Difficulty of diagnosing Wegener's granulomatosis in the head and neck region

doi:10.1016/j.anl.2008.02.003

Auris Nasus Larynx

Volume 36, Issue 1, February 2009, Pages 64-70

https://doi.org/10.1016/j.anl.2008.02.003 Get rights and content

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

Introduction

Wegener's granulomatosis (WG) is an idiopathic systemic disease [1] primarily characterized by vasculitis of small vessels that produces necrotizing granulomas. There are three classic pathologic features of WG—vasculitis of small arteries and veins, infiltrations of giant cells, and epithelioid cell granulomas. Of these vasculitis is thought to be strongly associated with antineutrophil cytoplasmic antibodies (ANCAs). The association with ANCA suggests that the vasculitis of WG constitutes an autoimmune disease [2]. Cytoplasmic pattern ANCA (cANCA) with antigen specificity for proteinase 3 (PR3) is a very sensitive serologic marker for WG [3], [4]. Perinuclear pattern ANCA (pANCA) with antigen specificity for myleoperoxidase (MPO) is also a marker of vasculitis [5].

Virtually any organ system can be affected by WG. The clinical onset is various and non-specific. To clarify the complicated features associated with WG, a classification system based on E (ear, nose, throat, and eye), L (lung), and K (kidney) was proposed [6]. WG was expediently divided into a limited form (e.g., E alone, L alone, and EL) and a generalized form (ELK). Many patients with WG predominantly develop the disease via lesions of the upper airway tract. In particular, the nasal mucosa may be the initial region of development [7], and patients with WG often consult otolaryngologists. Therefore, otolaryngologists play an essential role in the treatment of WG.

This study analyzed the clinical profile of WG in the head and neck region. We present patients in whom WG was clinically difficult to be diagnosed in the early stage and discuss the important lessons, which should not be overlooked.

Section snippets

Patients

Between January 1998 and August 2007, WG was primarily diagnosed and treated in 16 patients (4 males and 12 females) aged 15–76 years (mean age: 57.7 ± 13.6 years) at the Department of Otolaryngology, Hyogo College of Medicine. This study involved a retrospective analysis of clinical and operating records. The patients were followed up for between 9 months and 32 years (mean period: 73.8 ± 23.2 months) after diagnosis.

Diagnosis

Clinical features were carefully documented in each case, and hematologic

Patients with WG

Based on the Japanese criteria, 10 patients (62.5%) had a definite diagnosis of WG, and the other 6 patients (37.5%) had a probable diagnosis of WG (Table 1). The period of time from the onset to diagnosis was between 1 month and 30 years. The generalized form of WG was observed in three patients (18.8%). All three patients with the generalized form had a diagnosis of definite WG. The other 13 patients (81.2%) had the limited form of WG. In the limited form, 7 patients had a definite diagnosis

Discussion

We presented the clinical profiles of patients in whom it was difficult to diagnose WG. We based our diagnoses on the criteria of Ministry of Health, Labor and Welfare of Japan (1998). The criteria substantially consider systemic clinical features, typical pathologic features, and cANCA. It is unusual for all patients to meet all criteria, even if WG present. Very few cases exhibited all three classical pathologic features. The low diagnostic ratio on biopsy also makes the WG diagnosis

