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This retrospective analysis is concerned with 10 patients suffering from granulomatosis with polyangitis (GPA, Wegener's disease), who were followed up in a tertiary care Ear, Nose, and Throat (ENT) department. The inaugural events took place in the ENT field (8 patients), the lung (2 patients), the vestibule (1 patient), or the oral cavity (1 patient). The ENT manifestations during the disease evolution involved the rhinologic (osetocartilaginous--6 cases; mucosal--9 cases), the otologic (3 cases), or the laryngeal area (2 cases). Facial pain was noted in 6 cases and residual hyposmia in 5. We observed 5 cases of lung involvement, 3 cases of renal involvement, and 4 cases of ocular involvement. An aseptic meningitis was seen in 1 case and the muscles were affected in 6 cases. The average delay between symptom onset and diagnosis was 26 months. Endoscopy, imaging techniques, and determination of antineutrophil antibodies (ANCA) were used to reach the diagnosis. Sinus biopsies were contributive in 6 cases. The patients were treated with immunosuppressive drugs and/or surgery. After treatment, remission was obtained in 6 patients.

Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Orbital tumor lesions in pediatric population encompass a wide range of pathological processes, which are very different in etiology and prognosis. They usually require an emergency in histological diagnosis because of their quick growth. Beside malignant and benign tumors, the inflammatory pseudo-tumors group included dysimmune orbital involvement secondary to systemic vasculitis such as granulomatosis with polyangiitis (ex-Wegener's granulomatosis). We report the case of a seven-year-old girl suffering from a severe primitive ANCA vasculitis, revealed by an orbital mass., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target., (Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Antimyeloperoxidase antibodies are a variety of antineutrophil cytoplasm antibodies (Anca), which can be detected in systemic small-sized vessel vasculitides such as microscopic polyangiitis, Wegener's granulomatosis and Churg-Strauss syndrome. Antimyeloperoxidase antibodies have been also associated with the development of lung fibrosis. Their pathogenic role has been well established, both in vitro and in vivo. These autoantibodies can activate neutrophils and trigger their oxidative burst leading to the release of free oxygen species and cytotoxic proteins. The oxidative burst is deleterious for the endothelium. Another mechanism by which antimyeloperoxidase may act is the activation of myeloperoxydase leading to an increased production of hypochlorous acid, which is highly toxic for the endothelial cells. These mechanisms contribute to the development of vasculitis., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Introduction: Central nervous system involvement is rare in Wegener granulomatosis. Stroke is the most common event suggestive of the disease., Comment: A 35-year-old woman, who was followed for rhinitis and mild asthma, described gradual decline of visual acuity in the right eye over two months, persistent nasal obstruction and fronto-orbital headache since a few weeks. She presented left hemiparesis due to a stroke, associated with exophthalmos and deficits of the optic nerve and abducens of the right eye. The otolaryngological examination found signs of crusty rhinitis and right nasal stenosis. The diagnosis of Wegener's granulomatosis was established on the basis of the clinical findings, radiological aspects and the presence of ANCA. The patient was treated by antiplatelet agents and high-dose corticosteroids associated with immunosuppressive drugs including cyclophosphamide in a monthly bolus., Discussion: This case illustrates two of the three pathogenic mechanisms that may account for central nervous system involvement in Wegener granulomatosis: vasculitis, extension by contiguity of granulomatous tissue from the nasal cavity or sinuses, and in situ formation of a granuloma into the brain parenchyma or meninges., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Wegener's granulomatosis (WG) is a rare systemic necrotizing granulomatous vasculitis affecting small- to medium-sized vessels, associated with antineutrophil cytoplasm antibodies (ANCA), mainly anti-proteinase 3. Rarely, ANCA may be directed against myeloperoxidase. We report a 58-year-old woman who developed an uveitis as the presenting manifestation of Wegener's granulomatosis who highlight the usefulness of internist and ophthalmologist collaboration., (Copyright © 2010. Published by Elsevier SAS.)

Introduction: Pulmonary fibrosis secondary to antineutrophil cytoplasmic antibodypositive vasculitis is rarely reported. Most cases have occurred in association with microscopic polyangiitis., Case Report: We report the case of an 82-year-old man presenting with pulmonary fibrosis. The CT scan showed honeycombing and traction bronchiectasis with peripheral and basal predominance. The diagnosis of Wegener's granulomatosis was based on the association of positive antineutrophil cytoplasmic antibodies, urinary sediment abnormalities and renal biopsy findings., Conclusion: We emphasize, through this case, the rarity of interstitial fibrosis as a pulmonary manifestation of vasculitis and we discuss the pathogenesis of this association.

