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OBJECTIVES: Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three single nucleotide polymorphisms of ACE2 (C>G rs879922, G>A rs2285666 and A>G rs1978124) were found to increase the risk for development of arterial hypertension (AH) and cardiovascular (CVS) diseases in different ethnicities. We investigated associations of polymorphisms rs879922, rs2285666 and rs1978124 with the development of SSc. METHODS: Genomic DNA was isolated from whole blood. Restriction-fragment-length polymorphism was used for genotyping of rs1978124, while detection of rs879922 and rs2285666 was based on TaqMan SNP Genotyping Assay. Serum level of ACE2 was assayed with commercially available ELISA test. RESULTS: 81 SSc patients (60 women, 21 men) were enrolled. Allele C of rs879922 polymorphism was associated with significantly greater risk for development of AH (OR=2.5, p=0.018), but less frequent joint involvement. A strong tendency to earlier onset of Raynaud's phenomenon and SSc was seen in carriers of allele A of rs2285666 polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less frequent gastrointestinal involvement. Women with genotype AG of rs1978124 polymorphism had significantly more frequent digital tip ulcers and lower serum level of ACE2. CONCLUSIONS: Polymorphisms of ACE2 may account for the development of AH and CVS disorders in SSc patients. Strong tendencies to more frequent occurrence of disease specific characteristics distinct to macrovascular involvement will require further studies evaluating significance of ACE2 polymorphisms in SSc.
Subject(s)
Cardiovascular Diseases , Hypertension , Scleroderma, Systemic , Female , Humans , Male , Angiotensin-Converting Enzyme 2/genetics , Angiotensins/genetics , Polymorphism, Single Nucleotide , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/geneticsABSTRACT
Internal medicine emerged as a new medical specialty in the second half of the 19th century. It was based on a novel diagnostic and therapeutic paradigm, and included pathophysiologic interpretation of physical examination, laboratory tests, and imaging techniques, in contrast with previous descriptive approach to clinical problems. Professor Edward J. Sas-Korczynski in 1891 proposed to organize Polish meetings on internal medicine. The proposal was implemented only in 1906 by Antoni W. Gluzinski, a famous Polish internist. Despite obstacles set by the partitioning powers, the Society of Internists of the Polish Lands was founded. The name of the association was changed to the Polish Society of Internal Medicine during the congress held in Vilna (now Vilnius) in 1923, the first one organized in the independent Poland. The journal of the Society, Polish Archives of Internal Medicine, was founded and Antoni W. Gluzinski was its first editor-in-chief. Later, the journal was edited by Wladyslaw Janowski, Witold E. Orlowski, Andrzej Biernacki, Tadeusz Orlowski, Artur Czyzyk, and Anetta Undas. Witold E. Orlowski was a father of modern Polish internal medicine, and contributed to the development of its subspecialties and their societies. Most of them had roots in the specialist sections of the Polish Society of Internal Medicine. The journal supported the newly founded societies by publication of issues focused on selected subspecialties. Despite the development of subspecialties, the role of internal medicine as a holistic discipline covering the diagnosis and therapy of many organs does not decrease.
