phenylephrine-hydrochloride and Granulomatosis-with-Polyangiitis

Granulomatosis with polyangiitis (Wegener's, GPA) is an uncommon disease of unknown etiology classically involves the ELK triad of the ear, nose, throat (E), lungs (L) and kidneys (K) with necrotizing granulomatous inflammation and vasculitis. Most of the initial symptoms begin in the head and neck region with a wide spectrum of involvement of any site ranging from the nasal septum, paranasal sinuses, oral mucosa, larynx and even the external, middle and internal ear. Diagnosis may be delayed because the onset is heterogeneous and sometimes limited to one organ. The pathologic findings of a characteristic inflammatory reaction pattern, and the serum findings of elevated antineutrophil cytoplasmic antibodies can help to establish the diagnosis. The differentiation from other conditions that mimic GPA such as lymphoma and infections is of critical importance to initiate appropriate treatment. Treatment of the underlying disease is medical with the use of immunosuppressive agents and will not be reviewed here. This review focuses on the otorhinolaryngologic manifestation and complication of GPA as well as their surgical management and specifies the role of the otorhinolaryngologist as an integral member of the multidisciplinary care team for patients with GPA.

Topics: Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Nose; Paranasal Sinuses

Topics: Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Humans; Nose; Nose Deformities, Acquired; Sinusitis

We describe a 36-year-old patient with an aggressive, midline intranasal and naso- and oropharyngeal destructive process. For months the patient denied heavy abuse of nasal cocaine, but finally admitted it. Necrosis and atrophy of the inferior and middle nasal turbinates bilaterally, prominent naso and oropharyngeal ulcers, nasal septal as well as hard palate perforation were observed clinically. Repeated biopsies revealed focal areas of chronic inflammation and necrosis, but there was no evidence of vasculitis or granuloma formation. Since serum was slightly positive for antineutrophil cytoplasmic antibody, the initial diagnosis was Wegener's granulomatosis. In the United States there have been a few reports on a new cocaine-associated syndrome presenting as an aggressive, midline, intranasal and intrapharyngeal destructive process mimicking limited Wegener's granulomatosis and midline reticulosis. We report the first such case in Europe and offer guidelines for the diagnostic work-up of such cases.

Topics: Adult; Biopsy; Cocaine-Related Disorders; Diagnosis, Differential; Disease Progression; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Male; Necrosis; Nose; Palate

The ureter is an unusual location for lesions of Wegener's granulomatosis (WG). A patient in whom recurrence of WG after kidney transplantation was manifested by obstructive uropathy due to granulomatous vasculitis (WG) at the ureterovesicle anastomosis, as well as nasal and lung involvement, is reported. The occurrence of WG in the ureter in relation to the processes causing ureteral obstruction and the recurrences of WG after kidney transplantation and its treatment are briefly reviewed.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Child; Combined Modality Therapy; Diagnostic Errors; Female; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Kidney Glomerulus; Kidney Transplantation; Lung; Male; Nose; Postoperative Complications; Recurrence; Ureteral Obstruction

Topics: Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Eye; Granulomatosis with Polyangiitis; Humans; Hypersensitivity; Lung; Nose; Prednisolone

Topics: Blood Protein Electrophoresis; Cilia; Diagnosis, Differential; Granuloma; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Herpes Simplex; Humans; Kidney Transplantation; Leishmaniasis, Mucocutaneous; Leprosy; Lysosomes; Microscopy, Electron; Mycoses; Nasal Polyps; Nose; Postoperative Complications; Prognosis; Respiratory Tract Diseases; Rhinitis; Rhinoscleroma; Sarcoidosis; Syphilis; Transplantation, Homologous; Tuberculosis; Tuberculosis, Laryngeal

The aim of this study was to evaluate whether chronic nasal carriage of Staphylococcus aureus (SA) is related to relapses in patients with newly diagnosed ANCA-associated vasculitis (AAV).. In two clinical trials (n = 200), for early systemic (n = 83) and generalized (n = 117) AAV, nasal swabs were obtained monthly and at the time of a relapse. Chronic nasal SA carriage (CNSAC) was defined as ⩾ 75% of cultures being SA positive, with non-carriers being SA negative in all cultures and remaining patients being intermittent carriers. Fifty-five of 200 (27.5%) patients received prophylactic trimethoprim/sulfamethoxazole (T/S) against Pneumocystis jirovecii .. Of the total AAV patients, 24/200 (12%) were chronic, 102/200 (51%) intermittent and 74/200 (37%) non-carriers. Of 65 relapsing patients, 10/24 (41.7%) were chronic, 32/102 (31.4%) intermittent and 23/74 (31.1%) non-carriers (P = 0.59). For all AAV patients, CNSAC was not associated with an increased relapse risk [odds ratio (OR) = 1.57, 95% CI: 0.66, 3.76; P = 0.31]. However, 23/24 chronic carriers had granulomatosis with polyangiitis (GPA). In the 73 patients with generalized GPA (hazard ratio = 4.10, 95% CI: 1.37, 12.25; P = 0.01) and the 78 patients with early systemic GPA during immunosuppression (hazard ratio = 2.73, 95% CI: 0.95, 7.87; P = 0.06), relapse rates were higher for chronic SA carriers. Prophylactic T/S was not associated with a reduced relapse risk (OR = 0.71, 95% CI: 0.36, 1.41; P = 0.33). Nevertheless, prophylactic T/S reduced CNSAC (OR = 0.19, 95% CI: 0.04, 0.91; P = 0.04).. The frequency of CNSAC in newly diagnosed GPA paralleled that in the general population. This subset of GPA patients (23/151, 15.2%) has a high relapse rate despite immunosuppression and prophylactic T/S treatment, requiring further investigations on pathogenesis and therapy.

