Dental conditions in rheumatic diseases.

Objectives. Review oral manifestations of rheumatic diseases since these can be a diagnostic challenge.Procedures. We performed a PubMed search using terms of rheumatic diseases, autoimmune disease and oral manifestations and also reviewed related guidelines and classifications.Results. We describe the clinical presentations of rheumatic diseases, such as scleroderma, rheumatoid arthritis, Sjögren's syndrome, Systemic lupus erythematosus and others that present specific oral manifestations. We also review the association between periodontal disease and autoimmunity that has been recently described in the literature.Conclusions. The oral manifestations of rheumatic diseases are diverse and can represent a challenge for medical and dental professionals

Oral fluids and auxiliary diagnostic techniques in autoimmune and neuropathic disorders of the oral cavity. Local and systemic implications. Fluidi orali e tecniche ausiliarie diagnostiche nei disordini autoimmuni e neuropatici del cavo orale. Implicazioni locali e sistemiche.

In this dissertation different features of oral fluids were analyzed in order to verify whether saliva and/or the crevicular fluid may be helpful in diagnosing underlying pathologies, monitorizing systemic diseases activity or contributing to a better understanding of idiopathic oral pathologies. - In the first study, saliva was quantitatively analyzed through the spitting method in a group of patients affected by the most common idiopathic psychosomatic disorder of the oral cavity, known as Burning Mouth Syndrome. This study showed how saliva is a complex fluid, and that the central nervous system and emotional attitudes are very strong influencing agents on the oral health. - In the second study, 35 patients affected by Oral Lichen Planus, an autoimmune disorder, were recruite. Salivary fluid and crevicular fluid samples were collected to measure the presence of Human f2-defensin, an antimicrobial peptide involved in immunomodulatory functions. It was observed that HBD-2 could become a very important index to measure the disease\u2019s activity and its evolution in the future. - In the third study it was demonstrated that periodontal pockets and saliva contain Helicobacter pylori and that oral hygiene is useful in preventing the formation of a reservoir of microorganisms involved in gastritis and gastric cancer. - In the fourth study, a total group of 34 patients affected by Rheumatoid Arthritis were examined and several links between rheumatic factors and periodontal indices were found. In the end, a total number of 240 patients were recruited in this experimental work and each study contributed to new topics in the research on saliva and crevicular fluid as potential diagnostic tools for oral pathologies and systemic diseases

Attitudes towards Oral Health in Patients with Rheumatoid Arthritis: A Qualitative Study Nested within a Randomized Controlled Trial

Introduction: Patients with rheumatoid arthritis (RA) present a higher incidence and severity of periodontitis than the general population. Our study, Outcomes of Periodontal Treatment in Patients with Rheumatoid Arthritis (OPERA), was a randomized waiting-list controlled trial using mixed methods. Patients randomized to the intervention arm received intensive periodontal treatment, and those in the control arm received the same treatment with a 6-mo delay. Aim: The nested qualitative component aimed to explore patients’ experiences and priorities concerning oral health and barriers and facilitators for trial participation. Methods: Using purposive sampling until thematic saturation was reached, we conducted 21 one-to-one semistructured interviews with randomized patients in either of the 2 treatment arms as well as with patients who did not consent for trial participation. Results: The patients described their experiences about RA, oral health, and study participation. Previous experiences with dental care professionals shaped patients’ current perceptions about oral health and the place of oral health on their list of priorities compared with other conditions. Patients also highlighted some of the barriers and facilitators for study participation and for compliance with oral health maintenance. The patients, in the control arm, presented their views regarding the acceptable length of waiting time for the intervention. Conclusion: The associations between periodontal and systemic health are increasingly recognized by the literature. Our study provided an insight into RA patients’ experiences and perceptions about oral health. It also highlighted some of the barriers and facilitators for participating in a periodontal interventional study for this group. We hope that our findings will support the design of larger interventional periodontal studies in patients with RA. The complex challenges faced by the burden of RA and the associated multimorbidities in this patient group might highlight opportunities to improve access to oral health services in this patient population. Knowledge Transfer Statement: This article provided insights into the experiences and perceptions of rheumatoid arthritis patients about their oral health to improve patient participation in a definitive clinical trial

Prevalence of disorders recorded in Cavalier King Charles Spaniels attending primary-care veterinary practices in England

Concerns have been raised over breed-related health issues in purebred dogs, but reliable prevalence estimates for disorders within specific breeds are sparse. Electronically stored patient health records from primary-care practice are emerging as a useful source of epidemiological data in companion animals. This study used large volumes of health data from UK primary-care practices participating in the VetCompass animal health surveillance project to evaluate in detail the disorders diagnosed in a random selection of over 50% of dogs recorded as Cavalier King Charles Spaniels (CKCSs). Confirmation of breed using available microchip and Kennel Club (KC) registration data was attempted

Oral fluids and auxiliary diagnostic techniques in autoimmune and neuropathic disorders of the oral cavity. Local and systemic implications. Fluidi orali e tecniche ausiliarie diagnostiche nei disordini autoimmuni e neuropatici del cavo orale. Implicazioni locali e sistemiche.

