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Granulomatosis
Kinds of Granulomatosis Selected AbstractsWEGENER'S GRANULOMATOSIS COMPLICATED WITH APHTHOID COLITISDIGESTIVE ENDOSCOPY, Issue 3 2006Yasushi Umehara A 58-year-old man was admitted with upper abdominal pain and high fever. There was no abnormality on chest X-ray, abdominal ultrasonography, abdominal CT and upper gastrointestinal endoscopy. Antineutrophil cytoplasmic antibodies (C-ANCA) titers were high and a chest CT scan depicted multiple nodules in the bilateral lungs. A diagnosis of Wegener's granulomatosis was therefore made. Three weeks after admission, diarrhea and bloody stool developed. Colonoscopy revealed many aphthoid lesions surrounded by redness in the entire colon. Although the biopsy from aphtha did not show vasculitis or granuloma, the aphthoid lesions were suspected as a complication of Wegener's granulomatosis. As a result of predonisolone medication (60 mg/day), the plasma C-reactive protein (CRP) and high fever improved promptly. In conclusion, although colonic involvement in a patient with Wegener's granulomatosis is extremely rare, it is important to keep in mind that colonic lesions might be due to vasculitis in ANCA-positive disease, such as Wegener's granulomatosis. [source] Severe Intestinal Involvement In Wegener's GranulomatosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2003Fiona YF Chow No abstract is available for this article. [source] Otological Wegeners Granulomatosis: a diagnostic dilemmaCLINICAL OTOLARYNGOLOGY, Issue 6 2000M. A. Thornton No abstract is available for this article. [source] WEGENER'S GRANULOMATOSIS COMPLICATED WITH APHTHOID COLITISDIGESTIVE ENDOSCOPY, Issue 3 2006Yasushi Umehara A 58-year-old man was admitted with upper abdominal pain and high fever. There was no abnormality on chest X-ray, abdominal ultrasonography, abdominal CT and upper gastrointestinal endoscopy. Antineutrophil cytoplasmic antibodies (C-ANCA) titers were high and a chest CT scan depicted multiple nodules in the bilateral lungs. A diagnosis of Wegener's granulomatosis was therefore made. Three weeks after admission, diarrhea and bloody stool developed. Colonoscopy revealed many aphthoid lesions surrounded by redness in the entire colon. Although the biopsy from aphtha did not show vasculitis or granuloma, the aphthoid lesions were suspected as a complication of Wegener's granulomatosis. As a result of predonisolone medication (60 mg/day), the plasma C-reactive protein (CRP) and high fever improved promptly. In conclusion, although colonic involvement in a patient with Wegener's granulomatosis is extremely rare, it is important to keep in mind that colonic lesions might be due to vasculitis in ANCA-positive disease, such as Wegener's granulomatosis. [source] Single-stage surgical repair of benign laryngotracheal stenosis in adultsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2004Jolanda van den Boogert PhD Abstract Background. Benign laryngotracheal stenosis causes considerable morbidity. In a retrospective study, we describe the results of our surgical treatment. Methods. Between June 1999 and June 2002, 14 adults with laryngotracheal stenosis were referred to our hospital. Stenosis resulted from mechanical ventilation in 11 patients, from Wegener's granulomatosis in 2 patients, and from strangulation in 1 patient. Eleven patients had a tracheotomy. One patient was found unfit for surgery. Nine patients underwent cricotracheal resection (CTR) with end-to-end anastomosis, and four patients underwent single-stage laryngotracheoplasty (SS-LTP) without stenting. Results. There were no perioperative deaths. Patients were extubated after mean of 3 days (range, 0,10 days; CTR 2.3 days vs SS-LTP 3.5 days, p = .45). There were in-hospital complications in five patients. Mean hospital stay was 19 days (range, 8,53 days; after CTR 24 days vs SS-LTP 9 days, p = .015). With regard to airway patency and voice recovery, 10 patients (77%) had good results, including 1 patient with two readmissions, and 3 (23%) had satisfactory results, including 1 patient with 11 additional nonsurgical interventions. Conclusions . Benign laryngotracheal stenosis in the adult patient can be repaired successfully using a strategy of two single-stage surgical procedures. All patients had good or satisfactory functional results. A multidisciplinary approach was essential to achieve these good results. © 2004 Wiley Periodicals, Inc. Head Neck26: 111,117, 2004 [source] Epidemiology of primary systemic vasculitis in the Australian Capital Territory and south-eastern New South WalesINTERNAL MEDICINE JOURNAL, Issue 11 2008A. S. Ormerod Abstract Background:, The aim of the study was to determine the epidemiology of primary systemic vasculitis in the Australian Capital Territory and the surrounding rural region between 1995 and 2005. Methods:, Cases were ascertained by a medical record search according to international consensus classification criteria. For antineutrophil cytoplasmic antibody-associated vasculitides, ascertainment was corroborated by a search of all positive antineutrophil cytoplasmic antibody serology during the study period. Denominators were obtained from region-specific census data collected during the study period. Prevalence, incidence and patient characteristics for primary systemic vasculitides were determined for two 5-year periods, 1995,1999 and 2000,2004. Results:, We identified 41 cases of primary systemic vasculitides (Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg,Strauss syndrome or polyarteritis nodosa) between 1995 and 1999 and 67 between 2000 and 2004, giving prevalences of 95/million (95% confidence interval (CI) 76.9,116.1) and 148/million (95%CI 125.1,173.9), respectively. Annual incidence was similar in both periods (approximately 17/year per million adult population). Disease-specific incidences (per million per year) for each of the two periods were 8.8 and 8.4 for WG, 2.3 and 5.0 for MPA, 2.3 and 2.2 for Churg,Strauss syndrome and 2.3 and 1.1 for polyarteritis nodosa. The rural incidence of MPA was 13.9 (95%CI 7.7,23.5) compared with 1.6 (95%CI 0.2,7.2) in the city and there was a trend towards a higher incidence of WG in rural than urban areas. Conclusion:, The overall incidence of primary systemic vasculitides is similar to that reported from other developed countries. WG is more common in south-eastern Australia than in southern Europe, whereas MPA is less common. There was a trend towards higher incidence of antineutrophil cytoplasmic antibody-associated vasculitides in rural than urban areas. [source] Cutaneous sarcoid-like granulomas with alveolar hemorrhage and c-ANCA PR-3INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004Natividade Rocha MD A 28-year-old woman, employed as a leather factory worker, noted asymptomatic, well-delimited plaques on both knees, 6 years ago. The plaques were violaceous with a smooth surface. One appeared over a post-traumatic scar from childhood (Fig. 1). Two years later, she began to complain of symptoms suggestive of polyarthritis, first of the small joints of the hands (proximal interphalanges) and then of the larger joints (wrists, elbows, and knees). She was diagnosed with rheumatoid arthritis and began treatment with nonsteroidal anti-inflammatory drugs for 1 month without any change. Deflazacort, 12 mg/day, and hydroxychloroquine, 400 mg/day, were administered for 3 months, with improvement of her articular complaints, but not her skin lesions. Figure 1. Well-delimited, violaceous plaques with a smooth surface on the knees, one over an old post-traumatic scar One year later, she complained of dysphonia, which remitted spontaneously after some weeks. After one additional year, she noted papules, with similar characteristics to the plaques, on the elbows, and two well-delimited orange-to-brown plaques on the forehead (Fig. 2). Figure 2. Orange,brown plaques symmetrically placed on the forehead During the fifth year of the disease, she was referred for the first time to a dermatologist, who biopsied one of the knee lesions. The histologic result was compatible with "sarcoid granuloma." At that time, she presented with skin lesions as her only complaint. Sarcoidosis was suspected based on a chest X-ray, which revealed hilar lymphadenopathy and diffuse accentuation of the interstitium. In November 2000, she suddenly developed fever (40 °C), cough with hemoptysis, dysphonia, and subcutaneous nodules on the palmar surface of the fingers of both hands that were painless, well-delimited, 5 mm in diameter, and firm (Fig. 3). She reported a weight loss of 12 kg in the previous 3 months. Pulmonary condensation was found on auscultation, and she had palpable hepatomegaly. Peripheral lymphadenopathy was not present. Figure 3. Painless, well-delimited, firm subcutaneous nodules on the palmar surface of the fingers Laboratory investigations revealed normochromic, normocytic anemia (hemoglobin, 7.7 g/dL), iron