A 51-year-old woman presented with crusting rhinitis, bilateral serous otitis, inflammatory arthralgias, fever, weight loss and signs of temporal arteritis. Temporal arteries were increased in size, painful, with inflammatory signs. There was microscopic hematuria and inflammatory parameters were increased. The renal function was normal. Anticytoplasmic neutrophils antibodies were detected (anti-PR3). Temporal artery biopsy did not show signs of giant cell arteritis. A diagnostic of Wegener's granulomatosis was established and steroid treatment allowed disappearance of clinical and biologic features.

Wegener's granulomatosis and microscopic polyangiitis are among the main systemic necrotizing vasculitides predominantly affecting small vessels. Their prevalences range from 24 to 157 cases per million inhabitants. Mean age at onset is usually 40 to 60 years old. Most common and suggestive features of Wegener's granulomatosis are upper (sinusitis, crusting rhinitis, saddle nose deformity, otitis media) and lower (excavated lung nodules, alveolar hemorrhage) respiratory tract, and kidney involvements. Alveolar hemorrhage and crescentic necrotizing glomerulonephritis are also characteristic manifestations of microscopic polyangiitis. Mononeuritis multiplex and necrotic purpura are frequent symptoms in both diseases. Antineutrophil cytoplasm autoantibodies (ANCA) directed against proteinase 3 can be found in the serum of 90% of the patients with diffuse forms of Wegener's granulomatosis, whereas ANCA with anti-myeloperoxidase specificity, whose pathogenic role is now well documented, can be detected in more than 60% of those with microscopic polyangiitis. Histologically, Wegener's granulomatosis can be differentiated from its counterpart when the inflammatory infiltrates have a granulomatous pattern. Therapy relies on the combination of corticosteroids and pulse intravenous cyclophosphamide, which can be switched, as soon as remission is achieved, to azathioprine or methotrexate, for a total duration of treatment of at least 18 months. Ten-year survival rate now exceeds 80%, but relapses are frequent. The precise place of new biologics, such as rituximab, needs to be further defined.

Multiple mechanisms contribute to the pathogenesis of systemic vasculitides: 1. vasculitides resulting from the deposition of circulating immune complexes, comprising polyarteritis nodosa associated with hepatitis B virus infection, cryoglobulinemia associated systemic with vasculitides, mainly the consequence of hepatitis C virus infection, and Schonlein Henoch purpura, which results from the deposition in the mesangium and vessels of IgA forming complexes; 2. vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA), comprising Wegener's granulomatosis associated with anti-proteinase 3 ANCA, and microscopic polyangiitis and Churg-Strauss syndrome, associated with anti-myeloperoxydase ANCA. The pathogenic role of ANCA has been demonstrated in vitro and in vivo in the case of anti-myéloperoxydase antibodies, whereas it has only been demonstrated in vitro in the case of anti-proteinase 3 antibodies; 3. polyarteritis nodosa unrelated to viral infection results from rheologic phenomenon that explain the localisation of vasculitis lesions at the bifurcation of arteries and the presence of microaneurysm.

