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To date, belimumab is the only biological drug approved for the treatment of patients with active refractory SLE. We compared and critically analyzed the results of 11 observational clinical-practice-based studies, conducted in SLE referral centers. Despite the differences in endpoints and follow-up duration, all studies remarked that belimumab provides additional benefits when used as an add-on to existing treatment, allowing a higher rate of patients to reach remission and to taper or discontinue corticosteroids. In the OBSErve studies, 2–9.6% of patients discontinued corticosteroids and 72–88.4% achieved a ≥ 20% improvement by physician’s judgment at 6 months. In Hui-Yuen’s study, 51% of patients attained response by simplified SRI at month 6. In Sthoeger’s study, 72.3% of patients discontinued corticosteroids and 69.4% achieved clinical remission by PGA after a median follow-up of 2.3 years. In the multicentric Italian study, 77 and 68.7% of patients reached SRI-4 response at months 6 and 12, respectively. In all the studies, disease activity indices decreased over time. Retention rates at 6, 9, and 12 months were 82–94.1, 61.2–83.3, and 56.7–79.2%, respectively. The main limitations of these studies include the lack of a control group, the short period of observation (6–24 months) and the lack of precise restrictions regarding concomitant medication management. This notwithstanding, these experiences provide a more realistic picture of real-life effectiveness of the drug compared with the randomized controlled clinical trials, where stringent inclusion/exclusion criteria and changes in background therapy could limit the inference of data to the routine clinical care.

Psoriasis is a chronic immune-mediated inflammatory disease. Up to 40% of patients with psoriasis may develop psoriatic arthritis. Currently, interleukin (IL)-17/IL-23 pathways are identified as key factors in the immunopathogenesis of both conditions. Here we describe the case of a patient who developed psoriasiform skin lesions 10 months after the initiation of anti-IL17 therapy for psoriatic arthritis. The underlying disease had responded well to the therapy, but the patient developed a striking pustular eruption at the fingers with nail involvement, onycholysis, yellow discoloration, and subungual keratosis. Clinical and histological findings were consistent with an acrodermatitis continua of Hallopeau-like eruption. Skin lesions subsided after discontinuation of the responsible anti-IL17 agent. The interpretation of this paradoxical side effect of biological therapies remains unclear but may relate to an unbalanced inflammatory cytokine response induced by the inhibition of TNF activity. It is likely that patients, who are genetically prone, may respond exaggeratedly to a cytokine imbalance. The identification of this kind of patient, in the future, could be useful in order to choose the correct therapy.

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sj&ouml, gren&rsquo, s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p &lt, 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p &le, 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc&ndash, CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Objective To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. Methods Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti–double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into “classical” (CLP) and “rheumatoid-like”; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). Results Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P

Objective To evaluate the prevalence of different definitions of remission and their effect on damage in systemic lupus erythematosus (SLE). Design and method We considered 293 caucasian SLE patients followed-up for 7 years (2009–2015): 253 (86.3%) were female, mean ±SD disease duration 11.1±7.8 years. Disease activity was assessed by clinical SLEDAI-2K (c-SLEDAI) and damage by SLICC/ACR Damage Index (SDI). We evaluate the effect of different definitions of remission (c-SLEDAI=0; c-SLEDAI ≤1; c-SLEDAI=0 and prednisone ≤5 mg/day; c-SLEDAI ≤1 and prednisone ≤5 mg/day; c-SLEDAI=0 and PGA Results Frequency of remission achieved during the 7 year follow-up are reported in table 1 according to the different definitions. The mean increase in SDI and the percentage of patients with increased of SDI from the baseline to the end of follow-up were significantly higher in unremitted and 1 year remitted patients compared with patients with 2-, 3-, 4- and ≥5 year remission, irrespective of the definition of remission. 5 year remitted patients had lower damage compared with 2 year (p Conclusions The inclusion of PGA