deficit, a white blood cell count of 16,000/µL with neutrophilia, an erythrocyte sedimentation rate of 130 mm/h, elevation of liver enzymes, a slight increase in angiotensin-converting enzyme (ACE) level (72 U/L), hypergammaglobulinemia (IgG, 3350 mg/dL), antinuclear antibody (ANA) of 1 : 320, and a slight increase in CD4 and decrease in CD8 lymphocytes with normal cellular morphology in blood. Renal function, urine sediment, urine and serum calcium, complement (C4), dsDNA, antimitochondrial antibody, direct and indirect Coombs test, antineutrophil cytoplasmic antibody (ANCA), tuberculin skin tests, viral markers of hepatitis B, C, and human immunodeficiency virus (HIV), electrocardiogram (ECG), ophthalmic examinations, and culture for infectious agents in blood and sputum were all normal or negative. Computed tomography (CT) scan showed an infiltrate in the upper right pulmonary lobule with a central cavity and bilateral hilar lymphadenopathy (Fig. 4). Homogeneous hepatosplenomegaly was present. The bronchoalveolar lavage (BAL) showed a slight lymphocytic increase predominantly of CD8 cells and hemosiderosis. Stains for infectious agents, including acid-fast bacillus, fungi, Mycoplasma, and Legionella, were negative. Three biopsies from the forehead, elbows, and knees showed well-formed noncaseating epithelioid cell granulomas with giant cells of the Langhans type in the dermis, suggestive of sarcoidosis (Figs 5 and 6). A fourth biopsy from a finger nodule demonstrated inflammatory infiltration of the dermis and necrosis with cellular debris. Vasculitis was not seen (Fig. 7). Figure 4. Computed tomography scan showing an infiltrate in the upper right pulmonary lobule with a central cavity Figure 5. Beneath a flattened epidermis, several sarcoid granulomas composed of epithelioid histiocytes and several multinucleated giant cells of Langhans type can be seen (hematoxylin and eosin, ×10) Figure 6. Less well-formed sarcoid granulomas in a hyperkeratotic area, surrounded by a sparse rim of lymphocytes (hematoxylin and eosin, ×20) Figure 7. Foci of necrosis and fibrinoid degeneration with some neutrophil infiltration and nuclear dusting (hematoxylin and eosin, ×40) The patient was treated with a broad-spectrum empirical antimicrobial (levofloxacin, 500 mg daily intravenously) over 12 days, with prompt improvement in her symptoms and remission of the forehead and finger lesions. Nevertheless, on the first evaluation after hospitalization, the CT scan showed persistence of the pulmonary cavity (Fig. 8). A repeat ANCA determination was positive (cytoplasmic pattern, c-ANCA) at 1 : 640 by indirect immunofluorescence (IIF). Antiproteinase-3 antibody was demonstrated at 78 by enzyme-linked immunosorbent assay (ELISA). Figure 8. Computed tomography scan showing persistence of the pulmonary cavity She underwent an open lung biopsy which revealed intra-alveolar hemorrhage and scanty noncaseating epithelioid cell granulomas of the sarcoidosis type in the peripheral blood vessels without vasculitis. A diagnosis of Wegener's granulomatosis was made and she began prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). One year later, she is asymptomatic, the skin lesions have completely remitted, c-ANCA is negative, and the CT scan shows partial regression of the pulmonary cavity. [source] Cutaneous Wegener's granulomatosis (malignant pyoderma) in a patient with Crohn's diseaseINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2003Sharon E. Jacob MD We report a case of an unusual presentation of Wegener's granulomatosis (WG) in a patient with Crohn's disease (CD). She presented to our Wound Care Center with 7th cranial nerve palsy and facial pyoderma-like ulcerations. Although WG has a predilection for the lung, kidney, and eyes, cutaneous involvement can be seen in 50% of the cases, and it can be the presenting sign in 9,14%. Because of the lethality of WG if not properly treated, the diagnosis is imperative. [source] Wegener's granulomatosis presenting as pyoderma gangrenosumINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2003Hajnal Irén Szőcs MD A 59-year-old male patient developed a necrotizing ulceration on the right shin. Both clinical and histopathologic examinations suggested pyoderma gangrenosum. After temporary improvement of skin symptoms under peroral glucocorticoid treatment, a hemorrhagic-purulent discharge started from the nose, he began to have fever, malaise, cough, and a chest X-ray revealed inflammation in the lung. Cerebral