Topics: Adolescent; Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Nose; Prospective Studies; Recurrence; Specimen Handling; Staphylococcal Infections; Staphylococcus aureus; Young Adult

A 15-year-old boy presented with acne and ulceration since 2 years. After treatment with antibiotics, excision and isotretinoïne, he developed progressive complaints of malaise and respiratory complaints including formation of nasal crusts. Diagnostic evaluation (CT-thorax, ANCA anti-PR3) revealed the diagnosis granulomatosis with polyangiitis (GPA).

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Face; Granulomatosis with Polyangiitis; Humans; Isotretinoin; Male; Nose

Granulomatosis with polyangiitis is a rare chronic rheumatologic systemic disease with a vasculitis of small- and medium-size vessels. Mostly the upper airways, lung and kidneys are affected. Symptoms are unspecific. Patients complain about stuffy nose, crustiness of nasal secretions, ulcera of the oral mucosa or epistaxis. The otorhinolaryngologist may be the first one to evaluate the patient's health condition. Long term complications may be cardial, renal or pulmonal failure. To this day the aetiology is still unknown. Severe disease is treated with a combination of immunosuppressive medications. Clinic examinations and laboratory tests should be carried out for life-time.. Die Granulomatose mit Polyangiitis ist eine seltene chronische rheumatologische Systemerkrankung, die mit einer Vaskulitis der kleinen und mittleren Gefäße einhergeht. Am häufigsten betrifft sie die oberen Atemwege, die Lunge und die Nieren. Die Beschwerden sind unspezifisch, häufig beklagen die Patienten anfangs eine Nasenatmungsbehinderung, Borkenbildung in der Nase, Ulzera der Mundschleimhäute oder Epistaxis. Nicht selten wird deshalb der Hals-Nasen-Ohren-Arzt zu Beginn der Krankheit hinzugezogen. Langfristig können schwerwiegende kardiale, renale oder pulmonale Komplikationen auftreten. Die Ätiologie ist bis heute nicht komplett geklärt. Als Therapie wird eine Immunsuppression eingeleitet. Klinische und laborchemische Kontrollen sind lebenslang obligat.

Topics: Granulomatosis with Polyangiitis; Humans; Nose

Topics: Biopsy; Granulomatosis with Polyangiitis; Head; Humans; Neck; Nose

Topics: Adult; Female; Granulomatosis with Polyangiitis; Humans; Nose; Paranasal Sinuses; Sinusitis; Tomography, X-Ray Computed

Granulomatosis with polyangiitis (GPA) is an autoimmune disease leading to necrotizing lesions in the affected tissues. Computed tomography (CT) of paranasal sinuses reveals multiple lesions in patients with GPA, for example, sinus opacification, bone / cartilage destruction, and neoosteogenesis.. We aimed to describe and compare CT lesions found in patients with GPA and those with chronic rhinosinusitis (CRS) and to propose a new radiological marker of GPA-nasal strands.. This retrospective study (2014-2019) included 53 patients with GPA (22 men, 31 women) at a median (interquartile range) age of 45 (34-60) years. Computed tomography findings of mucosal lesions in paranasal sinuses, neoosteogenesis, bony and cartilaginous lesions, and nasal strands were analyzed. Nasal strands were described as intermucosal adhesions resembling bands. A total of 71 patients with CRS (reference group) were assessed for the presence of the same parameters.. Computed tomography scans showed mucosal lesions in the sinuses of 35 patients (66%) with GPA. Nasal septum perforation was observed in 19 patients (35.8%), neoosteogenesis in 17 (32.1%), and bone damage in 14 (26.4%). External nose deformity was present in 16 patients (30.2%). Nasal strands on CT were found in 36 patients with GPA (68%) and 32 patients with CRS (45%). The presence of 5 or more strands was more characteristic of GPA than CRS (P <0.001). A positive correlation was found between the number of strands greater than or equal to 5 and the presence of proteinase 3 antineutrophil cytoplasmic antibodies (P = 0.046).. Nasal strands, a parameter reflecting pathologic mucus and atrophic lesions (tissue loss), should have a place in CT evaluation of the nasal cavities in patients suspected of or diagnosed with GPA.

Topics: Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Nose; Paranasal Sinuses; Retrospective Studies; Sinusitis

Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap.. The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B. Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Female; Granulomatosis with Polyangiitis; Humans; Male; Metagenome; Microbiota; Middle Aged; Nose; Pilot Projects; Staphylococcal Infections; Staphylococcus; Young Adult

