Ear involvement in Wegener's granulomatosis

In 16 of 19 patients with biopsy-proved Wegener's granulomatosis the early manifestations were limited to the ear and nose. The audiological data of 13 patients revealed middle ear involvement in 16 of 26 ears. Twenty-one of 26 ears presented with a low to moderate sensorineural hearing loss. One ear remained deaf after a sudden hearing loss in the early stage of the disease. Serologically, 4 of 6 tested patients with sensorineural hearing loss demonstrated antibodies against sarcolemma. One patient showed antinuclear antibodies. It is remarkable that these antibodies can often be detected in classic inner ear disorders. The course of inner ear function, serum findings and the success of immunosuppressive therapy in Wegener's granulomatosis are comparable with immunologically mediated vasculitis in the inner ear.     

Wegener肉芽肿病的耳部表现

目的探讨Wegener肉芽肿病耳部表现的临床特征，组织病理学和实验室检测特点，做到早诊断和早治疗。方法回顾性分析14例Wegener肉芽肿病耳部表现的临床资料。结果14例中包括慢性化脓性中耳炎10例，其中合并周围性面神经麻痹2例；分泌性中耳炎3例；感音神经性聋1例。14例中3例慢性化脓性中耳炎，1例分泌性中耳炎和1例周围性面神经麻痹是Wegener肉芽肿病的首诊表现，开始表现为耳部单独受累，余9例开始即有多器官受累表现，全部病例均呈现多系统多器官受累。14例组织病理学诊断均符合Wegener肉芽肿病的特点。13例抗中性粒细胞胞质抗体阳性，14例有红细胞沉降率升高，13例C反应蛋白升高。所有病例经糖皮质激素和环磷酰胺治疗后病情均得到控制。11例随访时间3年以上，病情稳定无复发。结论Wegener肉芽肿病的耳部表现常缺乏特异性，早期诊断有赖于临床表现、组织病理学检查和抗中性粒细胞胞质抗体的及时检测。规范使用糖皮质激素和环磷酰胺可以有效地控制病情。     

Clinical characteristics,the diagnostic criteria and management recommendation of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) proposed by Japan Otological Society

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a form of necrotizing vasculitis with few or no immune deposits. It primarily affects small and medium blood vessels. AAV is classified into three categories, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangitis (EGPA), and two major ANCAs, proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA are involved in their pathogenesis. Intractable otitis media frequently occurs in patients with GPA, MPA or EGPA, although all patients show similar clinical features, regardless of the type of AAV. Furthermore, approximately 15% patients with otitis media caused by AAV do not show ANCA positivity, histopathological evidence, or any other AAV-related lesions at the initial visit; therefore, these patients do not fulfill the ordinary diagnostic criteria for systemic AAV. Thus, we first proposed that this condition could be categorized as “otitis media with AAV (OMAAV)”. Subsequently, the Japanese Otological Society (JOS) conducted a nationwide survey between December 2013 and February 2014 and identified 297 patients with OMAAV. The survey revealed that OMAAV is a disease that initially occurs in the middle ear and subsequently spreads to other organs such as the lungs and kidneys, with eventual involvement of all body organs. Severe sequelae such as facial palsy, hypertrophic pachymeningitis, complete deafness, and subarachnoid hemorrhage resulting in death can also occur. In this review, we introduce the clinical features, diagnostic criteria, and treatment strategies recommended by JOS for early diagnosis and treatment of OMAAV.     

Intractable otitis media - Pathogenesis and treatment of Eosinophilic otitis media (EOM) and otitis media with Antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (OMAAV)

Intractable otitis media is resistant to antimicrobial therapy, tympanostomy ventilation tube insertion, and surgery. In children, intractable acute otitis media, pathological tympanic membrane due to prolonged otitis media with effusion (OME), tympanic membrane atelectasis, and adhesive otitis media are common. Contrarily, in adults, otitis media caused by drug-resistant pathogens, tuberculous otitis media, cholesterol granuloma, malignant otitis externa (skull base osteomyelitis), eosinophilic otitis media (EOM), and otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) are common and require differentiation. Among them, EOM is increasing along with eosinophilic upper respiratory tract diseases, such as bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP). EOM is associated with adult-onset bronchial asthma and is characterized by viscous middle ear effusion and middle ear mucosa thickness with eosinophilic infiltration, which requires treatment with glucocorticoids according to disease activity and symptoms. Recently, OMAAV was proposed because of the similarities in clinical features and therapeutic effects. The clinical course of OMAAV is characterized by a relatively rapid increase in the bone conductive hearing threshold, which progresses over 1-2 months, without response to antimicrobial agents or tympanostomy ventilation tube insertion, and in some cases, is complicated by facial paralysis and hypertrophic pachymeningitis. This new concept may explain the pathogenesis and clinical presentation of many cases of intractable otitis media, the cause of which was previously unknown. Although making a diagnosis of OMAAV is relatively easy based on the clinical course, such as vascular dilatation of the tympanic membrane and positive ANCA titer, it is often difficult because the ANCA titer becomes negative with previous administration of glucocorticoids. In adults with intractable otitis media, ANCA titers must be measured before glucocorticoid administration. Treatment consisted of remission induction therapy with a combination of glucocorticoids and immunosuppressive drugs.     