CT and MRI disclosed midline bone loss within the nasal septum and granulomatosus tissue masses protruding into the right orbit. The c-ANCA test was positive, serum IgA was elevated, and he had microhaematuria and proteinuria. In this severe case of Wegener's granulomatosis prolonged methylprednisone and cyclophosphamide treatment was initiated. Both the skin symptoms and the granulomatosus infiltrations resolved. [source] Hyperbaric oxygen therapy for Wegener's granulomatosis with cyclophosphamide-induced hemorrhagic cystitisINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2002Isao Kuroda Abstract A 49-year-old man with Wegener's granulomatosis, who had been treated with cyclophosphamide, was admitted to our hospital experiencing gross hematuria. The hemorrhage was refractory to multiple conventional treatments. It progressed but later was resolved after a course of hyperbaric oxygen therapy. [source] Cutaneous manifestations of Wegener's granulomatosis: a clinicopathologic study of 17 patients and correlation to antineutrophil cytoplasmic antibody statusJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2007Nneka I. Comfere Background:, Wegener's granulomatosis (WG), a systemic vasculitis, can be associated with cutaneous signs and symptoms before, during or after the diagnosis of systemic disease. Methods:, We reviewed clinical and histologic features of cutaneous lesions from 17 patients with WG. The temporal relationship between development of cutaneous symptoms and onset of systemic disease was determined, and antineutrophil cytoplasmic antibody (ANCA) status of the patients was also established. Results:, In six patients, systemic and cutaneous disease developed concurrently. In eight patients, cutaneous disease developed after patients received the diagnosis of systemic disease. In three patients, cutaneous disease preceded systemic disease. Cytoplasmic ANCA or proteinase-3-ANCA [c-ANCA/proteinase 3 (PR3)-ANCA] serologic test results were negative for one patient when cutaneous disease developed, and one patient had c-ANCA/PR3-ANCA seroconversion a year before systemic disease developed. Histopathologic features of cutaneous WG were not limited to leukocytoclastic vasculitis; they also included acneiform perifollicular and dermal granulomatous inflammation and palisaded neutrophilic and granulomatous inflammation. Conclusions:, Patients with WG can present initially with cutaneous symptoms. Histopathologic patterns vary, but leukocytoclastic vasculitis is most commonly noted. Patients with WG and skin lesions are likely to have positive c-ANCA/PR3-ANCA serologic test results. [source] Collagenolytic (necrobiotic) granulomas: part II , the ,red' granulomasJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2004Jane M. Lynch The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red). These color distinctions can be used as a simple algorithm for the diagnosis of collagenolytic granulomas, i.e. ,blue' granulomas vs. ,red' granulomas. Eight diagnoses are included within these two groupings, which are discussed in this two-part article. In the previously published first part, the clinical presentation, pathogenesis and histologic features of the ,blue' collagenolytic granulomas were discussed. These are the lesions of granuloma annulare, Wegener's granulomatosis, and rheumatoid vasculitis. In this second half of the series, the ,red' collagenolytic granulomas are discussed; these are the lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg,Strauss syndrome, and eosinophilic cellulitis (Well's Syndrome). [source] Collagenolytic (necrobiotic) granulomas: part 1 , the ,blue' granulomasJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2004Jane M. Lynch A collagenolytic or necrobiotic non-infectious granuloma is one in which a granulomatous infiltrate develops around a central area of altered collagen and elastic fibers. The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red). These color distinctions can be used as a simple algorithm for the diagnosis of collagenolytic granulomas, i.e. ,blue' granulomas vs. ,red' granulomas. Eight diagnoses are included within these two groupings, which are discussed in this two-part article. In this first part, the clinical presentation, pathogenesis, and histologic features of the ,blue' collagenolytic granulomas are discussed. These are the lesions of granuloma annulare, Wegener's granulomatosis, and rheumatoid vasculitis. In the subsequent half of this two-part