Different Forms Of Vasculitis Research Articles

P036 A rare case of new onset large vessel vasculitis/aortitis, in a patient with Jak2 positive myelofibrosis

Abstract Background/Aims Large vessel vasculitis refers to inflammation of the wall of the aorta or its main branches; it can be primary (giant cell and Takayasu arteritis) or secondary to infections or autoimmune diseases. We are reporting a rare case of aortitis co-existed with Jak2 positive myelofibrosis. Methods In June 2017, a 57-year-old man who was previously fit and well presented to haematology clinic with tiredness, weight loss, night sweat for the preceding 3 months. Investigations showed pancytopenia and bone marrow biopsy showed dysplasia and grade3 myelofibrosis. He was diagnosed with JAK2 positive myelofibrosis with myelodysplasia and was commenced on ruxolitinib. Three months later, he was admitted with fever and other constitutional symptoms but no evidence of active synovitis or vasculitic skin lesions or temporal arteritis. Investigations showed CRP of more than 200mg/l, HB: 41g/l, WBC: 38.4 x109/l, Neutrophil 18.2 x109/l, Blasts: 1.73 x109/l and Platelet: 68 x109/l; Total protein:creatinine ratio: 30.4 mg/mmol, whereas anti CCP, ANA, ANCA, T-spot test and Syphilis antibody were all negative. Blood cultures were negative. CT-chest abdomen and pelvis showed splenomegaly and subtle fat haziness in the mediastinum adjoining the distal aortic arch with new onset (compared to a previous CT scan) mild thickening of distal aortic arch and descending aorta. Cardiac MRI confirmed active aortitis and PET-CT scan showed focal increased uptake within the arch of the aorta. He was diagnosed with aortitis and cellulitis of the left arm and foot and commenced on antibiotics and prednisolone 40mg. After one month, the patient was doing well, with significant improvement of symptoms and inflammatory markers (CRP: 7mg/l). Prednisolone was tapered and stopped after one year, as there was no evidence of flare up of vasculitis. Results In the literature, there are only few reported cases linking haematological malignancies to different forms of vasculitis. In one case, aortitis was reported as a manifestation of myelodysplastic syndrome whereas the coexistence of aortitis with chronic myeloid leukemia and chronic myelomonocytic leukemia was reported in 2 separate cases raising the possibility of coincidental or paraneoplastic phenomenon. Vasculitic skin ulcers preceded the appearance of myelofibrosis in another case report. In the above case, aortitis can also be related to the chemotherapeutic agents; leukocytoclastic vasculitis was possibly induced by ruxolitinib in a case report. Moreover, bacterial Infection, as a common cause of aortitis can still be the cause here. Conclusion Early recognition of coexistent disorders in patients with haematological malignancies is crucial for successful management. However, it can prove a challenge as malignancy, vasculitis and infection share common clinical features and investigations. Vasculitis can be primary or secondary to a wide variety of disorders, and further research is required to confirm the relation between myelofibrosis and aortitis. Disclosure Z. Alkutobi: None. A. Ugwoke: None. A. Nandagudi: None.

Vasculitis

Vasculitis is a group of clinicopathological entities involving inflammation of the blood vessel walls. The different forms of vasculitis may vary in terms of aetiology, pathogenesis, type, and calibre of vessel involved, type of inflammation, preferential organ distribution, clinical manifestations, genetic predisposition, and demographic characteristics. The classification most widely used currently is based on the nominal definitions proposed by the International Chapel Hill Consensus Conference (CHCC) in its 2012 revision. The aetiology of vasculitis is still not fully understood, despite recent advances in the study of genetics and pathogenesis. Due to the variability of vasculitis, there is no single, uniform diagnostic method. Diagnosis of vasculitis is challenging in most cases. However, a detailed clinical history, careful physical examination and appropriate laboratory tests from the information obtained from them are necessary in all types of vasculitis to establish a correct diagnosis, its probable date and manner of onset, the organs or systems affected and the extent of disease.

CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

Vasculitis refers to inflammation of blood vessels and can cause a variety of serious complications depending on which vessels are affected. Two different forms of vasculitis are Giant Cell Arteritis (GCA) and Granulomatosis with Polyangiitis (GPA). GCA is the most common form of vasculitis in adults affecting the large arteries and can lead to visual impairment and development of aneurysms. GPA affects small- and medium-sized blood vessels predominantly in the lungs and kidneys resulting in organ failure. Both diseases can potentially be fatal. Although the pathogenesis of GCA and GPA are incompletely understood, a prominent role for CD4+ T cells has been implicated in both diseases. More recently, the role of CD8+ T cells has gained renewed interest. CD8+ T cells are important players in the adaptive immune response against intracellular microorganisms. After a general introduction on the different forms of vasculitis and their association with infections and CD8+ T cells, we review the current knowledge on CD8+ T-cell involvement in the immunopathogenesis of GCA and GPA focusing on phenotypic and functional features of circulating and lesional CD8+ T cells. Furthermore, we discuss to which extent aging is associated with CD8+ T-cell phenotype and function in GCA and GPA.

The European Vasculitis Society 2016 Meeting Report

The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the Netherlands, was centered around phenotypic subtyping in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). There were parallel meetings of the EUVAS petals, which here report on disease assessment; database; and long-term follow-up, registries, genetics, histology, biomarker studies, and clinical trials. Studies currently conducted will improve our ability to discriminate between different forms of vasculitis. In a project that involves the 10-year follow-up of AAV patients, we are working on retrieving data on patient and renal survival, relapse rate, the cumulative incidence of malignancies, and comorbidities. Across Europe, several vasculitis registries were developed covering over 10,000 registered patients. In the near future, these registries will facilitate clinical research in AAV on a scale hitherto unknown. Current studies on the genetic background of AAV will explore the potential prognostic significance of genetic markers and further refine genetic associations with distinct disease subsets. The histopathological classification of ANCA-associated glomerulonephritis is currently evaluated in light of data coming out of a large international validation study. In our continuous search for biomarkers to predict clinical outcome, promising new markers are important subjects of current research. Over the last 2 decades, a host of clinical trials have provided evidence for refinement of therapeutic regimens. We give an overview of clinical trials currently under development, and consider refractory vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in clinical, serological, and histological management and techniques for patients with systemic vasculitis, with an outlook on the applicability for clinical trials.

ANCA-associated vasculitis with renal involvement.

Systemic vasculitis is a rare but severe group of diseases characterized by inflammation and necrosis of blood vessels. The size of the vessel affected varies among the different forms of vasculitis and there are three main subgroups: large, medium and small vessel vasculitis. Among small vessel vasculitis, the antineutrophil cytoplasmic antibody (ANCA)-associated forms are of particular importance. This subgroup includes: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener's), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) and the form limited to the kidney. ANCA are serum autoantibodies directed against proteins present in the cytoplasmic granules of neutrophils and represent the serological markers of small vessel vasculitis. Renal involvement is present in the majority of patients with ANCA-associated vasculitis (AAV) and the consequences of a missed or delayed diagnosis of renal vasculitis are potentially life threatening. Patient survival and the risk of end-stage renal disease are closely associated with renal function at presentation. The gold standard for diagnosis remains renal biopsy. In 2010, a new histopathological classification based on the percent of normal glomeruli, cellular crescent or global sclerotic glomeruli was proposed. The aim of this classification was to predict the renal prognosis. Nowadays, remission can be achieved and maintained in most cases with a combination of high-dose steroid and immunosuppressive drugs. This therapy has to be continued for at least 24months after a substantial remission has been obtained because early cessation of treatment is associated with an increased risk of relapse. For this reason, patients should be regularly monitored in order to promptly diagnose and treat a possible recurrence of AAV. This review will focus on kidney involvement in AAV with an overview of the clinical-pathological characteristics and therapeutic strategy for these conditions.