Head and neck manifestations of Wegener's granulomatosis

Wegener's granulomatosis is an idiopathic, granulomatous disease with the potential for multiple head and neck manifestations. The otolarygologist is an essential part of the multidisciplinary team involved in establishing the diagnosis and providing ongoing care for patients with Wegener's granulomatosis. Diagnostic difficulties abound in Wegener's granulomatosis, making repeat biopsies and the use of ANCA imperative. Medical therapy consisting of corticosteroids and immunosuppressive agents is the mainstay of treatment in Wegener's granulomatosis, whereas surgery is reserved for selected head and neck manifestations. With appropriate medical and surgical treatment, many patients living with Wegener's granulomatosis can enjoy a good quality of life.     

Acute onset Wegener's granulomatosis presenting as otitis media; a case report

We report the case of a 57-year-old woman with Wegener's granulomatosis who presented with otitis media. The patient presented with a 2-month history of bilateral hearing loss and dizziness. Antibiotic treatment was not effective, and the patient was confirmed to have bilateral sensorineural hearing loss. Serum was positive for cytoplasmic anti-neutrophil cytoplasmic antibody [C (PR3)-ANCA] but negative for P(MPO)-ANCA (perinuclear ANCA). While the test results were pending, the patients' general condition worsened ; in particular, signs of active inflammation, cardiorespiratory failure and scleritis developed suddenly. Emergency chest computed tomography revealed evidence of lung involvement and hydrothorax; thus, the patient was diagnosed to have the generalized form of Wegener's granulomatosis. The patient was started on pulse methylprednisolone therapy at 1000mg/day for 3 days, which resulted in marked clinical improvement, and then, the drug therapy was switched to prednisolone 60mg/day and cyclophosphamide 50mg/day and gradually tapered. Early diagnosis of Wegener's granulomatosis is often difficult because of atypical manifestations of the disease; particular attention must be paid to acute onset of the disease, such as in our case. ANCA is a very useful marker for early diagnosis, but about one week is needed to obtain the test results. We believe that early steroid and cyclophosphamide therapy is an effective therapeutic option for patients with signs of severe inflammation and generalized involvement.     

Ear involvement in Wegener's granulomatosis*

In 16 of 19 patients with biopsy-proved Wegener's granulomatosis the early manifestations were limited to the ear and nose. the audiological data of 13 patients revealed middle ear involvement in 16 of 26 ears. Twenty-one of 26 ears presented with a low to moderate sensorineural hearing loss. One ear remained deaf after a sudden hearing loss in the early stage ofthe disease. Serologically, 4 of 6 tested patients with sensorieneural hearing loss demonstrated antibodies against sarcolemma. One patient showed antinuclear antibodies. It is remarkable that these antibodies can often be detected in classic inner ear disorders. The course of inner ear function, serum findings and the success of immunosuppressive therapy in Wegener's granulomatosis are comparable with immunologically mediated vasculitis in the inner ear.     

Early diagnosis of Wegener's granulomatosis presenting with bilateral facial paralysis and bilateral serous otitis media

Wegener's granulomatosis (WG) is a multi-system disease characterized by granuloma formation and widespread necrotizing vasculitis. It classically presents with involvement of the upper and lower respiratory tracts and renal system. Facial nerve palsy and otologic manifestations have been reported during the course of the disease but it is extremely rare as the presenting features. In Literature only one case of bilateral facial palsy as presenting sign of WG is reported. The testing of anticytoplasmic antibodies versus neutrophil polymorphonucleate granules (c-ANCA) are highly specific for the diagnosis of WG, being positive in 97% of the cases. The early diagnosis and the timely medical treatment lead to high rates of remission of an otherwise lethal disease. A case of WG presenting with bilateral facial paralysis and bilateral serous otitis media is reported.     

