The multiform and variable patterns of onset of orofacial granulomatosis

BACKGROUND: The recurrent chronic orofacial swelling caused by orofacial granulomatosis (OFG) can cause significant cosmetic and functional problems but can be prevented if the disease is diagnosed early and promptly treated. Although the enlargement of the lips is described to be the most common presenting complaint, the clinical onset of OFG may be characterized by minor associated mucosal and neurological manifestations, making early diagnosis very difficult or, sometimes, merely presumable. PATIENTS AND METHODS: We retrospectively analyzed the clinical manifestations of 19 patients with OFG, who were examined at our institution between 1998 and 2002, in order to determine their initial manifestations and presenting symptoms. RESULTS: A total of 10 patients showed classical recurrent enlargement of the lips (six lower; four upper) as presenting symptom. In the other nine patients, OFG onset was characterized by transient unilateral facial nerve palsy (two cases), intraoral manifestations (two cases), recurrent swelling of the periorbital area (two cases), of the chin (one case), of the zygomatic area (one case), and of the cheeks (one case). CONCLUSION: Our data underlined that OFG onset could be frequently characterized by widely variable, multiform, and temporary clinical findings. Involvement of atypical sites of the orofacial region and presence of single minor manifestations may occur as presenting symptoms, often preceding the development of traditional clinical findings.     

淋巴瘤样肉芽肿与韦格内肉芽肿临床特点的比较

目的 总结淋巴瘤样肉芽肿病(lym phom atoid granulom atosis,LG)与韦格内肉芽肿( egener granulo Wm atosis,W G)的临床特点,从临床上加以鉴别。 方法 回顾性总结我院与北京协和医院 1989 年以来收治的 6 例 LG和20 例 W G 患者的临床资料,并进行比较。 结果 发热、咳嗽及呼吸困难在 LG 中较常见,流涕、鼻衄及关节痛以W G 为多,肺受累以 LG 为多,耳鼻喉、眼及肾病变在 W G 中明显增多,皮肤受损两者相似。W G 患者常有 c-ANCA 阳性及尿沉渣异常。 LG X 线胸片为双侧多发结节,边界不清,多无肺门、纵隔淋巴结肿大; G 则为双侧多发边界清晰W的结节, 易形成空洞, 肺门和纵隔淋巴结可肿大。LG 病理改变为血管中心性淋巴增生性病变, 浸润的细胞主要是小淋巴细胞和不同数量大的不典型淋巴细胞; 而在 W G 中可见坏死性血管炎及大量中性白细胞、浆细胞及少量嗜酸细胞浸润形成的肉芽肿, 部分有多核巨细胞。W G 经治疗后, 多数患者病情缓解; 则疗效不佳。 结论 LG 和 W G 在临 LG床表现、实验室检查、 影像及病理诸方面的差异有利于两者的鉴别诊断。     

Reizhusten, Belastungsdyspnoe und zystische Lungenveränderungen bei einem 28jährigen Patienten

Zusammenfassung Eine neu aufgetretene Dyspnoesymptomatik und eine symmetrische, apikal betonte retikulonodul?re Zeichnungsvermehrung im R?ntgen-Thorax bei jungen rauchenden Erwachsenen müssen an das seltene Krankheitsbild der pulmonalen Histiocytosis X denken lassen. Klinischer Befund, laborchemische- und Lungenfunktionsuntersuchungen zeigen unspezifische Befunde. Neue radiologische Verfahren wie die hochaufl?sende Computertomographie (HRCT) leisten bei gezielter Indikationsstellung eine entscheidende differentialdiagnostische Hilfestellung. Dieser Fall verdeutlicht die M?glichkeit einer Diagnosesicherung durch transbronchiale Biopsien unter Verzicht auf offene Lungenbiopsien. Eine ambulante Diagnostik war m?glich, das h?here Risiko eines operativen Eingriffes konnte vermieden werden. Die Indikation zur Therapie ist nicht gesichert und wird daher durch den Grad der subjektiven bzw. funktionellen Einschr?nkung sowie den Verlauf bestimmt.     

Central Nervous System Lymphomatoid Granulomatosis Presenting with Parkinsonism

Lymphomatoid granulomatosis (LG) is a potentially malignant lymphoproliferative disorder. The lung is the most common involved site, followed by the skin and nervous system. However, LG of the central nervous system presenting with Parkinsonism is very rare. We report a patient with LG who presented with parkinsonian features such as bilateral rigidity, bradykinesia, and agitation. Brain magnetic resonance imaging showed multifocal punctuate enhanced lesions in both supra- and infratentorial areas. Steroid pulse therapy resulted in a dramatical improvement in the symptoms and MRI abnormalities.     

