Hypersensitivity Vasculitis joseph July 18, 2012 No Comments What is Hypersensitivity vasculitis? Hypersensitivity vasculitis (HV) is often used to ... blood vessels, called a leukocytoclastic vasculitis. What causes Hypersensitivity vasculitis? HV may be caused by a specific ...
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Synopsis Childhood vasculitis is a challenging and complex group of conditions that are multisystem in nature and often require integrated care from multiple subspecialties including rheumatology, dermatology, cardiology, nephrology, neurology, and gastroenterology. Vasculitis is defined as the presence of inflammation in the blood vessel wall. The site of vessel involvement, size of the affected vessels, extent of vascular injury, and underlying pathology determine the disease phenotype and severity. This review explores the classification and general features of pediatric vasculitis as well as the clinical presentation, diagnostic evaluation, and therapeutic options for the most common vasculitides.
Weiss, Pamela F.
Wegeners Granulomatosis (Granulomatosis With Polyangiitis); Microscopic Polyangiitis; Churg Strauss Syndrome (Eosinophilic Granulomatosis With Polyangiitis); Polyarteritis Nodosa; Takayasu Arteritis; Primary CNS Vasculitis; Unclassified Vasculitis
Background: Systemic vasculitis is an unusual complication of sarcoidosis. Over a 10-year period, the authors have provided care for six patients who had features of both sarcoidosis and vasculitis. Vasculitis could not be attributed to other causes. Objectives: To report six patients (five children) who had sarcoidosis and systemic vasculitis and compare our experience with previous literature. To better delineate
Sandra R. M. Fernandes; Bernhard H. Singsen; Gary S. Hoffman
The vasculitides encompass a rare subset of autoimmune diseases. Reports of the concurrent association of malignancies with some forms of vasculitis raise the possibility that patients with certain types of vasculitis may be at increased risk of cancer. Conversely, some forms of vasculitis may be a manifestation of malignancy. We review cancer risk in patients with large vessel vasculitis (giant cell arteritis and Takayasu arteritis), polyarteritis nodosa, and the circulating antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. In addition we discuss vasculitis as a paraneoplastic phenomenon, highlighting polyarteritis nodosa in association with hairy cell leukemia and reviewing the most common vasculitic manifestation of cancer, cutaneous vasculitis.
Kermani, Tanaz A.; Warrington, Kenneth J.; Amin, Shreyasee
Vasculitis resulting from drug use includes a wide variety of clinical and pathologic conditions that are, in general, empirically defined and poorly understood. Further complicating our grasp of these disorders are ambiguous terms such as hypersensitivity vasculitis, allergic vasculitis, leukocytoclastic vasculitis, serum sickness, and others, which are often used interchangeably without clear definition. The clinical picture varies widely from self-limiting to progressive and even fatal illness. These syndromes have now been reported in association with newer classes of therapeutic agents including biologic response modifiers. Vasculitis affecting the central nervous system may be related to a variety of drugs and remains one of the more important syndrome sets within the spectrum of drug-induced vasculitis. These disorders are clinically important, because removal of the offending drug often is associated with regression of the vasculitic condition. PMID:8867537
Calabrese, L H; Duna, G F
Sjögren's syndrome is a chronic autoimmune disease that is commonly manifested by immune attack on the exocrine glands with resultant dry eyes and dry mouth. Sjögren's syndrome patients also have disease in other organs. One of the most common extraglandular manifestations is vasculitis. Skin vasculitis, with palpable purpura clinically and leukocytoclastic vasculitis on pathological examination, is common. Although half of those individuals with subcutaneous vasculitis have only a single episode, skin vasculitic involvement is associated with more severe disease. Necrotizing vasculitis of medium-sized vessels resembling polyarteritis nodosa can occur in Sjögren's syndrome patients. Experience in therapy for vasculitis is limited, but intravenous IgG may be effective. Recent data support a relationship between neuromyelitis optica (Devic disease) and Sjögren's syndrome. Sjögren's syndrome patients with optic neuritis or transverse myelitis have anti-aquaporin-4, which are characteristic of Devic disease. Devic disease patients have salivary lymphocytic infiltration similar to that found among Sjögren's syndrome patients. PMID:21870104
Scofield, R Hal
Panniculitides encompass a great number of different entities; however, once a vasculitis has been detected histopathologically within the subcutaneous tissue, the differential diagnosis is mainly restricted to polyarteritis (panarteritis) nodosa (PAN), nodular vasculitis (NV), and Bazin's erythema induratum (EI). Patients with PAN may have the disease confined to the skin, but must be followed over a long period because many of them develop late systemic disease. The NV/EI group represents by far the most common type of lobular panniculitis with vasculitis; we prefer keeping the distinction between the two entities by underlining the equation NV positive tuberculin skin test = EI. Other lobular panniculitides with vasculitis are exceedingly rare and set in a systemic background which can be infectious (lepromatous leprosy panniculitides) or autoimmune/dysreactive (neutrophilic lobular panniculitis in rheumatoid arthritis, lobular panniculitis in inflammatory bowel disease). PMID:23900160
Ferrara, G; Stefanato, C M; Gianotti, R; Kubba, A; Annessi, G
Introduction:Elderly patients are particularly vulnerable to adverse drug reactions as a result of polypharmacy and metabolic changes associated with aging. We present a case of leukocytoclastic vasculitis induced by olanzapine, a medication commonly used in elderly patients.
Mahesh K. Duggal; Amritpal Singh; Arunabh; James D. Lolis; Howard J. Guzik
Objectives Systemic vasculitis is often mistakenly assumed to be a common cause of retinal vasculitis. We sought to determine the relationship between retinal vasculitis and systemic vasculitis. Methods A selected review was performed on 1390 charts of patients attending the uveitis clinic at the Oregon Health & Science University between 1985 and 2010. Included in the review were all patients with diagnoses commonly associated with retinal vasculitis and all patients who were diagnosed with a systemic vasculitis. Retinal vasculitis was identified by perivascular exudates, intraretinal hemorrhage, or cotton wool spots as seen on clinical examination or by vascular occlusion or leakage as identified by fluorescein angiogram. Results 207 or 14.9% of patients with uveitis had retinal vasculitis as a component of the intraocular inflammation. Thirty-five patients had retinal vasculitis which was primary, i.e. not associated with a systemic disease, and the dominant manifestation of the uveitis. Fourteen of the patients with retinal vasculitis had Behcet’s disease. Only 11 of the 1390 patients with uveitis had a systemic vasculitis. Of these 11, four had retinal vasculitis including one secondary to a CMV retinitis. Thus, systemic vasculitis was directly responsible for 1.4% or 3 of 207 cases of retinal vasculitis. No-vasculitic systemic diseases such as sarcoidosis (n=13), syndromes confined to the eye such as pars planitis (n=36), and intraocular infections (n=29) were far more common causes of retinal vasculitis. Conclusion Retinal vasculitis is a relatively common feature of uveitis. Patients with retinal vasculitis, however, rarely suffer from one of the classical systemic vasculitides.
Rosenbaum, James T.; Ku, Jennifer; Ali, Amro; Choi, Dongseok; Suhler, Eric B.
Diagnostic confusion can often delay treatment of patients with systemic vasculitis. The clinicopathologic classification presented here has been found useful in determining the etiology of vasculitis so that appropriate therapy can be initiated more rapi...
R. D. DeShazo
Retinal vasculitis is a diagnosis that is generally suggested by an ophthalmologist. Frequently patients with the disorder are referred to nonophthalmologists for further diagnostic evaluation or treatment. The criteria for defining vasculitis differ greatly between ophthalmologists and other physicians. To facilitate collaboration between ophthalmologists and their colleagues, we have sought to clarify the term "retinal vasculitis" by discussing its subcategories, the potential role of antiphospholipid antibodies, and the etiology of retinal vasculitis. We offer guidelines for evaluating the disorder and treating patients. Images
Rosenbaum, J. T.; Robertson, J. E.; Watzke, R. C.
The revival of interest in systemic necrotizing vasculitis was initiated by the discovery of its association with anti-neutrophil cytoplasmic antibodies (ANCA). The close association of certain ANCA subspecificities, for example, proteinase 3 (Pr3) and myeloperxoidase ANCA, with Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome has led to their designation as 'ANCA-associated vasculitides'. This article describes the common and divergent clinical and immunological features of the members of this 'new' family of systemic necrotizing vasculitis, which continues to grow with the widespread use of ANCA testing. In addition, the 'standard' treatment for systemic necrotizing vasculitis (daily 'low dose' cyclophosphamide plus glucocorticosteroids or 'Fauci's scheme') is compared with new stage and activity adapted therapeutic regimens. PMID:9220078
Gross, W L
Case reportWe present a case of a 47 year-old woman, infected with human immunodeficiency virus (HIV) diagnosed 5 years ago without receiving any treatment, who had floaters in her left eye. A peripheral retinal vasculitis was discovered and confirmed by an angiography. No source of infection was found, antiretroviral and corticosteroid treatment was given, with a complete resolution of the
P. Drake-Casanova; J. Paz Moreno-Arrones; M. Gorroño Echebarría; I. Dapena-Sevilla; J. Pareja-Esteban; E. Vleming-Pinilla
1. Vasculitis syndromes in children present with special features. The hypersensitivity vasculitides predominate with Henoch-Schoenlein purpura as a typical representative. Within the polyarteritis-nodosa-group we can distinguish an infantile form with involvement of coronary vessels. This disease resembles Kawasaki's syndrome. 2. The different vasculitis syndromes show a great variety in their clinical presentation; overlapping syndromes are possible. Diagnosis, however, is mostly based on clinical features, supported by laboratory data. In doubtful cases histologic and immunohistologic findings can prove helpful. Their diagnostic value should only be interpreted together with the clinical picture. Since specific findings are often missing we have to exclude all similar diseases. Especially systemic juvenile chronic arthritis, connective tissue diseases, several infections and sometimes malignancies have to be considered. 3. For the future we expect further differentiation and identification of new disease entities, thus hoping for a better classification. PMID:3063001
Three patients with retinal vasculitis are reported who were found to be seroreactive for Lyme borreliosis. Careful investigation revealed no other apparent etiology for the angiitis, and improvement of the retinal vasculitis on tetracycline therapy was documented by fluorescein angiography in one of them. Two cases of retinal vasculitis were presented at the International Conference on Lyme Borreliosis in Stockholm 18-21 June 1990, and two cases of cerebral vasculitis due to Borrelia burgdorferi have been published. To our knowledge, this is the first published report of retinal vasculitis occurring in patients seroreactive for Lyme borreliosis. Although further investigation will be necessary to prove a cause-and-effect relationship, ophthalmologists encountering patients with otherwise unexplained cases of retinal vasculitis, or Eales disease, are encouraged to study these patients carefully for the possibility of Borrelia burgdorferi infection. PMID:1827466
Smith, J L; Winward, K E; Nicholson, D F; Albert, D W
The pediatric small vessel vasculitides reviewed in this article are Henoch–Schönlein purpura (HSP) and the anti-neutrophil\\u000a cytoplasmic antibody-associated vasculitides (AAV). The new classification criteria for HSP and Wegener’s granulomatosis are\\u000a now validated and will facilitate the conduct of future epidemiological studies and clinical trials. The clinical manifestations\\u000a of small vessel vasculitis in children are described, and current therapies discussed. There
Paul Brogan; Despina Eleftheriou; Michael Dillon
Background: Our studies had indicated that optic disc vasculitis (ODV) is a distinct clinical entity. We investigated the presentation\\u000a and clinical characteristics of ODV and determined the efficacy of systemic corticosteroids in its management. Methods: From 1973 to 1997, we investigated 32 patients (34 eyes) with ODV. The information was obtained by complete medical and ophthalmic\\u000a history taking and a
K. T. Oh; D. M. Oh; S. S. Hayreh
Central nervous system vasculitides are defined as the invasion of the vascular wall by blood-borne inflammatory cells. In childhood, they may be classified according to their trigger event (infectious vs. non-infectious), their temporal course (time-limited vs. chronic), and the size of the affected vessel. Diseases apparently confined to the central nervous system are also distinguished from secondary forms, associated with infection or rheumatic or systemic inflammatory disorders. Large-vessel vasculitis, the most frequent form, causes stroke and presents with acute focal deficits. MR, or more seldom contrast angiography is required for the positive diagnosis, while the child's medical history conveys the etiological diagnosis. The clinical manifestations of small-vessel vasculitis include headaches, seizures, focal deficits, cognitive decline, and behavior changes that can occur insidiously over a few weeks or a few months. The diagnosis is based on the associated clinical and biological symptoms in secondary forms and on cerebromeningeal biopsy in primary forms. Secondary forms of vasculitides are treated according to the etiology. The injury of large basal arteries is often observed after infection, especially varicella, and is also called transient focal cerebral arteriopathy (TCA) or post-varicella arteriopathy (PVA). This focal, monophasic, and time-limited entity is highly specific of childhood. There are no arguments in the current literature supporting the hypothesis that an aggressive immunomodulatory treatment would be more effective, in terms of recurrence rate or functional outcome, than aspirin alone. In contrast, the diffuse, prolonged, and aggressive course of the rare primary vasculitis of the central nervous system requires a prolonged immunosuppressive treatment. The management of associated symptoms, treatment-related adverse effects, and sequelae is based on a multidisciplinary approach. PMID:24998326
Chabrier, S; Darteyre, S; Mazzola, L; Stéphan, J-L
Intraocular tuberculosis (TB) infection can have different clinical manifestations including retinal vasculitis. It more frequently involves the veins and is associated with retina haemorrhages and neovascularisation. The diagnosis may be difficult and presumptive being based on clinical findings and evidence of systemic TB infection. The authors present a case of a 61-year-old woman with blurred vision and floaters in her left eye for 6 years, associated with recurrent vitreous haemorrahages. A temporal branch retinal vein occlusion was presumed. Four years later her right eye was also involved. Her best-corrected visual acuity (BCVA) was 20/50 in both eyes. Fundoscopic examination showed bilateral venous occlusion with vascular staining on fluorescein angiography suggestive of vasculitis secondary to Eales Disease (ED). The interferon gamma release assay (IGRA-QuantiFERON-TB Gold) was positive and antituberculosis treatment (ATT) was started. Her final BCVA was 20/20 bilaterally, without recurrences over a follow-up of 15 months. The use of ATT is likely to reduce recurrent vitreous haemorrhages and eliminate future recurrences. PMID:23737572
Patricio, Maria Sara; Portelinha, Joana; Passarinho, Maria Picoto; Guedes, Marta Esteves
Vasculitis, the inflammation of blood vessels, can produce devastating complications such as blindness, renal failure, aortic rupture and heart failure through a variety of end-organ effects. Noninvasive imaging with cardiovascular magnetic resonance (CMR) has contributed to improved and earlier diagnosis. CMR may also be used in serial evaluation of such patients as a marker of treatment response and as an indicator of subsequent complications. Unique strengths of CMR favoring its use in such conditions are its abilities to noninvasively visualize both lumen and vessel wall with high resolution. This case-based review focuses on the large- and medium-vessel vasculitides where MR angiography has the greatest utility. Because of increasing recognition of cardiac involvement in small-vessel vasculitides, this review also presents evidence supporting greater consideration of CMR to detect and quantify myocardial microvascular disease. CMR’s complementary role amidst traditional clinical, serological and other diagnostic techniques in personalized care for patients with vasculitis is emphasized. Specifically, the CMR laboratory can address questions related to extent and severity of vascular involvement. As ongoing basic and translational studies better elucidate poorly-defined underlying molecular mechanisms, this review concludes with a discussion of potential directions for the development of more targeted imaging approaches.
Neoadjuvant chemotherapy consisting of cisplatin and gemcitabine was given to a 50-year-old woman suffering from transitional cell carcinoma of the bladder. Whereas the first cycle was administered without major side effects, the patient experienced a generalized tonic-clonic seizure and a prolonged cognitive deficit with the second cycle. Magnetic resonance imaging of the brain was consistent with cerebral vasculitis. The short interval between the application of gemcitabine and the neurological deterioration suggests a causal relationship. Although recent reports have linked this drug with leukoencephalopathy and vasculitis in various localizations, this is the first case of cerebral vasculitis associated with gemcitabine. PMID:20063084
Schmorl, P; Heer-Sonderhoff, A; Vosshenrich, R; Conrad, S
Neoadjuvant chemotherapy consisting of cisplatin and gemcitabine was given to a 50-year-old woman suffering from transitional cell carcinoma of the bladder. Whereas the first cycle was administered without major side effects, the patient experienced a generalized tonic-clonic seizure and a prolonged cognitive deficit with the second cycle. Magnetic resonance imaging of the brain was consistent with cerebral vasculitis. The short interval between the application of gemcitabine and the neurological deterioration suggests a causal relationship. Although recent reports have linked this drug with leukoencephalopathy and vasculitis in various localizations, this is the first case of cerebral vasculitis associated with gemcitabine. PMID:20213928
Schmorl, P; Heer-Sonderhoff, A; Vosshenrich, R; Conrad, S
Urticarial vasculitis is a relatively rare diagnosis in a patient presenting with urticaria. The process is classically described as a generalized eruption, painful more so than pruritic, lasting longer than 24 hours. Two forms of urticarial vasculitis have been described: ahypocomplementemic form more commonly associated with systemic disease, and a normocomplementemic form that is generally limited to the skin. We report on a uniquely distributed vasculitic eruption restricted mainly to the anterior belt line area in a patient presenting with urticaria and intense pruritus. Urticarial vasculitis as a unique entity is reviewed along with its clinical and histopathologic presentation and the pharmacologic agents used for treatment. PMID:19373142
Stigall, Landon E; Sigmon, Justin R; Leicht, Stuart S
Giant cell arteritis (GCA) and Takayasu arteritis (TA) are the two diseases characterized as large vessel vasculitis (LVV) and are autoimmune diseases with granulomatous inflammation that affect medium and large sized arteries. These diseases are accompanied by symptoms of systemic inflammatory reactions typically including fatigue, weight loss and low grade fever as well as elevation of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. More specific symptoms include headache and visual symptoms for GCA and arm or leg claudication, renal hypertension and angina pectoris for TA. Imaging studies to demonstrate inflammatory vascular wall lesions and biopsy of the temporal artery for GCA are the most relevant diagnostic procedures. Treatment relies mainly on glucocorticoids. Methotrexate seems to have a moderate glucocorticoid-sparing effect but evidence for other immunosuppressants, including azathioprine, tocilizumab and cyclophosphamide is limited. Revascularization methods might also be required in TA. PMID:24924731
Weigand, S; Fleck, M
Purpose of Review Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with vasculitis. Current therapy involves administration of toxic therapy that is not optimally effective. The review will summarize evidence for the pathogenicity of ANCA, which will suggest possible strategies for improving treatment. Recent Findings Pauci-immune small vessel vasculitis is associated with antibodies against myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). One research group has reported a high frequency of autoantibodies against lysosomal-associated membrane protein 2 (LAMP-2) in patients with MPO-ANCA or PR3-ANCA. Epigenetic dysregulation appears to be the basis for increased MPO and PR3 neutrophil gene expression in ANCA disease. Release of neutrophil extracellular traps (NETS) may be involved in initiating the ANCA autoimmune response and causing vessel injury. Generation of C5a by alternative pathway activation is involved in pathogenesis in mouse models. Intervention strategies in mice that target antigens, antibodies and inflammatory signaling pathways may translate into novel therapies. Animal models of LAMP-ANCA and PR3-ANCA disease have been proposed. Molecular mimicry and responses to complementary peptides may be initiating events for ANCA. T cells, including regulatory T cells, have been implicated in the origin and modulation of the ANCA, as well as in the induction of tissue injury. Summary Our basic understanding of the origins and pathogenesis of ANCA disease is advancing. This deeper understanding already has spawned novel therapies that are being investigated in clinical trials. This brief review shows that there are more questions than answers, and new questions are emerging faster than existing questions are being answered.
Jennette, J. Charles; Falk, Ronald J.; Gasim, Adil Hussein
Active immunologic vasculitis was produced in eyes of rabbits following active sensitization with a soluble protein antigen. The sequence of events following intravitreal injection of antigen was observed by immunofluorescent techniques and correlated wit...
R. A. Levine P. A. Ward
Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.
Abu El-Asrar, Ahmed M.; Herbort, Carl P.; Tabbara, Khalid F.
\\u000a Abstract\\u000a Cutaneous vasculitis is a clinical entity with a broad differential diagnosis, including an adverse drug reaction. It is defined\\u000a as inflammation of skin blood vessel walls. During a 7-year-period, we observed three patients who developed isolated cutaneous\\u000a vasculitis during antibiotic therapy of bacterial infection. All were treated with a fluoroquinolone (ciprofloxacin or levofloxacin)\\u000a combined with rifampin (two cases) or
G. Maunz; T. Conzett; W. Zimmerli
Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral\\u000a nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. Vasculitis\\u000a is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous\\u000a system
For most patients with vasculitis, treatment will result in prevention of mortality and also lead to clinical remission. This increased survival is of course most welcome, but the burden of surviving an episode of acute vasculitis consists of the effects of the disease as well as the adverse events from treatment. Therefore, we have begun to explore the possibility of withdrawing treatment in order to avoid long-term medication toxicities. Whilst this will reduce short-term side effects, if withdrawal leads to subsequent uncontrolled flares of disease, the need for additional therapy may outweigh any benefit from a drug-free holiday. For very mild forms of vasculitis, such as isolated skin vasculitis, the best option may be to avoid treatment altogether. In those patients with vasculitis secondary to an identifiable agent such as drug toxicity or an infectious organism, discontinuing the offending drug or treating the infection will usually resolve or cure the vasculitis. In patients with localised vasculitis, surgical removal of the affected area can be curative. Other forms of vasculitis have a self-limited duration, after which there does not appear to be any clinical evidence of disease, such as is the case for the majority of patients with giant cell arteritis. By contrast, in many forms of vasculitis, especially those associated with the presence of anti-neutrophil cytoplasm antibody (ANCA), relapse occurs in at least half the patients. Where glucocorticoid therapy is used for any length of time, in doses of >5 mg/day, side effects are almost universal. Adding a concomitant agent in the attempt to shorten the course and/or reduce the dose of glucocorticoid treatment may be effective, but can also result in toxicity from the alternative agent, and leaves the patient on immunosuppressive therapy. More toxic therapy, such as cyclophosphamide, usually is administered only for a limited time or cumulative amount, in order to achieve induction of remission or flare in severe disease. The advent of targeted biologic therapy offers the opportunity to provide more effective, less toxic and perhaps more long-lasting control of disease. Rituximab in small-vessel vasculitis can result in long-lasting control of disease, for 18 months or more, from a single course of treatment. Suppression of the interleukin-6 pathway may be effective in large-vessel vasculitis. Unfortunately, none of these therapies is capable of 'cure' for the majority of patients. Therefore, discontinuation of therapy remains unachievable for most patients with vasculitis, at least in the first few years of disease. Short courses of intensive, aggressive therapy are followed by the use of maintenance treatment. Long-term follow-up studies are required to determine the potential benefit of early, more effective control of vasculitis. PMID:24129146
Luqmani, Raashid A
Systemic lupus erythematosus (SLE) is a complex heterogeneous autoimmune disease with a wide variety of clinical and serological manifestations that may affect any organ. Vasculitis prevalence in SLE is reported to be between 11 % and 36 %. A diverse clinical spectrum, due to inflammatory involvement of vessels of all sizes, is present. Even though cutaneous lesions, representing small vessel involvement, are the most frequent, medium and large vessel vasculitis may present with visceral affection, with life-threatening manifestations such as mesenteric vasculitis, pulmonary hemorrhage, or mononeuritis multiplex, with detrimental consequences. Early recognition and an appropriate treatment are crucial. Recent studies have shown that vasculitis in patients with SLE may present different clinical forms based on the organ involved and the size of the affected vessel. It is noteworthy that the episodes of vasculitis are not always accompanied by high disease activity. Recent articles on this topic have focused on new treatments for the control of vascular disease, such as biological therapies such as Rituximab and Belimumab, among others. PMID:25023725
Barile-Fabris, L; Hernández-Cabrera, M F; Barragan-Garfias, J A
Rarely, leukocytoclastic vasculitis can result from ischemic colitis, inflammatory bowel disease, and cryoglobulinemia. There is no established standard for the treatment of leukocytoclastic vasculitis associated with gastroenterologic diseases. This paper presents three cases of leukoytoclastic vasculitis, each of which is associated with a different gastroenterologic condition: ischemic colitis, Crohn's disease, and chronic hepatitis C. Each condition went into remission by treatment of leukocytoclastic vasculitis, regardless of the underlying disease.
Arabaci, Elif; Yildiz, Kemal; Cakirca, Mustafa; Cikrikcioglu, Mehmet Ali; Ergun, Fatih; Danalioglu, Ahmet; Kocaman, Orhan; Senturk, Hakan
A case of leukocytoclastic vasculitis in a 24-year-old woman is described. A severe eruption of vasculitis occurred after placebo-controlled oral challenge with 50 mg ponceau. The patient was asked to adhere to a diet free from food additives, and the vasculitis faded after a period of 2 months. PMID:1676224
Veien, N K; Krogdahl, A
Work in Department of Energy (DOE) facilities has exposed workers to multiple toxic agents leading to acute and chronic diseases. Many exposures were common to numerous work sites. Exposure to crystalline silica was primarily restricted to a few facilities. I present the case of a 63-year-old male who worked in DOE facilities for 30 years as a weapons testing technician. In addition to silica, other workplace exposures included beryllium, various solvents and heavy metals, depleted uranium, and ionizing radiation. In 1989 a painful macular skin lesion was biopsied and diagnosed as leukocytoclastic vasculitis. By 1992 he developed gross hematuria and dyspnea. Blood laboratory results revealed a serum creatinine concentration of 2.1 mg/dL, ethrythrocyte sedimentation rate of 61 mm/hr, negative cANCA (antineutrophil cytoplasmic antibody cytoplasmic pattern), positive pANCA (ANCA perinuclear pattern), and antiglomerular basement membrane negative. Renal biopsy showed proliferative (crescentric) and necrotizing glomerulonephritis. The patient's diagnoses included microscopic polyangiitis, systemic necrotizing vasculitis, leukocytoclastic vasculitis, and glomerulonephritis. Environmental triggers are thought to play a role in the development of an idiopathic expression of systemic autoimmune disease. Crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, rapidly progressive glomerulonephritis and some of the small vessel vasculitides. DOE workers are currently able to apply for compensation under the federal Energy Employees Occupational Illness Compensation Program (EEOICP). However, the only diseases covered by EEOICP are cancers related to radiation exposure, chronic beryllium disease, and chronic silicosis.
Mulloy, Karen B
We present the case history of a 48-year-old male patient with Chlamydophila (Chlamydia) pneumoniae who developed a nodular vasculitis. He developed a cutaneous vasculitis with the onset of respiratory symptoms. The diagnosis of Chlamydophila pneumoniae infection was based on serology. Since this infection is very common in our population, although often asymptomatic, it should be systematically considered as a causative agent of nodular vasculitis.
Sakuma, H.; Niiyama, S.; Amoh, Y.; Katsuoka, K.
Behcet's Disease; Churg-Strauss Syndrome; Vasculitis, Central Nervous System; Giant Cell Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu's Arteritis
The skin not only represents the organ which often reveals the first signs of systemic vasculitis, but also the organ which is most frequently involved in vasculitis. These diseases encompass systemic vasculitides and those which appear to involve the skin only. Among those vasculitides restricted to the skin, some are yet typically associated with other systemic diseases, such as nodular vasculitis, which often occurs during infections by M. tuberculosis, or erythema elevatum diutinum in patients with gammopathy. The type and localization of skin lesions give valuable indications as to the type of vasculitis. Subcutaneous nodules which ulcerate and are surrounded by livedo racemosa are suggestive of polyarteritis nodosa, a palpable purpura with predilection for the lower legs is almost pathognomonic for immune complex vasculitis (e.g. IgA vasculitis or cutaneous leukocytoclastic vasculitis), hemorrhagic papules and necrotic plaques which occur in acral areas after cooling indicate cryoglobulinemic vasculitis, hemorrhagic papules and macules which develop in patients who start to feel worse and develop fever should arouse suspicion of septic vasulitis, while the simultaneous presence of ulcerating nodules and hemorrhagic papules without predilection for the lower legs will suggest ANCA-associated vasculitis. The different morphology of the cutaneous signs of the various vasculitides depends to a large extent on the size of the vessels primarily involved. In this review the cutaneous signs of vasculitides will be presented with reference to the revised nomenclature of the Chapel Hill Consensus Conference from 2012. PMID:23743986
Antituberculosis therapy-associated cutaneous leukocytoclastic vasculitis (CLV) has been rarely reported. We describe a case of CLV induced by rifampicin and pyrazinamide. A 14-year-old male diagnosed with disseminated tuberculosis developed purpuric lesions after 1.5 months of treatment. Histopathology was consistent with leukocytoclastic vasculitis. Skin lesion improved after cessation of the two drugs and treatment with corticosteroids. PMID:23780994
Bhatia, Vidyut; Sibal, Anupam; Rajgarhia, Shilpy
Antineutrophil cytoplasm antibody associated vasculitis has been transformed from life-threatening conditions to chronic relapsing long-term diseases as a result of significant advances in immunosuppressive therapy. Although mortality still occurs, it is much less frequent, with an average 5-year survival of over 70 %. In the setting of chronic conditions, it becomes increasingly important to monitor the burden of disease in terms of both active inflammation requiring immunosuppression and chronic damage (scarring) from vasculitis and its treatment and associated comorbidity. The damage that accumulates in patients with vasculitis does not respond to immunosuppressive treatment. It is important to distinguish disease activity from disease damage to prevent unnecessary immunosuppression, but it is equally important to recognize damage for what it is, so that it can be addressed appropriately. Damage is an inevitable consequence of long-term vasculitis for over 80 % of patients, which should not surprise us given the severity of the original illness. There is potential value in measuring damage as a means of providing prognostic information. Using a quantified score such as the Vasculitis Damage Index (VDI) allows us to predict mortality. Patients with at least five items of damage on the VDI score have substantially worse mortality (7- to 11-fold worse risk), as compared with those with lesser amounts of damage. These findings should be taken into context when planning the management of patients with vasculitis, as well as in clinical trials of vasculitis. Disease damage is an important surrogate for long-term outcome in vasculitis, and studies should be designed to limit the amount of damage accumulating as a result of therapeutic intervention, rather than simply controlling disease activity, as is currently the aim in recent randomized controlled trials in vasculitis. Furthermore, careful cataloguing of damage, as well as disease activity items, provides much greater detail in describing and observing the long-term natural history of primary systemic vasculitis in patients treated with immunosuppressive agents who survive their initial disease process. PMID:22983618
Bhamra, Kuljeet; Luqmani, Raashid
The treatment of systemic necrotizing vasculitis has made great strides in both efficacy and outcomes. Standard therapies, however, are associated with numerous side effects, and not all patients will respond to conventional immunosuppression. These realities have prompted the search for safer and more efficacious treatments, most notably among biologic agents. For example, the role of TNF-? in the pathophysiology of several vasculitides has led to the investigation of targeted inhibitors of this cytokine, albeit with mixed results. There have been some disappointing results in the area of giant cell arteritis and Wegener’s granulomatosis (granulomatosis with polygiitis), but anti-TNF therapy has shown promise in the treatment of Takayasu’s arteritis, although additional trials to demonstrate its efficacy are required. Anti-B-cell therapy seems to be the most promising advance in the management of these diseases. Complete and partial responses have been seen in both primary and secondary mixed cryoglobulinemic vasculitis. Recent trials have demonstrated that rituximab is effective for the treatment of Wegener’s granulomatosis and microscopic polyangiitis. These trials have, however, raised concerns regarding the long-term safety of these agents. The future holds promise for additional targeted therapies with improved patient response and fewer side effects.
Henderson, Charles F; Seo, Philip
Vasculitis is rarely associated with lymphoma; however, most cases associated with lymphoma are cutaneous. Systemic vasculitis in association with lymphoma is usually an indolent and non-fatal complication. Two patients presented to our department with fulminant vasculitis with a fatal course and were later diagnosed with lymphoma. A search of the literature for systemic fulminant vasculitis in association with lymphoma disclosed
Eyal Leshem; Yaron Davidovitz; Eyal Meltzer; Paul Fefer; Efrat Ofek; Yechezkel Sidi
A 71-year-old woman presented with a high-grade fever, neck pain, anemia and thrombocytopenia. After performing further examinations, we concluded that she had simultaneously developed large vessel vasculitis and myelodysplastic syndrome (MDS). Although glucocorticoid administration improved her clinical symptoms, the MDS transformed into acute myeloid leukemia and she died one year after receiving the diagnosis. The occurrence of immune-mediated disorders in patients with MDS is a well-known phenomenon; however, large vessel vasculitis is a rare complication of MDS. Our case suggests that the association between systemic vasculitis and MDS may result in poor outcomes. PMID:24390531
Katsuyama, Takayuki; Uchida, Haruhito Adam; Toma, Kishio; Maeda, Yoshinobu; Hirota, Daisho; Umebayashi, Ryoko; Sada, Ken-Ei; Makino, Hirofumi
In younger patients with stroke, cerebral vasculitis and hereditary small vessel diseases should be considered as important differential diagnoses. Since the clinical course of cerebral vasculitis is highly variable, diagnostic workup, which includes laboratory tests, CSF analysis, cranial magnetic resonance imaging and biopsy, is often challenging. Therapy should be initiated on an interdisciplinary basis and includes immunosuppressive induction and maintenance regimes. Hereditary small vessel diseases, e.g. CADASIL or Fabry's disease, can mimic clinical features of cerebral vasculitis. Their diagnosis which is based on family history, typical clinical features and genetic analysis often has implications for treatment and genetic counselling. PMID:19838657
Opherk, C; Peters, N; Dichgans, M
A literature review utilizing Fepafem, Bireme, LiLacs, Scielo Colombia, Scielo Internacional, former MedLine, Pubmed, and BVS Colombia as well as manual searches in the libraries of major Latin American universities was performed to study vasculitis in Latin America. Since 1945, a total of 752 articles have been published by Latin American authors. However, only a minority are devoted to primary vasculitides, and even fewer have been published in indexed journals. Approximately 126 are in OLD, Medline, Pubmed, Bireme, and Scielo. Most publications are from Mexico, followed by Brazil and Colombia. Systematic studies of the epidemiology of primary idiopathic vasculitis are available for a few countries, i.e. Brazil, Mexico, Colombia, Chile, and Peru. Takayasu arteritis and ANCA-associated vasculitis are the best studied forms of vasculitis in Latin America. Interest and expertise in vasculitis is growing in Latin America, as reflected in the increased number of published articles from this region of the world in the last decade. Racial and environmental factors are possibly responsible for the differential expression of various types of primary vasculitis observed in Latin America. With time, the unique features, epidemiology, and better treatment strategies for idiopathic vasculitides in Latin America will emerge. PMID:20190698
Iglesias Gammara, Antonio; Coral, Paola; Quintana, Gerardo; Toro, Carlos E; Flores, Luis Felipe; Matteson, Eric L; Restrepo, José Félix
The multidisciplinary guideline 'Diagnostics of small-vessel vasculitis' gives recommendations for the diagnostics of small-vessel vasculitis, which is often associated with cutaneous manifestations. The aim of this guideline is to accelerate the diagnostic process to prevent or reduce irreversible organ damage. The clinical presentation of small-vessel vasculitis is variable and often atypical. The most common general symptoms are general malaise, unexplained fever, weight loss, fatigue, loss of appetite, and night sweats. If these symptoms are accompanied by one or more organ-specific symptoms, the probability of the diagnosis 'small-vessel vasculitis' is increased. When small-vessel vasculitis is suspected a comprehensive history should be taken and a physical examination focused on internal organs, joints, skin and nervous system should be performed. With additional laboratory investigations possible organ involvement can be demonstrated and the small-vessel vasculitis can be further classified. To make a definite diagnosis histological examination of an affected organ is necessary. Because of the possible involvement of multiple organ systems, multidisciplinary collaboration is essential in the diagnostic work-up. PMID:22617066
Thio, H Bing; Balak, Deepak M W; Meilof, Jan F; Stegeman, Coen A; Voskuyl, Alexandre E
Anti-neutrophil cytoplasm antibodies are important markers of certain small vessel necrotizing vasculitides, but the optimal use of laboratory results in daily clinical practice necessitates collaboration between clinicians and laboratory specialists. Physicians must familiarize themselves with ANCA tests in ANCA-related vasculitides as well as in differential diagnostic patient populations in order to define cutoff values. Indirect immunofluorescence with a consensus-agreed technique combined with standardized enzyme immunoassays is the modality for detecting the main SSV-associated ANCA specificities using cutoff values that can sufficiently distinguish SVV from non-SVV patients. The combined use of IIF and direct EIA to demonstrate proteinase 3-ANCA and myeloperoxidase-ANCA at significant levels leads to a very high diagnostic specificity towards SVV conditions such as Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and limited forms of these such as renal-limited focal necrotizing glomerulonephritis. A strong reactivity of ANCA against several azurophil granule components indicates a drug-induced syndrome. ANCA-related SVV and drug-induced vasculitis or lupus syndromes have characteristic ANCA profiles that can help distinguish these conditions from other inflammatory diseases. PMID:11344841
Vasculitides includes a heterogeneous group of disorders with the common histologic findings of vascular wall inflammation. Systemic or localized disease (eg, renal vasculitis) has serious consequences. The incidence of isolated gynecologic vasculitis diagnosed on pathology specimens and its significance is little known. We performed a 20 year retrospective review including 53 cases with vasculitis diagnosis affecting the female genital tract identified in pathology reports. None had prior symptoms or were diagnosed with generalized vasculitis, while one patient had prior diagnosis of fibromyalgia. Most patients presented with abnormal bleeding and were treated for conditions unrelated to vasculitis. The different types of vasculitis were: predominantly lymphocytic (nonspecific) 30 cases, necrotizing 17 cases and granulomatous 6 cases. Only 2 patients had additional serologic tests. None of the patients with isolated gynecologic vasculitis received corticosteroids or additional treatment related to the vasculitis. None of the patients developed systemic vasculitis at follow-up (2 months-19.5 years; mean, 5.5 years). Isolated gynecologic vasculitis diagnosed on pathology slides is rarely associated with systemic vasculitis. Potential isolated gynecologic vasculitis causes include: previous surgical interventions and vascular inflammation secondary to local neoplasm. In almost all cases, clinicians did not perform a thorough laboratory analysis to exclude systemic vasculitis and therapy was not required in any case, suggesting minimal clinical significance. PMID:24846840
Roma, Andres A; Amador-Ortiz, Catalina; Liapis, Helen
Background Systemic vasculitis may cause life threatening complications requiring admission to an intensive care unit (ICU). The aim of this study was to evaluate outcomes of systemic vasculitis patients admitted to the ICU and to identify prognosis factors. Methods During a ten-year period, records of 31 adult patients with systemic vasculitis admitted to ICUs (median age: 63 y.o, sex ratio M/F: 21/10, SAPS II: 40) were reviewed including clinical and biological parameters, use of mechanical ventilation, catecholamine or/and dialysis support. Mortality was assessed and data were analyzed to identify predictive factors of outcome. Results Causes of ICU admissions were active manifestation of vasculitis (n?=?19), septic shock (n?=?8) and miscellaneous (n?=?4). Sixteen patients (52%) died in ICU. By univariate analysis, mortality was associated with higher SOFA (p?=?0.006) and SAPS II (p?=?0.004) scores. The need for a catecholamine support or/and a renal replacement therapy, and the occurrence of an ARDS significantly worsen the prognosis. By multivariate analysis, only SAPS II (Odd ratio: 1.16, 95% CI [1.01; 1.33]) and BVAS scores (Odd ratio: 1.16, 95% CI?=?[1.01; 1.34]) were predictive of mortality. Conclusion The mortality rate of severe vasculitis requiring an admission to ICU was high. High levels of SAPS II and BVAS scores at admission were predictive of mortality.
Ischemic retinal vasculitis is an inflammation of retinal blood vessels associated with vascular occlusion and subsequent retinal hypoperfusion. It can cause visual loss secondary to macular ischemia, macular edema, and neovascularization leading to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment. Ischemic retinal vasculitis can be idiopathic or secondary to systemic disease such as in Behçet's disease, sarcoidosis, tuberculosis, multiple sclerosis, and systemic lupus erythematosus. Corticosteroids with or without immunosuppressive medication are the mainstay treatment in retinal vasculitis together with laser photocoagulation of retinal ischemic areas. Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia. Antitumor necrosis factor agents have shown promising results in controlling refractory retinal vasculitis excluding multiple sclerosis. Interferon has been useful to control inflammation and induce neovascular regression in retinal vasculitis secondary to Behçet's disease and multiple sclerosis. The long term effect of these management strategies in preventing the progression of retinal ischemia and preserving vision is not well understood and needs to be further studied.
Giant Cell Arteritis; Takayasu's Arteritis; Polyarteritis Nodosa; Wegener's Granulomatosis; Microscopic Polyangiitis; Churg-Strauss Syndrome; Behcet's Disease; Kawasaki Disease; Henoch-schoenlein Purpura; Vasculitis, Central Nervous System; Drug-induced Necrotizing Vasculitis
Cerebral vasculitis following acute post-streptococcal glomerulonephritis (APSGN) is a rare neurological complication. An 11-year-old girl with biopsy proven APSGN developed an acute seizure disorder. Clinical and computed tomography findings were consistent with vasculitis. PMID:11903844
Wong, W; Morris, M C
Retinal vasculitis is a rare, but potentially blinding intraocular inflammatory condition with diverse aetiology. Although commonly idiopathic, it has a strong association with systemic inflammatory diseases known to involve other areas of the central nervous system, most notably Behcet's disease, sarcoidosis, systemic lupus erythematosis and multiple sclerosis. This article describes the clinicopathologic features of retinal vasculitis and its visually damaging sequelae, reviewing available human histopathologic studies and work with experimental models to discuss the pathogenesis and immunopathology. Evidence indicates that noninfective retinal vasculitis is an autoimmune condition that may be induced by antecedent infection with microbes cross-reacting with putative autoantigens, influenced by genetic susceptibility of both HLA associations and cytokine polymorphisms. The growing understanding of the cellular mechanisms involved in the effector immune response is already providing a rationale for more specific therapeutic approaches. PMID:12887593
Hughes, E H; Dick, A D
Introduction Central nervous system involvement in rheumatoid arthritis is infrequent. The most frequent neurological manifestations of rheumatoid arthritis are peripheral neuropathy and cervical spinal cord compression due to subluxation of the cervical vertebrae. Cerebral rheumatoid vasculitis is an uncommon and serious complication which can be life-threatening. Case presentation A 52-year-old North African Tunisian Caucasian woman presented with a six-week history of headache. She had suffered seropositive and destructive rheumatoid arthritis for nine years without any extra-articular complications. Magnetic resonance imaging of the brain with the T2 sequence showed high-intensity signal images at the frontal and parietal cortico-subcortical junction suggesting hemispheric vasculitis. Conclusions Cerebral vasculitis is an infrequent complication in rheumatoid arthritis which is associated with high morbidity and in some cases can be life-threatening. Early assessment and a high index of suspicion to recognize such complications are essential in managing these patients.
Although the effectiveness of biological agents in systemic vasculitis is unproven, their introduction heralds a new era of vasculitis treatment. These agents offer the promise of targeted immunotherapies; the possibility of greater efficacy (and fewer side-effects) than conventional vasculitis treatments; and the potential to provide novel insights into the pathophysiology of these diseases—insights that may be gained only by using
Stuart M Levine; John H Stone
Antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) are a group of systemic vasculitis characterized by inflammation and necrosis of blood vessel walls. Genetic, epigenetic and environmental factors contribute to the etiology and pathogenesis of AAV. Based on currently available clinical and experimental evidence, it is reasonable to conceptualize that in predisposed patients, different triggers can lead to the production of autoantibodies (ANCA) that in the context of an inflammatory environment can cause tissue inflammation and vascular injury. Several different pathways and mechanisms in the pathogenesis of AAV are described in this contemporary review.
