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Feline chronic gingivostomatitis: current concepts in clinical management
貓類慢性牙齦口炎：臨床管理的當前概念
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Maria Soltero-Rivera msoltero@ucdavis.edu, Stephanie Goldschmidt, and Boaz Arzi 查看所有作者和隸屬機構
Maria Soltero-Rivera msoltero@ucdavis.edu, Stephanie Goldschmidt, and Boaz Arzi 查看所有作者和隸屬機構
Abstract 摘要
Practical relevance: 實際相關性：
Feline chronic gingivostomatitis (FCGS) is a debilitating disease for cats and a challenge for veterinarians and cat caregivers alike. Recent literature indicates that the disease is immune-mediated in nature and likely associated with a chronic viral infection in patients with higher alpha diversity of their subgingival microbiome.
貓咪慢性牙齦口炎（FCGS）對貓咪來說是一種使人虛弱的疾病，對獸醫和貓咪照顧者來說也是一個挑戰。最近的文獻表明，該疾病本質上是免疫介導的，並且可能與具有較高亞牙齦微生物群α多樣性的患者的慢性病毒感染有關。
The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings.
FCGS 的免疫介導特性包括局部和系統性影響，受影響患者的轉錄組分析支持這些發現。
貓咪慢性牙齦口炎（FCGS）對貓咪來說是一種使人虛弱的疾病，對獸醫和貓咪照顧者來說也是一個挑戰。最近的文獻表明，該疾病本質上是免疫介導的，並且可能與具有較高亞牙齦微生物群α多樣性的患者的慢性病毒感染有關。
The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings.
FCGS 的免疫介導特性包括局部和系統性影響，受影響患者的轉錄組分析支持這些發現。
Treatment options: 治療選擇：
Localized therapy in the form of surgical extraction of all, or nearly all, teeth continues to be the mainstay of treatment. For cats that do not respond to surgical management, medical management, in the form of immunosuppressive or immunomodulatory therapy, remains an option. Analgesia is of fundamental importance.
局部療法以手術拔除所有或幾乎所有牙齒的形式仍然是治療的主要方法。對於對手術管理無反應的貓，醫療管理以免疫抑制或免疫調節療法的形式仍然是一個選擇。鎮痛是基本的重要性。
Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described.
利用間充質基質細胞療法的免疫調節為難治性患者提供了一種替代治療途徑，並可能針對此疾病中存在的慢性病毒感染。隨著參與此疾病的分子途徑得到更好的描述，治療分層和使用新型全身治療選擇的潛力可能會顯現出來。
局部療法以手術拔除所有或幾乎所有牙齒的形式仍然是治療的主要方法。對於對手術管理無反應的貓，醫療管理以免疫抑制或免疫調節療法的形式仍然是一個選擇。鎮痛是基本的重要性。
Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described.
利用間充質基質細胞療法的免疫調節為難治性患者提供了一種替代治療途徑，並可能針對此疾病中存在的慢性病毒感染。隨著參與此疾病的分子途徑得到更好的描述，治療分層和使用新型全身治療選擇的潛力可能會顯現出來。
Aims: 目標：
This review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease.
本綜述概述了當前和新興的概念，將有關 FCGS 的可用科學與該疾病的臨床管理聯繫起來。
本綜述概述了當前和新興的概念，將有關 FCGS 的可用科學與該疾病的臨床管理聯繫起來。
Evidence base: 證據基礎：
The article draws on the best evidence base at this juncture and is also driven by the authors’ collective experience of working on the disease for over a decade.
該文章基於目前最佳的證據基礎，並且也受到作者們在這種疾病上工作超過十年的集體經驗的驅動。
該文章基於目前最佳的證據基礎，並且也受到作者們在這種疾病上工作超過十年的集體經驗的驅動。
Introduction 引言
Feline gingivostomatitis is a chronic oral mucosal disease that affects up to 26% of domestic cats.1-4 Affected cats typically develop extensive inflammatory lesions throughout the oral cavity, including in the area lateral to the palatoglossal folds.5 There appear to be two clinical phenotypes of the disease - ulcerative and proliferative - though some patients will display both, as shown in Figure 1. Lesions are typically associated with moderate to severe oral pain, decreased or absent appetite, poor grooming and reduced socialization.5-7 Cats affected with feline chronic gingivostomatitis (FCGS) may be euthanized due to an insufficient response to therapy or a lack of resources for treatment.
貓咪牙齦口炎是一種慢性口腔黏膜疾病，影響多達 26%的家貓。受影響的貓咪通常會在口腔內部發展出廣泛的炎症病變，包括在腭舌摺的側面區域。該疾病似乎有兩種臨床表型 - 潰瘍型和增生型 - 雖然一些患者會同時顯示兩者，如圖 1 所示。病變通常與中度至重度的口腔疼痛、食慾減退或缺失、梳理不良和社交減少有關。受貓咪慢性牙齦口炎（FCGS）影響的貓咪可能因對治療反應不足或缺乏治療資源而被安樂死。
貓咪牙齦口炎是一種慢性口腔黏膜疾病，影響多達 26%的家貓。受影響的貓咪通常會在口腔內部發展出廣泛的炎症病變，包括在腭舌摺的側面區域。該疾病似乎有兩種臨床表型 - 潰瘍型和增生型 - 雖然一些患者會同時顯示兩者，如圖 1 所示。病變通常與中度至重度的口腔疼痛、食慾減退或缺失、梳理不良和社交減少有關。受貓咪慢性牙齦口炎（FCGS）影響的貓咪可能因對治療反應不足或缺乏治療資源而被安樂死。
The current body of literature supports that FCGS is immune-mediated in nature,8 as outlined in this review which includes a comparison of the local host response in FCGS and in the healthy oral mucosa (see box ‘The oral mucosa in health’). Furthermore, it is becoming unquestionable that the immune response is somehow related to feline calicivirus (FCV) infection.
目前的文獻支持 FCGS 本質上是免疫介導的， 8 如本綜述所述，其中包括 FCGS 與健康口腔黏膜的局部宿主反應比較（見框框「健康狀態下的口腔黏膜」）。此外，免疫反應與貓卡利病毒（FCV）感染之間的關係已變得無可置疑。
Targeted studies on the oral mucosa have evaluated the qualitative histomorphological structure, as well as characterizing and quantifying the immune cell types and host response in health and FCGS. In addition, untargeted, multiomic approaches have taken charge over recent years in describing the microbial landscape of FCGS,9,10 and the genetic11 and metabolic12 pathways involved in this disease.
針對口腔黏膜的針對性研究已評估其定性組織形態結構，並對健康和 FCGS 中的免疫細胞類型及宿主反應進行了特徵化和量化。此外，近年來，無針對性的多組學方法已開始描述 FCGS 的微生物景觀，以及參與此疾病的遺傳和代謝途徑。
目前的文獻支持 FCGS 本質上是免疫介導的， 8 如本綜述所述，其中包括 FCGS 與健康口腔黏膜的局部宿主反應比較（見框框「健康狀態下的口腔黏膜」）。此外，免疫反應與貓卡利病毒（FCV）感染之間的關係已變得無可置疑。
Targeted studies on the oral mucosa have evaluated the qualitative histomorphological structure, as well as characterizing and quantifying the immune cell types and host response in health and FCGS. In addition, untargeted, multiomic approaches have taken charge over recent years in describing the microbial landscape of FCGS,9,10 and the genetic11 and metabolic12 pathways involved in this disease.