In this dissertation different features of oral fluids were analyzed in order to verify whether saliva and/or the crevicular fluid may be helpful in diagnosing underlying pathologies, monitorizing systemic diseases activity or contributing to a better understanding of idiopathic oral pathologies. - In the first study, saliva was quantitatively analyzed through the spitting method in a group of patients affected by the most common idiopathic psychosomatic disorder of the oral cavity, known as Burning Mouth Syndrome. This study showed how saliva is a complex fluid, and that the central nervous system and emotional attitudes are very strong influencing agents on the oral health. - In the second study, 35 patients affected by Oral Lichen Planus, an autoimmune disorder, were recruite. Salivary fluid and crevicular fluid samples were collected to measure the presence of Human ß2-defensin, an antimicrobial peptide involved in immunomodulatory functions. It was observed that HBD-2 could become a very important index to measure the disease’s activity and its evolution in the future. - In the third study it was demonstrated that periodontal pockets and saliva contain Helicobacter pylori and that oral hygiene is useful in preventing the formation of a reservoir of microorganisms involved in gastritis and gastric cancer. - In the fourth study, a total group of 34 patients affected by Rheumatoid Arthritis were examined and several links between rheumatic factors and periodontal indices were found. In the end, a total number of 240 patients were recruited in this experimental work and each study contributed to new topics in the research on saliva and crevicular fluid as potential diagnostic tools for oral pathologies and systemic diseases

Rheumatoid Arthritis Therapy Reappraisal

Rheumatoid Arthritis (RA) is a chronic inflammatory disease leading to joint inflammation and destruction. Treatment of RA includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs), and oral or intraarticular (IA) glucocorticoids (GCs). All different classes of drugs have shown to halt disease progression in clinical studies. In real life, a physician has more options than just adding or switching to a new ts/bDMARD if any kind of DMARDs has failed. They can modify or optimize the therapy with concomitant csDMARDs, and oral or IA-GC can be added to the treatment regimen. The EULAR states that therapeutic adjustment including the "optimization of csDMARDs dose or route of administration or intra-articular injections of GCs" is recommended. Thus, a new therapeutic agent can be embedded in a whole strategy with parallel optimization of the csDMARD and GC treatment. The idea of treating to target (T2T) for the treatment of RA patients has been around since the late 1990s. Many clinical studies (Ticora, BsSt, Camera) have demonstrated the superiority of a T2T approach. When I talk to physicians, I understand that most of them only rarely inject joints with GC. Therefore, I would like to create an issue on the T2T approach in reality including primary data, reviews, and real-life data demonstrating the general opinion and execution of T2T in treating RA

Assessing Nurse Practitioners\u27 Knowledge and Clinical Practice with Regard to the Oral-Systemic Link

Nurse Practitioners (NPs) comprise a significant portion of the U.S. primary care workforce and play an essential role in patients\u27 health awareness, prevention strategies, disease management, and in providing appropriate provider referrals. Nurse Practitioners receive education on the oral-systemic connection, yet there have been limited studies on the clinical practice of NPs assessing the oral cavity to evaluate the condition of the teeth and the oral tissues. The purpose of this study was to explore the nurse practitioners’ knowledge and practice habits of assessing the oral cavity for diseases or abnormalities in the mouth that can, in turn, affect overall health. A total of 66 NPs were included in the study, primarily female (91%) with master’s degrees (77%). While knowledge and education were not significantly associated, this research found significant associations between confidence and assessments, less than one-third (30.3%) were confident in their knowledge and ability to evaluate oral abnormalities

