State of the Art Review on the Treatment of Psoriatic Disease.

Introduction: Psoriasis is an inflammatory skin disease that in some cases is accompanied by systemic manifestations. Given the varied clinical manifestations, the term psoriatic disease probably better reflects the clinical picture of these patients. Literature review: In most cases, the skin lesions precede joint involvement as well as other potentially involved organs such as the intestine and the eye. Various immune-mediated cellular pathways such as that of TNFα, IL-23, IL-17 as well as other cytokines are involved in the pathophysiology of the psoriatic disease. Future insights: A better understanding of the way they interfere with our immune system has led to remarkably better disease control and outcomes. This review aims to highlight the newest treatments for psoriatic disease, which are expected to significantly reduce unmet needs and treatment gaps.

Development of Morphea Following Treatment with an ADA Biosimilar: A Case Report.

BACKGROUND: Tumor necrosis factor alpha (TNFα) is a pivotal cytokine involved in the pathogenesis of certain inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthropathies, and inflammatory bowel diseases. In the last two decades, TNFα inhibitors (TNFi) have revolutionized the treatment and outcome of the above disorders. However, the use of TNFi has been associated with the development of many autoimmune phenomena and paradoxical skin manifestations that may present as the same type of clinical indications for which the TNFi effectively used. Thus, they may display as arthritis, uveitis, colitis, psoriasis, and several other cutaneous clinical manifestations, among them the development of morphea, a localized scleroderma skin lesion. CASE PRESENTATION: We describe a 58-year-old woman with seronegative RA, refractory to methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was discontinued and two months later, she had substantial skin improvement. CONCLUSION: This is the first report of morphea manifestation during TNFi biosimilar since the patient had no other trigger factors for morphea development like trauma and infections. Physicians dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions, among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow- up check are required.

Immune-Mediated Inner Ear Disease Associated with Type 1 Autoimmune Hepatitis: A Challenging Coexistence.

Autoimmune hepatitis (AIH) is characterized by elevated serum transaminase, increased immunoglobulin G levels, presence of autoantibodies, and hepatocellular damage. Coexistence with other autoimmune diseases has been reported in almost half of patients with AIH. Here, we report a 60-year-old man who developed rapidly progressive, bilateral, asymmetrical, and asynchronous sensorineural hearing loss that was consistent with immune-mediated inner ear disease (IMIED). This devastating presentation evolved as a late manifestation in the context of a six-month systemic illness that had previously resulted in type 1 AIH. A biochemical remission with normalization of aminotransferases achieved within two months after the initiation of corticosteroids with azathioprine. Further, an acceptable response has also been achieved at the patient regarding the right ear-hearing impairment; though, treatment could not reverse the substantial decrement in hearing capability of the left ear. To our knowledge, this is the first case report of the concurrent development of type 1 AIH and IMIED.

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses.

BACKGROUND: Interstitial lung disease (ILD) is the most important pulmonary manifestation of connective tissue diseases (CTDs) since it is associated with high morbidity and mortality. However, there is uncertainty on what constitutes the optimal treatment options from a variety of competing interventions. The aim of the overview is to summarize existing evidence of the effectiveness and harm of pharmacological therapies for adults with CTD-ILD. METHODS: A literature search will be conducted in MEDLINE, the Cochrane Database of Systematic Reviews, DARE, the Centre for Reviews and Dissemination Health Technology Assessment database, Epistemonikos.org, KSR Evidence, and PROSPERO. We will search for systematic reviews with or without meta-analysis that examine pharmacological treatment for CTD-ILD. Updated supplemental search will also be undertaken to identify additional randomized controlled trials. The primary outcomes will be changes in lung function measures and adverse events. The methodological quality of the included reviews will be assessed using the AMSTAR 2 tool. The overall quality of the evidence will be evaluated using the GRADE rating. Summarized outcome data extracted from systematic reviews will be described in narrative form or in tables. For each meta-analysis we will estimate the summary effect size by use of random-effects and fixed-effects models with 95% confidence intervals, the between-study heterogeneity expressed by I², and the 95% prediction interval. If feasible, given sufficient data, network meta-analysis will be conducted to combine direct and indirect evidence of class and agent comparisons. DISCUSSION: While many factors are crucial in selecting an appropriate treatment for patients with CTD-ILD, evidence for the efficacy and safety of a drug is essential in guiding this decision. Thus, this overview will aid clinicians in balancing the risks versus benefits of the available therapies by providing high-quality evidence to support informed decision-making and may contribute to future guideline development. SYSTEMATIC REVIEW REGISTRATION: MedRxiv: DOI 10.1101/2022.01.25.22269807 PROSPERO: CRD42022303180.