針對口腔黏膜的針對性研究已評估其定性組織形態結構，並對健康和 FCGS 中的免疫細胞類型及宿主反應進行了特徵化和量化。此外，近年來，無針對性的多組學方法已開始描述 FCGS 的微生物景觀，以及參與此疾病的遺傳和代謝途徑。
In compiling this review, the authors’ aim has been to provide a cohesive summary of currently available scientific evidence that supports the immune-mediated nature of this disease. This is discussed in relation to etiologies and clinical management. The authors also highlight limitations within the current evidence base that inform recommendations for further research.
在編寫這篇綜述時，作者的目標是提供一個連貫的摘要，總結目前可用的科學證據，以支持這種疾病的免疫介導性質。這與病因和臨床管理相關進行了討論。作者還強調了當前證據基礎中的局限性，這些局限性為進一步研究的建議提供了信息。
Furthermore, they illuminate various aspects of surgical and clinical management, and make the case that a ‘personalized medicine’ approach (ie, tailored to the individual patient using different types of biomarkers) is appropriate for managing cats that are non-responsive to dental extraction therapy.
此外，他們闡明了手術和臨床管理的各個方面，並主張“個性化醫療”方法（即根據不同類型的生物標記量身定制以適應個別患者）對於管理對牙齒拔除療法無反應的貓是合適的。
在編寫這篇綜述時，作者的目標是提供一個連貫的摘要，總結目前可用的科學證據，以支持這種疾病的免疫介導性質。這與病因和臨床管理相關進行了討論。作者還強調了當前證據基礎中的局限性，這些局限性為進一步研究的建議提供了信息。
Furthermore, they illuminate various aspects of surgical and clinical management, and make the case that a ‘personalized medicine’ approach (ie, tailored to the individual patient using different types of biomarkers) is appropriate for managing cats that are non-responsive to dental extraction therapy.
此外，他們闡明了手術和臨床管理的各個方面，並主張“個性化醫療”方法（即根據不同類型的生物標記量身定制以適應個別患者）對於管理對牙齒拔除療法無反應的貓是合適的。
圖 1 貓咪慢性齦口炎（FCGS）的臨床表現可能略有不同，但其特徵是炎症不僅影響齦部，還擴展到牙槽和頰黏膜。(a,b) 一名患有難治性潰瘍性 FCGS 的病人，亦影響到舌下組織。(c) 一例顯示潰瘍和增生的情況。
Note the proliferation on the right side affecting the buccal and sublingual mucosa. (d) A case of FCGS where spontaneous bleeding from the areas of ulceration was noted. (e) Concurrent inflammation of the gingiva and alveolar mucosa is typical of patients with FCGS and in this case surrounds the left maxillary fourth premolar tooth.
注意右側的增生影響到頰黏膜和舌下黏膜。(d) 一例 FCGS 的病例，注意到潰瘍區域自發性出血。(e) 牙齦和牙槽黏膜的同時發炎是 FCGS 患者的典型特徵，在這個案例中圍繞著左側上頜第四前磨牙。
(f) In this cat with FCGS there is mild inflammation on the left side of the buccal mucosa, while the right side has moderate inflammation
在這隻患有 FCGS 的貓咪中，左側頰黏膜有輕微的炎症，而右側則有中度炎症
圖 2 先天免疫是由抗原呈現細胞（APCs）在損傷部位啟動的快速且非特異性的反應。適應性免疫在損傷發生後需要幾天到幾週，具有高度特異性並且持續長期。適應性免疫也可以是耐受性的。
To activate lymphocytes, APCs travel to inductive sites including tonsils, salivary glands, lymphoid follicles and draining lymph. Effector sites include the epithelium, lamina propia and salivary glands. Activated and expanded lymphocytes migrate from the effector to inductive areas to mediate the immune response.
為了激活淋巴細胞，抗原呈遞細胞(APCs) 會移動到誘導部位，包括扁桃體、唾液腺、淋巴濾泡和引流淋巴。效應部位包括上皮、固有層和唾液腺。活化和擴增的淋巴細胞從效應部位遷移到誘導區域，以介導免疫反應。
T cells are believed to help during rapid responses of antigen recall by providing protective responses while preventing adverse allergic reactions. The primary function of CD4+ cells is helping to regulate other immune cells either directly or indirectly. In health, lymphocytes are predominantly a memory population
T 細胞被認為在抗原回憶的快速反應中提供保護反應，同時防止不良的過敏反應。CD4+細胞的主要功能是幫助直接或間接調節其他免疫細胞。在健康狀態下，淋巴細胞主要是一種記憶細胞群體。
Local host response in FCGS
FCGS 中的局部宿主反應
The typical appearance of the mucosal epithelium of FCGS-affected cats is hyperplastic, with prominent rete pegs that extend deep into the submucosa (Figure 3). The submucosal capillaries are typically congested and lined with plump endothelial cells. The mucosa can also show ulceration; in those cases, neutrophils are primarily observed dispersed or aggregated within the lamina propria/ submucosa underlying areas of epithelial degeneration.8,21 Increased numbers of mast cells have been documented in gingival biopsies from cats with FCGS.22 Though their role in this disease is not entirely characterized, mast cells release a range of pro-inflammatory and immunomodulatory mediators, and it is possible that, even in small numbers, these cells could be involved in the initiation, propagation and perpetuation of local inflammatory and immunologic responses in FCGS.21
FCGS 受影響貓咪的黏膜上皮典型外觀為增生性，具有明顯的網狀突起，深入到黏膜下層（圖 3）。黏膜下層的毛細血管通常充血，並且被豐滿的內皮細胞所覆蓋。黏膜也可能出現潰瘍；在這些情況下，中性粒細胞主要分散或聚集在基底層的固有層/黏膜下層，位於上皮退化區域。 8,21 在 FCGS 貓咪的牙齦活檢中已記錄到肥大細胞數量增加。 22 雖然它們在這種疾病中的作用尚未完全確定，但肥大細胞釋放一系列促炎和免疫調節介質，即使數量不多，這些細胞也可能參與 FCGS 中局部炎症和免疫反應的啟動、傳播和持續。 21
FCGS 受影響貓咪的黏膜上皮典型外觀為增生性，具有明顯的網狀突起，深入到黏膜下層（圖 3）。黏膜下層的毛細血管通常充血，並且被豐滿的內皮細胞所覆蓋。黏膜也可能出現潰瘍；在這些情況下，中性粒細胞主要分散或聚集在基底層的固有層/黏膜下層，位於上皮退化區域。 8,21 在 FCGS 貓咪的牙齦活檢中已記錄到肥大細胞數量增加。 22 雖然它們在這種疾病中的作用尚未完全確定，但肥大細胞釋放一系列促炎和免疫調節介質，即使數量不多，這些細胞也可能參與 FCGS 中局部炎症和免疫反應的啟動、傳播和持續。 21
