IVIG in the treatment of severe SSc are required.

Dietary Habits in Patients with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are often interested in which diets to follow. Our aim was to investigate which dietary habits were common among our patients, and which of them were in correlation with laboratory parameters of disease activity, such as complement values and 24-h proteinuria. This study included 76 patients with SLE in clinical remission with a 6-month flare free period. They completed a specialized, self-administered, 23-item food frequency questionnaire about their weekly dietary habits. Basic anthropometric data, levels of C3 and C4, and 24-h proteinuria were recorded and analyzed with respect to their dietary habits. The majority of patients had a normal body mass index of 18.5-25 kg/m2, and worked out regularly. The most frequently consumed foods reported by the patients were fruits, milk, vegetables, meat, pasta, rice, and bread. Decreased values of C3 were found in 34 (44.7%) patients, and decreased values of C4 in 28 (36.8%) patients. Decreased values of C3 were found in patients who often consumed meat (P = .015), and decreased values of C4 in patients who often consumed fast food (P = .043). Patients who often consumed fast food demonstrated a decreasing trend of C3 (P = .060), and patients who often consumed fried food had a decreasing trend of C4 (P = .051). Significant correlation between daily proteinuria and dietary habits was not found. Dietary habits can influence the disease course of SLE. Our study confirms that decreased levels of complement compounds C3 and C4, which are possible predictors of disease activation, are associated with frequent consumption of low quality proteins and food rich in calories.

Biomarkers of skin and lung fibrosis in systemic sclerosis.

Introduction: Excessive fibrosis is the hallmark of systemic sclerosis (SSc) and numerous experts are investing efforts into identifying parameters that could predict disease course and prognosis. Here, we review the available and potential biomarkers of lung and skin fibrosis in SSc.Areas covered: Specific autoantibodies are important for the determination of clinical subsets of SSc, making them routine in clinical practice. Physical parameters, such as modified Rodnan skin score (mRSS) and pulmonary function tests are standardized in evaluating the skin and lung involvement. High resolution computed tomography is the gold standard for SSc-related interstitial lung disease (ILD) diagnostics, as well as progress evaluation. Nowadays, the main focus is on specific autoantibodies, various genetic pathways, and different cytokines. In addition to the profibrotic role of interleukin 6 and transforming growth factor-ß, newer studies stress on glycoprotein Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D) and chemokine (C-C motif) ligand 18 (CCL18) as potential biomarkers of skin and lung fibrosis in SSc.Expert opinion: Skin and lung biomarkers in SSc frequently mirror the typical signs of fibrosis, overlapping sporadically. There is an urgent need for better diagnostic distinction and evaluation; therefore, further investigations are critical to establish more suitable biomarkers of SSc.

Prediabetes awareness among Southeastern European physicians.

AIMS/INTRODUCTION: Prediabetes (PD) represents a transitional state where the glucose levels are higher than normal, but not enough for diabetes mellitus diagnosis. As there is a growing number of the population with PD, its early detection and treatment could prevent the development of diabetes mellitus and its complications. We aimed to assess the overall knowledge of PD among medical professionals of different varieties. MATERIALS AND METHODS: A questionnaire-based study addressing PD and type 2 diabetes mellitus knowledge among Southeastern European general practitioners, postgraduates, physicians and superior specialists was carried out. RESULTS: A total of 397 physicians completed the questionnaire. The total rate of correct answers from diabetologists, non-diabetologist internists, residents and general practitioners was 69, 56.1, 54 and 53%, respectively. Questions related to the PD definition achieved a total of 46.6% correct answers. Correct responses considering the numerical definition of impaired fasting glucose and impaired glucose tolerance were 46.3 and 46.8%, respectively. Younger physicians had better knowledge of numerical values regarding PD and type 2 diabetes mellitus criteria (P < 0.001). CONCLUSIONS: The present results show that overall knowledge of PD is poor among Southeastern European physicians, which necessitates adequate educational programs on PD in this region.