To date, belimumab is the only biological drug approved for the treatment of patients with active refractory SLE. We compared and critically analyzed the results of 11 observational clinical-practice-based studies, conducted in SLE referral centers. Despite the differences in endpoints and follow-up duration, all studies remarked that belimumab provides additional benefits when used as an add-on to existing treatment, allowing a higher rate of patients to reach remission and to taper or discontinue corticosteroids. In the OBSErve studies, 2–9.6% of patients discontinued corticosteroids and 72–88.4% achieved a ≥ 20% improvement by physician’s judgment at 6 months. In Hui-Yuen’s study, 51% of patients attained response by simplified SRI at month 6. In Sthoeger’s study, 72.3% of patients discontinued corticosteroids and 69.4% achieved clinical remission by PGA after a median follow-up of 2.3 years. In the multicentric Italian study, 77 and 68.7% of patients reached SRI-4 response at months 6 and 12, respectively. In all the studies, disease activity indices decreased over time. Retention rates at 6, 9, and 12 months were 82–94.1, 61.2–83.3, and 56.7–79.2%, respectively. The main limitations of these studies include the lack of a control group, the short period of observation (6–24 months) and the lack of precise restrictions regarding concomitant medication management. This notwithstanding, these experiences provide a more realistic picture of real-life effectiveness of the drug compared with the randomized controlled clinical trials, where stringent inclusion/exclusion criteria and changes in background therapy could limit the inference of data to the routine clinical care.

Objectives To evaluate survival of prednisone (PDN) – free remission in systemic lupus erythematosus (SLE) patients and to investigate the potential predictors of disease flares. Methods Inclusion criteria were: (1) Diagnosis of SLE according to American College of Rheumatology (ACR) Classification Criteria of SLE; (2) Caucasian ethnicity; (3) Clinical remission (clinical SLEDAI-2K=0) at the time of PDN-withdrawal; (4) Stop of PDN treatment between 2010 and 2016; (5) At least two visits per year between January 2010 and April 2016. Disease activity was assessed according to SLE Disease Activity Index-2000 (SLEDAI-2K). Damage was measured by the SLICC/American College of Rheumatology Damage Index (SDI). Flares were defined according to Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI criteria. We evaluated whether gender, age, age at PDN-stop, disease duration, duration of corticosteroid therapy, duration of remission before PDN withdrawal, time to flare, SLICC/American College of Rheumatology Damage Index (SDI) – score >3, positive anti-dsDNA antibodies (abs) and-or low C3/C4, type of SLE-involvement and concomitant immunosuppressive treatment could be predictors of flare. Multivariate logistic regression analysis was run to investigate the predictors of flare. Covariates included in the analysis were all variables reaching p Results Among 400 patients evaluated, 104 (26%) fulfilled inclusion criteria. Baseline characteristics are reported in table 1. Twenty-two (21.2%) patients flared. Mean time to flare was 19.91±13.14 months. Types of flare were 7 renal, 7 articular, 4 cutaneous, 2 haematological, 1 serositic and 1 neurological. Variables included in the multivariate logistic regression analysis were: positive anti-dsDNA abs and-or low C3/C4, skin, articular and haematological involvement. Skin involvement resulted predictive of flare (OR 3.07, 95% CI 1.11–8.53, P 0.031) as reported in table 2. Conclusions In SLE patients who stopped corticosteroid therapy, previous skin involvement resulted to be a predictor of disease flare. Disclosure of Interest None declared

Background Celiac disease (CD) is an inflammatory and immune-mediated gluten-dependent enteropathy occurring in genetically susceptible individuals. CD is recognized to affect between 0.6% and 1% of worldwide population, with wide regional differences. Disease clinical features are protean and highlight the systemic nature of the disease. In recent years, an increased prevalence of CD has been also reported in patients with connective tissue diseases (CTDs). This association may be due to a shared genetic predisposition, to immunological mechanisms and/or exposure to a common triggering event. However, this observation remains controversial since data are usually based on descriptive case reports. Different methods of antibody detection and enrolled population sample size may contribute to result discordance. Moreover, CD diagnosis is often delayed because disease clinical spectrum may be atypical mimicking rheumatologic conditions and autoimmune disease itself may display typical symptoms of CD. Undoubtedly, awareness of CD occurrence in CTDs is important to prevent potential long-term systemic complications related to an unrecognized CD in these patients. Objectives To evaluate the prevalence of overt and subclinical CD and features of the disease in a large cohort of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and primary Sjogren9s syndrome (pSS) with a multicenter prospective study involving 9 Italian Rheumatology Units. Methods Data from consecutive 580 SLE, 354 pSS and 524 SSc patients were collected. Disease-specific features were registered in patients with known CD. Remaining patients were tested for IgA transglutaminase (Eu-tTG® human IgA new, Eurospital S.p.A., Trieste). Anti-endomysium (EMA) IgA and IgG were tested in IgA tTG positive and borderline patients. Esophagogastroduodenoscopy with duodenal biopsy was proposed in IgA tTG+/EMA+, IgA tTG-/EMA+ and IgA tTG±/EMA+ patients. Results CD prevalence was 1,7% in SLE, 7% in pSS and 1,3% in SSc patients. Higher frequency of elevated liver enzymes was detected in SLE-CD and of herpetiform dermatitis in SSc-CD patients in comparison to the other groups (p Conclusions The results of the present large multicenter study confirm higher prevalence of CD in CTD patients, especially in pSS. Screening of CD may be considered in younger patients with CTD and lower age at diagnosis. The strong association of CD with the diffuse type of SSc is of note and suggests that different, still unexplored, pathogenic mechanisms may characterize the two subsets of the disease. Disclosure of Interest None declared