The non-inflamed feline oral mucosa is an active immunologic site, with a cell population that is predominantly biased toward a type 1 cytokine expression profile. Conversely, the mucosa of patients with FCGS shows a mixed type 1 and type 2 profile, indicating the development of a solid cellular and humoral response.23 The mucosa of cats affected by FCGS is characterized by a heavy infiltration of lymphocytes and plasma cells, with occasional to abundant Mott cells. T cells are present in the superficial mucosa and submucosa (CD3), whereas B cells and Mott cells appear to be restricted to the submucosa (CD20).8 Most of the plasma cells are of the IgG isotype, with fewer IgA+ and IgM+ plasma cells described.21
未發炎的貓口腔黏膜是一個活躍的免疫學場所，細胞群體主要偏向於 1 型細胞激素表達型。相反，FCGS 患者的黏膜顯示出混合的 1 型和 2 型表型，表明發展出穩固的細胞和體液反應。受 FCGS 影響的貓的黏膜特徵是淋巴細胞和漿細胞的重度浸潤，偶爾可見到豐富的莫特細胞。T 細胞存在於表層黏膜和黏膜下層（CD3），而 B 細胞和莫特細胞似乎僅限於黏膜下層（CD20）。大多數漿細胞為 IgG 亞型，描述的 IgA+和 IgM+漿細胞較少。
未發炎的貓口腔黏膜是一個活躍的免疫學場所，細胞群體主要偏向於 1 型細胞激素表達型。相反，FCGS 患者的黏膜顯示出混合的 1 型和 2 型表型，表明發展出穩固的細胞和體液反應。受 FCGS 影響的貓的黏膜特徵是淋巴細胞和漿細胞的重度浸潤，偶爾可見到豐富的莫特細胞。T 細胞存在於表層黏膜和黏膜下層（CD3），而 B 細胞和莫特細胞似乎僅限於黏膜下層（CD20）。大多數漿細胞為 IgG 亞型，描述的 IgA+和 IgM+漿細胞較少。
Immunolabeling of CD4+ and CD8+ T cells in affected mucosa has revealed an approximately equal ratio of these cells in the lamina propria in edentulous patients,20 though cats with teeth remaining show a predominance of CD8+ cells.21 These inflammatory cells are frequently distributed in a band-like pattern that obscures the border between epithelium and submucosa.8 The number of cells labeled for CD3+, CD4+, CD8+, CD79a+, IgG+, IgM+, IgA+ or L1+ (neutrophils) within the lamina propria/submucosa is significantly increased in FCGS as compared with the healthy oral mucosa; so too is the number of mast cells.
在受影響的黏膜中對 CD4+和 CD8+ T 細胞的免疫標記顯示，在無牙患者的固有層中這些細胞的比例大致相等，儘管有牙齒的貓則顯示出 CD8+細胞的優勢。這些炎症細胞經常以帶狀模式分佈，模糊了上皮和黏膜下層之間的邊界。在 FCGS 中，固有層/黏膜下層中標記為 CD3+、CD4+、CD8+、CD79a+、IgG+、IgM+、IgA+或 L1+（中性粒細胞）的細胞數量顯著增加，相較於健康的口腔黏膜；肥大細胞的數量也是如此。
Furthermore, correlations between the severity of inflammation and the number of plasma cells (CD79a+ cells), neutrophils (L1+ cells), helper T cells (CD3+) and MHC II glycoprotein levels have been noted.21 Mast cell densities were found to be significantly increased in gingival tissues adjacent to teeth affected by FCGS, although not significantly different from those observed in cats with periodontal disease and feline resorptive lesions (Figure 4).22
此外，已注意到炎症嚴重程度與漿細胞（CD79a+細胞）、中性粒細胞（L1+細胞）、輔助 T 細胞（CD3+）及 MHC II 糖蛋白水平之間的相關性。 21 在受 FCGS 影響的牙齦組織中，肥大細胞密度顯著增加，儘管與患有牙周病和貓咪吸收性病變的貓所觀察到的並無顯著差異（圖 4）。 22
在受影響的黏膜中對 CD4+和 CD8+ T 細胞的免疫標記顯示，在無牙患者的固有層中這些細胞的比例大致相等，儘管有牙齒的貓則顯示出 CD8+細胞的優勢。這些炎症細胞經常以帶狀模式分佈，模糊了上皮和黏膜下層之間的邊界。在 FCGS 中，固有層/黏膜下層中標記為 CD3+、CD4+、CD8+、CD79a+、IgG+、IgM+、IgA+或 L1+（中性粒細胞）的細胞數量顯著增加，相較於健康的口腔黏膜；肥大細胞的數量也是如此。
Furthermore, correlations between the severity of inflammation and the number of plasma cells (CD79a+ cells), neutrophils (L1+ cells), helper T cells (CD3+) and MHC II glycoprotein levels have been noted.21 Mast cell densities were found to be significantly increased in gingival tissues adjacent to teeth affected by FCGS, although not significantly different from those observed in cats with periodontal disease and feline resorptive lesions (Figure 4).22
此外，已注意到炎症嚴重程度與漿細胞（CD79a+細胞）、中性粒細胞（L1+細胞）、輔助 T 細胞（CD3+）及 MHC II 糖蛋白水平之間的相關性。 21 在受 FCGS 影響的牙齦組織中，肥大細胞密度顯著增加，儘管與患有牙周病和貓咪吸收性病變的貓所觀察到的並無顯著差異（圖 4）。 22
圖 3 來自 FCGS 患者的頰黏膜組織切片。注意增生的上皮和延伸深入黏膜下層的顯著網狀突起（指狀結構）。20×放大；比例尺 = 20 微米
Cytokine expression has been correlated with disease severity in FCGS-affected cats. This mirrors what is observed in human periodontal disease, which is not surprising considering that the majority of cats affected by FCGS have concurrent periodontitis.23,24 Although the immunologic host response at the level of the gingiva of patients with FCGS has not been fully characterized, dental radiography demonstrates that FCGS is associated with widespread and severe periodontitis, with a high prevalence of external inflammatory root resorption and retained roots, suggesting a highly inflammatory, destructive process (Figure 5).24 This response could also reflect the collection of cytokines that are expressed during chronic inflammation of the oral mucosa arising from various etiologies, as these seem to have little to no variation.25
細胞激素的表達與受 FCGS 影響的貓的疾病嚴重程度相關。這與人類牙周病的觀察相似，這並不令人驚訝，因為大多數受 FCGS 影響的貓都有同時存在的牙周炎。 23,24 雖然 FCGS 患者在牙齦層面的免疫宿主反應尚未完全特徵化，但牙科 X 光檢查顯示 FCGS 與廣泛且嚴重的牙周炎相關，並且外部炎性根吸收和保留根的高發生率，這表明一個高度炎症性、破壞性的過程（圖 5）。 24 這種反應也可能反映在由各種病因引起的口腔黏膜慢性炎症期間表達的細胞激素的集合，因為這些似乎幾乎沒有變化。 25
細胞激素的表達與受 FCGS 影響的貓的疾病嚴重程度相關。這與人類牙周病的觀察相似，這並不令人驚訝，因為大多數受 FCGS 影響的貓都有同時存在的牙周炎。 23,24 雖然 FCGS 患者在牙齦層面的免疫宿主反應尚未完全特徵化，但牙科 X 光檢查顯示 FCGS 與廣泛且嚴重的牙周炎相關，並且外部炎性根吸收和保留根的高發生率，這表明一個高度炎症性、破壞性的過程（圖 5）。 24 這種反應也可能反映在由各種病因引起的口腔黏膜慢性炎症期間表達的細胞激素的集合，因為這些似乎幾乎沒有變化。 25
Figure 4 Histologic sections from the buccal mucosa and palatoglossal folds of a healthy cat (a,bi-iv), and from the gingiva and affected buccal mucosa of a patient with FCGS (c-f). LP = lamina propia; SE = subepithelium.