Cartin-Ceba, Rodrigo; Peikert, Tobias; Specks, Ulrich
Two cases of systemic vasculitis are described; one presenting with adult Henoch-Schonlein purpura secondary to a concomitant Chlamydia infection and the other with leucocytoclastic vasculitis and mesangioproliferative glomerulonephritis secondary to a recent parvovirus B19 infection. Association of chlamydial infection has not previously been described with Henoch-Schonlein purpura and this infection should, perhaps, be added to the list of aetiologies of this disease. Parvovirus B19 causing significant urinary sediment abnormalities associated with mesangioproliferative glomerulonephritis and leucocytoclastic vasculitis has also not been described previously.???Keywords: vasculitis; Henoch-Schonlein purpura; Chlamydia infection; leucocytoclastic vasculitis; mesangial proliferative glomerulonephritis; parvovirus B19
Chakravarty, K.; Merry, P.
A 29 year old male was admitted at the emergency room suffering from gradually worsening headache followed by nausea. In the hospital patient presented with lethargy, reduction of consciousness level and bilateral hypoacusis. Ophthalmic examination and fluorescein angio- graphy showed retinal vasculitis. This finding was crucial to the diag- nosis of Susac syndrome, a rare disease characterized by vasculopathy of
Francisco Azevedo Marquardt; Heriberto Pinto; Guimarães Neto; Daniel Azevedo Marquardt
Glomerulonephritis (GN) is a common manifestation of the antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASV), which include granulomatosis with polyangiitis and microscopic polyangiitis. The level of renal involvement at presentation is highly predictive of survival and should be assessed early so that kidney function can be preserved. AASV patients with urinary sediment but normal function have a twofold greater risk of death than those with no renal involvement. Those with impaired renal function at diagnosis have a fivefold greater risk of death. Renal vasculitis is most prevalent in older patients, who have more severe disease and poorer prognoses. Renal biopsy not only establishes diagnosis but provides information on severity of renal-function impairment and prognosis. Induction of remission with cyclophosphamide is standard treatment. For patients with crescentic, rapidly progressive GN, adjunctive plasma exchange can promote renal recovery. Renal failure occurs in one-fourth of AASV patients after 3 to 4 years; 60% of patients receiving dialysis for acute GN can recover independent renal function. Renal transplant patients with vasculitis fare as well as renal transplant patients without vasculitis. Lastly, renal vasculitis is an independent risk factor for cardiovascular events. PMID:23203640
de Groot, Kirsten
A 39-year-old woman experienced severe headache, epilepsy and rapidly progressive aphasia and hemianopia. Carotid angiograms displayed segmentary narrowing of intracranial arteries as previously described in benign cerebral vasculitis. Her superficial temporal artery was also involved, allowing a biopsy of the abnormal part of the vessel. Microscopical study of this artery was normal. A second carotid angiogram, 14 days later, showed
M Serdaru; J Chiras; M Cujas; F Lhermitte
Propylthiouracil (PTU) is a common drug used in patients with hyperthyroidism. It may cause perinuclearantineutrophil cytoplasmic antibodies (p-ANCA) in few patients with Graves’ disease. This antibody has been associated with different forms of vasculitis. We report a patient who presented with cutaneous manifestations of leukocytoclasticvasculitis with simultaneous development of p-ANCAs during PTU therapy for Graves’ disease.
Ayturk, Semra; Demir, Mustafa Volkan; Yaylac?, Selcuk; Tamer, Ali
We report the occurrence of cryoglobulinemia and cutaneous vasculitis in three patients with brucellosis caused byBrucella melitensis. The isolated cryoglobulins were characterized as mixed polyclonal or type III. Brucella agglutinin activity was not detected in any of the cryoglobulins analyzed. However, the same agglutinin titer and the presence of precipitin lines of identity in immuno-diffusion gels were observed in the
Juan L. Yrivarren; Luis R. Lopez
Optic disc vasculitis may be of 2 different types, hence the fundus may show either marked edema of the optic disc or signs of central retinal vein obstruction without other ocular or systemic abnormality. 42 cases of this disease (51 eyes) are presented ...
C. Qingkui Z. Qi
Seventeen patients with retinal vasculitis, eleven with the peripheral type (Eales' disease) and six with the central type, were investigated to detect the presence of circulating immune complexes (IC) which might then be related to the pathogenesis of their disease. A systemic disease process was identified in six. IC in serum were inferred by the presence of complement (C) activation, rheumatoid factor, Clq or monoclonal rheumatoid factor precipitins, anticomplementary activity, elevated cryoglobulins, inhibition of erythrocyte-antibody (IgG-EA) rosette formation, increased numbers of peripheral blood lymphocytes bearing surface Ig, and spontaneous neutrophil chemotatic activity in plasma. Two or more parameters were positive in thirteen of seventeen patients, with chemotactic activity (69%) and inhibition of EA-rosette formation (59%) being the most frequently positive tests. No immunological differences were detected between the peripheral and central retinal-vasculitis groups. Several IC systems may operate in a give patient.
Andrews, B S; McIntosh, J; Petts, V; Penny, R
A 39-year-old woman experienced severe headache, epilepsy and rapidly progressive aphasia and hemianopia. Carotid angiograms displayed segmentary narrowing of intracranial arteries as previously described in benign cerebral vasculitis. Her superficial temporal artery was also involved, allowing a biopsy of the abnormal part of the vessel. Microscopical study of this artery was normal. A second carotid angiogram, 14 days later, showed normal intracranial arteries. These findings suggest arterial spasm rather than distal arteritis. Images
Serdaru, M; Chiras, J; Cujas, M; Lhermitte, F
Small-vessel vasculitis is defined by the presence of blood vessel inflammation involving the arterioles, venules, or capillaries.\\u000a This can be seen in a broad spectrum of settings, but it is most commonly associated with Wegener’s granulomatosis, microscopic\\u000a polyangiitis, and Churg-Strauss syndrome. Although prednisone combined with cyclophosphamide induces remission and prolongs\\u000a survival in these diseases, this regimen is toxic and does
Carol A. Langford
Malignant angioendotheliomatosis is a rare disease characterized by an intravascular proliferation of atypical mononuclear cells. Manifestations result from occlusion of small blood vessels. Multiple organ systems are involved and the clinical presentation resembles a systemic necrotizing vasculitis with skin and central nervous system most commonly involved. The clinical course is characterized by progressive organ failure with death usually within 2 years after presentation. Based on its assumed origin as an intravascular lymphoma, patients may respond to chemotherapy. PMID:1512773
Kao, N L; Broy, S; Tillawi, I
Current data on therapeutic immunomodulation used to treat systemic vasculitides are reviewed in this paper, which also discusses ongoing and future developments in the field. In vasculitides associated with anti-neutrophil cytoplasmic antibodies, rituximab is a validated induction treatment that can serve as an alternative to cyclophosphamide and must be followed by maintenance treatment. In addition, the usefulness of rituximab as maintenance treatment was established recently. Immunoglobulins can be helpful adjuncts, most notably in patients with severe immunodepression. Plasmapheresis is indicated in patients with severe renal failure and may have a role in the treatment of alveolar hemorrhage syndromes. Mepolizumab has produced encouraging preliminary results in eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Rituximab can be used in cryoglobulinemic vasculitis associated with hepatitis C virus infection when antiviral therapy fails or the disease is severe. Very low doses of interleukin-2 may be helpful in refractory forms. Rituximab is also an option in essential mixed cryoglobulinemia with uncontrolled vasculitis despite glucocorticoid and/or immunosuppressive treatment. In polyarteritis nodosa associated with the hepatitis B virus, a combination of short-course glucocorticoids, plasmapheresis, and antiviral therapy produces excellent outcomes. Intravenous immunoglobulins are used to treat Kawasaki disease, in which they diminish the incidence of coronary artery aneurysms. Several prospective controlled trials are currently assessing tocilizumab in giant-cell arteritis. Rituximab has useful effects in systemic vasculitis associated with rheumatoid arthritis. In Goodpasture's syndrome, plasmapheresis is indicated to clear the antibodies to glomerular membrane antigen, which can induce glomerulonephritis. PMID:23237994
Puéchal, Xavier; Guillevin, Loïc
Vasculitis, an inflammatory condition affecting the blood vessels, may be restricted to a single organ or involve several organ systems. The size of the involved vessels is an important criterion for categorization of vasculitides, which is a prerequisite for rapid diagnosis and initiation of treatment. In pediatric patients, this particularly applies to Kawasaki disease. However, making the diagnosis can be challenging for dermatologists as skin involvement may be variable and non-specific. In contrast, Henoch-Schönlein purpura (IgA vasculitis) presents with the classic picture of palpable purpura. It predominantly affects postcapillary venules frequently following upper respiratory tract infections. Severe organ involvement is relatively rare in children and the prognosis is good. As renal involvement may occur during the course of disease, continuous monitoring is required. Acute hemorrhagic edema of infancy is considered as a distinct type of immune complex vasculitis and is characterized by a triad of fever, edema and rosette-shaped purpura. The clinical course of this rare disease is usually benign and self-limited. Due to the variability of clinical symptoms and manifestations, management of childhood vasculitides represents a special challenge requiring interdisciplinary collaboration. Dermatologists should be aware of their important role especially for making an early diagnosis. PMID:24494640
Sandrine, Benoit; Goebeler, Matthias
Herpes zoster infection occurs more frequently and severely in immunosuppressed populations. However, the condition sometimes presents with atypical clinical manifestations of the skin, which makes it difficult to reach a correct diagnosis. We experienced a case of acral gangrene caused by varicella zoster virus (VZV)-related vasculitis in a rheumatoid arthritis (RA) patient. Histologically, necrotic vasculitis was observed; however, there were initially no findings in the epidermis suggestive of a viral infection. We thought that the skin ulcer was related to rheumatoid vasculitis. However, an immunohistochemical analysis for VZV confirmed VZV infection in the vascular endothelium of the dermis, leading to effective treatment with intravenous acyclovir. Since various pathogenic skin phenotypes are observed in RA patients, modified according to the status of immunosuppression, clinicians must recognize the variation in typical and atypical manifestations in order to manage these patients. PMID:24761143
Tanaka, Aya; Hayaishi, Nagako; Kondo, Yukari; Kurachi, Kishiro; Tanemura, Atsushi; Katayama, Ichiro
Cryoglobulinemic vasculitis is extremely rare in patients with systemic sclerosis (SSc). So far, only two cases of cryoglobulinemic vasculitis in SSc were described in the literature. This report is about a patient with SSc and secondary Sj?gren's syndrome, who developed typical clinical features of small-vessel vasculitis, including arthritis, purpura, microhaematuria, gangrene of fingers, and toes and myocardial ischemia, in the presence of mixed cryoglobulinemia, ANA, rheumatoid factor, and anti-SSA/Ro antibodies. Symptoms and signs of vasculitis worsened despite initial treatment with corticosteroids and cyclophosphamide, but improved significantly when mycophenolate mofetil was used instead cyclophosphamide. PMID:23271426
Background\\/Aims: Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis patients with renal involvement have been shown to have a progressive clinical course. In this study, we compared the clinical utility of the Japanese Vasculitis Activity Score (JVAS) with the Birmingham Vasculitis Activity Score (BVAS) for predicting death in patients with MPO-ANCA-associated renal involvement. Methods: Sixty-nine patients with MPO-ANCA-associated vasculitis with renal involvement
Kiyomi Koike; Kei Fukami; Koji Yonemoto; Ryuji Iwatani; Rimi Obata; Kaoru Ueda; Maki Toyonaga; Seiji Ueda; Atsuko Ohara; Kazuhito Takeda; Sho-ichi Yamagishi; Seiya Okuda
Background: Livedoid vasculitis is characterized clinically by smooth or depressed ivory-white scars surrounded by hyperpigmentation and telangiectasia with or without preceding purpuric infiltrated papules and plaques and histologically by intravascular deposition of fibrin. Its etiology remains obscure and therapy very difficult. Objective: Our purpose was to test the efficacy of low-dose danazol in the treatment of livedoid vasculitis. Methods: Seven
G.-H. Hsiao; H.-C. Chiu
A 21-year-old male presented with acute onset, sharp right sided testicular pain. The testicle was removed with a histological diagnosis of testicular vasculitis. Anti-neutrophil cytoplasmic antibodies were negative. Although rare, males who present with acute onset pain should be screened for testicular vasculitis with a scrotal ultrasound and blood investigations including tumor markers and anti-neutrophil cytoplasmic antibodies.
Lintern, Narelle; Johnson, Nigel R.; Mckenzie, Ian; Martin, Ben
Antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAV) are a group of systemic vasculitis syndromes characterized by inflammation and necrosis of blood vessel walls. Genetic, epigenetic, and environmental factors contribute to the etiology and pathogenesis of AAV. On the basis of currently available clinical and experimental evidence, it is reasonable to believe that, in predisposed patients, different triggers can lead to the production of autoantibodies (ANCA) that, in the context of an inflammatory environment, can cause tissue inflammation and vascular injury. Several different pathways and mechanisms in the pathogenesis of AAV are described in this contemporary review. PMID:22927039
Cartin-Ceba, Rodrigo; Peikert, Tobias; Specks, Ulrich
Classification criteria have an important role and practical use in everyday rheumatology. Improvement in therapy and our understanding of the aetiopathogenesis of vasculitis have driven the need to have better descriptors and groupings of diseases. This in turn will allow newer therapy and further understanding to have a greater impact. The American College of Rheumatology (ACR) classification criteria have been an important advance but have limitations. There remains confusion between classification and diagnostic criteria and definitions. We hope to resolve this using evidence-based improvements in classification and diagnostic criteria. Further understanding of the underlying causative mechanisms could lead to diagnostic testing, eliminating the need for classification criteria. PMID:23507053
Waller, Rosemary; Ahmed, Azeem; Patel, Ishita; Luqmani, Raashid
Anti-neutrophil cytoplasmic antibodies (ANCA) are important diagnostic markers in vasculitic disorders. In a study of 164 patients with various clinical syndromes associated with vasculitis, 60 were found to have the antibody, as detected by indirect immunofluorescence; 23 had the so-called perinuclear antibody pattern, and of these, 15 had antibodies to neutrophil myeloperoxidase in an ELISA. These patients had multi-system involvement, and 14 of the 15 had histological evidence of small-vessel arteritis in the kidneys. In preliminary experiments, the isolated IgG from one patient was shown to inhibit luminol-dependent chemiluminescence of fluid phase myeloperoxidase. Images Fig. 3 Fig. 4
Lee, S S; Adu, D; Thompson, R A
Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are systemic or more limited conditions characterized by necrotizing destruction of small and medium-sized vessels (eg, capillaries, venules, and arterioles). ANCAs are the most predominant autoantibodies in patients affected by vasculitis, but other autoantibodies may also occur, probably reflecting pathogenetic events in affected tissue. These autoantibodies are assumed to play a role in the initiation and propagation of chronic inflammation. ANCAs are valuable for clinical diagnosis, follow-up, and guidance in therapy. PMID:20688245
Wiik, Allan S
It is essential to be aware of both neoplastic and paraneoplastic vasculitides, vasculopathy, and hypercoagulability, considering the importance of an accurate diagnosis and timely treatment of the underlying malignancy. Characteristics such as the type of vasculitis, age, gender, atypical presentation, and lack of response to common therapies should prompt investigation for an occult malignancy, whereas vasculitis such as GPA require due malignancy vigilance given a significantly increased risk of malignancy at the time of diagnosis and in the following years. Vasculopathies are rarer than vasculitides, but are associated with specific malignancies and, in the context of such malignancies, should be kept in mind. Hypercoagulability is a well-documented neoplastic phenomenon with an increased risk of thrombosis in the setting of positive aPLs. Most neoplastic and paraneoplastic vascular syndromes require no specific treatment outside of treatment of the underlying malignancy. The two key exceptions are PACNS, because of its poor prognosis, and erythromelalgia, in which aspirin is an effective agent. PMID:22075199
Park, Hyon Ju; Ranganathan, Prabha
The aim of this study is to describe the childhood vasculitis hospital burden in Spain (1997-2011), considering type of disease, hospitalization rates and time trends. Data were obtained from the National Discharges Basic Minimum Data Set (National Patient Data Base). Inpatient events of children younger than 15 years of age were analyzed. Principal diagnosis of vasculitis were selected according Ninth Revision of the International Classification of Diseases: Takayasu arteritis, Polyarteritis nodosa, Kawasaki disease, Wegener`s granulomatosis, Churg-Strauss syndrome, and Henoch-Schönlein purpura. A total of 14518 children hospitalizations related to vasculitis were identified in Spain from 1997 to 2011. The average hospitalization rate for children was 13.33±1.71 per 100,000. Henoch-Schönlein purpura and Kawasaki disease were the most common type of vasculitis, hospitalization rates were 11.00 and 3.97 per 100,000 children, respectively. Other vasculitis hospitalizations are much rare in childhood. Average length of stay was 6.04 days and estimated cost per inpatient hospital care was 2,847€. Hospital case fatality rate was 0.05% for overall vasculitis. In conclusion, epidemiological data of childhood vasculitis are useful both to health decision-making and to identify research priorities. PMID:24940860
Villaverde-Hueso, A; Alonso, V; Morales-Piga, A; Hens-Pérez, M; Abaitua, I; Posada-de-la-Paz, M
Acute multifocal posterior placoid pigment epitheliopathy (APMPPE) is an unusual self-limited retinal disorder that has been associated with various systemic complications. To our knowledge, three prior cases associated with cerebral vasculitis have been described. This article describes a patient with APMPPE and angiographically documented cerebral vasculitis who was notable because of (a) the presence of two different cerebral ischemic events, occurring 1 month apart, and (b) the long latency (3 months) between the onset of ocular symptoms and the second cerebral ischemic event. Recognition of the association between APMPPE and cerebral vasculitis may permit early treatment of CNS involvement and prevention of morbidity. PMID:2971684
Weinstein, J M; Bresnick, G H; Bell, C L; Roschmann, R A; Brooks, B R; Strother, C M
Dermatomyositis of childhood onset is characterized by vasculitic lesions and often complicated by calcinosis. We describe 32 patients with juvenile dermatomyositis. All suffered from vasculitic skin changes like facial erythema often with edema, Gottron's sign, telangiectasias, erythematous eruptions, different rashes and necrotic ulcerations. Vasculitis appeared also in inner organs as gastrointestinal ulceration, neurologic and cardiac manifestation. 4 children complained of Raynaud's phenomenon. Calcinosis of soft tissues developed in 21 patients within 0.5 to 10 years after onset. In 6 of them we saw regression of calcium deposits after a progressive phase of 1 to 5 years. Functional outcome in juvenile dermatomyositis depends mainly on the degree of calcinosis together with shortening of diseased muscles. PMID:1845413
Truckenbrodt, H; Häfner, R
TNF-? is a pleiotropic cytokine, which plays a major role in the pathogenesis of numerous autoimmune and/or inflammatory systemic diseases. Systemic vasculitis constitutes a group of rare diseases, characterized by inflammation of the arterial or venous vessel wall, causing stenosis and thrombosis. Treatment of the different type of vasculitis mainly relies on steroids and immunosuppressive drugs. In case of refractory or relapsing diseases, however, a second line of treatment may be required. Anti-TNF-? drugs have been used in this setting during the last 15 years with inconsistent results. We reviewed herein the use of anti-TNF-? therapy in different kind of vasculitis and concluded that, except for Behcet's disease, this therapeutic option has not demonstrated significant improvement in the treatment of vasculitis.
BackgroundTuberculous cerebral vasculitis is a complication of tuberculous meningitis. This study was undertaken to determine the epidemiological characteristics, context, diagnostic means and outcomes under treatment of tuberculous cerebral vasculitides.
Nicolas Javaud; Rita Da Silva Certal; Jérôme Stirnemann; Anne-Sophie Morin; Jean-Marie Chamouard; Alexandre Augier; Olivier Bouchaud; Antoine Carpentier; Robin Dhote; Jean-Luc Dumas; Bruno Fantin; Olivier Fain
23 patients with rheumatoid arthritis and high rheumatic factors (mean titres of rheumatic factors 1 : 1 434) within a prospective study on the diagnostic and prognostic significance of the rheumatoid vasculitis which was performed together with the Research Institute for Rheumatism Moscow underwent examinations for the proof of an extraarticular organ manifestation. In correspondence with the data in literature we found rheumatic nodes (70%) as most frequent extraarticular organ manifestation. In 1 patient each a participation of the lungs and a rheumatic exudate of the pleura, respectively, could be diagnosed. In another patient there were references to a vasculitis at the fundus of the eye. In only 2 patients there was a vasculitis of the digital arteries with necroses, in one of them a generalized vasculitis. 5 of the 13 neurologically examined patients showed polyneuropathic symptoms. Of the biochemical findings the C-reactive protein and the blood sedimentation rate showed clear increases and correlations. PMID:6730586
Häntzschel, H; Otto, W; Nasonova, V; Alekberova, Z; Reinelt, D; Berger, H D; Seidel, W; Brehme, M; Krause, T; Lössner, J
Diffuse alveolar hemorrhage is a clinical syndrome that can be a manifestation of multiple different causes. Identification of the underlying etiology is of utmost importance and dictates treatment. Pulmonary vasculitis including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of diffuse alveolar hemorrhage. For AAV, treatment includes induction followed by maintenance therapy. Rituximab has an increasing role in the treatment of AAV. PMID:23102067
Krause, Megan L; Cartin-Ceba, Rodrigo; Specks, Ulrich; Peikert, Tobias
Skin vasculitis may be associated with infections and autoimmune diseases. Furthermore, vasculitis may appear as a paraneoplastic\\u000a symptom. A 19-year-old male patient was examined with swollen joints and papules presented on lower extremitis. Laboratory\\u000a results showed high erythrocyte sedimentation ratio, positive C reactive protein, increased number of leukocytes and high\\u000a circulating immune complex level. Histopatology of skin biopsy specimen proved
Zsófia Simon; Tünde Tarr; László Tóth; Gabriella Sz?cs; Árpád Illés
A 10-year-old girl with acute-onset hemichorea had multiple areas of abnormal signal seen on magnetic resonance imaging of the brain, associated with middle and anterior cerebral artery vasculitis seen on cerebral angiography. Her serology and clinical course were supportive of the diagnosis of Sydenham's chorea. Other causes of cerebral vasculitis were excluded. Follow-up studies revealed resolution of changes seen on
Monique M. Ryan; Jayne H. Antony
This review focuses on vasculitides with prominent pulmonary manifestations and discusses key contributions from the recent\\u000a literature. Pulmonary vasculitis should be considered when clinical findings include alveolar hemorrhage, nodular and cavitary\\u000a lung disease, airway stenosis, pulmonary artery aneurysms, or pulmonary artery stenosis. The differential diagnostic considerations\\u000a for common clinical presentations of vasculitis in the lung are important, and several recent
Jennifer Ramsey; Mohammed Amari; Stephen P. Kantrow
Chronic periaortitis (CP) is usually accompanied by at least mild manifestations of systemic autoimmunity; however, skin manifestations are rare. Here, we report an 82-year-old woman presenting with a pruritic annular eosinophilic dermatosis that led to the diagnosis of recurrent cutaneous eosinophilic vasculitis (RCEV) coexisting with a latent CP. The present paper is reminder that a CP should be included as a potential differential diagnosis in the elaboration of patients with cutaneous vasculitis that is suspicious of underlying autoimmunity.
Kiorpelidou, Despoina; Gaitanis, Georgios; Zioga, Aikaterini; Tsili, Athina C.; Bassukas, Ioannis D.
Vasculitis affecting the peripheral nerves predominantly manifests as subacute, progressive, asymmetric sensorimotor polyneuropathy or mononeuritis multiplex, and more rarely as painful mononeuropathy, pure sensory neuropathy, neuropathy of the cranial nerves, plexopathy, or as autonomic neuropathy. Vasculitic neuropathy may occur isolated or non-isolated (systemic) together with involvement of other organs. Systemic vasculitis with involvement of the peripheral nerves is further subdivided into primary (Takayasu syndrome, giant cell arteritis, classical panarteritis nodosa, thrombangitis obliterans, Kawasaki disease, Churg-Strauss syndrome, Wegener granulomatosis, cryoglobulinemic vasculitis, Behcet disease, microscopic polyangitis, Schoenlein Henoch purpura) or secondary systemic vasculitis (autoimmune connective tissue diseases, vasculitis from infection, sarcoidosis, malignancy, drugs, radiation, or diabetes). In addition to routine laboratory investigations and nerve conduction studies, nerve biopsy is essential for diagnosing the condition and to delineate it from differentials, although its sensitivity is only approximately 60%. Therapy of non-viral vasculitic neuropathy is based on corticosteroids and cyclophosphamide alone or in combination. Additional options include azathioprine, methotrexate, mycophenolate mofetil, or rituximab. In single cases immunoglobulins, immunoadsorbtion, or plasma exchange have been successfully applied. In case of virus-associated vasculitis interferon-alpha plus lamivudine or ribaverin may be beneficial. PMID:19681441
Background Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis. Methods The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis. Results We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only. Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy. Conclusion Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis.
In the Brown-Norway rat, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by high IgE levels. There is widespread necrotizing leukocytoclastic vasculitis involving lung, skin, mucous membranes, pancreas, liver, and gut, with tissue injury being most marked in the cecum. As in systemic vasculitis in man, there are neutrophils at the site of tissue injury and the animals develop anti-neutrophil cytoplasmic antibodies, which in the Brown-Norway rat are directed against myeloperoxidase. To determine whether neutrophils are involved in the pathogenesis of the vasculitis, we have used a monoclonal antibody that was reported to deplete neutrophils in other rat strains. Rats treated with HgCl2 received antibody by intravenous injection at various time points. Serial blood samples were taken for neutrophil counts and to assay for anti-myeloperoxidase and IgE antibodies. The guts of animals killed after antibody therapy were scored for vasculitic changes and neutrophils infiltrate. RP3 (but not the control antibody MAC6) was shown to bind to Brown-Norway rat neutrophils and to block glycogen-induced influx of neutrophils into the peritoneum. When given at peak disease, RP3 caused a dose-dependent reduction in tissue injury with a marked reduction in circulating blood neutrophil numbers and in tissue neutrophil infiltrate. RP3 treatment did not affect the rise in titer of IgE and anti-myeloperoxidase antibodies. The data presented demonstrate that in this model neutrophils are necessary for the induction of vasculitis and that the degree of vasculitis correlates with neutrophil number. To our knowledge, this study is the first to provide direct evidence for a role for neutrophils in vasculitis. We suggest that antibodies directed against neutrophils, especially if they deplete neutrophils, may be useful in the therapy of vasculitis in man. Images Figure 4
Qasim, F. J.; Mathieson, P. W.; Sendo, F.; Thiru, S.; Oliveira, D. B.
Autoimmune disease such as systemic lupus erythematosus or rheumatoid arthritis are connected with higher risk of atherosclerosis and cardiovascular complications and mortality. This results from inflammatory damage to the vessel wall by vasculitis. The aim of the present study was to evaluate whether patients with Wegener's granulomatosis (WG) and pulmonary involvement have an increased prevalence of atherosclerotic disease as characterized traditional risk factors. Twenty one patients with WG in remission and 15 control subject were entered to the study. Traditional risk factor for cardiovascular disease such as hyperglycemia, hypertension, smoking, obesity, and dyslipidemia were assessed. Both systolic and diastolic blood pressure were higher in WG patients (p<0.025). Total cholesterol, LDL and TG levels were markedly elevated in 18 of the 21 in pulmonary WG patients. Compared with controls, plasma levels of hsCRP were raised in WG patients; 3.68 (0.79-9.75) mg/l vs. 0.14 (0.12-0.59) mg/l (p<0.01). We conclude that non-pharmacological and pharmacological treatments of traditional risk factors are crucial to prevent cardiovascular disease in WG patients and thus should be part of therapy to control WG activity and damage caused by it. PMID:22826078
Zycinska, K; Wardyn, K; Zielonka, T M; Nitsch-Osuch, A; Smolarczyk, R; Zarzycki, S; Demkow, U; Lukas, W; Pirogowicz, I
Mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS) is a mitochondrial genetic disorder caused by a point mutation, resulting in the substitution of guanine for adenine at nucleotide 3243 (A3243G). It is a multisystem disorder with variable manifestations and typically presents between the first and third decades of life. It should be suspected if a patient exhibits stroke-like episodes before age 40, encephalopathy characterized by seizures, dementia, or both, and lactic acidosis, ragged-red fibers in muscle, or both. We present the case of a 26-year-old white man suspected with primary central nervous system vasculitis admitted to our facility with profound constipation from severe intestinal dysmotility. Although his gastrointestinal and neurologic symptoms did not meet criteria for a specific vasculitic syndrome, his symptoms and blood test abnormalities were concerning for such a process. MELAS was included in our differential diagnosis because his symptoms failed to fit a defined vasculitic process. When genetic testing documented the presence of the point mutation A3243G, his diagnosis was changed. This case illustrates the importance of considering a mitochondrial genetic disorder in the differential diagnosis of patients who present to Rheumatologists with suspected unusual or atypical vasculitic symptoms. PMID:18176143
Carroll, Matthew B
OBJECTIVETo study immunological markers and compare these markers with standard measures for the clinical and immunological follow up of vasculitis activity in hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV).METHODSSerial serum samples from eight patients with newly diagnosed HCV associated CV were followed during interferon ? treatment induced remission of the CV. Vasculitis activity and disease extent were evaluated with
P Lamprecht; F Moosig; A Gause; K Herlyn; E Csernok; H Hansen; W L Gross
BACKGROUND AND PURPOSE: MR findings in CNS vasculitis and their correlation with angiography have not been clearly defined. We therefore explored three hypotheses regarding CNS vasculitis associated with autoimmune disease: 1) MR imaging is highly sensitive; 2) a typical MR appearance exists; and, 3) MR and angiographic findings correlate well. METHODS: We studied 18 patients with CNS vasculitis associated with
Martin G. Pomper; Timothy J. Miller; John H. Stone; William C. Tidmore; David B. Hellmann
Purpose: To determine if a molecular imaging approach targeting the highly oxidative enzyme myeloperoxidase (MPO) can help noninvasively identify and confirm sites of vascular wall inflammation in a murine model of vasculitis. Materials and Methods: Animal experiments were approved by the institutional animal care committee. Twenty-six mice were studied, including eight MPO-deficient and six sham-operated mice as controls. Vasculitis was induced with intraperitoneal injection of Candida albicans water-soluble fraction (CAWS). Aortic root magnetic resonance imaging was performed after intravenous injection of the activatable MPO sensor (bis-5-hydroxytryptamide-diethylenetriaminepentatacetate gadolinium) (n = 23), referred to as MPO-Gd, or gadopentetate dimeglumine (n = 10). Seven mice were randomly assigned to receive either MPO-Gd or gadopentetate dimeglumine first. Aortic root specimens were collected for biochemical and histopathologic analyses to validate imaging findings. Statistical significance was calculated for contrast-to-noise ratios (CNRs) by using the paired t test. Results: In the aortic root, the mean MPO-Gd CNRs after agent injection (CNR = 28.1) were more than 2.5-fold higher than those of sham-operated mice imaged with MPO-Gd and vasculitis mice imaged with gadopentetate dimeglumine (CNR = 10.6) (P < .05). MPO-Gd MR imaging helped identify areas of vasculitis that were not seen at unenhanced and contrast material–enhanced imaging with gadopentetate dimeglumine. Histopathologic and biochemical analyses for MPO and myeloid cells confirmed imaging findings. In MPO-deficient mice, injection of CAWS did not result in a vasculitis phenotype, implying a key role of the imaging target in disease cause. Conclusion: Molecular imaging targeting MPO can be a useful biomarker to noninvasively detect and confirm inflammation in vasculitis by using a murine model of Kawasaki disease. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110040/-/DC1
Su, Henry S.; Nahrendorf, Matthias; Panizzi, Peter; Breckwoldt, Michael O.; Rodriguez, Elisenda; Iwamoto, Yoshiko; Aikawa, Elena; Weissleder, Ralph
Although, erythema nodosum is a common skin manifestation associated with syphilis, nodular vasculitis is a rare feature. Here, we describe a case of a 22-year-old, human immunedeficiency virus negative, non-immunocompromised man who developed recurrent oral and scrotal ulcers with nodular lesions of the lower extremitie. Behçet's disease was initially suspected, however, his serologic test for syphilis was positive, and he was thus diagnosed with secondary syphilis, with a skin biopsy showing nodular vasculitis. The patient was treated with benzathine penicillin, and the skin lesions disappeared after treatment.
Jo, Jaemin; Kim, Jae Wang; Kim, Jinseok; Yu, Jung Re
A 24-year-old Caucasian female presented with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and associated infiltration round some of the larger choroidal blood vessels. This infiltration dissipated as the patient's clinical condition improved and did not induce any permanent alteration of the overlying retinal pigment epithelium. We suggest that the infiltration round the choroidal vessels was due to a choroidal vasculitis. The finding of choroidal inflammation in this case lends support to the hypothesis that choroidal vasculitis is an underlying pathological process in APMPPE. Images
Spaide, R. F.; Yannuzzi, L. A.; Slakter, J.
A 24-year-old Caucasian female presented with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and associated infiltration round some of the larger choroidal blood vessels. This infiltration dissipated as the patient's clinical condition improved and did not induce any permanent alteration of the overlying retinal pigment epithelium. We suggest that the infiltration round the choroidal vessels was due to a choroidal vasculitis. The finding of choroidal inflammation in this case lends support to the hypothesis that choroidal vasculitis is an underlying pathological process in APMPPE. PMID:1793461
Spaide, R F; Yannuzzi, L A; Slakter, J
Treatment with antithyroid drugs may be accompanied by side effects. We present a patient diagnosed with Grave's Disease who developed extensive vasculitis in the lower limbs during methimazole use. After suspension of the methimazole and the introduction of prednisone in immunesupressor doses the cutaneous lesions started to involute. PMID:23739718
Ribeiro, Carla de Oliveira; Magrin, Paula Ferrazzi; Vilar, Enoí Aparecida Guedes; Durães, Sandra Maria Barbosa; Estrella, Rogério Ribeiro
We report a rare case of lobular panniculitis with small vessel vasculitis, presenting with fever, cutaneous lesions, and systemic manifestations involving the visceral fat and associated with ulcerative colitis. The patient was treated with cyclophosphamide and prednisolone, which successfully cured the systemic disease, with resolution of the inflammatory infiltrates. PMID:21336974
Beccastrini, Enrico; Emmi, Giacomo; Squatrito, Danilo; Nesi, Gabriella; Almerigogna, Fabio; Emmi, Lorenzo
Systemic vasculitis is an uncommon manifestation of X-linked lymphoproliferative disease (XLP), a disorder in which there is a selective immune deficiency to Epstein-Barr virus (EBV). The molecular basis for XLP has recently been ascribed to mutations within SLAM-associated protein (SAP), an SH2 domain-containing protein expressed primarily in T cells. The authors describe a patient who died as a result of chronic systemic vasculitis and fulfilled clinical criteria for the diagnosis of XLP. Sequencing of this patient's SAP gene uncovered a novel point mutation affecting the SH2 domain. The patient presented with virus-associated hemophagocytic syndrome (VAHS) and later had chorioretinitis, bronchiectasis, and hypogammaglobulinemia develop. He further developed mononeuritis and fatal respiratory failure. Evidence of widespread small and medium vessel vasculitis was noted at autopsy with involvement of retinal, cerebral, and coronary arteries as well as the segmental vessels of the kidneys, testes, and pancreas. Immunohistochemical analysis using antibodies to CD20, CD45RO, and CD8 revealed that the vessel wall infiltrates consisted primarily of CD8(+) T cells, implying a cytotoxic T-lymphocyte response to antigen. EBV DNA was detected by polymerase chain reaction (PCR) in arterial wall tissue microdissected from infiltrated vessels further suggesting that the CD8(+) T cells were targeting EBV antigens within the endothelium. The authors propose that functional inactivation of the SAP protein can impair the immunologic response to EBV, resulting in systemic vasculitis. PMID:11133747
Dutz, J P; Benoit, L; Wang, X; Demetrick, D J; Junker, A; de Sa, D; Tan, R
We have previously shown that microvascular smooth muscle activates CD4+ T lymphocytes in sterile co-culture, presents antigen, and produces inflammatory cytokines. Adoptive transfer of lymphocytes co-cultured with syngeneic smooth muscle cells to healthy recipient mice results in vasculitic lesions predominantly in postcapillary venules. The present study assessed the pathogenic role of immunoglobulin and B cells in a murine model of vasculitis. Here, we show that transferred B cells, including plasmablast cells, accumulated, persisted, and proliferated in lung and secondary lymphoid organs of recipient mice. The induction of vasculitis was accompanied by production of IgM and IgG2a autoantibodies specific for vascular smooth muscle intracellular antigens. Circulating immunoglobulin had a pathogenic role in this vasculitis model, because the disease could be induced by transfer of serum from vasculitic mice to untreated animals but not by transfer of serum depleted of anti-smooth muscle autoantibodies. Additionally, the pathogenic mechanisms triggered by the transfer of vasculitogenic serum were dependent on T lymphocytes because both wild-type and B cell-deficient mice developed the disease after serum transfer, whereas RAG2-deficient mice did not. Thus, immunoglobulin and cell-mediated pathways work in concert to produce vasculitis in this model.
Baiu, Dana Carina; Barger, Brittany; Sandor, Matyas; Fabry, Zsuzsa; Hart, Michael Noel
The conduct of randomized controlled trials for vasculitis, especially for the antineutrophil cytoplasmic antibody-associated vasculitides [AAV, granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis], has been greatly advanced by the development, use, and acceptance of validated outcome measures. Trials have subsequently provided the opportunity to validate and refine reliable, valid outcome measures for these multisystemic and relapsing rare diseases. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group was formed in 2004 to foster development of validated and widely accepted outcomes in vasculitis using data-driven analyses, a dedication to building consensus, and adherence to, and guidance by, the principles of the OMERACT approach. This work led to the endorsement by OMERACT of the core set of domains and associated outcome measures for AAV. Next steps for the study of existing outcome tools in AAV include better definition of response criteria through development of more data-driven weighting of the elements of activity and damage assessment. The Working Group is now also embarking on a series of linked projects to develop validated patient-reported outcomes for use in clinical research in vasculitis. Additionally, the Working Group is studying how current methods of disease assessment and plans for new outcomes can be informed by the conceptual framework of the International Classification of Function of the World Health Organization. The success of the Group's work in AAV has also led to a formal process for developing outcomes for the large vessel vasculitides (Takayasu arteritis and giant cell arteritis) and Behçet disease. PMID:24429177
Merkel, Peter A; Aydin, Sibel Z; Boers, Maarten; Cornell, Christina; Direskeneli, Haner; Gebhart, Don; Hatemi, Gulen; Luqmani, Raashid; Matteson, Eric L; Milman, Nataliya; Robson, Joanna; Seo, Philip; Tomasson, Gunnar
Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, considerable progress has been made refining immunosuppressive regimens with a focus on minimising toxicity. There is, however, a high unmet need in the treatment of AAV. A proportion of patients are refractory to current therapies; 50% experience a relapse within 5 years and treatment toxicity contributes to mortality and chronic disability. As knowledge of the pathogenesis of vasculitis grows, it is mirrored by the availability of biological agents, which herald a revolution in the treatment of vasculitis. Lymphocyte-targeted and cytokine-targeted agents have been evaluated for the treatment of AAV and are entering the routine therapeutic arena with the potential to improve patient outcomes. As rare diseases, treatment advances in vasculitis depend on international collaborative research networks both to establish an evidence base for newer agents and to develop recommendations for patient management.
Objectives. Current measures of damage in vasculitis do not account for the possibility that some forms of damage may exert greater impact than others. As part of an international effort to revise how damage is quantified in vasculitis clinical research, an exercise was performed to measure expert ratings of damage items. Methods. Members of the Vasculitis Clinical Research Consortium and European Vasculitis Study Group were given a list of 129 items of damage related to WG and microscopic polyangiitis (MPA). Participants were asked to rate each item of damage on an integer scale from 0 to 10, where 10 represented the most severe form of damage and 0 indicated ‘no impact’. Results. A multidisciplinary panel of 50 investigators from North America, Europe and Australia–New Zealand participated. The highest median ratings (8–10) were assigned to items of damage associated with malignancy, tissue ischaemia, the central nervous system and cardiopulmonary manifestations. The mean scores ranged from 1.3 to 9.5. The highest s.d.s (?2.5) were associated with forms of damage that may benefit from surgical intervention or may not be causally associated with WG or MPA. Lower scores were assigned by nephrologists in comparison with rheumatologists and by Americans in comparison to Europeans, although the difference in median ranks used by these groups was not statistically significant (P > 0.05 for the comparisons). Conclusions. This exercise represents an important step in the development of a weighting system that may increase the utility of damage index scores for the assessment of patients with vasculitis.
Jayne, David; Luqmani, Raashid; Merkel, Peter A.
Introduction Vasculitis has been associated with malignancies, more commonly hematological rather than solid malignancies. Due to the rarity of these conditions and the lack of a temporal association, the relationship between vasculitis and malignancy remains unclear. Paraneoplastic vasculitis as a phenomenon of lung cancer has been described in the literature. To the best of our knowledge, this is the first case report of leukocytoclastic vasculitis being an initial presentation of malignant pleural mesothelioma. Case presentation We report the case of an 84-year old Greek man who presented to our facility with an erythematous, pruritic and purpuric rash affecting his limbs. This was biopsy-proven to be leukocytoclastic vasculitis and treated conservatively with topical corticosteroids as well as oral prednisolone, with good results. Six months later, he was diagnosed as having malignant pleural mesothelioma. As he remained asymptomatic from his malignancy, no systemic chemotherapy was instituted. He had a recurrence of biopsy-proven leukocytoclastic vasculitis two months after he was diagnosed as having mesothelioma, which again settled with conservative measures. Conclusions It is important to remain vigilant with regard to the association between leukocytoclastic vasculitis and malignancies. A diagnosis of vasculitis requires a search for malignancies as well as other possible etiologies. This is particularly of relevance when the vasculitis becomes chronic, recurrent or treatment is no longer effective. Should our patient have experienced refractory vasculitis, we would have instituted systemic chemotherapy to treat the underlying malignancy.
Angiitis of the central nervous system (CNS) remains a poorly understood and clinically challenging form of vascular inflammatory disease. Primary angiitis of the CNS (PACNS) has been viewed as a relentless and uniformly fatal disorder if untreated. In addition, recent trends have demonstrated an increasing reliance on angiographic diagnosis without tissue confirmation. It has been suggested that PACNS is clinically more heterogeneous than previously appreciated and may include relatively benign subsets. A reappraisal of diagnostic approaches has suggested caution in the diagnosis of CNS angiitis on purely angiographic grounds. Secondary vasculitis of the CNS is even more heterogeneous. Clinicians involved in the evaluation of patients with presumed CNS vasculitis need to be aware of the clinical spectrum of vascular inflammatory disease within the CNS as well as the strengths and limitations of currently available diagnostic modalities. PMID:7718420
Calabrese, L H; Duna, G F
The median arcuate ligament syndrome is an uncommon condition characterized by the triad of postprandial abdominal pain, unintentional weight loss, and an epigastric bruit. This condition is diagnostically challenging and patients often undergo extensive laboratory, radiographic, and invasive evaluations before it is identified. Physicians should consider this syndrome in the differential diagnoses of chronic abdominal pain and mesenteric vasculitis. Once diagnosed, treatment is generally surgical with known predictors of favorable and unfavorable outcomes. Surgical candidates should be selected carefully. We describe the cases of two young active duty patients diagnosed with median arcuate ligament syndrome after suffering from chronic abdominal pain. Both were referred to our rheumatology department to evaluate for mesenteric vasculitis. Each had a different therapeutic outcome. PMID:23929065
Kay, Johnson C; Arroyo, Ramon A
An international meeting, The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012, was held on March 28-31, 2012 at Shinagawa, Tokyo, Japan. The meeting focused on vasculitis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the Asia-Pacific area. This was a high-profile event and attracted scientists and physicians from around the world, all of whom are committed to the care of patients with vasculitis, ANCA and related diseases. The Asia Pacific international meeting was able to extend insights into Kawasaki disease, Takayasu arteritis, and myeloperoxidase ANCA-associated vasculitis. The program addressed the multidisciplinary nature of vasculitis, including genomics, genetics, pathogenesis, epidemiology, biomarkers, clinical features, and therapeutic trials. PMID:23615782
The central nervous system (CNS) may be involved by a variety of inflammatory diseases of blood vessels. These include primary angiitis of the central nervous system (PACNS), a rare disorder specifically targeting the CNS vasculature, and the systemic vasculitides which may affect the CNS among other organs and systems. Both situations are severe and convey a guarded prognosis. PACNS usually presents with headache and cognitive impairment. Focal symptoms are infrequent at disease onset but are common in more advanced stages. The diagnosis of PACNS is difficult because, although magnetic resonance imaging is almost invariably abnormal, findings are non specific. Angiography has limited sensitivity and specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis when disclosing blood vessel inflammation and are also useful to exclude other conditions presenting with similar findings. However, since lesions are segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS involvement by systemic vasculitis occurs in less than one fifth of patients but may be devastating. A prompt recognition and aggressive treatment is crucial to avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are recommended for patients with PACNS and for patients with secondary CNS involvement by small-medium-sized systemic vasculitis. CNS involvement in large-vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell arteritis) or glucocorticoids and immunosuppressive agents (Takayasu’s disease). However, in large vessel vasculitis, where CNS symptoms are usually due to involvement of extracranial arteries (Takayasu’s disease) or proximal portions of intracranial arteries (giant-cell arteritis), revascularization procedures may also have an important role.