series, the ,red' collagenolytic granulomas will be discussed; these are the lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg,Strauss syndrome, and eosinophilic cellulitis (Well's syndrome). [source] Cutaneous vasculitis: a reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2003A. Neil Crowson As the skin is commonly involved in systemic vasculitic disorders as well as those hypersensitivity states whose expression is largely skin-confined, cutaneous vasculitic lesions offer a window to diagnosis and a ready source of accessible tissue for biopsy. In this review, we discuss the pathologic manifestations of chronic vasculitic syndromes such as granuloma faciale and erythema elevatum diutinum; IgA-associated vasculitis including Henoch-Schonlein purpura; vasculitis seen in the setting of cryoglobulinemia and hypergammaglobulinemia of Waldenstrom, hereditary deficiencies of complement, and IgA deficiency; those leukocytoclastic vasculitides resulting from hypersensitivity reactions to drug, chemical and foodstuff ingestion; and those vasculitides seen in patients with systemic diseases such as polyarteritis nodosa, rheumatoid arthritis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome, relapsing polychondritis, Behcet's disease, Wegener's granulomatosis, and allergic granulomatosis of Churg and Strauss. [source] Effector memory T cells as driving force of granuloma formation and autoimmunity in Wegener's granulomatosisJOURNAL OF INTERNAL MEDICINE, Issue 3 2006P. Lamprecht First page of article [source] Cerebral and Oculorhinal Manifestations of a Limited Form of Wegener's Granulomatosis With c-ANCA,Associated VasculitisJOURNAL OF NEUROIMAGING, Issue 1 2001Peterus Thajeb MD ABSTRACT The authors report on cerebral and oculorhinal manifestations in a patient with a cytoplasmic pattern of antineutrophil cytoplasmic autoantibody (c-ANCA),associated vasculitis. Recurrent Tolosa-Hunt syndrome, cavernous sinus syndrome, Raeder's paratrigeminal neuralgia, and seizures were the major clinical manifestations. Brain MRI showed localized enhancing lesions initially in the cavernous sinus and later in the convexity pachymeninges. The lesions disappeared following 9 months of oral prednisolone (15 mg/day) and cyclophosphamide (100 mg/day) therapy. The presence of c-ANCA, demonstration of vasculitis, and depositions of immunoglobulin G (IgG) and fibrinogen in the vessel walls of pachymeninges of the patient confirmed an immune-mediated cause of the vasculitis. Cranial pathology without renal and pulmonary involvement suggests a variant of Wegener's granulomatosis, which is called the "limited" form of Wegener's granulomatosis. [source] Antineutrophil cytoplasmic antibody-associated glomerulonephritis in TaiwaneseNEPHROLOGY, Issue 5 2004PEIR-HAUR HUNG SUMMARY: Aims: This retrospective study defined the clinical features and outcome of antineutrophil cytoplasmic antibody-associated glomerulonephritis in 18 seropositive Taiwanese patients (11 male, seven female; median age 64 years; range 21,82 years) with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis. Results: Fourteen patients had a diagnosis of systemic vasculitis including 10 with microscopic polyangiitis and four with Wegener's granulomatosis; the remaining four had only glomerulonephritis. At onset, 100% of the systemic vasculitis patients had pulmonary lesions with or without haemoptysis, and 29% presented with seizure in the absence of a defined brain lesion. Median serum creatinine concentration was 362.4 µmol/L (range 61.9,857.5 µmol/L) and dialysis therapy was needed in six patients. During follow up (median 16.5 months; range 2,72 months), treatment included cyclophosphamide and corticosteroids (n = 8) or corticosteroids alone (n = 7). In some patients, treatment improved (n = 4) or stabilized (n = 4) renal function. But chronic dialysis was needed in the other 10 patients. Follow-up death occurred because of sepsis (n = 3) and haemorrhage (n = 2). Patient survival rates were 78% (1 year) and 72% (5 years). Renal survival rates were 56 and 39% at 1 and 5 years, respectively. Of the candidate clinical and pathological parameters, chronic glomerular lesions in renal biopsy were the only determinant of poor renal outcome (P = 0.006). Conclusion: Antineutrophil cytoplasmic antibody-associated glomerulonephritis should be considered in nephritic patients with extrarenal manifestations, especially pulmonary infiltrate, unexplained seizure, and fever of an unknown origin