Maria Letizia Urban

Rituximab therapy for chronic periaortitis

Chronic periaortitis (CP) is a rare condition, hallmarked by periaortic fibro-inflammatory tissue which often causes ureteral obstruction, and encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (IAAA). CP usually responds to glucocorticoids, but some patients may be steroid-refractory or not tolerate standard glucocorticoid doses. For such cases, valid therapeutic alternatives are lacking.1 2 Combinations of prednisone and immunosuppressants (eg, cyclophosphamide, mycophenolate mofetil) are not of proven superiority to prednisone alone, and their effectiveness in refractory CP is unknown.3 4 Because B cells abundantly infiltrate CP lesions,5 and CP is often associated with autoimmune diseases,6 we used rituximab in two patients with CP, one refractory to conventional treatments, and the other with contraindications to standard-dose glucocorticoids. Our first patient, a 49-year-old woman, was hospitalised for malaise and back pain. Abdominal CT revealed a soft-tissue-density periaortic mass suggesting CP, a diagnosis confirmed by laparoscopic biopsy (figure 1). The patient responded to prednisone (initial dose, 1 mg/kg/day), with symptom remission and reduction in CP thickness, but relapsed with back pain and CP enlargement when the prednisone dose was 5 mg/day (8 months after treatment initiation). …

Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis

BACKGROUND AND OBJECTIVES Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). cAP dysregulation is also a major determinant of thrombotic microangiopathies (TMA), which can in turn complicate AAV. We explored the prognostic significance of cAP activation and of histologic evidence of TMA in a cohort of patients with renal AAV. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 46 patients with AAV diagnosed between January 1990 and December 2011 at the Nephrology Unit of Parma University Hospital; 30 of them had undergone renal biopsy. We analyzed serum levels of C3 (sC3) and C4 (sC4) and, for 19 patients who had frozen plasma, plasma Bb and C5b-9 levels. We also reviewed all kidney biopsy specimens, specifically searching for histologic signs of TMA, and performed immunofluorescence or immunohistochemistry for C3d, C4d, Bb and C5b-9. RESULTS sC3 was below the lower limit of normal in 35% of the patients, whereas C4 was low in only 2%. Patients with low sC3 tended to be older (P=0.04) and to have lower eGFR at diagnosis (P=0.06). The median follow-up was 78 months (interquartile range, 18-135 months); 18 patients reached ESRD (10 of 14 and 8 of 26 in the low and normal sC3 groups, respectively). Death-censored renal survival was lower in the low sC3 group than in the normal sC3 group (log-rank test, P=0.01). Eight of the 30 patients who had undergone biopsy (27%) had histologic signs of TMA; these signs were more frequent in patients with low sC3 (5 of 10 versus 3 of 20; P=0.04). Notably, patients with histologic signs of TMA had a dramatically worse death-censored renal survival than patients without TMA (log-rank test, P=0.01), with ESRD occurring in 8 of 8 patients with TMA versus 8 of 22 patients without TMA. CONCLUSIONS Low sC3 levels and histologic signs of TMA are associated with a poor renal prognosis in patients with AAV.

Methotrexate plus prednisone in patients with relapsing idiopathic retroperitoneal fibrosis

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease, characterised by a fibroinflammatory tissue surrounding the aortoiliac axis and frequently entrapping the ureters.1 ,2 Glucocorticoids effectively induce remission, but 24% to 72% of patients relapse, half of them repeatedly.3 ,4 Immunosuppressants and glucocorticoids are usually required in relapsing IRF but no studies are available. In this prospective, open-label trial we enrolled 16 relapsing patients with IRF (July 2004 to April 2011) aged 18–85 years and with an estimated glomerular filtration rate (eGFR)>50 ml/min5 after ureteral decompression (if required), and treated them with methotrexate and prednisone for 12 months. Relapse was defined in case of mass enlargement, hydronephrosis, or disease-related symptoms associated with high inflammatory markers.3 Prednisone was given at 0.5–1 mg/kg/day depending on flare severity, tapered to 12.5–10 mg/day by month 3, 7.5–5 mg/day by month 6 and maintained at 5–2.5 mg/day until month 12. Methotrexate was given at 15–20 mg/week until month 12. After month 12, the clinician was free to continue or withdraw the treatment. The primary endpoint was remission (at month 12) defined as a stable, reduced mass and absence of hydronephrosis, disease-related symptoms and normal inflammatory markers.3 Secondary endpoints were changes in erythrocyte sedimentation …

Asbestos and Smoking as Risk Factors for Idiopathic Retroperitoneal Fibrosis: A Case–Control Study