Relapsing polychondritis: a chameleon among orphan diseases.

Relapsing polychondritis (RPC) is a rare disease with recurrent episodes of inflammation of cartilage tissue leading to fibrosis and organ damage. Despite unknown etiology, there is some evidence of a genetic predisposition. The clinical presentation is heterogeneous and an association with other autoimmune disorders such as rheumatoid arthritis or different forms of vasculitis has been described. All organ systems containing cartilage can be affected, such as ear, nose, joints, trachea, aorta, and coronary arteries. Given the broad spectrum of potential manifestations, a variety of medical specialists may be involved in the management of RPC patients. As establishing the diagnosis of RPC may be difficult, an interdisciplinary approach may be preferable. Treatment options include glucocorticoids, dapsone, disease-modifying antirheumatic drugs, and biologics. Prognosis is as heterogeneous as the clinical picture, depending on the severity of organ damage. In this paper we give an overview of the current knowledge with regard to pathogenesis, clinical picture, diagnosis, and therapy of RPC.

Diagnosis and/or classification of vasculitis: different?

Currently, there are no diagnostic criteria for vasculitides. To this end, there is a current European League Against Rheumatism and American College of Rheumatology initiative for formulating separate classification and diagnostic criteria for different forms of vasculitis. The authors of this review previously disagreed to separate classification and diagnostic criteria. They now expand this disagreement in light of both of more recent information and a reassessment of older communications. We still can find no clear methodologies proposed to prepare separate diagnostic and classification criteria. Furthermore, the inadequate importance given to probabilities in discussing disease criteria was strikingly apparent. Among 77 articles on diagnostic/classification criteria making, not more than 4% discussed Bayes' theorem or predictive values or confidence intervals. The misconceptions related to the worry about circularity and the proper role of nomenclature in classification and diagnostic criteria continue. Separate diagnostic and classification criteria are unrealistic. Classification criteria and nomenclature are only tools to a proper diagnosis, essentially not different for patient care or research. A frank discussion of probabilities in diagnosis is essential not only with the patients but also with all the stakeholders.

14‐3‐3 in Thoracic Aortic Aneurysms: Identification of a Novel Autoantigen in Large Vessel Vasculitis

Large vessel vasculitides (LVV) are a group of autoimmune diseases characterized by injury to and anatomic modifications of large vessels, including the aorta and its branch vessels. Disease etiology is unknown. This study was undertaken to identify antigen targets within affected vessel walls in aortic root, ascending aorta, and aortic arch surgical specimens from patients with LVV, including giant cell arteritis, Takayasu arteritis, and isolated focal aortitis. Thoracic aortic aneurysm specimens and autologous blood were acquired from consenting patients who underwent aorta reconstruction procedures. Aorta proteins were extracted from both patients with LVV and age-, race-, and sex-matched disease controls with noninflammatory aneurysms. A total of 108 serum samples from patients with LVV, matched controls, and controls with antinuclear antibodies, different forms of vasculitis, or sepsis were tested. Evaluation of 108 serum samples and 22 aortic tissue specimens showed that 78% of patients with LVV produced antibodies to 14-3-3 proteins in the aortic wall (93.7% specificity), whereas controls were less likely to do so (6.7% produced antibodies). LVV patient sera contained autoantibody sufficient to immunoprecipitate 14-3-3 protein(s) from aortic lysates. Three of 7 isoforms of 14-3-3 were found to be up-regulated in aorta specimens from patients with LVV, and 2 isoforms (ε and ζ) were found to be antigenic in LVV. This is the first study to use sterile, snap-frozen thoracic aorta biopsy specimens to identify autoantigens in LVV. Our findings indicate that 78% of patients with LVV have antibody reactivity to 14-3-3 protein(s). The precise role of these antibodies and 14-3-3 proteins in LVV pathogenesis deserves further study.