Wegener's granulomatosis is described by the Chapel Hill nomenclature (1994) as a systemic necrotizing vasculitis affecting small to medium-sized vessels. Cytoplasm-labeling antineutrophil cytoplasmic autoantibodies (cANCA) directed against proteinase 3 (PR3) are detected in the sera of approximately 90% of patients. Reported incidence varies from 2 to 12 cases/million inhabitants/year and prevalence from 24 to 157 cases/million inhabitants, depending on the series. While still rare, incidence seems to have increased slightly over the past few decades. Most new cases involve adults aged 45-60 years. Many of the immune mechanisms involved in its pathogenesis have been identified. These involve cANCA as well as neutrophils, various lymphocyte subtypes, activation molecules, and cytokines. Genetic and environmental factors have been observed in some cases. However, the precise causes of the disease and of the initial immune process leading to cANCA production remain unknown. The most characteristic clinical manifestations are involvement of the upper and lower respiratory tracts and glomerulonephritis. Diffuse/systemic forms may be clinically distinguished from localized/limited forms: the former are mainly associated with vasculitis, and the latter with granulomatous inflammation. Diagnosis relies largely on the combination of characteristic clinical symptoms and cANCA anti-PR3, but histological confirmation should always be obtained when biopsy of affected organs is feasible and safe. Kidney biopsy is particularly useful in cases with renal manifestations, because it also provides some prognostic information. Current recommendations for treatment of systemic forms call first for an induction phase that combines corticosteroids and intravenous cyclophosphamide; the first three pulses are given every 2 weeks and then every 3 weeks until remission is achieved, followed by a maintenance phase with a less toxic immunosuppressant. The optimal duration of this regimen has not yet been determined, but it must certainly not be less than 18 months. Continuation of cotrimoxazole for two additional years is advised once immunosuppressants have been withdrawn. Remission is obtained in more than 85% of the cases to date, but the high relapse rate remains a matter of concern: approximately half of all patients will relapse within the five years following diagnosis. Promising new therapeutic agents, including rituximab, anti-TNF-alpha, and abatacept, are currently under evaluation and may substantially modify management of this disease in the years to come. Today, however, they are reserved for refractory cases.

Vasculitides are defined by inflammation of blood vessel walls leading to vascular stenosis or occlusion, with various degrees of fibrinoid necrosis of the media and inflammatory infiltration, mainly neutrophilic and sometimes granulomatous. Various classifications of the vasculitides have been proposed. The classifications used most today are the 1990 American College of Rheumatology classification and the Chapel Hill nomenclature, published in 1994 . Only the latter distinguished between polyarteritis nodosa and microscopic polyangiitis and stressed the importance of antineutrophil cytoplasm autoantibodies (ANCA). In practice, primary systemic vasculitides are classified according to their clinical presentations, their precise histological features, and the size of the predominantly affected vessels. Some small-vessel vasculitides are associated with the presence of ANCA: 90% of patients with systemic Wegener's granulomatosis (mainly ANCA with cytoplasm labeling on indirect immunofluorescence and proteinase 3 specificity), 80% of the subjects with microscopic polyangiitis (mostly pANCA with myeloperoxidase specificity), and more than one third of those with Churg-Strauss syndrome (mostly pANCA).

Recent studies provided new insights into the pathogenesis of vasculitides associated with antineutrophil cytoplasm antibodies (ANCA). They yield more information about the pathogenic role of ANCA, the initiation of the immune response against proteinase 3, the expression of ANCA target antigens on neutrophil surfaces, endothelial damage and the mechanisms of vasculitis associated with propylthiouracil. The pathogenic role of antimyeloperoxidase antibodies has been established in vitro and in vivo in animal models and in human. A pathogenic role for antiproteinase 3 antibodies has not yet been clearly established in vivo although it is well documented in vitro.

The pathogenesis of different types of systemic vasculitis positive for antineutrophil cytoplasmic antibodies (ANCA) remains incompletely understood. ANCA constitute a heterogeneous group of antibodies that are associated with different types of small-vessel vasculitis, including Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS). Anti-proteinase 3 ANCA are present in more than 90% of patients with systemic WG, and anti-myeloperoxidase (MPO) ANCA in 50-75% of those with MPA and 40-60 % of those with CSS. The pathogenic role of ANCA has been well documented in vivo: passive transfer of anti-MPO ANCA in an MPO knockout mouse model immunized with MPO is sufficient to induce the disease. In vitro, mouse and human anti-proteinase 3 ANCA can activate neutrophils primed with TNF-a and contribute to vasculitic lesions. T-cells are also involved: type 1 helper cytokines have been detected in tissue lesions of limited forms of WG, while type 2 helper cytokines have been identified in its systemic forms. Eosinophils may play a key role in the development of vasculitic lesions in CSS, although this remains to be proved.

