Wegener's granulomatosis: A challenging disease for otorhinolaryngologists

Conclusions

Diagnosis of Wegener's granulomatosis (WG) can be delayed because of its aspecific presenting symptoms. Detection of serum circulating antineutrophil cytoplasm antibodies (c-ANCAs), in combination with histology, permits one to identify WG at an early stage and to implement stage-adapted therapy. c-ANCA levels may also help to evaluate the response to medical therapy. Recently, the quality of life of WG patients has been improved by administering cotrimoxazole in order to prevent infections and recurrent diseases during the remission period.

Objective

WG is of special significance to the otorhinolaryngologist because it is often initially limited to the upper respiratory tract before becoming systemic. The aim of this paper was to describe a series of WG patients and underline the difficulties involved in diagnosing and treating this challenging disease.

Material and methods

This was a prospective study in 23 consecutive patients with head and neck manifestations of WG (17 systemic, 6 limited). Diagnosis was performed by means of both c-ANCAs detection using indirect immunofluorescence and histology in biopsy specimens. Treatment consisted of daily cyclophosphamide (CYC; 2?mg/kg/day) and glucocorticoids (prednisone; 1?mg/kg/day). If an improvement or toxic events occurred, CYC was discontinued and methotrexate was started. If, during remission of the disease, low serum c-ANCAs levels were detected, CYC was suspended and cotrimoxazole (1?g/day) was introduced.

Results

Serum c-ANCAs detection was positive for all patients. Biopsy was diagnostic from the beginning in 19/23 cases. The six patients with limited WG did not show a progression to systemic disease. Only 3 patients with a diagnosis of delayed systemic WG died, whereas 19/23 patients were alive with good control of relapses.     

Wegener's granulomatosis: an analysis of 33 patients seen over a 10‐year period

Wegener's granulomatosis: an analysis of 33 patients seen over a 10‐year period 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.     

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.     

HLA antigen frequencies and Wegener's granulomatosis

Previous reports of an association between HLA tissue type and Wegener's granulomatosis are contradictory. By using for the first time a highly sensitive restriction fragment-length polymorphism (RFLP) analysis in addition to standard microcytotoxicity assays, the largest series yet investigated (41 patients) was tissue typed. No association was found between any specific HLA antigen and Wegener's granulomatosis. Although the condition appears to be immunologically mediated, this study indicates that the HLA antigens do not have a major role.     

General and rhinosinusitis-related quality of life in patients with Wegener's granulomatosis

OBJECTIVES: The objectives of this cross-sectional study were to outline the pattern of sinonasal morbidity and determine its effects on the quality of life (QOL) of patients with Wegener's granulomatosis (WG). METHODS: The authors conducted a survey of 199 patients with WG, including two validated (QOL) instruments to assess general (SF-36) and rhinosinusitis-specific quality of life (Sinonasal Outcome Test [SNOT-22]). RESULTS: Patients with WG who have sinonasal involvement reported significantly lower general QOL scores than their unaffected counterparts (P = .000006-0.04) for all SF-36 subsets except for emotional role. WG-related sinonasal morbidity was comparable to the high levels previously demonstrated in the general rhinosinusitis population. A total of 38.2% of all patients with WG reported a nasal symptom as their most troublesome from a list of nasal and constitutional symptoms. Twenty-three percent of all patients with WG rated nasal crusting and 17% rated epistaxis as one of their top three most troublesome symptoms even in the setting of multisystem disease. The inclusion of crusting, bleeding, and nasal deformity in the SNOT scoring significantly increased average scores of patients with WG (P = .024, paired t test). CONCLUSIONS: Sinonasal involvement impacts significantly on the general QOL of patients with WG and is at least as significant as that of the general rhinosinusitis population. Nasal symptoms that are of particular relevance to this patient group include nasal crusting and epistaxis.     

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.     

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.     

