Periaortitis and Aortic Dissection due to Wegener’s Granulomatosis

We describe here a patient with abdominal periaortitis and intramural dissection as early manifestations of Wegener’s granulomatosis (WG). Surgical biopsies taken from the retroperitoneal inflammatory tissue surrounding the aorta showed granulomatous vasculitis. The patient had antiproteinase-3 antibodies and suffered from nasal, pulmonary, nervous and renal WG involvement. Although being a vasculitis of medium size and small vessels, WG should be included in the systemic vasculitides which can give rise to (peri)aortic inflammation. Received: 6 July 1999 / Accepted: 24 September 1999     

Treatment of primary systemic vasculitis with TNF alpha-antagonists

After the introduction of the TNF alpha blocking drugs Etanercept and Infliximab for the standard therapy of rheumatoid arthritis these effective substances have also been used successfully in many patients with primary systemic vasculitides, who were unresponsive to standard therapy. From pathophysiologic findings their use is justified by the prominent role of TNF alpha in the inflammation of small and large vessels. So far only open studies with a maximum of 20 patients and case reports are published. In summary there are reports of the successful treatment of 7 patients with rheumatoid vasculitis, 39 patients with Wegener's granulomatosis, 3 patients each with microscopic Polyangiitis, and 5 patients each with temporal Arteritis or Takayasu disease with Etanercept as well as with Infliximab. In addition, Infliximab was also used with a good response in severe Polymyalgia rheumatica in 4 cases and in one case of a cryoglobulinemic vasculitis. More than 60 patients with Panuveitis and other manifestations of Beh?et's disease were treated with Infliximab or Etanercept according to preliminary reports. Because of the overall positive reports with TNF alpha collected in this review controlled investigations for their use in primary systemic vasculitis are necessary.     

Ocular manifestations of vasculitis.

Systemic necrotizing vasculitis is characterized by inflammation of blood vessels and often affects the eyes. Ocular manifestations of vasculitis may involve any part of the eye or orbit. The frequency of ocular involvement generally is dependent on the size and type of blood vessels affected by the vasculitis. This article reviews the major types of ocular inflammation and then addresses the ocular manifestations of specific systemic vasculitides.     

Interdisciplinary management of vasculitis patients: internist/rheumatologist

Systemic vasculitides (SV) represent a heterogeneous group of different entities with varying clinical and pathological-anatomical characteristics that physicians of diverse disciplines are involved in the treatment of patients with SV. At the onset of disease organ manifestations often present as a single symptom without appearance of indirect signs of vasculitides as musculoskeletal complaints and constitutional symptoms indicating inflammatory systemic disease. Therefore early interdisciplinary care is extremely important to avoid major organ involvement with the development of fatal disease. Besides the multidisciplinary physical examination serological and immunological parameters, particularly in small vessel vasculitides are relevant in establishing the diagnosis. Regarding the interdisciplinary care we differentiate between primary diagnostic procedures and continuous follow-up to observe therapeutic and side effects of medications. Instruments for the assessment of disease extent (DEI), activity (BVAS) and irreversible damage (VDI) were developed in recent years to document prospectively the disease status and support activity-adjusted treatment. Because of the chronic relapsing character of systemic vasculitides, the measurement of health-related quality of life gained progressive interest in the longitudinal follow-up. In addition in these rare diseases early patient education with information on the disease, treatment, side effects and training in self management strategies will enable patients to actively participate in the management of their disease and bear responsibility.     

Churg-Strauss syndrome presenting as spontaneous subarachnoid haemorrhage

Churg–Strauss syndrome (CSS) is a systemic small-vessel vasculitis characterised by the presence of asthma and eosinophilia. Central nervous system involvement (cerebral infarctions or intracerebral haemorrhage) is rare in CSS. Spontaneous subarachnoid hemorrhage (SAH) has been described in other systemic vasculitides. SAH is exceptional in CSS. We present a 47-year-old woman with CSS presenting as a spontaneous SAH with cerebral angiography findings consistent with vasculitis of the basilar artery and without aneurysms or arteriovenous malformations. She received treatment with prednisone and cyclophosphamide, and 2 months later the basilar artery was normal on magnetic resonance angiography. Received: 27 May 2001 / Accepted: 17 November 2001     