Alba, Marco A; Espigol-Frigole, Georgina; Prieto-Gonzalez, Sergio; Tavera-Bahillo, Itziar; Garcia-Martinez, Ana; Butjosa, Montserrat; Hernandez-Rodriguez, Jose; Cid, Maria C
PURPOSE: To describe two cases of retinal vasculitis shortly after the initiation of ticlopidine hydrochloride (Ticlid, Roche, Kingsland St, NJ) therapy.METHODS: Case reports of two patients. The first patient was a 43-year-old white woman complaining of spots, floaters, and flashes of lights in both eyes 3 weeks after the initiation of treatment with ticlopidine hydrochloride. The second patient was a
Adiel Barak; Lawrence S Morse; Ivan R Schwab
Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a common autoimmune disease in China. AAVs in the majority of Chinese patients are microscopic polyangiitis with antigenicity to myeloperoxidase. Propylthiouracil is the leading cause of drug-induced AAV. The genetic background and immunological characteristics of ANCA, such as the epitope, IgG subclass and avidity, might contribute to various clinical phenotypes of AAV. PMID:23180038
Xu, Peng-cheng; Chen, Min; Zhao, Ming-hui
The cause of the majority of childhood vasculitides is unknown although it is likely that a complex interaction between environmental\\u000a factors and inherited host responses trigger the disease and determine the vasculitis phenotype. Epidemiological clues continue\\u000a to implicate infectious triggers in Kawasaki syndrome (KS) and Henoch Sch?nlein purpura (HSP). Several genetic polymorphisms\\u000a have now been described in KS and HSP
Paul A. Brogan
Summary Leukocytoclastic vasculitis is the dominant lesion of mixed cryoglobulinemia (MC). The high prevalence of antibodies to hepatitis\\u000a C virus (HCV) in association with the higher concentration of HCV RNA genomic sequences in the cryoglobulins suggests a close\\u000a relationship between MC and HCV infection and strongly supports the view that this virus plays a key role in causing vascular\\u000a damage. Analysis
Franco Dammacco; Domenico Sansonno
Ulcerative colitis may be associated with a number of skin lesions such as erythema nodosum and pyoderma gangrenosum. We here describe an unusual case of a 33-year-old-caucasian male with ulcerative colitis and skin lesions diagnosed as leukocytoclastic vasculitis. An initial treatment with oral deflazacort led to little benefit, while treatment with oral mesalazine caused remission of the skin and intestinal manifestations in 2 weeks. PMID:18799375
Tripodi Cutrì, F; Salerno, R; Lo Schiavo, A; Gravina, A G; Romano, M; Ruocco, E
The diagnostic value of c-ANCA as a specific marker of systemic vasculitis (particularly Wegener's granulomatosis) is well established. The prognostic value of c-ANCA for determining disease activity is controversial. We have prospectively studied in ten patients with systemic vasculitis over a mean period of 34 months (extreme 2-61 months). All patients had c-ANCA at the moment of the diagnosis: four patients had high titer of c-ANCA all over the period study; three clinical and biological exacerbations of the disease was observed without variation of the c-ANCA titer. In four patients c-ANCA disappeared within 6 months after the beginning of the treatment correlated with disease activity. Sometimes a rise of c-ANCA titer was observed with or without disease activity. In one case c-ANCA titer had a serrated evolution. The sensitivity and the specificity of the c-ANCA for disease activity in the ten studied patients were respectively 1 and 0.28. In patients with systemic vasculitis and c-ANCA at the time of the diagnosis, variation in c-ANCA titer alone is of limited prognostic value for predicting disease course. PMID:7914710
Hachulla, E; Hatron, P Y; Brouillard, M; Cesbron, J Y; Reumaux, D; Devulder, B
Viral vasculitides have been previously reported in the literature, the role of infections in their pathogenesis ranging from direct cause to trigger event. Here we report the case of a 3-year-old immunocompetent girl who developed a systemic vasculitis leading to ileal perforation, mimicking a full blown picture of Henoch-Schönlein purpura. High dosage steroid treatment was started, with good response. The anatomopathological examination of the resected gastrointestinal tract showed features of necrotising vasculitis and cytomegalovirus (CMV)-related inclusion bodies in the endothelial cells, with direct correlation to vascular damage. The causative role of viral infection was revealed by the presence of CMV DNA in patient's blood and positive IgG titer against the virus. Steroid therapy was then tapered: the patient achieved clinical remission, which still persists after a six-months follow-up. Our report suggests that CMV vasculitis is probably more frequent than previously thought, even in immunocompetent patients, with a protean clinical presentation, mimicking other types of vasculitides. PMID:24854375
D'Alessandro, Matteo; Buoncompagni, Antonella; Minoia, Francesca; Coccia, Maria C; Martini, Alberto; Picco, Paolo
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small-to-medium-sized blood vessel vasculitis and the presence of ANCA. Although our understanding of the causes of AAV remains limited, new information supporting an autoimmune basis is emerging. This review highlights recent progresses in etiology, pathogenesis, classification, and treatment. A genome-wide association study has confirmed a role for genetic susceptibility in AAV, and links between environmental factors and AAV induction through abnormal neutrophil extracellular traps has been demonstrated. Ongoing international consensus initiatives have revised approaches to the classification of vasculitis that has been enhanced by the analysis of large-scale prospective clinical data sets. New autoantibodies to human lysosome-associated membrane protein-2 antibody, moesin, and plasminogen have been detected in AAV sera and a prognostic classification of renal biopsies developed. Clinical trial networks have extended the evidence base for the treatment of AAV, and rituximab has emerged as an alternative to cyclophosphamide for remission induction. Long-term outcomes following current treatment strategies have been determined and increased risks for cardiovascular and malignant disease reported. PMID:23423257
Furuta, Shunsuke; Jayne, David R W
X-linked lymphoproliferative syndrome (XLP) is a rare, often fatal, primary immunodeficiency disease characterized by an abnormal response to Epstein-Barr virus (EBV) infection. The gene responsible for XLP has been identified as SH2D1A/DSHP/SLAM-associated protein (SAP). The major clinical manifestations include fulminant infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia. Affected males uncommonly present with lymphocytic vasculitis in addition to aplastic anemia. In this study, we describe a Japanese XLP patient who presented with hypogammaglobulinemia following acute EBV-induced infectious mononucleosis in the infancy and later had systemic lymphocytic vasculitis and hemophagocytic lymphohistiocytosis in the adulthood, which resolved by steroid pulse therapy. The patient's SAP gene was found to harbor a missense mutation (His8Asp), presumably resulting in defective expression of SAP in T cells. Biopsy specimens of lung and skin disclosed that CD8+ T cells predominantly infiltrated vascular vessels. However, immunohistochemical examination showed that EBV-infected cells were not identifiable in the vessels. We propose that T-cell-mediated immune dysregulation in XLP can cause vasculitis by EBV infection-unrelated mechanism. PMID:15682426
Kanegane, Hirokazu; Ito, Yoshikiyo; Ohshima, Koichi; Shichijo, Takeshi; Tomimasu, Kunio; Nomura, Keiko; Futatani, Takeshi; Sumazaki, Ryo; Miyawaki, Toshio
Whereas systemic vasculitis is the most common form of vasculitis, vasculitis restricted to a single organ system is rare. Primary vasculitis restricted to striated skeletal muscle has been described in few case reports for polyarteritis nodosa and leucocytoclastic vasculitis, but not for small vessel vasculitis, type microscopic polyangiitis. The authors describe three patients with primary small vessel vasculitis of the skeletal muscle without evidence of other major organ involvement. All three patients presented with myalgias and highly elevated acute phase reactants while muscle weakness and elevated creatine kinase levels were not consistently present. Diagnoses were established by muscle biopsy and extensive search for potential causes of secondary vasculitis. Complete remission could be accomplished by steroids alone in only one case, while additional immunosuppressants were needed in the other two cases. Primary small vessel vasculitis of the skeletal muscle should be considered in patients presenting with myalgia and signs of systemic inflammation in the absence of other organ manifestations. Once diagnosed, aggressive systemic immunosuppression is appropriate.
Benz, Nadja; Daikeler, Thomas; Frank, Stephan; Mehling, Matthias; Tyndall, Alan; Trendelenburg, Marten
Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis is one of the rare complications of propylthiouracil treatment. Having a variable clinical spectrum, it may be presented with both skin limited vasculitis and life-threatening systemic vasculitis. In this study, we present a case that developed ANCA-positive vasculitis with skin and kidney involvement (hematuria and proteinuria) six months after propylthiouracil treatment was initiated for toxic nodular goiter. Proteinuria recovered dramatically subsequent to radioactive iodine treatment following ceasing the drug. PMID:23884029
Bes, C; Dikba?, O; Keskin, E; Kaptano?ullar?, Ö; Soy, M
The development of antineutrophil cytoplasmatic antibody (ANCA) during therapy with propylthiouracil (PTU) is not uncommon but occasionally has clinical significance. Risk factors associated with the development of ANCA associated systemic vasculitis when taking PTU have been described. We report and discuss a case with PTU-induced ANCA vasculitis with severe systemic manifestations. PMID:24435037
Silva, Sara Vieira; Ferreira, João Pedro; Carvalho, Sandrine; Seabra, Filipa; Marinho, António
Despite advances in the treatment of vasculitis, modern therapies fail to induce or maintain remission in a significant proportion of patients. Mycophenolic acid is increasingly used to treat vasculitis syndromes. Here, we consider relevant pharmacokinetic and pharmacodynamic properties of mycophenolate, with emphasis on the impact of renal impairment, and we review the existing evidence for and current trials of mycophenolate
Thomas F. Hiemstra; Rachel B. Jones; David R. W. Jayne
ANCA may be a pathogenetic force, but to date, support for this contention remains indirect. Active immunization with antigen or passive transfer of ANCA has not reproduced small vessel vasculitis (SVV). It is more than likely that if ANCA are pathogenetic, they are involved as one of many simultaneously occurring mechanisms acting in concert with other synergistic inflammatory mediators of disease. These include not only environmental factors such as infection or environmental toxins such as silica, but also genetic factors that are only now being described. The paradigm for this autoimmune process must include several events that occur simultaneously or sequentially, including ANCA, leukocyte activation and injured endothelium. Images Fig. 1 Fig. 2
Falk, R. J.
Primary CNS vasculitis (PCNSV) is an uncommon disorder of unknown cause that is restricted to brain and spinal cord. Glucocorticoids alone or in combination with cyclophosphamide achieve a favorable response in most patients.(1,2) However, some patients are intolerant or respond poorly to cyclophosphamide; therefore, there is the need for new treatment options. We report a patient with PCNSV who appeared to respond to treatment with corticosteroids and rituximab. This study was approved by the Mayo Clinic Institutional Review Board and written informed patient consent to perform the study was obtained. PMID:24598711
Salvarani, Carlo; Brown, Robert D; Huston, John; Morris, Jonathan M; Hunder, Gene G
To report a case of triple association of juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis and urticarial vasculitis as well as a review of the relevant literature. A 12-year-old male patient diagnosed with overlap syndrome between SLE and juvenile dermatomyositis since 2004 evolved with erythematous plaques, which were compatible with an urticarial rash. Clinical, laboratory and histopathological findings indicated a diagnosis of urticarial vasculitis. The patient previously had a C1q deficiency. Using the established treatment with methylprednisolone (1 g/day for 3 days), increasing doses of deflazacort and introduction of a dapsone, as well as mycophenolate mofetil regimen, with the suspension of azathioprine resulted in complete resolution of skin lesions. Urticarial vasculitis can present in various diseases. In SLE, presentation of urticarial vasculitis in children is rarely found. The triple association of juvenile-onset SLE, juvenile dermatomyositis and urticarial vasculitis is unusual, and this is the first case described in literature. PMID:20429007
Macêdo, Patrícia A; Garcia, Carolina B; Schmitz, Monique K; Jales, Levi H; Pereira, Rosa M R; Carvalho, Jozélio F
Vasculitis is characterized by a circumferential vessel-wall thickening ('halo'), which can be visualized by modern imaging techniques. In particular, the resolution of ultrasound has increased to 0.1 mm. Ultrasound detects abnormalities that are pathognomonic even in arteries with a diameter below 1 mm. It is particularly helpful in the diagnosis of large-vessel vasculitides, such as classic temporal arteritis, large-vessel giant-cell arteritis (GCA), Takayasu arteritis and idiopathic aortitis. Echocardiography is important for determining cardiac involvement in Takayasu arteritis and also for examining the coronary arteries of children with suspected Kawasaki disease, which is a medium-vessel vasculitis. In small vessel vasculitides ultrasound has only a role for determining the distribution or organ involvement. Fast-track clinics for the diagnosis of GCA help to initiate treatment before complications such as blindness occur; patients receive appointments within 24 h in these clinics. Clinical examination and ultrasound of temporal and axillary arteries are performed by an experienced rheumatologist. In most cases this is able to determine if GCA is present. Temporal artery biopsy can be still carried out in ambivalent cases. The wall swelling of temporal arteries disappears after 2-3 weeks of glucocorticoid treatment. After 3 days of treatment, diagnosis becomes more difficult with ultrasound in some cases. In larger arteries, such as the axillary arteries, wall thickening disappears within months. It tends to be darker (more hypoechoic) in acute disease because of oedema. PMID:24688604
Schmidt, Wolfgang A
Vasculitis is characterized by a circumferential vessel-wall thickening (‘halo’), which can be visualized by modern imaging techniques. In particular, the resolution of ultrasound has increased to 0.1 mm. Ultrasound detects abnormalities that are pathognomonic even in arteries with a diameter below 1 mm. It is particularly helpful in the diagnosis of large-vessel vasculitides, such as classic temporal arteritis, large-vessel giant-cell arteritis (GCA), Takayasu arteritis and idiopathic aortitis. Echocardiography is important for determining cardiac involvement in Takayasu arteritis and also for examining the coronary arteries of children with suspected Kawasaki disease, which is a medium-vessel vasculitis. In small vessel vasculitides ultrasound has only a role for determining the distribution or organ involvement. Fast-track clinics for the diagnosis of GCA help to initiate treatment before complications such as blindness occur; patients receive appointments within 24 h in these clinics. Clinical examination and ultrasound of temporal and axillary arteries are performed by an experienced rheumatologist. In most cases this is able to determine if GCA is present. Temporal artery biopsy can be still carried out in ambivalent cases. The wall swelling of temporal arteries disappears after 2–3 weeks of glucocorticoid treatment. After 3 days of treatment, diagnosis becomes more difficult with ultrasound in some cases. In larger arteries, such as the axillary arteries, wall thickening disappears within months. It tends to be darker (more hypoechoic) in acute disease because of oedema.
Mycobacterium chelonae is a non-tuberculous, rapidly growing mycobacteria and is widely distributed in the natural environment. In the immunocompetent status, localized cutaneous infections such as cellulitis and subcutaneous abscesses commonly occur after traumatic injury. However, disseminated cutaneous infections occur on a background of immunosuppression. Cutaneous M. chelonae infection presents with a variety of skin eruptions. We report a case of disseminated M. chelonae infection mimicking cutaneous vasculitis. The patient was treated with long-term oral corticosteroids and injected etanercept for the treatment of rheumatoid arthritis and asthma. Because the skin eruptions were preceded by asthma and rheumatoid arthritis and the pathological findings showed fibrinoid necrosis around the vascular of dermis, cutaneous vasculitis was first suspected. The culture from the pus revealed the bacterium which grew within 5 days on Ogawa's culture medium suggesting a rapidly growing mycobacteria. This bacterium was identified as M. chelonae by the DNA-DNA hybridization method. We chose 800 mg/day clarithromycin and 500 mg/day levofloxacin as a result of the drug-sensitivity test. After 6 months of the treatment, infection symptoms disappeared. Rapidly growing mycobacteria should be considered in the differential diagnosis of infections in patients under immunosuppression caused by diseases or drugs such as corticosteroids and biologic agents. Repeated bacterial examinations are important and required for the diagnosis of rapidly growing mycobacteria. PMID:24801916
Ichihara, Asako; Jinnin, Masatoshi; Fukushima, Satoshi; Inoue, Yuji; Ihn, Hironobu
Abstract Purpose: To investigate the ocular and systemic manifestations of retinal vasculitis in HLA-B27-positive patients. Methods: Retrospective noncomparative case series of 9 HLA-B27-positive patients with uveitis and retinal vasculitis. Main outcome measures consisted of ocular and angiographic findings and assessment of any additional systemic disorders. Results: Three male and 6 female HLA-B27-positive patients with a median age of 32 years were diagnosed with retinal vasculitis. Concurrent intraocular inflammation was noted in all patients. All patients suffered from extensive vasculitis of the large retinal veins. Five patients developed retinal vasculitis at the onset of uveitis and the remaining 4 exhibited retinal vasculitis 1-15 years after the onset of uveitis. Vascular occlusions occurred in 4 patients and subsequent neovascularizations developed in 3. Three patients were diagnosed with an HLA-B27-associated systemic disease. Conclusion: Retinal vasculitis may develop in the wake of HLA-B27-associated uveitis and might represent a rare manifestation of HLA-B27-associated disease. PMID:24102118
Braakenburg, Arthur Menno; Rothova, Aniki
The idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome is a rare retinal vascular disorder characterized by multiple leaking aneurysmal dilations, retinal vasculitis, neuroretinitis and peripheral vascular ischemia. Visual loss mainly occurs due to the development of retinal neovascularization and/or exudative maculopathy. Although the treatment of choice has not yet been established, retinal photocoagulation seems to be the best option to control the disease and to prevent its progression. Herein, we report a case of idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome with both retinal neovascularization and macular exudation successfully managed with intravitreal ranibizumab (Lucentis®) as adjunctive therapy to retinal photocoagulation.
Marin-Lambies, Cristina; Gallego-Pinazo, Roberto; Salom, David; Navarrete, Javier; Diaz-Llopis, Manuel
A fundamental change in management of antineutrophil cytoplasmic antibody-associated vasculitis in the past 10 years is the early focussed use of aggressive immunosuppression, using regimens comprised of widely available medications. Using a clinical framework to quantify morbidity, we can induce remission in most patients within 3-6 months using glucocorticoids plus methotrexate, cyclophosphamide or rituximab, with additional plasmapheresis when indicated. Difficulty in maintaining remission probably relates to the difference between true pathophysiological remission and the absence of clinical, serological or radiological evidence of disease activity. For surviving patients, the cumulative problems of relapse, burden of disease, or its treatment are coupled with pre-existing diseases or new conditions arising since diagnosis. Initial early control should reduce subsequent damage, but what effect it will have on relapse is not clear. In the absence of a cure, future trials should focus on reducing toxicity and comorbidity as well as controlling disease. PMID:23147895
Angiotropic large cell lymphoma (ALCL), the so-called malignant angioendotheliomatosis, is characterised by proliferation of tumorous cells within small vessels. Manifestations in the CNS and cutaneous lesions prevail in the clinical presentation, although any organ can be involved. The recent classification of this lymphoma as part of the large cell lymphomas has modified the therapeutic approaches employed. This should improve the prognosis of this usually fatal disease. An unusual case presenting with fever, mononeuritis multiplex, and cutaneous lesions is reported. Peripheral neuropathy without other neurological symptoms is uncommon, and, to our knowledge, such isolated mononeuritis multiplex with nerve lesions has not been previously reported in ALCL. The clinical diagnosis was a systemic necrotising vasculitis and it is considered that its differential diagnosis must include angiotropic large cell lymphoma. Images
Roux, S; Grossin, M; De Bandt, M; Palazzo, E; Vachon, F; Kahn, M F
BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)
Stone, John H.; Merkel, Peter A.; Spiera, Robert; Seo, Philip; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Turkiewicz, Anthony; Tchao, Nadia K.; Webber, Lisa; Ding, Linna; Sejismundo, Lourdes P.; Mieras, Kathleen; Weitzenkamp, David; Ikle, David; Seyfert-Margolis, Vicki; Mueller, Mark; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina A.; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Specks, Ulrich
The authors present a case of isolated central nervous system vasculitis documented by cerebral arteriography in which remission, using a treatment regimen of prednisone and cyclophosphamide, was guided by serial arteriography during a 15-month period.
Stein, R.L.; Martino, C.R.; Weinert, D.M.; Hueftle, M.; Kammer, G.M.
Urticarial vasculitis is a rare clinicopathologic entity characterized by urticarial lesions that persist for more than 24 hours and histologic features of leukocytoclastic vasculitis. Patients can be divided into normocomplementemic or hypocomplementemic. The authors report the case of a healthy 49-year-old woman with a 1-year history of highly pruritic generalized cutaneous lesions and finger clubbing. Laboratory tests together with histopathologic examination allowed the diagnosis of hypocomplementemic urticarial vasculitis, chronic hepatitis C and type II mixed cryoglobulinemia. The patient started symptomatic treatment and was referred to a gastroenterologist for management of the hepatitis C, with progressive improvement of the skin condition. The development of hypocomplementemic urticarial vasculitis in the context of chronic hepatitis C is exceedingly rare and possible pathogenic mechanisms are discussed. PMID:24474109
Pinto-Almeida, Teresa; Caetano, Mónica; Alves, Rosário; Selores, Manuela
This study examines the distinct gene expression profile of peripheral blood mononuclear cells from patients with chronic hepatitis C infection and mixed cryoglobulinemic (MC) vasculitis. Our DNA microarray analysis indicates that hepatitis C virus (HCV)-associated MC vasculitis is characterized by compromised neutrophil function, impaired chemotaxis, and increased interferon-stimulated gene (ISG) expression, contributing to overall MC pathogenesis and end-organ damage. Increased ISG expression is suggestive of an enhanced endogenous interferon gene signature. PBMC depletion assays demonstrate that this increased expression is likely due to an activation of monocytes and not a direct result of B cell expansion. Notably, this monocyte activation of ISG expression in HCV-associated MC vasculitis suggests a poor predictor status of interferon-based treatment. Further analysis of PBMC gene expression profiles before and after in vivo B cell depletion therapy is critical to completely understanding the mechanisms of MC vasculitis pathogenesis.
Sidharthan, Sreetha; Kim, Cheol-Woo; Murphy, Alison A.; Zhang, Xiaozhen; Yang, Jun; Lempicki, Richard A.; Sneller, Michael C.; Kottilil, Shyam
The systemic vasculitides are a group of uncommon diseases characterized by blood vessel inflammation. There are currently no diagnostic criteria for the primary systemic vasculitides and physicians must rely on experience and disease definitions. The absence of validated criteria can result in delays in making the correct diagnosis and starting appropriate therapy. With the increased understanding of the pathophysiology of vasculitis and newer diagnostic tests in widespread clinical use, it is an appropriate time for classification criteria for primary vasculitis to be revised. The Diagnostic and Classification Criteria for Vasculitis (DCVAS) study is a multinational observational study designed to develop and validate diagnostic criteria and to improve and validate classification criteria for primary systemic vasculitis. The analytic approach will be based on the traditional approach of vessel size for classification of vasculitis but will also incorporate detailed clinical data, evaluation of anti-neutrophil cytoplasm antibody diagnostic testing, biopsy and imaging data. The study is following the guidelines for the development of classification criteria established by the American College of Rheumatology and the European League against Rheumatism. The study will incorporate the use of pre-defined cases of each condition to reduce the inherent circularity when developing new classification criteria and will explore alternative approaches to deriving reference standards by creating data-driven classification algorithms. We anticipate recruiting >2,000 patients with primary systemic vasculitis and 1,500 patients with autoimmune diseases and other conditions that mimic vasculitis. As of June 2013, >100 medical centers across 31 countries in Asia, Australasia, Europe, North America, and South America were contributing data to the study. The DCVAS study provides a unique opportunity to increase generalizability and collate a large dataset on the occurrence, presentation, and outcome of vasculitis in different populations. PMID:23996327
Craven, Anthea; Robson, Joanna; Ponte, Cristina; Grayson, Peter C; Suppiah, Ravi; Judge, Andrew; Watts, Richard; Merkel, Peter A; Luqmani, Raashid A
The aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis has not been well defined. Here we review two factors which may play a role in the pathogenesis of the disease: genetics and infection. In particular, we discuss the role of autoantibodies to LAMP-2, which may arise following infection with Gram-negative bacteria, and may contribute to the development of ANCA-associated systemic vasculitis in genetically susceptible individuals.
Cutaneous leukocytoclastic vasculitis (CLV) is a small-vessel vasculitis localized to the skin. Many possible causes exist for this pathological condition, including drugs, infection, collagen vascular disease, and malignancy. However, Mycobacterium tuberculosis is rarely reported to be associated with CLV. Here, we report a 49-year-old male patient that presented with fever, myalgia, and multiple palpable purpura on both of his legs.
Hee Man Kim; Yong-Beom Park; Ho Young Maeng; Soo-Kon Lee
Drug-induced hypersensitivity syndrome (DIHS) is a multi-system syndrome resulting from an idiosyncratic reaction to medication. While it commonly results in multi-organ involvement, particularly the liver, there are few reports of DIHS causing cerebral vasculitis and neurological deficits. We report the case of a 63-year old woman with DIHS secondary to allopurinol leading to multiple neurological deficits with magnetic resonance imaging findings consistent with a cerebral vasculitis. PMID:23330880
Lim, David; Rademaker, Marius; Asztely, Fredrik; Ratnaweera, Manjula; Coltman, Glenn
Herein we report a case of acute renal failure as a complication of Mediterranean spotted fever in a patient who was diagnosed as having cytoplasmic staining antineutrophil cytoplasmic antibody (C-ANCA) vasculitis. During the infection we observed a rise in C-ANCA titer without a relapse of vasculitis, 1 year ago. The patient, a 35-year-old woman, was admitted to our division in
G. Cabiddu; P. Altieri; A. Pani; P. Melis; M. Conti; O. Ledda; P. G. Bolasco
Vasculitis (angiitis) is a systemic autoimmune disease that often causes fatal symptoms. We aimed to isolate cDNA markers that would be useful for diagnosing not only vasculitis but also other autoimmune diseases. For this purpose, we used stepwise subtractive hybridization and cDNA microarray analyses to comprehensively isolate the genes whose expressions are augmented in peripheral blood mononuclear cells (PBMCs) pooled from vasculitis patients. Subsequently, we used quantitative real-time polymerase chain reaction (qRT–PCR) to examine the mRNA levels of each candidate gene in individual patients. These analyses indicated that seven genes exhibit remarkably augmented expression in many vasculitis patients. Of these genes, we analyzed G0/G1 switch gene 2 (G0S2) further because G0S2 expression is also enhanced in the PBMCs of patients with systemic lupus erythematodes (SLE). We generated G0S2 transgenic mice that ubiquitously overexpress human G0S2. Although we did not observe any obvious vasculitis-related histopathologic findings in these mice, these mice are unhealthy as they produce only few offspring and showed elevated serum levels of two autoimmunity-related antibodies, anti-nuclear antibody, and anti-double strand DNA antibody. Thus, our large-scale gene profiling study may help finding sensitive and specific DNA markers for diagnosing autoimmune diseases including vasculitis and SLE.
Kobayashi, Shigeto; Ito, Akihiko; Okuzaki, Daisuke; Onda, Hiroaki; Yabuta, Norikazu; Nagamori, Ippei; Suzuki, Kazuo; Hashimoto, Hiroshi; Nojima, Hiroshi
Macrophage migration inhibitory factor (MIF) is recognized to be an important mediator in several inflammatory disorders,\\u000a including rheumatoid arthritis (RA) and vasculitis. To evaluate the role of MIF in rheumatoid vasculitis (RV), we determined\\u000a serum levels of MIF by enzyme-linked immunosorbent assay in RA patients with and without vasculitis and assessed their relationship\\u000a to disease activity. Serum was obtained from
Kuninobu WakabayashiKumiko; Kumiko Otsuka; Michihito Sato; Ryo Takahashi; Tsuyoshi Odai; Takeo Isozaki; Nobuyuki Yajima; Yusuke Miwa; Tsuyoshi Kasama
Aims: To provide a fact file on the etiology, clinical presentations and management of retinal vasculitis in Eastern India. Materials and Methods: Retrospective, record based analysis of retinal vasculitis cases in a tertiary care center in Eastern India from January 2007 to December 2009. Results: One hundred and thirteen eyes of 70 patients of retinal vasculitis were included in this study. Sixty (85.7%) patients were male (mean age 33± 11.1 years) and 10 (14.3%) were female (mean age 32.4 ± 13.6 years). Vasculitis was bilateral in 43 (61.4%) and unilateral in 27 (38.6%) patients. Commonest symptoms were dimness of vision (73; 64.6%) and floaters (36; 31.9%). Vascular sheathing (82; 72.6%) and vitritis (51; 45.1%) were commonest signs. Mantoux test was positive in 21 (30%) patients but tuberculosis was confirmed in only four (5.71%) patients. Raised serum angiotensin-converting enzyme level and positive antinuclear antibody level were reported in four (5.71%) patients each. Human leukocyte antigen B5 (HLA B5) marker was present in one (1.4%) patient. However, none of the total 70 patients were found to have a conclusively proven systemic disease attributable as the cause of retinal vasculitis. Oral corticosteroid (60; 85.7%) was the mainstay of treatment. Forty-eight (42.5%) eyes maintained their initial visual acuity and 43 (38%) gained one or more line at mean follow-up of 16.6± 6.3 months. Conclusion: Retinal vasculitis cases had similar clinical presentations and common treatment plan. There was no systemic disease association with vasculitis warranting a careful approach in prescribing investigations.
Saurabh, Kumar; Das, Radha R; Biswas, Jyotirmay; Kumar, Amitabh
Neuroborreliosis affects the nervous system after systemic infection with the spirochete Borrelia burgdorferi. Previously, cerebral vasculitis has been regarded as an extremely rare complication of neuroborreliosis. The data on the long-term outcome in patients with cerebral vasculitis due to neuroborreliosis are limited. The objective of this study was to perform a longitudinal analysis of cases of neuroborreliosis-associated cerebral vasculitis. We recruited all patients (n = 11) diagnosed with neuroborreliosis-associated in three neurological departments in an East German region. Inclusion criteria were sudden neurological deficits, magnetic resonance (MR) imaging findings that conform to cerebral ischemia or brain infarction, intrathecal synthesis of borrelia-specific antibodies, and non-atherosclerotic pathology of brain supplying arteries. Vasculitic changes were detected by digital subtraction angiography, MR angiography and/or transcranial Doppler ultrasound. Outcomes were measured by the modified Rankin scale (mRS) and EuroQoL Index. Cerebral vasculitis is a rare complication of Lyme disease (0.3% of all cases in the endemic area). Ten out of 11 patients diagnosed with neuroborreliosis-associated vasculitis cerebral vasculitis using clinical, radiological and immunological criteria developed ischemic stroke or transient ischemic attacks (TIA), 7 patients had recurrent stroke. Vasculitic alterations could be demonstrated in 8 patients that all except one developed ischemic lesions. The median mRS was 3 (range 0-4) at admission and 2 (range 0-6) at discharge. The posterior circulation was affected in 8 of 11 patients; thrombosis of the basilar artery was detected in 2 patients, one died in the acute stage. Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis. Lumbar puncture is needed for detection of this potentially life-threatening condition. Early recognition and adequate therapy would possibly improve outcome. PMID:23329377
Back, Tobias; Grünig, Steffi; Winter, Yaroslav; Bodechtel, Ulf; Guthke, Kersten; Khati, Diana; von Kummer, Rüdiger
Leukocytoclastic vasculitis (LV) is characterized by neutrophilic invasion and fibrinoid necrosis along with endothelial enlargement in postcapillary venules. Annular appearance of LV (ALV) is rare, but it can be accompanied by several systemic diseases. One of these systemic diseases is ulcerative colitis (UC), a subgroup of inflammatory bowel disease. Only one case was previously reported in which ALV was associated with UC, and herein we present one more case. A 66-year-old woman presented with painful polycyclic erythema on both palms, which had been present for 4 days. She had suffered from UC for 5 years. The patient had no fever or other systemic symptoms, and histological examination demonstrated typical LV. 200 mg of oral dapsone was taken daily to rapidly reduce her symptoms and signs, and after 1 week all lesions resolved completely without any adverse events. ALV is not a distinct condition and it can appear in a broad range of small vessel vasculitides. Although ALV in patients with UC is a very rare combination, clinicians need to be aware of this possible association.
Hong, Jong Soo; Jin, Seon Pil; Choi, Mira; Lee, Kook Lae; Lee, Jong Hee
OBJECTIVES--To assess the vascular involvement in labial salivary gland (LSG) from patients with rheumatoid vasculitis (RV). METHODS--Forty seven patients with rheumatoid arthritis (RA) took part in a prospective study. Among them, 12 had proven RV. LSG biopsy was performed after local anaesthesia. RESULTS--Histological appearance of inflammatory vascular damage was observed in all but one patient with proven RV (92%). Inflammatory vascular involvement was also identified in LSG biopsy of seven patients with RA (20%) and only one patient in the control group (8%). A second specimen of LSG was studied after a mean treatment period of six months and failed to show any feature of inflammatory vascular involvement in three of the five cases that were analysed. CONCLUSIONS--The study emphasises the high incidence of immunopathological features of microvascular damage in patients with RV. LSG biopsy is minimally invasive and may be a potential useful tool for the diagnosis of RV especially when skin lesions are absent or impossible to biopsy. The assessment of the predictive value of positive LSG biopsy in RA requires a long term prospective study. Images
Flipo, R M; Janin, A; Hachulla, E; Houvenagel, E; Foulet, A; Cardon, T; Desbonnet, A; Grardel, B; Duquesnoy, B; Delcambre, B
Mast cells contribute to the modulation of the immune response, but their role in autoimmune renal disease is not well understood. Here, we induced autoimmunity resulting in focal necrotizing GN by immunizing wild-type or mast cell-deficient (KitW-sh/W-sh) mice with myeloperoxidase. Mast cell-deficient mice exhibited more antimyeloperoxidase CD4+ T cells, enhanced dermal delayed-type hypersensitivity responses to myeloperoxidase, and more severe focal necrotizing GN. Furthermore, the lymph nodes draining the sites of immunization had fewer Tregs and reduced production of IL-10 in mice lacking mast cells. Reconstituting these mice with mast cells significantly increased the numbers of Tregs in the lymph nodes and attenuated both autoimmunity and severity of disease. After immunization with myeloperoxidase, mast cells migrated from the skin to the lymph nodes to contact Tregs. In an ex vivo assay, mast cells enhanced Treg suppression through IL-10. Reconstitution of mast cell-deficient mice with IL-10–deficient mast cells led to enhanced autoimmunity to myeloperoxidase and greater disease severity compared with reconstitution with IL-10–intact mast cells. Taken together, these studies establish a role for mast cells in mediating peripheral tolerance to myeloperoxidase, protecting them from the development of focal necrotizing GN in ANCA-associated vasculitis.
Gan, Poh-Yi; Summers, Shaun A.; Ooi, Joshua D.; O'Sullivan, Kim M.; Tan, Diana S.Y.; Muljadi, Ruth C.M.; Odobasic, Dragana; Kitching, A. Richard
Cogan's syndrome (CS) is a chronic inflammatory disorder of unknown etiology that most commonly affects young adults. Clinical hallmarks are bilateral interstitial keratitis and vestibuloauditory dysfunction. Association between CS and systemic vasculitis as well as aortitis also exists. The diagnosis of CS is based upon presence of characteristic inflammatory eye disease and vestibuloauditory dysfunction. We describe classic Cogan's syndrome in a 47-year-old female from Ardabil. The patient was admitted with headache, vertigo, nausea, vomiting, right leg claudication, musculoskeletal pains, bilateral hearing loss, and blindness for the past two months. Ophthalmologic examination revealed that visual acuity was 0.1 bilaterally. Conjunctival hyperemia, bilateral cataract, and interstitial keratitis were detected with a slit lamp examination. Pure tone audiogram (PTA) and auditory brain stem response (ABR) showed bilateral sensorineural hearing loss. The other differential diagnosis of CS was studied and ruled out. Pulse i.v. methylprednisolone and cyclophosphamide were given and were followed by oral prednisolone and cyclophosphamide. Clinical follow-up showed partial improvement.
Azami, Ahad; Kalantar Hormozi, Mohammadreza; Tavosi, Zahra
Cogan's syndrome (CS) is a chronic inflammatory disorder of unknown etiology that most commonly affects young adults. Clinical hallmarks are bilateral interstitial keratitis and vestibuloauditory dysfunction. Association between CS and systemic vasculitis as well as aortitis also exists. The diagnosis of CS is based upon presence of characteristic inflammatory eye disease and vestibuloauditory dysfunction. We describe classic Cogan's syndrome in a 47-year-old female from Ardabil. The patient was admitted with headache, vertigo, nausea, vomiting, right leg claudication, musculoskeletal pains, bilateral hearing loss, and blindness for the past two months. Ophthalmologic examination revealed that visual acuity was 0.1 bilaterally. Conjunctival hyperemia, bilateral cataract, and interstitial keratitis were detected with a slit lamp examination. Pure tone audiogram (PTA) and auditory brain stem response (ABR) showed bilateral sensorineural hearing loss. The other differential diagnosis of CS was studied and ruled out. Pulse i.v. methylprednisolone and cyclophosphamide were given and were followed by oral prednisolone and cyclophosphamide. Clinical follow-up showed partial improvement. PMID:24715922
Azami, Ahad; Maleki, Nasrollah; Kalantar Hormozi, Mohammadreza; Tavosi, Zahra
Hepatitis C virus (HCV) is now well recognised as the main etiologic agent of mixed cryoglobulinaemia vasculitis (cryovas). New opportunities and problems in developing therapy have therefore emerged. Antiviral therapy with pegylated interferon-? and ribavirin (plus protease inhibitor in the case of HCV genotype 1 infection) should be considered as induction therapy for HCV-cryovas with mild to moderate disease severity and activity. An early virologic response to antiviral therapy is correlated with a complete clinical response of HCV-cryovas. In patients presenting with more severe disease (ie, worsening of renal function, mononeuritis multiplex, extensive skin disease including ulcers and distal necrosis), an immunosuppression induction phase is often necessary while awaiting the generally slow response to antiviral treatments. Combination therapy with rituximab plus an optimal antiviral agent is recommended, as it may target the downstream B cell arm of autoimmunity and the viral trigger. Careful monitoring for adverse effects is mandatory, since some manifestations of HCV-cryovas, such as peripheral neuropathy or skin ulcers, may worsen with interferon-based therapy. Clinicians should be aware of the possibility of malignant lymphoma when patients develop a relapse of cryovas without virological relapse. Room for other treatment strategies is very limited. Low-dose corticosteroids may help to control minor intermittent inflammatory signs such arthralgia but do not succeed in case of major organ involvement. Other immunosuppressants should be given only in case of refractory forms of HCV-cryovas, which are frequently associated with an underlying B cell lymphoma. PMID:23921995
Cacoub, Patrice; Terrier, Benjamin; Saadoun, David
A 28-year-old man with a bicuspid aortic valve presented with facial droop and slurred speech with several months of constitutional symptoms of night sweats, weight loss and productive cough. Examination confirmed aortic regurgitation, palpable spleen and left facial droop. Multiple peripheral blood cultures were negative. Inflammatory markers, cytoplasmic staining antineutrophil cytoplasmic antibodies (cANCA) and anti-PR3 antibody were all elevated. MRI of the brain and CT of the chest and abdomen confirmed embolic infarcts to brain, kidney and spleen. Transoesophageal echocardiogram (ECG) showed valve vegetations and severe aortic regurgitation. Endocardial Wegener's granulomatosis was considered. Aortic valve replacement was performed. Grindings from aortic valve leaflets were analysed for rpoB gene, which confirmed the presence of Bartonella henselae. Serological assays demonstrated B henselae IgM 20 (normal <20) and IgG >2048 (normal < 64). The patient completely recovered after prolonged antibiotic treatment. Culture-negative infective endocarditis may mimic vasculitis and be associated with positive cANCA. Serology and molecular techniques may aid diagnosis. PMID:22791485
Teoh, Laurence S G; Hart, Hamish H; Soh, May Ching; Christiansen, Jonathan P; Bhally, Hasan; Philips, Martin S; Rai-Chaudhuri, Dominic S
Purpose: To report on the clinical features and etiology of patients with retinal vasculitis (RV). Materials and Methods: We reviewed medical records of 47 patients (75 affected eyes) diagnosed with RV. Clinical presentations, ocular complications, associated systemic diseases, and treatment regimens were registered. Results: Etiology of RV included infectious causes in 10/47, (21%) while an association with systemic and/or ocular non-infectious disorders was noted in 22/47 (47%). Eales’ disease and Behcet's disease represented the most common clinical entities in non-infectious group while tuberculosis-associated RV was diagnosed in 6/10 (60%) among those with infectious disorders. RV was bilateral in 28/47 (60%) patients. Retinal veins were most commonly affected (72%, 34/47). Involvement of arteries was present in 12/47 (25%) and was associated with viral infections and Behcet's disease. Ocular complications developed in 60/75 (80%) eyes. The most common complications were elevated intraocular pressure and/or glaucoma (33/75, 44%). Retinal detachment, vitreous hemorrhage, and cystoid macular edema developed in similar percentages (15%). Conclusions: RV in Thailand manifested mostly in male patients, was typically bilateral and involved mostly veins. Involvement of arteries was observed in patients with viral infections and Behcet's disease. Tuberculosis was the most common infectious cause.
Apinyawasisuk, Supanut; Rothova, Aniki; Kunavisarut, Paradee; Pathanapitoon, Kessara
We present three cases describing the various skin manifestations of presumed levamisole-contaminated cocaine use. Antibody-mediated vasculitis and neutropenia were consistent findings in these cases and repeat exposure resulted in distinct dermatologic complications. This phenomenon of levamisole-induced vasculitis and neutropenia is being increasingly described and has characteristic wound manifestations that must be recognised and treated early. PMID:22716045
Belfonte, Cassius D; Shanmugam, Victoria K; Kieffer, Nicole; Coker, Shodeinde; Boucree, Suelyn; Kerr, Gail
Background ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. Methods Neutrophils from Healthy Blood Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal transplant recipients (TP) were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-?, C/EBP-? and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. Results AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50±14% vs. HBD 64±11%, p<0.0001). In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-?, C/EBP-? were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. Conclusion Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.
Abdgawad, Mohamed; Pettersson, Asa; Gunnarsson, Lena; Bengtsson, Anders A.; Geborek, Pierre; Nilsson, Lars; Segelmark, Marten; Hellmark, Thomas
Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.
Nabel, Elizabeth G.; Plautz, Gregory; Nabel, Gary J.