Causal Attributions about Disease Onset and Relapse in Patients with Systemic Vasculitis

Patients vary in their beliefs related to the cause of serious illness. The effect of these beliefs among patients with systemic vasculitis is not known. Our study aimed to describe causal attributions about disease onset and relapse in systemic vasculitis and to examine whether causal beliefs differ by type of vasculitis or are associated with negative health outcomes. Patients with vasculitis were recruited to complete an online questionnaire. Categories of causal beliefs were assessed with the Revised Illness Perception Questionnaire (IPQ-R). Differences in beliefs about disease onset versus relapse were compared across different forms of vasculitis. Causal beliefs were assessed in association with several health outcomes including fatigue, functional impairments, and personal understanding of the condition. The questionnaire was completed by 692 patients representing 9 forms of vasculitis. The majority (90%) of patients had beliefs about the cause of their illness. Causal attributions were highly variable, but altered immunity and stress were the most commonly agreed-upon causal beliefs. Frequencies of causal beliefs were strikingly similar across different forms of vasculitis, with a few notable exceptions primarily in Behçet disease. Beliefs differed about causes of disease onset versus relapse. Specific beliefs about disease onset and relapse were weakly associated with fatigue, functional impairments, and understanding of the condition. Patient beliefs related to the cause of systemic vasculitis are highly variable. Patterns of causal beliefs are associated with important negative health outcomes. Clinicians who care for patients with vasculitis should be mindful of these associations and consider asking about patients' causal beliefs.

Illness Perceptions and Fatigue in Systemic Vasculitis

To compare illness perceptions among patients with different forms of vasculitis, identify risk factors for negative illness perceptions, and determine the association between illness perceptions and fatigue. Participants were recruited from an online vasculitis registry to complete the revised Illness Perception Questionnaire (IPQ-R). The mean scores on each IPQ-R dimension were compared across different types of vasculitis. Cluster analysis and stepwise regression identified predictors of negative illness perception. Fatigue was measured using the general subscale of the Multidimensional Fatigue Inventory (MFI-20). Patient-reported measures of disease activity and IPQ-R dimensions were assessed in relation to MFI-20 scores using linear regression in sequential, additive models with model-fit comparisons. In total, 692 participants with 9 types of vasculitis completed the IPQ-R. For 6 of the 8 IPQ-R dimensions, there were no significant differences in mean scores between the different vasculitides. Scores in the identity and cyclical dimensions were significantly higher in Behçet’s disease compared with other types of vasculitis (13.5 versus 10.7 for identity and 4.0 versus 3.2 for cyclical [P < 0.05]). Younger age (odds ratio [OR] 1.04, 95% confidence interval [95% CI]1.02–1.06), depression (OR 4.94, 95% CI 2.90–8.41), active disease status (OR 2.05, 95% CI 1.27–3.29), and poor overall health (OR 3.92, 95% CI 0.88–17.56) were associated with negative illness perceptions. The sequential models demonstrated that the IPQ-R dimensions explained an equivalent proportion of variability in fatigue scores compared with measures of disease activity. Illness perceptions are similar across different types of vasculitis, and younger age is a risk factor for negative illness perceptions. Illness perceptions explain differences in fatigue scores beyond what can be explained by measures of disease activity.