Manifestations of primary vasculitis in the ENT region

The primary ANCA associated vasculitides, Wegener's granulomatosis (WG), Churg Strauss syndrome (CSS) and microscopic polyangiitis (MPA), frequently affect the ENT region. For several reasons WG is of special significance for the otorhinolaryngologist. First, disease activity limited to the upper respiratory tract (localized WG) often proceeds the systemic vasculitis (generalized WG). The early diagnosis therefore has decisive consequences for stage adapted therapy. Second, in most cases (nearly 80%) WG is diagnosed histologically on biopsy specimens from the ENT region. During the initial phase of WG this is of diagnostic relevance, because at this stage the serologic parameters (acute-phase proteins) usually have a normal value and PR3-ANCA is (still) negative in 2/3 of the patients. Third, in many cases recurrences reveal increased activity in the ENT region, or start in this area. Clinically in most cases chronic rhinosinusitis with crusting and epistaxis is seen, sometimes with septal perforation and/or saddle nose. Apart from this there are often unclear middle ear symptoms with recurrent effusions and the inner ear is sometimes also affected. Laryngeal manifestations are typically located in the subglottic area and lead to subglottic stenosis. In the differential diagnosis, diseases in which epitheloid cell granulomas occur, such as sarcoidosis and TBC, need to be considered, but also foreign body granulomas and fungus diseases. Finally malignant tumours, especially malignant lymphomas, have to be ruled out.     

Vasculitis--interdisciplinary diagnosis: radiology

Determination of disease extension and disease activity are in the foreground of diagnostic imaging in vasculitides. There are several radiologic modalities available each having specific indications. Magnetic resonance imaging (MRI) readily depicts granulomas and mucosal inflammations in the paranasal sinuses, nasal cavity and orbits. Computed tomography detects osseous lesions of the skull. Due to its superb sensitivity MRI is an established screening modality for CNS vasculitides, although there are limitations with regard to specificity. In spite of its limited accuracy in most institutions angiography is still required for radiological confirmation of CNS vasculitis. Perfusion and diffusion MR-imaging may combine the advantages of 'conventional' MRI and angiography. By now the method is not fully validated for vasculitides, however. Vascular disease in Takayasu's arteritis and in giant cell arteritis involving predominantly large and medium sized vessels is readily diagnosed by non invasive magnetic resonance angiography. Percutaneous transluminal angioplasty has proven to be an effective and save therapeutic modality for the cure of vascular stenoses and occlusions. Plain film radiography in two planes is the established modality for pulmonary imaging. In pulmonary vasculitides a more thorough analysis of lung disease is provided by high resolution computed tomography. Diagnostic imaging does substantially assist in the interdisciplinary management of patients suffering from vasculitides.     

Systemic vasculitis in adults in northwestern Spain, 1988-1997. Clinical and epidemiologic aspects.

The vasculitides constitute a heterogeneous group of diseases characterized by blood vessel inflammation and necrosis with different but frequently overlapping clinical and pathologic manifestations. The incidence of these conditions is frequently controversial. To further investigate the incidence and clinical manifestations of vasculitides, we reviewed the spectrum of these diseases in an unselected population of adults (age > 20 years) from northwestern Spain during a 10-year period. From January 1988 through December 1997, 267 adults were diagnosed as having vasculitis. The overall average annual incidence rate of vasculitis in the region of Lugo, Spain, between 1988 and 1997 for the population older than 20 years was 141.54/million. Primary vasculitis (115.04/million for the population older than 20 years; 81.3%), especially giant cell arteritis (GCA) was the most common group. Small vessel primary vasculitis (hypersensitivity vasculitis and Henoch-Sch?nlein purpura) was the second most common group. Both GCA and small vessel primary vasculitis had a good outcome. However, although less common, patients with medium and small vessel primary vasculitis, in particular those with polyarteritis nodosa, had a high mortality related to the systemic manifestations of the disease or to the immunosuppressive therapy. Among the group of adults with secondary vasculitis (26.51/million; 18.7%), rheumatic diseases and specifically those occurring in the context of rheumatoid arthritis were the most common group. Patients with secondary vasculitis had clinical or laboratory data that may suggest the presence of an underlying disease. In summary, systemic vasculitides are somewhat more common than previously considered. As in other western countries, GCA constitutes the most common type of vasculitis in northwestern Spain. Better physician awareness may contribute to the progressive increase in the recognition of these conditions.     