Antibodies as pathogenic factors and biomarkers in rheumatoid arthritis

Ever since the evolution of an adaptive immune system capable of creating immune receptors that may recognize self-antigens, we have been at risk of autoimmunity. There are over 100 different types of autoimmune diseases targeting almost every available tissue from head to toe, with joints and connective tissues being a common target. In addition to autoimmune diseases, infections and degenerative joint diseases can cause joint inflammation making differential diagnosis between them difficult. The most common autoimmune disease to afflict the joints is rheumatoid arthritis (RA), affecting nearly 1% of the world population, predominantly women. The etiology of RA is not known, although it involves interaction between multiple genes and environmental risk factors. It is characterized by chronic inflammation of the joints, which without successful treatment can lead to joint destruction. One of the hallmarks of RA is the presence of autoantibodies, often observed in serum several years before any symptoms of disease. The two classes of autoantibodies focused on today are rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA), the latter being a highly specific biomarker for a large subset of RA-patients. The ACPA have greatly aided in diagnosing RA in many patients. Yet their function and origin are still not known. Nevertheless, a subset of patients still lacks a specific biomarker. All studies in this thesis have autoantibodies in arthritis as a common theme, and four of them use a bead-based multiplex platform established during the PhD-project. In Study I, we explored the hypothesized link between periodontitis induced by the oral pathogen P.gingivalis, and its effect on arthritis progression and the production of ACPA. This study revealed a citrulline specific antibody response against P.gingivalis peptidyl arginine deiminase derived peptide, although the link to the arthritis development could not be confirmed. In Study II, we synthesized a library of triple helical peptides (THP) as a tool to characterize antibodies against type II collagen (CII). The peptides were tested in two cohorts of RA patients, as well as on monoclonal antibodies (mAb), and in collagen induced arthritis. The THPs were subsequently used in Study III to elucidate the specificity and function of antibodies against type XI collagen (CXI), revealing a shared epitope between CXI and CII in mice, rats and humans with arthritis. In addition, the THPs were also used in Study IV to explore the cross-reactivity of a joint-reactive mouse ACPA, demonstrating a molecular mechanism of how an ACPA can trigger arthritis. For Study V, the specificity of several human ACPA were dissected with a bead based multiplex assay and compared to polyclonal responses in two RA cohorts. Crystal structures of the ACPA revealed for the first time the structural basis of how human ACPA bind citrulline residues on different peptides. The data presented in this thesis provide further evidence that the major determinant of the arthritogenicity of antibodies lies in their ability to cross-react to joint proteins. Dissecting these specificities may lead to the establishment of new clinical biomarkers

From oral infection to autoimmunity : studies of antibodies and B cells on the path towards rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial joints, which can lead to irreversible joint destruction and disability if not treated properly. The majority of patients are seropositive, defined by presence of autoantibodies, i.e., rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA). My thesis work focuses on ACPA+ RA, which is known for its more severe disease course. ACPA can be detected in the blood years before clinical signs of RA and were for a long time suggested to contribute to pathology, an hypothesis which is currently under debate. Still, the presence of ACPA, and the successful use of B-cell depleting therapies in RA, points to an important role for autoantibodies and B cells in the development of RA. Notably, most known risk factors for RA, in particular smoking and HLA-DRB1 shared epitope (SE) alleles, are specifically linked to onset of ACPA+ RA. My studies have investigated another potential risk factor for RA, namely the oral pathogen Porphyromonas gingivalis (Pg), one of the main drivers of periodontitis (PD). PD is a common disease that is driven by dysbiosis in the oral cavity triggering gingivitis and eventually leads to destruction of the jawbone and toothsupporting surrounding soft tissues. PD has a higher prevalence in RA than in the general population. Interestingly, Pg has the unique characteristic to express its own citrullinating enzyme and has therefore been suggested to contribute to the generation of RA autoantigens, break of tolerance and systemic ACPA production. The overall aims of my thesis were: 1) to determine if presence of antibodies against the Pg virulence factor RgpB could serve as biomarker to identify patients with PD at increased risk for systemic autoimmunity and onset of RA; 2) to explore the gingiva as a site for ACPA production, and Pg as a driver of the ACPA response; and 3) to phenotypically characterise peripheral blood B cells in the risk-RA phase, to understand B-cell dysregulation prior to RA onset. Investigating the anti-Rgp IgG response in two PD cohorts showed that this antibody response could only poorly discriminate PD from controls. However, elevated anti-Rgp IgG levels defined a subset of PD patients with active gingivitis and advanced marginal jawbone loss. We also showed a higher prevalence of ACPA+ individuals in PD versus controls, and higher anti-Rgp IgG levels in ACPA+ versus ACPA- individuals. Moreover, in a prospective study of ACPA+ individuals at increased risk for RA we found significantly higher anti-Rgp IgG levels compared to controls, but antibody levels did not differ between those who progressed to arthritis and those who remained arthritis free. Generation of monoclonal antibodies derived from RA gingival tissue B cells demonstrated the presence of citrulline-reactive clones binding epitopes on both Pg and self-proteins, and this cross-reactivity was also shown for an RA peripheral blood-derived ACPA+ clone. Investigating the serum polyclonal response, 11% of patients with early RA were positive for antibodies targeting a citrullinated Pg peptide. When assessing peripheral blood B cells in ACPA+ Risk-RA individuals, we detected dysregulation of B-cell subsets already before clinical onset, specifically showing loss of CD27 on class-switched IgG+ memory B cells, a feature previously described in autoimmunity. Collectively, these studies can link anti-Pg antibodies – as a proxy for Pg infection – to severe forms of PD and to the ACPA response, but not to arthritis onset. Thus, suggesting Pg-infection could be an early event in the natural history of RA, possibly triggering ACPA production in the gum mucosa by mechanisms of molecular mimicry. Moreover, the detection of B-cell changes already in the at-risk phase, supports the use of immune monitoring to capture individuals at risk of RA onset, that may benefit the most from pre-clinical intervention