Major cluster of chilblain cases in a cold dry Western Australian winter

Primary chilblains are an idiopathic cold-induced vasculopathy affecting the soft tissues of the hands and feet. Secondary chilblains occur in different forms of vasculitis and chronic autoimmune connective tissue disorders. Idiopathic chilblains are rarely reported in children and may generate significant anxiety to doctors and patients. We describe a cluster of idiopathic chilblains encountered over the winter of 2010 in Perth, Western Australia. This is a retrospective review of patients identified from a prospectively compiled database of all new cases seen in our department. Data on history, examination, investigations, prescribed treatments and outcomes were collected. Thirty-two patients with isolated idiopathic chilblains were included, including 20 females and 12 males with a median age at onset of 13.5 years. Lesions were papular with signs of peripheral vasoconstriction causing acrocyanosis, and uncomfortable due to pain and/or pruritis in most. Thickening of the small joints was common where lesions involved these areas. Ulceration of lesions also occurred in some. One patient required hospitalisation for secondary bacterial infection. Most received some form of treatment including non-steroidal anti-inflammatory drugs, prednisolone or nifedipine. Most patients improved spontaneously with warmer weather or responded to cold protection advice. All had resolved completely by late spring (November). Our cluster of chilblains was associated with an unusually cold winter in Perth 2010. It is the largest series reported in the literature, suggesting that chilblains may be more common than previously thought. Chilblains are almost always benign in nature and patients are systemically well and usually need no further investigation and only symptomatic treatment. Prompt recognition can avoid excessive investigation and anxiety, allowing appropriate simple advice and treatment.

Propylthiouracil induced leukocytoclastic vasculitis: A rare manifestation

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.

Rheumatic masks of plasma cell dyscrasias

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Genetics of vasculitis

Evidence for a genetic contribution to risk for developing different forms of vasculitis has accumulated recently. Cohorts have been assembled that are of sufficient size to allow application of up-to-date methods of genetic analysis. This review will summarize the current understanding of the genetics of several forms of vasculitis. The first genome-wide association studies (GWAS) in vasculitis have been published, in Behçet's disease and Kawasaki disease; none of the genes identified in these studies had been previously investigated. Associations of various HLA alleles with different vasculitides have been replicated. Other genes associated with Wegener's granulomatosis in replicated candidate gene studies are also associated with other autoimmune diseases. Consistent with this finding, epidemiologic data suggest a familial link between risk of Wegener's granulomatosis and rheumatoid arthritis. Among the most interesting genes clearly associated with vasculitis, however, are uncommon alleles that also cause monogenic recessive diseases: MEFV in Behçet's disease and Henoch-Schönlein purpura, and A1AT in Wegener's granulomatosis. At the same time as candidate gene studies in vasculitis are identifying both common polymorphisms associated with other autoimmune diseases and rare alleles associated with recessive inherited diseases, early GWAS results are identifying completely different associations. The tools are available to more comprehensively delineate the genetic component of risk for these rare diseases.

The Clinical Spectrum of Primary Renal Vasculitis

The vasculitides are potentially severe and often difficult to diagnose syndromes. Many forms of vasculitis may involve the kidneys. This review will focus on the clinical and histopathological aspects of renal involvement in the systemic vasculitides. We searched the MEDLINE database using as key terms the MeSH terms and textwords for different forms of vasculitis and for renal involvement, creating a database of more than 2200 relevant references. The frequency of renal involvement in vasculitis varies among different syndromes. It is more frequent in Wegener's granulomatosis and microscopic polyarteritis, while it is uncommon to rare in other forms of vasculitis such as Behçet's disease and relapsing polychondritis. The vessels affected include the renal artery in Takayasu arteritis, medium-size renal parenchymal artery in classic polyarteritis nodosa, and glomerular involvement in Wegener's granulomatosis and microscopic polyarteritis. The clinical expression of renal vasculitis depends on the size of the affected vessels and includes renovascular hypertension, isolated nonnephrotic proteinuria, interstitial nephritis, and glomerulonephritis, which can be rapidly progressive. Diagnosis is established by a combination of history, clinical manifestations, laboratory findings (eg, urine sediment, urine protein, antineutrophil cytoplasmic antibodies), imaging techniques (renal angiography, especially when there is a suspicion of medium-to-large vessel disease, and chest radiograph), and finally, renal biopsy. Prognosis varies from unfavorable in the rapidly progressive glomerulonephritis of microscopic polyarteritis, which can lead to renal failure, chronic dialysis, and renal transplantation, to benign, as in the case of Henoch Schonlein purpura, in which the majority of patients recover. The manifestations and prognosis of renal vasculitis range widely. Renal involvement greatly influences prognosis and dictates the need for early and prompt immunosuppressive therapy. Thus, the clinician should be alert for the timely diagnosis and treatment of renal vasculitis.