BACKGROUND Idiopathic retroperitoneal fibrosis (RPF) is a rare disease. Asbestos exposure has been proposed as a risk factor for idiopathic RPF. OBJECTIVE To investigate the role of asbestos and other occupational agents (such as silica, metals, and organic solvents), as well as environmental agents (such as smoking), and their interactions as potential risk factors for idiopathic RPF. DESIGN Case-control study. SETTING National referral hospital for idiopathic RPF. PATIENTS 90 patients with idiopathic RPF and 270 control participants matched for age, sex, and region of residency. MEASUREMENTS Occupational history was obtained using structured questionnaires administered by blinded specialists in occupational medicine. Exposure to nonoccupational agents and presence of diseases that were potentially predisposing to idiopathic RPF were assessed through patient interviews and examination of medical records. RESULTS A history of asbestos exposure was associated with idiopathic RPF (odds ratio [OR], 4.22 [95% CI, 2.14 to 8.33]). Both current smoking (OR, 3.21 [CI, 1.46 to 7.07]) and former smoking (OR, 2.93 [CI, 1.39 to 6.14]) were more prevalent among patients than among those who never smoked. A multiplicative effect was found between tobacco smoke and both occupational asbestos exposure (OR, 12.04 [CI, 4.32 to 38.28]) and extraoccupational asbestos exposure (OR, 8.42 [CI, 2.77 to 30.58]). LIMITATION Retrospective, questionnaire-based assessment of occupational exposure. CONCLUSION Exposure to asbestos and tobacco smoke resulted in strong risk factors for idiopathic RPF. Coexposure to asbestos and smoke had a multiplicative effect on risk compared with single exposure. PRIMARY FUNDING SOURCE None.

Association between idiopathic retroperitoneal fibrosis and autoimmune thyroiditis: A case–control study ☆

BACKGROUND Idiopathic retroperitoneal fibrosis (IRF) is a rare disease often associated with autoimmune disorders. Whether IRF is associated with Hashimotos thyroiditis (HT) is poorly understood and only addressed by case-reports. We evaluated the prevalence of HT in a large IRF cohort and in matched controls. METHODS We studied 73 consecutive patients with new-onset IRF and 71 controls. The association between HT and IRF was cross-sectionally evaluated in a referral center. Longitudinally, thyroid function tests were also performed. Serum concentrations of FT4, TSH, and anti-thyroperoxidase antibodies (AbTPO) were evaluated together with thyroid ultrasound (US). Lymphocytic infiltrates were characterized in thyroid nodule fine needle aspirates (FNAB). In patients undergoing thyroidectomy, thyroid histology was also reviewed. RESULTS A higher prevalence of AbTPO positivity (P<0.03) and US findings suggestive of autoimmune thyroiditis (US-AIT) (P<0.0001) were found in IRF patients compared to controls. In the logistic regression analysis, the risk of AbTPO-diagnosed HT and that of US-AIT was significantly higher in IRF patients than in controls (ORs, 3.56, 95% CI 1.48-8.59, P=0.004 and 4.74, 95% C.I., 2.34-9.61, P<0.0001 in AbTPO-diagnosed HT and US-AIT, respectively). Thyroid histology in IRF patients showed either classical or the fibrous variant of HT. At the end of the follow-up (median, 45 and 36 months in patients and controls, respectively), 25% of IRF patients and 3% of controls were receiving l-thyroxine. CONCLUSIONS IRF patients have a higher risk of HT compared to controls. Thyroid function should be monitored in patients with IRF.

Complement blockade in ANCA-associated vasculitis: an index case, current concepts and future perspectives

Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation was identified. We treated our patient with the standard immunosuppressive therapy, but disease progression was only reversed after the addition of eculizumab, a monoclonal antibody against C5; the patient eventually achieved an almost complete renal function recovery. A review of the available literature about the role of complement targeted therapies in the treatment of AAV is discussed.

Repeated low-dose courses of rituximab in SLE-associated antiphospholipid syndrome: Data from a tertiary dedicated centre

We read with interest the recent article by Wang and Liu [1], describing their experience with rituximab (RTX) in 6 systemic lupus erythematosus (SLE)-associated antiphospholipid syndrome (APS) patients. These data support the idea that, in line with previous sporadic cases reported in literature, RTX at different regimens is able to reduce thrombotic recurrences and to improve SLE activity, with an overall good safety profile. Moreover, they

Brief Report : Rituximab for the Treatment of Adult-Onset IgA Vasculitis (Henoch-Schönlein)

Adult‐onset IgA vasculitis (Henoch‐Schönlein) (IgAV) is a rare systemic vasculitis characterized by IgA1‐dominant deposits. The treatment of adult‐onset IgAV is controversial and is based on the combination of glucocorticoids and immunosuppressive agents, but many patients have refractory or relapsing disease despite treatment. Rituximab (RTX) is a B cell–depleting antibody of proven efficacy in antineutrophil cytoplasmic antibody–associated vasculitis. We undertook this study to test the efficacy and safety of RTX in a multicenter cohort of patients with adult‐onset IgAV.

Changing patterns in clinical–histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis

Objectives To evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time. Patients and methods We studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test. Results A progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD. Conclusions Clinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

Use of Interleukin-1 Blockers in Pericardial and Cardiovascular Diseases

Purpose of ReviewThis review aims to summarize the role of the interleukin-1 (IL-1) blocking agents in cardiovascular diseases, briefly describing the pathogenetic rationale and the most relevant clinical studies.Recent FindingsIL-1 is a pivotal cytokine of the innate immune system. Anti-IL-1 agents are currently used for the treatment of several autoimmune and autoinflammatory conditions. Recently, the role of IL-1 has also emerged in cardiovascular diseases. Indeed, two recent randomized controlled trials have shown that the IL-1 receptor antagonist anakinra is effective for the treatment of idiopathic recurrent pericarditis and the IL-1β blocking agent canakinumab is effective in reducing myocardial infarction in people at risk. Interestingly, interfering with IL-1 has proved to be also effective in other cardiovascular manifestations, such as myocarditis, arrhythmias, and heart failure.SummaryBlocking the IL-1 pathway is a possible new therapeutic strategy, potentially leading to innovative therapies in many acute and chronic cardiovascular diseases.