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.     

Roadmap to vasculitis: a rheumatological treasure hunt: Part III. Laboratory evaluation and imaging

In the third part of this four part review, we already have the stop sign and our three road signs pointing to secondary vasculitides, pseudovasculitides and primary vasculitides behind our back and we have also passed the first milestone, where “patient history and physical examination” was written with large black block letters. GP can get far with simple blood, urine and stool tests and routine X-rays (second milestone). Almost all vasculitides of clinical significance are characterized by increased ESR and raised C-reactive protein levels and often also by normocytic normochromic anaemia, leucocytosis, eosinophilia and thrombocytosis. Urine test may demonstrate haematuria, proteinuria and cylindruria, X-ray of the paranasal cavities chronic sinusitis and chest X-ray shadowing and cavitations. Serological tests may disclose an unexpected hepatitis B or C or perhaps ANCA. The possibilities described form such a cornucopia that we need to have our patient history and physical examination right for the right picks. This is even more pertinent when we take to the sledgehammer in the referral centres (third milestone) and deal with the histopathology of vasculitides as hopefully seen in biopsies rather than autopsies or perform invasive radiology. High resolution colour Doppler ultrasound offers a useful, non-invasive method for the diagnosis and guidance of an eventual biopsy site in temporal arteritis and is helpful in the diagnosis of Takayasu's arteritis and Kawasaki disease. Aortic arch, mesenteric, splanchnic or renal angiographies, MRI, contrast-enhanced CT, gadolinium-enhanced magnetic resonance angiography and positron emission tomography are dealt with but require the right patient and the right “doctor decision maker” not to cause harm and to avoid waste of scant resources.     

Large vessel involvement in ANCA-associated vasculitides: report of a case and review of the literature

Vasculitides are currently classified according to the size of the vessels involved and characteristic clinical and histopathologic findings. Antineutrophil cytoplasmic antibodies (ANCA) and other serologic tests have been used to further characterize small vessel vasculitides. Large vessel involvement in ANCA-associated small vessel vasculitides has been overlooked in the medical literature. Here, we report a case of fatal aortitis and aortic dissection in a patient with microscopic polyangiitis and review reported cases of large vessel involvement in ANCA-associated vasculitides since 1990. We have attempted to characterize this subgroup of patients. Large vessel disease in ANCA-associated vasculitis may present as stenosing large vessel arteritis, aneurysmal disease, aortic dissection, aortic rupture, aortic regurgitation, and death. Prominent perivascular inflammation may present as mediastinal, cervical or abdominal soft tissue masses. ANCA-associated large vessel disease should be considered in the differential diagnosis of these disorders. The epidemiologic, clinical and pathologic characteristics of these patients differ from those of the well-defined large vessel vasculitides such as giant cell (temporal) arteritis or Takayasus arteritis. We suggest that large vessel involvement is part of the spectrum of ANCA-associated vasculitis rather than an overlap with other large vessel vasculitides. It occurs in both myeloperoxidase- and proteinase 3-positive patients with either Wegeners granulomatosis or microscopic polyangiitis, but has not been reported in Churg–Strauss syndrome. Large vessel vasculitis can precede small vessel vasculitis or occur in the absence of small vessel involvement. We hope this report will contribute to the ongoing development of classification systems for the vasculitic syndromes.Abbreviations ANCA Antineutrophil cytoplasmic antibodies - CSS Churg–Strauss syndrome - ESR Erythrocyte sedimentation rate - MPA Microscopic polyangiitis - MPO Myeloperoxidase - PR3 Proteinase 3 - SVV Small vessel vasculitis - WG Wegeners granulomatosis     

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.     

Pulmonary vasculitis

Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody-associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex-mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody-associated disorder, vasculitides.     

Epidemiology and etiology of wegener granulomatosis, microscopic polyangiitis, churg-strauss syndrome and goodpasture syndrome: vasculitides with frequent lung involvement

This review focuses on the epidemiological characteristics and etiologies of four primary systemic vasculitides with frequent lung involvement, namely Wegener granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and Goodpasture syndrome (GPS). Elucidation of the mechanisms underlying these vasculitides with frequent lung involvement is complicated by their rarity, which hampers the undertaking of large-scale studies; difficulties in classification; and their multifaceted clinical presentations, which infer the existence of several etiologic pathways. Notwithstanding, epidemiological research showed some evidence for international, interethnic, and temporal variations of the frequencies of these four vasculitides; led to the identification of several genetic and environmental risk factors; and provided insight on the extent to which genes and environment might contribute to their development. Available data support the concept that WG, MPA, CSS, and GPS have unique and shared risk determinants. Although the precise causes of these vasculitides are not yet fully understood and the development of prevention strategies is out of our reach at present, current knowledge enables the formulation of etiologic hypotheses to provide caregivers and their patients with valuable information on the nature of these rare entities.     