The prevalence of cocaine adulterated with levamisole-induced vasculitis is increasing and physicians should be aware of this unique entity. There have been many reports of cutaneous vasculitis syndrome caused by cocaine which is contaminated with levamisole. Levamisole was used as an antihelminth drug and later was rescinded from use in humans due to adverse effects. Through this paper, we will report a 39-year-old crack cocaine user who presented with purpuric rash and skin necrosis of his ear lobes. Levamisole-induced vasculitis syndrome was suspected. A urine toxicology screen was positive for cocaine, opiates, and marijuana. Blood work revealed positive titres of ANA and p-ANCA, as well as anti-cardiolipin antibody. Biopsy taken from the left ear showed focal acute inflammation, chronic inflammation with thrombus formation, and extravasated blood cells. Treatment was primarily supportive with wound care. PMID:24778656
Souied, Osama; Baydoun, Hassan; Ghandour, Zahraa; Mobarakai, Neville
Renal involvement with significant organ damage is common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). As a result, it is independently referred to ANCA-associated renal vasculitis. Clinically, ANCA-associated renal vasculitis is characterized by rapidly progressive glomerulonephritis. Pathologically, it is defined by pauci-immune type necrotizing and crescentic glomerulonephritis. According to previous reports from all over the world, the etiology, prevalence, and prognosis of RPGN including ANCA-associated renal vasculitis varies among races and periods. To elucidate the clinical characteristics of Japanese RPGN patients, a registry derived from a questionnaire survey was established in 1999 and maintained until 2006. As a result, 1,772 cases were collected, analyzed, and reported previously. In this mini-review, we outline the characteristic clinical findings of Japanese patients (Asian) with ANCA-associated renal vasculitis, based on the registry data. PMID:23239119
Yamagata, Kunihiro; Usui, Joichi; Sugiyama, Hitoshi; Nitta, Kosaku; Wada, Takashi; Muso, Eri; Arimura, Yoshihiro; Koyama, Akio; Makino, Hirofumi; Matsuo, Seiichi
Behçet's disease is a chronic, relapsing, systemic vasculitis of unknown aetiology. Patients present manifestations of gastrointestinal complications, including mouth lesions, small and large intestinal lesions, and vascular lesions in the abdomen. In some cases, the intestinal ulcers of patients with Behçet's disease are indistinguishable from those of Crohn's disease, tuberculosis, vasculitis and other diseases. In this article, we present a case of atypical Behçet's disease with a complicated medical history and multisystem damage, for the purpose of better management of this disease. PMID:24744604
Yang, Xiao-Ning; Ye, Zhen-Shi; Fan, Yan-Yun; Hu, Yi-Qun
Henoch-Schönlein purpura, is one of the most common types of multisystemic vasculitis seen in childhood. The major clinical manifestations are cutaneous purpura, arthritis, abdominal pain, gastrointestinal bleeding, and nephritis. Isolated central nervous system vasculitis, seizures, coma and hemorrhage, Guillan--Barré syndrome, ataxia and central and peripheral neuropathy, ocular involvement, orchitis, epididymitis or testicular torsion are medical or surgical complications. In this study, we report a 7-year-old boy with scrotal swelling mimicking testicular torsion with ultrasonographic and clinical findings that the typical clinical features of Henoch-Schönlein purpura including rashes and arthritis were developed after one week of surgery (Ref. 15). PMID:22693978
Inflammatory large-vessel vasculitis in Behçet's disease may cause life-threatening arterial aneurysms that are prone to rupture. We report a patient with Behçet's disease with right ventricular thrombus and large aneurysms of the pulmonary arteries that led to recurrent episodes of hemoptysis. Following relapses and only partial response to repeated courses of cyclophosphamide and steroids, the patient was treated with adalimumab (Humira) and is now in clinical remission for over 30 months, with regression of her pulmonary lesions. Anti-TNF? treatment is a potential therapeutic option in patients with life-threatening complications due to large-vessel vasculitis. PMID:23412691
Aamar, Suhail; Peleg, Hagit; Leibowitz, David; Chajek-Shaul, Tova; Hiller, Nurith; Heyman, Samuel N
First manifestations of vasculitis can appear on the head and neck, still few physicians are aware of these diseases, as they are unspecific and because other conditions like infections and allergies are more frequent. Among them, signs and symptoms like epistaxis, nasal obstruction, discharge, burning pain, headache, sinus polyps and crusts, the latter found in people who live in highly
Olga E. Beltrán Rodríguez Cabo; Gabriel Tona
The recent development of biologic therapies capable of selectively targeting components of the immune system has revolutionised the treatment of inflammatory arthritides. The steady increase in use of biologic agents coupled with the expansion in the knowledge of the pathogenesis of vascular inflammation has led to their application in the treatment of primary systemic vasculitis. These agents may have a
A. T. Chan; O. Floßmann; C. Mukhtyar; D. R. W. Jayne; R. A. Luqmani
Kawasaki disease (KD) is a paediatric idiopathic vasculitis. In this study, on the basis of studies using an established animal model for KD, we report that mannose-binding lectin (MBL) is involved in the pathogenesis of the disease. KD-like experimental murine vasculitis was induced by intraperitoneally administering a Candida albicans water-soluble extract (CAWS). MBL-A gradually increased in the serum of the model mice treated with CAWS. Deposition of MBL-A and MBL-C was observed in the aortic root, including the coronary arteries, which is a predilection site in experimental vasculitis. Corresponding to the distribution patterns of MBLs, marked deposition of C3/C3-derived peptides was also observed. Regarding the self-reactivity of MBLs, we observed that MBLs interacted with core histones to activate the lectin pathway. These results suggest that some types of pathogens provoke the MBL-dependent complement pathway (lectin pathway) to cause and/or exacerbate KD-like vasculitis. PMID:24721319
Nakamura, Akihiro; Okigaki, Mitsuhiko; Miura, Noriko; Suzuki, Chinatsu; Ohno, Naohito; Kametani, Fuyuki; Hamaoka, Kenji
Objectives. To evaluate the use of the diagnostic criteria for Wegener's granulomatosis (WG) and microscopic polyangiitis (mPA) proposed by Sørensen et al. in the classification of primary systemic vasculitis (PSV). Methods. We applied to our cohort of PSV patients the American College of Rheumatology (ACR) criteria for WG, Churg-Strauss syndrome (CSS) and polyarteritis nodosa (PAN), the Chapel Hill Consensus Conference
R. A. Watts; T. H. W. Barker; D. G. I. Scott
Cerebral vasculitis and clinically important myocardial inflammation are rare in juvenile dermatomyositis. We report a previously healthy 6-year-old girl with dermatomyositis who died after a fulminating clinical deterioration. Postmortem examination of the heart revealed characteristic endothelial tubuloreticular aggregates and evidence of capillary necrosis and secondary thrombosis, associated with extensive hemorrhagic myocardial necrosis. Endothelial necrosis was also evident in the cerebrocortical
Cita Jimenez; Peter C. Rowe; Daniel Keene
Objective: To determine the causes of acute abdominal pain in systemic lupus erythematosus (SLE) and to compare the clinical and laboratory data, especially antiphospholipid antibodies and the SLE Disease Activity Index (SLEDAI), between lupus enteritis (gastrointestinal vasculitis) and acute abdominal pain without lupus enteritis in patients with SLE.Methods: A retrospective study was carried out for all patients admitted with SLE
C-K Lee; M S Ahn; E Y Lee; J H Shin; Y-S Cho; H K Ha; B Yoo; H-B Moon
We studied the distribution and characteristics of circulating rheumatoid factors (RF) and anti-nuclear antibodies (ANA) in 30 rheumatoid arthritis (RA) patients who had polyarthritis alone (group I), 28 RA patients with polyarthritis and extra-articular disease (group II), 28 RA patients with systemic vasculitis (group III) and 60 healthy matched controls. IgG RF occurred more frequently and in higher serum titres in group III (100%) than RA patients in group I (40%), or in group II (18%) or in normal controls (5.8%). The serum titre of IgM RF was higher in vasculitis patients than in other RA patients. ANA were found in 74% of all RA patients and although the frequency did not differ in the three patient groups, the serum titre was significantly higher in the vasculitis group. Antibodies to extractable nuclear antigen were found only in group III (18.7%). Antibodies to histones were also more prevalent in group III than in the other RA groups. The serological abnormalities in rheumatoid vasculitis differed quantitatively as well as qualitatively from other RA patients.
Quismorio, F P; Beardmore, T; Kaufman, R L; Mongan, E S
Hypernephroma can present as a variety of paraneoplastic, nonmetastatic conditions, including vasculitis, and rarely a lupus-type anticoagulant. Nephrectomy leads to the resolution of the systemic complaints. Malignancy, in this case hypernephroma, can present as an immune-mediated paraneoplastic syndrome which resolves after removal of the underlying tumor.
Murray, Nigel P.; Ruiz, Amparo; Reyes, Eduardo
The role of interleukin-6 (IL-6) in granulomatous vasculitis is not well understood. To investigate its involvement in this type of vasculitis a model of glucan-induced pulmonary vasculitis employed interleukin-6 deficient (IL-6-/-) mice. Briefly, IL-6-/- mice and C57B/J6 wild type (IL-6+/+) mice were injected intravenously with a suspension of glucan isolated from the cell wall of bakers yeast which results in a granulomatous vasculitis primarily in the pulmonary vasculature. Histological examination demonstrated no significant difference in the number of infiltrating leukocytes between the IL-6+/+ and IL-6-/- glucan-injured mice. Similar numbers of granulomas were noted in both the IL-6+/+ and IL-6-/- injured animals, while no granulomas were seen in saline injected control mice. Cells recovered from the bronchoalveolar lavage (BAL) fluid were differentially stained and counted. While there was a significant increase in infiltrating leukocytes recovered from the BAL following glucan-induced injury, there was no significant difference between the IL-6+/+ and IL-6-/- mice. In addition, no difference was demonstrated in total protein content in the BAL fluid between IL-6+/+ and IL-6-/- mice. However, myeloperoxidase (MPO) activity in the lungs of the IL-6-/- mice was less than in their IL-6+/+ counterparts suggesting that these animals have a partial defect in their ability to recruit neutrophils in this model. Studies done to look for levels of other cytokines/chemokines in these animals to compensate for the loss of IL-6 revealed that only IL-10 in the sera (p<0.016) and BAL fluid (p<0.05) of IL-6-/- mice was significantly higher then their IL-6+/+-injured counterparts. These studies suggest that IL-6, while possibly involved in early neutrophil accumulation in this model does not appear critical to the development of the TH-2 mediated granulomatous vasculitis. PMID:17222822
McClintock, Shannon D; Barron, Adam G; Olle, Eric W; Deogracias, Michael P; Warner, Roscoe L; Opp, Mark R; Johnson, Kent J
OBJECTIVE—To study immunological markers and compare these markers with standard measures for the clinical and immunological follow up of vasculitis activity in hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV).?METHODS—Serial serum samples from eight patients with newly diagnosed HCV associated CV were followed during interferon ? treatment induced remission of the CV. Vasculitis activity and disease extent were evaluated with the Birmingham vasculitis activity score (BVAS) and disease extent index (DEI). Cryoglobulinaemia, complement levels (C3c, C4, and CH50), rheumatoid factor (RF), autoantibodies such as antinuclear antibodies, soluble interleukin 2 receptor (sIL2r), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble CD30 (sCD30) were determined.?RESULTS—All patients achieved either complete or partial remission of their CV during interferon ? treatment. There was a significant reduction in vasculitis activity and disease extent (BVAS, DEI), cryoglobulinaemia, RF, sIL2r, sICAM-1, and sCD30. Complement C3c levels increased significantly during this period. Erythrocyte sedimentation rate and levels of complement C4 and CH50 did not change significantly. Both clinical measures (BVAS and DEI) correlated significantly only with C3c and sCD30.?CONCLUSIONS—Although this study was of only a small group of patients, it shows that BVAS and DEI as clinical measures and C3c and sCD30 as immunological markers may be useful in the follow up of disease activity of HCV associated CV. The data indicate that activity of the humoral (cryoglobulinaemia, RF, autoantibodies) and cellular (sIL2r, sICAM-1, sCD30) immune response and endothelial damage (sICAM-1) are found in HCV associated CV.??
Lamprecht, P; Moosig, F; Gause, A; Herlyn, K; Csernok, E; Hansen, H; Gross, W
ObjectiveTo optimise a strategy for identifying gene expression signatures differentiating systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis that provide insight into disease pathogenesis and identify biomarkers.Methods44 vasculitis patients, 13 SLE patients and 25 age and sex-matched controls were enrolled. CD4 and CD8 T cells, B cells, monocytes and neutrophils were isolated from each patient and, together with unseparated
Paul A Lyons; Eoin F McKinney; Tim F Rayner; Alexander Hatton; Hayley B Woffendin; Maria Koukoulaki; Thomas C Freeman; David R W Jayne; Afzal N Chaudhry; Kenneth G C Smith
This paper describes the ophthalmological features of 150 patients with idiopathic retinal vasculitis, 67 of whom had isolated retinal vasculitis (RV) and 83 had RV associated with systemic inflammatory disease (RV + SID). The diagnosis of retinal vasculitis was made by ophthalmoscopy and fluorescein angiography, and patients with any identifiable cause (infection, ischaemia, or malignancy) were excluded from the study. Patients with isolated RV tended to have peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. Those with RV accompanying Behçet's disease often had branch vein retinal occlusions and retinal infiltrates together with macular oedema and diffuse capillary leakage; the retinal infiltrates were pathognomonic for Behçet's disease. In sarcoidosis the retina typically showed features of periphlebitis associated with focal vascular leakage. Patients with uveomeningitis, multiple sclerosis, arthritis, or systemic vasculitis showed diffuse retinal capillary leakage associated with a mixture of the other features. Poor visual function was particularly associated with macular oedema and branch vein retinal occlusion, while the retina appeared to 'withstand' the impact of vascular sheathing, periphlebitis, or neovascularisation alone. Within the limitations of a point prevalence study it was concluded that different patterns of retinal vasculitis occur in different systemic inflammatory diseases, and that in isolated retinal vasculitis there is a particular association between peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. In Part 2 we describe the results of examining the sera of these patients for the presence of antiretinal antibodies and circulating immune complexes. Images
Graham, E M; Stanford, M R; Sanders, M D; Kasp, E; Dumonde, D C
Rapidly progressing glomerulonephritis like microscopic polyangiitis and allergic granulomatous angiitis are among the common presentations of perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) vasculitis. Involvement of central nervous system is rare in contrast to mononeuritis multiplex, which is a well-known neurological manifestation of this condition. We report a case presented with uraemic encephalopathy and posterior reversible encephalopathy syndrome (PRES)-related symptoms, which showed recovery after haemodialysis although PRES with seizures recurred later. As uraemic encephalopathy appears to be the underlying aetiology as per the temporal correlation of correction of uraemia and resolution of the symptoms of PRES, it becomes a rare case of uraemia-induced PRES as a presenting manifestation of p-ANCA-associated vasculitis along with necrotising crescentic glomerulonephritis. PMID:24855074
Patel, Upasana Vrijlal; Patel, Nirajkumar Jagjivan
Colitis in patients with systemic lupus erythematosus (SLE) is quite rare. It can be caused by intestinal vasculitis, mesenteric vascular thrombosis, concomitant inflammatory bowel disease or infectious colitis. It is important to make an accurate and early diagnosis as the treatments for each condition differ and a delayed diagnosis can result in life-threatening complications. However, non-specific gastrointestinal symptoms make a timely diagnosis challenging. Amoebic colitis is a rare condition in patients with SLE. Here we present a case of fulminant amoebic colitis in a patient with SLE which was initially misdiagnosed as ischemic colitis due to intestinal vasculitis. Her colitis was complicated with multiple intestinal perforations, disseminated intravascular coagulation and acute respiratory distress syndrome; but in the end, the patient was successfully treated with metronidazole and paromomycin. PMID:22570337
Lee, J; Jung, H-S; Nam, H-C; Kwok, S-K; Ju, J H; Park, K-S; Kim, H-Y; Park, S-H
Levamisole, an immunomodulator and anthelmintic medication, has been used in dermatology for years. Even though the adverse effects are usually mild and reversible, attention should be paid toward severe events such as vasculitis and neutropenia. To the best of our knowledge, this is the first case report on a patient presenting with myopathy caused by levamisole. Here, we report a 34-year-old woman with recalcitrant warts who received levamisole 100?mg daily for 5?days. Subsequently, bilateral lower limb weakness accompanied by multiple painful and non-blanchable purpura was noted. Levamisole-induced myopathy and leukocytoclastic vasculitis were diagnosed by skin histopathology, direct immunofluorescence, and electromyography. After discontinuing levamisole and giving a short course of systemic steroid, these symptoms demonstrated a resolving trend. PMID:24552411
Tsai, Meng-Hsuan; Yang, Jen-Hung; Kung, Sheng-Ling; Hsiao, Yu-Ping
Vasculitis is a heterogeneous group of rare disorders in which inflammation of blood vessels is the common feature. Due to the increasing number of diseases as well as overlaps and gaps in the definition and nomenclature, the classification criteria were constantly changing in the past decades. The classifications were based essentially on the size of affected blood vessels and pathologic characteristics of inflamed vessel walls. The standard procedures and validated diagnostic criteria are missing from the diagnostics of vasculitis, thus in clinical practice the classification criteria are applicable. The 2012 Chapel Hill Consensus Conference brought a change in the definition, nomenclature and classification of previously uncategorized diseases. The definitions of subgroups accurately determine the diagnosis of the specific disease, and they are suitable for establishing homogeneous disease groups. By better understanding of the etiopathogenetic factors, further diseases and subgroups may be defined in the near future. PMID:24077160
Cerebral vasculitis associated with acute post-streptococcal glomerulonephritis (APSGN) is rare. A 13-year-old girl presented with severe headache, vomiting, oedema and macroscopic haematuria. There was a history of upper respiratory infection 2 weeks previously. A diagnosis of APSGN was made. On admission, she was normotensive and biochemically well balanced. She experienced a tonic-clonic seizure 2 hours later. An MRI brain scan demonstrated multiple areas of abnormal signal intensity in the cerebral and cerebellar white matter, and subarachnoid haemorrhage consistent with vasculitis was diagnosed. A sixth-nerve palsy developed on the 6th day of admission. An elevated anti-streptolysin titre and low serum C3 complement level together with typical features on renal biopsy supported the diagnosis of APSGN. All clinical and laboratory abnormalities improved with corticosteroid therapy, pulse methyl-prednisolone. APSGN can present with central nervous system abnormalities without hypertension, uraemia and electrolyte disturbance. PMID:18510827
Dursun, Ismail; Gunduz, Zubeyde; Poyrazoglu, Hakan M; Gumus, Hakan; Yikilmaz, Ali; Dusunsel, Ruhan
We report a case of post-streptococcal uveitis mainly presenting with bilateral recurrent retinal vasculitis in Korea. A 14-year-old Asian female presented with decreased visual acuity of 20 / 30 in the right eye and 20 / 25 in the left eye. The patient had a history of glomerulonephritis nine months before onset of uveitis. The manifestation of uveitis was predominantly retinal vasculitis. We presumed post-streptococcal uveitis because probable streptococcal infection was confirmed by anti-streptolysin O titer elevation. With topical and oral steroid treatments, the patient experienced complete vision recovery. Post-streptococcal uveitis occurs rarely and mostly involves young patients in the form of non-granulomatous anterior uveitis. However, as this case shows, it may primarily involve the posterior uvea without anterior inflammation and may recur.
Han, Jinu; Lee, Sung Chul
Few adverse effects have been reported with adjunctive dexamethasone treatment in pneumococcal meningitis. Nevertheless, we report a case of cerebral vasculitis. A 49-year-old man was admitted for fever and altered mental status. Lumbar puncture revealed a high inflammatory response and Streptococcus pneumoniae was identified by culture. Antibacterial therapy and adjunctive dexamethasone treatment were initiated as recommended. The immediate outcome was favorable but due to the onset of focal cerebral abnormalities, a CT scan was performed on the ninth day showing cerebral vasculitis. The patient died on the thirteenth day despite antibacterial therapy and resuscitation. In our case, a secondary neurological worsening appeared when adjunctive dexamethasone treatment was stopped suggesting a rebound effect. Observation of similar cases may lead to modifying adjunctive dexamethasone treatment protocol in bacterial meningitis. PMID:17267155
Lefebvre, N; Carre, A-C; Delabranche, X; Guiot, P; Mootien, Y
A 68-year-old man who was treated for febrile angina with gentamicin, doxycycline, phenoxymethylpenicillin K, and minocycline developed a generalized pustular exanthema favoring the predilected areas (hands, feet). Apart from a subepidermal pustule, the most noteworthy histological finding was a pronounced leukocytoclastic vasculitis. After disappearance of the skin lesions an intradermal test using cilligen (penicilloyl-polylysin) was conducted. The test gave a strongly positive early reaction, and 48 h after this an acute pustular outbreak developed analogous to the original manifestation. Doxycycline tested late, produced no exacerbation even though it was positive in the intradermal test. This pustular allergical drug rash can be classified as a vasculitis leucocytoclastica allergica which, as we know, appears in various clinical forms. It does not form a new disease entity. Terms used so far, such as "pustular necrotizing angiitis", "generalized pustular drug rash", "acute generalized pustular bacterid", "pustulosis acuta generalisata", only partially correspond to the actual pathoetiology. PMID:6268571
Severe cutaneous allergic vasculitis in a 60 year-old Caucasian male following the bite of the tropical fire ant, Solenopsis geminata (F.) is reported. Over the course of 8 weeks, the pathology progressed from an extensive red papular urticaria to vasculitis with peri-vascular inflammation and ulceration of the skin on the feet, ankles and lower limbs. Many of the affected areas of the skin eventually became covered with black eschar associated with further tissue breakdown and ulcer formation. After debridement, compression dressings, antimicrobial ointment and corticosteroids, complete healing eventually took place with only residual scarring. An awareness of the severe dermatologic reactions caused by a bite of S. geminata, albeit rare, is clinically important. Recognizing the characteristic skin lesions caused by the bite of S. geminata, treated with prompt administration of appropriate chemotherapy will speed recuperation of the patient and reduce possible secondary complications. PMID:18041296
Knight, David; Bangs, Michael J
Vasculitides associated with serum positivity for anti-neutrophil cytoplasmic antibodies (ANCAs) that affect small- to medium-sized vessels are commonly known as ANCA-associated vasculitis (AAV) and include Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Evidence derived from both in vitro studies and recent animal models points to a pathogenic role of ANCAs in AAV. In 2002, the first in vivo breakthrough in the pathogenesis of ANCAs showed that mouse ANCAs against myeloperoxidase (MPO) led to intrinsic pauci-immune renal vasculitis in mice. In 2004, a report using both in vitro and in vivo studies proposed that proteinase 3 (PR3)-directed autoimmunity involved the complementary peptide of PR3 (cPR3), which is encoded by the antisense strand of the PR3 gene. The last breakthrough came in October 2008 with a previously undescribed molecular explanation for the origin and development of injury in pauci-immune renal vasculitis, with potential clinical implications. This report showed that infection by fimbriated bacteria may trigger cross-reactive autoimmunity to a previously characterized ANCA antigen, lysosomal membrane protein-2, which is contained in the same vesicles that harbor MPO and PR3. Infection by fimbriated bacteria resulted in the production of autoantibodies, which activated neutrophils and killed human microvascular endothelium in vitro and caused renal vasculitis in rats. Although the evidence for a pathogenic role of ANCAs, mainly MPO-ANCAs, is striking, various questions remain unanswered. Understanding the key pathogenic mechanisms of AAV may provide a safer, more rational therapeutic approach than the traditional (ie, corticosteroids and immunosuppressants) treatment strategy.
Gomez-Puerta, Jose A.; Bosch, Xavier
This paper presents the first conceptual study into creating a Plantae-inspired vascular network within a fibre-reinforced polymer composite laminate, which provides an ongoing self-healing functionality without incurring a mass penalty. Through the application of a ‘lost-wax’ technique, orthogonal hollow vascules, inspired by the ‘ray cell’ structures found in ring porous hardwoods, were successfully introduced within a carbon fibre-reinforced epoxy polymer composite laminate. The influence on fibre architecture and mechanical behaviour of single vascules (located on the laminate centreline) when aligned parallel and transverse to the local host ply was characterized experimentally using a compression-after-impact test methodology. Ultrasonic C-scanning and high-resolution micro-CT X-ray was undertaken to identify the influence of and interaction between the internal vasculature and impact damage. The results clearly show that damage morphology is influenced by vascule orientation and that a 10 J low-velocity impact damage event is sufficient to breach the vasculature; a prerequisite for any subsequent self-healing function. The residual compressive strength after a 10 J impact was found to be dependent upon vascule orientation. In general, residual compressive strength decreased to 70 per cent of undamaged strength when vasculature was aligned parallel to the local host ply and a value of 63 per cent when aligned transverse. This bioinspired engineering study has illustrated the potential that a vasculature concept has to offer in terms of providing a self-healing function with minimum mass penalty, without initiating premature failure within a composite structure.
Trask, R. S.; Bond, I. P.
PURPOSE: To evaluate the results of balloon angioplasty of 17 stenoses resulting from intracranial atherosclerosis and vasculitis. METHODS: Seventeen skull-base and intracranial lesions were dilated with a microballoon angioplasty catheter.RESULTS:Initially, 16 of the 17 stenoses showed improvement at angiography. Moderate residual stenosis was found in 2 of 12 atherosclerotic lesions, both in the distal vertebral artery. Angioplasty in 1 of
John D. McKenzie; Robert C. Wallace; Bruce L. Dean; Richard A. Flom; Mazen H. Khayata
Release of microparticles (MPs) from blood cells may occur upon various activation signals. MPs from neutrophil and platelet have been studied in systemic infectious diseases and cardiovascular diseases, respectively. They are here investigated in common nephropathies including vasculitis and dialysis, two conditions characterized by neutrophil activation. Flow cytometry analysis of neutrophil-derived (CD66b-positive) and platelet-derived (CD41a-positive) MPs was performed on 213 plasma samples from patients with various nephropathies, including 46 patients with vasculitis and 40 hemodialysis patients. MPs released ex vivo, during neutrophil activation in whole blood, were also measured in these patients. Correlations with clinical parameters and creatinine clearance were evaluated. The results show that MPs present in plasma from patients or healthy controls are from various origins: platelet-derived (38+/-22%), neutrophil-derived (2.8+/-3.8%) MPs, mixed aggregates of neutrophil/platelet MPs (28+/-15%) or neither from neutrophil or platelet (null) 31+/-20%. Acute vasculitis showed the highest level of all types of MPs, while other nephropathies did not result in significant changes of MP levels. A significant increase was observed during hemodialysis sessions. In patients with renal failure, no correlation was seen between MP levels and creatinine clearance. In conclusion, neutrophil and platelet MP levels are non-specific markers of neutrophil activation during vasculitis acute phase and dialysis-induced inflammation. Circulating aggregates of neutrophil/platelet MPs co-express adhesion molecules of both cell types and may be thus endowed with inflammation and coagulation- thus modulating properties. PMID:16531979
Daniel, L; Fakhouri, F; Joly, D; Mouthon, L; Nusbaum, P; Grunfeld, J-P; Schifferli, J; Guillevin, L; Lesavre, P; Halbwachs-Mecarelli, L
Burkholderia gladioli is difficult to definitively identify within the laboratory using phenotypic testing alone. We describe a case of recurrent B. gladioli infection in a lung transplant recipient with underlying hypocomplementemic urticarial vasculitis syndrome, discuss the difficulties encountered with laboratory identification, provide a review of the methodology required for definitive identification, and discuss potential pathophysiologic mechanisms in this patient responsible for the difficulty in treatment. PMID:21504528
Thompson, G R; Wickes, B L; Herrera, M L; Haman, T C; Lewis, J S; Jorgensen, J H
Background: Cutaneous vasculitis is commonly recognized and biopsied, owing to ease of access. Most biopsies are also subjected to direct immunofluorescence (DIF), though the rates of positivity vary. This is an attempt to assess the utility of DIF and glean data that will help optimize the test. Objective: To assess the diagnostic utility of DIF in cutaneous vasculitis. Materials and Methods: All cases of suspected cutaneous vasculitis submitted for DIF between 2004 and 2010 were included. Clinical data, histopathologic diagnosis, DIF findings and additional tests such as anti nuclear antibody (ANA), anti neutrophil cytoplasmic antibody (ANCA) (where done) were noted. Results: There were 198 patients in the study group, with a female predominance. Purpura was the commonest clinical presentation. Extracutaneous involvement was noted in 29% of patients’ i.e., joint pain, abdominal pain and hematuria. Leukocytoclastic vasculitis was the commonest histologic diagnosis. DIF showed an overall positivity of 39% (n = 77) with C3 in 26% (n = 52) and IgA in 23% (n = 46) cases. Forty one cases of suspected Henoch Schonlein Purpura (HSP) showed IgA positivity. The timing of biopsy ranged from <3 days to six months, with 38% being done within seven days. DIF was positive in 86% of biopsies performed within seven days of onset of lesions. Sixty percent of patients with extracutaneous manifestations showed deposits. Vascular deposits were also noted in dermatitis herpetiformis, dematomyositis and prurigo. Conclusion: DIF positivity is strongly influenced by the timing of the biopsy and the presence of extracutaneous features. Its clinical value is greatest in patients with HSP, being contributory in 90% of cases. Vascular deposits may be seen in non-vasculitic conditions and need clinicopathologic correlation.
Nandeesh, BN; Tirumalae, Rajalakshmi
Chronic hepatitis B infection (HBI) has many extrahepatic manifestations such as vasculitis, glomerulonephritis, arthritis,\\u000a dermatitis, pulmonary disease, and skin manifestations. The mechanism of these manifestations is thought to be immune mediated.\\u000a Immune-suppressive treatment may enhance viral replication and worsen hepatic disease. Lamivudine is a nucleoside analogue\\u000a used in chronic HBI treatment that works by suppressing replication of the hepatitis B
Ozge Surmali Onay; Esra Baskin; Figen Ozçay; Engin Melek; Oguz Canan; Banu Bilezikçi
Background: Current therapies have changed systemic vasculitis from a disease with a high rate of mortality to a chronic curable condition. A limited percentage of patients either remains refractory to conventional treatment or experiences dose-limiting side effects. Methods: 11 patients (4 affected by idiopathic systemic microscopic polyangiitis, 5 by Wegener’s granulomatosis, and 2 by Churg-Strauss syndrome) intolerant or refractory to
Dario Roccatello; Savino Sciascia; Daniela Rossi; Mirella Alpa; Carla Naretto; Alessandra Russo; Elisa Menegatti; Simone Baldovino
The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's
S. Meusser; A. Rubbert; B. Manger; E. Bock; G. Platsch; H. Feistel; A. Engelhardt; F. Wolf; J. R. Kalden
An 81-year-old man presented with a generalized maculopapular rash, lymphadenopathy, conjunctivitis and arthritis. Vasculitis was confirmed by skin biopsy and by direct immunofluorescence, which showed perivascular C3 and granular IgM accumulation. Histology of an inguinal lymph node was diagnostic for angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), and this was confirmed by the finding of hypergammaglobulinaemia and elevated IgE levels. Immunohistology on a lymph node biopsy showed a T-helper cell (CD4) infiltrate expressing the interleukin (IL)-2 receptor alpha and beta chains. While receiving prednisone 100 mg/day, the patient developed new lesions, mimicking a relapse of vasculitis, which were subsequently shown to be necrotizing herpes zoster. Serum IL-2 and IL-6 levels were elevated. To our knowledge, this is the first report of simultaneous elevation of IL-2 and IL-6 in AILD: IL-2 may be involved in proliferation of the malignant cell clone, and IL-6 in the pathogenesis of both the vasculitis (via endothelial cell activation) and the hypergammaglobulinaemia. PMID:8547055
Böni, R; Dummer, R; Dommann-Scherrer, C; Dommann, S; Zimmermann, D R; Joller-Jemelka, H; Burg, G
Background Antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitides have a variety of presentations, but cardiac valvular involvement is rarely diagnosed and its management is not established. Case presentation We report the case of a 44 year old man who presented with an ANCA-associated systemic vasculitis and aortic regurgitation of unusual mechanism. Transthoracic and transesophageal echocardiography disclosed septal hypertrophy preventing a complete closure of the aortic valve and thus responsible for a massive aortic regurgitation. After 4 months of immunosuppressive therapy, the valve lesion did not subside and the patient had to undergo aortic valve replacement. This report also reviews the 20 cases of systemic ANCA-associated vasculitis with endocardial valvular involvement previously reported in the English language medical literature. Conclusions Valvular involvement in ANCA-associated systemic vasculitides is rarely reported. Most of these lesions are due to Wegener's granulomatosis and half are present when the diagnosis of vasculitis is made. The valvular lesion is usually isolated, aortic regurgitation being the most frequent type, and often requires valve replacement in the months that follow it's discovery.
The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)-associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA-associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long-term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate. PMID:23421384
Marco, Helena; Mirapeix, Eduard; Arcos, Emma; Comas, Jordi; Ara, Jordi; Gil-Vernet, Salvador; Puig, Josep; Vinyas, Odette; Perello, Manel; Oppenheimer, Federico; Poveda, Rafael; Ibernón, Meritxell; Díaz, Montserrat; Ballarin, Jose
Unlike Chlamydia trachomatis and C. psittaci, the association of C. pneumoniae infection with immunological complications, such as reactive arthritis (ReA) or erythema nodosum (EN) has been rarely reported. Here we present the case history of a patient with C. pneumoniae community acquired pneumonia (CAP) who subsequently developed a ReA and a cutaneous vasculitis. A 45-year-old HLA B27 negative male developed an asymmetric and additive arthritis and a cutaneous leukocytoclastic vasculitis with IgM and complement papillary deposition along hypodermic vessel walls about three weeks after the onset of respiratory symptoms. The diagnosis of chronic Chlamydia pneumoniae infection was based on serology and PCR. Cultural and serological investigations for other infectious agents commonly involved in ReA were negative. This is the first report on the occurrence of two immune-based complications, associated to Chlamydia pneumoniae infection. Therefore, since this infection is very common in our population, although often asymptomatic, should be systematically considered as a common causative agent of ReA and of vasculitis. PMID:12508779
Cascina, A; Marone Bianco, A; Mangiarotti, P; Montecucco, C M; Meloni, F
The purpose of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty for occlusive arterial disease associated with vasculitis. Eleven patients(10 women, 1 man; ages 35-82 years) with the diagnosis of vasculitis of the large vessels underwent interventional treatment during intraarterial angiography. The causes included giant cell arteritis(n = 8) and Takayasu arteritis (n = 3).Thirty-three occlusive lesions (including brachiocephalic and renalarteries, and arteries of upper and lower extremities) were treated with balloon angioplasty and/or stent placement. Follow-up included clinical examination, angiography, and color duplex ultrasound.Technical success was 100% (25/25) for stenoses and 50% (4/8) for occlusive lesions, representing all lesions combined from different anatomic locations. Dissection (n = 3) and arterial rupture with retroperitoneal hematoma (n = 1) was found in three patients. During follow-up (mean 12 months), restenoses(n = 8) and re-restenoses (n = 1)occurred in 8 vascular areas. Three of these lesions were treated with repeated PTA (n = 4). The cumulative primary clinical success rate was 67.6%, cumulative secondary success rate 74.4%, and cumulative tertiary success rate 75.9%. Interventional therapy in systemic vasculitis provides promising results in technical success rates and followup. Angioplasty may result in arterial injury, but the rate of complications is low.
Both, M.; Jahnke, T. [Department of Radiology, Christian-Albrechts-University of Kiel, Kiel(Germany); Reinhold-Keller, E. [Department of Rheumatology, University of Luebeck, Rheumaklinik Bad Bramstedt (Germany); Reuter, M.; Grimm, J.; Biederer, J.; Brossmann, J. [Department of Radiology, Christian-Albrechts-University of Kiel, Kiel (Germany); Gross, W.L. [Department of Rheumatology, University of Luebeck, Rheumaklinik Bad Bramstedt (Germany); Heller, M.; Mueller-Huelsbeck, S. [Department of Radiology, Christian-Albrechts-University of Kiel, Kiel (Germany)
Objective To identify biomarkers that distinguish between active ANCA-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV. 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Serum levels of E-selectin, ICAM-3, MMP1, MMP3, MMP9, P-selectin, thrombomodulin, and VEGF were measured at study screening (time of active disease) and at month 6. ESR and CRP levels had been measured at the time of the clinical visit. The primary outcome was the difference in marker level between screening and month 6 among patients in remission (BVAS/WG score of 0) at month 6. Results All subjects had severe active vasculitis (mean BVAS/WG score 8.6 +/? 3.2 SD) at screening. Among the 123 subjects clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP3 levels were also higher among the 23 subjects with active disease at month 6 than among the 123 subjects in remission. MMP3 levels correlated weakly with ESR and CRP. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers.
Monach, Paul A; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Cuthbertson, David; Krischer, Jeffrey; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Ikle, David; Kallenberg, Cees GM; Langford, Carol A; Mueller, Mark; Seo, Philip; St.Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Gu, Yi-Zhong; Snyder, Ronald D; Merkel, Peter A
The article reports a case and review of the literature of endophthalmitis presenting as isolated retinal vasculitis. A 26-year-old male was observed to have white-centered retinal hemorrhages and retinal vasculitis following an occult scleral perforation. At presentation, the visual acuity was 20/60. With clinical suspicion of early endophthalmitis, he underwent wound exploration, scleral tear repair, vitreous biopsy and administration of intravitreal antibiotics. Microbiology evaluation revealed significant presence of methicillin-resistant coagulase-negative Staphylococcus epidermidis. Final visual acuity improved to 20/20 at 6 weeks postoperatively. Literature search revealed eight similar cases, all of them due to Staphylococcus species. Retinal vasculitis and white-centered retinal hemorrhages can be a presenting sign of early endophthalmitis, especially with non-fulminant pathogens like S. epidermidis.
Relhan, Nidhi; Jalali, Subhadra; Nalamada, Suma; Dave, Vivek; Mathai, Annie
ABSTRACT A locally bred, 12-year-old, intact female Satsuma dog presented with generalized alopecia. Erythema, crusts and desquamation were observed primarily on the truck. Papules and erosions were present in the pinnae, and there were multiple areas of skin necrosis on the right forelimb. The cutaneous lesions had not responded to treatment with systemic antibiotics and prednisolone. The dog also had progressive anemia. Babesia gibsoni was detected in the blood, and the dog was treated with antiprotozoal agents. The skin lesions and anemia improved, but relapsed after the treatment was discontinued. Histopathological examination of skin biopsies revealed findings suggestive of early leukocytoclastic vasculitis or ischemic vasculopathy.
TASAKI, Yumi; MIURA, Naoki; IYORI, Keita; NISHIFUJI, Koji; ENDO, Yasuyuki; MOMOI, Yasuyuki
Positron emission tomography with 18F-fluorodesoxyglucose allows to locate pathological foci expressing a high metabolism. Originally shown in the investigation of neoplasia, this procedure is increasingly used as a new tool to search for inflammatory syndromes. Systemic vasculitis is a complex disorder, often manifested by non specific symptoms. Diagnosis at early stages allows early treatment, which may prevent progression to later complications. Through a case report and a review of the literature, this article describes the important role of PET/CT for the diagnosis when traditional tests remain unsuccessful. PMID:22574412
Stettler, Aline; Fumeaux, Christophe; Kamel, Ehab Mohamed; Petignat, Pierre-Auguste
Most patients presenting with systemic necrotizing vasculitides improve when they are adequately treated. The presence of life-threatening manifestations or visceral involvement modifying organ function characterizes severe vasculitis, confirmed by disease-severity scores. Sequelae cannot always be predicted and prevented but organ involvement present at disease onset requires rapid therapeutic intervention. Some patients present a persistent active disease, which does not respond to treatments and deserve other drugs or combination of drugs. The therapeutic options for severe and/or relapsing and refractory diseases are described. PMID:24925586
Neutrophil extracellular traps (NETs) are characterized by the presence of extracellular DNA fibers studded with antimicrobial proteins, including myeloperoxidase (MPO). Although NETs play an important role in the innate immune system, the scattered extracellular enzymes, such as MPO, pose risks to the host. Therefore, NETs are strictly regulated by DNase I in the serum, which prevents them from persisting. Recent studies have demonstrated that dysregulation of NETs could be involved in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. In this review, we interpret the association of disordered NETs with autoimmune diseases, especially propylthiouracil-induced MPO-ANCA-associated vasculitis. PMID:23224024
Nakazawa, Daigo; Tomaru, Utano; Ishizu, Akihiro
Segmental testicular infarction is an uncommon clinical entity marked by acute scrotal pain and swelling. Classically, these appear as wedge-shaped, avascular, hypoechoic lesions on a testicular ultrasound. We present a unique case of testicular infarct caused by an antineutrophil cytoplasmic antibody-positive vasculitis secondary to the use of the antibiotic minocycline. The patient's symptoms resolved with cessation of minocycline. We suggest that patients who present with otherwise unexplained testicular infarction undergo a careful review of medications to uncover a potential cause. PMID:24793001
Lyon, Timothy D; Ferroni, Matthew C; Casella, Daniel P; D'Agostino, Louis A; Jackman, Stephen V
We report the first case of combined retinal and CNS varicella zoster-associated vasculitis in a 49-year-old patient with multiple sclerosis who had been treated with natalizumab. He presented with a progressive bilateral visual loss. The diagnosis of a vasculitis was based on the fundoscopic examination and MRI findings. We confirmed the varicella zoster virus (VZV) infection of the CNS by PCR and increased intrathecal antibody indices in the cerebrospinal fluid. The patient was stabilized with antiviral treatment, methylprednisolone, plasmapheresis and cycophosphamide. Natalizumab was discontinued. This case illustrates the neuroimmunological and neuroinfectiological consequences of treatments with biologicals that influence the immune system.
Vasculitis of medium- and large-sized arteries is an inflammatory and stenotic disease characterized by a strong predilection for the aortic arch and its branches. It presents with symptoms and signs as per the vessels and organs involved. Pulmonary sequestration is a rare abnormality characterized by a mass of nonfunctioning lung tissue that receives its vascular supply from a systemic artery and is separated from the normal tracheobronchial tree. The following is a rare case report showing the presence of pulmonary sequestration in a patient with recently diagnosed hypertension and intestinal angina due to medium and large vessel vasculitis.
Malik, Sarthak; Khurana, Sakshi; Vasudevan, Vishnu; Gupta, Nikhil
Retinal vascular manifestation is the most common form of ophthalmic involvement in patients with systemic lupus erythematosus (SLE). Most frequently these consist of cotton-wool spots with or without intraretinal hemorrhages. Although rare, a more severe retinal vaso-occlusive disease, termed retinal vasculitis, has been described. We report on a 37-year-old white female with a 13-year follow-up of chronic discoid lupus erythematosus, which suffered massive bilateral visual loss coincident with the systemic exacerbation of her disease (proteinuria, pneumonia, serositis, leucopenia). The diagnosis of SLE was established with reference to the revised ARA-criteria (American Rheumatism Association). Ophthalmoscopy and fluorescein angiography revealed the typical aspect of a SLE-associated vaso-occlusive retinopathy on both eyes with marked ischemia of the macula. Immediate maximal immuno-suppressive therapy, early performed panretinal photocoagulation and subsequent cryoretinopexy did not stop the progression of the disease. Six months after the initial event vascularisations of the disc and rubeosis iridis occurred, but no secondary glaucoma up to date. In this patient, the almost complete absence of characteristic autoantibodies and immunological markers was striking. The correlation with other lupus manifestations, different therapeutic concepts and prognostic factors in SLE-associated retinal vasculitis are discussed. PMID:1479791
Koch, J W; al Nawaiseh, I; Koch, F H
Anti-neutrophil cytoplasmic antibody–associated (ANCA-associated) small vessel necrotizing vasculitis is caused by immune-mediated inflammation of the vessel wall and is diagnosed in some cases by the presence of myeloperoxidase-specific antibodies (MPO-ANCA). This multicenter study sought to determine whether differences in ANCA epitope specificity explain why, in some cases, conventional serologic assays do not correlate with disease activity, why naturally occurring anti-MPO autoantibodies can exist in disease-free individuals, and why ANCA are undetected in patients with ANCA-negative disease. Autoantibodies from human and murine samples were epitope mapped using a highly sensitive epitope excision/mass spectrometry approach. Data indicated that MPO autoantibodies from healthy individuals had epitope specificities different from those present in ANCA disease. Importantly, this methodology led to the discovery of MPO-ANCA in ANCA-negative disease that reacted against a sole linear sequence. Autoantibodies against this epitope had pathogenic properties, as demonstrated by their capacity to activate neutrophils in vitro and to induce nephritis in mice. The confounder for serological detection of these autoantibodies was the presence of a fragment of ceruloplasmin in serum, which was eliminated in purified IgG, allowing detection. These findings implicate immunodominant epitopes in the pathology of ANCA-associated vasculitis and suggest that autoantibody diversity may be common to other autoimmune diseases.