Background and aims To explore predictors of renal remission, insufficiency and damage in lupus nephritis (LN). Methods We retrospectively analysed our lupus cohort and studied LN patients with at least one renal biopsy since 1990 until 2016. Follow-up ended at last patient visit. Complete renal remission (CRR) was defined as proteinuria 0.5 g/day and/or requirement for treatment modifications. Damage was measured by SLICC damage index (SDI). Results 81 patients were studied (Table) who underwent 110 biopies. Forty patients (49.3%) went into CRR by the end of follow-up. Thirty-six (44.5%) had 2 renal flares while 21≥3 (26%). Six patients developed renal failure preceded by ≥3 flares in 5. One case of ESRD was reported. By the end of follow-up 30 patients (37%) had SDI≥2. At univariate analysis, increased proteinuria at 12 and 24 months from first biopsy and higher flare number were inversely associated with CRR, while long-lasting hypertension, abnormal SCr, decreased GFR and C4 at time of first biopsy were associated with renal failure. At multivariate analysis 24h-proteinuria at 24 months independently predicted lack of CRR (OR 3.7), while a higher number of renal flares (OR 5.27), higher SCr at 6 months from renal biopsy (OR 5.01) and a longer disease duration (OR 6.34) were independently associated with damage accrual. Conclusions Increased proteinuria and abnormal baseline renal function make CRR unlikely. Suboptimal control of LN activity and longer disease duration are associated with severe damage accrual.

To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting.Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0).Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P 0.001), particularly in those with CLP (P 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation.Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by inflammation of the skeletal muscle. Weakness, mainly affecting the proximal muscles, is the cardinal muscular symptom in IIM. In patients with dermatomyositis, peculiar skin lesions are observed. The assessment of patients with IIM includes clinical and laboratory evaluation, and clinimetric measurements. Different tools have been proposed to measure muscular and extramuscular disease activity and damage in patients with IIM. A core set of measurements to use in clinical practice was recently proposed. Among laboratory features the increase of serum creatine kinase (CK) is considered a hallmark of muscle inflammation/damage. However, subjects with persistent CK elevation, without any evidence of a definite myopathy, are often seen in clinical practice and need a careful assessment. Indeed, CK blood levels can also increase in non-myopathic conditions, e.g. in case of intense physical exercise, assumption of some drugs (statins), muscular dystrophy, muscular trauma or in case of neuro-muscular disorders which all should be considered in the diagnostic work-up. The assessment of patients with IIM and hyperCKemia will be discussed in this paper.

Patients with systemic lupus erythematosus (SLE) have a higher prevalence of clinical and subclinical atherosclerosis compared with age- and sex-matched controls. Atherosclerosis progression is also accelerated in SLE, and coronary heart disease (CHD) is a major cause of morbidity and mortality. Traditional cardiovascular (CV) risk factors, including hypertension, diabetes mellitus or dyslipidemia, are more prevalent in SLE patients than in the general population, but they cannot fully account for accelerated atherosclerosis in SLE. In fact, a number of nontraditional risk factors have been identified, including disease activity, damage and various treatments. Preventive strategies for CHD are mandatory in SLE patients and should include giving up smoking; performing regular physical activity; managing metabolic abnormalities such as dyslipidemia, insulin resistance, and diabetes; treating persistent disease activity; and minimizing chronic exposure to corticosteroids. Low-dose aspirin, angiotensin-converting enzyme (ACE) inhibitors, vitamin D supplementation, antimalarials and, when indicated, some immunosuppressants such as mycophenolate mofetil should also be considered.