Unlabelled: Wegener's Granulomatosis (WG) is a necrotizing granulomatous vasculitis that has a strong affinity for the upper respiratory tract., Objective: To retrospectively study the clinical features of otorhinolaryngological manifestations from 21 WG patients., Patients: Eleven men and 10 women were studied with respectively a mean age of 62.7 (23-79) and 63.9 (53-73)., Methods: Otorhinolaryngological manifestations were recorded before and during the course of WG., Results: Upper respiratory tract involvement occurred in 81% of cases (17/21 patients) and was isolated in 42.8% of cases (9/21 patients). Nasosinusal manifestations occurred in 71.4% of cases (15/21) before and at the time of GW diagnosis. They included bilateral sinusitis (7 cases), nasal crusting (6 cases), purulent rhinorrhea (5 cases), epistaxis (4 cases), nasal ulcers (2 cases), nasal congestion with obstruction (3 cases) and 4 cases of nose deformity (saddle nose or oedema). Otologic manifestations occurred in 28.5% of cases and were never isolated. They included otitis media (3 cases), sudden hearing loss (3 cases), tinnitus (1 case), facial palsy (1 case) and 2 cases of chondritis. Pharyngolaryngotracheal manifestations occurred in 33.3% of cases (7/21). Diagnosis of GW was based on positive ANCA test (95.2% of cases), presence of biologic inflammatory parameters (76% of cases) and histological features. 29 biopsies from nasosinusal lesions on 17 patients were made. 44.8% of the biopsies were contributive with at least one histologic feature of the combination including vasculitis, necrosis and granulomatous inflammation. The best contributive site of biopsy was the paranasal sinus., Conclusion: We report that otorhinolaryngological manifestations occurred in 81% of cases before and at the time of GW diagnosis. These findings indicate that otorhinolaryngologists have a central role to play in early diagnosis of the disease.

We report a case of sarcoidosis with mediastinal and pulmonary localizations associated with diffuse antineutrophil cytoplasmic antibodies (c-ANCA). This led to discuss the differential diagnosis with vascularitis and the specificity of c-ANCA in Wegener's granulocytosis.

We report a case of Wegener's disease with an exceptional 10-year course before diagnosis subsequent to the development of severe ENT features. Mucosal ulcerations involving the mouth and the pharynx were highly extensive and resolved completely, but temporarily, with cyclophosphamide and corticosteroid therapy.

Purpose: ANCA positive systemic vasculitis comprises Wegener granulomatosis (WG), microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS). In WG, anti-Pr3 ANCA are present in 90% of the cases, whereas in MPA and CSS ANCA are present in 40 to 80% and 25 to 60% of the cases, respectively, with anti-MPO specificity. The treatment of WG and MPA associates prednisone and cyclophosphamide, and clinical remission is obtained in 70 to 90% of the cases. However, relapses occur in 10 to 30% of the patients and tolerance of corticosteroids and immunosuppressive therapy is not always good., State of the Art: Intravenous immunoglobulins (IVIg) are well tolerated and indicated in a large number of autoimmune and systemic inflammatory diseases. In vitro IVIg specifically inhibit ANCA activity through V-region dependent interaction of anti-ANCA anti-idiotypic antibodies with ANCA. Several open studies and a few case reports of patients with WG or MPA treated with IVIg were published in the past seven years, with various results., Projects: A prospective controlled multicenter study is necessary to evaluate the efficacy of IVIg in the treatment of ANCA positive vasculitides.

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies mainly directed against alpha granules' components (especially proteinase 3 (PR 3) and myeloperoxidase (MPO). They are usually detected by indirect immunofluorescence (IIF) giving essentially two staining patterns, cytoplasmic and perinuclear. Nevertheless the IIF method does not allow to precise the true specificity of ANCA. From now on a better classification of systemic vasculitis requires such a determination. This can be done only by solid phase tests that require to be reliable, highly purified antigen, and, from a practical point of view, only a MPO-ELISA is currently available. We report on our experience with Western blot analysis of 67 IIF-ANCA positive sera. Using Western blot analysis to characterize ANCA specificity is not so easy as in the case of antibodies directed against extractable nuclear antigens: only PR 3 ANCA detection could be done reproducibly. PR 3 ANCA are mainly detected in the c-ACPN positive sera of patients with Wegener's granylomatosis. Nevertheless using both MPO-ELISA and PR 3 blot seems to increase the frequency of serum containing the two types of ANCA (anti PR 3 and anti MPO).

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.