Subject(s)
Educational Personnel , Internal Medicine , Humans , Poland , Internal Medicine/history , Societies, Medical/historyABSTRACT
OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Antibodies, Antineutrophil Cytoplasmic , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/epidemiology , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/epidemiology , Humans , Microscopic Polyangiitis/complications , Microscopic Polyangiitis/epidemiology , Recurrence , Registries , Retrospective StudiesABSTRACT
INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPOANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. OBJECTIVES: In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype. PATIENTS AND METHODS: We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol. RESULTS: In the ANCA-positive group (antiMPO, antiPR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. AntiMPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCAnegative GPA and EGPA as well as PR3+AAV. Moreover, ANCAnegative AAV was characterized by a low risk of endstage kidney disease and death. CONCLUSIONS: The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPOANCA-positive AAV constitute a clinically homogeneous group, whereas PR3ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Antibodies, Antineutrophil Cytoplasmic , Churg-Strauss Syndrome/complications , Demography , Female , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/diagnosis , Humans , Male , Microscopic Polyangiitis/complications , MyeloblastinABSTRACT
Systemic connective tissue diseases (CTDs) comprise a large group of diseases that are auto-immune in nature and characterized by the involvement of multiple systems and organs. Pul-monary hypertension (PH) of various etiologies may develop in the course of CTD, including pulmonary arterial hypertension (PAH), PH secondary to the lung disease, postcapillary PH in the course of left heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). In addition, the different forms of PH may coexist with each other. Among patients with CTD, PAH occurs most commonly in those with systemic sclerosis, where it affects ap-proximately 8%-12% of patients. The prognosis in patients with untreated PAH is very poor. It is particularly important to identify the high-risk CTD-PAH population and to perform effi-cient and accurate diagnostics so that targeted therapy of the pulmonary arteries can be intro-duced. Echocardiography is used to screen for PH, but clinical and echocardiographic suspicion of PH always requires confirmation by right heart catheterization. Confirmation of PAH ena-bles the initiation of life-prolonging pharmacological treatment in this group of patients, which should be administered in referral centers. Drugs available for pharmacological management include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclins.
Subject(s)
Connective Tissue Diseases , Hypertension, Pulmonary , Rheumatology , Connective Tissue Diseases/complications , Expert Testimony , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Poland , Pulmonary CirculationABSTRACT
Whipple's disease is a rare, chronic, systemic disorder caused by Tropheryma whipplei infection. The most common symptoms are weight loss, arthralgia, diarrhea and abdominal pain. Other organ involvement can also occur in the patients. Joint manifestations may mimic rheumatoid arthritis or spondyloarthritis. Arthalgia, arthritis, spondylodiscitis, bursitis and/or tenosynovitis are seen in the majority of the patients. This explains why some of the symptoms are misdiagnosed as those of rheumatic diseases. Understanding of Whipple's disease is important for differential diagnostics of several rheumatic symptoms.
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The aim of the study was to determine whether plasma levels of total glycosaminoglycans (GAGs), matrix metalloproteinases (MMPs) (MMP-3, MMP-10), and their tissue inhibitors (TIMPs) (TIMP-1, TIMP-2) as well as transforming growth factor ß (TGF-ß) differ in the patients with systemic sclerosis (SSc) in relation to the healthy subjects. Plasma samples were obtained from 106 people (64 patients with SSc and 42 healthy individuals) and measured for MMP-3, MMP-10, TIMP-1, TIMP-2, and TGF-ß levels using ELISA methods. GAGs isolated from plasma samples were quantified using a hexuronic acid assay. The plasma levels of total GAGs, TIMP-1, TIMP-2, and TGF-ß were significantly higher, while MMP-3 was significantly decreased in SSc patients compared to the controls. We have revealed a significant correlation between plasma GAGs and TGF-ß (r = -0.47) and TIMP-2 (r = 0.38), respectively. The results of this study revealed that remodeling of the extracellular matrix, reflected by quantitative changes in plasma glycosaminoglycans, occurs during systemic sclerosis. Thus, the alterations in GAG metabolism connected with SSc may lead to systemic changes in the properties of the connective tissue extracellular matrix.
Subject(s)
Glycosaminoglycans/blood , Matrix Metalloproteinase 10/blood , Matrix Metalloproteinase 3/blood , Scleroderma, Systemic/blood , Tissue Inhibitor of Metalloproteinase-1/blood , Tissue Inhibitor of Metalloproteinase-2/blood , Transforming Growth Factor beta/blood , Adult , Female , Humans , Male , Middle AgedABSTRACT
Coronavirus disease 2019 (COVID19) is an infectious disease that became a global health emergency. This review focuses on the aspects of COVID19 pertaining to rheumatology, including signs and symptoms akin to those observed in rheumatic disorders, risk of infection or severe course of the disease in patients with a pre existing rheumatic disease and those receiving antirheumatic or immunosuppressive medication, as well as potential use of antirheumatic or anticytokine therapeutic strategies that are already applied in rheumatology (among others, chloroquine, hydroxychloroquine, tocilizumab, and baricitinib) in patients with COVID19.
Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Rheumatic Diseases/drug therapy , Antirheumatic Agents/therapeutic use , COVID-19 , Chloroquine/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Pandemics , Rheumatologists/standards , COVID-19 Drug TreatmentABSTRACT
PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71). CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Drug-Related Side Effects and Adverse Reactions/diagnosis , Immunosuppressive Agents/adverse effects , Registries/statistics & numerical data , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Azathioprine/adverse effects , Cyclophosphamide/adverse effects , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , Male , Methotrexate/adverse effects , Middle Aged , Poland/epidemiology , Prognosis , Retrospective Studies , Rituximab/adverse effects , Survival RateABSTRACT
Systemic sclerosis (SSc) is a rare, chronic autoimmune disease with unknown etiology. Its prominent features are fibrosis, vasculopathy and impaired immune response. Disease can also affect eyes leading to various findings in ophthalmological examination. The objective of this study was to determine the prevalence and type of ocular involvement in patients with SSc. A systematic literature review was conducted using electronic databases. A combination of following keywords was used: "systemic sclerosis" and ophthalmology-related search terms, including the keywords "eye", "ocular" and "ophthalmic". In conclusion, eyelid and conjunctival abnormalities and dry eye disease are among the most common ocular manifestations of SSc. Their diversity is connected to complexity of the disease.
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Dercum's disease (adiposis dolorosa) is a rare disease of unknown etiology characterized by painful subcutaneous adipose tissue deposits with various localization over the body. The deposits occur histologically as lipomas and are associated with overweight or obesity and a variety of psychiatric disturbances (anxiety, depression, sleep disturbances). Classification of Dercum's disease is related to size and location of adipose nodules (generalized diffuse, generalized nodular, localized nodular and juxta-articular forms). Diagnosis in based on clinical presentation and exclusion of a number of other disorders associated with lipomas. There is no generally accepted management of the patients. Liposuction or lidocaine application has been reported successful in some cases. Other therapeutic methods have been reported but their effectiveness is based on anecdotal descriptions only, and were not confirmed in clinical trials.
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BACKGROUND: Sandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis. METHODS: EQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10-25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24. RESULTS: The least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between "continued SDZ ETN" (- 2.90 [0.12], n = 148) and "switched to SDZ ETN" (- 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the "continued SDZ ETN" and 38.0% in the "switched to SDZ ETN" groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected. CONCLUSIONS: The 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept. TRIAL REGISTRATION: EudraCT number 2012-002009-23 , Registered 19 April 2012-prospectively registered.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Etanercept/therapeutic use , Adult , Antirheumatic Agents/pharmacokinetics , Biosimilar Pharmaceuticals/pharmacokinetics , Double-Blind Method , Drug Substitution , Etanercept/pharmacokinetics , Female , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic , Therapeutic Equivalency , Treatment OutcomeABSTRACT
OBJECTIVES: Inflammation has been revealed to be associated with angiogenesis. Granulomatosis with polyangiitis (GPA) and immune complex small vessel vasculitis (ICSVV) are forms of systemic vasculitides of different pathogenesis. GPA is a necrotizing granulomatosis and ICSVV is associated with inflammation of postcapillary venules induced by deposits of immune complexes. The aim of the study was to determine serum levels of angiostatin and endostatin, natural angiogenesis inhibitors, in patients with GPA and ICSVV as well as healthy individuals. MATERIAL AND METHODS: Two groups of patients with GPA (20 patients) and ICSVV (20 patients) as well as 20 controls were investigated. All patients were investigated before initiation of immunosuppressive therapy or administration of corticosteroids. Angiostatin and endostatin levels were assayed with the ELISA method. RESULTS: Enhanced serum levels of angiostatin and endostatin were found in patients with GPA but not in those suffering from ICSVV. In patients with GPA increased levels of angiogenesis inhibitors correlated with the disease activity. A correlation between angiostatin and endostatin levels was observed in all groups of investigated individuals. CONCLUSIONS: It is suggested that formation of necrotizing granulation is associated with profound activation of angiogenesis and an increase in serum levels of inhibitors is a phenomenon occurring during blood vessel formation in the granulation tissue. The obtained results confirm involvement of angiogenesis in pathogenesis of at least some forms of vasculitides and suggest the need for continuation of investigations in this field.
