Publications by authors named "Eleftherios Pelechas"

45 Publications

Seronegative Erosive Arthritis Following SARS-CoV-2 Infection.

Rheumatol Ther 2021 Nov 16. Epub 2021 Nov 16.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affecting mostly the respiratory system, but several other organs and systems can be involved. Extrapulmonary manifestations and autoimmune phenomena following SARS-CoV-2 infection are frequent events occurring during the first 2 weeks or in later stages of the disease course. These can be expressed as an isolated discovery of autoantibodies, mostly antinuclear or antiphospholipid antibodies, through to full-blown autoimmune organ-specific and systemic diseases. Joint pain is a frequent complain in most patients, but to our knowledge, frank arthritis has not been reported so far. A 46-year-old woman developed symmetrical polyarthritis 2 months after SARS-CoV-2 infection. Laboratory tests showed high acute phase reactants, while the immunological profile was negative. Hand and wrists X-rays revealed soft tissue swelling as well as bone erosions at the ulnar base of the third and fourth metacarpophalangeal joint of the right hand and carpal bones. The patient responded well to small doses of prednisone and methotrexate and after 4 months she had a sustained clinical and laboratory improvement. This is the first report making an association between SARS-CoV-2 infection and erosive polyarthritis. Physicians dealing with patients infected from SARS-CoV-2 should be aware for the possible development of musculoskeletal disorders, among them symmetrical polyarthritis. Thus, a close follow-up and monitoring is mandatory.
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http://dx.doi.org/10.1007/s40744-021-00395-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594638PMC
November 2021

Clinical features and diagnostic tools in idiopathic inflammatory myopathies.

Crit Rev Clin Lab Sci 2021 Nov 12:1-22. Epub 2021 Nov 12.

Department of Neurology, University Hospital of Ioannina, Ioannina, Greece.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders affecting primarily muscles, but other organs can be involved. This review describes the clinical features, diagnosis and treatment for IIMs, namely polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and myositis associated with antisynthetase syndrome (ASS). The diagnostic approach has been updated recently based on the discovery of circulating autoantibodies, which has enhanced the management of patients. Currently, validated classification criteria for IIMs allow clinical studies with well-defined sets of patients but diagnostic criteria to guide the care of individual patients in routine clinical practice are still missing. This review analyzes the clinical manifestations and laboratory findings of IIMs, discusses the efficiency of modern and standard methods employed in their workup, and delineates optimal practice for clinical care. Α multidisciplinary diagnostic approach that combines clinical, neurologic and rheumatologic examination, evaluation of electrophysiologic and morphologic muscle characteristics, and assessment of autoantibody immunoassays has been determined to be the preferred approach for effective management of patients with suspected IIMs.
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http://dx.doi.org/10.1080/10408363.2021.2000584DOI Listing
November 2021

TNF-Induced Lupus. A Case-Based Review.

Curr Rheumatol Rev 2021 Nov 1. Epub 2021 Nov 1.

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina 45110. Greece.

Nowadays, tumor necrosis factor alpha (TNFα) inhibitors have revolutionised the treatment of inflammatory arthritides by demonstrating efficacy with an acceptable toxicity profile. However, autoimmune phenomena and clinical entities have been reported ranging from an isolated presence of autoantibodies to full-blown autoimmune diseases, among them, drug-induced lupus (DIL). Case Presentation: A 62-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate and prednisone, was treated with adalimumab (ADA). 4 months later, she presented acute cutaneous eruptions after sun exposure, positive ANA (1/640 fine speckled pattern), Ro (SSA) and anti-Smith (Sm) antibodies with no other clinical or laboratory abnormalities. The diagnosis of DIL was made, ADA was discontinued and she was treated successfully with prednisone plus local calcineurin inhibitors. Conclusion: Thus, we review the literature for cases of DIL development in patients treated with TNFα inhibitors. Rheumatologists should be aware of the possible adverse events and the requirement of careful clinical evaluation and monitoring.
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http://dx.doi.org/10.2174/1573397117666211102094330DOI Listing
November 2021

Biologic Therapies and Autoimmune Phenomena.

Mediterr J Rheumatol 2021 Jun 30;32(2):96-103. Epub 2021 Jun 30.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

The use of biologic medications has represented a great advancement in the treatment of autoimmune rheumatic diseases. Despite their excellent efficacy, during the last years, a growing number of reports of autoimmune phenomena and paradoxical inflammation has emerged. These phenomena may range from the discovery of an isolated autoantibody to full-blown autoimmune diseases, organ-specific and systemic. This review has been carried out in order to underline the multitude of the potential adverse manifestations from the use of biologic medications. Thus, early recognition of specific types of autoimmune phenomena is an imperative for the physicians allowing them to have an accurate diagnosis and treatment.
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http://dx.doi.org/10.31138/mjr.32.2.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369271PMC
June 2021

COVID-19 in patients with gout on colchicine.