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Granulomatosis with polyangiitis and facial palsy: Literature review and insight in the autoimmune pathogenesis
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Subsequently, Drinias et al. [36] and other authors also reported similar cases in the literature [36,53,69]. Otoscopy, pure-tone audiometry, temporal bone CT and cranio-cerebral MRI with contrast medium are considered essential tools in the evaluation protocol for patients with suspected or confirmed diagnosis of granulomatosis with polyangiitis [22–25,75]. CT and MRI scans are decisive for evaluating the characteristics of lesions and for suggesting a diagnosis of GPA disease in cases of facial palsy with or without middle ear involvement [22,26–28,32].
Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported.
Facial nerve palsy is usually reported during the clinical course of the disease but it might appear as the presenting sign of GPA. Necrotizing vasculitis of the facial nerve ‘vasa nervorum’ is nowadays the most widely accepted etiopathogenetic theory to explain facial damage in GPA patients. A central role for PR3-ANCA in the pathophysiology of vasculitis in GPA patients with oto-neurological manifestation is reported.
GPA requires prompt, effective management of the acute and chronic manifestations. Once the diagnosis of GPA has been established, clinicians should devise an appropriate treatment strategy for each individual patient, based on current clinical evidence, treatment guidelines and recommendations.
Wegener's granulomatosis causing subglottic stenosis: Experiences at a tertiary care hospital of the Eastern India
2016, Journal of Taibah University Medical Sciences
To study the clinical profile and management of Wegener's granulomatosis (WG) with subglottic stenosis (SGS) at a tertiary teaching hospital in Eastern India.
This prospective study incorporated a case series of six patients treated between 2007 and 2015 for WG with SGS. The demographic details of the patients, such as age, sex, clinical presentation, laryngeal endoscopy, imaging, laboratory tests, and medical and surgical options, are described.
Of the six patients, five had laryngeal symptoms, such as hoarseness or breathing difficulty, at the time of presentation. There were four female and two male patients ranging in age from 14 to 62 years. The diagnosis of all six patients was confirmed via histopathological examination. Of the six patients, one had isolated subglottic involvement, and four had a positive antineutrophilic cytoplasmic autoantibody (C-ANCA) test on presentation. All of the patients received immunosuppressant and steroid therapies at the time of diagnosis. Five patients required tracheostomy with subglottic dilatation with cold steel instruments followed by the local injection of steroids and mitomycin-C application. Four patients have shown clinical improvement.
Although WG is a rare clinical condition, it is often confused with common ailments, which delays diagnosis, and it may involve the subglottis. The subglottis is a vital part of the laryngotracheal airway, and mild obstruction can be life threatening. The accurate and timely diagnosis of WG helps to prevent life-threatening complications, such as SGS.
Clinical and imaging features predictive of orbital granulomatosis with polyangiitis and the risk of systemic involvement
2014, Ophthalmology
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Orbital involvement is uncommon but can lead to devastating complications with reduced orbital functions, visual loss, and facial deformity. The clinical features of orbital disease are mostly nonspecific, and early diagnosis may be delayed because systemic diagnostic criteria are not applicable.22,23 This study has identified several clinical and imaging features that can be predictive of orbital GPA, namely ocular inflammation, sinonasal involvement, and intranasal bone erosion, particularly loss of the nasal septum.
Granulomatosis with polyangiitis (GPA), previously Wegener's granulomatosis, requires prompt diagnosis and systemic review to exclude life-threatening disease. However, early diagnosis of orbital GPA may be difficult because anti–neutrophil cytoplasmic antibody (ANCA) and anti-PR3 antibody screening can be negative at presentation and orbital biopsies taken for diagnosis may not show the classic features of GPA. This study was designed to compare GPA with other causes of orbital inflammation and to identify the presenting clinical and imaging features most likely to predict GPA and its systemic spread.
Retrospective noninterventional comparative case series.
A total of 247 patients who had undergone orbital biopsies for clinical presentations with orbital inflammation were identified from the Institute of Ophthalmology pathology database.
Patients were divided into GPA and non-GPA groups on the basis of their final clinical diagnosis. Clinical and imaging features of these 2 groups were compared to determine those predictive of GPA, and patients with GPA also had long-term evaluation for systemic involvement.
A diagnosis of orbital GPA and development of systemic GPA were the main outcome measures.
Features highly suggestive of GPA were sinonasal symptoms, sinonasal changes, or paranasal bone erosion on imaging (P < 0.001). Bony erosion was independent of ANCA status or systemic involvement. Twenty-two percent of patients (8/37) with GPA had evidence of systemic involvement at presentation, and no patient presenting with solely orbital GPA developed later systemic disease over a median follow-up of 2.7 years.
A high index of suspicion should be maintained for GPA when a patient presents with an orbital mass and sinonasal symptoms or imaging shows sinonasal involvement or paranasal bone erosion. No patient with solely orbital GPA involvement at presentation developed systemic disease, suggesting that orbital GPA can remain localized in the long-term.
Pathogenesis and diagnosis of otitis media with ANCA-associated vasculitis
2014, Allergology International