Long-term follow-up of repair of external nasal deformities in patients with Wegener's granulomatosis

OBJECTIVE: Wegener's granulomatosis is a disorder of the upper airway, lungs, and kidneys characterized histologically by necrotizing granulomas and vasculitis. One common result of Wegener's granulomatosis is destruction of the framework of the nose, resulting in a saddle-nose deformity. The study was initiated to determine the efficacy and safety of reconstructing external nasal deformities in these patients. STUDY DESIGN: A retrospective review. METHODS: We searched for all patients with Wegener's granulomatosis who underwent an external nasal reconstruction between the years of 1976 and 2000. RESULTS: Thirteen patients met the search criteria. The average duration of follow-up is 59 months (range, 10-177 mo). The initial surgery resulted in a satisfactory outcome in 10 of 13 patients (77%). Two of the patients who failed the primary surgery underwent successful revision rhinoplasty, and one chose not to undergo revision surgery. This resulted in a 92% (12 of 13) overall patient success rate. Ten of the 13 patients had an improvement in their nasal airway postoperatively, and the remaining three had no mention of postoperative airway in the record. The postoperative airway was not made worse in any of the patients operated on in the series. All of the patients had reconstruction when their Wegener's granulomatosis was in remission. Twelve of the 13 patients with an external deformity had a saddle-nose defect. The remaining deformity was a defect of the alar rim. Sixteen surgeries were preformed in total (15 dorsal repairs [12 primary, 3 revisions] and 1 alar rim repair). The most common graft materials used in the reconstruction of the dorsal deformities were costal cartilage (40% [6 of 15]) and calvarial bone (27% [4 of 15]). The remaining dorsal defects were repaired with irradiated rib (1 of 15), irradiated dura (1 of 15), conchal cartilage (1 of 15), iliac crest (1 of 15), and bony septum (1 of 15). The alar rim defect was repaired using a composite auricular graft. The overall success rates by graft type were as follows: costal cartilage, 83% (5 of 6); calvarial bone, 75% (3 of 4); composite auricular, 100% (1 of 1); iliac bone, 100% (1 of 1); conchal cartilage, 100% (1 of 1); septal bone, 100% (1 of 1); irradiated rib, 0% (0 of 1); and irradiated dura 0% (0 of 1). CONCLUSIONS: Reconstruction of external nasal deformities in patients with Wegener's granulomatosis is safe. Surgery does not appear to either induce a flare-up or accelerate the course of Wegener's granulomatosis. There may be a higher risk of failure in primary nasal dorsal repair in patients with Wegener's granulomatosis than in other patients undergoing dorsal augmentation. Irradiated materials in the series also appear to be more prone to resorption.     

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.     

Management and Follow-up of Localized Wegener's Granulomatosis: A Review of Five Cases

Objective —To evaluate the complications, efficacy of surgical treatment and outcome in patients with the localized form of Wegener's granulomatosis (WG).

Materials and Methods —We reviewed a series of 5 patients (3 males, 2 females; age range 22–67 years; mean age 44.6 years) with WG in the upper and lower respiratory tracts.

Results —Aural, nasal and ocular complications were common in our patients. All patients responded to standard immunosuppressive treatment, and all surgical treatments had a favorable outcome in the remission stage. Although there was no life-threatening disease activity during the course of treatment, minor relapses occurred in three patients.

Conclusions —Patients with localized WG may have a better outcome than those with systemic WG, but complications due to the disease or medication must be actively managed. Reconstructive surgery for patients with WG is safe and effective during the remission stage.     

Wegener's granulomatosis in the head and neck region

Wegener's granulomatosis (WG) is defined as a granulomatous inflammation of the upper and lower respiratory tract and systemic vasculitis of small and medium sized vessels which is often accompanied by a necrotizing glomerulonephritis. The etiology of the disease is still unknown. In former times untreated WG usually ended deadly. Immunosuppressive therapy made WG a treatable disease with a chronically relapsing course. Therefore an early diagnosis of WG is of utmost importance. WG usually starts as a limited and localized organ manifestation in the upper respiratory tract and it generalizes, if untreated, with pulmonary and renal involvement. Symptoms in the head and neck region are observed in up to 95% of the patients with WG. Sinusitis, crusting of the nose, development of a saddle nose, middle and inner ear symptoms and subglottic stenosis are common manifestations. Due to the early and common manifestation of WG in the head and neck region the otorhinolaryngologist plays an important role for the early diagnosis and the fast initiation of immunosuppressive therapy but also during follow-up for activity assessment.     

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.     

