The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3 years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.

A unique phenotype of acquired Glanzmann thrombasthenia due to non-function-blocking anti-αIIbß3 autoantibodies.

Essentials Acquired Glanzmann thrombasthenia (aGT) is generally caused by function-blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of αIIbß3 with anti-αIIbß3 Abs. The anti-αIIbß3 Abs of the patient did not inhibit platelet function but reduced surface αIIbß3. Internalization of αIIbß3 induced by the Abs binding may be responsible for the phenotype. SUMMARY: Background Acquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function-blocking anti-αIIbß3 autoantibodies. Aim We characterize an unusual case of aGT caused by marked reduction of surface αIIbß3 with non-function-blocking anti-αIIbß3 antibodies (Abs). Methods A 72-year-old male suffering from immune thrombocytopenia since his 50s showed exacerbation of bleeding symptom despite mild thrombocytopenia. Platelet aggregation was absent with all agonists but ristocetin. Analysis of αIIbß3 expression and genetic analysis were performed. We also analyzed effects of anti-αIIbß3 Abs of the patient on platelet function and αIIbß3 expression. Results Surface αIIbß3 expression was markedly reduced to around 5% of normal, whereas his platelets contained αIIbß3 to the amount of 40-50% of normal. A substantial amount of fibrinogen was also detected in his platelets. There were no abnormalities in ITGA2B and ITGB3 cDNA. These results indicated that reduced surface αIIbß3 expression caused a GT phenotype, and active internalization of αIIbß3 was suggested. Anti-αIIbß3 IgG Abs were detected in platelet eluate and plasma. These Abs did not inhibit PAC-1 binding, indicating that the Abs were non-function-blocking. Surface αIIbß3 expression of a megakaryocytic cell line and cultured megakaryocytes tended to be impaired by incubation with the patient's Abs. After 2 years of aGT diagnosis, his bleeding symptom improved and surface αIIbß3 expression was recovered to 20% of normal with reduction of anti-αIIbß3 Abs. Conclusion We demonstrated a unique aGT phenotype due to marked reduction of surface αIIbß3. Internalization induced by anti-αIIbß3 Abs may be responsible in part for the phenotype.

Púrpura trombocitopénica inmune secundaria a infección por Helicobacter pylori / Immune thrombocytopenic purpura secondary to Helicobacter pylori infection

La púrpura trombocitopénica inmune es un trastorno inmunológico caracterizado por la disminución del recuento de plaquetas de forma transitoria o persistente. Puede ser primaria o secundaria en función a la presencia o ausencia de trastornos asociados. Algunos casos se asocian con la infección por Helicobacter pylori, y en estos pacientes el tratamiento erradicador tiene impacto positivo en el recuento de plaquetas. Presentamos cuatro pacientes adultos (dos varones y dos mujeres) con púrpura trombocitopénica inmune secundaria a infección por Helicobacter pylori, los cuales mostraron respuestas favorables al tratamiento erradicador, con mejoría de los recuentos plaquetarios y remisión de las manifestaciones hemorrágicas. Consideramos que debe realizarse la detección rutinaria de esta bacteria en pacientes con púrpura trombocitopénica inmune debido a la elevada prevalencia de la infección en nuestra región y el impacto favorable del tratamiento en el recuento de plaquetas

Immune thrombocytopenic purpura is an immune disorder characterized by a decrease in platelet count transiently or persistently. It can be primary or secondary depending on the presence or absence of associated disorders. Some cases are associated with Helicobacter pyloriinfection, and in these patients eradication treatment has a positive impact on the platelet count. We present four adult patients (two males and two females) with immune thrombocytopenic purpura secondary to Helicobacter pylori infection, which showed favorable responses to eradication treatment, with improvement of platelet counts and remission of hemorrhagic manifestations. We believe that routine detection of this bacterium should be performed in patients with immune thrombocytopenic purpura due to the high prevalence of infection in our region and favorable impact of treatment on the platelet count.

Bevacizumab for Epistaxis in Hereditary Hemorrhagic Telangiectasia: An Evidence-based Review.