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.     

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.     

Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations

This paper has reviewed current knowledge of clinical, biochemical, and morphological manifestations of extracranial GRH-producing tumors. Excessive GRH release stimulates pituitary somatotrophs causing elevation of blood GH levels and acromegaly. In some patients with GRH-containing tumor, blood GH concentrations are normal and no acromegaly develops. GRH-producing tumors associated with acromegaly are rare. Based on a critical analysis of the literature, 30 tumors are accepted as definitive. They possess unique features: occurrence in young age, female preponderance, foregut derivation, benign biological behavior, small secretory granules, and frequent association with MEN type I syndrome. The pancreas and lung are common primary sites. GRH-containing tumors unassociated with acromegaly include those of gut and thymus, small cell carcinoma of lung, and medullary carcinoma of thyroid. Several tumors are plurihormonal. In contrast to somatotroph adenoma seen in patients with classical acromegaly, the hypophysial lesion represents somatotroph hyperplasia in acromegalic patients with GRH-producing tumor. This finding indicates that GRH not only increases somatotroph secretory activity but causes somatotroph proliferation. Studies of GRH-producing tumors are of fundamental importance in obtaining a deeper insight into endocrine activity of pituitary somatotrophs and the pathogenesis of GH-secreting pituitary adenomas associated with acromegaly; the importance of GRH in the etiology of acromegaly is still unresolved. The relationship between GRH-secreting tumors and MEN type I syndrome is controversial; further studies are required to elucidate whether they represent two distinct entities or whether GRH-producing tumors accompanied by acromegaly are only forme fruste manifestations of MEN type I syndrome.     

Primary Sj?gren's syndrome with antibodies to HTLV-I: clinical and laboratory features.

The prevalence of antibodies to human T lymphotropic virus type I (HTLV-I) was studied in patients with primary Sjögren''s syndrome. Thirteen of 36 serum samples were positive by enzyme linked immunosorbent assay (ELISA) and particle agglutination assay for antibodies to HTLV-I and were confirmed by western blotting. The presence of antibodies to HTLV-I may signify an HTLV-I carrier state. These patients had a high occurrence of extraglandular manifestations such as uveitis, myopathy, and recurrent high fever compared with patients who did not have antibodies to HTLV-I. Patients with antibodies to HTLV-I had an increased spontaneous proliferation of peripheral blood mononuclear cells compared with those without the antibodies. The proportions of activated and memory T cells (HLA-DR+ CD3+, CD25+ CD3+, and CD29+ CD4+ cells) were higher in HTLV-I carriers than in non-carriers. The presence of antibodies to HTLV-I in some patients with primary Sjögren''s syndrome suggests that HTLV-I may cause primary Sjögren''s syndrome or its extraglandular manifestations, or both.     

Pulmonary vasculitis: CT features

The pulmonary vasculitides are a heterogeneous group of inflammatory disorders that may be primarily localized to the pulmonary vasculature or be systemic in nature. The primary pulmonary vasculitides usually affect small vessels, whereas the systemic vasculitides can involve any size pulmonary vessels. For all types of vasculitis, there is a high degree of overlap within groups in regard to their appearance at computed tomography (CT). The most common CT findings are the result of either diffuse or focal pulmonary hemorrhage, are nonspecific, and include ground-glass opacity, consolidation, and small centrilobular nodules. Therefore, the CT findings must be considered in concert with the history, physical examination, and laboratory examination when a specific diagnosis is sought. This review will discuss the typical CT features of both the systemic and the primary pulmonary vasculitides, drawing a distinction where CT is helpful in differentiating among the various causes.     

Neues zur Pathogenese prim?r systemischer Immunvaskulitiden

Primary systemic vasculitides are defined according immunopathological features and the size of the involved vessels. Three anti-neutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitides (Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis) can be distinguished from the so-called Non-ANCA-associated vasculitides, i.e. granulomatous vasculitides of large vessels (giant cell arteritis, Takayasu arteritis) and immune complex-mediated vasculitides of medium-sized and small vessels (Polyarteriitis nodosa, Kawasaki disease and Henoch-Schönlein purpura, cryoglobulinemic vasculitis, cutaneous leukocytoklastische angiitis). Predisposing genetic and other endogenous and exogenous factors facilitate the activation of innate immunity and induce persisting inflammatory reactions resulting in different forms of (auto)-immune vasculitides.     