圖 4 健康貓咪的頰黏膜和腭舌摺的組織學切片（a, bi-iv），以及 FCGS 患者的牙齦和受影響的頰黏膜（c-f）。LP = 固有層；SE = 上皮下層。
圖 4 健康貓咪的頰黏膜和腭舌摺的組織學切片（a, bi-iv），以及 FCGS 患者的牙齦和受影響的頰黏膜（c-f）。LP = 固有層；SE = 上皮下層。
(a) Buccal mucosa ((immunohistochemistry [IHC] stain of CD1c+; 600× magnification; bar = 40 μm). Note the intraepithelial dendritic cells demonstrating characteristic mature dendritic cell morphology (arrow).
(a) 頰黏膜（（免疫組織化學 [IHC] 染色 CD1c+；600× 放大；標尺 = 40 μm）。注意上皮內樹突細胞顯示出特徵性的成熟樹突細胞形態（箭頭）。
(a) 頰黏膜（（免疫組織化學 [IHC] 染色 CD1c+；600× 放大；標尺 = 40 μm）。注意上皮內樹突細胞顯示出特徵性的成熟樹突細胞形態（箭頭）。
(b) Palatoglossal fold (400× magnification; bar = 40 μm): (i) note the subepithelial leukocyte clusters (arrow) (hematoxylin and eosin [H&E] stain); (ii) subepithelial collection of CD4+ T cells (IHC stain of CD4+); (iii) subepithelial cluster of CD1c+ denritic cells (IHC stain of CD1c+); (iv) subepithelial sets and diffuse MHC II+ cells (IHC stain of MHC II+). Reproduced from Arzi et al,20 with permission of Wiley and Sons.
(b) 腭舌摺 (400× 放大; 標尺 = 40 μm): (i) 注意上皮下白血球聚集 (箭頭) (蘇木精-伊紅 [H&E] 染色); (ii) 上皮下 CD4+ T 細胞的聚集 (CD4+ 的免疫組織化學染色); (iii) 上皮下 CD1c+ 樹突細胞的聚集 (CD1c+ 的免疫組織化學染色); (iv) 上皮下 MHC II+ 細胞的集合和散佈 (MHC II+ 的免疫組織化學染色)。轉載自 Arzi 等人， 20 ，經 Wiley and Sons 授權。
(b) 腭舌摺 (400× 放大; 標尺 = 40 μm): (i) 注意上皮下白血球聚集 (箭頭) (蘇木精-伊紅 [H&E] 染色); (ii) 上皮下 CD4+ T 細胞的聚集 (CD4+ 的免疫組織化學染色); (iii) 上皮下 CD1c+ 樹突細胞的聚集 (CD1c+ 的免疫組織化學染色); (iv) 上皮下 MHC II+ 細胞的集合和散佈 (MHC II+ 的免疫組織化學染色)。轉載自 Arzi 等人， 20 ，經 Wiley and Sons 授權。
(c) Gingiva adjacent to teeth affected by FCGS (toluidine blue stain, 400× magnification). Note the submucosal mast cells (small black arrows), lymphocytes (black arrowheads), neutrophils (large black arrow), plasma-like cells (white arrows) and macrophage-like cells (white arrowhead). Reproduced from Arzi et al,22 with permission of Elsevier.
(c) 受 FCGS 影響的牙齦（托烏藍染色，400×放大）。注意到黏膜下的肥大細胞（小黑箭頭）、淋巴細胞（黑箭頭）、中性粒細胞（大黑箭頭）、漿細胞樣細胞（白箭頭）和巨噬細胞樣細胞（白箭頭）。經 Arzi 等人重製， 22 ，經 Elsevier 許可。
(c) 受 FCGS 影響的牙齦（托烏藍染色，400×放大）。注意到黏膜下的肥大細胞（小黑箭頭）、淋巴細胞（黑箭頭）、中性粒細胞（大黑箭頭）、漿細胞樣細胞（白箭頭）和巨噬細胞樣細胞（白箭頭）。經 Arzi 等人重製， 22 ，經 Elsevier 許可。
(d) Abundant plasma cells, occasional Mott cells (ie, plasma cells that have spherical inclusions, or Russell bodies, packed in their cytoplasm) and proportionately fewer lymphocytes and neutrophils (H&E stain; 100× magnification).
(d) 豐富的漿細胞，偶爾出現的莫特細胞（即，細胞質中含有球形包涵體或拉塞爾小體的漿細胞）以及相對較少的淋巴細胞和中性粒細胞（H&E 染色；100× 放大）。
(d) 豐富的漿細胞，偶爾出現的莫特細胞（即，細胞質中含有球形包涵體或拉塞爾小體的漿細胞）以及相對較少的淋巴細胞和中性粒細胞（H&E 染色；100× 放大）。
(e) Note how T lymphocytes cluster in the epithelium (IHC stain of CD3+; 100× magnification).
(e) 注意 T 淋巴細胞在上皮中的聚集（CD3+的免疫組織化學染色；100×放大）。
(e) 注意 T 淋巴細胞在上皮中的聚集（CD3+的免疫組織化學染色；100×放大）。
(f) B lymphocytes are highly present in the submucosal compartment (IHC stain of CD20+; 100× magnification)
(f) B 淋巴細胞在黏膜下腔室中高度存在（CD20+ 的免疫組織化學染色；100× 放大）
(f) B 淋巴細胞在黏膜下腔室中高度存在（CD20+ 的免疫組織化學染色；100× 放大）
Figure 5 Intraoral radiographs of a 5-year-old domestic shorthair cat with clinically and histopathologically confirmed FCGS.
圖 5 一隻 5 歲的家用短毛貓的口內 X 光片，臨床和組織病理學確認為 FCGS。
圖 5 一隻 5 歲的家用短毛貓的口內 X 光片，臨床和組織病理學確認為 FCGS。
(a) Occlusal view of the maxillary incisor teeth. (b) Occlusal view of the mandibular incisor teeth. (c) Right mandibular PM3 to M1. (d) Left mandibular PM3 and PM4.