Topics: Granulomatosis with Polyangiitis; Humans; Nose; Staphylococcus

Nasal biopsy is the essential method for differentiating and diagnosing granulomatosis with polyangiitis (GPA) in patients with chronic rhinosinusitis. Nevertheless, in the real clinical settings, there are several cases unable for nasal biopsy. Hence, in this study, we investigated initial clinical manifestations and laboratory factors which could be helpful for diagnosing GPA in cases unable for nasal biopsy performance. We retrospectively reviewed the medical records of 45 patients with GPA. Twenty-five patients exhibited chronic rhinosinusitis, among which 16 patients underwent nasal biopsy. We applied the 2007 European Medicines Agency algorithm for the classification of GPA, the 2012 Chapel Hill Consensus Conferences Nomenclature of Vasculitis and the 2017 American College of Rheumatology/European League Against Rheumatism provisional classification criteria for GPA to them for reclassifying GPA. Among six patients without granuloma on nasal biopsy, three patients with only antineutrophil cytoplasmic antibody (ANCA) and chronic rhinosinusitis could be classified as GPA due to proteinase 3 (PR3)-ANCA (or cytoplasmic (C)-ANCA) positivity. Among nine patients without nasal biopsy, three patients with only chronic rhinosinusitis could be classified as GPA due to GPA-specific lung lesions. When we excluded an item of granuloma in ten GPA patients with granuloma on nasal biopsy, four patients without ANCAs could be classified as GPA due to GPA-specific lung lesions and cartilaginous involvement. In conclusion, PR3-ANCA (or C-ANCA) positivity, GPA-specific lung lesions and cartilaginous involvement could help physicians in charge make a final diagnosis of GPA in cases unable for nasal biopsy.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Cartilage Diseases; Child; Female; Granulomatosis with Polyangiitis; Humans; Lung Diseases; Male; Middle Aged; Myeloblastin; Nose; Retrospective Studies; Rhinitis; Sinusitis; Young Adult

Topics: Adult; Aged; Chronic Disease; Eosinophils; Female; Granulomatosis with Polyangiitis; Humans; Intercellular Adhesion Molecule-1; Leukocyte Count; Male; Middle Aged; Nasal Polyps; Nose; Prospective Studies; Sinusitis; Vascular Cell Adhesion Molecule-1

Topics: Adult; Continuous Positive Airway Pressure; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Masks; Nose; Nose Deformities, Acquired; Polysomnography; Sleep Apnea, Obstructive; Treatment Outcome; Weight Gain

Topics: Adult; Female; Granulomatosis with Polyangiitis; Humans; Nose; Nose Deformities, Acquired; Rhinoplasty; Treatment Outcome

Topics: Granulomatosis with Polyangiitis; Humans; Nose; Nose Deformities, Acquired; Nose Diseases; Rhinoplasty

Objective To determine the predictive value of nasal endoscopic findings and symptoms in the diagnosis of granulomatosis with polyangiitis (GPA). Study Design A cross-sectional study. Setting A tertiary university hospital. Subjects and Methods A total of 116 adults were enrolled in the study: 19 patients with GPA, 29 patients with other rheumatic diseases, and 68 healthy volunteers. All patients were examined with a flexible endoscope, and nasal endoscopic images were recorded and evaluated blindly. The medical history of each patient was taken by a physician blinded to the patient's diagnosis. Results Univariate analysis indicated a statistically significant difference in rhinorrhea ( P = .002), postnasal drip ( P = .015), epistaxis ( P < .001), and saddle nose ( P = .017). However, binary logistic regression analysis demonstrated that only history of epistaxis ( P = .012; odds ratio, 5.6) was statistically significant in predicting GPA. Univariate analysis showed a statistically significant difference in nasal secretion ( P = .028), nasal septal perforation ( P < .017), nasal crusting ( P < .001), nasal adhesion ( P < .001), nasal granuloma ( P = .017), and hemorrhagic fragile nasal mucosa ( P < .001). A binary logistic regression analysis demonstrated that only hemorrhagic fragile nasal mucosa ( P < .001; odds ratio, 52.9) was a statistically significant predictor of GPA. Conclusions Given the results of this study, we believe that hemorrhagic fragile nasal mucosa and history of recurrent epistaxis may put patients at risk for GPA and should be investigated accordingly.

Topics: Cross-Sectional Studies; Endoscopy; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Nose; Predictive Value of Tests

The authors present four cases of Wegener's granulomatosis patients with multiorganic manifestation forms, but with a prevalent involvement in upper-airway. Granulomatosis diseases of the nose include bacterial infections (rhinoscleroma, tuberculosis, syphilis, lupus, and leprosy), fungal infections (rhinosporidiosis, aspergillosis, mucormycosis, candidosis, histoplasmosis, and blastomycosis) and diseases with unspecified etiology (Wegener's granulomatosis, mediofacial malignant granuloma, and sarcoidosis). We consider an interesting experience regarding Wegener's granulomatosis due to its rarity, being an autoimmune systemic disease, with continuous evolution and multiorganic involvement. The beginning of the disease is like upper airway affection, a kind of "persistent cold", being difficult to differentiate it from a common cold in the head, with a prolonged evolution. It is important to mention that we establish the diagnosis of Wegener's granulomatosis starting with Ear Nose and Throat (ENT) clinical exam, followed by other tests and investigations realized in our Clinic and completed with specialty tests (nephrology, internal medicine and dermatology), meaning that we need a close cooperation with these medical specialties. All the patients presented multiorganic involvement. Notably significant for our four cases is the prolonged evolution in a stable condition in one patient.