Unspecific parotitis can be the first indication of a developing Wegener’s granulomatosis

In an unusual course of Wegener’s granulomatosis (WG), a 71-year-old woman presented a 3-week history of unilateral painful parotid swelling unresponsive to antiphlogistic and antibiotic treatment. Following lateral parotidectomy with unspecific inflammatory histopathological findings, the patient developed disturbance of wound healing and high recurrent fever. Control chest X-ray showed several pulmonary round lesions. Immunologic testing for antinuclear cytoplasmatic antibodies (ANCA) was positive and CT navigated puncture revealed pronounced necrotic vasculitis of small arteries and veins. Consequently, systemic WG was diagnosed and specific immunosuppressive therapy was started. Long-term follow-up of 6 months showed a decline in the ANCA course, full remission of the presented symptoms and prevention of renal manifestations. Isolated inflammatory parotid enlargement can be the initial symptom of systemic WG and should be considered as differential diagnosis, especially when nondiagnostic histopathological results are obtained. Early testing for c-ANCA supplies valuable information and therefore should be prompted when additional symptoms occur. Once diagnosed as WG, appropriate therapy is able to prevent progression to severe clinical courses.     

Otologic manifestations of Wegener's granulomatosis

OBJECTIVE/HYPOTHESIS: To evaluate the clinical features, treatment, and outcomes of otologic manifestations in Wegener's granulomatosis (WG) treated at Hokkaido University Graduate School of Medicine, Sapporo, Japan. STUDY DESIGN: We retrospectively reviewed 15 cases of WG with ear involvement. METHODS: Twenty-five patients with WG were treated at Hokkaido University Graduate School of Medicine between 1992 and 2001. Fifteen of these patients had otologic symptoms. We evaluated the clinical course, method of therapy, and outcomes in all cases. Diagnosis of WG was made when the patients had clinical findings and a positive titer of cytoplasmic pattern antineutrophil cytoplasmic antibodies (c-ANCA), or when there were clear histologic findings. We also present three case reports. RESULTS: In 15 cases, the most frequent finding was chronic otitis media. Sensorineural hearing loss was present in 2 patients. In 7 patients whose otologic manifestations were the primary involvement of WG, all were confirmed positive for c-ANCA and were treated with glucocorticoids and immunosuppressive drugs. Three patients who could be treated within 1 month of symptom onset showed marked improvement. CONCLUSIONS: In localized cases, biopsy specimens are often small, and it is frequently difficult to make a histologic diagnosis. The prognosis for hearing was poor when appropriate treatment was not given in the early stages of the disease. Therefore, WG should be included in the differential diagnosis in cases of atypical inflammatory states of the ear. Early diagnosis and appropriate treatment are important to prevent irreversible changes in the middle ear and inner ear.     

Reversible cochlear disorders with normal vestibular functions in three cases with Wegener's granulomatosis

Patients with Wegener's granulomatosis (WG) often suffer from hearing loss, but its precise mechanisms have not been well understood. We experienced 3 WG cases whose initial symptoms were bilateral progressive mixed (both conductive and sensorineural) hearing loss, followed by systemic symptoms one year later. They were diagnosed as WG based on positive serology of anti-neutrophil cytoplasmic antibodies (ANCAs) and pathologic findings of affected lesions in addition to systemic symptoms. Although they were different in the type of ANCAs and systemic lesions, all showed considerably reversible cochlear disorders with normal vestibular functions. Moreover, their initial otologic manifestations shared same characteristic features, (1) thick ear drums with pulsatile serous intratympanic effusion, (2) poor speech discrimination ability, and (3) steroid-dependent changes of hearing levels (HLs). They exhibited no significant vestibular abnormalities in chair vestibule-ocular reflex (VOR) testing and cold air caloric tests even when they had severe hearing loss. On the basis of these results, we hypothesized that vasculitis of stria vascularis which generates endocochlear potential might cause these reversible cochlear-specific dysfunctions.     

The hearing loss in Wegener's granulomatosis: relationship between hearing loss and serum ANCA.

We observed the change of hearing for 1 year in a patient with Wegener's granulomatosis. We also studied anti-human neutrophil cytoplasm antibody (ANCA), which is believed to be specific for this disease and to be associated with disease activity. From these progresses, changes in hearing were considered to be generally related with the general condition and with the ANCA titer level. Because hearing loss in our case was improved by steroids and immunosuppressants, and because ANCA is the autoantibody observed in angiitis syndrome, hearing loss in this case of Wegener's granulomatosis was suspected of being caused by angiitis of the middle and inner ear induced by autoimmune reaction.     