An Introduction to Vascular Biology: From Basic Science to Clinical Practice

The revised and updated second edition of An Introduction to Vascular Biology is broader in scope than its predecessor and more clinically oriented. The extent to which vascular biology and pathophysiology impacts upon clinical medicine is perfectly illustrated by the varied departmental affiliations of the four editors—haematology, rheumatology, obstetrics and vascular surgery. The book includes nineteen short, digestible chapters grouped under basic science, pathophysiology and clinical practice. Contributors include respected names such as Peter Weissberg, Patrick Vallance, Caroline Savage, Allun Hughes and John Tooke. Each chapter has a list of useful up-to-date references, but the illustrations would have benefited from a splash of colour (especially the clinical photographs and histological sections). The basic science section is comprehensive, with useful introductory chapters on topical subjects such as angiogenesis, vascular cell apoptosis, and the biology of wound healing. The whole area of angiogenesis is particularly relevant clinically. Sprouting of new blood vessels from existing vascular structures plays an important part in collateral vessel formation, tumour growth and tissue remodelling and regeneration. This chapter describes the regulation of endothelial cell migration and proliferation, with connective tissue expansion and the gradual creation of new vascular architecture. Numerous growth factors stimulate angiogenesis while other anti-angiogenic molecules inhibit new vessel formation. The basic science is outlined in a clinical context with reference to conditions in which therapeutic manipulation of angiogenic pathways has potential benefits. This might be achieved, for example, by gene therapy whereby DNA for a powerful angiogenic growth factor, VEGF, is administered locally in the leg or the heart to enhance new vessel formation in patients with critical ischaemia. Conversely, there is a rationale for inhibition of angiogenesis as a way to block tumour growth in primary or metastatic disease. The chapter on angiogenesis will appeal to many different clinical and research specialties. The section on pathophysiology also includes topical updates in fields that are rapidly changing—for example, the status of candidate genes for hypertension, the many aspects of endothelial dysfunction, and the growing importance of nitric oxide in health and disease. Imaging of the cardiovascular system has undergone enormous change over the past ten years, particularly with techniques such as spiral CT and MR. Alan Moody (radiologist) has written a chapter illustrating the versatility of these techniques not simply in arterial disease but also in assessing patients with venous disease and venous thrombosis. CT and MR angiography are becoming especially useful in the assessment of patients with carotid and renovascular disease. It is a pity that the images have not reproduced well, but in other respects the chapter is excellent. The third section becomes more focused on therapeutic strategies for improving symptoms and prognosis in patients with assorted vascular conditions, including the cardiovascular complications of diabetes, aortic aneurysms, pulmonary hypertension, and the different forms of vasculitis. Each of these chapters is well illustrated with simple, practical guides to diagnosis and treatment based on a clear understanding of the pathophysiological processes. Beverley Hunt and her co-editors have succeeded in putting together a collection of varied chapters in which the underlying structural and functional abnormalities in blood vessels are described scientifically in the context of clinical disorders. Individual chapters are easy to read and should provide helpful guidance to clinicians and those interested in the pathophysiological basis of vascular medicine.