Topics: Adult; Endoscopy; Female; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Inflammation; Larynx; Male; Middle Aged; Nose; Skin

To raise awareness of granulomatosis with polyangiitis by summarizing its nasal mani- festations and treatment experience.. Retrospective studies were done to the nasal clinical manifestations and treatment processes of 21 GPA patients in this study. All were treated by the combined treatment of glucocorticoid, cyclophosphamide as well as tripterygium wilfordii, and 4 of them who had much heavier nasal symptoms were treated by endoscopic sinus operation at the same time.. Eighteen cases were effective treated by medical treatments besides 3 were died of all 21 cases. The nasal symptoms of those 4 patients were obviously improved, and still had effective drainage of sinus after operation with 8-22 months follow up, although the sinus ostiums were reduced comparing to themselves intraoperation at different degree.. GPA is always been ignored which will lead to delay treatment due to the lack of specificity of its clinical manifestations. So, enough attention is the key point of avoiding misdiagnosis as well as providing timely treatment for these patients.

Topics: Combined Modality Therapy; Diagnostic Errors; Drainage; Endoscopy; Granulomatosis with Polyangiitis; Humans; Nose; Paranasal Sinuses; Retrospective Studies

Topics: Aged; Biopsy; Diagnosis, Differential; Endoscopy; Granulomatosis with Polyangiitis; Humans; Male; Nose; Orbital Diseases; Tomography, X-Ray Computed

Wegener granulomatosis (WG) has previously been associated with increased nasal carriage of Staphylococcus aureus, but no studies have investigated the occurrence of pathogen growth in the lower airways.. To culture bronchoalveolar lavage fluid (BALF) from patients with WG, patients with idiopathic pulmonary fibrosis (IPF) and normal controls.. 33 patients with WG, 22 with IPF and 8 normal controls underwent bronchoscopy and bronchoalveolar lavage. Quantitative culture established bacterial levels in the lower airways. Culture experiments were designed to investigate whether BALF is a supportive environment for S aureus growth. BALF cytokines were measured by ELISA.. Pathogens were commonly grown from BALF of patients with WG and those with IPF. S aureus was particularly associated with patients with WG both in relapse and in remission. BALF levels of interleukin 1 receptor antagonist (IL1ra) were statistically significantly elevated in those patients who grew a pathogen from lavage fluid. BALF from patients with WG and IPF stimulated S aureus growth compared with normal lavage fluid.. Pathogens are more commonly isolated from BALF from patients with WG than from that of patients with IPF or normal controls, and with a different culture profile. IL1ra was associated with pathogen growth in WG and IPF. WG BALF is a trophic environment for S aureus growth. Pulmonologists treating patients with acute or relapsing WG should consider bronchoscopic microbiological sampling and consider antibiotics with antistaphylococcal activity.

Topics: Aged; Bronchoalveolar Lavage Fluid; Cytokines; Female; Granulomatosis with Polyangiitis; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Nose; Staphylococcus aureus

The objective of this study was to review the various clinical features associated with Wegener's granulomatosis (WG) in the head and neck region and to discuss the difficulty of diagnosing patients with early stage WG.. Between January 1998 and August 2007, WG was diagnosed and treated in 16 patients at the Department of Otolaryngology, Hyogo College of Medicine. Clinical and operating records of these patients were analyzed retrospectively. Diagnosis was based on the Japanese criteria proposed by the Japanese Ministry of Health and Welfare in 1998.. Ten patients (62.5%) had a definite diagnosis of WG, and the other six patients (37.5%) had a probable diagnosis of WG. The period from the onset to diagnosis was between 1 month and 30 years. The generalized form of WG was observed in three patients (18.8%), and the limited form of WG was observed in the other 13 patients (81.2%). Nasal, aural, and ophthalmic symptoms were initially presented in 10, 3, and 3 patients, respectively. Cytoplasmic pattern antineutrophil cytoplasmic antibodies (cANCAs) and perinuclear pattern ANCA (pANCA) were positively detected in 68.8% (11/16) and 27.2% (3/11) of the patients, respectively. Five of 14 patients (35.7%) had pathologic features of WG in biopsy samples from the head and neck region. Three patients in whom a diagnosis of WG was difficult are presented, and immediate lessons of our experience were discussed.. This study emphasized the difficulty of diagnosing WG, particularly at an early stage and when limited to the head and neck region. The biggest challenge faced in diagnosing WG is that it requires a high index of suspicion. When WG was suspected, we should obtain an accurate medical history from patients and repeat serologic and histopathologic examinations.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Blood Sedimentation; C-Reactive Protein; Cerebrospinal Fluid Otorrhea; Cranial Nerve Diseases; Dacryocystitis; Diplopia; Earache; Epistaxis; Exophthalmos; Female; Follow-Up Studies; Granulomatosis with Polyangiitis; Hearing Loss; Humans; Immunosuppressive Agents; Male; Middle Aged; Nasal Obstruction; Nose; Retrospective Studies; Scleritis; Tinnitus; Visual Acuity

Increased amounts of anti-neutrophil cytoplasm antibody (ANCA) directed against proteinase 3 (PR3) are a diagnostic and pathogenic hallmark of full-blown Wegener's granulomatosis (WG). Aggregates of B lymphocytes proximal to PR3+ cells as well as plasma cells have been described as substantial components of Wegener's granuloma and could participate in forming tertiary lymphoid structures, which might promote autoantibody formation. Our aim was a molecular analysis of single B cells in order to develop a methodological approach that allows examination of potential ANCA formation in the tissue. Single B cells from cryo-conserved endonasal biopsies of three WG patients were isolated, using laser-assisted microdissection. Subsequently, their immunoglobulin variable heavy (VH) and light (Vkappa, Vlambda) chain genes were analysed by single cell polymerase chain reaction and direct sequencing. Sixteen immunoglobulin VH-Vkappa or VH-Vlambda chain gene couples were characterized. Twelve of these immunoglobulin gene couples resembled memory B cells. Two offsprings of one B cell were detected, indicating clonal expansion. VH genes representing 39 single B cells of WG tissues displayed significantly more mutations when compared with VH genes from peripheral blood of a healthy donor. The findings confirm and extend our previous results, arguing for an initial selection and affinity maturation of B cells within Wegener's granuloma. Further, the methodology provides the initial basis for the recombinant generation of antibodies derived from tissue cells.