The antineutrophil cytoplasmic antibody-associated vasculitides

Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome are small- to medium-vessel vasculitides linked by overlapping pathology and the presence of antineutrophil cytoplasmic antibodies (ANCA). Commonly referred to as the ANCA-associated vasculitides, these diseases are challenging to diagnose and to treat. Distinguishing the ANCA-associated vasculitides from other forms of vasculitis or nonvasculitic processes (such as infection) can be particularly difficult. This review describes the clinical and pathologic hallmarks of the ANCA-associated vasculitides, discusses the role of ANCA assays in diagnosis and treatment, and outlines an approach to the evaluation and management of these diseases.     

Familial vasculitides: Churg-Strauss syndrome and Wegener's granulomatosis in 2 first-degree relatives

Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG) are uncommon primary vasculitides, characterized by the involvement of the small to medium size vessels and by the frequent presence of serum antineutrophil cytoplasmic antibodies (ANCA). The pathogenesis of ANCA associated vasculitides is unclear, but roles for both genetic and environmental factors have been suggested. Familial cases of WG, but not CSS, have been reported. We describe the occurrence of CSS in a man and, 5 years later, WG in his son. These patients live together in an urban area of Northern Italy and share the HLA haplotype A*03; B*07; C*w07; DRB 1*0404, DQB 1*0302. To our knowledge, this is the first report of the familial clustering of CSS and WG in first-degree relatives.     

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.     

Les vascularites du système nerveux central : mise au point

Central nervous system (CNS) vasculitides are a heterogeneous group of diseases that can lead to severe disability and death. Given the poor performance of available diagnostic procedures (magnetic resonance imaging, angiography and brain biopsy), the diagnosis of isolated CNS vasculitis is challenging. Differential diagnosis includes secondary CNS vasculitides (infection, cancer, drug exposure or systemic inflammatory disorders) and several non-inflammatory cerebral vasculopathies, such as the reversible cerebral vasoconstriction syndrome. Despite recent advances in neuroradiology and the publication of large retrospective case series, primary angiitis of the CNS remains a heterogeneous and challenging nosological entity. Prospective interdisciplinary studies are necessary to improve our approach to these patients.     

Systemic vasculitis in childhood

Systemic vasculitis is a group of disorders with multiorgan involvement. These disorders have diverse clinical manifestations associated with significant morbidity and mortality. The most common vasculitides in children—Henoch-Schönlein purpura and Kawasaki disease—are self-limiting conditions. The lifelong and chronic vasculitides (eg, giant cell arteritis, Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, polyarteritis nodosa, and Takayasu arteritis) are rarely seen in children. Therefore, the outcome in general is more favorable in children. This article offers an overview of the epidemiologic, etiologic, pathophysiologic, and clinical features of vasculitis in children, with emphasis on common conditions.     

Takayasu's arteritis and posterior reversible encephalopathy syndrome: a case-based review

Autoimmune vasculitides can have diverse neurological manifestations, including posterior reversible encephalopathy syndrome (PRES). Takayasu's arteritis (TA) is an uncommon vasculitis rarely associated with PRES. Common clinical features of TA include hypertension, audible arterial bruits, absence of peripheral pulses, claudication of the extremities, reduced blood pressure in one or both arms, and angiographic abnormalities. PRES has been mostly associated with severe hypertension, endothelial injury, and conditions such as renal disease, immunosuppressive medication use, and rheumatologic diseases. Headaches, seizures, and altered mental status are the main clinical features as well as characteristic findings in magnetic resonance imaging. TA frequently presents with hypertension and is associated with endothelial injury, making this entity an ideal setting for the development of PRES. We report the case of a 17-year-old female who presented to the emergency department with severe hypertension, headache, and seizures. Magnetic resonance imaging findings were suggestive of PRES. She had absent pulses in the right upper extremity, abdominal bruits, and angiographic findings included subclavian and renal artery stenoses. The diagnosis of TA was made, and she responded well to treatment. We found ten additional cases of TA and PRES in the literature. All patients were females under the age of 40, had renovascular hypertension, and presented with headaches and seizures. Current literature relevant to this rare association is presented and discussed.     

Pulmonary vasculitis

This review summarizes the radiological manifestations of the vasculitides of proven or presumed immunologic origin in which the inflammatory reaction is directed primarily against the vessel wall. These include Wegener's granulomatosis, Churg-Strauss syndrome, Takayasu's arteritis, Beh?et's syndrome, Goodpasture's syndrome, and microscopic polyangiitis. Chest radiography is used routinely in the initial evaluation and follow-up of these patients. The radiographic findings however are nonspecific and need to be interpreted together with the clinical findings. Computed tomography (CT) plays an increasingly important role in the assessment of patients with vasculitis and, in the proper clinical context, allows a confident diagnosis of some of these entities. Magnetic resonance imaging and positron emission tomography play a limited role. The characteristic imaging manifestations of the various vasculitides are reviewed and illustrated.