(a) 上顎切牙的咬合面視圖。 (b) 下顎切牙的咬合面視圖。 (c) 右側下顎 PM3 至 M1。 (d) 左側下顎 PM3 和 PM4。
The radiographs demonstrate mild to moderate, semi-generalized horizontal alveolar bone loss (†) and type I tooth resorption (*) at the furcation of affected teeth, as well as a missing left mandibular first molar tooth and buccal bone expansion of the mandibular canine teeth
放射線影像顯示輕度至中度的半廣泛性水平牙槽骨喪失（†）以及受影響牙齒分叉處的 I 型牙齒吸收（*），還有缺失的左下頜第一磨牙和下頜犬齒的頰骨擴張
(a) 上顎切牙的咬合面視圖。 (b) 下顎切牙的咬合面視圖。 (c) 右側下顎 PM3 至 M1。 (d) 左側下顎 PM3 和 PM4。
The radiographs demonstrate mild to moderate, semi-generalized horizontal alveolar bone loss (†) and type I tooth resorption (*) at the furcation of affected teeth, as well as a missing left mandibular first molar tooth and buccal bone expansion of the mandibular canine teeth
放射線影像顯示輕度至中度的半廣泛性水平牙槽骨喪失（†）以及受影響牙齒分叉處的 I 型牙齒吸收（*），還有缺失的左下頜第一磨牙和下頜犬齒的頰骨擴張
Systemic manifestations 全身表現
As we deepen our understanding, it has become apparent that FCGS is not only a local disease but one with systemic ramifications.8,26-29 Affected cats have high circulating CD8+ effector memory cell levels with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-).8 Memory CD8+ T cells are the principal component of immunity against intracellular pathogens such as viruses. This means there is an unresolved inflammation in which CD8+ T cells are activated more than once and remain activated.
隨著我們對此病的理解加深，FCGS 不僅是一種局部疾病，還具有系統性影響。受影響的貓咪有高水平的循環 CD8+ 效應記憶細胞，並伴隨中央記憶細胞的減少以及循環活化的 CD8+ T 細胞（CD25+，CD62L-）的證據。記憶 CD8+ T 細胞是對抗細胞內病原體（如病毒）的免疫主要成分。這意味著存在未解決的炎症，其中 CD8+ T 細胞被多次激活並保持激活狀態。
The predominance of CD8+ T cells in lesions and increased circulatory effector memory cells in FCGS confirm that an intracellular organism - most likely one involved in a viral infection - causes inflammation.
在病變中 CD8+ T 細胞的佔主導地位以及 FCGS 中循環效應記憶細胞的增加確認了一種細胞內生物體 - 很可能與病毒感染有關 - 造成了炎症。
隨著我們對此病的理解加深，FCGS 不僅是一種局部疾病，還具有系統性影響。受影響的貓咪有高水平的循環 CD8+ 效應記憶細胞，並伴隨中央記憶細胞的減少以及循環活化的 CD8+ T 細胞（CD25+，CD62L-）的證據。記憶 CD8+ T 細胞是對抗細胞內病原體（如病毒）的免疫主要成分。這意味著存在未解決的炎症，其中 CD8+ T 細胞被多次激活並保持激活狀態。
The predominance of CD8+ T cells in lesions and increased circulatory effector memory cells in FCGS confirm that an intracellular organism - most likely one involved in a viral infection - causes inflammation.
在病變中 CD8+ T 細胞的佔主導地位以及 FCGS 中循環效應記憶細胞的增加確認了一種細胞內生物體 - 很可能與病毒感染有關 - 造成了炎症。
Most affected cats also exhibit elevated serum and salivary immunoglobulin levels.28 Salivary immunoglobulins are likely produced by the mucosal plasma cells and reach the oral cavity via the gingival crevicular fluid or by leaking across the mucosa. The hypergammaglobulinemia, a polyclonal gammopathy seen in these cases, could be secondary to upregulation of IL-6 in FCGS.23 Additionally, it is suspected that cats with FCGS are more likely to have a systemic inflammatory response.26 Other evidence of systemic inflammation in cats with FCGS includes increased expression of proinflammatory serum cytokines, such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6, as well as blood neutrophil counts (Figure 6).29
大多數受影響的貓也表現出血清和唾液免疫球蛋白水平升高。唾液免疫球蛋白可能是由黏膜漿細胞產生，並通過牙齦溝液或穿過黏膜進入口腔。這些病例中出現的高免疫球蛋白血症是一種多克隆γ球蛋白病，可能是由於 FCGS 中 IL-6 的上調所致。此外，懷疑 FCGS 的貓更可能有全身性炎症反應。FCGS 貓的全身性炎症的其他證據包括促炎性血清細胞因子的表達增加，如干擾素-伽瑪（IFN-γ）、腫瘤壞死因子-α（TNF-α）、白介素-1β（IL-1β）和 IL-6，以及血液中中性粒細胞計數（圖 6）。
大多數受影響的貓也表現出血清和唾液免疫球蛋白水平升高。唾液免疫球蛋白可能是由黏膜漿細胞產生，並通過牙齦溝液或穿過黏膜進入口腔。這些病例中出現的高免疫球蛋白血症是一種多克隆γ球蛋白病，可能是由於 FCGS 中 IL-6 的上調所致。此外，懷疑 FCGS 的貓更可能有全身性炎症反應。FCGS 貓的全身性炎症的其他證據包括促炎性血清細胞因子的表達增加，如干擾素-伽瑪（IFN-γ）、腫瘤壞死因子-α（TNF-α）、白介素-1β（IL-1β）和 IL-6，以及血液中中性粒細胞計數（圖 6）。
Though originally thought to be a local disease impacting only the oral cavity, in a controlled study evaluating the prevalence of esophagitis in cats with FCGS, evidence of esophagitis was found via esophagoscopy in 98% of affected cats, compared with 0% of control cats.30 Affected patients showed microscopic evidence of inflammation and metaplasia in otherwise grossly normal-appearing tissues and in the absence of clinical signs consistent with gastrointestinal disease. Endoscopic re-examination of cats treated for FCGS that no longer showed clinical signs of that disease also demonstrated macroscopic healing of esophagitis.
