Renal and overall outcomes of double-positive (ANCA and anti-GBM antibodies) patients compared to ANCA-associated vasculitis patients with severe renal involvement: A multicenter retrospective study with systematic renal pathology analysis.

OBJECTIVE: Double-positive patients (DPPs), combining serum and/or histological findings for glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic antibodies (ANCAs), are rare and poorly described. This study aimed to compare characteristics between DPPs and ANCA-associated vasculitis (AAV) patients with severe renal involvement. METHOD: This retrospective multicentre study compared 33 DPPs and 45 AAV patients with severe renal involvement (serum creatinine > 300 µmol/L), all with biopsy-proven nephropathy. RESULTS: All DPPs (including 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histological GBM involvement. Compared to AAV patients, they had higher serum creatinine (719 vs 501 µmol/L; p = 0.006) and a higher proportion of patients requiring initial renal replacement therapy (82% vs 36%; p < 0.001). Berden classification differed significantly (p = 0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPPs. One-year renal survival was significantly lower in DPPs than in AAV patients (27% vs 64%; p < 0.0002). With comparable proportions of ANCA subtypes (two-thirds with anti-myeloperoxidase autoantibodies), numbers of extrarenal manifestations (mostly pulmonary in two-thirds), remission-inducing immunosuppressants, and median follow-ups (3 years) between groups, relapse rates were similar: 9.1% of DPPs and 10% of AAV patients. CONCLUSION: Although DPPs have features of both kinds of vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAV patients with severe renal failure. Simultaneous testing of both antibodies and systematically performed renal biopsy should be recommended in all rapidly progressing glomerulonephritis patients to recognize this difficult-to-treat, rare disease.

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.

Effect of intra-articular Botulinum toxin injections on temporo-mandibular joint pain.

Temporo-mandibular joint dysfunction can be painful and disabling. In some cases, it is refractory to classical treatment. Intra-articular Botulinum toxin injections have been shown to have an anti-inflammatory and analgesic effect. The aim of this study was to evaluate the effectiveness of such injections on severe, refractory temporo-mandibular joint pain. This was a retrospective study. Patients were included if they still had joint pain≥5 on a Visual Analogue Scale following completion of all other treatments. A complete treatment protocol (including physiotherapy, tongue splints, intra muscular injections of Botulinum toxin and injections of hyaluronic acid, excluding surgery) having being done before the injection of 30 Botox* units (Botulinum toxin A), the treatment being considered clinically successful if the Visual Analogue Scale decreases by at least 2 points. Seventy-seven patients were included. Sixty-six percent of patients have a significant reduction in pain at 1 month which lasted at least until 3 months. Mouth opening and quality of life also improved. Moreover, no complications were reported. Further randomized, controlled studies are needed to confirm the results, however this study suggests intra-articular injection of Botulinum toxin is a safe and effective treatment for severe, refractory temporo-mandibular joint pain, avoiding surgery.

[Cryofibrinogenemia: a single-center study at the University Hospital of Toulouse, France]. / Cryofibrinogénémie : étude monocentrique au CHU de Toulouse.

PURPOSE: Cryofibrinogenemia is an unknown disorder and studies dedicated to it are limited. The aim of our study was to report on the incidence, clinical manifestations and associated diseases in patients with isolated cryofibrinogenemia. METHODS: This is a retrospective single-center study. Patients included in this study had a positive and isolated detection of cryofibrinogen between January 1st, 2011 and December 31st, 2012. Identification was possible through the database of the laboratory of immunology. RESULTS: Two hundred and eighty-one consecutive orders of cryofibrinogenemia were identified. Seventy-three patients had a positive detection of cryofibrinogenemia. Among them, 12 had an isolated cryofibrinogenemia and sixty-one patients (84%) had concomitant cryofibrinogenemia and cryoglobulinemia. The mean age was 59±19years. Seven patients were female (58%). Cutaneous manifestations were present in half case. Peripheral nerve involvement was present in 5 cases (42%) and rheumatic manifestations in 4 patients (33%). A thrombotic event was reported in 7 patients (58%). Renal impairment was present in 7 patients. The median cryofibrinogen concentration was 254±304mg/L. Five patients had a secondary cryofibrinogenemia. The most often prescribed treatment was corticosteroids. CONCLUSION: Cryofibrinogenemia is an unknown disorder. Testing for cryoglobulinemia is more frequent than for cryofibrinogenemia whereas clinical manifestations are similar. Detection of cryofibrinogen is positive in most of the cases, with an important prevalence of thrombotic events in this population. This study confirms the importance of conducting prospective studies on cryofibrinogenemia.

Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients.