ANCA mainly recognize proteinase 3 (cytoplasmic fluorescence) in Wegener's granulomatosis and myeloperoxidase (perinuclear fluorescence) in other types of vasculitis. A causative role of ANCA seems not obvious because: a) active generalized Wegener's granulomatosis may exist with no detectable ANCA, b) ANCA titres don't reliably parallel clinical activity and c) of the increasing diversity of clinical situations where ANCA are described. Nevertheless, some lines of evidence point to a pathogenetic role of ANCA, especially in vascular lesions genesis: a) ANCA may prevent inactivation of antigenic proteases by antiproteases, b) translocation at the outer membrane of intracellular antigens make them accessible to ANCA, c) activation of polymorphonuclear leucocytes and increase of their aggregation and cytotoxicity to endothelial cells are specifically induced by ANCA, d) proteinase 3 and myeloperoxidase may adhere to the endothelial cell membrane and then be recognized by ANCA, e) a specific T-lymphocyte response to ANCA antigens could be elicited in Wegener's granulomatosis and f) an in vivo model of ANCA-related glomerulonephritis has recently been established.

In retrospective and prospective studies the sera of 442 patients recruited from an Internal Medicine department were examined by acetone indirect immunofluorescence and immunoblot in search of anti-neutrophil cytoplasm antibodies (ANCA). Twenty-three patients had Wegener's granulomatosis, and 419 had various control diseases including connective tissue diseases, vasculitis and granulomatosis. The sera from 100 healthy blood donors were used as controls. Among the 23 patients with generalized (n = 15) or localized (n = 8) Wegener's granulomatosis (active in 21/23), the indirect immunofluorescence test was positive in 92 percent of those with the generalized form and in 62 percent of those with the localized form. Nine of the 13 sera examined by immunoblot (69 percent) were positive (31 +/- 57 kDa bands). On the other hand, the sera from 38 (6.9 percent) patients with control diseases were positive at immunofluorescence: vasculitis (14 cases, 50 percent), connective tissue diseases (4 cases, 14.3 percent) and miscellaneous diseases including 3 neoplasms (10 cases, 35.7 percent). Only 6 of these 28 sera showed a 1/100th titer of ANCA. The sera of all healthy controls were negative. The sensitivity of ANCA for Wegener's granulomatosis at all stages was 72.2 percent, and its specificity 94.4 percent. This study confirms the value of ANCA as third diagnostic criterion of Wegener's granulomatosis, after the clinical and histological criteria.

Microscopic polyarteritis is an idiopathic necrotising vascularitis of the small vessels. Manifestations include diffuse alveolar haemorrhage, segmentary necrotising glomerulonephritis, and a cutaneous, articular, neurological or digestive vascularitis. The absence of a histological granulomas and medium calibre vessel involvement distinguishes Wegener's syndrome from polyarteritis nodulosa. The diagnosis is facilitated when anti-neutrophil cytoplasm antibodies are found in the serum. These auto-antibodies are suspected to be the cause based on clinical and experimental data, although this aetiology has not been confirmed. Corticosteroids, immunosuppressors and plasmapheresis can improve the prognosis of this severe and evolving affection which may be fatal.

The pathogenic mechanisms underlying Lyme disease remain uncertain but an increasing number of reports suggest a vascular inflammatory process. On the other hand, the so-called systemic vasculitides, even though they remain of pathological definition, have recently been characterized by the presence, in the serum, of anti-neutrophil cytoplasmic antibodies (ANCA). We report on a patient, finally diagnosed as having neuroborreliosis, who presented initially with multiple mononeuropathy, ANCA, vascular lesions at muscle biopsy and lymphocytic meningitis. Despite antibiotherapy, he presented with two recurrent strokes, from which he completely recovered. He also developed oto-sinusitis. The disease was finally clinically and biologically controlled by immunosuppressive therapy. The relationship between angiitis and Lyme disease are discussed. It is hypothesized that Borrelia burgdorferi infection may cause a systemic vasculitis following its own course and requiring its own treatment.

ANCA antibodies represent a family of autoantibodies directed against neutrophil enzymes. Immunofluorescence patterns allow to distinguish c-ANCAs from p-ANCAs. The detection of ANCAs is often a key element for the diagnosis of Wegener's granulomatosis, microperiarteritis, Churg-Strauss syndrome and idiopathic rapidly progressive glomerulonephritis. Although the pathogenic role of ANCAs is not firmly established, their detection often allows an early therapeutic decision in necrotizing vasculitides.