Rheumatol Int 2021 08 5;41(8):1503-1507. Epub 2021 Jun 5.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

Current data demonstrated that severe cases of coronavirus-disease-19 (COVID-19) require treatment with antiviral therapy, dexamethasone, supportive care, as well as some anti-rheumatic drugs, among them, cytokine inhibitors and colchicine. Colchicine is an anti-inflammatory drug that is being used in rheumatology for many years to treat mostly gout, calcium pyrophosphate deposition disease, and Familial Mediterranean Fever. Here, we present for the first time, two patients suffering from gout being treated with colchicine, who were affected from severe acute respiratory coronavirus-2 (SARS-CoV-2) syndrome. Both patients presented with mild symptoms of COVID-19 expressed with myalgias, arthralgias, and sore throat, while laboratory investigations showed only high acute phase reactants. Four weeks later, both patients were free of symptoms with negative SARS-CoV-2 tests and without any complications. To our knowledge, there are no other studies of gout arthritis and SARS-CoV-2 infection published so far. Thus, our preliminary conclusion is that chronic use of colchicine may mitigate the clinical picture and disease course of COVID-19 in gout arthritis patients. Further studies with a large number of patients are needed to confirm the above beneficial effect of colchicine.
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http://dx.doi.org/10.1007/s00296-021-04902-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178663PMC
August 2021

Use of conventional synthetic and biologic disease-modifying anti-rheumatic drugs in patients with rheumatic diseases contracting COVID-19: a single-center experience.

Rheumatol Int 2021 05 3;41(5):903-909. Epub 2021 Mar 3.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

To examine whether patients with inflammatory arthritis (IA) treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and/or biologic (b) DMARDs, could be affected from SARS-CoV-2 infection and to explore the COVID-19 disease course and outcome in this population. This is a prospective observational study. During the period February-December 2020, 443 patients with IA who were followed-up in the outpatient arthritis clinic were investigated. All patients were receiving cs and/or bDMARDs. During follow-up, the clinical, laboratory findings, comorbidities and drug side effects were all recorded and the treatment was adjusted or changed according to clinical manifestations and patient's needs. There were 251 patients with rheumatoid arthritis (RA), 101 with psoriatic arthritis (PsA) and 91 with ankylosing spondylitis (AS). We identified 32 patients who contracted COVID-19 (17 RA, 8 PsA, 7 AS). All were in remission and all drugs were discontinued. They presented mild COVID-19 symptoms, expressed mainly with systemic manifestations and sore throat, while six presented olfactory dysfunction and gastrointestinal disturbances, and all of them had a favorable disease course. However, three patients were admitted to the hospital, two of them with respiratory symptoms and pneumonia and were treated appropriately with excellent clinical response and outcome. Patients with IA treated with cs and/or bDMARDs have almost the same disease course with the general population when contract COVID-19.
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http://dx.doi.org/10.1007/s00296-021-04818-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925256PMC
May 2021

Insulin resistance in patients with rheumatoid arthritis.

Rheumatol Int 2021 06 26;41(6):1185-1186. Epub 2021 Feb 26.

Department of Internal Medicine, Medical School, Rheumatology Clinic, University of Ioannina, 45110, Ioannina, Greece.

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http://dx.doi.org/10.1007/s00296-021-04814-6DOI Listing
June 2021

Correspondence on 'Cardiovascular effects of biological versus csDMARD therapy in treatment naive, early rheumatoid arthritis'.

Ann Rheum Dis 2021 Feb 8. Epub 2021 Feb 8.

Rheumatology Clinic, Internal Medicine, University of Ioannina Faculty of Medicine, Ioannina, Epirus, Greece

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http://dx.doi.org/10.1136/annrheumdis-2021-219891DOI Listing
February 2021

Cutaneous Autoimmune Phenomena of the Anti-TNFa Biosimilars. Casebased Review.

Curr Rheumatol Rev 2021 ;17(2):267-270

Department of Internal Medicine, Rheumatology Clinic, Medical School, University of Ioannina, Ioannina, Greece.

Background: Psoriasis (Pso) is a common chronic inflammatory disease affecting the skin, both sexes, and all ages. It can be associated with other chronic inflammatory musculoskeletal disorders and certain drugs, including tumor necrosis factor α (TNFα) antagonists.

Case Presentation: A 64-year-old man with seronegative rheumatoid arthritis (RA) refractory to leflunomide and prednisone was treated with SB-4 (Benepali), an etanercept biosimilar 50mg/week subcutaneously. He responded well to the treatment, but a year later, he developed erythematous skin eruptions affecting mainly in the palms of both hands. Skin biopsy showed a picture compatible with Pso. SB-4 was discontinued, and the skin lesions disappeared with the addition of topical steroid therapy. This is the only case of psoriatic skin lesions associated with SB-4 treatment.

Conclusion: Thus, we review and discuss the relevant literature of Pso cases related to SB-4 and other anti-TNFα biosimilars. Rheumatologists dealing with patients on anti-TNFα biosimilars should be aware of and recognize these complications.
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http://dx.doi.org/10.2174/1573397116666201119151349DOI Listing
January 2021

Calcified constrictive pericarditis resulting in tamponade in a patient with systemic lupus erythematosus.