雖然最初被認為是一種僅影響口腔的局部疾病，但在一項評估貓咪慢性牙齦口腔炎（FCGS）患病率的控制研究中，通過食道鏡檢查發現 98%的受影響貓咪有食道炎的證據，而對照組貓咪則為 0%。受影響的患者在其他外觀正常的組織中顯示出微觀的炎症和化生證據，且缺乏與胃腸疾病一致的臨床症狀。對於已經不再顯示該疾病臨床症狀的 FCGS 治療貓咪進行的內窺鏡重新檢查也顯示出食道炎的宏觀癒合。
The investigators of the study proposed that esophagitis in these cases is due to a concurrent dysbiosis in the esophagus promoting the production of certain proinflammatory cytokines.30
研究人員提出，這些案例中的食道炎是由於食道中同時存在的微生物失調，促進了某些促炎細胞因子的產生。
雖然最初被認為是一種僅影響口腔的局部疾病，但在一項評估貓咪慢性牙齦口腔炎（FCGS）患病率的控制研究中，通過食道鏡檢查發現 98%的受影響貓咪有食道炎的證據，而對照組貓咪則為 0%。受影響的患者在其他外觀正常的組織中顯示出微觀的炎症和化生證據，且缺乏與胃腸疾病一致的臨床症狀。對於已經不再顯示該疾病臨床症狀的 FCGS 治療貓咪進行的內窺鏡重新檢查也顯示出食道炎的宏觀癒合。
The investigators of the study proposed that esophagitis in these cases is due to a concurrent dysbiosis in the esophagus promoting the production of certain proinflammatory cytokines.30
研究人員提出，這些案例中的食道炎是由於食道中同時存在的微生物失調，促進了某些促炎細胞因子的產生。
圖 6 對 FCGS 患者系統免疫反應的評估顯示，60%的患者有高球蛋白血症，IFN-γ、TNF-α和 IL-1β的循環水平升高，30-40%的患者有中性粒細胞增多，以及 CD8+效應記憶細胞。 29 這些發現與評估局部免疫反應的研究結果相符。
Current knowledge of the etiology of FCGS
FCGS 的病因目前的知識
Several conditions and infectious agents have been implicated as the inciting factor of the immune response seen in FCGS,31–33 without proof of causation. An association between the clinical severity of FCGS and the presence of FCV (toll-like receptor [TLR] 7) and Tannerella forsythia (TLR2) has also been noted, sparking an interest in these as possible etiologic agents.34,35 Unbiased metagenomic and tran-scriptomic analyses of FCGS patients revealed that the only microbe strongly associated with FCGS was FCV, which was detected in 21/23 FCGS-affected cats and not in any of the control cats.10 This study also showed that coinfection of FCGS-affected cats with FCV and puma feline foamy virus (PFFV) might adversely affect the response to treatment.10 This finding was supported by an approximately 40-fold higher expression of guanylate binding protein-1 (GBP-1) in FCGS patients compared with controls, a gene known to have antiviral effects.10
幾種病症和感染性病原被認為是引發 FCGS 中免疫反應的因素， 31–33 但尚無因果關係的證據。FCGS 的臨床嚴重程度與 FCV（類 Toll 受體 [TLR] 7）和 Tannerella forsythia（TLR2）的存在之間也有關聯，這引發了對這些可能的病因病原的興趣。 34,35 對 FCGS 患者進行的無偏見宏基因組和轉錄組分析顯示，與 FCGS 強烈相關的唯一微生物是 FCV，該微生物在 23 隻 FCGS 受影響的貓中檢測到 21 隻，而在任何對照貓中均未檢測到。 10 這項研究還顯示，FCGS 受影響的貓與 FCV 和美洲獅貓泡沫病毒（PFFV）的共感染可能會對治療反應產生不利影響。 10 這一發現得到了 FCGS 患者中鳥苷酸結合蛋白-1（GBP-1）表達量約高於對照組 40 倍的支持，該基因已知具有抗病毒作用。 10
幾種病症和感染性病原被認為是引發 FCGS 中免疫反應的因素， 31–33 但尚無因果關係的證據。FCGS 的臨床嚴重程度與 FCV（類 Toll 受體 [TLR] 7）和 Tannerella forsythia（TLR2）的存在之間也有關聯，這引發了對這些可能的病因病原的興趣。 34,35 對 FCGS 患者進行的無偏見宏基因組和轉錄組分析顯示，與 FCGS 強烈相關的唯一微生物是 FCV，該微生物在 23 隻 FCGS 受影響的貓中檢測到 21 隻，而在任何對照貓中均未檢測到。 10 這項研究還顯示，FCGS 受影響的貓與 FCV 和美洲獅貓泡沫病毒（PFFV）的共感染可能會對治療反應產生不利影響。 10 這一發現得到了 FCGS 患者中鳥苷酸結合蛋白-1（GBP-1）表達量約高於對照組 40 倍的支持，該基因已知具有抗病毒作用。 10
Yet, FCV oral load in cats with FCGS, as evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) testing on oropharyngeal swabs, was not correlated with the severity of oral lesions or treatment outcome.7 Furthermore, studies attempting to prove Koch’s postulate by inoculating healthy cats with FCV to recapitulate FCGS have failed to prove causation.35,36 Although acute stomatitis occurred, the chronic carrier state did not.36 It is important to note that one of these studies35 involved 16-week-old specific pathogen-free cats. The oral cavity of kittens may not mimic the clinical scenario necessary for the disease to occur, in terms of genetic basis, oral microbiome and microenvironment. Additionally, three studies have documented decreased viral load or resolution of FCV along with the resolution of clinical signs and gross lesions in FCGS.10,37,38 In short, despite inconsistencies, the literature largely supports a role for FCV, at least in modulating the severity of disease.
然而，通過對咽喉拭子進行實時反轉錄聚合酶鏈反應（RT-PCR）測試評估的貓咪 FCGS 中的 FCV 口腔載量，與口腔病變的嚴重程度或治療結果並無相關性。此外，試圖通過接種健康貓咪 FCV 以重現 FCGS 來證明科赫法則的研究未能證明因果關係。儘管出現了急性口炎，但並未出現慢性攜帶狀態。值得注意的是，其中一項研究涉及 16 週大的特定病原體陰性貓咪。小貓的口腔可能無法模擬發生該疾病所需的臨床情境，無論是在遺傳基礎、口腔微生物組還是微環境方面。此外，三項研究記錄了隨著臨床症狀和 FCGS 的明顯病變的消退，FCV 的病毒載量減少或消失。簡而言之，儘管存在不一致性，文獻在很大程度上支持 FCV 在調節疾病嚴重性方面的作用。
然而，通過對咽喉拭子進行實時反轉錄聚合酶鏈反應（RT-PCR）測試評估的貓咪 FCGS 中的 FCV 口腔載量，與口腔病變的嚴重程度或治療結果並無相關性。此外，試圖通過接種健康貓咪 FCV 以重現 FCGS 來證明科赫法則的研究未能證明因果關係。儘管出現了急性口炎，但並未出現慢性攜帶狀態。值得注意的是，其中一項研究涉及 16 週大的特定病原體陰性貓咪。小貓的口腔可能無法模擬發生該疾病所需的臨床情境，無論是在遺傳基礎、口腔微生物組還是微環境方面。此外，三項研究記錄了隨著臨床症狀和 FCGS 的明顯病變的消退，FCV 的病毒載量減少或消失。簡而言之，儘管存在不一致性，文獻在很大程度上支持 FCV 在調節疾病嚴重性方面的作用。
Historically, feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) have been inconclusively linked to FCGS.39 More compelling evidence has been provided in a study comparing the clinical outcome of cats with FCGS, with and without FIV and FeLV infection, which showed different phenotypic manifestations as well as an effect on response to full mouth extractions (FMEs) or partial mouth extractions (PMEs) and adjuvant medical support.40 Phenotypically, FeLV-positive cats had significantly less proliferative stomatitis and fewer resorptive lesions, though they tended to have more lingual ulcers. This study concluded that FeLV-positive cats had a 7.5-times greater chance of having no improvement after dental extractions than cats that did not carry retroviral disease.40
歷史上，貓白血病病毒（FeLV）和貓免疫缺陷病毒（FIV）與貓慢性齦口炎（FCGS）之間的關聯尚無定論。 39 一項研究提供了更有說服力的證據，該研究比較了有無 FIV 和 FeLV 感染的 FCGS 貓的臨床結果，顯示出不同的表型表現以及對全口拔牙（FMEs）或部分口拔牙（PMEs）和輔助醫療支持的反應影響。 40 在表型上，FeLV 陽性的貓有顯著較少的增生性口炎和較少的吸收性病變，儘管它們往往有更多的舌部潰瘍。這項研究得出結論，FeLV 陽性的貓在牙齒拔除後沒有改善的機會是未感染逆轉錄病毒的貓的 7.5 倍。 40
歷史上，貓白血病病毒（FeLV）和貓免疫缺陷病毒（FIV）與貓慢性齦口炎（FCGS）之間的關聯尚無定論。 39 一項研究提供了更有說服力的證據，該研究比較了有無 FIV 和 FeLV 感染的 FCGS 貓的臨床結果，顯示出不同的表型表現以及對全口拔牙（FMEs）或部分口拔牙（PMEs）和輔助醫療支持的反應影響。 40 在表型上，FeLV 陽性的貓有顯著較少的增生性口炎和較少的吸收性病變，儘管它們往往有更多的舌部潰瘍。這項研究得出結論，FeLV 陽性的貓在牙齒拔除後沒有改善的機會是未感染逆轉錄病毒的貓的 7.5 倍。 40
The subgingival microbiome has also been characterized in cats with FCGS.9 A higher alpha diversity was found in these patients, together with a higher relative abundance of Peptostreptococcus species as compared with healthy cats (P = 0.0052) and cats with periodontitis (P = 0.0127).9 The implications of these findings are unclear at this time.