Topics: Adult; Aged; B-Lymphocytes; Cell Differentiation; Complementarity Determining Regions; Genes, Immunoglobulin Heavy Chain; Genes, Immunoglobulin Light Chain; Granulomatosis with Polyangiitis; Humans; Immunoglobulin Variable Region; Microdissection; Middle Aged; Mutation; Nose; Polymerase Chain Reaction; Receptors, Antigen, B-Cell

Wegener's granulomatosis is an idiopathic, granulomatous disease with the potential for multiple head and neck manifestations (80 % of the patients). Sinonasal symptoms are observed in more than 60 % of the patients. Due to these facts the otorhinolaryngologist plays an essential role in the multidisciplinary team involved in establishing the diagnosis early, initiating immunosuppressive therapy and providing ongoing care. The treatment is based on medical therapy consisting of corticosteroids and immunosuppressive agents, whereas surgery is reserved for selected head and neck manifestations. By means of 3 patients presenting with distinct visual loss in consequence of orbital complications with sinonasal origin the course of disease and theoretical background are reviewed. In our patients Wegener's granulomatosis was diagnosed by histopathological examination and serological detection of ANCA, cANCA. The progression of the granulomatous process and an additional purulent inflammation in 2 cases led to a temporary amaurosis and in another case to a visual loss of 50 %. Immediate orbital decompression in combination with sufficient systemic immunosuppressive treatment relieved the compression of the optical nerve and preserved vision. We conclude that early orbital decompression either by external or endonasal approach and concomitant immunosuppression is necessary to determine or improve rapidly decreasing vision subsequent to high intraorbital pressure produced by a granulomatous process and inflammation.

Topics: Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Combined Modality Therapy; Decompression, Surgical; Follow-Up Studies; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Nose; Nose Diseases; Orbit; Orbital Diseases; Paranasal Sinus Diseases; Paranasal Sinuses; Tomography, X-Ray Computed; Vision, Low

Pseudovasculitis is a disease process that mimics the presentation and possibly the laboratory findings of true vasculitis. However, biopsy specimens do not reveal the typical histopathologic findings expected in vasculitis. One often overlooked cause of pseudovasculitis is cocaine use, which has been described in case reports to cause aggressive nasal destruction and various skin lesions and thus has been confused with Wegener granulomatosis or leukocytoclastic vasculitis. Unfortunately, serologic tests such as antinuclear antibody or antineutrophil cytoplasmic antibody cannot reliably differentiate between these entities. We describe a patient who presented with what was believed to be Wegener granulomatosis affecting the skin and upper airway. However, findings from repeated biopsies did not support this diagnosis, and the only unifying diagnosis was cocaine-induced pseudovasculitis. The ability to recognize and differentiate between true vasculitis and pseudovasculitis is essential for the clinician because treatment options are radically disparate.

Topics: Adult; Biopsy; Cocaine; Cocaine-Related Disorders; Diagnosis, Differential; Dopamine Uptake Inhibitors; Face; Female; Granulomatosis with Polyangiitis; Humans; Nose; Oropharynx; Skin; Vasculitis

To explore the characteristic and management of Wegener's granulomatosis in head and neck.. Forty-two cases with Wegener's granulomatosis were retrospectively analyzed clinical characteristics, head and neck manifestations, biopsy, ANCA test, and management were respectively recorded. Cyclophosphamide and Prednisone are the mainstay of medical therapy.. All cases presented with multiple organ systems involvement. Nasal involvement occurred most in head and neck, the occurred rate was 81.0%, the rate of first-occurred signs and symptoms was 47.6%. The diagnosis rate by biopsy was 67.6%. The total positive rate of ANCA test was 97.4%.. Head and neck involvement in Wegener's granulomatosis is most common and complicated. ANCA test and biopsy are the most main means in the diagnosis of Wegener's granulomatosis. Medical therapy is the mainstay of treatment in Wegener's granulomatosis, whereas surgery is reserved for selected head and neck manifestations.

