Nuovi aspetti classificativi e terapeutici del lupus eritematoso sistemico : centralità dell'interessamento renale

Systemic lupus erythematosus (SLE) is an autoimmune condition with a wide range of manifestations. Among the various targets of the disease, the kidney holds a very important place. In fact, renal involvement is one of the most important and frequent features of the disease, deeply affecting a patient's prognosis and influencing the therapeutic approach. In the last few years, some progress has been achieved in terms of both disease classification and treatment. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) published the new classification criteria for SLE and the American College of Rheumatology established recommendations for the screening, treatment, and management of SLE nephritis. These new points of view derived from the recent evolution of medical knowledge, technology, and practice in the field of SLE in general, and lupus nephritis in particular. Moreover, it is important to remember that SLE still remains a systemic disorder and that a multi-disciplinary approach is the optimal way to manage these patients

Nuovi aspetti classificativi e terapeutici del lupus eritematoso sistemico: centralità dell'interessamento renale

Systemic lupus erythematosus (SLE) is an autoimmune condition with a wide range of manifestations. Among the various targets of the disease, the kidney holds a very important place. In fact, renal involvement is one of the most important and frequent features of the disease, deeply affecting a patient's prognosis and influencing the therapeutic approach. In the last few years, some progress has been achieved in terms of both disease classification and treatment. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) published the new classification criteria for SLE and the American College of Rheumatology established recommendations for the screening, treatment, and management of SLE nephritis. These new points of view derived from the recent evolution of medical knowledge, technology, and practice in the field of SLE in general, and lupus nephritis in particular. Moreover, it is important to remember that SLE still remains a systemic disorder and that a multi-disciplinary approach is the optimal way to manage these patient

The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation

Genetics and novel aspects of therapies in systemic lupus erythematosus

Autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis and inflammatory bowel disease, have complex pathogeneses and the factors which cause these disorders are not well understood. But all have in common that they arise from a dysfunction of the immune system, interpreting self components as foreign antigens. Systemic lupus erythematosus (SLE) is one of these complex inflammatory disorders that mainly affects women and can lead to inflammation and severe damage of virtually any tissue and organ. Recently, the application of advanced techniques of genome-wide scanning revealed more genetic information about SLE than previously possible. These case-control or family-based studies have provided evidence that SLE susceptibility is based (with a few exceptions) on an individual accumulation of various risk alleles triggered by environmental factors and also help to explain the discrepancies in SLE susceptibility between different populations or ethnicities. Moreover, during the past years new therapies (autologous stem cell transplantation, B cell depletion) and improved conventional treatment options (corticosteroids, traditional and new immune-suppressants like mycophenolate mofetile) changed the perspective in SLE therapeutic approaches. Thus, this article reviews genetic aspects of this autoimmune disease, summarizes clinical aspects of SLE and provides a general overview of conventional and new therapeutic approaches in SLE

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)