Rheumatol Int 2021 Mar 18;41(3):651-670. Epub 2020 Nov 18.

Rheumatology Clinic, Department of Internal Medicine, School of Health Sciences, University Hospital of Ioannina, University of Ioannina, 45110, Ioannina, Greece.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan involvement, including heart. Pericarditis-the most common cardiac manifestation-occurs in up to 50% of cases, resulting in positive treatment outcomes. Rarely, it evolves to hazardous complications. A 50-year-old woman with SLE in clinical remission, receiving hydroxychloroquine 400 mg/day, presented to us with severe chest pain and low-grade fever. Physical examination revealed a friction rub and decreased breath sounds at the right lung base. Laboratory evaluation demonstrated leukopenia, thrombocytopenia, low C4 levels, and high acute phase reactants. Chest X-ray exhibited cardiomegaly, calcified pericardium, and right pleural effusion, confirmed by CT scan. PPD skin test and IGRA were both negative. Pericardial fluid, blood, and urine cultures for bacteria and fungi, as well as Gram and Ziehl-Neelsen stains were negative. Serological tests for viruses were also negative. The patient was diagnosed with calcified constrictive pericarditis (CP) due to SLE. She was treated with cyclophosphamide and methylprednisolone pulses, without improvement. Her clinical condition deteriorated, developing signs and symptoms compatible with cardiac tamponade (TMP), which was confirmed by Doppler echocardiography. The patient underwent pericardiectomy. A dramatic response was noted and she was discharged with prednisone 50 mg/day and azathioprine 100 mg/day. Thus, we review and discuss the relevant literature of SLE cases with CP or TMP. When an SLE patient presents with CP, infectious causes should be excluded first. To the best of our knowledge, this is the only case of SLE and calcified CP leading to TMP, hence physicians should be aware of this complication.
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http://dx.doi.org/10.1007/s00296-020-04747-6DOI Listing
March 2021

Anti-Rheumatic Drugs for the Fight Against the Novel Coronavirus Infection (SARSCoV-2): What is the Evidence?

Mediterr J Rheumatol 2020 Sep 21;31(Suppl 2):259-267. Epub 2020 Sep 21.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

SARS-CoV-2 is a positive-sense single-stranded RNA virus that causes the COVID-19 infection. Spike proteins are the most important proteins found on its capsule using the host's ACE2 receptors to invade respiratory cells. The natural course of the COVID-19 infection is variable, from asymptomatic to severe and potentially fatal. A small percentage of the severely infected patients will end up in an intensive care unit for ventilatory support. Elderly male patients with pre-existing medical conditions and smokers are at a disproportionate high risk to develop severe complications. Studies have shown that deaths occur due to a dysregulated immune system that overreacts, producing a plethora of cytokines, leading to the so-called "cytokine storm" phenomenon. In this direction, many drugs that are used in the everyday practice of Rheumatologists have been used. Indeed, pro-inflammatory cytokines such as the IL-1 and IL-6 have been shown to be the pivotal cytokines expressed, and anti-cytokine treatment has been tried so far with various results. In addition, hydroxychloroquine, an antimalarial drug, has been shown to reduce COVID-19 symptoms. Other drugs have also been used, such as intravenous pulses of immunoglobulins, and colchicine. Robust clinical trials are needed in order to find the suitable treatment. Current data indicate that hydroxychloroquine and cytokine targeting therapies may prove helpful in the fight of SARS-CoV-2 in appropriately selected patients.
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http://dx.doi.org/10.31138/mjr.31.3.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656133PMC
September 2020

Preclinical discovery and development of adalimumab for the treatment of rheumatoid arthritis.

Expert Opin Drug Discov 2021 03 18;16(3):227-234. Epub 2020 Nov 18.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by progressive joint disorders with significant pain and stiffness. In the past, RA was a difficult -to-treat ailment, but nowadays with the advent of biologics and better treatment strategies, disease remission is an achievable goal. Tumor necrosis factor α (TNFα) inhibitors were the first category of biologics to emerge with adalimumab being the first fully human TNFα.: the authors provide an overview of the historical events that led to the discovery of TNFα inhibitors and more specifically the drug adalimumab. Several key trials are presented regarding the safety of the drug as well as its successful journey, but there is also a narrative description of the drug's future after patent expiration.: Adalimumab is a fully human TNFα inhibitor with a fairly rapid onset of action. It has a generally good safety and efficacy profile. Clinicians must be aware of the possible side effects and treat them in a timely manner or discontinue the drug where appropriate. Due to the success of the bio-originator adalimumab, a multitude of biosimilars have emerged but not, thus far, for all of the indications of the bio-originator.
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http://dx.doi.org/10.1080/17460441.2021.1846516DOI Listing
March 2021

Recent advances in the opioid mu receptor based pharmacotherapy for rheumatoid arthritis.