Wegener肉芽肿病的头颈部临床表现及处理

目的：探讨Wegener肉芽肿病（wG）在耳鼻咽喉-头颈部的临床表现及处理方法。方法：回顾性分析42例WG患者的临床资料,分别对其临床特征、耳鼻咽喉-头颈外科表现、活检及抗中性粒细胞细胞质抗体（ANCA）检测及治疗方法进行记录分析。治疗主要采用环磷酰胺加泼尼松联合应用的内科治疗。结果：全部病例均呈现多系统、多器官受累,34例（81．0％）以鼻部受累为最明显,32例（76．2％）肺受累。首发症状以鼻部为首位20例（47．6％）,其次发热11例（26．2％）。37例行活检,其中25例确诊,确诊率为67．6％。ANCA检测总阳性率为97．4％。结论：WG在耳鼻咽喉-头颈部表现复杂多变,ANCA检测和活检是诊断的主要手段。主要以内科治疗为主,手术治疗是有选择性的。     

Wegener肉芽肿病的眼部表现及其与鼻部的关系

目的探讨韦格纳肉芽肿病（Wegener granulomatosis,WG）的眼部表现及其与鼻部的关系。方法收集2005年6月至2009年9月解放军总医院收治的有眼部表现的19例WG患者,回顾分析其眼部临床表现、实验室指标和确诊途径。结果在WG患者中,眼部受累的表现多样,且常伴发鼻部和鼻窦的改变。19例患者中,10例（52．6％）有眼眶受累的表现并同时伴有鼻窦的改变;有2例（10．5％）为慢性泪囊炎,1例（5．3％）为鼻泪管狭窄。17例（89．5％）通过对不同部位的病变组织进行活检得到证实,其中鼻粘膜活检有12例（63．2％）;19例患者均行影像学检查,16例（84．2％）患者符合WG影像学的表现,其中14例（73．7％）单纯或合并有鼻窦的表现。所有患者的ANCA结果阳性。结论WG是一种严重的临床疾病．需要得到早期的诊断和正确的治疗,该病常伴发鼻部和异窦的改变,可考虑将鼻粘膜的活检、鼻窦的影像学检查和ANCA检查作为该病的常规检查手段之一。     

Antineutrophil cytoplasmic antibodies in chronic rhinosinusitis may be a marker of undisclosed vasculitis

BACKGROUND: Upper airway manifestations are common features of antineutrophil cytoplasmic antibody (ANCA)-related vasculitis. Determining the presence of this antibody in patients with chronic rhinosinusitis (CRS) may allow early identification and treatment of underlying vasculitis. Methods Forty-nine consecutive CRS patients and 165 age- and sex-matched healthy controls were evaluated for vasculitis complaints. ANCA were detected by indirect immunofluorescence, and antibodies to proteinase 3 (PR3) and myeloperoxidase were determined by ELISA. RESULTS: Patients and controls were comparable concerning the mean age (47.2 +/- 15 years versus 45 +/- 12.5 years; p = 0.303) and female predominance (73.5% versus 60%; p = 0.502). Vasculitis-associated complaints were reported in 8/49 (16.3%) patients: 7 patients reported a 10-year history of asthma and 1 patient had red/painful eyes associated with epistaxis. ANCA was positive in 5/49 (10%) patients and absent in controls (p < 0.0001). One patient had high titer cytoplasmic ANCA/PR3 and during the investigation developed clinical features of Wegener's granulomatosis. The other four patients had perinuclear ANCA, of whom three were asymptomatic and one is currently under surveillance for Churg-Strauss syndrome. Sinus computed tomography scan revealed that patients who were ANCA(+) had more extensive disease involvement than ANCA(-) patients (Lund-Mackay score median value, 21 versus 13; p = 0.008). CONCLUSION: ANCA may identify a subset of difficult to treat CRS patients with underlying vasculitis and may be useful for establishing an early diagnosis of vasculitis in CRS.     