AIMS: The purpose of this study was to evaluate the renal side-effects of adefovir therapy in kidney-transplant (KT) recipients with chronic hepatitis B virus (HBV) infection, who have become resistant to lamivudine therapy. PATIENTS AND METHODS: 11 kidney-transplant (KT) patients (10 men, 1 woman, median age 54 (46 - 67) years) had lamivudine-resistant chronic HBV infection. With respect to HBV markers, all were HBs Ag-positive, 8 were HBe Ag-negative/HBe antibody- (Ab) positive, i.e. precore mutant, and 3 were HBe Ag-positive/HBe Ab-negative. They were all given adefovir at 10 mg/d (3 cases) or 5 mg/d (6 cases) or 2.5 mg/d (2 cases) according to creatinine clearance. RESULTS: Compared to baseline without adefovir therapy, at last follow-up, adefovir therapy was associated, at 1 and 2 years post therapy, with a significant decrease in aspartate (AST) (28 (17 - 53), 28 (10 - 79) vs. 58 (24 - 1,282) IU/l, p = 0.001), alanine (ALT) (38 (13 - 55), 36 (17 - 92) vs. 72 (31 - 1,594) IU/l, p = 0.0032] aminotransferase levels, and gammaGT (31 (14 - 51), 25 (14 - 196) vs. 44 (25 - 742) IU/l, p = 0.03). With respect to HBV DNA, when compared to baseline, there was a significant decrease at both years 1 and 2 post therapy (p = 0.01). With respect to KT function at 2 years after starting adefovir, there was a significant increase in serum creatinine from 125 (+/- 35) to 141 (+/- 32) micromol/l, (p = 0.02) and a significant increase in 24-h proteinuria. With respect to renal tubular parameters, as compared to baseline without adefovir therapy, one year after adefovir therapy was commenced there was a significant decrease in urinary pH from 6.6 (+0.6) to 5.65 (+/- 0.7); p = 0.03, a significant decrease in bicarbonaturia (from 0.33 +/- 0.7 to 0.1 +/- 0.3 mmol/h, p = 0.01), an increase in urinary excretion of H+ (1.79 (+/- 1.33) to 2.44 (+/- 1.18) mmol/l (p = 0.03)), a significant decrease in phosphatemia (0.82 +/- 0.19 vs. 0.65 +/- 0.13 mmol/l, p = 0.04) and a significant decrease in phosphaturia threshold, a significant decrease in tubular phosphorus reabsorption (75.5 +/- 9.4% vs. 61.8 +/- 16%, p = 0.05), and a significant increase in the phosphorus index of excretion (0.18 +/- 0.114 vs. 0.35 +/- 0.164, p = 0.01). CONCLUSION: We have demonstrated that low-dosage adefovir therapy in kidney-transplant patients is relatively safe as far as renal parameters are concerned, even though we observed a slight impairment of renal proximal-tubular function.

ANCA-related crescentic glomerulonephritis in systemic sclerosis: revisiting the "normotensive scleroderma renal crisis".

The scleroderma renal crisis is characterized by acute onset of severe hypertension and by rapidly progressive hyperreninemic renal failure. There is, however, a very limited subset of patients with rapidly progressive renal failure who remain normotensive and develop ANCA-positive crescentic glomerulonephritis. We report a case of normotensive acute renal failure secondary to anti-MPO antibody-associated crescentic glomerulonephritis in a patient with diffuse systemic sclerosis. She was referred to our department with normal blood pressure and no extrarenal clinical manifestation ofvasculitis. She presented with rapidly progressive renal failure, microscopic hematuria and minimal proteinuria. P-ANCA were positive by immunofluorescence, with ELISA-confirmed specificity for myeloperoxidase. Renal biopsy revealed typical features of pauciimmune glomerulonephritis with crescent formation and fibrinoid necrosis. The patient was initially treated with i.v. cyclophosphamide only. Because of ongoing deteriorating renal function, additional treatment with intravenous pulses of methylprednisolone followed by oral prednisone was started and allowed renal function improvement. After 9 months, serum creatinine had almost returned to normal level with minimal proteinuria, no hematuria and negative ANCA testing. Control kidney biopsy only revealed scar lesions. The association of ANCA-positive crescentic glomerulonephritis and systemic sclerosis is a very rare event. Treatment with intravenous cyclophosphamide and corticosteroids allows rapid and long-term improvement of renal function. The onset of typical scleroderma renal crisis triggered by high-dose corticosteroids is unlikely but requires a close follow-up of patients with overlapping systemic sclerosis. Diagnosis and treatment are discussed and previously published cases are reviewed.

Sarcoidosis-related hypercalcemia in 3 chronic hemodialysis patients.