Objective Epistaxis is a primary complaint in 90% to 96% of patients with hereditary hemorrhagic telangiectasia (HHT). Numerous surgical and medical treatments aim to decrease the frequency and severity of epistaxis in this patient population. Bevacizumab is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, an angiogenic factor elevated in HHT. It has been used in several forms to treat epistaxis in HHT but thus far, evidence-based recommendations are limited. Study Design Systematic review with evidence-based recommendations. Methods A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using Embase, MEDLINE, MEDLINE In-Process/Epub, and Cochrane databases. English language abstracts were reviewed for relevance. Results Eleven manuscripts met inclusion criteria and were analyzed. Submucosal injection, submucosal injection plus laser coagulation, intravenous (IV), and topical formulations of bevacizumab were evaluated for their therapeutic impact on epistaxis in patients with HHT. Three randomized controlled trials failed to show topical bevacizumab to be more effective in controlling epistaxis than saline or other moisturizers. Conclusions The use of submucosal and IV bevacizumab shows promise, but further study is necessary to determine the true efficacy in the treatment of epistaxis as only grade C level exists currently. Based on the available literature, the use of topical bevacizumab is not recommended (grade B).

Nonallergic rhinitis: therapeutic options.

PURPOSE OF REVIEW: The purpose of this review is to briefly discuss methods for classifying Nonallergic rhinitis (NAR), the current understanding of its immunopathogenesis, scientific evidence-based treatment options along with anecdotal clinical experience for selecting different treatment regimens for these challenging patients. RECENT FINDINGS: NAR also known as idiopathic rhinitis, irritant-induced rhinitis and vasomotor rhinitis is a heterogeneous condition that has been classified many different ways, but currently there is no consensus on definition for this condition due to its poorly elucidated mechanism(s) of action. A typical patient presents with nasal congestion, postnasal drainage with or without a cough associated with, to a lesser extent, some degree of sneezing, itching, and rhinorrhea. Recent studies have proposed more specific approaches for characterizing rhinitis subtypes. It is speculated that this condition is due to an autonomic imbalance resulting in an overactive parasympathetic and perhaps an underactive sympathetic nervous system. Our poor understanding of NAR mechanism(s) of action has significantly hindered progress in developing novel therapies for this condition. SUMMARY: Further investigation is required to understand the neurogenic signaling pathways that lead to this aberrant response. Until we have selective therapies for NAR, treatment requires selecting the medication or combination of medications best suited to the symptomatic needs of the patient.

Effects of dilution and prolonged storage with preservative in a polyethylene container on Bevacizumab (Avastin™) for topical delivery as a nasal spray in anti-hereditary hemorrhagic telangiectasia and related therapies.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia and severe, recurrent epistaxis is a common clinical phenotype associated with HHT. An intranasal treatment regime of diluted Avastin™ (Bevacizumab; recombinant humanized anti-vascular epithelial growth factor immunoglobin G1) using apulsatile nasal irrigator has proven efficacious in clinical practice. However, concerns regarding the stability of Avastin™ following dilution and prolonged storage in standard containers used for drug delivery, such as polyethylene bottles, have so far prevented a more widespread clinical use. Compatibility with the preservative benzalkonium chloride was also unknown. OBJECTIVE: This study aimed at determining, whether dilution, prolonged refrigerated storage and the presence of the preservative benzalkonium chloride - as required for novel Avastin™ formulations - affected the biochemical and electrochemical properties of the drug. METHODS: We performed a detailed biochemical and electrochemical analysis of Avastin™, including native and sodium dodecyl sulfate polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay and isoelectric focusing. RESULTS: We did not detect any evidence of degeneration or aggregation following dilution and prolonged, refrigerated storage or from the presence of benzalkonium chloride. All biochemical and electrochemical properties of Avastin™ after dilution and prolonged, refrigerated storage were undistinguishable from control. CONCLUSIONS: Our data provide important insight into the stability of Avastin™ and allow the consideration of novel Avastin™ formulations, including its use in a metered-dose nasal spray for the treatment of HHT and other applications.

[Serious bleeding in systemic lupus erythematosus complicated by lupus anticoagulant-hypoprothrombinaemia syndrome]. / Alvorlig blødning ved systemisk lupus erythematosus kompliceret med lupusantikoagulans-hypoprotrombinaemisyndromet.