Resumen El sindrome de secrecion inadecuada de hormona antidiuretica o vasopresina (SIADH) es una entidad de etiologia muy variada que cursa con hiponatremia, hipoosmolalidad plasmatica, osmolalidad urinaria inadecuadamente elevada y natriuresis altas. Al tratarse de un diagnostico por exclusion, se precisa descartar previamente estados que cursan con disminucion de la volemia eficaz, y polidipsia primaria. Ademas, el estado acido-base, el potasio, la funcion cardiaca, renal, suprarrenal y tiroidea deben ser normales. Junto con las neoplasias e infecciones, los farmacos son una causa habitual, y con incidencia en aumento, de este sindrome. Tanto su diagnostico como su tratamiento suelen ser poco complejos, y conciernen con frecuencia al ambito de la Atencion Primaria. Se describen cuatro casos de SIADH atribuido a farmacos, y se revisan las caracteristicas generales de la entidad.

Around 1980 antinuclear antibody testing became widely used in routine laboratory practice leading to a tapering in the lag time between SLE onset and diagnosis. Since then nothing relevant has been introduced which could help us in making the diagnosis of SLE earlier than now. Notably, there is increasing evidence that early diagnosis and treatment could increase SLE remission rate and improve patient prognosis. Although it has been shown that autoantibodies appear before clinical manifestations in SLE patients, currently we cannot predict which autoantibody positive subjects will eventually develop the disease. Thus, great effort should be made in order to identify new biomarkers able to improve our diagnostic potential. B lymphocyte stimulator (BLyS), anti-ribosomal P protein and anti-C1q antibodies are among the most promising. In recent years, some therapeutic options have emerged as appropriate interventions for early SLE treatment, including antimalarials, vitamin D, statins and vaccination with self-derived peptides. All these immune modulators seem to be particularly useful when introduced in an early stage of the disease.

Impairment of the clearance of apoptotic material seems to contribute to autoantigen exposure, which can initiate or maintain an autoimmune response in predisposed individuals. Complement component C1q, Creactive protein (CRP), serum amyloid P (SAP), mannose-binding lectin (MBL), apolipoprotein A-1 (Apo A-1) and long pentraxin 3 (PTX3) are molecules involved in the removal of apoptotic bodies and pathogens, and in other antiinflammatory pathways. For this reason they have been called “protective” molecules. C1q has a key role in the activation of the complement cascade and acts as a bridging molecule between apoptotic bodies and macrophages favouring phagocytosis. In addition to other functions, CRP, SAP and MBL bind to the surface of numerous pathogens as well as cellular debris and activate the complement cascade, thus stimulating their clearance by immune cells. The role of PTX3 is more controversial. In fact, PTX also promotes the clearance of microorganisms, but the activation of the complement cascade through C1q and removal of apoptotic material can be either stimulated or inhibited by this molecule. Antibodies against protective molecules have been recently reported in systemic lupus erythematosus and other autoimmune rheumatic diseases. Some of them seem to be pathogenetic and others protective. Thus, protective molecules and their cognate antibodies may constitute a regulatory network involved in autoimmunity. Dysregulation of this system might contribute to the development of autoimmune diseases in predisposed individuals.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects fertile women, suggesting sex hormones are involved in disease pathogenesis. B lymphocyte stimulator (BLyS) has been found to be elevated in SLE patients and to drive a lupus-like syndrome in transgenic mice. Our aim was to evaluate the effects of estrogen administration on BLyS and nephritogenic anti-C1q and anti-dsDNA antibodies in lupus-prone NZB/WF1 mice. We implanted pellets releasing 17-β-estradiol (18.8 µg/day) on the back side the ear of 10 NZB/WF1 mice (group 1), and compared them with 10 mice intraperitoneally injected with PBS 200 μl twice a week (group 2), as controls. We evaluated BLyS, anti-dsDNA and anti-C1q serum levels starting one week after pellet implantation. We also analyzed time to proteinuria onset, proteinuria-free survival and overall survival. Kidneys, spleen, liver and lungs were harvested for histological analysis. Mice were bred until natural death. BLyS serum levels were higher in group 1 than in group 2 mice at each evaluation. Group 1 mice developed nephritogenic antibodies and proteinuria significantly earlier and at higher levels than controls. Direct correlation between BLyS and anti-C1q ( R2 = 0.6962, p 2 = 0.5953, p 2 = 0.5615, p Estrogen administration is associated with increased levels of BLyS as well as of anti-C1q and anti-dsDNA antibodies, leading to accelerated glomerulonephritis and disease progression in NZB/WF1 mice.