Updates in antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis for the ENT surgeon

ENT involvement is common in ANCA‐associated vasculitis (AAV), particularly in GPA and EGPA. Early recognition and treatment is important for good outcomes, yet evidence suggests that UK ENT surgeons may not consistently recognise the early features of AAV, despite a similar incidence to vestibular schwannoma. AAV is a rapidly advancing field, with significant developments in the understanding of its pathogenesis, classification and treatment over the past decade. Relevant vasculitis mimics are also discussed with a particular focus on the increasing prevalence of vasculitis mimics driven by an increase in recreational cocaine use, as well as the emergence and reclassification of several other vasculitis mimics in the head and neck. This article reviews key recent updates in the vasculitis literature, with a particular focus on those relevant to recognition and diagnosis of AAV for the ENT surgeon. Strengths and limitations of relevant diagnostic testing are discussed, and a method of evaluation of patients with features of AAV presenting to ENT services is outlined.     

Clinical outcomes of rhabdomyosarcoma and Ewing's sarcoma of the head and neck in children

Objective

To review our experience and critically evaluate treatment strategy and results in children with head and neck rhabdomyosarcoma and Ewing's sarcoma.

Methods

Retrospective charts review of children affected by non-orbital rhabdomyosarcoma or Ewing's sarcoma of the head and neck who were treated at our institution from January 1996 to August 2009.

Results

Seven consecutive children with head and neck rhabdomyosarcoma or Ewing's sarcoma were identified. Four children had rhabdomyosarcoma, 3 children had Ewing's sarcoma. Regions involved were: cheek, ethmoid and maxillary sinuses, nasopharynx, middle ear/mastoid and frontal bone. In one case, surgery was performed as primary treatment modality; the other children were treated firstly with chemotherapy. Three patients underwent surgical resection after chemotherapy, while 4 patients received radiotherapy. Five children are disease free after a median of 7.7 years from initial diagnosis. Two patients relapsed after 10 and 29 months from initial diagnosis respectively; despite the administration of additional therapy both children died of disease.

Conclusion

Treatment for rhabdomyosarcoma and Ewing's sarcoma consists in a multimodal therapy involving chemotherapy, radiotherapy and surgery. The optimum use, timing and intensity of these three treatments are still matters of international debate. Chemotherapy in association with radiotherapy has proven capable to obtain local and distant control of disease. But when surgery is unfeasible or fails in radicality, local control is difficult without radiotherapy. Despite additional therapeutic efforts, prognosis of relapsing disease remains poor.     

Carcinoma-associated monoclonal antibodies in head and neck carcinoma

Summary Monoclonal antibodies (mAbs) 175F4 (IgG1) and 175F11 (IgG2a), originally raised against the human mammary carcinoma cell line (ZR-75-1), react with a carcinoma-associated antigen in both adenocarcinomas and squamous cell carcinomas of different origins. Immunohistochemically, the mAbs exhibited reactivity with 42 out of 43 squamous cell carcinomas of the head and neck. Normal squamous epithelia were also reactive with the antibodies in the basal and suprabasal cell layer. In 175F4 F(ab)2 fragments localized a squamous cell carcinoma xenograft (HT-6) in nude mice with low blood pool activity, indicating a potential clinical usefulness for staging of squamous cell carcinomas in the head and neck.     

Local treatment of AIDS-associated bulky Kaposi's sarcoma in the head and neck region

Kaposi’s sarcoma (KS) is frequently seen in the head and neck regions of HIV-infected patients. We report two cases of patients with AIDS who consulted the ENT clinic. One patient came to our clinic complaining of abnormal sensations in the pharynx, and dysphasia due to a gross KS in the oropharynx. The excision of the tumor improved the difficulty of swallowing. The other patient complained of masticatory problems and tongue pain due to a bulky KS on the dorsal side of the tongue. We treated the tongue lesion with intralesional chemotherapy. The administration of intralesional vinblastine resulted in a partial response. Unless systemic chemotherapy is effective enough to improve a functional disorder, it is thought that local therapy employing excision or intralesional chemotherapy is one of the common therapeutic option of the otolaryngologist, because this treatment avoids severe side effects caused by systemic chemotherapy or radiotherapy.