Severe hemorrhagic diathesis due to lupus anticoagulant complicated by hypoprothrombinaemia resulting from prothrombin autoantibodies is a rare disorder and is often associated with systemic lupus erythematosus (SLE). We report a case in which a 15-year-old girl with SLE developed marked haemorrhagic manifestations due to menorrhagia and nosebleeds. The acute bleeding episode was treated with SAGM, tranexamic acid and recombinant factor VIIa. Lupus anticoagulant, cardiolipin antibodies and antiprothrombin antibodies were successfully depressed within weeks after corticosteroid therapy was begun.

[Eales disease and tuberculous allergy]. / Maladie de Eales et allergie tuberculinique.

The authors report the case of a 25-year-old woman who presented unilateral Eales disease associated with biologically confirmed pulmonary tuberculosis. The patient, from a family with a history of tuberculosis, showed a painless and abrupt decrease in visual acuity of the right eye with venous and arterial vasculitis. Fluorescein angiography confirmed the existence of peripheral ischemia and vascular abnormalities. The biological exam showed a positive PPD and the BK was isolated. Antibiotic and corticosteroid drugs were used in the treatment. The clinical, immunopathological and therapeutic aspects of this disease are discussed.

An unusual, severe adverse reaction to silver nitrate cautery for epistaxis in an immunocompromised patient.

Silver nitrate cautery is frequently used to control epistaxis. Although relatively free of side effects, we have encountered a case of a severe mucocutaneous reaction to silver nitrate cautery to the nose. The pathogenesis of this adverse effect is discussed.

A clinical and immunological study on 92 workers occupationally exposed to anhydrides.

This study aimed at investigating sensitizing and hazardous effects of a new acid anhydride, pyromellitic dianhydride (PMDA), in addition to those of phthalic anhydride, maleic anhydride and trimellitic anhydride, in a group of 92 exposed workers in two German chemical plants. Of the 92 workers, 56 reported work-related complaints with a predominance of phlegm and dyspnoea in those exposed to anhydride dust for less than 1 year. Haemorrhagic rhinitis occurred only after a prolonged exposure of more than 15 years. Specific IgE antibodies to anhydride-HSA conjugates could be detected in 15 exposed subjects, 12 of whom had work-related symptoms. The IgE-positive group had significantly more impaired lung function parameters than the IgE-negative group. The proportion of IgE-positive subjects was highest in the groups with dyspnoea (5/18), cough (6/24) and rhinitis (11/44) whereas only 1 of 11 workers with haemorrhagic rhinitis had such antibodies. A follow-up study of 23 affected workers was performed after 10 months to assess clinical symptoms, lung function and IgE antibody levels. This follow-up study showed the absence of obstructive ventilation patterns in three out of six subjects in addition to cessation of symptoms in most initially affected workers who were no longer exposed. On the other hand, 14 workers under continuous exposure had comparable pathological findings on re-examination. Our results confirm that anhydrides including the lesser known PMDA, behave as respiratory irritants and as immediate-type sensitizers. They predominantly induced reversible symptoms in workers whose exposure stopped after a working period of about 0.7 years. Abnormal lung function parameters normalized in nearly 50% of these subjects.

Hemorrhagic rhinitis. An immunologic disease due to hexahydrophthalic anhydride.

This is a descriptive study of six men who had been occupationally exposed to heated epoxy resin containing hexahydrophthalic anhydride (HHPA) who presented with rhinitis, nasal mucosal erosions, and significant epistaxis; three also had asthma. When they were removed from exposure to HHPA, the rhinitis symptoms, nasal erosions, and epistaxis resolved spontaneous. All six had high titers of IgG and IgE against HHP-HSA as determined by an enzyme-linked immunosorbent assay (ELISA). Other asymptomatic workers with similar HHPA exposure had ver low or negative titers of IgG and IgE against HHP-HSA. We conclude that these results are very suggestive of an immunologic mechanism being responsible for the rhinitis, nasal mucosal erosions, and epistaxis that occurred in the six described HHPA workers.