Raffaele D’Amelio

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFα blockers: Safety and immunogenicity

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.

Infection risk in Rheumatoid Arthritis and Spondyloarthropathy patients under treatment with DMARDs, Corticosteroids and TNF-α antagonists

BackgroundInfections which complicate rheumatic diseases such as Rheumatoid Arthritis (RA) and Spondyloarthropathy (SpA) (Psoriatic Arthritis [PA] and Ankylosing Spondylitis [AS]), may cause significant morbidity and mortality. However, among the studies on the incidence rate (IR) of infections in such patients, very few have involved controls and the results have been controversial, probably due to methodological difficulties.To estimate infection rates in RA and SpA patients under disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids (CS) and tumor necrosis factor (TNF)α antagonists, alone or combined, a single-centre retrospective observational cohort study has been performed.Patients and methodsIncidence rates/100 patient-years of any infections were evaluated in RA and SpA outpatients observed in the period November 1, 2003 through December 31, 2009 and stratified according to therapy. Infection incidence rate ratios (IRR) were calculated using Poisson regression models which adjusted for demographic/clinical characteristics of the patients.ResultsThree hundred and thirtyone infections [318 (96.1%) non-serious and 13 (3.9%) serious] have been registered among 176 of the 341 patients (52%). The IR/100 patient-years of all infections was 36.3 ranging from 12.4 (DMARDs + CS) to 62.7 (anti-TNFα + CS). The most frequent infection site was respiratory tract, and bacteria were responsible for three quarters of all infections. In the multivariate analysis, adding anti-TNFα to DMARDs doubled the IRR compared to DMARDs alone, anti-TNFα + CS significantly tripled it, whereas anti-TNFα + CS + DMARDs only increased the risk 2.5 times. The degree of disease activity was strongly and significantly associated with the infection risk (severe or moderate versus mild, IRR = 4). Female sex was significantly associated with increased infection risk, while duration of disease and anti-influenza vaccination were protective, the latter even for cutaneous/soft-tissue (mainly herpetic) infections.ConclusionThe combination anti-TNFα with CS was found to be the most pro-infective treatment, whereas DMARDs alone were relatively safe. Physicians, therefore, should be aware that there may be an increased risk of infection when using anti-TNFα and CS therapy together. Anti-influenza vaccination appears to provide broad protection, adding evidence to support its use in these patients, and deserves further study.

Probable Dengue Virus Infection Among Italian Troops, East Timor, 1999–2000

To investigate the attack rate and risk factors for probable dengue fever, a cross-sectional study was conducted of an Italian military unit after its deployment to East Timor. Probable dengue was contracted by 16 (6.6%) of 241 army troops and caused half of all medical evacuations (12/24); no cases were detected among navy and air force personnel.

Modulation of T-cell co-stimulation in rheumatoid arthritis: clinical experience with abatacept.

Rheumatoid arthritis (RA), characterized by progressive joint destruction, deformity, disability and impaired quality of life (QOL), is a prevalent autoimmune disease affecting 1% of adults in the US. The goal of therapy in patients with RA is to arrest the disease and to achieve remission by preventing or controlling joint damage, preventing loss of function and providing pain relief, thereby improving QOL. Non-biological disease-modifying antirheumatic drugs (DMARDs) have been the mainstay of early intervention in RA, of which methotrexate has been used most frequently. However, in the long term, patients treated with non-biological DMARDs (including methotrexate) may experience joint deterioration and subclinical inflammation even after clinical remission, emphasizing the need for alternative therapies. Several biological therapies, such as anti-tumour necrosis factor (TNF)-α agents, have been developed in the last decade and may be used either as monotherapy or in combination with non-biological DMARDs. Although anti-TNFα therapy is generally associated with an improvement in symptoms of RA, some patients may experience inadequate response to or may not tolerate these agents. The new biological agent abatacept, a recombinant protein consisting of the extracellular region of the human cytotoxic T-lymphocyte-associated antigen (CTLA)-4 receptor fused to the constant fragment (Fc) region of IgG1, binds to the CD80/CD86 molecules on antigen-presenting cells and modulates T-cell activation. Clinical trials have shown that abatacept is effective in reducing disease activity, structural joint damage and improving QOL in patients with RA who had inadequate response to prior methotrexate or anti-TNFα therapy. Pooled analysis of these trials showed that abatacept was also generally well tolerated in these patients. Thus, abatacept therapy may be an option for the treatment of RA in patients who have had an inadequate response to prior DMARD therapy.

Could early rheumatoid arthritis resolve after periodontitis treatment only?: case report and review of the literature.

AbstractRheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge.A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy.It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.

Being positive despite illness: The contribution of positivity to the quality of life of cancer patients.

Objective: The purpose of this study was to examine the longitudinal relationship between Positivity (POS), defined as a stable disposition to view at experience under a positive outlook, and physical and psychological functioning in a sample of cancer patients immediately after diagnosis and one year later. Methods: A total of 110 patients (40% males) with pulmonary, colorectal and breast cancer, aged 30–75 (M age = 59.62; SD = 10.33), have been prospectively enrolled between 2012 and 2013, at the S. Andrea Hospital in Rome. All patients were previously aware of their diagnosis. A follow-up one year after diagnosis was conducted. We used structural equation modeling in order to analyse the specific effects of POS on functioning impairment from diagnosis to follow up. Results: POS was associated with less functioning impairment both at diagnosis and follow-up assessments. Furthermore, POS level at diagnosis continued to be associated with less functioning impairment one year later, after controlling for its stability. Conclusions: Patients with higher level of POS tended to report less symptoms associated with negative affect such as anxiety and despondency and to preserve their habitual relationships and social roles. POS may act as a basic disposition that sustains patients’ efforts to deal efficaciously with severe illness, by complying with medical treatment and using cognitive strategies that enable individuals to cope with concurrent and prospective challenges of illness.