Wegener's granulomatosis of the orbit: a clinicopathological study of 15 patients

OBJECTIVES: Wegener's granulomatosis is a granulomatous and necrotizing vasculitis that classically involves the respiratory and renal systems. The goal of the study was to define clinical and pathological characteristics in a subgroup of patients with the changes of Wegener's granulomatosis involving the orbit. STUDY DESIGN: Retrospective study. METHODS: A database search identified 15 patients with the histological changes of Wegener's granulomatosis of the orbit presenting over a 23-year period. A review of the histological specimens, radiological studies, and patient charts was performed. Additional follow-up data were obtained through patient interviews. RESULTS: Of 15 patients (median age, 54 y) with Wegener's granulomatosis of the orbit identified, the disease was limited to the orbit in 12 patients; 3 patients had additional sinonasal involvement. All patients underwent various surgical procedures followed by medical treatment (cyclophosphamide and prednisone). Specimens showed characteristic histopathological features of Wegener's granulomatosis. Follow-up data were available for 12 patients with a median period of 5 years. In the group with only orbital involvement, none of the patients developed systemic progression of Wegener's granulomatosis. Only one patient had multiple local recurrences and later developed contralateral orbital Wegener's granulomatosis. CONCLUSIONS: Wegener's granulomatosis limited to the orbit is a localized form of the disease without systemic progression. Diagnostic surgical procedures followed by aggressive medical treatment results in good outcome, although local recurrence may occur.     

Wegener's granulomatosis with otological disorders as primary symptoms

Otological symptoms as initial manifestations of Wegener's granulomatosis have been observed in 3 patients. In one of them, symptoms consisted of a bilateral sensorineural hearing loss, improved by corticoid therapy. No other organ system was involved and laboratory tests remained within normal limits for 2 years after the onset of otological signs. In the other 2 patients, Wegener's granulomatosis manifested mainly as serous otitis media. Otologic involvement underscores the role of the otolaryngologist in the early diagnosis and treatment of this disease.     

Wegener's granulomatosis (WG) presented with hearing loss and without positive serologic ANCA

BACKGROUND: Wegener's granulomatosis (WG) is a granulomatous inflammation involving the upper and lower respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels. In contrast to a generalised WG with glomerulonephritis initial or isolated forms of the upper respiratory tract may be a diagnostic challenge. PATIENT: We report the case of a 33 year old man with clinical signs of a limited WG exhibiting an imminent irreversible hearing loss, negative PR3-ANCA (anti neutrophil cytoplasmic antibodies with proteinase 3 as target) in serum and an ambiguous histology. CONCLUSION: In case of a chronic otitis media and rhinitis as well as signs of a labyrinthine deafness a limited form of a WG has to be taken into account, even with an ambiguous histology and negative PR3-ANCA. This diagnosis is supported by high inflammation parameters, e. g. ESR and CRP, exclusion of infectious cause and response to corticosteroids. A quick therapeutic intervention with corticosteroids and cyclophosphamide is required in order to interrupt the vasculitis of the inner ear with consequential deafness.     

Bilateral parotid and submandibular gland enlargement: rare features of Wegener's granulomatosis

Wegener's granulomatosis is a potentially fatal disease of unknown origin affecting mainly the upper and lower respiratory tracts and kidneys. Prompt recognition of the more unusual presentations of the disease is necessary to ensure early treatment. We present a case of a 46-year-old female with bilateral submandibular and parotid gland enlargement. Parotid or submandibular salivary gland enlargement is a rare presenting feature of Wegener's granulomatosis. Common to 80 per cent of these cases is nasal involvement, while ear pathology or lung lesions may occur in the remaining cases. The diagnosis is both clinical and pathological, biopsy of suspicious tissue, serum c-ANCA levels and a chest X-ray are valuable investigations. Treatment with immunosuppressive therapy is essential, and usually ensures a long-term remission.     

Otological manifestations of wegener's granulomatosis

The otological manifestations of Wegener's granulomatosis were studied in 13 patients; diagnosis was confirmed histologically in 10, and in 1 patient periarteritis nodosa presented similar appearances. One patient had destruction of the external ear, and several had refractory otitis externa, usually associated with otitis media: 3 patients had serous otitis media, 4 had purulent otitis media of a fairly mild course, while 6 had otitis media of a fulminant and long-lasting course, accompanied in 5 cases by cranial nerve palsy and in 2 by widespread destructions. Most patients had major sensory hearing loss. Two had short-lasting anacusis during exacerbation of the pulmonary lesions. Often, otological manifestations were the initial signs of the disease. It is important to bear this diagnosis in mind in cases of long-lasting and atypical inflammations and in the presence of peculiar constellations of symptoms from several different organ systems.