Topics: Adolescent; Adult; Aged; Child; Female; Granulomatosis with Polyangiitis; Head; Humans; Male; Middle Aged; Neck; Nose; Retrospective Studies; Young Adult

Antiendothelial cell antibodies (AECA), usually detected using human umbilical vein endothelial cells (HUVEC), are frequently observed in systemic vasculitis, but their pathogenic role is unclear. Heterogeneity of endothelial cells necessitates use of clinically relevant endothelial cells for elucidation of the role of AECA in systemic vasculitis involving small blood vessels of specific organs.. Human endothelial cells were isolated from normal tissue specimens from the nose, kidney, lung, liver, and umbilical vein. Using flow cytometry, AECA were detected against both unstimulated and cytokine-stimulated [tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] endothelial cells. Functional capacity of AECA was determined by complement fixation assay. Sera from patients with Wegener's granulomatosis (16), limited Wegener's granulomatosis (8), renal limited disease (4), microscopic polyangiitis (MPA) (5), rheumatoid arthritis (10), and systemic lupus erythematosus (SLE) (9), and from healthy controls (20) were analyzed.. Compared with controls (1) Wegener's granulomatosis is significantly associated with noncytotoxic AECA that selectively bind surface antigens on unstimulated nasal, kidney, and lung endothelial cells; (2) binding of Wegener's granulomatosis AECA to kidney and nasal endothelial cells in particular was lost upon treatment with IFN-gamma and TNF-alpha; (3) the two cytokines per se were cytotoxic (30%) to nasal and lung endothelial cells and lysis was further increased (60%) by addition of systemic vasculitis serum; and (4) Wegener's granulomatosis serum caused agglutination of cytokine-stimulated nasal endothelial cells.. Based on these findings we suggest that AECA may be one factor involved in the initiation of Wegener's granulomatosis. Antigen identification and elucidation of the pathogenic roles of AECA and inflammatory cytokines in systemic vasculitis using these cells will be particularly important.

Topics: Autoantibodies; Complement Fixation Tests; Endothelial Cells; Endothelium, Vascular; Granulomatosis with Polyangiitis; Humans; Immunophenotyping; Interferon-gamma; Kidney; Lung; Nose; Organ Specificity; Tumor Necrosis Factor-alpha; Umbilical Veins

This retrospective study examined 33 patients with Wegener's granuloma seen between 1990 and 1999 in the Ayrshire and Arran region of Scotland. There was an estimated annual incidence of 10/million/year. The diagnosis in this series was based on the presence of one or more of the following: a positive histology, a positive c-ANCA or a typical clinical course. Twenty-eight patients were diagnosed based on either a positive histology and/or c-ANCA, whereas the remaining five were diagnosed based on the clinical course. c-ANCA was positive in 79.3% but correlated poorly with disease activity. Nasal biopsies were positive in 40%, whereas 94% of renal biopsies were positive, thereby making nasal biopsies unreliable in the diagnosis. Significantly elevated levels of erythrocyte sedimentation rate (ESR) averaging 77 mm/h were found in 32 patients at diagnosis. This showed fluctuation with disease activity. Thirteen patients died, 12 within 5 years. The best prognostic indicator statistically was age.

Topics: Adolescent; Adult; Age Factors; Aged; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Blood Sedimentation; Child; Female; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Incidence; Male; Nose; Predictive Value of Tests; Prognosis; Retrospective Studies; Scotland

Topics: Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; History, 20th Century; Humans; Kidney; Lymphomatoid Granulomatosis; Nervous System; Nose; Scotland; Urethra

Destructive lesions of the sinonasal tract, lacking a discernible etiology and referred to as midline destructive disease, have been pathologically classified in accordance with a variety of confusing terms. Development of new pathologic concepts and immunohistochemical techniques has provided a fresh understanding of these lesions, and, as a result, they can be unified into two distinct pathologic groups: Wegener's granulomatosis and non-Hodgkin's T-cell lymphoma.. We retrospectively reviewed the imaging studies and pathologic specimens of seven patients with prior diagnoses included in the midline destructive disease group. The specimens were reviewed by an oral pathologist using currently accepted pathologic criteria and the newly available immunohistochemical markers CD20, CD45, and CD45RO. Lesions were classified as non-Hodgkin's T-cell lymphomas when positive for CD45 and CD45RO and negative for CD20, and as Wegener's granulomatosis in the presence of noncaseating multinucleated giant cell granulomas and necrotizing vasculitis.. Three of the lesions were reclassified as Wegener's granulomatosis and four as T-cell lymphomas after applying these pathologic criteria. There were no distinguishing imaging findings between Wegener's granulomatosis and non-Hodgkin's T-cell lymphoma.. The current pathologic classification for midline destructive disease should be incorporated into the radiologic lexicon and the use of terms from the old classification system, such as idiopathic midline granuloma and lethal midline granuloma, should be abandoned and no longer be used in radiologic reports.

Topics: Antigens, CD20; Diagnosis, Differential; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Leukocyte Common Antigens; Lymphoma, T-Cell; Magnetic Resonance Imaging; Nose; Nose Diseases; Nose Neoplasms; Retrospective Studies; Sensitivity and Specificity; Terminology as Topic; Tomography, X-Ray Computed

In Wegener's granulomatosis (WG), a pathogenic role of infections, in particular of a chronic colonization of the nasal mucosa with Staphylococcus aureus, has been postulated. Nitric oxide (NO), which is thought to play a role in primary host defence and inflammation, is produced endogenously within the respiratory tract, mainly from the paranasal sinuses. In order to further characterize its role in WG, nasal and pulmonary NO excretion in WG patients in comparison to healthy volunteers was measured. Seventeen patients with WG were included in the study. Five patients had active disease (bloody rhinitis with ulceration and crusting) and immunosuppressive therapy (IST), and 12 were in remission (six with, and six without, IST). S. aureus was found in the swabs of all patients with active WG and in three patients in remission. NO was measured in exhaled gas using a chemiluminescence analyser. The NO excretion rate in nasally sampled gas was significantly reduced (p<0.05) in patients with active WG ((mean+/-SD)102+/-100 nL x min(-1)) compared to healthy controls (299+/-13 nL x min(-1)), and patients in remission (281+/-86 nL x min(-1) with IST, 280+/-133 nL x min(-1) without IST). Pulmonary NO excretion in active or nonactive WG patients did not significantly differ from that of healthy volunteers (48+/-21 nL x min(-1)). These results demonstrate a reduced nasal NO excretion in active Wegener's granulomatosis. This may be caused by destruction and/or functional impairment of sinus epithelium. The reduced NO concentration may well compromise host defence in the upper airways, thus contributing to colonization with Staphylococcus aureus and further promoting Wegener's granulomatosis.