Anti-MPO-ANCA-Positive Microscopic Polyangiitis following Subacute Bacterial Endocarditis

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener’s granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis. Received: 2 February 2001 / Accepted: 6 June 2001     

Therapy insight: The recognition and treatment of retinal manifestations of systemic vasculitis

A variety of retinal signs can occur in patients who have systemic vasculitides, or who experience complications of these diseases or their treatment. Although treatment of these retinal manifestations is usually the treatment of the systemic disease, specific treatment is occasionally indicated to preserve vision. The more prevalent of the systemic vasculitides are giant cell arteritis, polyarteritis nodosa, Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and systemic lupus erythematosus. Less frequently occurring vasculitides include Takayasu's arteritis, Goodpasture's disease, microscopic polyangiitis and Henoch-Sch?nlein purpura, as well as vasculitis secondary to scleroderma and rheumatoid arthritis. This article describes the pathogenesis, clinical features and treatment of retinal manifestations of systemic vasculitides.     

Systemic Adverse Effect of Antithyroid Drugs

Antithyroid drugs adverse effects are varied and rare. Autoimmune disorders (vasculitis, lupus erythematosus, polyarthritis . . .) are unusual and serious complications of antithyroid drugs. Since 1945, fewer than 100 cases of systemic manifestations related to antithyroid drugs have been reported in the literature, most frequently with propylthiouracil. The outcome is usually good after drug discontinuation, but some fatal cases have been reported. Because possible cross-sensitivity with other antithyroid drugs, the appropriate treatment for hyperthyroidism relapse if a patient has had an antithyroid drug adverse reaction, should be 131I-Iodine or surgery. We report four new cases of systemic manifestations during propylthiouracil therapy. Received: 27 August 1996 / Accepted: 23 July 1998     

Vasculitides of the gastrointestinal tract

Systemic vasculitides, and especially their gastrointestinal manifestations, are a continuous challenge not only for gastroenterologists and rheumatologists but also for every practising physician. Owing to their chameleon-like appearance, overt clinical symptoms of vasculitides may be restricted to distinct parts of the human body including the intestine. In clinical practice, it is therefore essential to search for the systemic disease underlying the gastrointestinal symptoms such as abdominal pain, bleeding, ileus and necrosis in case vasculitis is suspected or likely as a cause for these sequelae. Classification of intestinal vasculitides is also difficult, since most of the criteria currently used have been established by rheumatologists and, in general, biopsies of the affected vessels cannot be obtained. However, there are increasing data that not only facilitate diagnosis but also allow adequate immunosuppressive and anti-inflammatory therapeutic approaches, which will be outlined in detail in this chapter.     

Management of systemic vasculitis.

The systemic vasculitides are a wide-ranging group of diseases that are characterized by the presence of blood vessel inflammation. Despite this common feature, each type of vasculitis has a unique variety of clinical manifestations that influences its degree of disease severity and ultimately its management. Immunosuppressive therapy forms the foundation of treatment for almost all forms of systemic vasculitis. Because of this, treatment can be associated with its own risk of morbidity, or even mortality, related to specific medication side-effects or infections which occur as a result of impaired host defences. This chapter seeks to review the approach to management in selected forms of systemic vasculitis. Questions examined include the following. When should one treat systemic vasculitis? How does the nature of the disease and its severity affect treatment decisions? What are the data regarding the effectiveness of individual therapeutic regimens?     

Update in the diagnosis and management of pulmonary vasculitis

The term vasculitis encompasses a number of distinct clinicopathologic disease entities, each of which is characterized pathologically by cellular inflammation and destruction of the blood vessel wall, and clinically by the types and locations of the affected vessels. While multiple classification schemes have been proposed to categorize and simplify the approach to these diseases, ultimately their diagnosis rests on the identification of particular patterns of clinical, radiologic, laboratory, and pathologic features. While lung involvement is most commonly seen with the primary idiopathic, small-vessel or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides of Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, one should remember that medium-vessel vasculitis (ie, classic polyarteritis nodosa), large-vessel vasculitis (ie, Takayasu arteritis), primary immune complex-mediated vasculitis (ie, Goodpasture syndrome), and secondary vasculitis (ie, systemic lupus erythematosus) can all affect the lung. However, for the purpose of this review, we will focus on the ANCA-associated vasculitides.     

Treatment of Severe and/or Refractory ANCA-Associated Vasculitis

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.     