in Taiwanese patients. Renal biopsy should be performed before initiating immunosuppressive therapy because the most common cause of mortality was sepsis. [source] Distinguishing Wegener's granulomatosis from necrotizing community acquired pneumonia: A case report and comparison of radiographic findings,PEDIATRIC PULMONOLOGY, Issue 2 2009Steven J Spalding MD Abstract Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis, affecting medium to small vessels in the respiratory and renal vasculature. Patients with WG may present with clinical and radiographic features similar to community-acquired pneumonia (CAP), which may delay life-saving immunosuppressive therapy. We report a 14-year-old female originally diagnosed with recalcitrant, necrotizing CAP complicated by massive pulmonary cavitations eventually proven to be WG. We also compare the radiographic features of WG and necrotizing CAP. Pediatr Pulmonol. 2009; 44:195,197. © 2009 Wiley-Liss, Inc. [source] Microscopic polyangiitis or Wegener's granulomatosis?RESPIROLOGY, Issue 2 2006That is the question No abstract is available for this article. [source] New algorithm (KAWAKAMI algorithm) to diagnose primary cutaneous vasculitisTHE JOURNAL OF DERMATOLOGY, Issue 2 2010Tamihiro KAWAKAMI Abstract Palpable purpura tends to indicate involvement of small vessel vasculitis in the upper dermis. Livedo racemosa, nodular lesion and skin ulceration are indicative of involvement of small to medium-sized vessel vasculitis in the lower dermis to subcutaneous fat. We set out to establish a new algorithm (KAWAKAMI algorithm) for primary cutaneous vasculitis based on the Chapel Hill Consensus Conference classification and our research results, and apply to the diagnosis. The first step is to measure serum antineutrophil cytoplasmic antibodies (ANCA) levels. If myeloperoxidase-ANCA is positive, Churg,Strauss syndrome or microscopic polyangiitis can be suspected, and if the patient is positive for proteinase 3-ANCA, Wegener's granulomatosis is most likely. Next, if cryoglobulin is positive, cryoglobulinemic vasculitis should be suspected. Third, if direct immunofluorescence of the skin biopsy specimen reveals immunoglobulin A deposition within the affected vessels, Henoch,Schönlein purpura is indicated. Finally, the presence of anti-phosphatidylserine,prothrombin complex antibodies and/or lupus anticoagulant and histopathological necrotizing vasculitis in the upper to middle dermis (leukocytoclastic vasculitis) indicates cutaneous leukocytoclastic angiitis, whereas if necrotizing vasculitis exists in the lower dermis and/or is associated with the subcutaneous fat, cutaneous polyarteritis nodosa is indicated. The KAWAKAMI algorithm may allow us to refine our earlier diagnostic strategies and allow for efficacious treatment of primary cutaneous vasculitis. In cutaneous polyarteritis nodosa, warfarin or clopidogrel therapies should be administrated, and in cases that have associated active inflammatory lesions, corticosteroids or mizoribine (mycophenolate mofetil) therapy should be added. We further propose prophylactic treatment of renal complications in patients with Henoch,Schönlein purpura. [source] Glomerular and tubular induction of the transcription factor c-Jun in human renal disease,THE JOURNAL OF PATHOLOGY, Issue 2 2007MH De Borst Abstract The transcription factor c-Jun regulates the expression of genes involved in proliferation and inflammation in many cell types but its role in human renal disease is largely unclear. In the current study we investigated whether c-Jun activation is associated with human renal disease and if c-Jun activation regulates pro-inflammatory and pro-fibrotic genes in renal cells. Activation of c-Jun was quantified by scoring renal expression of phosphorylated c-Jun (pc-Jun) in control human renal tissue and in biopsies from patients with various renal diseases (diabetic nephropathy, focal glomerulosclerosis, hypertension, IgA nephropathy, membranous glomerulopathy, minimal change disease, membranoproliferative glomerulonephritis, systemic lupus erythematosus, acute rejection, and Wegener's granulomatosis); this was correlated with parameters of renal damage. Furthermore, we studied the functional role of c-Jun activation in human tubular epithelial cells (HK-2) stimulated with TGF-,. Activated c-Jun was present in nuclei of glomerular and tubular cells in all human renal diseases, but only sporadically in controls. Across the diseases, the extent of pc-Jun