Anti-Rheumatic Drugs May Ameliorate the Clinical Course and Outcome of COVID-19 In Rheumatoid Arthritis Patients.

Current data demonstrated that in patients with coronavirus disease-19 (COVID-19), there is a dysregulation of the immune system during the severe form of the disease. This dysregulation is expressed with an uncontrolled release of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-17, tumour necrosis factor alpha (TNFa) and chemokines, associated with increased serum ferritin levels and other acute phase reactants. On the other side, these cytokines play a pivotal role in autoimmune rheumatic diseases (ARD), mostly in rheumatoid arthritis (RA) and the spondyloarthropathies. Patients affected with ARD represent a particular vulnerable group, considering that they may be in an immunocompromised status due to their ailment and its treatment on one side, but on the other side, they may be protected from their immunosuppressive therapy. To this end, we present five patients with RA treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and biologic (b) DMARDs who were affected from COVID-19 and we will try to give answers to the above hypothesis.

Treatment strategies of COVID-19: A rheumatology perspective.

The clinical progression of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to critical illness is associated with a systemic and uncontrolled inflammatory response of the innate and adaptive immunity with the release of a plethora of proinflammatory cytokines termed "cytokine storm". In the absence of an effective treatment, many off-label agents from the armamentarium of rheumatology are used. Here, from the perspective of a rheumatologist, we will discuss the current therapeutic strategies in critically ill patients with SARS-CoV-2 pneumonia. Thus, we will discuss the agents that aim to target viral entry and its replication into the host cell and those focusing and targeting the inflammatory response. In this setting, many agents have been used with promising results but, not all have been approved by the International Authorities and Institutions. In the first step (viral entry), SARS-CoV-2 monoclonal antibodies and remdesivir have been approved to be used and, in the second step, corticosteroids along with interleukin-6 inhibitors, or Janus Kinase inhibitors are currently used.

State-of-the-art glucocorticoid-targeted drug therapies for the treatment of rheumatoid arthritis.

INTRODUCTION: Glucocorticoids are steroid hormones broadly used for the treatment of several inflammatory and autoimmune diseases among other numerous indications, including rheumatoid arthritis. AREAS COVERED: For the purposes of this article, the authors have performed an extensive review of the literature to present the latest studies on glucocorticoid use in rheumatoid arthritis. They also provide the reader with their expert perspectives on future developments. EXPERT OPINION: The authors do not anticipate that glucocorticoids with be replaced in the near future by newer drugs. As such, rheumatologists should be fully aware of the possible side-effects and educate appropriately their patients to recognize and report them. Newer formulations, such as the liposomal/nanoparticle-based treatments, will result in less pronounced adverse effects, but the input of clinical experience along with the current recommendations for the glucocorticoid use will benefit both clinicians and patients with rheumatoid arthritis.

The Immunogenetics of Vasculitis.

Vasculitides are a cluster of diseases defined by an immune attack targeting vessels of different sizes. While most types of vasculitis have an undetermined cause, progress has been achieved in the recent decade in elucidating the mechanisms that participate in the inflammatory damage of the blood vessel wall. Several studies have emphasized that genetic susceptibility is an important aspect of the pathogenesis of vasculitides. The most prominent genetic risk loci for vasculitides reside within the major histocompatibility complex region. This indicates that the immune system is a major contributor to the pathogenesis of this group of diseases. In this chapter, we provide an updated overview of the etiology and pathogenesis of these entities with an emphasis on the major insights gained from recent genetic studies in the highly studied types of vasculitides.