Expert Opin Pharmacother 2020 Dec 2;21(17):2153-2160. Epub 2020 Nov 2.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina , Ioannina, Greece.

Introduction: Opioids are used for severe forms of acute and cancer pain. Over the last years, their potential use in patients with noncancer pain such as those with rheumatoid arthritis (RA) has been postulated. A recent population-based comparative study showed that chronic opioid use was 12% vs. 4% among RA and non-RA patients, respectively. Another study showed an increase from 7.4% to 16.9% (2002 to 2015). In general, there has been an increasing tendency to use opioids in recent years.

Areas Covered: The authors have performed an extensive literature search using PubMed for articles including noncancer pain and the use of the mu opioid receptor (MOR) agonists in patients with RA.

Expert Opinion: Data is not sufficient to support opioid use for the treatment of chronic pain in patients with RA. Data is scarce and inconclusive. Rheumatologists should think and ponder the question: Why is this patient in pain? Differential diagnosis should include a disease flare, degenerative changes of the musculoskeletal system, and fibromyalgia. And while there are new strategies for opioid administration currently being researched, unfortunately, they are far from being applied to human subjects in the everyday clinical setting, and are still being evaluated at an experimental level. : Central nervous system; : delta opioid receptor agonists; : Gastrointestinal; : G protein-coupled receptors; Interleukin; Janus kinase; : kappa opioid receptor agonists; Metacarpophalangeal joints; Mu opioid receptor agonists; Metatarsophalangeal joints; Non-steroidal anti-inflammatory drugsOA: Osteoarthritis; : Opioid receptors; : Pharmacodynamic; Proximal interphalangeal joints; : Pharmacokinetic; : Peripheral nervous system; Rheumatoid arthritis; : Regulator of G protein signaling; : Selective serotonin reuptake inhibitors; Tumor necrosis factor.
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http://dx.doi.org/10.1080/14656566.2020.1796969DOI Listing
December 2020

Biosimilars and retention rates in patients with ankylosing spondylitis.

Clin Exp Rheumatol 2021 Mar-Apr;39(2):440. Epub 2020 Oct 18.

Division of Rheumatology, University of Ioannina Medical School, Greece.

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May 2021

Incidence of spondyloarthritis and its subtypes: a systematic review.

Clin Exp Rheumatol 2021 May-Jun;39(3):660-667. Epub 2020 Sep 4.

Division of Rheumatology, University of Ioannina Medical School, Greece.

Objectives: Several epidemiologic studies of spondylarthritis (SpA) and its subtypes have been reported during the last decades. The majority of these studies provided prevalence estimates and showed a considerable variation in the reported frequency of SpA subtypes. Most systematic reviews published in this field aimed to summarise the results of prevalence studies, however, incidence studies are important for an accurate picture of a disease occurrence in a defined population. We conducted a systematic review regarding the incidence of SpA subtypes on studies published during the last 25 years, to compare their methodology and summarise their results.

Methods: A systematic literature search of PubMed was performed to identify all published studies on the incidence of SpA subtypes between 1/1/1995 and 31/12/2019. Studies were considered eligible if the incidence of one or more SpA subtypes was measured in the general population, and met concrete inclusion criteria. Incidence rates (IR) were summarised using a random effect model.

Results: A total of 24 publications fulfilled the inclusion criteria. Most of them included results for two or more SpA subtypes. Sixteen studies presented the incidence of psoriatic arthritis, which gave an overall IR estimate of 9.7 cases per 100.000 person-years. Thirteen studies presented the incidence of ankylosing spondylitis with an overall IR estimate of 4.8, and eight studies presented reactive arthritis incidence with an overall IR estimate of 3.4. A small number of studies referred to the incidence of enteropathic arthritis or undifferentiated spondyloarthritis.

Conclusions: Incidence studies of SpAs differ considerably in their methods, and result in a wide variation of the IRs for all SpA subtypes. Methodological differences may only partly explain the differences in disease occurrence observed among studies. More studies from different populations based on specific classification criteria are needed for a more accurate picture of SpA epidemiology.
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May 2021

Therapeutic Options and Cost-Effectiveness for Rheumatoid Arthritis Treatment.

Curr Rheumatol Rep 2020 06 26;22(8):44. Epub 2020 Jun 26.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

Purpose Of Review: During the last two decades, the therapeutic decisions and strategies for rheumatoid arthritis (RA) management have improved dramatically. Today, the therapeutic armamentarium is significantly augmented, and by using both old and new drugs, remission or low disease activity is a reasonable goal. The use of conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) in combination with biologic (b) or targeted synthetic (ts) DMARDs has revolutionized RA treatment. Methotrexate administration is considered fundamental among other csDMARDs for the treatment of RA. It is recommended as the initial drug (monotherapy), or in combination with other csDMARDs, bDMARDs, and tsDMARDs in a step-up strategy. Furthermore, it can be used with other csDMARDs as initial combination-therapy. On the other hand, despite the fact that bDMARDs and ts DMARDs are highly efficacious and can also be used as monotherapy in certain cases, cost-effectiveness is still questionable when compared with csDMARDs. In this direction, the classic argument of utmost importance has to do with the most appropriate treatment strategy that shall be initially applied: csDMARD combination-therapy versus monotherapy, or step-up combinationtherapy with bDMARDs, especially tumor necrosis factor-α (TNFa) blockers. For this reason, a literature review of the most important csDMARDs combination and bDMARDs combination studies has been deployed.