Immunoregulatory defects of V alpha 24V+ beta 11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis

The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) V alpha 24(+)V beta 11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.     

Anti-endothelial cell antibodies in patients with Wegener's granulomatosis and micropolyarteritis

Anti-endothelial cell antibodies (AECA) have been detected by cell surface radioimmunoassay in nine out of 15 patients with micropolyarteritis (MPA) and in two out of five patients with Wegener's granulomatosis. AECA mostly belonged to the IgG isotype and were present in the active phase of the diseases. These antibodies were not detectable in 10 sera from patients with essential mixed cryoglobulinaemia, suggesting that they were not a mere epiphenomenon consequent to the inflammatory vascular injury. The binding activity was not related to ABH antigens or to HLA class I antigens displayed by resting human endothelial cells in culture and was not influenced by removing immune complexes. Absorption of the anti-neutrophil cytoplasmic antibodies (ANCA), present in MPA and Wegener's granulomatosis sera, did not affect the endothelial binding. AECA-positive sera did not display lytic activity against endothelial cells, neither alone nor after addition of fresh complement or normal human peripheral blood mononuclear cells. Although AECA are not cytolytic for endothelial cell monolayers in vitro, the reactivity against intact endothelial cells suggests their possible involvement in in vivo pathological processes affecting vascular structures in small vessel primary vasculitides.     

Unusual aspects of allergic bronchopulmonary fungal disease: Report of two cases due to Curularia organisms associated with allergic fungal sinusitis

We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg-Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions.     

Minor salivary glands: Clinical,histological and immunohistochemical features of common and less common pathologies

Hundreds of minor salivary glands (MiSGs) are scattered in the oral cavity located at the submucosa layer. Beside their role in the oral cavity lubrication and immunity defence system, MiSGs are beneficial tissue source for diagnosing oral and non-oral related diseases. The advantage of MiSGs as a diagnostic tool reside on their fairly simple excisional procedure on one hand and negligible impact of the normal secretion capability of the salivary gland system on the other hand. The review focuses on pathologies related to developmental, reactive, metabolic, inflammatory and immunologic conditions, Iatrogenic causes and other undefined causes.     

Gingival Swelling as the Initial Manifestation of Granulomatosis with Polyangiitis

We describe a case of granulomatosis with polyangiitis (GPA; formerly named Wegener granulomatosis) that presented initially as florid areas of gingival swelling. The patient also had upper respiratory symptoms that included sinus congestion and cough of recent onset. Clinical-pathologic correlation aided the interpretation of non-specific biopsy findings and immediate referral to an appropriate medical specialist. Treatment was rendered at an early stage of disease with a good response to date. Review of the literature indicates that gingival swelling, often with the characteristic appearance of “strawberry gingivitis” may represent the initial sign of disease in 2% of patients with GPA. Biopsy of gingival lesions often shows a non-specific histologic appearance that should be interpreted in the context of the clinical appearance and pertinent medical history. The clinical investigations that lead to definitive diagnosis and treatment are presented to facilitate the management of this uncommon but potentially fatal condition.     

韦格纳肉芽肿病自身抗原蛋白酶3的抗原决定簇研究

目的　研究韦格纳肉芽肿病患者血清中抗蛋白酶 3自身抗体的抗原决定簇。方法　应用免疫印记分析法 ,研究在还原和非还原条件下蛋白酶 3的抗原活性。应用竞争性抑制ELISA和免疫印记分析法 ,研究两个抗蛋白酶 3的单克隆抗体HZ1F12和HZ1H3之间 ,及单克隆抗体和 2 2份韦格纳肉芽肿活动期的抗蛋白酶 3血清之间 ,对蛋白酶 3的竞争抑制能力 ,并分析其可能的抗原决定簇。结果　患者血清及单克隆抗体均识别非还原条件下的蛋白酶 3。HZ1F12可以被HZ1H3抑制 74 %。 2 2份血清中 ,10份 (46 % )可以完全或部分被HZ1F12抑制 ,9份 (41% )可以部分被HZ1H3抑制 ,6份 (2 7% )可以被HZ1F12和HZ1H3二者抑制。单克隆抗体也可以明显抑制患者血清的结合能力。结论　韦格纳肉芽肿病自身抗体的抗原决定簇是三维立体构型。单克隆抗体HZ1F12和HZ1H3识别相似或相近的抗原决定簇。韦格纳肉芽肿病患者的抗蛋白酶 3阳性血清识别的抗原决定簇是不一致的。