Microbiota and chronic inflammatory arthritis: an interwoven link

BackgroundOnly recently, the scientific community gained insights on the importance of the intestinal resident flora for the host’s health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance.Main bodyCorrelations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course. In the context of dysbiosis it is also important to remember that different environmental factors like stress, smoke and dietary components can induce strong bacterial changes and consequent exposure of the intestinal epithelium to a variety of different metabolites, many of which have an unknown function. In this perspective, and in complex disorders like autoimmune diseases, not only the genetic makeup, sex and immunologic context of the individual but also the structure of his microbial community should be taken into account.ConclusionsHere we provide a review of the role of the microbiota in the onset, severity and progression of chronic inflammatory arthritis as well as its impact on the therapeutic management of these patients. Furthermore we point-out the complex interwoven link between gut-joint-brain and immune system by reviewing the most recent data on the literature on the importance of environmental factors such as diet, smoke and stress.

Infectious Agents and Inflammation: The Role of Microbiota in Autoimmune Arthritis

In higher vertebrates, mucosal sites at the border between the internal and external environments, directly interact with bacteria, viruses, and fungi. Through co-evolution, hosts developed mechanisms of tolerance or ignorance toward some infectious agents, because hosts established “gain of function” interactions with symbiotic bacteria. Indeed, some bacteria assist hosts in different functions, among which are digestion of complex carbohydrates, and absorption and supply of vitamins. There is no doubt that microbiota modulate innate and acquired immune responses starting at birth. However, variations in quality and quantity of bacterial species interfere with the equilibrium between inflammation and tolerance. In fact, correlations between gut bacteria composition and the severity of inflammation were first described for inflammatory bowel diseases and later extended to other pathologies. The genetic background, environmental factors (e.g., stress or smoking), and diet can induce strong changes in the resident bacteria which can expose the intestinal epithelium to a variety of different metabolites, many of which have unknown functions and consequences. In addition, alterations in gut permeability may allow pathogens entry, thereby triggering infection and/or chronic inflammation. In this context, a local event occurring at a mucosal site may be the triggering cause of an autoimmune reaction that eventually involves distant sites or organs. Recently, several studies attributed a pathogenic role to altered oral microbiota in rheumatoid arthritis (RA) and to gut dysbiosis in spondyloarthritis (SpA). There is also growing evidence that different drugs, such as antibiotics and immunosuppressants, can influence and be influenced by the diversity and composition of microbiota in RA and SpA patients. Hence, in complex disorders such RA and SpA, not only the genetic background, gender, and immunologic context of the individual are relevant, but also the history of infections and the structure of the microbial community at mucosal sites should be considered. Here the role of the microbiota and infections in the initiation and progression of chronic arthritis is discussed, as well as how these factors can influence a patient’s response to synthetic and biologic immunosuppressive therapy.

Vaccination policies in the military: an insight on influenza

Influenza, despite its generally benign clinical course, is accompanied by absenteeism from work, acute suffering and even mortality, mainly in the elderly and in subjects who have high-risk medical conditions. Its prevention consists of strain specific vaccination, which must be repeated annually due to the high antigenic variability of the influenza virus. Influenza may represent an important obstacle to military readiness, particularly when considering its infectivity within closed communities. Despite such epidemiological situations, influenza vaccination is seldom included in the compulsory vaccination programme of the military on a global level. This may be due to several reasons, namely, a lack of confidence in the vaccines effectiveness, the need for annual administrations (with expansion of economic and organisational efforts), false assumption that influenza is a disease with a minor impact, contradictory results of cost-effectiveness analyses (examples of which have yet to be made specifically for the military environment). The availability of more effective, economic and easy to administer vaccines, together with detailed and tailored cost-effectiveness analyses, may have a beneficial effect on the role the military plays in the fight against influenza across the globe.

Therapeutic management of patients with rheumatoid arthritis and associated interstitial lung disease: case report and literature review:

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that can present different extrarticular manifestations involving heart, lungs and kidneys. In recent years there has been a growing awareness of the central role played by the lungs in the onset and progression of RA. In particular interstitial lung disease (ILD) is a common pulmonary manifestation that may be related to the inflammatory process itself, infectious complications and to the treatments used. Management of patients with ILD/RA is still a challenge for clinicians, both synthetic [mainly methotrexate (MTX), leflunomide] and biologic immunosuppressors [mainly anti-tumor necrosis factor (TNF)α] have in fact been related to the onset or worsening of lung diseases with conflicting data. Here we report the case of a 61-year-old male patient with severely active early RA, previously treated with MTX, who developed subacute ILD, along with a review of ILD/RA topic. Tocilizumab (humanized monoclonal antibody against the interleukin-6 receptor) was introduced on the basis of its effectiveness in RA without concomitant MTX and the ability to overcome the profibrotic effects of interleukin (IL)-6. After 3 months of treatment the clinical condition of the patient strongly improved until it reached low disease activity. He no longer complained of cough and dyspnea and bilateral basal crackles were no more present. Considering its distinctive features, tocilizumab, in such a challenging clinical condition, appears to be a safe and effective therapy, thus it enables RA remission without deteriorating ILD, at 1-year follow up, as confirmed by ultrasonography of the affected joints and chest high-resolution computed tomography (HRCT).