Hypercalcemia is a frequent complication in chronic hemodialysis (CHD) patients. A rare cause of this condition is sarcoidosis, and has only been reported 6 times in CHD. Herein, we report on 3 cases of sarcoidosis-related hypercalcemia in CHD patients: an overt case, a probable case, and a recurrence of pre-dialysis sarcoidosis. Hypercalcemia is a frequent complication in chronic hemodialysis patients: it is often related to uncontrollable secondary hyperparathyroidism or to the inappropriate use of calcium phosphate binders, 1alpha-hydroxylated vitamin D metabolites, high dialysate calcium concentrations, or to aluminium-related bone disease [Uach and Bover 1996]. However, other rare causes should also be considered, such as multiple myeloma, non-Hodgkin lymphoma [Uach and Bover 1996], vitamin A intoxication [Fishbane et al. 1995], or granulomatous diseases such as sarcoidosis. The latter has only been described in a total of 6 hemodialysis patient reports [Barbour et al. 1981, Barnard et al. 2002, Herrero et al. 1998, Kalantar-Zadeh et al. 1994, Kuwae et al. 2003, Naito et al. 1999]. In the present paper, we report on 3 cases of sarcoidosis-related hypercalcemia in chronic hemodialysis patients with 3 different patterns, i.e. overt sarcoidosis, probable sarcoidosis, and recurrence of pre-dialysis sarcoidosis.

A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in 186 AIDS patients. The BIOTOXO Study Group.

OBJECTIVE: To define the factors associated with diagnosis of toxoplasmic encephalitis (TE) in AIDS patients; and to establish a rational procedure for the clinician faced with a decision concerning empiric antitoxoplasma therapy. DESIGN: A 15-month prospective multicentre cohort study in France. METHODS: One hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric antitoxoplasma therapy for a first episode of presumed TE were monitored. The clinician's initial estimation of the probability of response to antitoxoplasma therapy was recorded. In addition, a validation committee classified cases as TE or non-TE. RESULTS: Among the 186 patients, the following variables were significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever (59% versus 40%). headache (55% versus 33%), seizures (22% versus 11%), suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher in TE than in non-TE (27 x 10(6)/l versus 11 x 10(6)/l). The rate of TE in patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with 75% in patients without previous prophylaxis. Pre-therapy estimation of response to empiric therapy was highly correlated with final diagnosis. Multivariate logistic regression analysis showed that the following variables contributed independently to the diagnosis of TE: clinician's estimation of response to treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis; seizures; headache; suggestive lesions on CT or MRI brain scan; and positive Toxoplasma serology. CONCLUSIONS: A linear logistic model is proposed which uses significant variables, which are readily available. This model gives good accuracy to classify suspected cases of TE.

Penetration of foscarnet into cerebrospinal fluid of AIDS patients.

The diffusion of foscarnet into cerebrospinal fluid (CSF) was studied in 27 patients with AIDS. Foscarnet was administered intravenously at various dosages at 12-h intervals. Concentrations in plasma and CSF at the end of foscarnet infusion or 1, 3, 5, 6, and 12 h after infusion were determined by high-performance liquid chromatography. Thirty-seven samples were obtained. The median concentration of foscarnet in CSF was 80 mumol/liter (range, 0 to 500 mumol/liter). The CSF foscarnet concentration was greater than the 50% inhibitory concentration for human immunodeficiency virus type 1 and was equal to or greater than the 50% inhibitory concentration for cytomegalovirus in most cases. The penetration of foscarnet into CSF, as expressed by the ratio of the concentration in CSF to the simultaneous concentration in plasma, ranged from 0 to 3.4 (median, 0.27) and was highly correlated with the presence of cells within CSF and the length of foscarnet therapy. Good diffusion of foscarnet in CSF allows evaluation of this drug in central nervous system cytomegalovirus and human immunodeficiency virus infections in patients with AIDS.

[Sheep rearing in Shaba (Zaire): present-day situation]. / L'élevage ovin au Shaba (Zaïre): situation actuelle.

Four sheep rearing systems have been studied in Shaba (Zaire) to compare production and profit levels. Weight production per mother at nine months of age is 4.5 kg under traditional breeding conditions, versus 23 kg in the ranching system (with shepherd) and 30 kg under extensive rearing. Management of range by fire and rotation and feeding habits, principally explain variations in the production. Internal parasite control and housing conditions are next important. Extensive sheep breeding under the ranching system, succeeding to cattle on pasture, appears to be the most profitable rearing system in the region.

A case report of Nerium oleander poisoning in cattle.

Nerium oleander leaves caused the death within 36 hours of 7 of 17 cattle which had access to boughs of the plant. Arrhythmia and auriculo-ventricular block at ECG were found in three cattle surviving on day 4. In one animal which died on day 4, postmortem examination revealed subendocardial and abomasal hemorrhages. Epidermic tissues of the leaves of N oleander were found in the rumen content. Recovery occurred in the three animals with marked cardiac signs.