[TAFRO syndrome and cutaneous necrotizing vasculitis]. / Syndrome TAFRO et vascularite nécrosante cutanée : une association inédite.

INTRODUCTION: TAFRO syndrome is a systemic inflammatory syndrome in the spectrum of Castleman's disease, associating thrombocytopenia, anasarca, fever, renal failure and/or reticulin myelofibrosis and organomegaly. Its association with necrotizing cutaneous vasculitis has not yet been reported. CASE REPORT: A 69-year-old woman presented with weight loss, fever, anasarca, organomegaly, lymphadenopathy, anuria and extensive necrotic livedo occurring after acute diarrhea. Biology showed anemia, thrombocytopenia, renal failure, hypergammaglobulinemia, a circulating B-lymphocyte clone, hypoparathyroidism and autoimmune hypothyroidism. The skin biopsy showed small vessel vasculitis with fibrinoid necrosis. Methylprednisolone infusions associated with tocilizumab were ineffective and the patient became anuric. Rituximab and plasma exchanges associated to corticosteroids allowed remission for 2 months. Combination of rituximab, cyclophosphamide and dexamethasone resulted in a prolonged remission. CONCLUSION: We report here the first case of severe cutaneous necrotizing vasculitis in a patient suffering from TAFRO syndrome. The possible resistance to tocilizumab should be known.

Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. RESULTS: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ±â€¯78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.

Prevalence of cryoglobulinemia and autoimmunity markers in renal-transplant patients.

AIMS: To examine the prevalence of cryoglobulinemia (Cryo) and autoimmune markers in renal-transplant recipients in a stable condition, and to determine its risk factors and impact upon allograft function. PATIENTS AND METHODS: In May, 2006, 117 kidney-transplant (KT) recipients, aged 31 â 76 years, were tested for cryoglobulinemia, hepatitis B and C, complement C3, C4, CH50, antinuclear (ANAs), anticytoplasmic nuclear (ANCAs) and anticardiolipid antibodies, rheumatoid factor (RF), and lymphocyte subpopulations. Renal, liver, and hematological tests were also performed. Immunosuppressive regimens were based on calcineurin inhibitors (82%). RESULTS: Cryo was positive in 47 patients (Cryo(+): 40.2%), of whom 13 were HCV+ (27.7%), with characteristics of Type II in 21.2% and Type III in 78.8%. Cryo was positive in 13/16 (81.2%) of HCV+/RNA+ patients vs. 34/101 (33.6%, p = 0.0003) of HCV-negative patients. Cryo(+) RT patients had been recipients of a graft for longer (142 months) than Cryo(-) patients, i.e., 95 months (p = 0.02). Creatinine clearances were similar in the two groups (56 vs. 50 ml/mn, p = 0.5), as were microalbuminuria and albuminemia. There was no difference between Cryo(-) and Cryo(+) patients in terms of age, sex, HLA mismatch, daily steroid doses, liver and hematological tests, ANAs, anticardiolipid antibodies, serum complement, and lymphocyte subpopulations. RF occurred in all Cryo(+) patients and in 82.8% of Cryo(-) patients, with higher titers in the Cryo(+) group (23 vs. 9 UI/ml, p = 0.012). ANCA occurred in nine Cryo(-) but in no Cryo(+) patients (p = 0.013). Finally, a multivariate analysis was not able to determine any predictive factor associated with cryoglobulinemia. CONCLUSION: Cryoglobulinemia is frequent after KT, and is associated with HCV markers, RF, and absence of ANCA.

Hepatitis C virus viral load after conversion from tacrolimus to cyclosporine in liver transplant patients: a pilot study.

UNLABELLED: We assessed whether conversion from tacrolimus (TAC) to cyclosporine (CsA) was associated with a reduction in hepatitis C virus (HCV) viral load among HCV-positive liver transplant (OLT) patients. PATIENTS AND METHODS: Nine OLT patients with recurrent HCV have TAC and prednisone immunosuppression. None received any HCV antiviral therapy. After the last intake of TAC, the patients underwent a 12-hour area under the curve (AUC(12)) measurement of both TAC and HCV viral loads. The next morning (D(0)) patients were given CsA (4 mg/kg bid). At the first intake of CsA and at 1 month (M(1)) later, the patients underwent AUC(12) for CsA and HCV viral loads. Biological data, including aspartate (AST) and alanine (ALT) aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), and bilirubin levels, were collected during AUC(12), and at M(1) and M(3). RESULTS: With respect to liver enzymes (AST, ALT, GGT), there was no significant difference between D(0), M(1), and M(3). Conversely, there was a significant decrease in AP between D(0) and M(3) (P = .02), and a significant increase in total bilirubin between D(0) and M(1) (P = .04), and between D(0) and M(3) (P = .01). HCV viral load significantly increased by M(3) (P = .01). At no time (D(0), M(1)) was there any correlation between the AUC(12) of TAC or CsA, and between AUC(12) HCV viral load. CONCLUSION: This pilot study found no acute or chronic anti-HCV effects from CsA that were evident within 12 hours after CsA administrations or beyond 1 month of CsA therapy, respectively.

Linezolid-related pancytopenia in organ-transplant patients: report of two cases.

Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci infection. We herein report on the first two cases of linezolid-related pancytopenia in organ-transplant patients. Both patients had methicillineresistant Staphylococcus aureus infections. Pancytopenia, i.e. aregenerative anemia, neutropenia and thrombopenia, developed 3 weeks and 5 weeks after initiating linezolid therapy at a conventional dosage (600 mg bid). There were no other confounding causes of pancytopenia, which resolved promptly after withdrawing linezolid. Because of the potential hazards of pancytopenia in immunosuppressed organ-transplant patients, we advocate the cautious use of linezolid for transplant patients.

Treatment of focal segmental glomerular sclerosis with rituximab: 2 case reports.

BACKGROUND: Primary focal segmental glomerular sclerosis (FSGS) recurs in 20 - 40% of patients after kidney transplantation. Rituximab has been used to treat several glomerular diseases. PATIENTS AND RESULTS: We treated two renal-transplant patients with recurrence of FSGS with rituximab. Despite a prophylactic perioperative therapy of plasmapheresis (PE) and i.v. cyclosporine A, Patient 1 developed significant proteinuria, at 1 day after his first kidney transplantation. After two infusions of rituximab (375 mg/m2) he had complete remission. A second relapse, which occurred on Day 40, was also successfully treated by PE and one additional infusion of rituximab. 10 months after transplantation, he still has complete remission from recurrent nephrotic syndrome. Patient 2 also developed significant proteinuria, but 1 day after a second kidney transplantation. Nephrotic syndrome persisted despite 27 sessions of PE and cyclophosphamide therapy. At 13 months after transplantation, he received four infusions of rituximab (375 mg/m(2)), but this was ineffective. CONCLUSION: There is a need to demonstrate whether or not rituximab therapy is of interest to prevent and to treat nephritic syndrome in renal-transplant patients who suffer from FSGS.