Roth, Aleeza J.; Ooi, Joshua D.; Hess, Jacob J.; van Timmeren, Mirjan M.; Berg, Elisabeth A.; Poulton, Caroline E.; McGregor, JulieAnne; Burkart, Madelyn; Hogan, Susan L.; Hu, Yichun; Winnik, Witold; Nachman, Patrick H.; Stegeman, Coen A.; Niles, John; Heeringa, Peter; Kitching, A. Richard; Holdsworth, Stephen; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.
Cutaneous small-vessel vasculitis (CSVV) is a disorder characterized by neutrophilic inflammation predominantly limited to the superficial cutaneous postcapillary venules. CSVV may be idiopathic or may have a defined cause such as infection, medication, connective tissue disease, or malignancy. CSVV may also be associated with extracutaneous disease or systemic vasculitis. The most common clinical presentation of CSVV consists of symmetrically distributed palpable purpura of the lower extremities. In general, lesional skin biopsy samples should be examined with light microscopy and direct immunofluorescence for adult patients with suspected CSVV. A complete history, review of systems, physical examination, and selected laboratory studies also should be performed to assess for inciting causes or extracutaneous involvement of CSVV. Treatment varies and depends on the chronicity of CSVV, the severity of cutaneous involvement, and the presence or absence of both an underlying cause and extracutaneous involvement of CSVV. An isolated episode of CSVV associated with a known inciting factor may be managed by removal or treatment of the trigger, along with symptomatic measures. First-line systemic treatments for chronic, idiopathic CSVV include colchicine or dapsone, used singly or in combination. Recurrent, chronic, or severely symptomatic CSVV that does not respond to the aforementioned therapies may require initiation of an immunosuppressive agent such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, or rituximab. PMID:24756249
Goeser, Megan R; Laniosz, Valerie; Wetter, David A
Pneumatosis cystoides intestinalis (PCI) is an uncommon disorder usually associated with intestinal and pulmonary obstructive diseases, recent abdominal procedures and systemic illnesses. PCI has been reported in patients with systemic lupus erythematosus associated with intestinal vasculitis. We describe herein a patient with a month history of intermittent abdominal pain, diarrhoea, hyporexia, and weight loss who underwent intestinal resection for acute abdomen. Post-operatively she gave a three-month history of arthritis of the right knee, ankles and feet, arthralgia of the wrists, MCPs and shoulders. She also described weakness, weight loss, Raynaud's phenomenon, and a skin rash. Laboratory examination revealed an increased ESR, low haemoglobin and haematocrit, positive rheumatoid factor, a positive ANA with a speckled pattern, as well antibodies to DNA, SS-A and cardiolipin. The abdominal symptomatology especially pain, cramps and bouts of diarrhoea persisted after the surgery and became worse two months later. Abdominal X-ray showed distention of bowel with cyst formation in the wall of the entire colon. A diagnosis of PCI was made radiologically. The intestinal pathology was reviewed and vasculitis was identified. The patient received treatment with high dose prednisone with an excellent response; prednisone was progressively tapered and she has been asymptomatic without abdominal complaints or other symptoms for over a year. PMID:8088081
Cabrera, G E; Scopelitis, E; Cuellar, M L; Silveira, L H; Mena, H; Espinoza, L R
A 61-year-old man was admitted to our department with purpura and hemorrhagic bullae on his lower limbs, dull pain affecting the entire abdomen, and hematochezia. Histopathological examination and immunostaining revealed leukocytoclastic vasculitis of the small blood vessels of the dermis and IgA deposition; multiple ulcers were observed in the ileum during lower gastrointestinal (GI) endoscopy, so we made a diagnosis of IgA vasculitis (Henoch-Schönlein). Treatment with oral prednisolone (PSL) at a dose of 80 mg/day (1 mg/kg/day) for one week resolved the symptoms almost completely. However, when the PSL dose was later reduced, dull epigastric pain and discomfort flared up again. Multiple punched-out ulcers were observed in the duodenum during upper GI endoscopy, and immunostaining revealed cytomegalovirus (CMV) in vascular endothelial cells and infiltrating cells. The patient's serum was positive for CMV antigenemia. On the basis of these findings, we concluded that the CMV enteritis had developed as a complication arising from the patient's immunosuppressed state, which was itself a result of the steroid therapy. We treated the patient with ganciclovir, which relieved the abdominal symptoms. PMID:24614396
Ninomiya, Risa; Omi, Tokuya; Kato, Tokue; Mayumi, Nobuko; Kawarasaki, Mai; Kawana, Seiji
Immunoglobulin (Ig) A vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is a systemic IgA-mediated leukocytoclastic vasculitis that usually affects children. We report the usefulness of video capsule endoscopy in 2 adolescent patients with IgAV having gastrointestinal involvement. Both patient 1, a 15-year-old girl, and patient 2, a 14-year-old boy, presented with purpuric rash and abdominal pain. Video capsule endoscopy showed multiple areas of purpuric erythema throughout the small bowel in both patients and showed multiple ulcers with bleeding in patient 2. Patient 1 responded well to oral prednisolone at a dose of 0.5 mg/kg/day. However, in patient 2, prednisolone at a dose of 0.5 mg/kg/day failed to control the symptoms; therefore, the dose was increased to 1 mg/kg/day to provide relief. Video capsule endoscopy was safe in both cases and produced no side effects. In conclusion, video capsule endoscopy is a useful tool for evaluating small bowel lesions in patients with IgAV and provides valuable information for the treatment of IgAV with gastrointestinal involvement. PMID:24805100
Li, Min; Omi, Tokuya; Matano, Yoko; Fujimori, Shunji; Kawana, Seiji
PET/CT is starting to play an important role in evaluating fever of unknown origin (FUO), due to its ability to localize and delineate areas of high metabolic activity, such as neoplastic proliferation and inflammation, including vasculitis. We present a case of giant cell arteritis (GCA) in a 72-year-old female patient admitted to our department with a 4-month history of FUO, weight loss and fatigue, without specific symptoms or signs. Laboratory investigations suggested acute phase response, with a pronounced erythrocyte sedimentation rate, high CRP level and microcytic anemia. A thorough diagnostic evaluation was performed to exclude an unknown primary tumor, which was initially suspected due to a positive family history of cancer. Surprisingly, PET/CT revealed large vessel vasculitis affecting the ascending, descending and abdominal aorta, as well as subclavian, proximal brachial and carotid arteries bilaterally. Biopsy of the superficial temporal artery confirmed the diagnosis of GCA. Treatment with methylprednisolone and azathioprine led to resolution of clinical symptoms and normalization of laboratory parameters. In addition to the use of PET/CT in the evaluation of FUO, its value as a method complementary to temporal artery biopsy is also discussed. PMID:22453531
Bosni?, Dubravka; Bareši?, Marko; Padjen, Ivan; Balenovi?, Antonija; Zarkovi?, Kamelija; Ani?, Branimir
Immune-complex-mediated vasculitis is a frequent complication of rheumatoid arthritis and systemic lupus erythematosus. The mechanism of deposition of immune complexes within the vessel wall in these diseases remains unknown, but probably involves other proteins. Fibronectin is a likely candidate since it possesses the ability to bind to collagen, endothelial cells, and possibly immunoglobulins and immune complexes. In this study, the binding of fibronectin to IgG and IgM cryoglobulins, cold soluble IgM, IgG, IgG subclasses and IgG fragments was investigated in the solution phase. Static light scattering, fluorescence anisotropy, fluorescence intensity, and PEG precipitation studies were used to investigate binding under different conditions of temperature and ionic strength. These studies failed to demonstrate significant binding between fibronectin and IgM, IgG, IgG subclasses and IgG fragments under the conditions studied. These findings argue against solution phase binding of fibronectin and immunoglobulins contributing to immune complex vasculitis. The possibility of important surface interactions between these proteins has not been ruled out.
Brandau, D T; O'Donnell, R; Kimmel-Truitt, V L
Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkin's lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intellectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system.
Zhu, Jia; Zhang, Yu; Zhen, Zi-Jun; Chen, Yan; Wang, Juan; Cai, Rui-Qing; Sun, Xiao-Fei
Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkin's lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intellectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system. PMID:23816555
Zhu, Jia; Zhang, Yu; Zhen, Zi-Jun; Chen, Yan; Wang, Juan; Cai, Rui-Qing; Sun, Xiao-Fei
Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed. PMID:1864005
D'Cruz, D P; Houssiau, F A; Ramirez, G; Baguley, E; McCutcheon, J; Vianna, J; Haga, H J; Swana, G T; Khamashta, M A; Taylor, J C
Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI)=84%±52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI=45%±35.9). Seventy normal human sera had a mean BI of 10%±9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P<0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.
D'Cruz, D. P.; Houssiau, F. A.; Ramirez, G.; Baguley, E.; McCutcheon, J.; Vianna, J.; Haga, H.-J.; Swana, G. T.; Khamashta, M. A.; Taylor, J. C.; Davies, D. R.; Hughes, G. R. V.
Purpose. To report favorable outcome of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with cerebral vasculitis after treatment with immunosuppressive therapy by mitoxantrone. Design. Single case report. Method. A 22-year-old man presented with acute isolated bilateral loss of vision revealing APMPPE. Corticosteroid therapy was initiated and visual acuity gradually improved. Seventeen days later, visual function deteriorated again, associated with flu-like syndrome and severe headaches. A relapse of APMPPE was diagnosed, complicated with lymphocytic meningitis and cerebral ischemia. Intravenous therapy with mitoxantrone was performed in combination with methylprednisolone. Results. Headaches disappeared in a few days whereas visual acuity gradually improved and stabilized at 20/40 in the right eye and 20/32 in the left eye. No adverse event was observed. Clinical improvement was confirmed by magnetic resonance imaging. Conclusion. Cerebral vasculitis is the most severe complication of the extraocular manifestations of APMPEE. This diagnosis should be evoked when severe headaches or behavior disorder are associated with APMPEE. PMID:19710935
Massé, Hélène; Guyomard, Jean-Laurent; Baudet, Dominique; Pinel, Jean-François; Edan, Gilles; Charlin, Jean-François
Purpose. To report favorable outcome of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with cerebral vasculitis after treatment with immunosuppressive therapy by mitoxantrone. Design. Single case report. Method. A 22-year-old man presented with acute isolated bilateral loss of vision revealing APMPPE. Corticosteroid therapy was initiated and visual acuity gradually improved. Seventeen days later, visual function deteriorated again, associated with flu-like syndrome and severe headaches. A relapse of APMPPE was diagnosed, complicated with lymphocytic meningitis and cerebral ischemia. Intravenous therapy with mitoxantrone was performed in combination with methylprednisolone. Results. Headaches disappeared in a few days whereas visual acuity gradually improved and stabilized at 20/40 in the right eye and 20/32 in the left eye. No adverse event was observed. Clinical improvement was confirmed by magnetic resonance imaging. Conclusion. Cerebral vasculitis is the most severe complication of the extraocular manifestations of APMPEE. This diagnosis should be evoked when severe headaches or behavior disorder are associated with APMPEE.
Masse, Helene; Guyomard, Jean-Laurent; Baudet, Dominique; Pinel, Jean-Francois; Edan, Gilles; Charlin, Jean-Francois
ANCA, implicated as having a pathogenic role in systemic vasculitis, can activate tumour necrosis factor-alpha (TNF-?)-primed neutrophils by cross-linking surface-expressed ANCA antigens with neutrophil Fc?RIIa receptors to release reactive oxygen species. The Fc?RIIa receptor exists as polymorphic variants, R131 and H131, which differ in their ability to ligate human IgG2 and IgG3. Neutrophils homozygous for the Fc?RIIa-H131 allotype bind more efficiently to IgG3 than the Fc?RIIa-R131 allotype and are the only human Fc?R which bind IgG2. Our aim was to determine whether the homozygous Fc?RIIa-H131 individuals are more susceptible to developing ANCA-associated systemic vasculitis and nephritis due to differential IgG binding and activation. Fc?RIIa allotype was determined by both allele-specific polymerase chain reaction (PCR) and Southern blotting with allele-specific oligonucleotide probes end-labelled with 32P-?ATP, after PCR amplification of genomic Fc?RIIa DNA in 107 Caucasian patients with ANCA+ vasculitis (of whom 89 had renal disease) and 100 ethnically matched controls. Phenotyping of neutrophil Fc?RIIa alleles was confirmed in some patients by quantitative flow cytometry using murine MoAbs 41H16 and IV.3. Of the patients with ANCA+ systemic vasculitis, 75 had ANCA with specificity for proteinase 3 and 32 with specificity for myeloperoxidase. Overall, no skewing in Fc?RIIa allotypes was seen in patients compared with controls. No significant increase of the Fc?RIIa-H131 allotype was found amongst patients irrespective of ANCA specificity, and no association between the Fc?RIIa allotype and nephritis was found. Our data suggest that the Fc?RIIa receptor allotype is not a major factor predisposing to the development of ANCA+ systemic vasculitis, or to nephritis.
TSE, WY; ABADEH, S; MCTIERNAN, A; JEFFERIS, R; SAVAGE, COS; ADU, D
Background We report on the case of an established perinuclear antineutrophil cytoplasmic antibody (pANCA) associated renal vasculitis being treated with prednisolone and rituximab, where the patient presented with leg weakness, urinary and faecal incontinence and buttock pain consistent with transverse myelitis. Case presentation The patient underwent MRI scanning showing patchy cord enhancement from T10 to the conus, which was suggestive of a cord malignancy. Prior to a cord biopsy, he was treated with steroids and a repeat MRI showed resolution of the original lesion with a new similar lesion from C7 to T3. Conclusions He made a marked recovery after further treatment with high dose steroids and plasma exchange.
: Decorative tattoos are associated with a variety of adverse cutaneous reactions. We describe a unique fibrosing vasculitic reaction to red tattoo ink. The histopathology was similar to that in localized chronic fibrosing vasculitis (LCFV), but sharply limited to sites of red tattoo ink injection and associated with florid verrucoid epidermal hyperplasia. LCFV has been described in a broad variety of slowly progressive disorders with a firm consistency such as erythema elevatum diutinum, plasma cell granuloma, granuloma faciale, and IgG4-associated sclerosing diseases. It has been hypothesized that LCFV is the result of maladaptive immune reaction with failure to clear the causative antigen. To the best of our knowledge, this is the first case of LCFV associated with tattoo. We speculate on the implications our case holds for the pathogenesis of LCFV. PMID:24736671
Deeken, Audrey; Jefferson, Julie; Hawkinson, Dana; Fraga, Garth R
Vasculitis has long been associated with chronic viral infections, thus the twin perils of the infection and the immune response against it that bedevils the specialties of infection and immunity. After HIV was identified, it too became associated with vasculitic syndromes. Later, hepatitis C virus was also isolated, identified and described with its own spectrum of vasculitic diseases, including hepatitis C virus-associated cryoglobulinaemia. With the increasing prevalence of HIV and hepatitis C virus coinfection, there has come an increasing recognition of the range of vasculitides that can occur in this population leading to significant morbidity, diagnostic and treatment challenges. In this review, we examine the epidemiology, pathogenesis and general principles of treatment of these systemic diseases in HIV/hepatitis C virus coinfected individuals. PMID:23970639
Ojaimi, Samar; Lin, Ming-Wei; Singh, Kasha P; Woolley, Ian
A previously fit 66-years-old male primarily presented symptoms compatible with Henock-Schönlein's purpura, from which he seemingly recovered. Shortly hereafter he relapsed with an IgM lambda essential monoclonal cryoglobulinemia type I, presenting a systemic, necrotizing vasculitis, with low titer of circulating immune complexes and complement consumption. Glucocorticoid treatment and plasmapheresis did not prevent an ultimately lethal course. An indirect immunoperoxidase technique showed that the cryo-IgM bound to the interstitial connective tissue corresponding to the localization of collagen type I. In addition it bound to affinity purified human procollagen type I. These results indicate, that the IgM lambda of the proband was an autoantibody with collagen type I specificity. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5
Clemmensen, I; Jensen, B A; H?lund, B; Kappelgaard, E; Neilsen, H
Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease (ESRD). The optimal timing of kidney transplantation (KTX) for ESRD as a result of AAV and the risk of AAV relapse after KTX are not well defined. We report our experience with AAV patients who underwent KTX at our institutions between 1996 and 2010. Median follow-up was 64 months. Methods Retrospective multicenter cohort study. Results Eighty-five patients (45 men/40 women; mean age 49 years) received a KTX for ESRD secondary to microscopic polyangiitis (n=43) or Wegener’s granulomatosis (n=42). Twenty-four patients underwent preemptive KTX and 69 received a living-donor KTX. All patients were in remission at the time of KTX. Fifty-eight patients received induction therapy. In 64 patients, maintenance immunosuppression was with prednisone, mycophenolate mofetil, and tacrolimus. At the time of KTX, 29 patients were ANCA-positive. The vasculitis relapse rate was 0.02 per patient-years and was not influenced by disease category, ANCA subtype, or remission duration before KTX. There were 23 rejection episodes in 13 patients with seven graft losses. Median serum creatinine at 1 year was 1.3 mg/dL in 75 patients with more than 1 year follow-up and 1.4 mg/dL at last follow-up. The graft and patient survival rates were 100% at 1 year, 97.9% and 93.4% at 5 years, and 79.0% and 67.4% at 10 years, respectively. Conclusions KTX is a safe and an effective option for treating ESRD secondary to AAV. Relapses are rare with current immunosuppression.
Geetha, Duvuru; Eirin, Alfonso; True, Karin; Irazabal, Maria Valentina; Specks, Ulrich; Seo, Philip; Nachman, Patrick; Fervenza, Fernando C.
Background and objectives: Ongoing randomized trials seek to validate the efficacy of rituximab as an induction agent for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, no studies directly address the role of rituximab as maintenance therapy. Design, setting, participants, & measurements: This retrospective study reports the authors' experience with continuous rituximab administration in 39 patients in complete or partial remission at the time of rituximab initiation. All 39 patients had at least 1 year of follow-up, and 20 had 2 years of follow-up. Results: Disease activity, as measured by a modified Birmingham Vasculitis Activity Score, decreased from a median of 1 at baseline to 0 at 12 (P < 0.001) and 24 months (P = 0.02). Three patients experienced nonorgan-threatening flares during 708 patient-months of follow-up. Each flare occurred after at least 20 months of follow-up. The percentage of patients on cytotoxic immunosuppression decreased from 87% at baseline to 41% at 12 months (P < 0.001) and 30% at 24 months (P = 0.002). The percentage of patients on prednisone decreased from 92% at baseline to 59% at 12 months (P < 0.001) and 55% at 24 months (P = 0.02). Two patients developed late-onset neutropenia; both responded to treatment with recombinant granulocyte colony-stimulating factor. Conclusions: The successful use of continuous anti-B cell therapy in patients with AAV in complete or partial remission is reported. This extends the potential role of rituximab beyond induction to include maintenance therapy. However, more data are required regarding the delayed adverse effects of rituximab.
Rhee, Eugene P.; Laliberte, Karen A.
Background Previous studies observed the high prevalence of venous thromboembolism in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study analyzed the coagulation and fibrinolysis index profile in AAV patients. Methods The current study recruited 321 AAV patients in active stage and 78 AAV patients in quiescent stage. Coagulation and fibrinolysis index profiles in these AAV patients were analysed, and their associations with various clinical and pathological parameters were further investigated. Results The circulating levels of D-dimer, fibrin degradation products and platelet count were significantly higher in AAV patients in active stage compared with those in remission [0.8 (0.4, 1.5) mg/L vs. 0.28 (0.2, 0.55) mg/L, P<0.05; 5.6 (5.0, 10.0) mg/L vs. 1.9 (1.2, 2.8) mg/L, P<0.05; 269±127×109/L vs. 227±80×109/L, P<0.05, respectively]. Among the 321 AAV patients in active stage, compared with patients with normal levels of D-dimer, patients with elevated D-dimer levels had significantly higher levels of initial serum creatinine, erythrocyte sedimentation rate, C reactive protein and the Birmingham Vasculitis Activity Scores (P?=?0.014, P<0.001, P<0.001, P?=?0.002, respectively). Moreover, correlation analysis showed that the levels of D-dimer correlated with erythrocyte sedimentation rate and C reactive protein levels (r?=?0.384, P<0.001; r?=?0.380, P<0.001, respectively). Conclusion Patients with active AAV are in hypercoagulable states, and circulating levels of D-dimer are associated with disease activity of AAV.
Ma, Tian-Tian; Huang, Yi-Min; Wang, Chen; Zhao, Ming-Hui; Chen, Min
Leukocytoclastic vasculitis is a multicausal systemic inflammatory disease of the small vessels, histologically characterized by inflammation and deposition of both nuclear debris and fibrin in dermal postcapillary venules. The clinical picture typically involves palpable purpura of the lower legs and may be associated with general symptoms such as fatigue, arthralgia and fever. Involvement of the internal organs, most notably the kidneys, the central nervous system or the eyes, is possible and determines the prognosis. Oxaliplatin-induced leukocytoclastic vasculitis is a very rare event that limits treatment options in affected patients. We report 2 patients who developed the condition under chemotherapy for advanced rectal and metastatic colon carcinoma, respectively; a termination of the therapy was therefore necessary. While current therapies for colorectal cancer include the combination of multimodal treatment with new and targeted agents, rare and unusual side effects elicited by established agents also need to be taken into account for the clinical management. PMID:24474925
Quack, Henriette; Erpenbeck, Luise; Wolff, Hendrik A; Sprenger, Thilo; Seitz, Cornelia S; Schön, Michael P; Neumann, Steffen; Stanek, Kathrin; Ghadimi, B Michael; Michels, Beate; Middel, Peter; Schaefer, Inga-Marie; Liersch, Torsten; Conradi, Lena-Christin
A 62-year-old man was suffering from bronchial asthma and referred to our institution with dry cough and dyspnea on exertion in November, 2010. He was diagnosed with eosinophilic granulomatosis with polyangiitis (EPGA, formerly Churg-Strauss syndrome) by chest radiographic findings, blood eosinophilia, mononeuritis multiplex and cardiomyopathy. Steroid therapy was started and he was rapidly improved. Steroid therapy had been tapered off by May, 2012. After 2 months, however, progressive dyspnea, neural symptoms, deafness, re-elevation of blood eosinophils and bilateral multifocal infiltrations appeared. He was re-admitted to our institution. Transbronchial lung biopsy (TBLB) specimens revealed extra-vascular granuloma, eosinophilic vasculitis and eosinophilic pneumonia and we diagnosed him with the reccurence of EGPA. He was improved by steroid pulse therapy, then tapered. This case was the antineutrophil cytoplasmic autoantibodies negative EGPA. The case of EGPA with granuloma and vasculitis diagnosed by TBLB was rare. PMID:23760204
Hara, Yu; Kanoh, Soichiro; Fujikura, Yuji; Kawano, Shuichi; Misawa, Kazuhisa; Kawana, Akihiko
Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG PET) plays a major role in the management of oncology patients. Owing to the singular properties of the glucose tracer, many patients suffering from non-malignant diseases such as inflammatory or infectious diseases may also derive clinical benefit from the appropriate use of metabolic imaging. Large vessel vasculitides such as giant cell arteritis and Takayasu arteritis are other examples that may potentially extend the field of (18)FDG PET indications. The purpose of the present article is to assess the feasibility of metabolic imaging in vasculitis on the basis of the current literature data. In particular, the clinical context and the (18)FDG imaging patterns seen in patients with large vessel vasculitis are analysed in order to identify potential indications for metabolic imaging. PMID:12811529
Belhocine, Tarik; Blockmans, Daniel; Hustinx, Roland; Vandevivere, Johan; Mortelmans, Luc
Background Candida albicans water-soluble fraction (CAWS), a mannoprotein-?-glucan complex obtained from the culture supernatant of C. albicans NBRC1385, causes CAWS-mediated vasculitis (CAWS-vasculitis) in B6 and DBA/2 mice with mild and lethal symptoms, respectively. Why CAWS is lethal only in DBA/2 mice remains unknown. Results We performed DNA microarray analyses using mRNA obtained from peripheral blood mononuclear cells (PBMCs) of B6 and DBA/2 mice and compared their respective transcriptomes. We found that the mRNA levels of interferon-? (Ifng) and several genes that regulate the complement system, such as C3, C4, Cfb, Cfh, and Fcna, were increased dramatically only in DBA/2 mice at 4 and 8 weeks after CAWS administration. The dramatic increase was confirmed by quantitative real-time polymerase chain reactions (qRT-PCR). Moreover, mRNA levels of immune-related genes, such as Irf1, Irf7, Irf9, Cebpb, Ccl4, Itgam, Icam1, and IL-12rb1, whose expression levels are known to be increased by Ifng, were also increased, but only in DBA/2 mice. By contrast, the mRNA level of Dectin-2, the critical receptor for the ?-mannans of CAWS, was increased slightly and similarly in both B6 and DBA/2 mice after CAWS administration. Conclusions Taken together, our results suggest that CAWS administration induces Dectin-2 mediated CAWS-vasculitis in both B6 and DBA/2 mice and the expression of Ifng, but only in DBA/2 mice, which led to increased expression of C3, C4, Cfb, Cfh, and Fcna and an associated increase in lethality in these mice. This model may contribute to our understanding of the pathogenesis of severe human vasculitis.
There has been a marked increase in the past 15 years in the number and quality of clinical trials in the idiopathic inflammatory vasculitides, especially the small-vessel vasculitides known as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis [AAV; granulomatosis, with polyangiitis (Wegener's)]. These trials have been conducted by multicenter, international groups in Europe and the United States with financial support provided by government agencies and biopharmaceutical companies. This increased clinical trial activity in vasculitis has been accompanied by the development and validation of new outcome measures — a challenging process for these complex, multiorgan system diseases. The international OMERACT Vasculitis Working Group has developed and implemented an iterative research agenda that has utilized accumulated experience and datasets from several multicenter clinical trials and large cohort studies. This work has led to the development, evaluation, validation, and endorsement, through the OMERACT consensus and validation processes, of a “core set” of outcome measurements for use in clinical trials of AAV. The core set includes domains of disease activity, damage assessment, patient-reported outcomes, and mortality; there is at least one validated outcome measurement instrument available for each domain. This report reviews the domains of illness in AAV included in the OMERACT core set, describes the instruments validated to measure these domains, and presents the approved core set.
MERKEL, PETER A.; AYDIN, SIBEL Z.; BOERS, MAARTEN; DIRESKENELI, HANER; HERLYN, KAREN; SEO, PHILIP; SUPPIAH, RAVI; TOMASSON, GUNNAR; LUQMANI, RAASHID A.
A 53-year-old Caucasian woman with a history of anorexia nervosa developed a bilateral lower extremity rash comprised of palpable red to violaceous, sub-centimeter papular lesions that increased in quantity rapidly. She also noted a 2-month history of non-productive cough. Imaging modalities revealed a thin-walled cavitary lesion in the right lung apex and scattered nodular opacities. Acid fast bacilli (AFB) were found in sputum and subsequently identified by culture as Mycobacterium avium-intracellulare (MAI). Punch biopsies of her skin lesions yielded a histological diagnosis of small-to-medium vessel vasculitis. Stains and cultures for organisms were negative. Her skin lesions resolved quickly after the initiation of antimicrobial therapy for MAI. Hypersensitivity vasculitis associated with an atypical mycobacterial infection is unusual. The postulated underlying mechanism is the deposit of immune complexes and not the bacillus itself. While cutaneous leukocytoclastic vasculitis (CLV) due to MAI is certainly a rare entity, it should be entertained in patients with vasculitic skin lesions and a concomitant pulmonary disease. PMID:24363210
Walsh, T L; Baca, V; Stalling, S S; Natalie, A A; Veldkamp, P J
Antineutrophil cytoplasmic antibody (ANCA) is often used in the laboratory to confirm paucicellular vasculitis like Wegener's granulomatosis, Churg Strauss syndrome or polyarteritis nodosa in the presence of suggestive clinical features. In tropical countries, tuberculosis, leprosy and, occasionally, malaria can produce clinical features similar to a vasculitic illness and all the three infections are known to be associated with auto antibodies. We tested 318 patients suffering from malaria, tuberculosis or leprosy for ANCA positivity. ANCA positivity was found in 19%, 32% and 30% of malaria, tuberculosis and leprosy patients (Pradhan V, Badakere S, Shankarkumar V, Iyer Y, Ghosh K, Karnad D, Indian J Malariol, 39:51-59, 2002; Pradhan V, Badakere S, Ghosh K, Pawar A, Indian J Med Sci, 58:283-288, 2004a; Pradhan V, Badakere S, Shankarkumar V, Lepr Rev, 75:50-56, 2004b), respectively, raising the possibility that ANCA positivity with clinical features suggestive of vasculitis in tropical countries may even be related to the background noise of this seropositivity caused by one of these three infections rather than confirming the diagnosis of paucicellular vasculitis. Hence, one should be careful about the background noise of ANCA positivity caused by these infections while diagnosing a vasculitic illness. PMID:18297472
Ghosh, Kanjaksha; Pradhan, Vandana; Ghosh, Kinjalka
Microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) are conditions classified under the general heading of antinuclear cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Lung lesion is a very common and important clinical feature in AAV. In MPA, diffuse alveolar hemorrhage and pulmonary fibrosis (PF) are the most frequent manifestations. High-resolution computed tomography (HRCT) chest findings associated with MPA in PF patients demonstrate a high frequency of usual interstitial pneumonia (UIP), fibrotic-nonspecific interstitial pneumonia (F-NSIP), and combined PF and emphysema (CPFE) pattern with honeycombing, traction bronchiectasis, ground-glass opacity, and emphysema. In most of these cases, the histologic pattern of PF has been classified as UIP and/or fibrotic NSIP. In addition, a high incidence of histological findings, such as extensive interstitial fibrosis, lymphoid hyperplasia, and bronchiolitis, are characteristics observed in PF associated with collagen vascular diseases and which are not observed in idiopathic PF (IPF). In some cases, PF precedes the development of MPA. Indeed, there are some cases of pulmonary-limited MPA in this group. Therefore, clinicians should be aware of MPA as an underlying feature of PF in order to avoid overlooking and misdiagnosing this condition as IPF. The median survival time (MST) in UIP pattern/MPA is comparable with that of IPF. In GPA, almost all patients have either upper airway or lower respiratory tract lesions. Solitary or multiple nodules (frequently cavitated) and masses are the most common findings on chest images. Asthma is a cardinal symptom of Churg-Straus syndrome, often preceded by allergic rhinitis. To induce remission, a severity-based regimen was given to patients according to the appropriate protocol of the Japanese patients with myeloperoxidase (MPO)-ANCA-associated vasculitis (JMAAV) study group: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; severe-form regimen plus plasmapheresis in those with the most severe form. PMID:23188194
Homma, Sakae; Suzuki, Aika; Sato, Keita
Prior to the 1970s, severe cases of antineutrophil cytoplasmic antibody associated vasculitis (AAV) were thought to be invariably fatal. However, the use of cyclophosphamide-based treatment regimens fundamentally altered disease outcomes, transforming AAV into a manageable, chronic illness. Despite the tremendous success of cyclophosphamide in the treatment of AAV, there remained a need for alternative therapies, due to high rates of treatment failures and significant toxicities. In recent years, with the introduction of targeted biologic response modifiers into clinical practice, many have hoped that the treatment options for AAV could be expanded. Rituximab, a chimeric monoclonal antibody directed against the B-lymphocyte protein CD20, has been the most successful biologic response modifier to be used in AAV. Following the first report of its use in AAV in 2001, experience with rituximab for treatment of AAV has rapidly expanded. Rituximab, in combination with glucocorticosteroids, is now well established as a safe and effective alternative to cyclophosphamide for remission induction for severe manifestations of granulomatosis with polyangiitis and microscopic polyangiitis. In addition, initial experiences with rituximab for remission maintenance in these diseases have been favorable, as have experiences for remission induction in eosinophilic granulomatosis with polyangiitis.
Clain, Jeremy M.; Cartin-Ceba, Rodrigo; Fervenza, Fernando C.
Large vessel vasculitis (LVV) covers a spectrum of primary vasculitides predominantly affecting the aorta and its major branches. The two main subtypes are giant cell arteritis (GCA) and Takayasu arteritis (TA). Less commonly LVV occurs in various other diseases. Clinical manifestations result from vascular stenosis, occlusion, and dilation, sometimes complicated by aneurysm rupture or dissection. Occasionally LVV is discovered unexpectedly on pathological examination of a resected aortic aneurysm. Clinical evaluation is often unreliable in determining disease activity. Moreover, the diagnostic tools are imperfect. Acute phase reactants can be normal at presentation and available imaging modalities are more reliable in delineating vascular anatomy than in providing reliable information on degree of vascular inflammation. Glucocorticoids are the mainstay of therapy of LVV. Patients may develop predictable adverse effects from long-term glucocorticoid use. Several steroid-sparing agents have also shown some promise and are currently in use. Endovascular revascularization procedures and open surgical treatment for aneurysms and dissections are sometimes necessary, but results are not always favorable and relapses are common. This article, the first in a series of two, will be devoted to GCA and isolated (idiopathic) aortitis, while TA will be covered in detail in the next article. PMID:24893935
Chatterjee, Soumya; Flamm, Scott D; Tan, Carmela D; Rodriguez, E Rene
ANCA-associated vasculitis (AAV) is a subgrouping of autoimmune disorders characterized by a chronic relapsing course. Induction therapy is usually effective, but 70% of patients will relapse and 20% develop refractory disease. In the relapsing and refractory subgroups, treatment is complicated by the cumulative exposure to toxic drugs that contribute to poor long-term outcomes. The anti-CD20 monoclonal antibody rituximab (RTX) depletes B cells, and the success of this targeted therapy has contributed to the evidence supporting a central role for B cells in AAV pathogenesis. Initial proof of RTX effectiveness originated from small, prospective trials and retrospective surveys conducted in AAV patients with relapsing and refractory disease; high remission rates permitted the reduction of glucocorticoids (GCS) doses and withdrawal of immunosuppressives. There has been controversy over the effectiveness of RTX in patients with predominantly granulomatous manifestations, where response rates have varied between studies, in part due to different RTX dosing regimens. These studies were followed by comparison of RTX against cyclophosphamide (CYC) for remission induction of new or relapsing AAV in two randomized trials, which led to the licensing of RTX for this indication. Subsequent attention has been turned to the use of RTX as a relapse prevention agent, to the potential for GCS sparing and to RTX-associated toxicity. We will discuss the impact that the results of RTX clinical trials have had on the management of AAV patients. PMID:24126571
Alberici, Federico; Jayne, David R W
Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA-associated vasculitis (AAV) by stimulating polymorphonuclear leucocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are stimulated more readily by ANCA compared with PMNs from healthy controls (HCs). Differences in ANCA characteristics that can account for different stimulation potential were also studied. PMNs from five AAV patients and five HCs were stimulated with 10 different immunoglobulins (Ig)Gs, purified from PR3-ANCA-positive patients, and ROS production, degranulation and neutrophil extracellular trap (NET) formation was measured. ANCA levels, affinity and clinical data of the AAV donors were recorded. The results show that PMNs from AAV patients produce more intracellular ROS (P?=?0·019), but degranulate to a similar extent as PMNs from HCs. ROS production correlated with NET formation. Factors that may influence the ability of ANCA to activate PMNs include affinity and specificity for N-terminal epitopes. In conclusion, our results indicate that PMNs from AAV patients in remission behave quite similarly to HC PMNs, with the exception of a greater intracellular ROS production. This could contribute to more extensive NET formation and thus an increased exposure of the ANCA autoantigens to the immune system. PMID:24666336
Ohlsson, S M; Ohlsson, S; Söderberg, D; Gunnarsson, L; Pettersson, A; Segelmark, M; Hellmark, T
Introduction Anti-neutrophil cytoplasmic antibody-associated vasculitis has been associated with many drugs and it is a relatively rare side effect of the antihypertensive drug hydralazine. The diagnosis and management of patients who have anti-neutrophil cytoplasmic antibody-associated vasculitis may be challenging because of its relative infrequency, variability of clinical expression and changing nomenclature. The spectrum of anti-neutrophil cytoplasmic antibody-associated vasculitis is wide and can be fatal. This case documents a 62-year-old woman who presented with hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis with a puzzling cutaneous rash. Case presentation We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis in a 62-year-old Caucasian woman who presented with a vasculitic syndrome with a sore throat, mouth ulcers and otalgia after several months of constitutional symptoms. She then proceeded to develop a rash over her right lower limb. Clinically, the rash had features to suggest Sweet’s syndrome, but also had some appearances consistent with embolic phenomena and did not have the appearance of palpable purpure usually associated with cutaneous vasculitis. Differential diagnoses were hydralazine-associated Sweet’s syndrome, streptococcal-induced cutaneous eruption or an unrelated contact dermatitis. A midstream urine sample detected glomerular blood cells in the setting of anti-neutrophil cytoplasmic antibody-positive renal vasculitis and Streptococcus pyogenes bacteremia. A renal biopsy revealed a pauci-immune, focally necrotizing glomerulonephritis with small crescents. Her skin biopsy revealed a heavy neutrophil infiltrate involving the full thickness of the dermis with no evidence of a leucocytoclastic vasculitis, but was non-specific. She was initially commenced on intravenous lincomycin for her bloodstream infection and subsequently commenced on immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. Conclusion Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present with a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titres of anti-myeloperoxidase-anti-neutrophil cytoplasmic antibody with multi-antigenicity, positive anti-histone antibodies and the lack of immunoglobulin and complement deposition histopathogically. A rash that is characteristic of Sweet’s syndrome has also been described as an association. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed for definite treatment.
Synchronous malignant B-cell lymphoma and gastric tubular adenocarcinoma associated with paraneoplastic cutaneous vasculitis: hypereosinophilic syndrome with mixed cryoglobulinemia is an important sign of paraneoplastic syndrome
Gastric adenocarcinoma developing concomitantly with a lymphoma is rare. Furthermore, B-cell lymphoma, originating from lymph nodes, with eosinophilia is extremely rare. We report here a case with a synchronous diffuse large B-cell lymphoma (DLBCL) and an early adenocarcinoma of the stomach. In addition, this case seemed to be associated with paraneoplastic cutaneous vasculitis caused by hypereosinophilic syndrome (HES) with mixed cryoglobulinemia (MC). Many neoplastic diseases that affect internal organs display cutaneous manifestations, which may be the presenting signs and symptoms of the underlying malignancy. In particular, the association between cutaneous vasculitis and malignancy has been widely reviewed, and recently neoplasms have been suggested to produce antigens and the resultant immune complex formations, activating the serum complement, thus cause paraneoplastic vasculitis. In this case, severe eosinophilia and cryoglobulinemia with low complements were observed in a laboratory test. A biopsy specimen from a skin lesion revealed leukocytoclastic vasculitis with severe perivascular infiltration of eosinophils. The cutaneous vasuculitis was considered to be a manifestation of HES with MC, although there were no etiological factors of HES and MC. Therefore, the vasculitis seems to be a symptom of paraneoplastic syndrome in this case. Our finding suggests that the potential presence of malignancies should be kept in mind as a possible underlying disorder especially in the presence of HES with MC; this possibility is interesting also as regards at least part of the pathogenesis for paraneplastic syndrome.
Nozawa, Kazuhisa; Kaneko, Hiroshi; Itoh, Tomoyasu; Katsura, Yoko; Noguchi, Masaaki; Suzuki, Fujihiko; Takasaki, Yoshinari; Ogawa, Hideoki; Takamori, Kenji; Sekigawa, Iwao
Objectives To characterize patient perceptions, related to eight self-management behaviours relevant for adults with ANCA-associated small vessel vasculitis (ANCA-SVV), and to determine if these perceptions were associated with performance of each behaviour. Methods Adults with ANCA-SVV (n=202) completed a self-administered questionnaire that assessed eight self-management behaviours (adherence to recommendations for medication, health service use, diet, exercise, infection avoidance and symptom monitoring; prompt reporting of symptoms and side effects; and adjusting activities in response to symptoms), perceptions about these behaviours, socio-demographics, clinical factors and social desirability bias. Descriptive statistics were generated to characterize patients’ perceptions about difficulty of, importance of, and specific barriers to performing each behaviour. Regression analyses explored whether these variables were associated with performing each behaviour, controlling for potential confounders. Results With few exceptions, higher perceived importance and lower perceived difficulty of each behaviour were associated with more frequent performance of the behaviour. For each behaviour, several specific barriers were frequently endorsed by patients and a number of these were associated with lower levels of self-management. Conclusion This study reveals that patient perceptions about the illness and its treatment influence ANCA-SVV self-management. Perceived barriers to medication, health services, diet and exercise adherence were similar to those in other illnesses. This study also provides insight into barriers experienced by patients in performing behaviours (infection avoidance, symptom monitoring, reporting symptoms and side-effects and adjusting activities) not often previously studied. How the identification of these barriers can help inform future interventions for ANCA-SVV patients is to be discussed.
Thorpe, C. T.; DeVellis, R. F.; Blalock, S. J.; Hogan, S. L.; Lewis, M. A.; DeVellis, B. M.
Summary Background and objectives This study aimed to evaluate dialysis and transplant outcomes of patients with ESRD secondary to ANCA-associated vasculitis (AAV). Design, setting, participants, & measurements All ESRD patients who commenced renal replacement therapy in Australia and New Zealand between 1996 and 2010 were included. Outcomes were assessed by Kaplan–Meier, multivariable Cox regression, and competing-risks regression survival analyses. Results Of 36,884 ESRD patients, 228 had microscopic polyangiitis (MPA) and 221 had granulomatosis with polyangiitis (GPA). Using competing-risks regression, compared with other causes of ESRD, MPA patients (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.73–1.08; P=0.24) and GPA patients (HR, 0.94; 95% CI, 0.74–1.19; P=0.62) experienced comparable survival on dialysis. Forty-six MPA patients (21%) and 47 GPA (20%) patients received 98 renal allografts. Respective 10-year first graft survival rates in MPA, GPA, and non-AAV patients were 50%, 62%, 70%, whereas patient survival rates were 68%, 85% and 83%, respectively. Compared with non-AAV patients, MPA transplant recipients had higher risks of graft failure (HR, 1.87; 95% CI, 1.07–3.25; P=0.03) and death (HR, 1.94; 95% CI, 1.02–3.69; P=0.04), whereas GPA transplant recipients experienced comparable renal allograft survival (HR, 0.91; 95% CI, 0.43–1.93; P=0.81) and patient survival (HR, 0.58; 95% CI, 0.23–2.27; P=0.58). AAV recurrence was observed in two renal allografts (2%). Conclusions Compared with ESRD patients without AAV, those with GPA have comparable renal replacement therapy outcomes, whereas MPA patients have comparable dialysis survival but poorer renal transplant allograft and patient survival rates.
Tang, Wen; Bose, Bhadran; McDonald, Stephen P.; Hawley, Carmel M.; Badve, Sunil V.; Boudville, Neil; Brown, Fiona G.; Clayton, Philip A.; Campbell, Scott B.; Peh, Chen Au
Names influence how something is perceived. Diagnostic terms (diagnoses) are the names of diseases that are usually derived either from some distinctive characteristic of the disease or include an eponym recognizing someone who elucidated the disease. No matter how logical and appropriate a name may be, if it is not usable and used it is of no lasting value. This brief commentary focuses on the nomenclature of systemic vasculitides, and uses as a prime example Wegener's granulomatosis, which has been renamed recently ‘granulomatosis with polyangiitis’, in part because of concerns about the suitability of Friedrich Wegener as the source of an eponym. The most distinctive pathological feature of Wegener's granulomatosis is multi-focal necrotizing inflammation that has long been called granulomatosis. The systemic variant of Wegener's granulomatosis also is characterized by inflammation in many different vessels or different types, i.e. polyangiitis. Thus, granulomatosis with polyangiitis is a very appropriate alternative term for Wegener's granulomatosis. This term also is in accord with the name for a closely related vasculitis, i.e. microscopic polyangiitis. Terms that indicate aetiology and pathogenesis, when known, are useful to include in names for diseases (diagnoses). Anti-neutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA) are implicated in the cause of granulomatosis with polyangiitis and thus also should be specified in the diagnosis (e.g. PR3-ANCA-positive granulomatosis with polyangiitis or MPO-ANCA-positive microscopic polyangiitis). As our understanding of the clinical manifestations, pathogenesis and aetiology of vasculitides change over time, the names and approaches for diagnosing these diseases will change accordingly.