Antineutrophil Cytoplasmic Antibodies An Update on Clinical Utility

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against components of neutrophils and monocytes, and are helpful in identifying different forms of vasculitis. Until the discovery of ANCA, there was no specific laboratory method for the investigation of systemic vasculitis. Many issues regarding ANCA, such as their role in the pathogenesis of vasculitis, sensitivity, specificity, predictive value, and antigen specificity are still unclear. The differential diagnosis of the vasculitic syndromes is often difficult because of the variable presentation, but is important because of the variable outcome.Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome are three vasculidities that commonly are associated with a positive ANCA. The "gold standard" for a precise diagnosis of vasculitis depends on both the clinical and pathologic features. ANCA testing is used to support the clinical and pathologic findings. The ANCA pattern, determined by indirect immunofluorescence, can be either cytoplasmic (C-ANCA), perinuclear (P-ANCA), or atypical perinuclear (X-ANCA). Interpretation of the ANCA pattern can be problematic, and a reactive antinuclear antibody can contribute to the confusion, requiring testing for reactivities to specific autoantigens. Proteinase-3 and myeloperoxidase are the most common autoantigens and are commonly associated with C-ANCA and P-ANCA, respectively. ANCA reactivity to other autoantigens is associated with the X-ANCA pattern.

Wegener's granulomatosis in a patient receivingpropylthiouracil for Graves' disease

Context: The use of propylthiouracil (PTU) in patients with Graves' disease hasbeen associated with multiple complications including rash, leukocytoclastic vasculitis, pulmonary hemorrhage, glomerulonephritis, and the presence of perinuclear antineutrophilic cytoplasmic antibodies (pANCA). Objectives: To report the association of Wegener's granulomatosis (WG) withthe use of PTU in a patient with Graves' disease and to review the spectrum of systemic vasculitis seen in patients with Graves' disease taking PTU. Design: Retrospective review of data collected in a patient with WG. Inaddition, a Medline search (1980 to present) for PTU-associated vasculitis was conducted. Results: We report WG in a patient treated with PTU who fulfilled the criteria ofthe American College of Rheumatology for this disease. Furthermore, his serum was positive for cytosolic antineutrophil cytoplasmic antibodies (cANCA) and anti-proteinase-3 (PR3) antibodies by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA), respectively. WG is associated with high morbidity and mortality and usually requires extensive therapy with prednisone and cyclophosphamide. Our patient, however, did not need specific therapy except discontinuation of PTU to make a full recovery. In previous reports, PTU has been associated with different forms of vasculitis, but this is a the first description of classic WG in a patient treated with PTU. Conclusions: PTU is capable of causing WG in susceptible patients with Graves' disease. Our patient did not require specific therapy for vasculitis and improved after discontinuation of PTU.

Influence of age on Henoch Schonlein purpura

There are different forms of vasculitis, depending on size of vessel and suspected inciting factors such as drugs or infection. The diagnosis is difficult unless there are obvious signs such as purpura or biopsy evidence. Commonly the diagnosis is made despite signs that are only suggestive, to justify immunosuppressive therapy. Equally common is missing the diagnosis.

Birmingham Vasculitis Activity Score (BVAS) Dim system necrotizinig vasculitis

The continuing morbidity of patients with vasculitis, despite the improved prognosis with aggressive therapy, underlines the need for accurate disease assessment. We have devised a clinical index of disease activity, and evaluated its use in several forms of necrotizing vasculitis. The weighted score is based on symptoms and signs in nine separate organ systems. Disease features are only scored if they are attributable to active vasculitis. The Birmingham Vasculitis Activity Score (BVAS) was compared with two other published vasculitis activity scores, with the physician's global assessment (PGA), with outcome, and with serological markers of disease activity. In a cross-sectional study of 213 consecutive patients with different forms of vasculitis, all 107 vasculitis patients who were judged completely well on clinical assessment had a BVAS score of 0. Twenty-two patients with active vasculitis prior to treatment had a median score of 7.5 (range 4-30) and 69 with active disease on treatment had a median score of 10 (1-29). Of the 12 who died, median score immediately prior to death was 20.5 (9-30). In a serial prospective study, 30 cases had documented episodes of active disease. During periods of disease activity, the median BVAS values were significantly higher than in remission (15 [range 3-32] vs. 0 [0-2], p < 0.001); the same was true for CRP values (80 [9-361] vs. 13.5 [5-68], p < 0.001). This was not true for erythrocyte sedimentation rate (ESR), haemoglobin (Hb) or von Willebrand factor (VWF).(ABSTRACT TRUNCATED AT 250 WORDS)