expression correlated with the degree of focal glomerulosclerosis, interstitial fibrosis, cell proliferation, kidney injury molecule-1 (Kim-1) expression, macrophage accumulation, and impairment of renal function. In HK-2 cells, TGF-, induced c-Jun activation after 1 h (+40%, p < 0.001) and 24 h (+160%, p < 0.001). The specific c-Jun N-terminal kinase (JNK) inhibitor SP600125 abolished c-Jun phosphorylation at all time points and blunted TGF-,- or BSA-induced procollagen-1, 1 and MCP-1 gene expression in HK-2 cells. We conclude that in human renal disease, the transcription factor c-Jun is activated in glomerular and tubular cells. Activation of c-Jun may be involved in the regulation of inflammation and/or fibrosis in human renal disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Granuloma formation in ANCA-associated vasculitidesAPMIS, Issue 2009PETER LAMPRECHT Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg,Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing ,NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity. [source] Epidemiological features of Wegener's granulomatosis and microscopic polyangiitis: two diseases or one ,anti-neutrophil cytoplasm antibodies-associated vasculitis' entity?APMIS, Issue 2009ALFRED D. MAHR Because of their multiple overlapping clinical characteristics, Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have increasingly been conceptualized as different expressions of a unique anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AAV) disease spectrum. However, this continuum theory remains hindered by uncertainty surrounding a potentially common etiology. This review sheds light on our current understanding of the epidemiology of WG and MPA with the aim of weighing the evidence supporting whether or not these two vasculitis forms are distinct diseases. At present, some epidemiological evidence exists that WG and MPA might correspond to mere variants of a single AAV entity. [source] Most proteinase3- and myeloperoxidase-antineutrophil cytoplasmic antibodies enzyme-linked immunosorbent assays perform less well in treated small-vessel vasculitis than in active diseaseAPMIS, Issue 2009JUDY SAVIGE Antineutrophil cytoplasmic antibodies (ANCA) levels have been thought to follow disease activity, with levels being high at presentation, declining with treatment and increasing just before relapse. However, we have shown that ANCA often persist for many years in patients with clinically inactive Wegener's granulomatosis. ANCA assays are less sensitive for treated disease than for active disease, and the levels in treated patients produce different results in different assay systems. ANCA often persist for years without relapse, and the risk of relapse probably depend on levels that are critical for any individual patient. The capture enzyme-linked immunosorbent assays may be more sensitive in detecting early relapse. Relapse is more common when ANCA levels are high but, although elevated, ANCA levels are lower in relapse than at presentation. Standardized ANCA levels for the definitions of remission and relapse may not be possible, and the optimal ANCA testing protocol for treated disease remains unclear. [source] Epitope-specific anti-neutrophil cytoplasmic antibodies: Do they matter?APMIS, Issue 2009Can they be detected? Proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase (MPO)-ANCA are suggested to play a pathogenic role as they are closely related to the small-vessel vasculitis syndromes, Wegener's granulomatosis and microscopic polyangiitis. A large body of in vitro and animal experiments supports this concept. The mechanisms of action involve a direct interaction between ANCA and its antigen. The epitope specificity of ANCA may therefore influence the functional effects of ANCA and/or may reflect the mechanisms behind different disease manifestations or disease courses. [source] Transcription of proteinase 3 and related myelopoiesis genes in peripheral blood mononuclear cells of patients with active Wegener's granulomatosisARTHRITIS & RHEUMATISM, Issue 6 2010Chris Cheadle Objective Wegener's granulomatosis (WG) is a systemic inflammatory disease that is associated with substantial morbidity. The aim of this study was to understand the biology underlying WG and to discover markers of disease activity that would be useful for prognosis and treatment guidance. Methods Gene expression profiling was performed using total RNA from peripheral blood mononuclear cells (PBMCs) and