在患有貓咪慢性齦口炎（FCGS）的貓隻中，牙齦下微生物組也已被特徵化。 9 這些患者的α多樣性較高，與健康貓隻（P = 0.0052）和患有牙周炎的貓隻（P = 0.0127）相比，Peptostreptococcus 物種的相對豐度也較高。 9 這些發現的意義目前尚不清楚。
在患有貓咪慢性齦口炎（FCGS）的貓隻中，牙齦下微生物組也已被特徵化。 9 這些患者的α多樣性較高，與健康貓隻（P = 0.0052）和患有牙周炎的貓隻（P = 0.0127）相比，Peptostreptococcus 物種的相對豐度也較高。 9 這些發現的意義目前尚不清楚。
Finally, a study evaluating whether the number of cohabiting cats represents a risk factor for FCGS showed that cats in shared households had significantly increased odds of FCGS (seven-fold) compared with those from single-cat households.41 Each additional cat in the household increased the odds of FCGS by more than 70%.41
最後，一項研究評估了共同居住的貓隻數量是否構成 FCGS 的風險因素，結果顯示，共同居住的貓隻相比單貓家庭的貓隻，FCGS 的發生機率顯著增加（增加七倍）。每增加一隻貓，FCGS 的機率增加超過 70%。
最後，一項研究評估了共同居住的貓隻數量是否構成 FCGS 的風險因素，結果顯示，共同居住的貓隻相比單貓家庭的貓隻，FCGS 的發生機率顯著增加（增加七倍）。每增加一隻貓，FCGS 的機率增加超過 70%。
Clinical management of FCGS
FCGS 的臨床管理
The clinical management goals for FCGS are to decrease or eliminate antigenic stimulation and modulate the abnormal immune response. Given that nearly all affected cats will exhibit moderate to severe periodontitis and tooth resorption, surgical management in the form of dental extractions is the starting point.
FCGS 的臨床管理目標是減少或消除抗原刺激並調節異常的免疫反應。考慮到幾乎所有受影響的貓都會出現中度至重度的牙周炎和牙齒吸收，外科管理以牙齒拔除的形式作為起點。
Periodontitis is a substantial inflammatory burden on the oral mucosa and the immune system. Therefore, extraction of teeth will effectively reduce a portion of the chronic inflammatory burden, allowing for a subpopulation of patients to achieve a significant improvement or even a cure.
牙周炎對口腔黏膜和免疫系統造成了相當大的炎症負擔。因此，拔除牙齒將有效減少部分慢性炎症負擔，使一部分患者能夠實現顯著改善甚至治癒。
FCGS 的臨床管理目標是減少或消除抗原刺激並調節異常的免疫反應。考慮到幾乎所有受影響的貓都會出現中度至重度的牙周炎和牙齒吸收，外科管理以牙齒拔除的形式作為起點。
Periodontitis is a substantial inflammatory burden on the oral mucosa and the immune system. Therefore, extraction of teeth will effectively reduce a portion of the chronic inflammatory burden, allowing for a subpopulation of patients to achieve a significant improvement or even a cure.
牙周炎對口腔黏膜和免疫系統造成了相當大的炎症負擔。因此，拔除牙齒將有效減少部分慢性炎症負擔，使一部分患者能夠實現顯著改善甚至治癒。
However, it is unclear at this juncture how removal of teeth is associated with reduction or elimination of FCV from the oral mucosa.10 It is plausible that tooth extraction removes the characteristic subgingival microbiome that may play a role in this disease, thereby reducing the inflammatory burden and freeing the immune system to focus on concurrent chronic viral infections. Alternatively, by reducing inflammation, the environment may be less favorable for these viruses to thrive.
然而，目前尚不清楚拔牙與減少或消除口腔黏膜中的 FCV 之間的關聯。 10 拔牙可能去除了可能在此疾病中發揮作用的特徵性牙齦下微生物群，從而減輕了炎症負擔，並使免疫系統能夠專注於同時存在的慢性病毒感染。或者，通過減少炎症，環境可能對這些病毒的生存不再那麼有利。
然而，目前尚不清楚拔牙與減少或消除口腔黏膜中的 FCV 之間的關聯。 10 拔牙可能去除了可能在此疾病中發揮作用的特徵性牙齦下微生物群，從而減輕了炎症負擔，並使免疫系統能夠專注於同時存在的慢性病毒感染。或者，通過減少炎症，環境可能對這些病毒的生存不再那麼有利。
Preoperative evaluation 術前評估
FCGS-affected cats should be evaluated for risks associated with a relatively long anesthetic procedure when either full-mouth or partial tooth extractions are being planned (complete blood count, serum biochemistry panel, etc). In addition, viral disease testing to assess FeLV, FIV, FCV and PFFV status should be performed due to the potential prognostic significance.10,40 Repeat testing 30 and 60 days after possible FeLV and FIV exposure, respectively, should be considered to confirm a negative status.42 Combined virus isolation and RT-PCR techniques using samples obtained from the conjunctiva or oropharynx is recommended to increase detection rates for FCV.43 To the authors’ knowledge, commercial PFFV testing is not available at this time.
FCGS 受影響的貓應在計劃進行全口或部分拔牙時，評估與相對較長的麻醉程序相關的風險（完整的血液計數、血清生化面板等）。此外，應進行病毒疾病檢測以評估 FeLV、FIV、FCV 和 PFFV 的狀態，因為這可能具有預後意義。 10,40 應考慮在可能的 FeLV 和 FIV 接觸後的 30 天和 60 天進行重複檢測，以確認陰性狀態。 42 建議使用從結膜或口咽獲取的樣本進行病毒分離和 RT-PCR 技術的結合，以提高 FCV 的檢測率。 43 據作者所知，目前尚無商業 PFFV 檢測可用。
FCGS 受影響的貓應在計劃進行全口或部分拔牙時，評估與相對較長的麻醉程序相關的風險（完整的血液計數、血清生化面板等）。此外，應進行病毒疾病檢測以評估 FeLV、FIV、FCV 和 PFFV 的狀態，因為這可能具有預後意義。 10,40 應考慮在可能的 FeLV 和 FIV 接觸後的 30 天和 60 天進行重複檢測，以確認陰性狀態。 42 建議使用從結膜或口咽獲取的樣本進行病毒分離和 RT-PCR 技術的結合，以提高 FCV 的檢測率。 43 據作者所知，目前尚無商業 PFFV 檢測可用。
A standardized activity index has been developed to monitor clinical manifestations associated with inflammation in the oral cavity of cats with FCGS. The Stomatitis Disease Activity Index (SDAI), initially devised by Dr Jamie Anderson and used in several previous studies,29,44-46 has been a valuable tool to assist the diagnostic process and status monitoring. The index considers both the client’s assessment of quality of life of the affected patient at home and the gross evaluation of the oral cavity by the veterinary practitioner. However, at times, disparities arise between the owner and clinical assessment of patient disease status.