Recent Findings: The results showed that the triple csDMARDs therapy approach is more effective and less expensive. In addition, workers' productivity is higher than any other treatment options for RA. Triple-therapy constitutes a smart, efficacious, and significantly cheaper choice for RA therapeutic management.
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http://dx.doi.org/10.1007/s11926-020-00921-8DOI Listing
June 2020

Bertolotti syndrome: a not-to-miss cause of chronic low back pain in young adults.

Acta Reumatol Port 2020 Jan-Mar;45(1):58-60

University Hospital of Ioannina.

Low back pain (LBP) in young adults is a common condition that needs to be appropriately examined in cases of refractory to classic treatment strategies. We present two cases of chronic LBP with challenging diagnosis and treatment refractoriness. The first case corresponds to a young lady that has been treated mistakenly with an anti-tumor necrosis factor because her treating doctors diagnosed unilateral sacroiliitis which turned out to be a magnetic resonance imaging (MRI) artifact (partial volume artifact). The second case is about another young lady with chronic LBP that did not respond to the classic treatment with non-steroidal anti-inflammatory drugs. Both cases have been diagnosed as having Bertolotti syndrome. Bertolotti syndrome is an anatomical abnormality consisting of partial unilateral or bilateral fusion of the transverse process of the lowest lumbar vertebrae to the sacrum. The presentation of both cases highlights the importance of a minute history taking and clinical examination especially in young patients with chronic LBP.
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June 2021

The lipid paradox in rheumatoid arthritis: the dark horse of the augmented cardiovascular risk.

Rheumatol Int 2020 Aug 10;40(8):1181-1191. Epub 2020 Jun 10.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation that, if left untreated, can cause joint destruction and physical impairments. The inflammatory process is systematic, and it is associated with increased morbidity and mortality. Over the last years, mortality presents a decreasing trend; still, there is a high burden of cardiovascular disease (CVD) in RA that seems to be related to coronary atherosclerosis. Chronic inflammation, physical inactivity, and drugs used to treat RA are some of the reasons. Thus, the management of CVD risk is essential and involves the patient's stratification using distinct parameters that include assessment of the blood lipid profile. However, 'dyslipidemia' in RA patients follows a different pattern under the impact of inflammatory processes, while therapies that target the underlying disease change the levels of specific lipid components. In this review, we explore the relationship between blood lipids and inflammation in the so-called ΄lipid paradox΄ in RA, and we present the existing knowledge over the influence of antirheumatic drugs on the lipid profile of RA patients.
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http://dx.doi.org/10.1007/s00296-020-04616-2DOI Listing
August 2020

Neuroinflammatory events after anti-TNFα therapy.

Ann Rheum Dis 2020 May 20. Epub 2020 May 20.

Internal Medicine, Division of Rheumatology, University of Ioannina Faculty of Medicine, Ioannina, Greece

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http://dx.doi.org/10.1136/annrheumdis-2020-217723DOI Listing
May 2020

Radiological Findings of the Cervical Spine in Rheumatoid Arthritis: What a Rheumatologist Should Know.

Curr Rheumatol Rep 2020 05 13;22(6):19. Epub 2020 May 13.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

Purpose Of Review: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mainly the peripheral skeleton in a symmetrical manner rather than the axial skeleton, but when it occurs it can affect the cervical spine (CS). Although CS involvement is a frequent radiographic finding in RA, the clinical features are scarce, but potentially life-threatening with severe neurological deficits or even death due to brain stem compression. The commonest site of inflammation of the CS is the articulation between C and C vertebrae, the atlanto-axial region. The radiological finding observed in this region is the atlanto-axial subluxation (AAS). For the evaluation of CS in RA the classical diagnostic technique used mostly is conventional radiography (CR). Since CR does not provide good information regarding synovial inflammation, other imaging modalities are used such as magnetic resonance imaging and computed tomography. However, CR is the most valuable tool for screening CS in RA patients. Thus, we reviewed the literature until December 2019 for studies regarding CS radiological manifestations using CR in RA patients.

Recent Findings: We found that the frequency of radiological findings varies substantially, ranging between 0.7-95% in different studies. The commonest radiological feature was the AAS followed by subaxial subluxation. Because CS involvement can often be clinically asymptomatic, its assessment should not be forgotten by physicians and should be assessed using CR which is an easy to perform technique and gives important information as a screening tool.
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http://dx.doi.org/10.1007/s11926-020-00894-8DOI Listing
May 2020

Adalimumab-induced myasthenia gravis: case-based review.