Jennette, J C
51 patients with rheumatoid arthritis and high rheumatoid factors (mean titres 928) underwent examination for the demonstration of an extraarticular organ manifestation within the scope of the cooperation between the Department of Medicine of the Karl-Marx-University Leipzig and the Institute for Rheumatology of the Academy of Medical Sciences of the USSR in Moscow. The frequency of nodous rheumatism (about 60%) is comparable with the frequency of polyneuropathy. In 20% of the patients a systemic muscle atrophy, a hepatomegaly as well as a Raynaud-syndrome were stated. By means of skin biopsy in 28% perivascular infiltrates were found. Altogether in 6 patients (12%) a participation of the lungs and the pleura, respectively, could be proved. Only rarely a clinically manifest heart disease caused by the rheu-we we found an pericardial effusions in 3 cases. In systemic manifestation, such as myositis, participation of the eyes or vasculitis of the digital arteries with necrosis, were only sporadically to be established. Among 22 patients we found an pericardial effusions in 3 cases. In systemic manifestation in most cases increased parameters of activity were found. From the practical point of view apart from increased titers of the rheumatoid titres and circulating immune complexes (C1q-BT) increased concentrations of the C-reactive protein are prognostically significant. The presence of high rheumatoid factor titres alone as well as the isolated presence of rheumatic nodes must not always be connected with an unfavourable prognosis. When severe extraarticular manifestations are present a possibly early, intensive occasionally extracorporeal treatment is indicated. PMID:3716509
Häntzschel, H; Seidel, W; Otto, W; Arnold, S; Fischer, H; Krüger, W; Gruber, G; Treutler, H; Lasek, G; Sack, G
A forty year old man was seen in 1984 with a four year history of a painful vasculitis that responded transiently to plasma exchange. Diagnosis was revised to atypical pyoderma gangrenosum with further temporary benefit from lamprene and continuing maximally tolerated corticosteroids. The course fluctuated over the next ten years with gradual and increasing soft-tissue damage coupled with superimposed skin infections. A variety of organisms were isolated from the ulcerated areas, with each episode successfully managed on the basis of local debridement and appropriate antibiotic administration. In 1995, with extending skin devascularization, infectious bacterial episodes became more frequent and deep non-healing ulcers led to constant pain with virtual incapacity. In response to protocol hyperbaric oxygen therapy there was immediate reversal of the cutaneous damage, granulation tissue formed and new skin grew to cover the previous extensive deficits. As the lesions in his hands and feet improved so did his quality of life, with the patient again becoming ambulant and returning to work. Vascular access had become a major problem, and venography showed extensive occlusion with collateral circulation. A standard Hickman catheter was placed through the femoral vein into the inferior vena cava and functioned well over the next five years. At the end of 1996 the patient was admitted with an acute chest pain that was complicated by a major pulmonary embolus, from which he could not be resuscitated. This anecdotal experience demonstrates the important but underutilised benefits of hyperbaric oxygen in managing refractory, painful and penetrating skin ulcers. The cost of obtaining wound healing with reduction in pain by this form of treatment was approximately one-fifth of expenditure on previously ineffective management. PMID:11399612
Jacobs, PETER; Wood, LUCILLE; Van Niekerk, GERHARD D.
Background The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon ? (PegIFN)-? plus ribavirin and/or rituximab. About 30–40% of patients are non-responders or relapsers to such combination. Objective To analyse the safety and efficacy of Peg-IFN?/ribavirin/protease inhibitor combination in HCV-MC vasculitis. Patients and methods Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFN?/ribavirin was associated to telaprevir (375?mg three times daily, for 12?weeks, (n=15)) or boceprevir (800?mg three times daily, for 44?weeks, (n=8)) for 48?weeks. Results The median age was 59 (52.5–66)?years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06?g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15?g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). Conclusions Peg-IFN?/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.
Saadoun, David; Resche Rigon, M; Thibault, V; Longuet, M; Pol, S; Blanc, F; Pialoux, G; Karras, A; Bazin-Karra, D; Cazorla, C; Vittecoq, D; Musset, L; Decaux, O; Ziza, J M; Lambotte, O; Cacoub, Patrice
The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6?×?SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas?QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis. PMID:24654803
Hamano, Y; Abe, M; Matsuoka, S; Zhang, D; Kondo, Y; Kagami, Y; Ishigami, A; Maruyama, N; Tsuruta, Y; Yumura, W; Suzuki, K
We present a 42-year-old woman with pre-existing autoimmune polyendocrinopathy syndrome (APS) Type 2 and chronic kidney disease due to Type 1 diabetic nephropathy, who developed a rapid deterioration in renal function due to perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated vasculitis. Although possibly a chance occurrence, ANCA have been detected more frequently in patients with a history of certain autoimmune diseases. Such an association may simply reflect an underlying tendency to immune system dysfunction in these patients and the finding of positive ANCA serology does not reliably herald the development of ANCA-associated vasculitis. However, our case illustrates that positive ANCA serology in such circumstances is not always a benign phenomenon and should still be interpreted within the clinical context. Moreover, clinicians managing patients with pre-existing autoimmune disease should maintain a low threshold for appropriate assessment should such patients develop evidence suggestive of vasculitis. PMID:22541677
Murray, Jonathan S; Baines, Laura A; Pearce, Simon H S; Ball, Steve; Leech, Nicola; Wood, Katrina M; Kanagasundaram, Nigel S
Two patients both with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) developed leucocytoclastic vasculitis of the skin and nephropathy. Immunofluorescence studies showed that there was perivascular deposition of immunoglobulin A in the skin biopsy specimens of both patients and in the renal mesangium of one patient. Serum samples of the two patients contained IgA immune complexes. The absence of previous reports on such a combination of symptoms in IBD or AS suggests that these patients may have a disease entity which is distinct from uncomplicated IBD or AS, and which may combine the immunopathological features of both underlying disorders.
Peeters, A J; van den Wall Bake, A W; Daha, M R; Breeveld, F C
We present the case of an 11-year-old boy presenting with haemoptysis, dyspnoea and weight loss as a manifestation of isolated pulmonary vasculitis, leading to pulmonary hypertension. He also appeared to have a longstanding dural venous sinus thrombosis. This rare presentation, especially in childhood, might represent a case of the seldomly reported Hughes-Stovin syndrome. The patient achieved remission after therapy with cyclophosphamide pulses and high-dose steroids. Based on the presented case and review of the literature, we propose that this syndrome might be a variant of polyarteritis nodosa. This report highlights diagnostic issues and describes a successful treatment regimen.
Introduction Increasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody (ANCA) directed to myeloperoxidase (MPO) might provide clues to the pathogenesis of propylthiouracil (PTU)-induced ANCA-associated vasculitis (AAV). This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA (with or without vasculitis) and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV. Methods Six recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis, and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay by using the recombinant fragments as solid-phase ligands. Results Compared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO (optical density values: 0.17 (0.10 to 0.35) versus 0.10 (0.04 to 0.21), P?=?0.038) and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P?=?0.026). Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment (47.1% versus 14.1% P?0.001; 41.2% versus 14.1%, P?=?0.034, respectively), and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P?=?0.013]. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset (two (none to four) versus none (none to 0.75), P?0.001]. Conclusions Linear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.
Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.
DIRESKENELI, HANER; AYDIN, SIBEL Z.; KERMANI, TANAZ A.; MATTESON, ERIC L.; BOERS, MAARTEN; HERLYN, KAREN; LUQMANI, RAASHID A.; NEOGI, TUHINA; SEO, PHILIP; SUPPIAH, RAVI; TOMASSON, GUNNAR; MERKEL, PETER A.
Background: This case report represents one of the estimated 17,000 aneurysms clipped annually in the United States, often with nickel-containing clips. The authors highlight the development of life-threatening allergic vasculitis in a 33-year-old woman after aneurysm clipping. Case Description: After suffering subarachnoid hemorrhage, the patient had coil embolization at another facility for rupture of a right internal carotid artery (ICA) aneurysm. An incidental finding, an unruptured left posterior communicating artery aneurysm unamenable to coiling, was then successfully clipped via a left pterional craniotomy. Arriving in our emergency department 11 days later, she progressively declined during the next weeks, facing deteriorating clinical status (i.e. seizures) and additional infarctions in the left frontal lobe, midline shift, and new infarctions in the bilateral frontal lobe, right sylvian, right insular regions, and posterior cerebral artery distribution. During decompressive surgery, biopsy findings raised the possibility of lymphocytic vasculitis; consultations with rheumatology, allergy, and immunology specialists identified that our patient had a nickel allergy. After reoperation to replace the nickel-containing clip with one of a titanium alloy, the patient had an uncomplicated postoperative course and was discharged 6 days later to a rehabilitation facility. Conclusions: Nickel-related allergies are more common than appreciated, affecting up to 10% of patients. Fortunately, severe reactions are rare; nevertheless, vascular neurosurgeons should be aware of this potential complication when using cobalt alloy aneurysms clips. The use of titanium alloy clips eliminates this risk.
Grande, Andrew; Grewal, Sanjeet; Tackla, Ryan; Ringer, Andrew J.
Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are systemic inflammatory disorders that include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), Churg-Strauss syndrome and renal limited vasculitis (RLV). Extracellular high-mobility group box 1 (HMGB1) acts as an alarmin and has been shown to be a biomarker of disease activity as well as an autoantigen in systemic lupus erythematosus (SLE) and, possibly, in AAV. This study aims to assess antibodies against HMGB1 and HMGB1 levels as biomarkers for AAV disease activity and predictors of relapsing disease. Methods AAV patients with active disease and healthy controls (HC) were evaluated for anti-HMGB1 antibodies while serum HMGB1 levels were measured longitudinally in AAV patients at presentation, during remission, prior to and at relapses. Results HMGB1 levels were similar between AAV patients at presentation (n = 52) and HC (n = 35) (2.64 ± 1.80 ng/ml vs. 2.39 ± 1.09 ng/ml; P = 0.422) and no difference regarding HMGB1 levels could be found among AAV disease subsets (GPA: 2.66 ± 1.83 ng/ml vs. MPA: 3.11 ± 1.91 ng/ml vs. RLV: 1.92 ± 1.48 ng/ml; P = 0.369). AAV patients with renal involvement had lower HMGB1 levels than patients without renal involvement at presentation (2.35 ± 1.48 ng/ml vs. 3.52 ± 2.41 ng/ml; P = 0.042). A negative correlation was observed between HMGB1 levels and 24-hour proteinuria (? = -0.361, P = 0.028). Forty-nine AAV patients were evaluated for HMGB1 levels during follow-up and no differences were observed between relapsing and nonrelapsing patients (P = 0.350). No significant increase in HMGB1 levels was observed prior to a relapse compared with the remission period and changes in HMGB1 levels were not associated with an increased risk for relapse in AAV. Positivity for anti-HMGB1 antibodies was low in patients with active AAV (three out of 24 patients). Conclusions Serum HMGB1 levels at presentation are not increased and are lower in patients with renal involvement. Relapses are not preceded or accompanied by significant rises in HMGB1 levels and changes in HMGB1 levels are not related to ensuing relapses. Anti-HMGB1 antibodies are present in only a few patients in AAV. In contrast to SLE, HMGB1 is not a useful biomarker in AAV.
Introduction We investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study. Methods In total, 156 Japanese patients with newly diagnosed AAV were classified according to the European Medicines Agency (EMEA) algorithm with exploratory surrogate markers for AAV-related non-granulomatous pulmonary lesions, predefined as alveolar haemorrhage and interstitial lung disease (ILD), and their clinical and serological features were evaluated. Results Using the EMEA algorithm, we identified 14 patients (9.0%) with eosinophilic granulomatosis with polyangiitis (EGPA), 33 (21.2%) with granulomatosis with polyangiitis (GPA), 78 (50.0%) with microscopic polyangiitis and renal-limited vasculitis (MPA/RLV), and 31 (19.9%) with unclassifiable vasculitis. The average ages of patients with EGPA (male/female, 5/9), GPA (12/21), and MPA/RLV (35/43) and unclassifiable (9/22) were 58.0, 63.6, 71.1, and 70.6 years, respectively. Myeloperoxidase (MPO)-ANCA and proteinase-3 ANCA positivity was 50.0% and 0% for EGPA, 54.6% and 45.5% for GPA, 97.4% and 2.6% for MPA/RLV, and 93.5% and 3.2% for unclassifiable, respectively. According to the Birmingham Vasculitis Activity Score (BVAS), cutaneous (71.4%) and nervous system (92.9%) manifestations were prominent in EGPA and ear, nose, and throat manifestations (84.9%) and chest manifestations (66.7%) in GPA. Renal manifestations developed frequently in MPA/RLV (91.0%) and GPA (63.6%). The average serum creatinine levels were 0.71 mg/dL for EGPA, 1.51 mg/dL for GPA, 2.46 mg/dL for MPA/RLV, and 0.69 mg/dL for unclassifiable. The percentages of patients with ILD were 14.3% for EGPA, 9.0% for GPA, 47.4% for MPA/RLV, and 61.3% for unclassifiable. Patients with ILD (n?=?61) had significantly lower BVAS (P?=?0.019) with fewer ear, nose, and throat and cardiovascular manifestations than patients without ILD (n?=?95). Conclusions MPO-ANCA-positive MPA/RLV is the most common form of AAV in Japanese patients, and one-half of patients with GPA were positive for MPO-ANCA. ILD is an important clinical manifestation in Japanese patients with AAV. Unclassifiable vasculitis with MPO-ANCA positivity and ILD may represent a novel variant of MPA. Trial Registration The University Hospital Medical Information Network Clinical Trials Registry: UMIN000001648. Registered 28 February 2009.
Most of the published descriptions of adverse soft tissue reactions that have been reported in the context of a metal-on-metal articulation have been in cases of total hip arthroplasty or resurfacing arthroplasty. Recently, several case reports have been published describing aseptic lymphocyte dominated vasculitis-associated lesions (ALVAL) in metal-on-polyethylene. To our knowledge, there has not been a description of a similar, aggressive reaction secondary to metal debris from the head-neck junction of a unipolar hemiarthroplasty component. In this case report, we describe a patient with a catastrophic failure of a unipolar hip hemiarthroplasty, secondary to aggressive osteolysis and an inflammatory mediated immunological reaction to metal debris. PMID:22795878
Khair, M Michael; Nam, Denis; DiCarlo, Edward; Su, Edwin
Indirect immunofluorescence (IIF) techniques have shown that ANCA are useful serological markers for some small vessel vasculitides, and ELISA assays, using purified molecules as solid-phase ligand, have helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a substantial number of serum samples, which are positive by IIF, yet recognize neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis of soluble neutrophil granule proteins, that certain of these double-negative samples recognized a 55-kD doublet of which the first eight residues shared N-terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram-negative bacteria. We developed a simple, quick and robust two-step immunobiochemical method to purify BPI. This was then employed to detect anti-BPI autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative samples and 400 consecutive new samples sent for routine ANCA testing in the anti-BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M:F ratio 55:34), a mean age of 60.4 years and clinical diagnoses ranging from organ limited vasculitis to widespread systemic vasculitis. Images Fig. 2 Fig. 5
Zhao, M H; Jones, S J; Lockwood, C M
Classically presenting with multiple or single peripheral cytopenias of variable severity, the myelodysplastic syndromes may occasionally present with bizarre manifestations that confuse the clinical picture and result in significant delays in making the correct diagnosis. We describe the case of an elderly male patient whose presentation with prolonged unexplained fever coupled with cutaneous, pulmonary and other systemic features of inflammation was finally diagnosed as having a primary myelodysplastic syndrome with associated vasculitis after a delay of 4 years.
Hassan, Imad Salah; Dar, Javeed
Introduction Behçet’s disease commonly presents with recurrent oral and genital mucocutaneous ulcerations, uveitis and various skin manifestations. Other clinical symptoms include gastrointestinal ulcerations, arthritis, venous thrombosis, arterial aneurysms and central nervous system affection. Vasculitis underlies most clinical symptoms of Behçet’s disease. Case presentation We report the case of a 62-year-old European Caucasian woman with Behçet’s disease who presented with persistent fever and neck soft-tissue swelling, despite broad antibiotic treatment, two weeks after acute tonsillitis and a tonsillectomy. Diffuse epi- and mesopharyngeal swelling shown on a computed tomography scan of her neck and persistently elevated serum markers of inflammation initially prompted suspicion of an infectious etiology. Magnet resonance imaging of her neck and a neck tissue biopsy finally confirmed small vessel vasculitis involving skin, subcutaneous tissue and muscle. Considering the clinical presentation, past medical history and histological findings, we interpreted our patient’s symptoms as a flare of Behçet’s disease. Immunosuppressive treatment led to rapid clinical improvement. Conclusion A patient with Behçet’s disease developed small vessel vasculitis of the soft tissue of her neck after tonsillitis and a tonsillectomy. Infection and surgery probably triggered a flare of Behçet’s disease.
Levamisole-induced vasculitis is a relatively new entity in people who use cocaine. We describe a 44-year-old woman with a history of cocaine use who presented with a complaint of a painful rash of 2-3 month’s duration on her extremities, cheeks, nose, and earlobes. She had not experienced fever, weight loss, alopecia, dry eyes, oral ulcers, photosensitivity, or arthralgia. Examination revealed tender purpuric eruptions with central necrosis on her nose, cheeks, earlobes, and extremities. Laboratory investigations revealed neutropenia, an elevated erythrocyte sedimentation rate (ESR), presence of lupus anticoagulant, low complement component 3 (C3), and presence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). A urine toxicology screen was positive for cocaine, and gas chromatography–mass spectrometry was positive for levamisole. Skin biopsy showed leukocytoclastic vasculitis and small vessel thrombosis. Necrotic lesions of the nose led to its self-amputation. Large bullae on the lower extremities ruptured, leading to wound infection and extensive necrosis that required multiple surgical debridements. When necrosis progressed despite debridement, bilateral above-knee amputation of the legs was performed. Once new lesions stopped appearing, the patient was discharged home. Two months later, she had a recurrence related to cocaine use. To the best of our knowledge, this is only the second reported case of levamisole-induced vasculitis that required above-knee amputation.
The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides. Images Figure 1 Figure 3 Figure 4 Figure 6
Heeringa, P.; Foucher, P.; Klok, P. A.; Huitema, M. G.; Tervaert, J. W.; Weening, J. J.; Kallenberg, C. G.
Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare dermatologic condition which shows various clinical and histopathological features. Although the PNGD lesions have been suggested to begin as leukocytoclastic vasculitis (LCV), there is still insufficient clinicopathological information in the reported cases of PNGD in acute stage with LCV. The relationship between PNGD and interstitial granumatous dermatis (IGD) also remains unclear. This report presents the case of a 60-year-old female patient with multiple erythematous nodules on the extremities. She had no underlying systemic disease detected to date, although transient, abnormal liver function tests were seen. The histopathological examination of an erythematous nodule revealed the features of PNGD in the acute stage. The patient presented the characteristic features of LCV including palisaded granulomatous pattern, and the interstitial granulomatous pattern was seen together, suggesting that PNGD with LCV can show an interstitial granulomatous pattern. The present case also suggested that PNGD in the acute stage with LCV tends to clinically manifest as erythematous nodules on the extremities and histopathologically shows a remarkable papillary edema and an extensive fibrin deposition in and around the vessel wall. PNGD may be associated with transient liver dysfunction. PMID:19903215
Misago, Noriyuki; Shinoda, Yohsuke; Tago, Masaki; Narisawa, Yutaka
The epidemiology of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is considerably different between European and Asian populations. Whereas granulomatosis with polyangiitis is the most common form of AAV in northern European populations, microscopic polyangiitis (MPA) accounts for the majority of AAV in Japan. This difference may at least in part derive from the difference in genetic background. In this review, I focus on our observation on HLA, an obvious candidate gene for immune disorders, and discuss its potential implication. In Japanese AAV, significant association was detected with HLA-DRB1*09:01, the carrier frequency of which was increased in MPA [P=0.0087, odds ratio (OR) 1.90, 95% confidence interval (CI) 1.17-3.08] and in myeloperoxidase (MPO)-ANCA-positive AAV (P=0.0016, OR 2.05, 95% CI 1.31-3.23) when compared with healthy Japanese controls. HLA-DRB1*09:01 is one of the most common HLA-DRB1 alleles in Asians but is rare in Caucasian populations. Interestingly, HLA-DRB1*09:01 has been shown to be associated with multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, suggesting that either HLA-DRB1*09:01 itself or other genes in tight linkage disequilibrium may play a role in a molecular pathway shared by various autoimmune diseases in Japanese and possibly in other Asian populations. PMID:23180035
A 23-year-old single female patient developed constitutional manifestations in the form of fever, weight loss, anorexia, malaise, fatigue, and generalized aches in January 1995, 2 weeks after an attack of German measles. This was followed by painful, reddish, macular skin lesions over both legs which healed by dark pigmentation (leucocytoclastic vasculitis), mononeuritis multiplex, and Raynaud's phenomena of both hands and feet. Angiography of lower limbs was done to visualize the arterial tree of both lower limbs and revealed typical beading of distal arterial branches, a diagnosis compatible with polyarteritis nodosa (PAN). At that time, the patient received prednisone (45 mg/day) and azatioprin (100 mg/day) and responded well to treatment. In a second presentation in June 2005, the patient developed sudden attack of loss of vision in her left eye. Ophthalmological examination of the patient revealed evidence of left central retinal artery occlusion, ischemic optic neuropathy. The patient received methyl prednisolone, 1 g IV infusion, daily infusion for three consecutive days followed by oral prednisolone, 30 mg/day. The patient received pulse cyclophosphamide IV infusion (0.6 g/m2) on the fourth day. One week after receiving therapy, the patient progressed from having light perception to counting of fingers from a distance of 1 m. PMID:16575492
Emad, Y; Basaffar, S; Ragab, Y; Zeinhom, F; Gheita, T
It has been shown previously that proteinase 3 (PR3), a neutrophil intracellular protease that is the main antigen of antineutrophil cytoplasm (ANCA) autoantibodies, is present on the plasma membrane of a subset of freshly isolated neutrophils. This study shows that the size of this subset of membrane PR3-positive (mPR3+) neutrophils is a stable feature of a given individual, most likely genetically controlled. It ranges from 0 to 100% of neutrophils and allows us to define a new polymorphism in the healthy population, with three discrete phenotypes corresponding respectively to less than 20% mPR3 + neutrophils (mPR3low) or to a mean percentage of 47% (mPR3intermediate) and 71.5% (mPR3high) mPR3+ neutrophils. The frequency of the mPR3high phenotype was significantly increased in patients with ANCA-associated vasculitis (85% versus 55% in healthy subjects). The percentage of mPR3+ neutrophils was not affected by disease activity, relapses, or therapy, and did not reflect in vivo cell activation. In addition, mPR3+ phenotypes were normally distributed in cystic fibrosis patients, indicating that infection and/or inflammation per se do not lead to a high percentage of mPR3+ neutrophils. The frequency of the mPR3high phenotype was not related to anti-PR3 autoimmunization, since it was increased in vasculitic patients regardless of the ANCA specificity (anti-PR3, anti-myeloperoxidase, or unknown). Interestingly, the frequency of the mPR3high phenotype was also increased in patients with rheumatoid arthritis. It was normal in type I-diabetes, a T cell-dependent autoimmune disease. It is proposed here that a high proportion of membrane PR3-positive neutrophils could favor the occurrence or the progression of chronic inflammatory diseases. PMID:10361860
Witko-Sarsat, V; Lesavre, P; Lopez, S; Bessou, G; Hieblot, C; Prum, B; Noël, L H; Guillevin, L; Ravaud, P; Sermet-Gaudelus, I; Timsit, J; Grünfeld, J P; Halbwachs-Mecarelli, L
Background Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may present with pulmonary involvement ranging from mild to life-threatening disease such as diffuse alveolar hemorrhage. There is a paucity of information regarding morbidity outcomes for AAV subjects presenting with lung involvement. This study determines the relationship between disease activity and damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS 3) and Vasculitis Damage Index (VDI) respectively. Results 151 patients with AAV were included with 59 presenting initially with pulmonary involvement. The initial BVAS scores recorded at time of diagnosis were positively correlated with the final VDI scores at 24 months (p?0.0001, rs?=?0.5871). No differences between BVAS and VDI scores were seen for both groups, however in the lung-involvement group only, BVAS scores were significantly higher at 6, 12 and 24 months whilst the VDI scores were significantly higher at 12 and 24 months. Subjects presenting with pulmonary involvement had an increased likelihood for cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p?=?0.032) and renal (OR 1.32, 95% CI 1.22, 1.39; p?=?0.005) involvement. Subjects presenting with lung involvement with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month VDI scores that were significantly higher (p?=?0.027, p?=?0.045), and more likely to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p?0.001). Conclusion AAV subjects with lung involvement at presentation had a higher disease activity and damage scores at 6, 12 and 24 months follow-up representing a considerable burden of disease despite improvement in overall survival due to the introduction of immunosuppressive therapy.
Background: Fever of unknown origin (FUO) is a diagnostic challenge. Rheumatologists are often in charge of patients with FUO because the vasculitides, especially, are potential and common causes of FUO. Objective: To evaluate the value of a standardised investigation to identify the cause of FUO. Methods: A standardised work-up programme for patients with FUO was started at the beginning of September 1999. The rate of identified causes of FUO was compared between all patients with FUO admitted to a tertiary care centre of rheumatology between January 1996 and August 1999 (control group) and September 1999 and January 2003 (work-up group). In January 2002 magnetic resonance imaging (MRI) was added to the investigation. Results: 67 patients with FUO were identified—32 before and 35 after institution of the work-up programme. Before implementation 25% of all patients with FUO remained undiagnosed, after implementation 37%. After institution of the investigation the percentage of patients with vasculitides increased significantly from 6% (n = 2) to 26% (n = 9, p = 0.047, Fisher's exact test). This increase could be attributed to the addition of MRI in 2002. When all patients with FUO before 2002 (n = 55) and thereafter (n = 12) were compared the prevalence of systemic vasculitis increased from 11% (n = 6) to 42% (n = 5, p = 0.021). Conclusion: Implementation of a standardised work-up programme for FUO did not improve the overall rate of diagnosis. Addition of MRI significantly increased the diagnosis of systemic vasculitis as the underlying cause of FUO. MRI should be included in the investigation of patients with FUO when vasculitis is suspected.
Wagner, A; Andresen, J; Raum, E; Lotz, J; Zeidler, H; Kuipers, J; Jendro, M
Background The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53?year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.
Introduction Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterised by the autoinflammation and necrosis of blood vessel walls. The renal involvement is commonly characterised by a pauci-immune crescentic glomerulonephritis (PiCGN) with a very rapid decline in renal function. Cathelicidin LL37, an endogenous antimicrobial peptide, has recently been implicated in the pathogenesis of autoimmune diseases. To assess whether serum LL37 reflects renal crescentic formation, we measured the serum levels of LL37 in AAV patients with and without crescentic glomerulonephritis (crescentic GN) as compared to healthy controls (HCs). We also analysed the correlation of the serum levels of LL37 and interferon-? (IFN-?) with the clinical characteristics of the patients. Methods The study population consisted of 85 AAV patients and 51 HCs. In 40 ANCA-positive patients, a parallel analysis was performed, including the assessment of LL37 and IFN-? levels in the serum and renal biopsies. Of those studied, 15 AAV patients had biopsy-proven crescentic GN, and 25 AAV patients lacked crescent formation. The serum levels of cathelicidin LL37 and IFN-? were both measured by ELISA, and the clinical and serological parameters were assessed according to routine procedures. Immunofluorescence staining was performed on frozen sections of kidney needle biopsies from AAV patients with crescentic GN. Results The serum levels of LL37 and IFN-? were significantly increased in AAV patients with crescentic GN compared to AAV patients without crescentic formation and HCs, and patients with high LL37 and IFN-? levels were more likely to be in the crescentic GN group. The LL37 levels were positively correlated with the IFN-? levels, and both LL37 and IFN-? levels showed a positive correlation with serum creatinine and no correlation with complement C3. The renal tissue of crescentic GN patients showed expression of LL37 and IFN-? at the Bowman’s capsule and extracellular sites, suggesting the active release of LL37 and IFN-?. Conclusions Significantly higher levels of LL-37 and IFN-? were observed in AAV patients, particularly those with crescentic formation, and LL37 and IFN-? were expressed in the renal tissue of patients with crescentic GN. These data suggest that serum levels of LL37 and IFN-? may reflect both local renal inflammation and systemic inflammation.
Although primary systemic vasculitides (PSV) are infrequent diseases, basic and clinical research have increased the knowledge of these autoimmune conditions substantially. Some PSV seem to be more frequent in certain countries. Here we present a brief history of the modest, but important contributions made in Mexico in this area of research. PMID:23229651
Flores-Suárez, Luis Felipe
Before the mid-1980s the only autoantibody widely used to assist in diagnosing vasculitic disease was IgG antibody to the alpha(3) domain of the noncollagenous part of type IV collagen (anti-glomerular basement membrane). Since that time, antineutrophil cytoplasmic antibodies (ANCAs) directed at the azurophilic granule proteins proteinase-3 and myeloperoxidase have been established as clinically useful autoantibodies to support a diagnosis of Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and limited forms of these primary, small vessel necrotizing and often granulomatous vasculitides. The establishment of standardized methods for identifying those antibodies was needed before they could be used in clinical practice. The levels of both types of ANCAs tend to increase in parallel with the degree of clinical disease activity, and they decrease with successful immunosuppressive therapy. More than one assay may have to be used to discover imminent exacerbations in proteinase-3-ANCA associated syndromes. Although autoantibodies to endothelial cells may be important players in the pathogenesis of several vasculitic conditions, they have not gained clinical popularity because of lack of standardized detection methods. PMID:12723981
Before the mid-1980s the only autoantibody widely used to assist in diagnosing vasculitic disease was IgG antibody to the ?3 domain of the noncollagenous part of type IV collagen (anti-glomerular basement membrane). Since that time, antineutrophil cytoplasmic antibodies (ANCAs) directed at the azurophilic granule proteins proteinase-3 and myeloperoxidase have been established as clinically useful autoantibodies to support a diagnosis of Wegener's granulomatosis, microscopic polyangiitis, Churg–Strauss syndrome and limited forms of these primary, small vessel necrotizing and often granulomatous vasculitides. The establishment of standardized methods for identifying those antibodies was needed before they could be used in clinical practice. The levels of both types of ANCAs tend to increase in parallel with the degree of clinical disease activity, and they decrease with successful immunosuppressive therapy. More than one assay may have to be used to discover imminent exacerbations in proteinase-3-ANCA associated syndromes. Although autoantibodies to endothelial cells may be important players in the pathogenesis of several vasculitic conditions, they have not gained clinical popularity because of lack of standardized detection methods.
Systemic Sclerosis (SSc) is a connective tissue disorder which involves multiple systems in a chronic progressive manner. Micro–angiopathic haemolytic anaemia is a distinguished feature of “scleroderma renal crisis”, which is manifested by severe hypertension, a rapidly progressing renal dysfunction and hyperreninaemia and is seen in patients with an early, diffuse form of the disease. A nervous system involvement is rare, though entrapment neuropathies have been reported. Who presented with a sequential loss of vision in both eyes; due to retinal vasculitis in right eye and optic nerve demyelination in the left eye. She also had severe Coombs’ negative haemolytic anaemia in absence of any renal dysfunction or hypertension. Both the ophthalmologic and the haematologic manifestations are very rare and both responded well to oral prednisolone therapy.
Moulick, Avijit; Sarkar, Biswanath Sharma; Jana, Anirban; Guha, Pradipta; Das, Anjan
We systematically reviewed the peer-reviewed literature to determine a pooled estimate of the incidence of pseudotumor and acute lymphocytic vasculitis associated lesions (ALVAL) in adult patients with primary metal-on-metal (MoM) total hip arthroplasty or resurfacing. Fourteen eligible articles were identified, with a total of 13,898 MoM hips. The incidence of pseudotumor/ALVAL ranged from 0% to 6.5% of hips with a mean follow-up ranging from 1.7 to 12.3 years across the studies. The pooled estimated incidence of pseudotumor/ALVAL is 0.6% (95% CI: 0.3% to 1.2%). The rate of revision for any reason ranged from 0% to 14.3% of hips, with a pooled estimate of 3.9% (95% CI: 2.7% to 5.3%). PMID:23660012
Wiley, Kevin F; Ding, Kai; Stoner, Julie A; Teague, David C; Yousuf, Khalid M
A 16-year-old female with fever was admitted to our hospital. On admission, her serum IgM antibody against Epstein-Barr virus (EBV) was positive. Then, the disease aggravated and acute kidney injury occurred gradually. Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) was confirmed by serum test and kidney biopsy. The patient was treated with oral methylprednisolone. Along with the disappearance of the IgM anti-EBV antibody, the AAV also relieved without relapse during follow-up for half a year. Although a previous study indicated that there was a high positive rate of ANCA in the sera positive for IgM antibodies to EBV and EBV infection might trigger the relapse of AAV, this is the first case of incipient AAV associated with acute EBV infection. One possible explanation might be that EBV infection stimulated the production of ANCA. PMID:24610176
Xu, P; Lin, S; Wei, L; Shang, W
Increasing evidence suggested that Toll-like receptors (TLRs) were critically involved in immune responses of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to investigate the expression of TLR-2, TLR-4 and TLR-9 in kidneys of patients with ANCA-associated vasculitis. Renal biopsy specimens were collected from 24 patients with AAV. The expression of TLR-2, TLR-4 and TLR-9 in kidneys was detected by immunohistochemistry. Double immunofluorescence staining was performed to detect the expression of TLRs on various kinds of cells. In renal specimens, immunohistochemical examination revealed that expression of TLR-2 and TLR-4 could be detected in the glomeruli of AAV patients, while TLR-2 and TLR-4 were scarcely detected in the glomeruli of normal controls. Double immunofluorescence staining of TLR-2, TLR-4 and CD31 indicated that TLR-4 and TLR-2 were expressed on endothelial cells in the glomeruli. In the tubulointerstitial compartment, expression of TLR-2, TLR-4 and TLR-9 could be detected in both AAV patients and normal controls. The mean optical density of TLR-2 and TLR-4 in the tubulointerstitial compartment in AAV patients were significantly higher than that in normal controls. Among AAV patients, correlation analysis showed that the mean optical density of TLR-4 in the glomeruli correlated inversely with the initial serum creatinine, the proportion of total crescents and the proportion of cellular crescents in renal specimens (r?=?-0·419, P?=?0·041; r?=?-0·506, P?=?0·012; r?=?-0·505, P?=?0·012, respectively). The expression of TLR-2 and TLR-4 was dysregulated in kidneys of AAV patients. The expression of TLR-4 in glomeruli was associated with the severity of renal injury. PMID:24773611
Wang, H; Gou, S-J; Zhao, M-H; Chen, M
Objective To develop a measure of illness self-management for adults living with antineutrophil cytoplasmic antibody (ANCA)–associated small-vessel vasculitis (ANCA-SVV) and to gather evidence of its reliability and validity. Methods Development of the Vasculitis Self-Management Scale (VSMS) was guided by previous research on self-management in other chronically ill populations, a review of the current treatment literature for ANCA-SVV, interviews with patients, and consultation with experts. A total of 205 patients living with ANCA-SVV or a closely related condition then completed the VSMS, along with measures of sociodemographic and clinical variables, social desirability bias, and general adherence to medical recommendations, using a self-administered mailed questionnaire. A principal components analysis was conducted on the VSMS items. Internal consistency reliability and construct validity of the resulting subscales were assessed. Forty-four patients completed the VSMS a second time, for the purpose of assessing test-retest reliability. Results Analyses suggested an 8-factor solution. The final VSMS consisted of 43 items representing these 8 behavioral domains. Correlations among the 8 domains were null to modest in magnitude. The internal consistency reliability of the 8 subscales ranged from minimally acceptable (? = 0.67) to excellent (? = 0.94), and correlations between subscale scores at time 1 and time 2 suggested good temporal stability. Preliminary evidence for validity was mixed. Conclusion These findings suggest that the VSMS is a promising method for assessing illness self-management in adults with ANCA-SVV. More research exploring the validity of the measure is warranted.
THORPE, CAROLYN T.; DEVELLIS, ROBERT F.; LEWIS, MEGAN A.; BLALOCK, SUSAN J.; HOGAN, SUSAN L.; DEVELLIS, BRENDA M.
An association between mixed cryoglobulinaemia (MC) and hepatotropic viruses, chiefly hepatitis C virus (HCV), has been widely reported. The presence of HCV genomic sequences or HCV-related viral proteins in the serum, purified cryoglobulins, peripheral blood mononuclear cells and into several tissues has suggested an important triggering role for HCV in MC patients. However, only few reports investigated the presence of HCV in cutaneous vasculitis and its potential pathogenetic role. Biopsies of cutaneous purpuric lesions from 5 MC female patients (aged from 40 to 80 years) were carried out for virological and histopathological evaluation. A leukocytoclastic vasculitis pattern was found in 4/5 subjects, while the presence of HCV RNA was detected in 3/5. In only 3 cases biopsy specimens were sufficient for immunohistochemical and direct immunofluorescence (DIF) studies. Immunohistochemical evaluation was performed by means of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP) immune-complexes. In the same skin specimen APAAP and DIF findings were compared with the presence/absence of HCV genomic sequences (PCR technique). In 1 MC patient, the detection of HCV-RNA was associated to a prevalent CD8+ T suppressor pattern with a perivascular and subjunctional distribution as well as an intense expression of second class (HLA-DR) and intercellular adhesion (ICAM-1) molecules on basal keratinocytes, endothelial cells and perivascular infiltrate. These findings suggest a marked inflammatory activation that spreads from endothelial cells to keratinocytes and Langerhans cells. In the 2 HCV-RNA negative specimens the scanty immunopathological staining could indicate a residual activity due to the previous inflammatory event triggered by cryoglobulins. The deposition of circulating HCV-containing immune complexes (CIC) in the skin could be the initial pathogenic event for cryoglobulinemic vasculitis; subsequently CIC could spread from the vascular bed to the perivascular tissue and then could be very rapidly eliminated. If confirmed in larger patients' series these findings could definitely demonstrate a direct role of HCV in the pathogenesis of cryoglobulinemic vasculitis. PMID:10597137
Bernacchi, E; Civita, L L; Caproni, M; Zignego, A L; Bianchi, B; Monti, M; Fabbri, P; Pasero, G; Ferri, C
Haematopoietic stem cell transplantation for vasculitis including Beh?et's disease and polychondritis: a retrospective analysis of patients recorded in the European Bone Marrow Transplantation and European League Against Rheumatism databases and a review of the literature
Objective To evaluate the feasibility of haematopoietic stem cell transplantation (HSCT) in vasculitis. Methods This is a retrospective analysis of patients who had received HSCT for vasculitic diseases and have been reported to the European League Against Rheumatism autoimmune disease or European Bone Marrow Transplantation ProMISe databases. Information about the disease and outcome was obtained by a questionnaire sent to the referring centres. Response of the disease to HSCT was defined as partial or complete responses according to the ability to reduce immunosuppression after HSCT. In addition, the Medline database was searched for reports on HSCT in patients with vasculitis. Results Detailed information was obtained for 15 patients, whose median age at HSCT was 37?years. The diagnoses were cryoglobulinaemia in four patients, Behçet's disease in three patients, Wegener's granulomatosis in three patients, and undifferentiated vasculitis, Churg–Strauss angiitis, polychondritis, Takayasu arteritis and polyarteritis nodosa in one patient each. 14 patients received autologous HSCT and 1 an allogeneic HSCT as the first transplant. In three patients, further transplantation was given because of relapse. The overall response, including all consecutive transplantations (HSCT/patient, n?=?1–3, median 1.3) to HSCT, was 93%, with 46% complete responses and 46% partial responses; median (range) duration of response at the time of reporting was 45 (16–84)?months. Three patients died, one from advanced disease, one from cancer and one from graft?versus?host disease. The Medline search showed five other patients who were effectively treated with HSCT for vasculitic diseases. Conclusion This retrospective study suggests that autologous HSCT is feasible for vasculitis. Its value remains to be tested in prospective controlled studies.
Daikeler, Thomas; Kotter, Ina; Tyndall, Chiara Bocelli; Apperley, Jane; Attarbaschi, Andishe; Guardiola, Philippe; Gratwohl, Alois; Jantunen, Esa; Marmont, Alberto; Porretto, Ferdinando; Musso, Maurizio; Maurer, Britta; Rinaldi, Nadia; Saccardi, Riccardo; Tyndall, Alan
We report a series of young adults with symptomatic cerebral arteriostenosis characterized by elevated serum immunoglobulin (Ig) E levels. All patients had no definite risk factors for cerebral vascular diseases. The clinical data of 26 young adults (age 18-50 years) with ischemic stroke, characterized only by increased serum IgE levels and without risk factors for cerebral vascular disease, were retrospectively reviewed. Arteriostenosis was surveyed and followed-up by digital subtraction angiography (DSA), and the stenosis rate was estimated using the warfarin-aspirin symptomatic intracranial disease technique. All patients were treated with corticosteroids according to the common strategy for vasculitis. There was no recurrent stroke during follow-up. The mean degree of stenosis before and after treatment was 69.3±29.8% and 47.9±45.1%, respectively. The difference of stenosis rates between initial and follow-up DSA evaluation was significant using a paired samples test (21.31±26.88, 95% confidence interval [CI] 13.58-29.03, t=5.55, p<0.001). Kaplan-Meier survival analysis revealed that the 13-month cumulative improved lesion rate was 40.3±8.7%. This remained the same at 18 months. The mean time to lesion improvement was 12.58 ± 0.96 months (95% CI 10.70-14.46) and median time was 13±3.88 months (95% CI 5.39-20.61). To our knowledge, cerebral arteriostenosis with only elevated IgE serum levels has not been reported. Our data showed that corticosteroid treatment can achieve clinical and artery improvement. This suggests that the cerebral arteriostenosis seen in our study might be caused by some specific type of vessel inflammation. PMID:24071054
Guo, Ruibing; Liu, Haibo; Li, Min; Liu, Ling; Yang, Fang; Yin, Qin; Xu, Gelin; Zhang, Renliang; Liu, Xinfeng
Circulating IgG autoantibodies to myeloperoxidase (MPO) are associated with renal vasculitis and have been implicated in its pathogenesis. However, raised levels of these autoantibodies may persist during clinical remission. We tested whether this paradox could be explained by immunoglobulin subclass switching during disease evolution, since different subclasses have different immunological and biochemical properties. Sera with anti-myeloperoxidase (anti-MPO) activity from 33 patients with active disease and 20 anti-MPO positive follow-up sera were studied by an ELISA using a panel of anti-human IgG subclass monoclonal reagents previously calibrated on human myeloma proteins. Anti-MPO subclass distribution in initial sera was: IgG1, 31 (94%); IgG2, 10 (30%); IgG3, 24 (73%); and IgG4, 22 (67%). IgG3 anti-MPO decreased during follow-up (P less than 0.02), with no change in IgG1 and IgG4. Relative functional affinity of anti-MPO antibodies in purified IgG subclasses was studied by the diethylamine method. IgG3 fractions consistently had a greater affinity for MPO than the other subclasses. Sequential studies in four patients demonstrated an affinity maturation for IgG1 and IgG4 anti-MPO as IgG3 anti-MPO disappeared. We conclude that dynamic changes of subclass distribution and affinity may explain discrepancies between anti-MPO antibody titre and disease expression.
Esnault, V L; Jayne, D R; Weetman, A P; Lockwood, C M
Background Granulomatosis with polyangiitis (GPA, Wegener’s) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses are associated with severe infections in patients with AAV. A randomized study of both plasma exchange and glucocorticoids is required to evaluate plasma exchange and oral glucocorticoid dosing in patients with AAV. Methods/design PEXIVAS is a two-by-two factorial randomized trial evaluating adjunctive plasma exchange and two oral glucocorticoid regimens in severe AAV. Five hundred patients are being randomized at centers across Europe, North America, Asia, and Australasia to receive plasma exchange or no plasma exchange, and to receive standard or reduced oral glucocorticoid dosing. All patients receive immunosuppression with either cyclophosphamide or rituximab. The primary outcome is the time to the composite of all-cause mortality and end-stage renal disease. PEXIVAS is funded by the National Institute of Health Research (UK), the Food and Drug Administration (USA), the National Institutes of Health (USA), the Canadian Institute of Health Research (Canada), the National Health and Medical Research Council (Australia), and Assistance Publique (France). Additional in-kind supplies for plasma exchange are provided by industry partners (TerumoBCT, Gambro Australia, and Fresenius Australia). Discussion This is the largest trial in AAV undertaken to date. PEXIVAS will inform the future standard of care for patients with severe AAV. The cooperation between investigators, funding agencies, and industry provides a model for conducting studies in rare diseases. Trial registration Current Controlled Trials: (ISRCTN07757494) and clinicaltrials.gov: (NCT00987389)
Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P = 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P = 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV.