Two main types of antineutrophil cytoplasmic antibodies (ANCA) have been recognized by indirect immunofluorescence. ANCA-D are defined by diffuse fluorescence and are directed against proteinase 3. They are highly specific for Wegener's granulomatosis, and their titre varies with disease activity. ANCA-P are responsible for perinuclear fluorescence and are principally found in other types of vasculitis and in idiopathic crescentic glomerulonephritis. In patients with suggestive clinical signs, ANCA are of considerable diagnostic value when specific histology is difficult to obtain. Therapeutic monitoring and prevention of Wegener's disease relapses could rely on regular measurements of ANCA titres. Moreover, studies on the pathogenetic role of ANCA may transform current physiopathological concepts and nosology of vasculitis.

Seventeen cases of Wegener's granulomatosis have been reviewed in search of articular involvement. Articular symptoms were present in 13 cases (76 p. cent), and were inaugural in 9 cases (53 p. cent). Six of these patients experienced arthralgias, which were most often migratory, and were inaugural in 3 cases. Seven patients had arthritides, which were inaugural in 6 cases; they were fixed and additive in 6 of these 7 cases, making up a distal polyarthritis in 3 patients, and an oligoarthritis in the 3 other ones; they were transient and migratory in 1 case. The 3 cases of distal polyarthritis were inaugural and fulfilled the ARA criteria for rheumatoid arthritis; two of them were accompanied by nodules which were quite identical to rheumatoid ones. There was no axial involvement. Joint involvement was not destructive and had a favourable course under disease treatment. Myalgias were present in 3 cases, one of which simulated Horton's disease. Biological manifestations chiefly consisted of marked inflammatory changes. Antineutrophil cytoplasm antibodies were present in 11 out of 16 patients in whom they were searched; among 6 of these patients who had active disease, they were present in 5. The antibody level decreased as treatment reduced disease activity and suppressed joint involvement. Joint involvement in Wegener's granulomatosis seems to be the inconstant hallmark of disease activity. It requires no specific treatment.

In the last 21 years, 22 histologically proven cases of Wegener's granulomatosis (WG) were observed and treated. In 19 patients WG appeared primarily in the ENT-area. Ten patients had middle ear involvement. Whereas, in 9 cases the inner ear was affected too. Before introduction of immunosuppressive therapy the patients (n = 8) died averagely after 5.6 months after onset of the first symptoms. Under therapy with cyclophosphamide and prednisone total remission of WG can be reached for long times (n = 14, 3.2 years of follow up). In 14 cases serologically anti-cytoplasmatic antibodies against neutrophil granulocytes were determined in high activity stage of WG. In combination with the clinical and histological findings the determination of these antibodies gives the possibility to solve difficulties in differential diagnosis of WG.

Autoantibodies to the cytoplasmic components of neutrophil polymorphonuclear granulocytes (ACPA) were searched for by indirect immunofluorescence on ethanol-fixed smears from normal white blood cells in 248 sera from patients with Wegener's granulomatosis, Kawasaki disease and various other vasculitides, connective tissue diseases, nephropathies and infiltrative pulmonary diseases. Apart from a weak positivity in a few Kawasaki disease sera, ACPA were found in Wegener's granulomatosis (and micropolyarteritis) only, with a correlation between ACPA titers and disease activity. These results confirm the value of ACPA in the diagnosis and evaluation of activity of Wegener's granulomatosis.

The demonstration of antibodies directed against granulocyte cytoplasm in Wegener's disease and in the microscopic forms of polyarteritis nodosa led to the proposal that these antibodies could be used as a diagnostic tool and a means to monitor the evolution of these diseases. However, the presence of these antibodies in different pathological situations and, in particular, in syndromes not related to vasculitides, poses the question as to their specificity. In addition, the observation of dissociated reactions between the methods available for the detection of these antibodies (indirect immunofluorescence, radioimmunological assay), like the existence of different morphological aspects seen in immunofluorescence, favor the hypothesis of different antigenic determinants, whose recognition could contribute to the nosology and pathophysiology of these diseases. We performed a retrospective study based on 42 positive results (paired execution of both detection techniques), in order to characterize the corresponding anatomic and clinical states. We confirmed the classical positivity in Wegener's disease and microscopic forms of polyarteritis nodosa, justified the paired running of both detection assays because of dissociated results and false positives found by immunofluorescence, corroborated the presence of antibodies in conditions apparently unrelated to vasculitides, and specified the different aspects observable by immunofluorescence, thus demonstrating the reality of different antigenic determinants.