granulocyte fractions from 41 patients with WG and 23 healthy control subjects. Gene set enrichment analysis (GSEA) was performed to search for candidate WG-associated molecular pathways and disease activity biomarkers. Principal components analysis was used to visualize relationships between subgroups of WG patients and controls. Longitudinal changes in proteinase 3 (PR3) gene expression were evaluated using reverse transcription,polymerase chain reaction, and clinical outcomes, including remission status and disease activity, were determined using the Birmingham Vasculitis Activity Score for WG (BVAS-WG). Results Eighty-six genes in WG PBMCs and 40 in WG polymorphonuclear neutrophils (PMNs) were significantly up-regulated relative to controls. Genes up-regulated in WG PBMCs were involved in myeloid differentiation, and these included the WG autoantigen PR3. The coordinated regulation of myeloid differentiation genes was confirmed by GSEA. The median expression values of the 86 up-regulated genes in WG PBMCs were associated with disease activity (P = 1.3 × 10,4), and WG patients with low-level expression of the WG signature genes showed expression profiles that were only modestly different from that in healthy controls (P = 0.07). PR3 transcription was significantly up-regulated in WG PBMCs (P = 1.3 × 10,5, false discovery rate [FDR] 0.002), but not in WG PMNs (P = 0.03, FDR 0.28), and a preliminary longitudinal analysis showed that the fold change in PR3 RNA levels in WG PBMCs corresponded to changes in the BVAS-WG score over time. Conclusion Transcription of PR3 and related myeloid differentiation genes in PBMCs may represent novel markers of disease activity in WG. [source] An increased risk of ischemic heart disease in Wegener's granulomatosis: Comment on the article by Faurschou et alARTHRITIS & RHEUMATISM, Issue 2 2010Matthew D. Morgan MRCP No abstract is available for this article. [source] Classification, presentation, and initial treatment of Wegener's granulomatosis in childhoodARTHRITIS & RHEUMATISM, Issue 11 2009David A. Cabral Objective To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA),associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Methods Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. Results MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4,17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0,49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). Conclusion The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers. [source] Cellular immunity in Wegener's granulomatosis: Characterizing T lymphocytesARTHRITIS & RHEUMATISM, Issue 6 2009Annelies E. Berden First page of article [source] Rituximab is effective in the treatment of refractory ophthalmic Wegener's granulomatosisARTHRITIS & RHEUMATISM, Issue 5 2009Simon R. J. Taylor Objective To investigate the efficacy of rituximab in patients with refractory ophthalmic Wegener's granulomatosis (WG). Methods Data from 10 consecutive patients with refractory ophthalmic WG treated with rituximab were retrospectively reviewed. In all patients, the ophthalmic disease was driving treatment decisions, and disease activity had persisted despite standard immunosuppressive treatment. Patients had refractory scleritis (n = 3), orbital granulomas causing optic nerve compromise (n = 4), or a combination of both conditions (n = 3). All patients had been treated with at least 3 different immunosuppressive agents, and 5 patients had previously been treated with tumor necrosis factor , blockade. Rituximab was administered intravenously in 2 doses, 2 weeks apart, in combination with standard treatment. Disease activity was monitored clinically by an interdisciplinary approach, including disease activity scoring, immunodiagnostics, and magnetic resonance imaging, as well as by corresponding reductions in the required dose of conventional medication. Results A beneficial response to treatment with rituximab was seen in all 10 patients, including induction of clinical remission. In all patients, the peripheral blood B cell count fell to zero during treatment with rituximab. Titers of classic antineutrophil cytoplasmic antibodies fell in association with B cell counts, and this reduction was correlated with improved clinical findings. Conclusion In contrast to previous observations, this study showed that treatment with rituximab was associated with clinical improvement in patients with refractory ophthalmic WG. [source] | |||||||||||||||||||||||||||||||