Levamisole-contaminated cocaine is an increasingly reported cause of a syndrome characterized by vasculitic skin lesions and immunologic abnormalities. With approximately 70% of cocaine in the United ...States now contaminated with levamisole, the incidence of this syndrome is likely to increase. We report the case of a 42 years-old Caucasian woman who presented with fronto-temporal pulsating headache and progressive bilateral loss of vision.
PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate ...the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations.
PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients 143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS) and in 945 healthy controls.
The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91, while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73).
The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.
Glassberg et al discuss the study by Fussner et al, a follow-up analysis of Plasma Exchange (PLEX) and Glucocorticoids (GCs) in Severe AAV: The PEXIVAS Trial published in 2020. The trial focuses on ...outcomes related to PLEX and steroid dosing in addition to induction therapy in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitide (AAV) with or without diffuse alveolar hemorrhage (DAH). The PEXIVAS Trial included GPA and MPA and excluded those with serumpositive for anti-glomerular basement membrane antibodies. Standard therapy for DAH-associated AAV has included high-dose steroids and induction medications (cyclophosphamide or rituximab) and consideration of PLEX to avoid or delay organ involvement.
Hereditary amyloidosis due to mutations of apolipoprotein A-I (apoA-I) is a rare disease characterized by the deposition of amyloid fibrils constituted by the N-terminal fragment of apoA-I in several ...organs. L75P is a variant of apoA-I associated with systemic amyloidosis predominantly involving the liver, kidneys, and testis, identified in a large number of unrelated subjects. Objective of the present paper was to evaluate the impact of the L75P apoA-I variant on HDL subpopulations and cholesterol esterification in carriers.
Plasma samples were collected from 30 carriers of the amyloidogenic L75P apoA-I (Carriers) and from 15 non affected relatives (Controls). Carriers displayed significantly reduced plasma levels of HDL-cholesterol, apoA-I, and apoA-II compared to Controls. Plasma levels of LpA-I, but not LpA-I:A-II, were significantly reduced in Carriers. HDL subclass distribution was not affected by the presence of the variant. The unesterified to total cholesterol ratio was higher, and cholesterol esterification rate and LCAT activity were lower in Carriers than in Controls.
The L75P apoA-I variant is associated with hypoalphalipoproteinemia, a selective reduction of LpA-I particles, and a partial defect in cholesterol esterification.
The first description of what is now known as antineutrophil cytoplasmic autoantibody-associated necrotizing vasculitis appeared more than 140 yr ago. Since then, many aspects of the pathogenic ...pathway have been elucidated, indicating the involvement of antineutrophil cytoplasmic autoantibodies, but why antineutrophil cytoplasmic autoantibodies are produced in the first place remains unknown. Over the years, many hypotheses have emerged addressing the etiology of antineutrophil cytoplasmic antibody production, but no exclusive factor or set of factors can so far be held responsible. Herein is reviewed the most influential hypotheses regarding the causes of antineutrophil cytoplasmic antibody-associated vasculitis with the aim of placing in an epidemiologic background the different hypotheses that are centered on environmental and genetic influences.
Background & Aims
: Hereditary systemic amyloidoses are autosomal dominant, late-onset disorders caused by mutations in the genes for a group of plasma proteins including transthyretin, lysozyme, ...fibrinogen Aα chain, gelsolin, apolipoprotein A-I, and apolipoprotein A-II. We investigated both phenotypic and genotypic aspects of apolipoprotein A-I amyloidosis unexpectedly disclosed by liver biopsy in 13 unrelated individuals with asymptomatic, persistent elevation of alkaline phosphatase and γ-glutamyltransferase levels.
Methods
: Immunoelectron microscopy was used for in situ characterization of amyloid deposits on liver biopsy specimens. Mutation analysis was performed by sequencing of the apolipoprotein A-I gene in all patients. Wild-type/variant apolipoprotein A-I ratio in plasma high-density lipoproteins was assessed by a peptide mass fingerprinting approach after purification of total apolipoprotein A-I of 2 patients.
Results
: Family history was informative in 5 cases. Renal failure developed in 9 cases. Hypogonadism due to testicular involvement was observed. Amyloid fibrils specifically stained with anti-apolipoprotein A-I antibody. A novel (Leu75Pro) heterozygous mutation in the apolipoprotein A-I gene was present in affected individuals but not in controls. Variant apolipoprotein A-I was about 10% of the total protein in high-density lipoproteins.
Conclusions
: The high number of individuals with apparently sporadic disease might reflect widespread occurrence of this mutation in the population and a milder phenotype of this variant compared with other apolipoprotein A-I amyloidogenic mutants. These findings suggest that specific staining for amyloid should be performed on liver biopsy of individuals with asymptomatic chronic elevation of alkaline phosphatase and γ-glutamyltransferase levels.
The long-term outcomes of systemic vasculitis Westman, Kerstin; Flossmann, Oliver; Gregorini, Gina
Nephrology, dialysis, transplantation,
04/2015, Letnik:
30 Suppl 1, Številka:
Jan 18
Journal Article
Recenzirano
Odprti dostop
Patients with generalized ANCA-associated small vessel vasculitis (AAV) have a very poor outcome if the ANCA-associated vasculitis is not diagnosed, evaluated and treated properly. The introduction ...of treatment with immunosuppressive therapy has improved patient survival dramatically but with considerable side effects. Besides, almost 50% of surviving patients experience a relapse of vasculitis. Since 1995, the European Vasculitis Society (EUVAS) has designed and conducted several clinical trials on patients with AAV independently of pharmaceutical companies. The studies included patients with newly diagnosed AAV and were stratified according to renal function and generalized versus more localized forms. As the immediate patient survival has improved, the longer term outcome has become more important. There are several reports on outcome of patients with ANCA-associated vasculitis, but the patient groups were heterogeneous regarding diagnosis as well as treatment and follow-up. Therefore, EUVAS decided to further evaluate the effect and possible adverse events of the original randomized trials. This review presents an overview on long-term follow-up of patients with ANCA-associated vasculitis, with focus on relapse rate, patient and renal survival and development of cardiovascular disease and malignancy.
This study aims to assess the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) on the course of COVID-19. It is a prospective study on 221 (M/F ...ratio= 143/78, mean age 72±13) consecutive hypertensive patients with COVID-19: 76 (34.4%) treated with ACEIs, 63 (28.5%) with ARBs and 82 (37.1%) with antihypertensives OTHER than ACEIs or ARBs. They were all followed up until discharge or death. BAD outcome was defined as the need for invasive mechanical ventilation or death. The three classes of medication were well balanced for confounding variables. BAD outcome was overall recorded in 63/221 (28%) patients, in 20/76 (26%) of ACEI, in 17/63 (27%) of ARB and in 26/82 (32%) of OTHER users, with no statistically significant difference in any comparison. These findings refute the hypothesis that treatment with ACEIs or ARBs may negatively affect the course of COVID-19.
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