AimTo assess the prevalence of prolonged remission in Caucasian patients affected with systemic lupus erythematosus (SLE) and its relationship with damage accrual.MethodsCaucasian patients diagnosed with SLE between 1990 and 2009 and quarterly seen from 2009 to 2013 were included in the study. We defined remission as prolonged when lasting ≥5 consecutive years. Three levels of remission were defined using the SLE Disease Activity Index-2000 (SLEDAI-2K): complete remission: no disease activity in corticosteroid-free and immunosuppressant-free patients; clinical remission off corticosteroids: serologically active clinical quiescent (SACQ) disease in corticosteroid-free patients and clinical remission on corticosteroids: SACQ disease in patients taking prednisone 1–5 mg/day. Damage was measured by the SLICC/American College of Rheumatology Damage Index (SDI).Results224 patients fulfilled inclusion criteria: 196 (87.5%) were women, mean±SD disease duration 11.2±6.8 years. During the 5-year follow-up, 16 patients (7.1%) achieved prolonged complete remission, 33 (14.7%) prolonged clinical remission off corticosteroids and 35 (15.6%) prolonged clinical remission on corticosteroids. At the multivariate analysis, vasculitis (OR 4.95), glomerulonephritis (OR 2.38) and haematological manifestations (OR 2.19) over the patients’ disease course were associated with an unremitted disease. SDI increased more frequently in unremitted (72/140, 51.4%) than in remitted patients (22/84, 26.2%; p=0.001); SDI median increase was higher in unremitted than in remitted patients: 1 (0–3) vs 0 (0–2), respectively (pConclusionsThirty-seven percent of our Caucasian patients achieved a prolonged remission, which was associated with a better outcome in terms of damage accrual.

In this paper, we report our experience with the use of rituximab (RTX) in the treatment of refractory idiopathic inflammatory myopathies (IIM) and review the literature on this topic. Six adult patients (5 female, 1 male) with active IIM, as defined by persistent proximal muscle weakness, elevated serum muscle enzymes, muscle magnetic resonance imaging, electromyographic and histological abnormalities, refractory to at least one immunosuppressant, including methotrexate, were treated with RTX (1,000 mg twice, 2 weeks apart). Patients were regularly followed up for serial assessment of muscle strength by manual muscle test 8 and creatine kinase serum levels. Three patients were affected with polymyositis (PM) and three with anti-t-RNA synthetase syndrome (ASS). A complete B-cell depletion was observed in all patients by 3 months after RTX. A significant clinical improvement was observed in 5 out of 6 cases 6 months after RTX. Only one mild infusion reaction and one case of Herpes zoster infection were observed. A review of the literature to find all the available cases of refractory patients affected with IIM from 1980 to 2012, using the PubMed database, was performed. We were able to find 27 papers, 18 on PM and dermatomyositis and 9 on ASS, including 88 and 40 patients, respectively. A significant improvement was observed in 80 % of patients overall and the drug was well tolerated in the majority of cases. In conclusion, RTX can be considered a therapeutic option in refractory IIM.

Primary systemic vasculitis are uncommon diseases that may affect young women in their childbearing age. To date, patients affected with primary systemic vasculitis are often diagnosed and treated earlier than in the past, due to improvement in diagnostic skills and a larger availability of effective drugs. The progressive achievement of a longer life expectancy and a better quality of life have progressively led to an increased number of pregnancies observed during the course of such diseases. Here, we review 567 pregnancies among patients with primary systemic vasculitis, in order to define the relationship between pregnancy and these conditions and to suggest guidelines for their management. However, data on pregnancy outcomes are limited and knowledge about their gestational risk is mostly provided by single case reports or at best by retrospective studies which may result in intrinsic observational bias; unfortunately, long term prospective studies are still lacking. Analysis of the data highlighted a reciprocal influence between disease course and gestational outcome, although no definite effects can be outlined. Indeed, either improvement or worsening of the different vasculitis can occur, probably due to diverse genetic, clinical and immunological background of the patients. Since disease course may vary over time, careful management of systemic vasculitis during gestation is required. Furthermore, organ failure or damage must be carefully considered, since it can lead to adverse obstetrical and fetal outcomes.