Rheumatol Int 2020 Nov 22;40(11):1891-1894. Epub 2020 Apr 22.

Department of Internal Medicine, Medical School, Rheumatology Clinic, University of Ioannina, 45110, Ioannina, Greece.

Myasthenia gravis (MG) is an autoimmune disease characterised by the presence of acetylcholine receptor antibodies and by blocking the transmission of the signal in the neuromuscular junction causing muscle weakness. It can be associated with several autoimmune diseases and certain drugs, between them Etanercept an anti-tumour necrosis factor (TNF) agent. A 42-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate, was treated with adalimumab (ADA), a human monoclonal antibody against the TNF, in a dosage scheme of 40 mg every 14 days subcutaneously. The patient responded well to ADA therapy with sustained remission for 18 months when she developed blurred vision and eyelid ptosis of the left eye. The diagnosis of ocular MG was made. ADA has been discontinued and she started a treatment with pyridostigmine showing an excellent response and complete remission within a 2-month period. This is the first report making an association of ADA and ocular MG. Thus, rheumatologists dealing with patients treated with TNF inhibitors should be aware of the possible development of neurological adverse events, among them MG.
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http://dx.doi.org/10.1007/s00296-020-04587-4DOI Listing
November 2020

Treatment strategies are more important than drugs in the management of rheumatoid arthritis.

Clin Rheumatol 2020 Apr 22;39(4):1363-1368. Epub 2020 Feb 22.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece.

The treatment of inflammatory arthritides has been changed dramatically in the past two decades with the introduction of the biological (b) disease-modifying anti-rheumatic drugs (DMARDs) as well as the targeting synthetic (ts) DMARDs that can be used as monotherapy or in combination with conventional synthetic (cs) DMARDs. The concept of treat to target (T2T) and tight control monitoring of disease activity represents a therapeutic paradigm of modern rheumatology. In rheumatoid arthritis (RA), this treatment approach has proven to be effective in many clinical trials and is now a well-established approach. The most common treatment strategies rely on the combination of csDMARDs (mainly methotrexate, sulfasalazine and hydroxychloroquine). This comes from different studies which compare the outcomes of combination therapies versus csDMARD monotherapy or versus methotrexate plus biologics in early RA patients. Here, we review the literature of the most important T2T studies for RA patients. The results showed that a tight control strategy appears to be more important than a specific drug to control RA. T2T approach aiming for remission or low disease activity can be achieved in early RA patients using less expensive drugs in comparison to newer drugs and this may need to be recognised in the future recommendations for the management of RA. KEY POINTS: • Tight-control and treat-to-target (T2T) strategies are the cornerstone in achieving remission or low disease activity in rheumatoid arthritis (RA) • A plethora of clinical trials has confirmed the efficacy of csDMARDs when the tight-control and T2T strategies are applied • T2T and tight-control strategies are a less expensive option in comparison to newer drugs and may be recognised in the future recommendations for the management of RA. • Treatment decisions and strategies are more important than just the drugs.
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http://dx.doi.org/10.1007/s10067-020-05001-xDOI Listing
April 2020

Clinical evaluation of the safety, efficacy and tolerability of sarilumab in the treatment of moderate to severe rheumatoid arthritis.

Ther Clin Risk Manag 2019 4;15:1073-1079. Epub 2019 Sep 4.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

Rheumatoid arthritis (RA) is an autoimmune disease that is characterised by synovial inflammation and progressive joint disorder with significant pain and stiffness, which lead to functional disability and systemic complications if left untreated. Although methotrexate (MTX) is the cornerstone in the RA therapy, it is ineffective or intolerable in up to 50% of patients. In addition, tumour necrosis factor (TNF) inhibitors which are regarded as the standard of care for those patients, have not been proven a panacea creating a therapeutic gap. In this direction, other cytokines such as the interleukin (IL)-6 in combination with MTX or as monotherapy have been approved. Sarilumab has already been approved for the treatment of moderate to severe RA, but more studies are on their way including polymyalgia rheumatica, giant cell arteritis, juvenile idiopathic arthritis, and indolent systemic mastocytosis. On the other hand, a study was prematurely discontinued after approximately 1.5 years, when the ankylosing spondylitis development program was discontinued due to lack of efficacy. Regarding safety, efficacy and tolerability of the molecule, three pivotal clinical trials have established sarilumab as one of the safe and efficacious choices for the treatment of RA (mobility, target and monarch trials). Significant decreases in progression of structural damage have been demonstrated. Infections and neutropenia are two of the most common adverse events. Sarilumab is beyond any doubt another molecule that can be added to the clinicians' armamentarium for the treatment of patients with moderate to severe RA with a good safety and efficacy profile.
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http://dx.doi.org/10.2147/TCRM.S167452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732515PMC
September 2019

Reply to the Editor.

Semin Arthritis Rheum 2020 04 1;50(2):e7. Epub 2019 Aug 1.