ANCA-associated vasculitis: diagnosis, clinical characteristics and treatment

The primary systemic vasculitides are a group of diseases characterized by an inflammatory process of the vessel walls and classified according to the smallest vessels involved. Small vessel vasculitides comprise the largest subgroup divided into diseases with a pauci-immune vasculitis and ANCA and diseases with deposition of immunoglobulin without ANCA. ANCA-associated systemic vasculitides include Wegener's granulomatosis, microscopic polyangiitis comprising renal-limited vasculitis and Churg-Strauss syndrome. Diagnosis is based on clinical manifestation, ANCA-testing and histology. Beside the role of ANCA as a diagnostic marker many studies and animal models have focused on the pathogenic role. The treatment of ANCA-associated vasculitis has changed from a standardized "Fauci-protocol" to an individualized less toxic strategy taking into consideration disease severity) organ manifestation, age of the patient and individual risk factors (e.g. increased bone marrow toxicity in patients with renal insufficiency). For remission induction patients are sub-grouped according to limited or generalized disease with moderate or severe renal involvement. Thus cyclophosphamide is only used in patients with generalized disease or - regarding Churg-Strauss-syndrome - patients with risk factors. For maintenance of remission azathioprine should be used in most of the patients.     

Vasculitis associated with anti-neutrophil cytoplasmic autoantibodies in rheumatoid arthritis. Report of a case of microscopic polyangiitis and another case of Wegener's granulomatosis

Vasculitis is an uncommon complication of rheumatoid arthritis that is associated with a clear increase in morbidity and mortality, although systemic manifestations such as glomerulonephritis, cerebral vasculitis or pulmonary vasculitis are very rare. Systemic vasculitis with renal involvement is associated with overt polyarthritis in less than 5% and association with rheumatoid arthritis is exceptional. Determination of anti-neutrophil cytoplasmic autoantibodies (ANCA), used in the appropriate clinical context, has become an important diagnostic tool in small-vessel systemic vasculitides. We present two patients with rheumatoid arthritis who subsequently developed systemic vasculitis. ANCA determination was decisive in the early diagnosis of these patients.     

Lung vasculitis and alveolar hemorrhage: pathology

Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Beh?et syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Sch?nlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis.     

Difficult to diagnose manifestations of vasculitis: does an interdisciplinary approach help?

In the early stages of disease, primary systemic vasculitides often present with non-specific symptoms that make early diagnosis a challenge. The variety of clinical manifestations found in systemic vasculitis is huge, and some manifestations are frequently not clinically overt at first presentation. A logical implication of the often non-specific and sometimes subclinical presentation of vasculitis is that a systematic diagnostic work-up is necessary. This requires a multidisciplinary approach involving the expert opinion of specialists from many disciplines, such as neurology, radiology, respiratory medicine, pathology and microbiology. There are no generally accepted diagnostic criteria for primary systemic vasculitides, and the application of classification criteria as diagnostic criteria is not feasible and may even be misleading. The demonstration of vasculitis on biopsy is still the gold standard for the diagnosis of vasculitis. In cases where biopsies cannot be obtained, surrogate parameters of vasculitis (e.g. glomerular hematuria or mononeuritis multiplex), along with serology and imaging, can support a clinical diagnosis of vasculitis. This review discusses the approach to the diagnosis of central nervous system and pulmonary manifestations of primary systemic vasculitis. These two examples of difficult to diagnose manifestations of vasculitis illustrate the necessity of an interdisciplinary approach to the diagnostic work-up.     

Abdominal and digestive manifestations in systemic vasculitides

Digestive involvement is frequent during the course of systemic small and medium-sized vessel vasculitides. Clinical manifestations range from rapidly regressive abdominal pain to surgical manifestations associated with poor prognosis. These are usually associated with extra-abdominal signs, reflecting vasculitis activity. Isolated gastrointestinal involvement is observed in only 16% of these patients. The main clinical manifestations are common to all vasculitides (ischemia, bowel infarction and perforations, gastrointestinal hemorrhage due to mucosal ulcerations or aneurysmal ruptures), but some are more specific to one type (granulomatous ileo-colitis during Wegener's granulomatosis, eosinophilic colitis during Churg-Strauss syndrome). Gastrointestinal arteriography can be helpful for diagnosis, but has no prognostic value, likewise for the presence of ANCA. As there are no identified factors predictive of a surgical abdomen, therapy must be adapted individually, using steroids and immunosuppressive agents, generally cyclophosphamide. Prompt surgical and medical care of these seriously ill patients has lowered mortality from nearly 100% twenty years ago to approximately 23 to 56% currently.