Relapses in three patients with Takayasu arteritis under tocilizumab treatment detected by contrast enhanced ultrasound.

Takayasu arteritis (TA) is a rare large vessel vasculitis, affecting the aorta and its major branches, typically in young women. In this case report, we present three cases of young women of Caucasian descent who experienced relapses while under treatment with the monoclonal humanized antibody to the interleukin 6 receptor, tocilizumab. Active vasculitic lesions of the supraaortic (common carotid and axillary) arteries were detected and characterized via high resolution contrast enhanced ultrasound. Based on these cases, we discuss the potential role of contrast enhanced ultrasound in the diagnosis and follow-up of TA as well as the current data on the efficacy of tocilizumab in the treatment of TA.

B-mode sonography wall thickness assessment of the temporal and axillary arteries for the diagnosis of giant cell arteritis: a cohort study.

OBJECTIVES: We aimed to determine the diagnostic accuracy of B-mode compression sonography of the temporal arteries (tempCS) and B-mode sonographic measurement of the axillary artery intima media thickness (axIMT) for the diagnosis of giant cell arteritis (GCA). METHODS: After having established measurement of tempCS and axIMT in our routine diagnostic workup, 92 consecutive patients with a suspected diagnosis of GCA were investigated. Clinical characteristics were recorded and wall thickening of the temporal arteries (tempCS) and axillary arteries (axIMT) was measured (mm). Using the final clinical diagnosis as the reference standard, receiver operator characteristics (ROC) analysis was performed. In a subgroup of 26 patients interobserver agreement was assessed using Spearman's rank correlation. RESULTS: Cranial GCA, extracranial GCA, and combined cranial/extracranial GCA were diagnosed in 18, 7, and 9 individuals, respectively. For the diagnosis of cranial GCA, tempCS had an excellent area under the curve (AUC) of 0.95, with a cut-off of ≥0.7 mm offering a sensitivity and specificity of 85% and 95%. The AUC of axIMT for the diagnosis of extracranial GCA was 0.91 (cut-off ≥1.2 mm: sensitivity and specificity 81.3 and 96.1%). Applying a combined tempCS/axIMT cut-off of ≥0.7mm/1.2 mm, we calculated an overall sensitivity and specificity for the final clinical diagnosis of cranial and/or extracranial GCA of 85.3% and 91.4%. Interobserver agreement was strong for both parameters assessed (Spearman's rho 0.72 and 0.77, respectively). CONCLUSIONS: The combination of tempCS/axIMT allows objective sonographic assessment in suspected GCA with promising diagnostic accuracy.

Hypothenar hammer syndrome.

The diagnosis of hypothenar hammer syndrome (HHS) should be considered in the case of hand ischemia in people who occupationally or recreationally use the hypothenar region literally as a “hammer”. Routine diagnostics should consist of physical examination including Allen’s test, acral plethysmography and duplex sonography. According to the prevailing opinion angiography remains the «gold standard test¼ for establishing the diagnosis of HHS. Early diagnosis allows more effective therapeutic strategies and is important to prevent long-term negative medical sequelae. Several basic principles apply to all patients, for example hand protection and smoking cessation. The optimal treatment options, particularly the indication for surgery, remain controversial due to a lack of sound data from case series or prospective randomized trials.

Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis.

BACKGROUND: The treatment of lupus nephritis (LN) remains problematic because the current treatment regimen based on unspecific immunosuppressants such as steroids, cyclophosphamide and mycophenolate has significant side effects and is often inefficient. B-cell ablation with the chimeric anti-CD20 antibody rituximab (RTX) has been considered as an alternative treatment option but the randomized controlled LUNAR trial failed to show any additive effect of RTX beyond a steroid-mycophenolate mofetil (MMF) combination for LN type III/IV/V in incident patients. At present, no such trial is available for the use of RTX in refractory LN. METHODS: We analysed existing evidence on this topic by performing a systematic analysis of reports that document outcomes of RTX treatment for refractory LN. RESULTS: Out of 233 reports, we selected 26 for analysis, which described 300 patients with a mean follow-up of 60 weeks. The complete or partial response criteria were met by 87% of patients with LN class III, 76% with class IV and 67% with class V, respectively. Mixed classes responded in 76% of patients. RTX induced complete responses in 60% (type III), 45% (type IV), 40% (type V) and 24% (mixed types), respectively. CONCLUSIONS: Our systematic review of existing evidence suggests that RTX effectively induces remission of LN in patients who have not achieved remission with standard therapies. Another randomized controlled trial should be conducted to test the efficacy of RTX in refractory LN.

Acute kidney injury after ingestion of rhubarb: secondary oxalate nephropathy in a patient with type 1 diabetes.

BACKGROUND: Oxalosis is a metabolic disorder characterized by deposition of oxalate crystals in various organs including the kidney. Whereas primary forms result from genetic defects in oxalate metabolism, secondary forms of oxalosis can result from excessive intestinal oxalate absorption or increased endogenous production, e.g. after intoxication with ethylene glycol. CASE PRESENTATION: Here, we describe a case of acute crystal-induced renal failure associated with excessive ingestion of rhubarb in a type 1 diabetic with previously normal excretory renal function. Renal biopsy revealed mild mesangial sclerosis, but prominent tubular deposition of oxalate crystals in the kidney. Oxalate serum levels were increased. CONCLUSION: Acute secondary oxalate nephropathy due to excessive dietary intake of oxalate may lead to acute renal failure in patients with preexisting renal disease like mild diabetic nephropathy. Attention should be payed to special food behaviors when reasons for acute renal failure are explored.

eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice.

BACKGROUND: All three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial- (L/E) and platelet/endothelial- (P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. PRINCIPAL FINDINGS: Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-)/eNOS(-/-)), while P/E-interactions did not differ, compared to apoE(-/-). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/-) vessels. CONCLUSION: Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-)/eNOS(-/-) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/-) atherosclerosis but does not negate the enzyme's strong protective effects.

Oxidative stress and compartment of gene expression determine proatherosclerotic effects of inducible nitric oxide synthase.

Genetic and pharmacological inhibition of inducible nitric oxide synthase (iNOS) decreases atherosclerosis development. Potential proatherogenic effects of iNOS include iNOS mediated oxidative stress and iNOS expression in different cellular compartments. Lesional iNOS can potentially produce nitric oxide radicals (NO), superoxide radicals (O2(-)), or both; these radicals may then react to form peroxynitrite. Alternatively, O2(-) radicals from oxidases co-expressed with iNOS could react with NO to produce peroxynitrite. Therefore, the expression profiles of the genes that modulate the redox system in different iNOS-expressing cell compartments may determine the role of iNOS in atherosclerosis. We used apoE (apoE(-/-)) and apoE/iNOS double knockout (apoE(-/-)/ iNOS(-/-)) mice to assess vascular NO, O2(-), and peroxynitrite formation by electron spin resonance spectroscopy, high performance liquid chromatography, and 3-nitrotyrosine staining. The relevance of the iNOS expressing cell compartment was tested by bone marrow transplantation. We show that iNOS significantly contributes to vascular NO production and itself produces O2(-), leading to peroxynitrite formation in atherosclerotic lesions. Our bone marrow transplantation experiments show that bone marrow derived cells exclusively mediate the proatherosclerotic effects of iNOS in males, while both parenchymal and bone marrow derived iNOS equally contribute to atherosclerosis in females. Moreover, iNOS expression affects vascular remodeling. These findings establish for the first time that the proatherosclerotic effects of iNOS vary with sex in addition to the compartment of its expression.