Hogan, Susan L.; Cooper, Glinda S.; Savitz, David A.; Nylander-French, Leena A.; Parks, Christine G.; Chin, Hyunsook; Jennette, Caroline E.; Lionaki, Sofia; Jennette, J. Charles; Falk, Ronald J.
We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10(6) cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4(+)CD25(+)Foxp3(+)) and a notable reduction in interferon-?, interleukin 6, and tumor necrosis factor serum levels. PMID:24079687
Gregorini, Marilena; Maccario, Rita; Avanzini, Maria Antonietta; Corradetti, Valeria; Moretta, Antonia; Libetta, Carmelo; Esposito, Pasquale; Bosio, Francesca; Dal Canton, Antonio; Rampino, Teresa
Myocarditis, pancreatitis, polyarthritis, mononeuritis multiplex and vasculitis with symmetrical peripheral gangrene of the lower extremities as a rare presentation of leptospirosis: a case report and review of the literature
Introduction Leptospirosis is a zoonosis caused by the spirochete, Leptospira interrogans. While most cases of leptospirosis are mild to moderate, the course may be complicated by multiorgan dysfunction. We present a rare case of leptospirosis with acute myocarditis, pancreatitis, polyarthritis, mononeuritis multiplex and severe vasculitis with necrosis of the extremities. Case presentation A 32-year-old man from Congo presented with high-grade fever, confusion and headache. He developed tachycardia and hypotension followed by electrocardiogram changes and elevation of troponin I levels suggesting myocarditis. A physical examination revealed conjunctival suffusion, polyarthritis of his lower extremities and cutaneous necrosis of his feet due to vasculitis. Laboratory findings included amylase levels 10-fold the upper normal serum levels and thrombocytopenia. The diagnosis was confirmed by a positive leptospira immunoglobulin M, negative immunoglobulin G and a positive rapid agglutination test. Our patient recovered progressively with antimicrobials and supportive care. Conclusions Because the clinical features and diagnostic findings of leptospirosis are not specific, a high index of suspicion must be maintained for the diagnosis. Serology is the most important tool for accurate and quick diagnosis in order to administer the appropriate therapy.
An infant with unexplained sideroblastic anaemia and severe protracted diarrhoea due to autoimmune gut disease is reported. Despite treatment with an exclusion diet and immunosuppressive agents she developed a severe systemic vasculitic illness. Intensive treatment with plasmapheresis resulted in resolution of the vasculitic process but the child subsequently died after overwhelming septicaemia.
Jenkins, H R; Jewkes, F; Vujanic, G M
Antineutrophil cytoplasmic autoantibody (ANCA)-associated diseases are small-vessel vasculitides, encompassing granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Once considered life-threatening diseases, the introduction of stage-adapted immunosuppressive therapy and medications with decreased toxicity has improved patients' survival. Treatment is biphasic, consisting of induction of remission (3-6 months) for rapid control of disease activity and maintenance of remission (at least 18 months) to prevent disease relapse using therapeutic alternatives that have reduced toxicity. This Review summarizes current treatment strategies for these diseases, with a special focus on long-term follow-up data from key randomized controlled trials and new developments in remission induction and maintenance therapy. Current treatment strategies have substantial short-term and long-term adverse effects, and relapses are frequent; thus, less-toxic and more-effective approaches are needed. Moreover, the optimal intensity and duration of maintenance therapy remains under debate. Clinical trials have traditionally considered ANCA-associated vasculitides as a single disease entity. However, future studies must stratify participants according to their specific disease, clinical features (different types of organ manifestation, PR3-ANCA or MPO-ANCA positivity) and disease severity. PMID:24189648
Schönermarck, Ulf; Gross, Wolfgang L; de Groot, Kirsten
A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia. Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved. Tissue surrounding the foci of necrosis contained cells with intranuclear an intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 micrometer in diameter and were located in enlarged cells. Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus. The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed. PMID:6268757
Koeppen, A H; Lansing, L S; Peng, S K; Smith, R S
A 57-year-old man was admitted with right arm weakness and numbness on the background of intermittent headaches. On examination he was found to have mildly decreased sensation, power was 4/5 on the right side. He had dyspraxia in the right hand and was unable to spell his name. His speech was hesitant and he had left-sided visual field impairment as well as some photophobia. MRI and CT revealed multiple areas of haemorrhage and infarctions raising the possibility of primary angitis of brain. The biopsy confirmed the diagnosis. The patient responded to steroids and immunosuppressants partially. PMID:23188852
Montefort, Maxine; Dashora, Umesh; Chowdhury, Muhammad
The systemic vasculitides are a group of inflammatory disorders characterised by relapses and remission. Before the introduction of immunosuppressive drugs, mortality was unacceptably high. Immunosuppressive therapy has had a therapeutic impact, but at the cost of increased risk of infection and other adverse effects. Differentiating infection from active disease can be difficult, and the inappropriate prescription of immunosuppressive drugs can be fatal. Hence disease indices which can aid physicians to identify the active phase of disease and enable early treatment, will be valuable in the management of this group of disorders.
Tse, W. Y.; Cockwell, P.; Savage, C. O.
The anti-neutrophil cytoplasmic antibody-associated vasculitides include granulomatosis with polyangiitis (Wegener's granulomatosis) and microscopic polyangiitis. The introduction of therapy with cytotoxic agents such as cyclophosphamide transformed these diseases from fatal diagnoses to chronic conditions characterized by cycles of relapse and remission. Modern treatment strategies have focused on minimizing cyclophosphamide exposure or eliminating its use altogether. Two randomized clinical trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in patients with severe granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis. For patients with non-life threatening disease, methotrexate may be used to induce and maintain remission, although some patients may have a higher long-term risk of relapse as a result. For patients with life-threatening disease, plasma exchange may be an effective adjuvant therapy. This article reviews seminal studies from the past decade that have contributed to the current standard of care. PMID:22895899
Geetha, Duvuru; Seo, Philip
METHODS: We analyzed the MR imaging features of a single pediatric center cohort of 45 cPACNS patients. MR imaging studies were performed for all patients, and both MR imaging and MRA were performed for 42 patients, who formed the cohort for review of the presence and correlation of lesions. Proportions were calculated by using the Fisher exact test, and agreement
R. I. Aviv; S. M. Benseler; E. D. Silverman; P. N. Tyrrell; G. DeVeber; L. M. Tsang; D. Armstrong
Levamisole-contaminated cocaine has recently been recognized in North America and Europe, and its use is associated with a variety of clinical and autoimmune abnormalities. The clinical characteristic seems to be the presence of a painful purpuric skin rash that predominantly affects the ear lobes and cheeks, often accompanied by systemic manifestations including fever, malaise, arthralgias, myalgias, and laboratory abnormalities, for example leukopenia, neutropenia, positive ANA, ANCA, and phospholipid antibodies. Most of these manifestations can be seen with the use of either drug, especially levamisole. There is no specific therapy, and discontinuation of its use is followed by improvement. Prednisone and immunosuppressive therapy may be needed at times. Further use of the drug is characterized by recurrence of most of the complaints. PMID:22875288
Espinoza, Luis R; Perez Alamino, Rodolfo
Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides—Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support—but do not prove—a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA–associated Wegener’s granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17–producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development.
Apoptosis is a biochemically and morphologically gene-regulated distinctive form of cell death playing a pivotal role in tissue homeostatis, viral infections and clearance of damaged cells. The process is initiated by a cascade of intercellular and intracellular signals through an intrinsic cell suicide program resulting in early DNA fragmentation characterized by nuclear and cytoplasmic condensation. Recently some authors have reported
S Barduagni; A Frezzolini; G Ferranti; M Papi; O De Pità
Takayasu arteritis (TA) is 1 of the 2 main causes of large vessel vasculitides (LVV), giant cell arteritis being the other. LVV can also develop in various other systemic diseases. In TA, a wide variety of symptoms result from vascular stenoses, occlusions, and dilation. Aneurysms may develop and may occasionally dissect or rupture. Disease activity can sometimes be difficult to assess clinically. Diagnostic modalities also have their shortcomings. Often, acute phase reactants do not accurately detect disease activity. Available vascular imaging modalities may be acceptable in defining vascular anatomy, but are notoriously inaccurate in delineating vascular inflammation. Glucocorticoids remain the cornerstone of therapy in TA, in spite of foreseeable long term side effects. In addition, several steroid-sparing agents are also being used, often based on promising results from small uncontrolled studies. Rarely, endovascular revascularization procedures are necessary. Resection of critical-sized aortic aneurysms and repair of aortic dissections are occasionally warranted as lifesaving procedures. The long term outcome of surgical intervention is often unfavorable and relapses are not uncommon. In addition to TA, other less commonly encountered causes of LVV are also briefly discussed in this review. PMID:24893936
Chatterjee, Soumya; Flamm, Scott D; Tan, Carmela D; Rodriguez, E Rene
Introduction Indirect immunofluorescence (IIF) employing ethanol-fixed neutrophils (ethN) is still the method of choice for assessing antineutrophil cytoplasmic antibodies (ANCA) in ANCA-associated vasculitides (AAV). However, conventional fluorescence microscopy is subjective and prone to high variability. The objective of this study was to evaluate novel pattern recognition algorithms for the standardized automated interpretation of ANCA patterns. Methods Seventy ANCA-positive samples (20 antimyeloperoxidase ANCA, 50 antiproteinase3 ANCA) and 100 controls from healthy individuals analyzed on ethN and formalin-fixed neutrophils (formN) by IIF were used as a 'training set' for the development of pattern recognition algorithms. Sera from 342 patients ('test set') with AAV and other systemic rheumatic and infectious diseases were tested for ANCA patterns using the novel pattern recognition algorithms and conventional fluorescence microscopy. Results Interpretation software employing pattern recognition algorithms was developed enabling positive/negative discrimination and classification of cytoplasmic ANCA (C-ANCA) and perinuclear ANCA (P-ANCA). Comparison of visual reading of the 'test set' samples with automated interpretation revealed Cohen's kappa (?) values of 0.955 on ethN and 0.929 on formN for positive/negative discrimination. Analysis of the 'test set' with regard to the discrimination between C-ANCA and P-ANCA patterns showed a high agreement for ethN (? = 0.746) and formN (? = 0.847). There was no significant difference between visual and automated interpretation regarding positive/negative discrimination on ethN and formN, as well as ANCA pattern recognition (P > 0.05, respectively). Conclusions Pattern recognition algorithms can assist in the automated interpretation of ANCA IIF. Automated reading of ethN and formN IIF patterns demonstrated high consistency with visual ANCA assessment.
The endothelial-specific Angiopoietin-Tie2 ligand-receptor system is an important regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to Tie2 receptor renders the endothelial barrier responsive to pro-inflammatory cytokines. We previously showed that circulating Ang-2 correlated with disease severity in a small cohort of critically ill patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The current study reassessed Ang-2 as a biomarker of disease activity and relapse in AAV. Circulating Ang-2 was measured in 162 patients with severe AAV (BVAS/WG?3, with or without glomerulonephritis) in a clinical trial. Ang-2 levels during active AAV were compared to levels in the same patients during remission (BVAS/WG?=?0). Levels in clinical subsets of AAV were compared, and association with future disease course was assessed. Ang-2 levels were elevated in severe disease (median 3.0 ng/ml, interquartile range 1.9–4.4) compared to healthy controls (1.2, 0.9–1.5). However, they did not reliably decline with successful treatment (median 2.6 ng/ml, interquartile range 1.9–3.8, median change ?0.1). Ang-2 correlated weakly with BVAS/WG score (r?=?0.17), moderately with markers of systemic inflammation (r?=?0.25–0.41), and inversely with renal function (r?=??0.36). Levels were higher in patients with glomerulonephritis, but levels adjusted for renal dysfunction were no different in patients with or without glomerulonephritis. Levels were higher in patients with newly diagnosed AAV and lower in patients in whom treatment had recently been started. Ang-2 levels during active disease did not predict response to treatment, and Ang-2 levels in remission did not predict time to flare. Thus, Ang-2 appears to have limited practical value in AAV as a biomarker of disease activity at time of measurement or for predicting future activity.
Monach, Paul A.; Kumpers, Philipp; Lukasz, Alexander; Tomasson, Gunnar; Specks, Ulrich; Stone, John H.; Cuthbertson, David; Krischer, Jeffrey; Carette, Simon; Ding, Linna; Hoffman, Gary S.; Ikle, David; Kallenberg, Cees G. M.; Khalidi, Nader A.; Langford, Carol A.; Seo, Philip; St. Clair, E. William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R.; Haubitz, Marion; Merkel, Peter A.
The discovery of a strong association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has led to an increasingly rare diagnosis of idiopathic essential MC (EMC). The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence, including HCV. The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation. In addition, although cryoglobulin testing is simple, improper testing conditions will result in false negative results. Here, we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations, highlighting the importance of extensive investigation to reach a proper diagnosis. We review the need for appropriate laboratory testing, which is often neglected in clinical practice and which can result in false negative results. This review also emphasizes the significance of an extended testing repertoire necessary for better patient management. Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation, EMC remains a separate entity. Correct diagnosis requires proper temperature regulation during sample handling, as well as characterization and quantification of the cryoprecipitate. Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring. Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome, which will reduce variability in inter-laboratory reporting. PMID:24868518
Anis, Sabiha; Abbas, Khawar; Mubarak, Mohammad; Ahmed, Ejaz; Bhatti, Sajid; Muzaffar, Rana
The first part of this review addresses the diagnosis and differential diagnosis of the primary vasculitides Wegener's granulomatosis, microscopic polyangiitis, Churg–Strauss syndrome and polyarteritis nodosa. Prompt diagnosis and treatment of these conditions ensures an optimal prognosis. The development of assays for antineutrophil cytoplasmic antibodies has aided the diagnosis of Wegener's granulomatosis and microscopic polyangiitis. However, even in cases where there is high clinical likelihood that these conditions are present, up to 20% may be antibody negative, whereas alternative diagnoses may be antibody positive. The final diagnosis rests on a balance of clinical, laboratory, radiological and histological features. The exclusion of alternative diagnoses is important in assuring appropriate therapy. Particular attention is paid to the more fulminant presentations of these conditions and the role of the critical care physician in their diagnosis and management.
Semple, David; Keogh, James; Forni, Luigi; Venn, Richard
We report here a case with hypereosinophilia and peripheral artery occlusion. A 32-yr-old Korean woman presented to us with lower extremity swelling and pain. Angiography revealed that multiple lower extremity arteries were occlusive. The biopsy specimen showed perivascular and periadnexal dense eosinophilic infiltration in dermis and subcutaneous adipose tissue. Laboratory investigations revealed a persistent hypereosinophilia. She was prescribed prednisolone 60 mg daily. Her skin lesion and pain were improved and the eosinophil count was dramatically decreased. After discharge, eosinophil count gradually increased again. Cyanosis and pain of her fingers recurred. She had been treated with cyclophosphamide pulse therapy. Her eosinophilia was decreased, but the cyanosis and tingling sense were progressive. The extremity arterial stenoses were slightly progressed. Skin biopsy showed perivascular eosinophilic infiltration in the dermis and CD40 ligand (CD40L) positive eosinophilic infiltration. The serum TNF-? was markedly increased. These results suggest that CD40L (a member of TNF-? superfamily) could play a role in the inflammatory processes when eosinophil infiltration and activation are observed. We prescribed prednisolone, cyclophosphamide, clopidogrel, cilostazol, beraprost and nifedipine, and she was discharged.
Kim, Sung-Hwan; Kim, Tae-Bum; Yun, Young-Sun; Shin, Jung-Im; Oh, Il-Young; Sir, Jung-Ju; Kim, Kyung-Mook; Park, Hye-Kyung; Kang, Hye-Ryun; Chang, Yoon-Seok; Kim, Yoon-Keun; Song, Yeong-Wook; Choi, Dong-Chul; Min, Kyung-Up; Kim, You-Young
Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66 year old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy demonstrated diffuse interstitial inflammation with non-caseating granulomas that exhibited the unusual feature
Varun Agrawal; Giovanna M. Crisi; Vivette D. D'Agati; Benjamin J. Freda
Anti-neutrophil cytoplasmic antibody associated vasculitides (AAV) are conditions defined by an autoimmune small vessel inflammation. Dying neutrophils are found around the inflamed vessels and the balance between infiltrating neutrophils and macrophages is important to prevent autoimmunity. Here we investigate how sera from AAV patients may regulate macrophage polarization and function. Macrophages from healthy individuals were differentiated into M0, M1, M2a, M2b or M2c macrophages using a standardized protocol, and phenotyped according to their expression surface markers and cytokine production. These phenotypes were compared with those of macrophages stimulated with serum from AAV patients or healthy controls. While the healthy control sera induced a M0 macrophage, AAV serum promoted polarization towards the M2c subtype. No sera induced M1, M2a or M2b macrophages. The M2c subtype showed increased phagocytosis capacity compared with the other subtypes. The M2c polarization found in AAV is consistent with previous reports of increased levels of M2c-associated cytokines. PMID:24631966
Ohlsson, Susanne M; Linge, Carl Petrus; Gullstrand, Birgitta; Lood, Christian; Johansson, Asa; Ohlsson, Sophie; Lundqvist, Andrea; Bengtsson, Anders A; Carlsson, Fredric; Hellmark, Thomas
Background. The (anti neutrophil cytoplasmatic autoantibody ANCA), associated small vessel vasculitides (ASVV) are relapsing-remitting inflammatory disorders, involving various organs, such as the kidneys. (Monocyte chemoattractant protein 1 MCP-1) has been shown to be locally up regulated in glomerulonephritis and recent studies have pointed out MCP-1 as a promising marker of renal inflammation. Here we measure urinary cytokine levels in different phases of disease, exploring the possible prognostic value of MCP-1, together with (interleukin 6 IL-6), (interleukin 8 IL-8) and (immunoglobulin M IgM). Methods. MCP-1, IL-6 and IL-8 were measured using commercially available ELISA kits, whereas IgM in the urine was measured by an in-house ELISA. Results. The MCP-1 levels in urine were significantly higher in patients in stable phase of the disease, compared with healthy controls. Patients in stable phase, with subsequent adverse events; had significantly higher MCP-1 values than patients who did not. MCP-1 and IgM both tended to be higher in patients relapsing within three months, an observation, however, not reaching statistical significance. Urinary levels of IL-6 correlated with relapse tendency, and IL-8 was associated with disease outcome. Conclusions. Patients with ASVV have raised cytokine levels in the urine compared to healthy controls, even during remission. Raised MCP-1 levels are associated with poor prognosis and possibly also with relapse tendency. The association with poor prognosis was stronger for U-MCP-1 than for conventional markers of disease like CRP, BVAS, and ANCA, as well as compared to candidate markers like U-IgM and U-IL-8. We thus consider U-MCP-1 to have promising potential as a prognostic marker in ASVV.
Ohlsson, Sophie; Bakoush, Omran; Tencer, Jan; Torffvit, Ole; Segelmark, Marten
The discovery of a strong association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has led to an increasingly rare diagnosis of idiopathic essential MC (EMC). The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence, including HCV. The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation. In addition, although cryoglobulin testing is simple, improper testing conditions will result in false negative results. Here, we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations, highlighting the importance of extensive investigation to reach a proper diagnosis. We review the need for appropriate laboratory testing, which is often neglected in clinical practice and which can result in false negative results. This review also emphasizes the significance of an extended testing repertoire necessary for better patient management. Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation, EMC remains a separate entity. Correct diagnosis requires proper temperature regulation during sample handling, as well as characterization and quantification of the cryoprecipitate. Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring. Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome, which will reduce variability in inter-laboratory reporting.
Anis, Sabiha; Abbas, Khawar; Mubarak, Mohammad; Ahmed, Ejaz; Bhatti, Sajid; Muzaffar, Rana
Carotidynia is a syndrome characterized by tenderness of the carotid artery near the bifurcation due to numerous, heterogeneous causes. Here we reported the case of a 31-year-old Moroccan woman with right-sided neck pain and tenderness with irradiation to ipsilateral ear, eye, and occipital region. Clinical symptoms and imaging findings were suggestive of primary variant of carotidynia syndrome. In particular, color-Doppler ultrasonography revealed a concentric wall thickening of the distal common carotid artery, while thoracic magnetic resonance showed localized perivascular enhancement of the soft tissue in the right medial-distal common carotid artery in T1-weighted images, without intraluminal diameter variation. Moreover, careful clinicoserological and imaging investigations (cranial, cervical, and thoracic angiocomputed tomography and magnetic resonance) excluded well-known disorders potentially responsible for carotidynia syndrome. The patient was scarcely responsive to nonsteroidal anti-inflammatory drugs, but clinical symptoms resolved after three months. Of interest, the patient showed latent Mycobacterium tuberculosis infection (positive tuberculosis interferon-gamma release assay; QuantiFERON-TB Gold); this finding suggested a possible triggering role of mycobacterial antigens in the immune-mediated mechanism responsible for localized carotid injury.
Cassone, Giulia; Colaci, Michele; Giuggioli, Dilia; Manfredi, Andreina; Sebastiani, Marco; Ferri, Clodoveo
Background/aims: Eales’ disease is an uncommon vasoproliferative retinal disease affecting otherwise healthy young men that is characterised by obliterative retinal periphlebitis, with sequelae such as recurrent vitreous haemorrhage and traction retinal detachment. This study was undertaken to determine whether visual prognosis of Eales’ disease could be improved by appropriate medical and surgical treatment. Methods: The authors retrospectively studied 30 patients (46 eyes) who were treated from 1992 to 2001. Recorded data included patient age, sex, race, medical history, medications, results of the ophthalmological examination, results of diagnostic laboratory evaluation, and details of systemic and surgical treatments. The mean follow up was 10.6 months. Results: 19 patients (23 eyes) who presented with active periphlebitis received systemic steroids and antituberculous therapy. Extensive full panretinal photocoagulation was performed in 21 eyes that presented with new vessel formation and peripheral capillary closure with or without vitreous haemorrhage. Vitrectomy and endolaser panretinal photocoagulation was necessary in 15 eyes, for severe non-clearing vitreous haemorrhage in 11 eyes and vitreous haemorrhage with traction retinal detachment in four eyes. Complete regression of the disease was achieved in all eyes. Vitrectomy resulted in a significant visual improvement with 14 of the 15 eyes (93.3%) achieving ?20/200 visual acuity. Overall, the distribution of visual acuities among eyes improved from presentation to final follow up, with 36.4% of eyes having 20/40 or better acuity at presentation compared with 63.6% of eyes by final follow up. Conclusions: These results suggest that aggressive treatment of Eales’ disease with systemic steroids and antituberculous therapy, full panretinal photocoagulation and early vitrectomy, when necessary, may result in improving the anatomic and visual outcome.
El-Asrar, A M Abu; Al-Kharashi, S A
Background. Investigating the mechanical properties of the arteries is essential in cardiovascular diseases. Recent imaging modalities allow mapping mechanical properties within the arterial wall. Aims. We report the potential of imaging-based biomarker (ImBioMark) to investigate the effect of aging on the rat. We also present preliminary data with ImBioMark characterizing vascular sequelae of Kawasaki disease (KD) in young humans. Methods. We investigated in vivo the effect of aging on male Brown Norway (BN) rats' (n = 5) carotid stiffness. In a second experiment, the impact of KD on the ascending aorta (AA) was examined in KD children (n = 2) aged 13 ± 1.41 years old compared to KD-free children (n = 5) aged 13.13 ± 0.18 years old. Results. The stiffness of BN's carotid artery was three times stiffer in the old rats, with a turning point at 40 weeks old (P = 0.001). KD had a very significant impact on the AA stiffness with strain estimates of 2.39 ± 0.51% versus 4.24 ± 0.65% in controls (P < 0.001). Conclusion. ImBioMark phenotypes hypertension in rat models noninvasively in vivo without resorting to euthanasia. Quantifying aortic wall remodeling is also feasible in humans. Future investigations target human cardiovascular disease. PMID:22919495
Maurice, Roch Listz; Dahdah, Nagib; Tremblay, Johanne
MRL-lpr\\/lpr mice spontaneously develop a lupus-like syndrome characterized by immunopathological manifestations such as necrotizing vascular lesions of ear tips and severe glomerulonephritis. Similar skin vascular and glomerular lesions associated with cryoglobulinemia can be induced in normal mice by injection of a monoclonal antibody (mAb)-6.19 (gamma 3 heavy chain and kappa light chain), exhibiting both cryoglobulin and anti-IgG2a rheumatoid factor (RF)
Luc Reininger; Thierry Berney; Takanori Shibata; Francois Spertini; Ramon Merino; Shozo Izui
Patients who are chronically infected with hepatitis C virus (HCV) often develop mixed cryoglobulinemia (MC), a B-cell proliferative disorder with polyclonal acti- vation and autoantibody production. We investigated if MC is associated with a deficit of CD4CD25 immunoregulatory T (Treg) cells, which have been shown to control autoimmunity. Because Treg cells express higher amounts of CD25 than activated CD4 T
Olivier Boyer; David Saadoun; Julien Abriol; Melanie Dodille; Jean-Charles Piette; Patrice Cacoub; David Klatzmann
Chronic infection with hepatitis C virus (HCV) may be complicated by the development of systemic vasculitis. Vasculitis is either caused by mixed cryoglobulinemia or a non-cryoglobulinemic vasculitis resembling polyarteritis nodosa (PAN). Antiviral treatment with interferon-? (IFN) and subsequent clearing of HCV mostly leads to improvement of vasculitic symptoms, but vasculitis may also be exacerbated and even cases of new onset
Wilke Beuthien; Hans-Ullrich Mellinghoff; Johannes von Kempis
Evidence is beginning to accumulate that p38 mitogen activated protein kinase (p38 MAPK) signaling pathway plays an important role in the regulation of cellular and humoral autoimmune responses. The exact mechanisms and the degree by which the p38 MAPK pathway participates in the immune-mediated induction of diseases have started to emerge. This review discusses the recent advances in the molecular dissection of the p38 MAPK pathway and the findings generated by reports investigating its role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and autoimmune hepatitis. Application of newly-developed protocols based on sensitive flow cytometric detection has proven to be a useful tool in the investigation of the phosphorylation of p38 MAPK within different peripheral blood mononuclear cell populations and may help us to better understand the enigmatic role of this signaling cascade in the induction of autoimmunity as well as its role in immunosuppressive-induced remission. Special attention is paid to reported data proposing a specific role for autoantibody-induced activation of p38 MAPK-mediated immunopathology in the pathogenesis of autoimmune blistering diseases and anti-neutrophilic antibody-mediated vasculitides. PMID:23207287
Mavropoulos, Athanasios; Orfanidou, Timoklia; Liaskos, Christos; Smyk, Daniel S; Billinis, Charalambos; Blank, Miri; Rigopoulou, Eirini I; Bogdanos, Dimitrios P
Introduction We report a rare case of fulminant vasculitic mononeuropathy resulting in brachial diplegia, with suspected brainstem and autonomic nervous system involvement in a patient with diabetes mellitus. Case presentation A 58-year-old Hispanic Caucasian man with diabetes mellitus presented with a 1-year history of progressive bilateral upper extremity weakness, orthostatic intolerance and progressive memory decline. Diagnostic evaluation including laboratory tests for progressive encephalopathies, systemic inflammatory and non-inflammatory neuropathies, cerebrospinal fluid analyses, electrodiagnostic studies, and nerve biopsy were performed. Clinical examination revealed moderate cognitive deficits on the Montreal Cognitive Assessment scale, bilateral facial weakness and weakness of bilateral shoulder girdle and intrinsic hand muscles. Cerebrospinal fluid analyses revealed elevated protein and an elevated immunoglobulin G synthesis rate, suggesting an immune-mediated process. Further laboratory work up was non-diagnostic. Electrodiagnostic studies demonstrated chronic asymmetric axonal mononeuropathies with ongoing denervation. A superficial radial nerve biopsy showed a chronic vasculitic neuropathy. Glucocorticosteroid treatment, symptomatic pharmacologic and supportive non-pharmacologic therapies resulted in improved clinical outcomes despite challenges with glycemic control. Conclusions This case report emphasizes the importance of a thorough evaluation of atypical or uncommon neuromuscular presentations in diabetic patients without etiological presumptions. This is necessary in order to promptly establish a diagnosis, initiate appropriate therapies and prevent irreversible nerve injury.
...such as autoimmune diseases (e.g., lupus, scleroderma, psoriasis, vasculitis...Interferon-alpha in auto-immune diseases such as lupus, scleroderma, psoriasis, and vasculitis...in part) by Interferon-alpha include lupus, scleroderma, psoriasis, and...
Background\\/Aim: Hepatitis C virus (HCV) infection is often associated with mixed cryoglobulins (MC) and may manifest as small-vessel vasculitis. It has been suggested that antibody (Ab) or sensitized T cells to HCV-containing endothelial cells may initiate the vasculitis process. Anti-endothelial cell antibodies (AECA) have been found in various connective tissue disorders, with a high prevalence in systemic vasculitis. The aim
Patrice Cacoub; Pascale Ghillani; Ronan Revelen; Vincent Thibault; Vincent Cálvez; Frédéric Charlotte; Lucile Musset; Pierre Youinou; Jean-Charles Piette
The manifestations of human immunodeficiency virus (HIV) infection are protean and vasculitides are one of the less common but nonetheless important consequences. A wide range of vasculitides can be encountered, ranging from vasculitis resulting from specific infective agents to a non-specific vasculitis. Among the infective causes, cytomegalovirus and tuberculosis are probably the most common. A polyarteritis nodosa-like vasculitis with important differences to classic polyarteritis nodosa is also described. Hypersensitivity vasculitis resulting in several patterns of vasculitis and angiocentric immunoproliferative vasculitis are well recognised. As part of the immunocompromise caused by HIV, a granulomatous inflammation involving small arteries and veins of the brain surface and leptomeninges, termed a primary angiitis of the central nervous system, is a rare vasculitis associated with high mortality. A recently described large vessel (aorta, femorals, carotids) vasculopathy resulting in either multiple aneurysm formation or occlusive disease is seen in young adults. An infective agent is not found but aetiologically some of these lesions might be the result of a leucocytoclastic vasculitis of vasa vasora or periadventitial vessels. A final group of non-specific vasculitides not fitting into any of the characteristic patterns described accounts for the residue of vasculitides associated with HIV. Key Words: human immunodeficiency virus • vasculitis • immunocompromise
Vasculitis is a hallmark lesion of the severe form of systemic porcine circovirus-associated disease (PCVAD). In 2 experimental studies with porcine circovirus type 2 serogroup b (PCV2b), 2 pigs developed fatal PCVAD with acute vasculitis, and 5 related pigs developed chronic lymphohistiocytic and plasmacytic peri- and endarteritis. Five of these pigs (1 with acute vasculitis and 4 with chronic vasculitis) had also been inoculated with bovine viral diarrhea virus type 1 (BVDV1) or BVDV1-like virus. Vascular lesions were similar, independent of whether pigs had been inoculated singly with PCV2b or dually with PCV2b and BVDV1 or BVDV1-like virus. The acute vasculitis was accompanied by marked pulmonary and mesenteric edema and pleural effusion. In situ hybridization demonstrated abundant intracytoplasmic porcine circovirus type 2 (PCV2) nucleic acid in endothelial, smooth muscle-like, and inflammatory cells within and around affected arteries. The pigs with lymphohistiocytic and plasmacytic vasculitis had lesions of systemic PCVAD, including multisystemic lymphoplasmacytic and histiocytic or granulomatous inflammation. PCV2 nucleic acid was detected in renal tubule epithelial cells, mononuclear inflammatory cells, and rare endothelial cells in noninflamed vessels in multiple tissues of these animals. The 2 pigs with acute vasculitis had no PCV2-specific antibodies (or a low titer of), whereas the pigs with lymphohistiocytic and plasmacytic vasculitis developed high antibody titers against this virus. These observations suggest that (1) acute vasculitis observed in the current studies is directly caused by PCV2b, (2) chronic vasculitis may in part be mediated by the subsequent immune response, and (3) host factors and viral strain may both contribute to vasculitis in animals infected with PCV2b. PMID:20080495
Langohr, I M; Stevenson, G W; Nelson, E A; Lenz, S D; HogenEsch, H; Wei, H; Pogranichniy, R M
Secondary systemic vasculitis and nonbacterial endocarditis are rare events. We report a case presented with different manifestations of underlying malignancy such as systemic vasculitis, non bacterial endocarditis and DIC (disseminated intravascular coagulopathy). Efforts to find the source of malignancy was unsuccessful and due to patient's unwillingness for further evaluation, finally under the diagnosis of metastatic disease of unknown primary, patient is receiving cyclic chemotherapy.
Mahmoodian, Reihaneh; Haghighi, Anoosheh; Vakili, Masoud; Shahriari-Ahmadi, Ali; Hajsadeghi, Shokoufeh; Arabi, Mohsen
BACKGROUND: Henoch Schonlein purpura (HSP) is a common vasculitis of small vessels whereas endothelin-1 (ET-1) is usually reported elevated in vasculities and systematic inflammation. The aim of the present study was to investigate whether ET-1 levels are correlated with the clinical presentation and the outcome of HSP. METHODS: The study sample consisted of thirty consecutive patients with HSP. An equal
S Fessatou; P Nicolaidou; D Gourgiotis; H Georgouli; K Douros; M Moustaki; A Fretzayas
BackgroundMixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune complex deposition in the small vessels. In the overwhelming majority of patients, hepatitis C virus (HCV) infection represents the triggering factor of the disease. MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral nerves, and less frequently by widespread vasculitis and cancer.
Clodoveo Ferri; Marco Sebastiani; Dilia Giuggioli; Massimiliano Cazzato; Giovanni Longombardo; Alessandro Antonelli; Rodolfo Puccini; Claudio Michelassi; Anna Linda Zignego
Forty-two cases of vasculitis coincident with hairy cell leukemia (HCL) havebeen reported, of which 17 had panarteritis nodosa (PAN), 21 had cutaneous leukocytoclastic vasculitis (LCV), and 4 had vessel wall infiltration by hairy cells. PAN generally occurred after the diagnosis of HCL, splenectomy, and infection. HBs antigen was detected in 3 of 12 patients tested, whereas immune complexes were positive
Paul Hasler; Hansjörg Kistler; Heini Gerber
In a patient with angiographically proven cerebral vasculitis five months after acute posterior multifocal placoid pigment epitheliopathy (APMPPE) neurological symptoms promptly responded to steroid treatment. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis. Magnetic resonance imaging (MRI) revealed multifocal white matter lesions in the hemispheres and the brain stem suggesting a diffuse subcortical vasculitis. Images
Stoll, G; Reiners, K; Schwartz, A; Kaup, F G; Althaus, C; Freund, H J
In a patient with angiographically proven cerebral vasculitis five months after acute posterior multifocal placoid pigment epitheliopathy (APMPPE) neurological symptoms promptly responded to steroid treatment. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis. Magnetic resonance imaging (MRI) revealed multifocal white matter lesions in the hemispheres and the brain stem suggesting a diffuse subcortical vasculitis. PMID:2010765
Stoll, G; Reiners, K; Schwartz, A; Kaup, F G; Althaus, C; Freund, H J
A study of the influence of embedded circular hollow vascules on structural performance of a fibre-reinforced polymer (FRP) composite laminate is presented. Incorporating such vascules will lead to multi-functional composites by bestowing functions such as self-healing and active thermal management. However, the presence of off-axis vascules leads to localized disruption to the fibre architecture, i.e. resin-rich pockets, which are regarded as internal defects and may cause stress concentrations within the structure. Engineering approaches for creating these simple vascule geometries in conventional FRP laminates are proposed and demonstrated. This study includes development of a manufacturing method for forming vascules, microscopic characterization of their effect on the laminate, finite element (FE) analysis of crack initiation and failure under load, and validation of the FE results via mechanical testing observed using high-speed photography. The failure behaviour predicted by FE modelling is in good agreement with experimental results. The reduction in compressive strength owing to the embedding of circular vascules ranges from 13 to 70 per cent, which correlates with vascule dimension.
Huang, C.-Y.; Trask, R. S.; Bond, I. P.
We report the first case of ischaemic optic neuropathy (ION) linked to chronic myelomonocytic leukaemia (CMML) and its associated vasculitis. We discuss the link between CMML and vasculitis and the evidence suggesting it can cause anterior ischaemic optic neuropathy through a vasculitic process. We highlight the difficulty and delay in diagnosis as the use of steroids masked an underlying systemic process. Recurrent ION and raised inflammatory markers should raise suspicion of vasculitis. Together with an elevated monocyte but low platelet count, CMML should be considered. PMID:23179230
De Smit, Elisabeth; O'Sullivan, Eoin
Henoch-Schönlein purpura represents the most common form of systemic vasculitis in children. Although a very common cause of vasculitis, seizures are a very rare complication of this disorder. We report a 5-year-old boy who presents with no other clinical symptoms of the disorder other than a seizure. By presenting this case, we hope to expand the differential diagnosis of repeated seizures to include diseases in which the pathogenesis of diseases with small vessel vasculitis such as Henoch-Schönlein purpura is considered. PMID:24892684
Camacho, Christina; Leva, Ernest G
Review of four cases of relapsing polychondritis (RP) seen at one hospital in the 12-year period 1963 to 1974 revealed that one patient had aortic insufficiency with large artery involvement, two others had involvement of medium and large arteries and the fourth may have had mucocutaneous vasculitis. Valvular disease has occurred in 9% of all cases of RP reported in the literature and, if vasculitis beyong the aortic root is included, 25% of cases of RP manifested inflammatory vascular disease. The frequency of pseudotumour of the orbit and cochlear-labyrinthine dysfunction is also high and may be a manifestation of vasculitis.
Esdaile, J.; Hawkins, D.; Gold, P.; Freedman, S. O.; Duguid, W. P.
...necrosis would be unexpected (by virtue of greater severity) if the investigator brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater...
Anaphylactoid purpura is characterized by a generalized vasculitis, the etiology and pathogenesis of which remain unknown. Immunofluorescent and electron microscopy suggest an immune pathogenesis with the deposition of antigen antibody complexes on the ba...
M. G. White N. A. Kurtzman P. W. Rogers S. M. Bunn
The present invention provides HLA-restricted antigens as vaccines for treating or preventing autoimmune diseases or conditions, transplant rejection or vasculitis in a patient. In particular aspects, there is provided Pr3, a myeloid tissue-restricted pro...
...in the diagnosis of any disease concerned with abnormal levels of plasma or serum proteins, e.g., agammaglobulinemia, allergies, multiple myeloma, rheumatoid vasculitis, or hereditary angioneurotic edema. (b) Classification. Class I...
...in the diagnosis of any disease concerned with abnormal levels of plasma or serum proteins, e.g., agammaglobulinemia, allergies, multiple myeloma, rheumatoid vasculitis, or hereditary angioneurotic edema. (b) Classification. Class I...
Tissue diagnosis is required to distinguish invasive infection from colonization with P aeruginosa. A necrotizing lesion with massive bacterial proliferation, relative tissue neutropenia, and 'Pseudomonas vasculitis' is characteristic of infection with th...
F. D. Foley K. A. Greenawald G. Nash B. A. Pruitt
Controversy surrounding the use of electrical impedance plethysmography for detection of intracranial vascular phenomena centers on the origin of the waves derived from the head by this technique, that is, whether rheoencephalographic waves reflect vascul...
A. F. Heck
The association of lung emphysema with severe systemic antineutrophil cytoplasm antibodies (ANCA)-positive vasculitis, such as Wegener's granulomatosis is unusual since only four cases have been described previously. We report the first case of a 30 year-old smoker man presenting with biopsy-proven Wegener's granulomatosis, who developed a bullous emphysema during severe active lung vasculitis, in association with positive ANCA disclosing an anti-myeloperoxydase pattern. Alpha 1-antitrypsin deficiency, a known risk factor of lung emphysema recently found to be associated with anti-proteinase 3-positive vasculitis, was not present in this patient. Cigarette smoking, in association with severe lung vasculitis, might have contributed to the development of this emphysematous lesion. PMID:11093604
Mouly, S; Brillet, G; Stern, M; Lesavre, P; Guillevin, L
Contents: Autopsy analysis of 200 stroke cases; Optic disc vasculitis--Report of 42 cases; Plasma progesterone levels in normal and pregnant Chinese women and effects of contraceptives on them; Flower intrauterine contraceptive device; Hairy cell leukemia...
... What is granulomatosis with polyangiitis? Granulomatosis with polyangiitis (GPA) is a condition that causes inflammation that primarily ... known as Wegener granulomatosis. A characteristic feature of GPA is inflammation of blood vessels (vasculitis), particularly the ...
... this form of vasculitis are common. What is Granulomatosis with Polyangiitis (Wegener's)? Most commonly, GPA affects the sinuses, lungs and ... resolve organ injury in many instances. What causes Granulomatosis with Polyangiitis (Wegener's)? The cause of GPA is unknown. Who gets ...
Polyarteritis nodosa (PAN) is a vasculitis characterized by inflammatory necrosis of medium-sized arteries. Juvenile PAN and Kawasaki disease (KD) both cause vasculitis of the medium-sized arteries, and share common features. They have overlapping clinical features. Treatment should be managed according to the severity of symptoms and persistence of clinical manifestations. Herein is described the case of a 14-year-old boy first diagnosed with KD, who then fulfilled the criteria for juvenile PAN due to the development of severe myalgia, persistent fever, polyneuropathy and coronary arterial dilatation. He also had acute toxoplasmosis at the onset of vasculitis symptoms. The final diagnosis was of juvenile PAN associated with toxoplasmosis infection. Toxoplasma infection can be considered as an etiological agent for PAN and other vasculitis syndromes. Awareness of toxoplasmosis-related PAN facilitates early diagnosis, and instigation of appropriate treatment. PMID:24730628
Ba?aran, Ozge; Cakar, Nilgün; Gür, Gökçe; Kocaba?, Abdullah; Gülhan, Belgin; Cayc?, Fatma ?emsa; Celikel, Banu Acar
...7540Disseminated intravascular coagulation with renal cortical necrosis: Rate as renal dysfunction. 7541Renal involvement in diabetes mellitus, sickle cell anemia, systemic lupus erythematosus, vasculitis, or other systemic disease processes. Rate...
PurposePolyarteritis nodosa (PAN) is a systemic vasculitis of small and medium size arteries. The purpose of this study is to evaluate imaging findings, especially angiographic features, of 17 patients with abdominal involvement from polyarteritis nodosa.
N. Mnif; M. Chaker; S. Oueslati; T. H. Ellouze; F. Tenzakhti; S. Turki; N. Ben Abdallah; H. Ben Maïz; R. Hamza
A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.
Benson, C.H.; Pennebaker, J.B.; Harisdangkul, V.; Songcharoen, S.