Department of Internal Medicine Medical School, University of Ioannina Rheumatology Clinic, 45110 Ioannina, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.semarthrit.2019.07.005DOI Listing
April 2020

Rheumatoid Arthritis Treatment. A Back to the Drawing Board Project or High Expectations for Low Unmet Needs?

J Clin Med 2019 Aug 16;8(8). Epub 2019 Aug 16.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece.

Despite the significant progress in Rheumatoid Arthritis (RA) therapeutics, there are several reports in the literature claiming that the size of unmet needs in RA is large. In the era before biologics, there was indeed a significant number of patients who did not achieve low disease activity (LDA) or disease remission due to limited therapeutic choices in the doctors' armamentarium. Treatment wise, great progress has been achieved over the last decades with the discovery and introduction in therapeutics of new molecules, such as the biological (b) disease-modifying anti-rheumatic drugs (DMARDs), and the targeted synthetic (ts) DMARDs. Today, with such a plethora of conventional synthetic (cs) DMARDs, tsDMARDs, and bDMARDs, why are we unable to successfully treat RA patients? What is wrong? However, a new drug for RA does not mean it is necessary to switch to a new treatment. It is very easy to change and switch therapies when the patient complains about pain and stiffness. In this setting, it is obligatory to rule out other comorbidities and disorders that may be the cause of the pain first. Thus, clinicians must have a deep knowledge of the drug therapy and be able to adjust the treatment when needed. A minute clinical examination must be carried out on every visit with close monitoring of the patient. A treat-to-target (T2T) approach and the application of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) recommendations and strategies should minimize the unmet needs.
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http://dx.doi.org/10.3390/jcm8081237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722985PMC
August 2019

Maintained Clinical Remission in Ankylosing Spondylitis Patients Switched from Reference Infliximab to Its Biosimilar: An 18-Month Comparative Open-Label Study.

J Clin Med 2019 07 2;8(7). Epub 2019 Jul 2.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece.

Background: Switching from reference infliximab (RI) to biosimilar infliximab (BI) had no detrimental effects on efficacy and safety. However, long-term follow-up data is missing.

Objective: To evaluate patients with Ankylosing Spondylitis (AS) in clinical remission who were switching from RI to BI, in terms of the safety and efficacy of this, in a long-term fashion.

Methods: One hundred and nine consecutive unselected AS patients were investigated. All were naïve to other biologics and were followed-up at predefined times receiving RI. Patients in clinical remission were asked to switch from RI to BI. Those who switched to BI were compared with a matched control-group receiving continuous RI. During follow-up, several parameters were recorded for at least 18 months. Disease activity was measured using the Bath Ankylosing Spondylitis disease activity index (BASDAI), and the Ankylosing Spondylitis disease activity score (ASDAS), using the C-reactive protein. Remission was defined as BASDAI < 4 and ASDAS < 1.3.

Results: Eighty-eight patients were evaluated (21 excluded for different reasons). From those, 45 switched to BI, while 43 continued receiving RI. No differences between groups regarding demographic, clinical and laboratory parameters were observed. All patients were in clinical remission. During follow-up, five patients from the BI-group and three from the maintenance-group discontinued the study (4 patients nocebo effect, 1 loss of efficacy). After 18 months of treatment, all patients in both groups remained in clinical remission. No significant adverse events were noted between groups.

Conclusion: BI is equivalent to RI in maintaining AS in clinical remission for at least 18 months.
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http://dx.doi.org/10.3390/jcm8070956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679061PMC
July 2019

Cochlear involvement in patients with systemic autoimmune rheumatic diseases: a clinical and laboratory comparative study.

Eur Arch Otorhinolaryngol 2019 Sep 30;276(9):2419-2426. Epub 2019 May 30.

Department of Rheumatology, University Hospital of Ioannina, Ioannina, Greece.

Purpose: Inner ear involvement has been reported in systemic rheumatic disease while detection of cochlin-specific antibodies has been reported in patients with idiopatic sensorineural hearing loss, suggesting cochlin's strong link to autoimmune hearing loss. The aim of this cross-sectional study was to calculate the prevalence of sensorineural hearing loss (SNHL) in patients with systemic rheumatic diseases, and to investigate any potential correlation with human antibodies to cochlin.

Methods: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and systemic sclerosis (SSc) according to the criteria of American College of Rheumatology were included in the study. All patients underwent a complete ear-nose-throat physical examination and audiological evaluation with pure tone audiometry and impedance audiometry. Pure tone average was calculated, taking as a starting point the hearing loss in dB according to the recommendation 02/1 of "Bureau International d' Audiophonologie" (BIAP) so as an average hearing threshold value. Sera of all patients were tested for the presence of IgG antibodies to human cochline (COCH-IgG). Sex and age-matched healthy subjects were included as controls to each group.