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OBJECTIVES: To demonstrate the equivalent efficacy and compare the safety and immunogenicity of an etanercept biosimilar, GP2015, with reference etanercept (ETN) in patients with moderate-to-severe, active rheumatoid arthritis (RA), characterised by an inadequate response to synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: In the EQUIRA study, eligible patients (n=376) were randomised 1: 1 to 50 mg GP2015 or ETN subcutaneously, once weekly, for 24 weeks (treatment period 1). Patients from both groups, with at least moderate European League Against Rheumatism response at week 24, received GP2015 up to week 48 (treatment period 2). All patients continued to receive concomitant methotrexate at a stable dose (10-25 mg/week) until end of the study. The 24-week results are presented here. RESULTS: Equivalent efficacy between GP2015 and ETN was demonstrated if the 95% CI for the difference in disease activity score 28-joint count C reactive protein (DAS28-CRP) change from baseline to week 24 between treatment arms was contained within the prespecified equivalence margin range of -0.6 to 0.6. The least squares mean difference (GP2015-ETN) in change from baseline in DAS28-CRP up to week 24 was -0.07 (95% CI -0.26 to 0.12 [primary endpoint)]. The incidence of treatment-emergent adverse events was comparable between GP2015 (43.5%) and ETN (49.5%). None of the GP2015-treated patients developed neutralising anti-drug antibodies (NAbs) whereas 1.6% and 0.6% of patients in ETN group were NAb positive at weeks 4 and 12, respectively. CONCLUSION: In patients with RA who had an inadequate response to DMARDs, GP2015 demonstrated a similar efficacy and a comparable safety and immunogenicity profile with ETN. TRIAL REGISTRATION: NCT02638259.
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INTRODUCTION: Tumour necrosis factor (TNF-α) is one of the main cytokines participating in inflammation and immune response. Biological effects of the cytokine action, mediated by two receptors: TNFRSF1A and TNFRSF1B involve activation of many signal paths, thus change the transcription activity of many genes. The mechanism of action of an anti-TNF medicine consists in blocking TNF-α though preventing activation of signal paths. AIM: To single out mRNA and microRNA genes relating to TNF-α signal paths, the expression of which could indicate sensitivity of cells to the medicine in question. MATERIAL AND METHODS: The material used in the research consisted in the cell line of regular human skin fibroblasts NHDF (CC-2511 Lonza, Basel, Switzerland) exposed to adalimumab with a concentration of 8.00 µg/ml of the medium for 2, 8 and 24 h, compared with the control material, i.e. non-stimulated cells. Molecular analysis was performed using the oligonucleotide expressive micro-matrices technology HG-U133A, miRNA 2.0 Array micro-matrices and RTqPCR. RESULTS: mRNA: BIRC5, MAP3K4, ZFAND5, JUN differentiate cells exposed to the anti-TNF medicine, regardless of the time of cell/medicine incubation. TNF-α transcription activity is reduced during exposure of NHDF cells to adalimumab. miRNA regulating transcription activity of the said 4 mRNA and miRNA related to TNF-α and its receptors was also singled out. CONCLUSIONS: It was ascertained that adalimumab has therapeutic potential and affects genes engaged in signal paths activated by TNF-α. The results indicate the TNF-α usefulness as the molecular, supplementary marker in diagnostics and control of treatment effects.