A Patient with Symmetrical Polyarthritis. The Value of Conventional Radiography for a Correct Diagnosis.

PURPOSE OF REVIEW: Among the imaging modalities for the investigation of articular damage of patients with peripheral inflammatory arthropathies, conventional radiography (CR) is the mostly used. Other imaging modalities such as the musculoskeletal ultrasonography, magnetic resonance imaging, and dual-energy computed tomography scans are often used depending on a patient's clinical needs. RECENT FINDINGS: With the publication of new classification criteria for rheumatoid arthritis (RA), spondyloarthropathies, polymyalgia rheumatica, and others, many physicians are not using any of the above imaging techniques because they believe that by relying only on the classification criteria of a disease the diagnosis can be an easy task. We present a patient with peripheral symmetrical polyarthritis involving the small joints of the hands, diagnosed and treated as RA and we discuss the role of imaging, especially the use of CR as an initial screening tool for the evaluation of the articular manifestations and joint damage, and its further usefulness in order to reach a definitive correct diagnosis.

Colchicine Against SARS-CoV-2 Infection: What is the Evidence?

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of concern worldwide and a huge challenge for rheumatologists. Indeed, several antirheumatic drugs are currently used at different stages of COVID-19, such as several cytokine inhibitors and colchicine. Colchicine is one of the oldest medicines with potent anti-inflammatory properties. In rheumatic diseases it is widely used for the treatment of gout, calcium pyrophosphate deposition disease, and familial Mediterranean fever. It is also used off-label in cardiology to treat atrial fibrillation, pericarditis, and myocardial infarction. Over the last few years, advances in the understanding of colchicine's mechanism of action and its pharmacology and safety have made colchicine a promising candidate agent for the fight against COVID-19. In this review, we discuss COVID-19 pathophysiology highlighting colchicine's mode of action, its pleiotropic effects on neutrophils, inflammasome inhibition, and its viral activity. Finally, we discuss the main clinical studies dealing with the use of colchicine in COVID-19. Given the large body of evidence that demonstrates its effectiveness, safety, and its simple way of administration, colchicine seems to be a promising drug to reduce the risk of severe COVID-19 disease.

Clinical features and diagnostic tools in idiopathic inflammatory myopathies.

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.

Seronegative Erosive Arthritis Following SARS-CoV-2 Infection.

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.

TNF-induced Lupus. A Case-Based Review.

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, including 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.

A not-to-miss Cause of Severe Cervical Spine Pain in a Patient with Rheumatoid Arthritis: A Case-Based Review.

BACKGROUND: Rheumatoid arthritis (RA) may affect any diarthrodial joint with a predilection on the peripheral skeleton in a symmetrical manner. When the axial skeleton is affected, it is the cervical spine (CS) that gets involved with potentially detrimental effects, if not treated promptly. CASE: A 60-year-old female suffering from RA presented with severe neck pain and stiffness, difficulty of standing and walking with brisk tendon reflexes, Babinski sign positive, and clonus. Despite the high inflammatory markers and high titres of autoantibodies (rheumatoid factor and anticitrullinated protein antibodies), she never received proper treatment. She was using only paracetamol and non-steroidal anti-inflammatory drugs. Conventional radiography (CR) of CS showed extensive degenerative changes affecting the C3-C5 vertebral level. Magnetic Resonance Imaging of the neck showed sub-axial subluxation (SAS) and spinal cord compression at C3 level, and to a lesser extent, in other levels. A multi-level cervical laminectomy and spinal cord decompression were deployed with good results. To this end, literature review was performed until September 2020 and showed that the frequency of radiological findings varies substantially, ranging between 0,7-95% in different studies. The most common radiological feature is the atlanto-axial subluxation (AAS) followed by SAS. 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. On the other hand, RA patients need to be treated in a prompt and efficient manner in order to avoid any potentially fatal complications.