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is histologically characterized by systemic necrotizing vasculitis and is clinically classified into two phases, systemic or localized. Recently, otologi- cal symptoms such as otitis media and hearing loss, not previously often associated with AAV, have been reported in AAV cases. In these cases we propose a diagnosis of otitis media with AAV (OMAAV). The ANCA titer is important for the diagnosis of OMAAV, and in most cases rapid progressive hearing loss is observed as localized AAV. Peripheral facial nerve palsy or hypertrophic pachymeningitis are coupled with 25% of cases and 18% of cases respectively. Proteinase 3-ANCA (PR3-ANCA) positive otitis media causes granulomatous formation or middle ear effusion in the middle ear, on the other hand myeloperoxidase-ANCA (MPO-ANCA) positive otitis media predominantly presents as otitis media with effusion. The early diagnosed case and the sensorineural hearing loss not progressed deaf could be recovered by the immunosuppressive therapy. Delayed diagnosis of AAV occasionally leads to progression to the irreversible phase; therefore, diagnosis at the early-localized stage is important for treating AAV. In this review, we discuss the current understanding of this newly proposed concept of OMAAV.
Ear, nose and throat manifestations of Wegener's granulomatosis (granulomatosis with polyangiitis)
2012, Acta Otorrinolaringologica Espanola
La granulomatosis con poliangeitis (GPA), previamente llamada granulomatosis de Wegener, es una vasculitis de pequeños vasos que con frecuencia se asocia a manifestaciones clínicas de cabeza y cuello, y en ocasiones constituyen los síntomas de presentación de la enfermedad. El objetivo de nuestro estudio fue identificar la afección otorrinolaringológica asociada a dicha enfermedad y proponer un protocolo diagnóstico de los pacientes con sospecha clínica o confirmada de la misma.
Se realizó un estudio retrospectivo descriptivo que incluyó los pacientes diagnosticados de GPA que recibieron asistencia por el Servicio de Otorrinolaringología de un hospital público de tercer nivel de Cantabria. El período de inclusión fue de 20 años. Se recogieron de la historia clínica diferentes variables clínicas concernientes al área de cabeza y cuello.
Veinticinco pacientes con edades comprendidas entre 30 y 81 años de edad fueron incluidos en nuestro estudio. El 88% de los mismos presentaron manifestaciones otorrinolaringológicas en algún momento de la evolución de la enfermedad, y en un 28% constituyeron la forma de presentación de la misma. Los síntomas nasosinusales fueron los más frecuentes (52%), seguido de los otológicos (32%). Un paciente desarrolló un carcinoma de nasofaringe 3 años después del tratamiento con ciclofosfamida.
Los pacientes con GPA presentan con frecuencia manifestaciones clínicas de cabeza y cuello. Es necesario realizar una exploración sistemática otorrinolaringológica en los pacientes con sospecha o diagnóstico confirmado de GPA, tanto para contribuir al diagnóstico de la enfermedad, si esta no estuviese confirmada, como para establecer el grado de afección sistémica de pacientes con esta vasculitis.
Granulomatosis with polyangiitis (GPA), previously called Wegener's granulomatosis, is a small vessel vasculitis often associated with clinical head and neck manifestations, which are sometimes the presenting symptoms of the disease. The aim of our study was to identify ear, nose and throat (ENT) manifestations associated with GPA and propose a work-up for the management and diagnosis for patients with suspicion or confirmed diagnosis of this ENT pathology.
Retrospective review of the medical records of all patients diagnosed with GPA who were seen at the Department of Otolaryngology from a tertiary public hospital in Cantabria (Spain) over a 20-year period. Clinical and laboratory data, in particular those concerning ENT manifestations, were retrieved from the patients’ medical records.
Twenty-five patients (age range: 30-81 years) were included in the study. Of these, 88% had ENT manifestations at some point in the course of the disease. In 28% of the cases, ENT features were the presenting manifestations. The most frequent ENT manifestations were sinonasal symptoms (52%), followed by otological manifestations (32%).
Patients with GPA often present with clinical ENT manifestations. Consequently, routine ENT physical examination must be performed in patients with suspected vasculitis to establish a diagnosis of GPA or to better determine the degree of organ system involvement in patients with GPA.
Reversible cochlear disorders with normal vestibular functions in three cases with Wegener's granulomatosis
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On the other hand, Case3 did not fulfill any of the ACR 1990 criteria for WG, but was also diagnosed as WG based on CHCC definitions including positive serology for ANCA and otitis media sustaining over 3 months which is one of WG surrogate markers of CHCC. Retrospectively, the initial bilateral progressive mixed hearing loss of all cases was thought as a manifestation of limited forms of WG [6]. All three WG patients were treated by PSL before the onset of the systemic symptoms.
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.

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View full text

Difficulty of diagnosing Wegener's granulomatosis in the head and neck region

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Diagnosis

Patients with WG

Discussion

Lancet

Otolaryngol Head Neck Surg

Ophthalmology

Lancet

Wegener's granulomatosis. Thoughts and observations of a pathologist

Eur Arch Otorhinolaryngol

Antineutrophil cytoplasmic antibodies

Arthritis Rheum

Anticytoplasmic antibodies in Wegener's granulomatosis

Lancet

Serum myeloperoxidase and serum cytokines in anti-myeloperoxidase antibody-associated glomerulonephritis

Clin Nephrol

Wegener's granulomatosis. Anatomic correlates, a proposed classification

Mayo Clin Proc

Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years

Ann Intern Med