Results: A total of 133 patients were studied; 60 with RA, 41 with SLE, 24 with SS and 8 with SSc. 61.4% of patients reported vertigo, 41% hyperacousis, 39% hearing loss, 38% tinnitus, 37.9% headache and 2.1% sensation of ear pressure with unremarkable otoscopy. The prevalence of SNHL calculated for patients affected by RA, SLE, SS and SSc was 66.6%, 31.71%, 54.17%, and 75% respectively. The calculated average hearing thresholds value in RA was increased in comparison to SLE (p < 0.05). In addition it was also higher in patients with RA and secondary SS, in comparison to RA patients (p > 0.05). There was statistically significant correlation of average hearing threshold with disease activity score 28 (DAS28) in RA, but no correlation observed with disease activity index (SLEDAI) in SLE. COCH-IgG antibodies were detected in only two samples. The results were compared with those of their respective sex and age-matched healthy subjects.

Conclusion: Our study revealed increased prevalence of SNHL in patients with systemic autoimmune rheumatic disease but no correlation of hearing loss with COCHIgG antibodies. The mechanism of inner ear damage remains unknown; thus, additional prospective studies will be needed to elucidate its pathogenesis.
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http://dx.doi.org/10.1007/s00405-019-05487-5DOI Listing
September 2019

Comment on: Assessments of the unmet need in the management of patients with rheumatoid arthritis: analyses from the NOR-DMARD registry.

Rheumatology (Oxford) 2019 10;58(10):1883-1884

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

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http://dx.doi.org/10.1093/rheumatology/kez206DOI Listing
October 2019

Conventional radiography of the hands and wrists in rheumatoid arthritis. What a rheumatologist should know and how to interpret the radiological findings.

Rheumatol Int 2019 Aug 22;39(8):1331-1341. Epub 2019 May 22.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, 45110, Greece.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, leading to joint damage and bone destruction. Conventional radiography (CR) of the hands and wrists has been, for many years, the primary imaging modality used to diagnose and monitor RA. On the other hand, many investigators in clinical trials and observational studies used CR of the hands and wrists to demonstrate drug effectiveness and structural damage progression. The purpose of this review is to discuss the evaluation and interpretation of the hands and wrists by CR in RA patients and the radiographic changes occurring in a specific joint. Thus, the literature was reviewed until January 2019 for studies regarding RA radiological evaluation of the hands and wrists, as well as radiological progression using CR. The assessment of joint pathology in RA patients should begin with CR which is the best imaging modality to evaluate any subtle changes occurring at the bone level. Once high-quality radiographs are obtained in appropriate views/projections, then an accurate evaluation can often be made without any further imaging studies. Therefore, CR is a valuable tool for RA screening. It is an easy-to-perform technique and gives important information assisting in differentiating between RA from other arthritides. In contrary CR does not provide good information when early RA changes start to appear, such as synovial inflammation or other soft-tissue structural changes. Nevertheless, it still remains the most commonly used imaging tool in rheumatology and has a number of advantages: it is easily available in most rheumatologists and readily accessible in most patients. It is inexpensive and relatively safe. It provides immediate information and can be interpreted easily by the requested rheumatologist. Finally, the data are reproducible and can be used for serial evaluation and follow-up.
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http://dx.doi.org/10.1007/s00296-019-04326-4DOI Listing
August 2019

The impact of temporal artery biopsy for the diagnosis of giant cell arteritis in clinical practice in a tertiary university hospital.

PLoS One 2019 29;14(3):e0210845. Epub 2019 Mar 29.

Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

Background: Temporal artery biopsy (TAB) is useful in assisting with giant cell arteritis (GCA) diagnosis but lacks sensitivity. The aim of our study was to assess the diagnostic impact of TAB histology in patients with suspected GCA on hospital admission.

Methods: A prospectively maintained database was queried for all TABs performed between 1-1-2000 until 31-12-2017 at the University Hospital of Ioannina. Thus, inclusion criteria were made on the grounds of every patient that underwent a TAB during the above-mentioned period, regardless of demographic, clinical and laboratory data.

Results: Two hundred forty-five TABs were included (149 females and 96 males), with a mean age of 64.5 (±3.5) years. The mean symptoms duration until admission to the hospital was 8.6 (±1.3) weeks and all had elevated acute phase reactants on admission. The reasons of admission were fever of unknown origin (FUO) in 114 (46.5%) patients, symptoms of polymyalgia rheumatica (PMR) in 84 (34.3%), new headache in 33 (13.5%), anemia of chronic disease (ACD) in 8 (3.32%) and eye disturbances in 6 (2.5%) patients. Positive results were found in 49 (20%) TABs. More specifically, in 14% of patients with FUO, 21% in those with PMR, while in patients with a new headache the percentage was 27%. Finally, 5 out of 6 (83.3%) of patients with ocular symptoms and only one (12.5%) of those suffering from ACD. Visual manifestations and FUO are correlated with a positive TAB.

Conclusion: It seems that TAB is useful in assisting with GCA diagnosis, but lacks sensitivity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210845PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440612PMC
November 2019
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