Topics: Adult; Aged; Biomarkers; Female; Granulomatosis with Polyangiitis; Humans; Lung; Male; Middle Aged; Nasal Mucosa; Nitric Oxide; Nose; Staphylococcus aureus; Tomography, X-Ray Computed

Two patients are presented with Wegener's granulomatosis (WG) and lower respiratory tract infections with Staphyloccus aureus (SA). It is posulated that there is a relationship between the infection and the induction or relapse of the disease. We suggest that bronchoalveolar lavages should be performed in cases of suspected WG to identify SA-infections. The co-existence of WG and SA support the reported beneficial effects of sulfamethoxazole/trimethoprim, but needs further evaluation in patients with and without SA-infection of the airways.

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Colony Count, Microbial; Female; Granulomatosis with Polyangiitis; Humans; Middle Aged; Nose; Recurrence; Respiratory Tract Infections; Sputum; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Autoimmunity; Carrier State; Granulomatosis with Polyangiitis; Humans; Nose; Recurrence; Staphylococcal Infections

To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis.. Observational cohort study.. Outpatient clinic at a university-affiliated hospital.. Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed.. Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria.. Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections.. Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Carrier State; Chronic Disease; Cohort Studies; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Nose; Proportional Hazards Models; Recurrence; Risk Factors; Staphylococcal Infections

There is presented an atypical case Wegener's granulomatosis of maxillo-nasal region without bony destruction. The case is unusual because of sepsis and purulent coxitis. The patient responded well to treatment with vincristine and cyclophosphamide. ANCA assays have very good sensitivity and specificity for Wegener's granulomatosis.

Topics: Adolescent; Bone Diseases; Granulomatosis with Polyangiitis; Hip; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunosuppression Therapy; Lymphocytes; Male; Maxilla; Neutropenia; Nose; Radiography

Topics: Biopsy; Granulomatosis with Polyangiitis; Humans; Inflammation; Larynx; Mouth; Nose; Organ Specificity; Respiratory System

Four cases, two personal, of mis-diagnosis of tuberculosis of the upper respiratory tract as Wegener's granulomatosis have been presented. Greater awareness of this possibility of mis-diagnosis may diminish the possibility of mis-treatment. It is suggested that fresh specimens should be sent for bacteriological examination and culture in all relevant upper respiratory tract lesions.

Topics: Adult; Aged; Diagnostic Errors; Female; Granulomatosis with Polyangiitis; Humans; Larynx; Nose; Nose Diseases; Respiratory Tract Infections; Tuberculosis; Tuberculosis, Laryngeal

For the understanding of the CT findings of polymorphic reticulosis involving the upper respiratory tract, we reviewed eleven cases of this disease with initial CT study before treatment. CT revealed masses or swelling in the nose or nasal chamber, often with involvement of paranasal sinuses and medial parts of the orbit. In some, nonspecific minimal bony change (either bone destruction or bone sclerosis) was found. These CT findings are not specific. Any large mass in the nose and nasal fossa with little associated bone destruction should, however, raise the differential diagnosis of polymorphic reticulosis.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Nasal Cavity; Nose; Nose Neoplasms; Tomography, X-Ray Computed

Intranasal adhesions are a common complication following nasal surgery. They may be prevented by the use of silastic splints, which are also a very effective treatment for established lesions. We report a patient where intranasal adhesions rapidly recurred despite the use of splints, who was found to be suffering from Wegener's granulomatosis.

Topics: Adult; Female; Granulomatosis with Polyangiitis; Humans; Nose; Nose Diseases; Postoperative Complications; Recurrence; Splints; Tissue Adhesions

Topics: Aged; Diagnosis, Differential; Female; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Nose; Skin

Twelve patients with Wegener's granulomatosis were treated with antimicrobial agents, chiefly trimethoprim-sulfamethoxazole. The clinical course improved in 11 of the 12 patients who received this treatment. The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity.