As soon as autoinflammatory diseases (AIDs) emerged as new entities, they have been linked to the well known world of autoimmunity. In fact, AIDs and systemic autoimmune diseases (ADs), share some characteristics: they start with the prefix "auto" to define a pathological process directed against self; they are systemic diseases, frequently involving musculoskeletal system; both include monogenic and polygenic diseases. From the pathogenetic point of view, they are characterized by a chronic activation of immune system, which eventually leads to tissue inflammation in genetically predisposed individuals. Nevertheless, the specific effectors of the damage are different in the two groups of diseases: in AIDs the innate immune system directly causes tissue inflammation, whereas in ADs the innate immune system activates the adaptive immune system which, in turn, is responsible for the inflammatory process. Mutations in inflammasome-related proteins, particularly in NOD-like receptor (NLR) genes, have been strongly associated to the occurrence of AIDs, whereas the link between inflammasome and ADs is less clear. However, a role for this multiprotein-complex in some ADs can be postulated, since a wide spectrum of endogenous danger signals can activate NLRs and inflammasome products, including IL-1ß, can activate adaptive immunity. An association between single nucleotide polymorphisms (SNPs) localized in the inflammasome gene NLRP1 and systemic lupus erythematosus has recently been reported. AIDs and ADs are currently subdivided into two different groups, but looking at their similarities they might be considered as a single group of diseases with a large immune pathological and clinical spectrum which includes at one end pure ADs and at the other end pure AIDs.

Annexins are a group of 12 highly conserved proteins which exert several regulatory functions on cell biology. There are involved in numerous cell processes including vesicle trafficking, calcium signaling, cell growth, division, and apoptosis. Autoantibodies directed toward annexin I, II, V and XI have been reported, but their role and their clinical correlates are controversial. Annexin I exerts an anti-inflammatory effect by suppressing the generation of inflammatory mediators and anti-annexin I antibodies were detected in patients affected with rheumatoid arthritis, systemic (SLE) and cutaneous lupus erythematosus. Annexin II and V have a high affinity for phospholipids playing a pivotal role in the regulation of coagulation cascade. Anti-annexin II and anti-annexin V antibodies were found in patients with arterial or venous thrombosis, especially in those with autoimmune rheumatic diseases (ARD) such as SLE, primary antiphospholipid syndrome (APS) or systemic sclerosis. Anti-annexin V antibodies were also found in patients with pregnancy loss with or without APS. Annexin XI is involved in several biological pathways, particularly apoptosis and cell proliferation. Anti-annexin XI antibodies have been found in patients with SLE, undifferentiated connective tissue disease, rheumatoid arthritis, Sjogren's syndrome and APS. The metanalysis of studies published up to now showed that the Odds Ratio for having an ARD in anti-annexin XI positive patients was 5.08 (95% CI 2.06-12.58).

Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive agents which exert multiple effects on immune cell functions. Although their use dates back 60 years, their functions and mode of action have not been completely elucidated yet. GCs act through different genomic and non genomic mechanisms which are mediated by the binding to cytosolic glucocorticoid receptor as well as to cell membrane receptors, or by interacting directly with enzymes and other cell proteins. T cell subtypes have a different sensitivity and response to GCs; in fact, GCs have an immunosuppressive effect on pro-inflammatory T cells, while they stimulate regulatory T cell activity. The effect of GCs on B cells is less clear. Interestingly, treatment with GCs may determine apoptosis of autoreactive B cells by reducing the B cell activator factor (BAFF). Tolerogenic dendritic cells which express low levels of Major Histocompatibility Complex class II, co-stimulatory molecules and cytokines, such as IL-1β, IL-6, and IL-12, can be induced by GCs. GCs at low levels stimulate and at high levels inhibit macrophage activity; moreover, they reduce the number of basophils, stimulate the transcription of inhibitors of leukocyte proteinases and the apoptosis of neutrophils and eosinophils. Finally, GCs inhibit the synthesis and function of some cytokines, particularly T helper type 1 cytokines, and to a lesser extent the secretion of chemokines and co-stimulatory molecules from immune and endothelial cells.