A 51-year-old woman developed a sensorimotor peripheral neuropathy and a systemic vasculitis secondary to hepatitis C-related essential mixed cryoglobulinemia. Therapy with interferon-a (IFN-a ) at 3 million units three times a week was initiated. While on interferon, the clinical features of cryoglobuline mia progressed rapidly and the patient eventually died due to severe systemic vasculitis. Based on several clinical trials,
Gad Friedman; Shailesh Mehta; Averell H. Sherker
Henoch-Schönlein purpura (HSP) is an acute small vessel leucocytoclastic vasculitis. It is the commonest vasculitis in children, with an incidence of about 10 cases per 100, 000 a year. Gastrointestinal manifestations are commonly encountered, however hematemesis and gastric outlet obstruction are rarely reported. The authors present the case of a 5-y-old boy having hematemesis, gastric outlet obstruction and multiple duodenal ulcers. He improved with steroids and conservative management. PMID:23564516
Rathore, Mukesh; Shrivastava, Rimjhim; Goyal, Ravinder; Radotra, B D; Thapa, B R
In the Brown Norway (BN) rat, chemical compounds (mercuric chloride (HgCl2), D-penicillamine or gold salts) induce a Th2-dominated autoimmune syndrome with tissue injury in the form of a vasculitis and arthritis. An early phase of vasculitis in the model occurs within 24 h of an injection of HgCl2 ,i s?? T cell independent and involves the mast cell. In addition,
Zhonglin Wu; David R. Turner; David B. G. Oliveira
Secondary systemic vasculitis and nonbacterial endocarditis are rare events. We report a case presented with different manifestations of underlying malignancy such as systemic vasculitis, non bacterial endocarditis and DIC (disseminated intravascular coagulopathy). Efforts to find the source of malignancy was unsuccessful and due to patient's unwillingness for further evaluation, finally under the diagnosis of metastatic disease of unknown primary, patient is receiving cyclic chemotherapy. PMID:24505550
Iranpour, Aida; Mahmoodian, Reihaneh; Haghighi, Anoosheh; Vakili, Masoud; Shahriari-Ahmadi, Ali; Hajsadeghi, Shokoufeh; Arabi, Mohsen
SCG\\/Kinjoh mice: A model of ANCA-associated crescentic glomerulonephritis with immune deposits.BackgroundSpontaneous crescentic glomerulonephritis-forming\\/Kinjoh (SCG\\/Kj) mice spontaneously develop crescentic glomerulonephritis (CGN), systemic vasculitis, and perinuclear ANCA (pANCA), and have been suggested as an animal model for human antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AASV). Since no systematic serologic, immunohistologic, or structural evaluation had been performed thus far, we reinvestigated the development of
Irmgard Neumann; Rainer Birck; Mark Newman; Peter Schnülle; Wilhelm Kriz; Kyuichi Nemoto; Benito Yard; Rüdiger Waldherr; Fokko J. Van Der Woude
A 31-year-old woman with Cogan syndrome (a rare form of systemic vasculitis) was evaluated for a cold, painful left foot with diminished pulses. Arteriography demonstrated thrombosis of the left popliteal artery with evidence of vasculitis. Thrombolytic therapy was begun with initial success but eventual rethrombosis. After reinitiating thrombolytic therapy combined with intraarterial vasodilator therapy, successful angioplasty was performed with sustained results, at 6-month follow-up.
Bastug, Demir E.; Dominic, Anthony; Ortiz, Orlando [Robert C. Byrd Health Sciences Center, Department of Radiology, West Virginia University (United States); DiBartolomeo, Anthony G. [Robert C. Byrd Health Sciences Center, Department of Medicine, Rheumatology Section, West Virginia University (United States); Kotzan, Jeffrey M. [Robert C. Byrd Health Sciences Center, Department of Radiology, West Virginia University (United States); Abraham, F. Matthew [Robert C. Byrd Health Sciences Center, Department of Medicine, West Virginia University (United States)
OBJECTIVEWegener’s granulomatosis (WG) is an inflammatory disorder characterised by granulomatous inflammation, vasculitis, and necrotising vasculitis and is strongly associated with anti-neutrophil cytoplasmic antibodies (ANCA). Activated monocytes\\/macrophages are present in renal biopsy specimens and participate in granuloma formation by synthesising and secreting a variety of chemoattractants, growth factors, and cytokines. In view of these findings, in vivo monocyte activation was evaluated
Anneke C Muller Kobold; Cees G M Kallenberg; Jan Willem Cohen Tervaert
In a patient with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), a pontine infarction occurred about 6 months after the ophthalmological manifestation. We report the first case with histopathologically proven vasculitis shown by muscle biopsy and the first positron emission tomographic documentation in APMPPE. The ophthalmological and cerebral symptoms responded well to steroid treatment. Long-term immunosuppression (e.g. azathioprine 1-2 mg/kg) seems to decrease the risk of recurrent systemic vasculitis. PMID:8138817
Bewermeyer, H; Nelles, G; Huber, M; Althaus, C; Neuen-Jacob, E; Assheuer, J
Abstract Rheumatoid arthritis (RA) is a systemic inflammatory disease often complicated by vasculitis. Pericarditis is a serious complication caused by vasculitis, resulting in retention of pericardial effusion that sometimes induces cardiac tamponade. We report a patient with RA in whom pericarditis improved after tocilizumab administration. A male patient was diagnosed with RA and chronic renal failure in 1980 and was treated with salazosulfapyridine, but disease activity remained high. In January 2012, at the age of 73 years, he developed organizing pneumonia as a complication and was admitted to our hospital. Treatment with prednisolone 30 mg/day was initiated. However, 20 days after initiation of treatment, chest pain and palpitation developed, and chest computed tomography (CT) and echocardiography (ECG) revealed retention of pericardial effusion without cardiac tamponade. Rheumatoid nodules and interstitial pneumonia were also observed, and serum C3 level was decreased. A diagnosis of pericarditis caused by vasculitis was made based on these findings, and tocilizumab 8 mg/kg was administered. His symptoms improved gradually, and chest CT and ECG showed no pericardial effusion after about 3 weeks. No adverse effects of tocilizumab were observed during the clinical course. Although there are only a few reports of the effects of tocilizumab on vasculitis associated with RA, tocilizumab administration appears worthwhile in RA patients with vasculitis who do not respond to conventional treatment. PMID:24517555
Yoshida, Shuzo; Takeuchi, Tohru; Sawaki, Hideaki; Imai, Tamaki; Makino, Shigeki; Hanafusa, Toshiaki
Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) has become an important tool for supporting a diagnosis of systemic necrotizing small vessel vasculitis: Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and oligo-symptomatic forms of these. These so-called ANCA-associated vasculitides most often necessitate the institution of therapies with cytotoxic as well as anti-inflammatory agents, and hence, a firmly established diagnosis is mandatory to avoid unnecessary and risky treatment. In the laboratory of today the most appropriate way to detect the presence of vasculitis-associated ANCA is by using both indirect immunofluorescence and direct enzyme immuno-assay for antibodies to proteinase 3 and myeloperoxidase. The diagnostic specificity of these latter assays towards systemic vasculitis can only be secured by setting a suitably high cut-off value, chosen in collaboration with clinicians after testing carefully selected disease control sera. When classical cytoplasmic ANCA as well as a significant level of proteinase 3-ANCA are found in a given serum this combined result strongly indicates vasculitis. Similarly, the combination of perinuclear ANCA and a significant level of myeloperoxidase-ANCA is close to 100% specific for vasculitis. PMID:11446667
The present study gives a detailed report of a patient with atypical Cogan's syndrome with uveitis and sensorineural hearing loss. Cogan's syndrome is characterized by nonsyphilitic interstitial keratitis and audiovestibular dysfunction. This syndrome can be divided into two groups, typical and atypical, based on the presence of interstitial keratitis. It may sometimes be associated with systemic vasculitis. Fluoro-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) scanning was used to investigate the presence of vasculitis. With FDG-PET/CT scanning, there is no pathological involvement in the walls of the arteries; thus the patient is protected from aggressive and long term immunosuppressive treatment's side effects. Hence, we can conclude that FDG-PET/CT may play an important role in excluding the presence of vasculitis. PMID:24963451
Orsal, Ebru; U?ur, Mahir; Seven, Bedri; Ayan, Arif Kür?ad; Içyer, Fatma; Y?ld?z, Asl?
The present study gives a detailed report of a patient with atypical Cogan’s syndrome with uveitis and sensorineural hearing loss. Cogan’s syndrome is characterized by nonsyphilitic interstitial keratitis and audiovestibular dysfunction. This syndrome can be divided into two groups, typical and atypical, based on the presence of interstitial keratitis. It may sometimes be associated with systemic vasculitis. Fluoro-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) scanning was used to investigate the presence of vasculitis. With FDG-PET/CT scanning, there is no pathological involvement in the walls of the arteries; thus the patient is protected from aggressive and long term immunosuppressive treatment’s side effects. Hence, we can conclude that FDG-PET/CT may play an important role in excluding the presence of vasculitis.
Orsal, Ebru; Ugur, Mahir; Seven, Bedri; Ayan, Arif Kursad; Icyer, Fatma; Y?ld?z, Asl?
Context: Anti-neutrophil p-ANCA antibodies are directed against antigens in the peripheral cytoplasm of both neutrophilic granulocytes and monocytes. They are detected in several autoimmune disorders and are particularly associated with systemic vasculitis. Case Report: We report a case of a 54-year-old female presenting with a pruritic rash, including purpura and diffuse erythema. A biopsy with hematoxylin and eosin (H & E) analysis, direct immunofluorescence (DIF), immunohistochemistry (IHC) and enzyme-linked immunosorbent assays for ANCAs were performed. The H & E staining demonstrated leukocytoclastic vasculitis, with focal vascular fibrinoid necrosis. The DIF revealed evidence of vasculitis, the presence of p-ANCAs and neutrophil extracellular traps (NETs). The IHC displayed autoreactivity to myeloperoxidase within the vessels. The IHC aided in ruling out any intrinsic autofluorescence of the vessels. Conclusions: By observing the deposition of neutrophil extracellular traps and myeloperoxidase in inflamed skin vessels, biopsy analysis may alert physicians for rapid therapeutic intervention in patients presenting with possible vasculitides.
Abreu-Velez, Ana Maria; Smith, J. Graham; Howard, Michael S.
We report the case of a patient with intestinal ischaemia and necrosis resulting from vasculitis of mesenteric veins and their intramural tributaries. This patient was otherwise healthy, had no prior history of inflammatory bowel disease nor clinical evidence of extra intestinal involvement or systemic vasculitis, and since four years, was treated with hydroxyethyl rutoside (Venoruton). He recovered completely after segmental resection of the affected portion of the bowel and had no recurrence of intestinal symptoms on follow-up of up to three years. The histopathological diagnostic hallmarks of this clinical entity are extensive lesions of lymphocytic phlebitis associated with thrombi of different ages and focal fibrinoid necrosis while arteries and arterioles are not affected. This unusual form of vasculitis affecting veins only is very rare and its etiology unknown. PMID:9457320
Chergui, M H; Vandeperre, J; Van Eeckhout, P
Propylthiouracil (PTU) is a frequently prescribed drug in the treatment of hyperthyroidism. The use of PTU is, however, accompanied by numerous potentially serious side effects including vasculitis. PTU-related vasculitides can present as haematuria, pulmonary haemorrhage, or cutaneous lesion together with aspecific symptoms such as fever, myalgia, arthralgia, and fatigue. Cerebral involvement is seldom observed. We present a 49-year-old female with Graves' disease and asthma, who developed paresis of the proximal extremities, eosinophilia, pulmonary, and cutaneous lesions following treatment with PTU. A cerebral vasculitis consistent with Churg-Strauss syndrome (CSS) was suspected. Although cerebral involvement is seldom observed with PTU treatment, cerebral vasculitis should be considered in patients developing CNS symptoms.
Quax, R. A. M.; Swaak, A. J. G.; Baggen, M. G. A.
Henoch-Shönlein purpura (HSP) is a systemic small vessel vasculitis. Most patients present during childhood. The characteristic association of purpura, arthralgia, abdominal pain, and nephritis reflects the predominant distribution of vasculitis. Headaches and mild behavioral changes suggest CNS involvement in one-third of HSP patients. Salient central nervous system (CNS) manifestations are rarer and mostly reported in adults and patients with a severe disease course. Diagnosis of CNS vasculitis is rarely confirmed by histopathology and generally relies on "suggestive" imaging showing brain hemorrhages, infarcts and edema, predominantly located in the parieto-occipital regions. Vessel wall friability and thrombogenicity of active vasculitis, antiphospholipid antibody synthesis, and other hemostatic disturbances may contribute to hemorrhagic and thrombotic complications of HSP. Posterior reversible encephalopathy syndrome and hypertensive encephalopathy occur in HSP and can be difficult to differentiate from CNS vasculitis. Some 53% of patients with neurologic complications experience seizures. Cerebral venous thrombosis, subdural hematoma, subarachnoidal hemorrhage, neuro-ophthalmologic complications, myelopathy, and diverse neuromuscular manifestations are also reported. In contrast with other systemic small vessel vasculitides, peripheral nervous system involvement is infrequent in HSP. Systemic involvement of HSP and homeostatic disorders such as hypertension, uremia, and electrolyte disturbances, as well as superimposed infections can affect the nervous system secondarily. Identification of nervous system complications of HSP is often challenging due to prominent systemic manifestations. HSP is usually a self-limiting disease that requires only supportive care. Patients with CNS vasculitis are commonly treated with corticosteroids. One-fifth of patients with CNS involvement remain with sequelae. PMID:24365374
Bérubé, Maxime D; Blais, Normand; Lanthier, Sylvain
Gastrointestinal manifestations of systemic lupus erythematosus (SLE) are common, occurring in about 50% of cases. They are usually mild, in the form of mouth ulcers, nausea, heartburn and mild abdominal pain, but they can be severe in cases of gastrointestinal vasculitis. In this report we describe an unusual combination of SLE complications, namely superior mesenteric artery syndrome (SMAS) and reversible acute obstructive renal failure. This was attributed to raised intra-abdominal pressure and hence intra-abdominal compartment syndrome (IACS) following weight loss secondary to an acute presentation of SLE with gastrointestinal vasculitis. PMID:24335010
Bedaiwi, M; Alkubeyyer, M A; Al Arfaj, A S
We describe a short history of Kawasaki disease. In 1967, we published a paper entitled 'Infantile acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes. Clinical observation of 50 cases'; this was the first report on what is now called Kawasaki disease. Since then, many reports on cardiology, treatment, epidemiology, pathology and etiology of Kawasaki disease have been published. Furthermore, a recent Chapel Hill Consensus Statement on Kawasaki disease in the classification of vasculitis is given, along with a figure on the relationship and classification of childhood vasculitis by autopsy material. PMID:24595558
Kawasaki, Tomisaku; Naoe, Shiro
Henoch-Schonlein Purpura (HSP) is a small vessel vasculitis mediated by IgA-immune complex deposition. It is characterized by the clinical tetrad of non-thrombocytopenic palpable purpura, abdominal pain, arthritis and renal involvement. Pathologically, it can be considered a form of immune complex-mediated leukocytoclastic vasculitis (LCV) involving the skin and other organs. Though it primarily affects children (over 90% of cases), the occurrence in adults has been rarely reported. Management often involves the use of immunomodulatory or immune-suppressive regimens.
Henoch-Schönlein purpura (HSP) is a common childhood systemic vasculitis with clinical characteristics of cutaneous palpable purpura, arthralgia/arthritis, bowel angina, and hematuria/proteinuria. HSP is identified mainly based on the above presentations. Combined with pathohistological findings of leukocytoclastic vasculitis (LCV) and IgA-immune deposits in vessel walls and/or glomeruli increase the diagnostic sensitivity and specificity. However, considering the accessibility of biopsy and some patients with atypical presentations, there are still medical unmet needs in HSP diagnosis. This article reviews the diagnosis of HSP including the aspects of classification criteria, differential diagnosis, and some laboratory findings as the biomarkers with diagnostic potential. PMID:24424188
Yang, Yao-Hsu; Yu, Hsin-Hui; Chiang, Bor-Luen
A 16-y-old boy presented with complaints of acute abdomen. Ultrasonography showed an enlarged and tender appendix suggestive of acute appendicitis. The patient underwent surgery and during surgery the appendix was found with a red vasculitis-like distal end, not typical for acute appendicitis. Further per operative examination of the intestines revealed a circular, vasculitis-like red band in terminal ileum. Four days after surgery, the patient developed skin purpura and complained of joint pain classical of Henoch-Schönlein disease. Pathological evaluation of the appendix and a skin biopsy confirmed the diagnosis and the patient was managed accordingly. PMID:23275184
de Castro, S M M; Joosse, P; Unlü, C; Steller, E Ph
A 61-year-old vascular patient presented with headache and subacute blindness in the left eye. Remaining American College of Rheumatology criteria were negative. Sonography of the temporal artery revealed no halo sign, but due to low sensitivity, vasculitis could not be excluded.(1) Transorbital examination revealed hyperechogenic retrobulbar spot sign (figure), which is highly specific for embolic occlusion of the central retinal artery.(2) Comprehensive diagnostic workup revealed paroxysmal atrial fibrillation as a putative cause for the embolus and no evidence for vasculitis. Thus, potentially harmful thrombogenic administration of steroids could be avoided. Transorbital sonography may help in cases of sudden visual loss of unclear etiology. PMID:24778291
Faissner, Simon; Grunwald, Christine; Meves, Saskia H; Gold, Ralf; Krogias, Christos
This review article discusses three topics related to pulmonary vascular disease: 1) pulmonary vascular changes associated with portal hypertension, 2) ANCA-associated pulmonary vasculitis, and 3) Takayasu's arteritis. Hepatopulmonary syndrome and pulmonary hypertension have recently been reported as pulmonary vascular changes accompanied with portal hypertension. Endogenous vasoactive agents that reach the pulmonary circulation through porto-systemic shunt vessels are thought to contribute to these vascular changes. In ANCA-associated vasculitis, hemorrhage, interstitial pneumonitis, and nodular lesions are common manifestations in the lung. In Takayasu's arteritis, CT occasionally demonstrates mosaic attenuation owing to pulmonary arteritis and peripheral reticulolinear changes probably due to thromboembolism. PMID:11321813
Clinical recognition of drug-induced vasculitic and lupus-like syndromes is very important because continued use of the offending drug can lead to irreversible and life-threatening vasculitic organ damage (e.g. end-stage renal disease or pulmonary haemorrhage). Withdrawal of the drug often leads to spontaneous recovery, meaning that immunosuppressive therapy can be avoided. The presence of myeloperoxidase-antineutrophil cytoplasmic antibodies, IgM anticardiolipin antibody, and antihistone antibodies in combination was found to be characteristic of drug-induced vasculitic syndromes caused by the antithyroid drugs propylthiouracil and methimazol. Clinically, skin vasculitis and arthralgias predominated and renal vasculitis was rare. PMID:16207347
Clinical recognition of drug-induced vasculitic and lupus-like syndromes is very important because continued use of the offending drug can lead to irreversible and life-threatening vasculitic organ damage (e.g. end-stage renal disease or pulmonary haemorrhage). Withdrawal of the drug often leads to spontaneous recovery, meaning that immunosuppressive therapy can be avoided. The presence of myeloperoxidase–antineutrophil cytoplasmic antibodies, IgM anticardiolipin antibody, and antihistone antibodies in combination was found to be characteristic of drug-induced vasculitic syndromes caused by the antithyroid drugs propylthiouracil and methimazol. Clinically, skin vasculitis and arthralgias predominated and renal vasculitis was rare.
Henoch-Schönlein purpura (HSP) is a vasculitis of small-sized blood vessels, resulting from immunoglobulin-A-mediated inflammation. It is the most common acute systemic vasculitis in childhood and mainly affects skin, gastrointestinal tract, joints, and kidneys. The characteristic rash of HSP consists of palpable purpuric lesions 2 to 10?mm in diameter concentrating in the buttocks and lower extremities. The occurrence of hemorrhagic bullae in children with HSP is rarely encountered. This report describes a 4.5-year-old female patient with HSP associated with hemorrhagic bullous lesions.
Kocaoglu, Celebi; Ozturk, Ramazan; Unlu, Yasar; Akyurek, Fatma Tuncez; Arslan, Sukru
OBJECTIVES--To determine the prevalence and clinical associations of autoantibodies to myeloperoxidase (MPO) in an unselected series of well-characterised outpatients with rheumatoid arthritis (RA) and to compare the distribution of IgG subclasses of anti-MPO antibodies in these patients with that in patients with systemic vasculitis. PATIENTS AND METHODS--A study was made of 97 patients with RA, who have been seen regularly in this department for up to 20 years, and 29 patients with anti-neutrophil cytoplasmic antibody (ANCA) positive systemic vasculitis. Anti-MPO antibodies were detected using a direct-binding enzyme-linked immunosorbent assay (ELISA) with MPO from human granulocytes as antigen. The IgG subclass of anti-MPO antibodies was determined by ELISA using isotype specific monoclonal antibodies. RESULTS--Anti-MPO antibodies were detected in 12% of patients with RA. Six sera contained IgG anti-MPO antibodies only, 1 IgM only and 5 antibodies of both classes. In the patients with RA the predominant subclasses were IgG1 and IgG3: only 2 sera contained detectable IgG4 antibodies. This was in contrast to patients with vasculitis, in whom most sera contained IgG1, IgG3 and IgG4 anti-MPO antibodies. Anti-MPO antibodies in sera from both patient groups bound only to the native protein. None of the patients studied with RA had evidence of vasculitis affecting the nerves or kidney: three patients (1 positive for anti-MPO antibodies and 2 negative) had cutaneous vasculitis. In the patients with RA, positivity for anti-MPO antibodies was associated with nodules and number of active joints. Three patients with anti-MPO antibodies, and none without, had pulmonary fibrosis. CONCLUSIONS--Twelve per cent of a group of unselected outpatients with RA, but without evidence of major systemic vasculitis, had anti-MPO antibodies in their serum. Positivity for anti-MPO antibodies was more common in patients with nodular disease and lung involvement but not in patients with cutaneous vasculitis. IgG4 sub-class anti-MPO antibodies were present in 90% of sera from patients with ANCA-positive vasculitis and only 2/11 (18%) of anti-MPO antibody containing sera from patients with RA.
Cambridge, G; Williams, M; Leaker, B; Corbett, M; Smith, C R
Takayasu arteritis is a chronic, progressive, autoimmune, idiopathic, large-vessel vasculitis that usually affects young adults. The disease has been reported to occur in all races and ethnicities. The diffuse nature of this vasculitis can affect multiple-organ systems to varying degrees. Herein, we report the case of a young woman whose exertional angina and claudication were the initial presentation of active Takayasu arteritis. During more than 4 years of ongoing treatment, therapy, and follow-up, she has displayed differing disease symptoms of varying intensity. We discuss the challenges of managing Takayasu arteritis in our patient and describe different treatments for this rare vasculitic disorder.
Saab, Fadi; Giugliano, Robert P.; Giugliano, Gregory R.
A steroid-sensitive meningo-encephalopathy developed in a healthy young woman 5 1/2 years after the occurrence of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The association of APMPPE with systemic and neurologic inflammatory disorders has been well documented, but to the knowledge of the authors, this is the first report of an APMPPE patient in which there was delayed onset of the meningo-encephalopathy. The association with dermal vasculitis, nephropathy, meningo-encephalitis, cerebral vasculitis, and thyroiditis suggests that APMPPE may be one manifestation of a diffuse systemic inflammatory condition. PMID:3587921
Kersten, D H; Lessell, S; Carlow, T J
A 7-year-old girl with IRVAN (idiopathic retinal vasculitis, aneurysms, and neuroretinitis) syndrome was monitored for 9 years. The patient had symmetric multiple aneurysmal dilations, retinal vasculitis, and severe hard exudation in the macula bilaterally. Long-term visual acuity in her untreated right eye was 20/25. In the left eye, treated with laser panretinal photocoagulation and intravitreal vascular endothelial growth factor inhibitor therapy, visual acuity decreased to 20/200 from macular hard exudates and central fibrovascular tissue. Observation is a consideration in IRVAN syndrome if the vision remains good with hard exudation. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:e18-e22.]. PMID:24766157
Basha, Madhi; Brown, Gary C; Palombaro, Geremie; Shields, Carol L; Shields, Jerry A
Shewanella algae is an emerging seawater-associated bacterium. In immunocompromised patients, infections may result in bacteremia, osteomyelitis, and necrotizing fasciitis. Our patient, suffering from autoimmune vasculitis and myasthenia gravis, developed typical hemorrhagic bullae and leg ulcers because of S algae. She was treated efficiently with a combination of ciprofloxacin and piperacillin. PMID:23809079
Wagner, Nicola; Otto, Lisa; Podda, Maurizio; Schmitt, York; Tappe, Dennis
Ocular manifestations resulting from Rift Valley fever (RVF) virus infection were studied during an extensive RVF epidemic in Egypt during 1977. Colour photography and fluorescein angiography of 7 serologically diagnosed patients showed the commonest manifestations to be macular, paramacular, and\\/or extramacular retinal lesions, often occurring bilaterally. Haemorrhage and oedema were frequently associated with the lesions, and vasculitis, retinitis, and vascular
A L Siam; J M Meegan; K F Gharbawi
This report describes an uncommon variant of humpy-back syndrome associated with multiple rib fractures and multisystemic vasculitis in several nursing piglets and, for the first time, a skin disease in swine consistent with alopecia areata. Both conditions were observed concurrently on the farm and occasionally in the same piglets. PMID:23372194
Drolet, Richard; Denicourt, Martine; D'Allaire, Sylvie
Neutrophils represent an important source of autoantigens for antineutrophil cytoplas- mic antibody associated with vasculitis. To date, two cytoskeletal proteins, vinculin and vimentin, have been reported to be expressed on the cell surfaces of activated macrophages, platelets, and apoptotic T lymphocytes. However, such cell sur- face expression has never been studied in human neutrophils. As we recently demonstrated that dif-
Eliane Moisan; Denis Girard
The Eales disease is a retinal idiopathic vasculitis which has raised big problems in diagnosis and especially in therapeutic approach. The complications secondary to neovascularization as well as fibrovascular proliferation has surpassed for many times the therapeutical possibilities from nowadays. PMID:12974039
Stanca, H T; M?gureanu, Marineta
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with propylthiouracil. We have experienced three adult cases of Graves' disease with main features being renal derangements. All three patients, who were between the ages of 22 and 82 years, had been treated with propylthiouracil for 2 to 5 years after a diagnosis of Graves' disease.
Masayuki Tanemoto; Hiroshi Miyakawa; Junichi Hanai; Masako Yago; Masafumi Kitaoka; Shunya Uchida
Background: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear.Objective: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary
William DuMouchel; Eric T. Smith; Richard Beasley; Harold Nelson; Xionghu Yang; David Fram; June S. Almenoff
Most hypersensitivity reactions to drugs occur within several weeks of administration; signs and symptoms are often consistent with known immune-mediated reactions, including anaphylaxis, rashes, fever, cytopenias and vasculitis. The culprit immune mechanisms range from immunoglobulin E antibody to T cells inducing apoptosis of keratinocytes, in the case of bullous exfolia- tive rashes. Many drugs induce reactions via altered hepatic metabolism,
GILLIAN M. SHEPHERD
Behçet's disease is a chronic multisystem vasculitis of unknown aetiology. This case report describes a patient who applied to the hospital because of dyspnoea, ascites, oedema of lower extremities and recurrent episodes of haemoptysis. For the last 12 yr, he had superior vena cava syndrome (SVCS) and cardiac and pulmonary involvement of Behçet's disease, and biochemical examination of ascite fluid
Ö. Abado?lu; E. Osma; E. S. Uçan; C. Çavdar; N. Akkoç; A. Küpelïo?lu; H. Akbaylar
Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis
Reversible cerebral vasoconstriction syndrome (RCVS) is an underdiagnosed condition which usually presents as severe headache with or without neurological deficit. We report the case of a 55-year-old woman who presented with headache and multifocal intracerebral haemorrhage. We review the literature regarding the presentation, pathophysiology and management of RCVS and discuss how to differentiate it from cerebral vasculitis. PMID:24087801
Lee, R; Ramadan, H; Bamford, J
HIV infection and AIDS have protean and multisystem manifestations throughout the various stages of infection. Progression from HIV infection to AIDS is associated with a gradual loss of immunocompetence and the occurrence of opportunistic infections and malignancies; it is also associated with immune dysregulation and persistent, prolonged immune activation that leads to autoimmune phenomena such as vasculitis and serological abnormalities.
Rashmi M Maganti; Frances M Williams; John D Reveille
Objective. To evaluate the prevalence of antineutrophil cytoplasmic antibodies (ANCA) and rheumatic manifestations associated with chronic haematological malignancies. Methods. Two groups of patients were prospectively studied (group I: 60 patients with myelodysplastic syndromes and group II: 140 patients with lymphoid malignancies) for clinical 'immune' manifestations and ANCA. Results. In the myelodysplastic group, six patients had ANCA-negative systemic medium- size vasculitis,
M. A. Hamidou; S. Derenne; M. A. P. Audrain; J. M. Berthelot; A. Boumalassa; J. Y. Grolleau
Pyoderma gangrenosum and Sweet's syndrome are classified as neutrophilic dermatoses as they exhibit intense dermal inflammatory infiltrates composed of neutrophils with little evidence of a primary vasculitis. They share several characteristics and respond to immunosuppressives. Aetiology is felt to represent a manifestation of altered immunologic reactivity. Patients with both conditions concurrently have been described. Diagnosis is based on clinical and
J. T. Lear; M. T. Atherton; J. P. Byrne
We describe 6 bilateral cases of progressive Mooren's ulcer treated by performing conjunctival excision (regional or 360° peritomy). The histopathological study of the conjunctiva adjacent to the lesion showed an hyperaemic and edematous stroma infiltrated mainly by plasma cells and lymphocytes without signs of vasculitis. The peripheral portion of the ulcer was characterized by necrobiotic and hemorrhagic elements along with
Christos D. Kalogeropoulos; Miltiadis B. Aspiotis; Konstantinos G. Psilas
Though uncommon, scorpion stings can cause cerebrovascular accidents by various mechanisms such as venom induced autonomic storm leading to hypertension, hypotension, myocarditis, DIC or vasculitis by direct actions. We present a case of intracerebral bleed following scorpion sting, which is a rare presentation and seldom reported. PMID:22010593
Dube, Simmi; Sharma, V K; Dubey, T N; Gouda, Narendra B; Shrivastava, Vikrant
Background and Design.- Malassezia is a dimorphic fungus which forms part of the normal skin flora, it may exist as budding yeasts in stratum corneum in patients with several cutaneous disease and can cause iatrogenic systemic infections such as fungemia, pulmonary vasculitis, peritonitis in predisposed neonates, children and adults. Malassezia may induce humoral and cellular immunity via activating the classical
A. Serda; Ayhan YÜCEL
Summary A patient with rheumatoid arthritis developed gold induced peripheral neuropathy after 255 mgms of aurothioglucose. This neuropathy is characterized by weakness and numbness of the hands and feet in association with hyperalgesia of the palmar surface of the hands. The absence of vasculitis permits differentiation of gold neuropathy from the neuritis associates with rheumatoid arthritis or systemic lupus erythematosus.
J. J. Weiss; G. R. Thompson; R. Lazaro
? All metals in contact with biological systems undergo corrosion. This electrochemical process leads to the for- mation of metal ions, which may activate the immune system by forming complexes with endogenous proteins. ? Implant degradation products have been shown to be associated with dermatitis, urticaria, and vasculitis. If cutaneous signs of an allergic response appear after implantation of a
NADIM HALLAB; KATHARINE MERRITT; JOSHUA J. JACOBS
Kawasaki syndrome (KS) is an acute multisystem vasculitis of infancy and early childhood associated with the development of myocarditis and coronary artery abnormalities. Despite the widely held belief that KS is caused by an infectious agent, there remains considerable controversy over its etiology. Recent immunologic and microbiologic studies suggest a potential role for staphylococcal and streptococcal toxins (superantigens) in the
Donald Y. M. Leung; H. Cody Meissner; David R. Fulton; Fred Quimby; Patrick M. Schlievert
To date, sarcocystis has been considered an asymptomatic infection in humans. Even though cases with glomerulonephritis have been reported in animals with sarcocystis, there have been no reports of a similar occurrence in humans. We report a case of acute proliferative glomerulonephritis and leukocytoclastic vasculitis in a patient with sarcocystis infestation. PMID:24152512
Balakrishna, Jayalakshmi P; Chacko, Geeta; Manipadam, Marie Therese
A patient with known Behcet's disease demonstrated intense colonic localization of In-111 labeled leukocytes. Gastrointestinal involvement had not been previously manifested, but extensive colonic inflammation was documented by endoscopy. This case illustrates the utility of In-111 labeled leukocyte imaging for detecting active bowel disease in a debilitated patient with documented Behcet's vasculitis.
Harre, R.G.; Conrad, G.R.; Seabold, J.E.
There are numerous causes of pulmonary cavitary lesions as infection (bacterial, parasitic and invasive fungal), Wegener granulomatosis (WG) and other vasculitis, sarcoidosis, malignancy, septic thromboembolism, airways disease (cystic bronchiectasis and bullae), pneumatoceles and traumatic parenchymal laceration. Herein, we present a case with perforated diverticulitis causing pulmonary cavitary lesions and a septic thrombus in the neighboring inferior vena cava. PMID:22453530
I?ik, Metin; Çinar, Esat; Cemal Kizilarslano?lu, M; Özbek, Emre; Etgül, Sezgin; Kiraz, Sedat
Autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS), systemic sclerosis and systemic vasculitis, affect a large number of people in whom one of the leading causes of morbidity and mortality is cardiovascular disease. Cardiovascular disease is associated with the development of accelerated atherosclerosis. It seems to occur at a younger age than in the
Simona Sitia; Fabiola Atzeni; Piercarlo Sarzi-Puttini; Vitantonio Di Bello; Livio Tomasoni; Luigi Delfino; Francesco Antonini-Canterin; Giovanni Di Salvo; Vito De Gennaro Colonna; Salvatore La Carrubba; Scipione Carerj; Maurizio Turiel
Objective: To investigate whether serum procalcitonin (PCT) levels could be useful to differentiate between systemic infection and the activity of the underlying disease in autoimmune disease.¶Methods: In 18 patients with systemic lupus erythematodes (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV) clinical disease activity was assessed by score systems. Infection was defined by clinical and microbiological means.
R. Brunkhorst; O. K. Eberhardt; M. Haubitz; F. M. Brunkhorst
Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and\\/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via the classical pathway has long been recognized in immune complex-mediated diseases such as cryoglobulinemic vasculitis and systemic
Min Chen; Mohamed R. Daha; Cees G. M. Kallenberg
... an ear or eye infection Bleeding within the brain Blockage of an artery supplying the nerve, as can result from diabetes, a stroke, a transient ischemic attack, or vasculitis (inflammation of blood vessels) Wernicke encephalopathy (commonly due to chronic alcoholism) Benign ...
Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN.
Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.
The term Pulmonary–renal syndrome refers to the combination of diffuse alveolar haemorrhage and rapidly progressive glomerulonephritis. A variety of mechanisms such as those involving antiglomerular basement membrane antibodies, antineutrophil cytoplasm antibodies or immunocomplexes and thrombotic microangiopathy are implicated in the pathogenesis of this syndrome. The underlying pulmonary pathology is small-vessel vasculitis involving arterioles, venules and, frequently, alveolar capillaries. The underlying
Spyros A Papiris; Effrosyni D Manali; Ioannis Kalomenidis; Giorgios E Kapotsis; Anna Karakatsani; Charis Roussos
Objectives. Rickettsiae, which causes vasculitis, has not been linked to atherosclerotic cardiovascular disease in contrast to Chlamydia pneumoniae whose association with coronary artery disease and with sclerotic heart valves in patients undergoing aortic valve replacement is well established, even if causality is yet to unproven. In the search for any of these infectious agents, 84 pathological and 15 normal aortic
K. Nilsson; A. Liu; C. Påhlson; O. Lindquist
ready administered at the time of recruit- ment. All patients had active disease, poorly controlled or difficult to manage with previous treatments, including corti- costeroids in all. Efficacy and safety of rituximab therapy were evaluated in the following 6 months. The overall follow-up after rituximab treatment ranged from 9 to 31 months. Rituximab proved effective on skin vasculitis manifestations (ulcers,
Francesco Zaja; Salvatore De Vita; Cesare Mazzaro; Stefania Sacco; Daniela Damiani; Ginevra De Marchi; Angela Michelutti; Michele Baccarani; Renato Fanin; Gianfranco Ferraccioli
Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis C. Three patients undergoing transplantation for end-stage chronic hepatitis C in whom cryoglobulinemia with vasculitis developed after transplantation are described. Hepatitis C virus (HCV) infection was confirmed in the 3 patients by the presence of HCV RNA detected by polymerase chain reaction. The time interval between transplantation and the first expression
J Gournay; LD Ferrell; JP Roberts; NL Ascher; TL Wright; JR Lake
IXED CRYOGLOBULINEMIA (MC) is a lympho- M proliferative disorder characterized clinically by purpura, arthralgias, weakness, and various organ involve- ments such as peripheral neuropathy, chronic hepatitis, glo- merulonephritis, and generalized vasculitis.' The typical pathologic lesions involving small- and medium-sized ves- sels are due to deposition of circulating immune-complexes (CIC) and complement.',' In MC patients, a monoclonal rheumatoid factor in the
Clodoveo Ferri; Monica Monti; Luca La Civita; Giovanni Longombardo; Francesco Greco; Giampiero Pasero
Takayasu's arteritis (TA) is a vasculitis of large and medium sized arteries. Involvement of bone in TA is very rare. We report a case of young woman who presented with multiple painful bone lesions which were identified as periostitis with new bone formation associated with TA. Our case is unique in that bony involvement in TA could occur independent of
Jee-Eun Kim; Eun-Mi Kolh; Duk-Kyung Kim
Langerhans' cell histiocytosis (LCH) is a rare condition of children and young adults in which Langerhans' cells proliferate. The clinical spectrum ranges from solitary or few focal lesions to multisystem involvement mimicking vasculitis or hematological malignancy. Focal bone lesions, known as eosinophilic granulomas, are the most common manifestations. Eosinophilic granuloma usually presents with a variable combination of pain, swelling, fracture,
Athan Baillet; Laurent Grange; Pierre-André Lafaix; Philippe Gaudin; Robert Juvin
Behcet's disease is an autoimmune multisystemic disorder on vasculitis base. Cardiovascular involvement is the most important predictor of morbidity and mortality. The treatment should be planned carefully for pathologies requiring interventions. In our report, we present a 45-year-old patient with spontaneous superficial femoral artery pseudoaneurysm, our treatment strategy, and circumstances we faced.
Sendil, Selin; Sayin, Omer Ali; Barburoglu, Mehmet; Gok, Emre; Turkyilmaz, Gulsum; Basaran, Murat; Alpagut, Ufuk; Dayioglu, Enver
Vasculitic lesions are defined by necrosis of the vascular wall with perivascular inflammatory infiltrates. Secondary forms of vasculitis are observed in some systemic diseases, after infections, secondary to drugs or to malignancies. Usually, these secondary forms are characterised by the presence of immunoglobulin and complement deposits and thus probably caused by immune complex deposits. Conversely, necrotizing vasculitis occurring without known causal factor are named primary vasculitis, are not associated with immune deposits. Wegener's granulomatosis, microscopic polyangitis, Churg and Strauss syndrome and the isolated form of necrotizing and crescent glomerulonephritis are closely associated with the anti-neutrophil cytoplasm auto-antibodies (ANCA). The two main auto-antigen targets recognised by ANCA are lysosomal enzymes, proteinase 3 and myeloperoxidase, both contained in azurophilic granules of polymorphonuclear neutrophils and in primary lysosomes of monocytes. It has been demonstrated that ANCA antigens are expressed at the neutrophil (and monocyte) membrane after preactivation and are accessible to antibodies. Thus, ANCA may amplify neutrophils and monocyte activation. However, the causal or induced nature of anti-neutrophil auto-immunity in vasculitis remains unknown. PMID:11923948
Lesavre, P; Noël, L H
Secondary glomerular lesions are associated with various diseases; diabetes, systemic lupus erythematosus, primary cryoglobulinaemia, cryoglobulinemia and membranoproliferative glomerulonephritis secondary to hepatitis C virus (HCV), ANCA associated vasculitis and their forms limited to kidney (necrotic and crescentic GN), Goodpasture syndrome, HIV associated nephropathies, AL amyloidosis, AA amyloidosis (secondary amyloidosis), GN with non-amyloid organised deposits. PMID:15008219
Alveolar hemorrhage (AH) is an important pulmonary manifestation of small vessel vasculitis because severe presentations are the most common vasculitic cause of early death. Renal vasculitis is usually present with AH; the combination is known as pulmonary-renal syndrome. Early diagnosis and intensive therapy are of particular importance to reduce early mortality and improve longer-term outcomes. The commonest immune-mediated cause of AH is anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (80%), with other vasculitides, including systemic lupus erythematosus and anti-glomerular basement membrane disease accounting for 20%. One quarter of AAV patients develop AH, which when mild is associated with a good outcome, but mortality rises to 50% for cases with respiratory failure requiring ventilator support. The prognosis of AH in the other vasculitides is generally favorable, but cases are rare and experience is limited. Treatment follows similar regimens to those for other AAV presentations, although when severe there is widespread use of parenteral glucocorticoids together with plasma exchange. These interventions have developed empirically supported by a theoretical rationale but have not been validated by randomized clinical trials. Sepsis and cardiovascular and thromboembolic events are important early complications. and long-term follow-up is required to monitor for and prevent relapse and manage disease-related damage. A minority of cases develop on a background of pulmonary fibrosis, or progressive pulmonary fibrosis develops after vasculitis has gone into remission. PMID:21674419
Casian, Alina; Jayne, David
The case is presented of a premature infant with Pseudomonas aeruginosa infection, apparently acquired in utero. After a complicated postnatal course, the child was noted to have a profound hearing loss. The infection itself, was rapid and progressive, with the infant showing signs and symptoms characteristic of Pseudomonas infection, such as necrotizing skin vasculitis and \\
Cecila Ruvalo; Charles R. Bauer
Introduction Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura. Case presentation A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature. Conclusions Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation.
A case of herpes zoster ophthalmicus was followed, after a latent period of four weeks, by contralateral hemiparesis. An attempt is made to clarify the anatomical relationships involved in the pathogenesis of postherpetic cerebral complications. Detailed presentation of neuropathological findings in this case may provide evidence of vasculitis in the syndrome, with better understanding of the pathological anatomy. Images
Gasperetti, C; Song, S K
Kawasaki disease (KD) is a pediatric vasculitis that damages the coronary arteries in 25% of untreated and approximately 5% of treated children. Epidemiologic data suggest that KD is triggered by unidentified infection(s) in genetically susceptible children. To investigate genetic determinants of KD susceptibility, we performed a genome-wide association study (GWAS) in 119 Caucasian KD cases and 135 matched controls with
David Burgner; Sonia Davila; Willemijn B. Breunis; Sarah B. Ng; Yi Li; Carine Bonnard; Ling Ling; Victoria J. Wright; Anbupalam Thalamuthu; Miranda Odam; Chisato Shimizu; Jane C. Burns; Michael Levin; Taco W. Kuijpers; Martin L. Hibberd
We describe a 15-year-old boy with acute transient encephalopathy complicating poststreptococcal glomerulonephritis. Based on advanced magnetic resonance imaging, cerebral alterations were related to cerebrovascular autoregulatory dysfunction (ie, a vasogenic edema) and vasculitis was excluded. These insights into the pathophysiology improve patient management and argue against the therapeutic immunosuppression postulated by some authors. PMID:16395114
Fux, Christoph A; Bianchetti, Mario G; Jakob, Stephan M; Remonda, Luca
This book contains 23 papers. Some of the titles are: Diagnostic Radiology in the Rheumatic Diseases; Laboratory Testing in Rheumatology; Arthritis Nursing and the Team Approach in the Management of Rheumatic Disease; The Surgical Management of Arthritis; Vasculities; Neoplasms of Bone and Joints; and Rheumatic Disease of Childhood.
Turner, R.A.; Wise, C.M.
Kawasaki disease (KD) is a systemic vasculitis associated with cardiovascular symptom. A previous study in the European descent has indicated that genetic variants of the transforming growth factor-? (TGF-?) pathway are involved in the KD susceptibility and clinical status. This study was conducted to investigate if polymorphisms in TGF-? signaling pathway are associated with KD susceptibility, and the coronary artery
Ho-Chang Kuo; Yoshihiro Onouchi; Yu-Wen Hsu; Wei-Chiao Chen; Jin-Ding Huang; Ying-Hsien Huang; Ya-Ling Yang; Mei-Chyn Chao; Hong-Ren Yu; Yung-Shun Juan; Chiu-Ming Kuo; Kuender D Yang; Jung-San Huang; Wei-Chiao Chang; W-C Chang
The lupus anticoagulant was found in the plasma of 31 of 60 patients with systemic lupus erythematosus and other connective tissue disorders (mixed connective tissue disease, systemic vasculitis, polyarteritis nodosa, primary sicca syndrome, discoid lupus, Behcet's syndrome, and systemic sclerosis). Strong associations were found with biological false positive seroreaction for syphilis and thrombocytopenia. The most striking association, however, was with
M L Boey; C B Colaco; A E Gharavi; K B Elkon; S Loizou; G R Hughes