Topics: Adult; Aged; Cyclophosphamide; Drug Combinations; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Lung; Male; Middle Aged; Nose; Prednisone; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Nose; Terminology as Topic

Thirteen patients with the clinical features of the midline granuloma syndrome are reported. Seven of the patients were determined to have Wegener's granulomatosis and had segmental necrotizing glomerulonephritis in their renal biopsies. Eighteen upper aerodigestive trace mucosal biopsies were available for review from the seven patients, and nine of these biopsies had a granulomatous angiodestructive inflammatory cell infiltrate considered "diagnostic" of Wegener's granulomatosis. The remaining nine biopsies lacked the specific histologic features of Wegener's granulomatosis but were considered consistent with mucosal involvement by the disease. Five of the remaining six patients had upper aerodigestive tract biopsies that were characterized by lymphocytic infiltrates. Three of the five patients had appreciable numbers of "atypical" cells in their biopsies and presented with radiologic evidence of lung involvement. It is our impression that patients with "significant cellular atypia" in their lymphocytic infiltrates have a disease indistinguishable from lymphomatoid granulomatosis, and these patients have a high propensity for either the presence or development of systematic disease that may require chemotherapy. Two patients had lymphocytic infiltrates with only minor degrees of cytologic atypia and no evidence of multisystem disease, and both of these patients responded to local radiation therapy. The remaining patient had a nonspecific histologic pattern in her numerous biopsies and was diagnosed as idiopathic midline destructive disease. She also had an adequate response to radiation therapy.

Topics: Adult; Aged; Biopsy; Diagnosis, Differential; Female; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Lymphomatoid Granulomatosis; Male; Middle Aged; Nose

Topics: Child; Diabetes Mellitus, Type 1; Exophthalmos; Female; Granulomatosis with Polyangiitis; Hematuria; Humans; Nose; Proteinuria

A series of 19 cases has been reviewed in which biopsy of an intra-nasal lesion revealed a granulomatous pathology. These have been classified on an aetiological basis. They include infections, Wegener's granuloma and neoplasms with a granulomatous stroma. One patient with sarcoidosis first presented with lesions in the nasal cavity. Cholesterol granulomata were seen in four lesions removed from the paranasal sinuses. In six cases clinical and histological examination failed to show a cause for the granulomata; in all of these patients the nasal cavity was free from disease at a subsequent examination.

Topics: Adult; Aged; Biopsy; Cholesterol; Female; Granuloma; Granulomatosis with Polyangiitis; Humans; Leprosy; Male; Middle Aged; Nose; Nose Diseases; Nose Neoplasms; Sarcoidosis; Tuberculosis

Wegener's granulomatosis and forms of giant cell arteritis result from vasculitis and masquerade with symptoms of common head and neck disease entities. Recognition of the manifestations of vasculitis can be made early in the disease course and confirmed pathologically, allowing effective therapy. Current therapy of Wegener's granulomatosis with Cytoxin and Imuran and steroids for giant cell arteritis frequently results in reversal of head and neck involvement, prevention of systemic disease, and prolonged survival.

Topics: Aortic Arch Syndromes; Diagnosis, Differential; Eye; Female; Giant Cell Arteritis; Granulomatosis with Polyangiitis; Head; Humans; Middle Aged; Mouth Mucosa; Neck; Nose; Paranasal Sinuses; Takayasu Arteritis

Topics: Adult; Autopsy; Female; Granulomatosis with Polyangiitis; Humans; Kidney; Lung; Myocardium; Nephrosclerosis; Nose; Tuberculosis, Pulmonary

Topics: Adult; Biopsy; Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Kidney; Male; Nose; Radiography; Skin

Topics: Adult; Autopsy; Brain; Diagnosis, Differential; Facial Neoplasms; Female; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Kidney; Male; Nose; Staining and Labeling

Topics: Diagnosis, Differential; Eosinophilic Granuloma; Female; gamma-Globulins; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Middle Aged; Nose; Nose Diseases; Prednisolone

Topics: Adolescent; Azathioprine; Epistaxis; Fluorescent Antibody Technique; Granulomatosis with Polyangiitis; Heparin; Humans; Kidney; Male; Nose; Phagocytosis; Prednisone

Topics: Adrenal Cortex Hormones; Azathioprine; Biopsy; Blood Sedimentation; Coombs Test; Female; Granulomatosis with Polyangiitis; Humans; Kidney; Leukocyte Count; Lung; Middle Aged; Nose; Paranasal Sinuses

Topics: Adult; Cortisone; Diagnosis, Differential; Face; Facial Neoplasms; Female; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Male; Middle Aged; Nasal Mucosa; Nose; Nose Neoplasms

Topics: Cervix Uteri; Diagnosis; Female; Granuloma; Granuloma, Lethal Midline; Granulomatosis with Polyangiitis; Humans; Nose; Pathology; Vagina

Topics: Diagnosis; Diagnosis, Differential; Granuloma; Granulomatosis with Polyangiitis; Hodgkin Disease; Humans; Kidney Diseases; Lung Diseases; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mastoid; Neoplasms; Nose; Nose Neoplasms; Paranasal Sinus Neoplasms; Prednisolone; Radiotherapy; Sarcoma

Topics: Ear Deformities, Acquired; Ear, External; Epistaxis; Granulomatosis with Polyangiitis; Hoarseness; Humans; Nose; Nose Deformities, Acquired; Otitis Media; Otolaryngology; Polyarteritis Nodosa

Topics: Granulomatosis with Polyangiitis; Hemoptysis; Humans; Larynx; Nose; Pneumonia; Respiratory Tract Diseases; Trachea; Ulcer

Topics: Collagen Diseases; Deafness; Granulomatosis with Polyangiitis; Hearing Loss; Humans; Keratitis; Nose; Paranasal Sinuses; Pharynx

Topics: Autopsy; Gangrene; Granulomatosis with Polyangiitis; Humans; Nose; Rhinitis

Topics: Granuloma; Granulomatosis with Polyangiitis; Humans; Medical Records; Nose; Polyarteritis Nodosa