已開發出一個標準化的活動指數，以監測與貓咪慢性牙齦口炎（FCGS）相關的口腔炎症的臨床表現。口腔炎疾病活動指數（SDAI）最初由 Jamie Anderson 博士設計，並在幾項先前的研究中使用， 29,44-46 成為協助診斷過程和狀態監測的有價值工具。該指數考慮了客戶對受影響患者在家中生活質量的評估以及獸醫對口腔的粗略評估。然而，有時候，飼主和臨床對患者疾病狀態的評估之間會出現差異。
Consequently, the authors of this review have created a modified score that considers objective criteria (see Appendix 1 in the supplementary material).
因此，本綜述的作者創建了一個修改過的評分標準，考慮了客觀標準（請參見補充材料中的附錄 1）。
已開發出一個標準化的活動指數，以監測與貓咪慢性牙齦口炎（FCGS）相關的口腔炎症的臨床表現。口腔炎疾病活動指數（SDAI）最初由 Jamie Anderson 博士設計，並在幾項先前的研究中使用， 29,44-46 成為協助診斷過程和狀態監測的有價值工具。該指數考慮了客戶對受影響患者在家中生活質量的評估以及獸醫對口腔的粗略評估。然而，有時候，飼主和臨床對患者疾病狀態的評估之間會出現差異。
Consequently, the authors of this review have created a modified score that considers objective criteria (see Appendix 1 in the supplementary material).
因此，本綜述的作者創建了一個修改過的評分標準，考慮了客觀標準（請參見補充材料中的附錄 1）。
The SDAI should be completed by the veterinarian at the patient’s first visit and used at each consecutive evaluation to monitor progress. The questions in the owner assessment portion can be incorporated into the veterinarian’s usual history-taking survey.
SDAI 應由獸醫在患者首次就診時填寫，並在每次後續評估中使用以監測進展。飼主評估部分的問題可以納入獸醫的常規病史調查中。
The veterinarian’s assessment is performed during the awake oral examination, although light sedation may be necessary in uncooperative patients, or the clinician may opt to wait until the patient undergoes general anesthesia to evaluate the oral cavity. The objective assessment is completed once all the diagnostic work-up for that patient has been returned.
獸醫的評估是在清醒的口腔檢查中進行的，儘管在不合作的病患中可能需要輕度鎮靜，或者臨床醫生可能選擇等到病患接受全身麻醉後再評估口腔。當該病患的所有診斷檢查結果返回後，客觀評估便完成。
Although it has been histopathologically validated,4,7,47 the SDAI has not undergone intra-and inter-reader variability studies and so, whenever possible, it should be the same veterinarian who completes this form for an individual patient.
儘管它已經在組織病理學上得到了驗證， 4,7,47 SDAI 尚未進行讀者內部和讀者之間的變異性研究，因此，無論何時可能，都應由同一位獸醫為個別患者填寫此表格。
Moreover, future studies should aim to assess the contribution of the different subsections of the SDAI (ie, veterinarian assessment, objective assessment and owner assessment) in obtaining a score of prognostic significance for the patient.
此外，未來的研究應旨在評估 SDAI 不同子部分（即獸醫評估、客觀評估和主人評估）在獲得對患者具有預後意義的分數中的貢獻。
SDAI 應由獸醫在患者首次就診時填寫，並在每次後續評估中使用以監測進展。飼主評估部分的問題可以納入獸醫的常規病史調查中。
The veterinarian’s assessment is performed during the awake oral examination, although light sedation may be necessary in uncooperative patients, or the clinician may opt to wait until the patient undergoes general anesthesia to evaluate the oral cavity. The objective assessment is completed once all the diagnostic work-up for that patient has been returned.
獸醫的評估是在清醒的口腔檢查中進行的，儘管在不合作的病患中可能需要輕度鎮靜，或者臨床醫生可能選擇等到病患接受全身麻醉後再評估口腔。當該病患的所有診斷檢查結果返回後，客觀評估便完成。
Although it has been histopathologically validated,4,7,47 the SDAI has not undergone intra-and inter-reader variability studies and so, whenever possible, it should be the same veterinarian who completes this form for an individual patient.
儘管它已經在組織病理學上得到了驗證， 4,7,47 SDAI 尚未進行讀者內部和讀者之間的變異性研究，因此，無論何時可能，都應由同一位獸醫為個別患者填寫此表格。
Moreover, future studies should aim to assess the contribution of the different subsections of the SDAI (ie, veterinarian assessment, objective assessment and owner assessment) in obtaining a score of prognostic significance for the patient.
此外，未來的研究應旨在評估 SDAI 不同子部分（即獸醫評估、客觀評估和主人評估）在獲得對患者具有預後意義的分數中的貢獻。
A summary of the preoperative diagnostic approach for these patients is available in Figure 7. Confirmation of the diagnosis is achieved via incisional biopsy performed under anesthesia. The information provided by histopathology may also have prognostic value or identify disease subtypes, as is the case for infiltrative gastrointestinal disease in dogs and cats.48-52 The authors are currently studying the effects of eosinophils in the outcome of FCGS patients.
這些患者的術前診斷方法摘要可在圖 7 中找到。通過在麻醉下進行切除活檢來確認診斷。組織病理學提供的信息也可能具有預後價值或識別疾病亞型，這在犬貓的浸潤性胃腸疾病中是如此。 48-52 作者目前正在研究嗜酸性粒細胞對 FCGS 患者結果的影響。
這些患者的術前診斷方法摘要可在圖 7 中找到。通過在麻醉下進行切除活檢來確認診斷。組織病理學提供的信息也可能具有預後價值或識別疾病亞型，這在犬貓的浸潤性胃腸疾病中是如此。 48-52 作者目前正在研究嗜酸性粒細胞對 FCGS 患者結果的影響。
Surgical management 外科管理
The success rate for dental extractions in cats affected by FCGS was first reported in 1997.53 Historically, this treatment was instituted based on the assumption that FCGS patients have a dysfunction of a protective mechanism or a detrimental immunologic reaction induced by bacterial periodontopathogens or viruses, and tooth extractions were thought to aid in reducing the chronic antigenic stimulation these patients were facing.53 While this may partly be the case given the characteristic subgingival microbiome of these patients,9 it has also been recognized that extractions are an effective therapy for treating moderate to severe periodontitis, which is present in up to 93% of affected cats, and tooth resorption and retained roots, which are seen in up to 66% of affected cats.6,24,53
在 1997 年首次報導了受 FCGS 影響的貓咪進行牙齒拔除的成功率。 53 歷史上，這種治療是基於假設 FCGS 患者存在保護機制的功能障礙或由細菌牙周病原體或病毒引起的有害免疫反應，因此認為拔牙有助於減少這些患者面臨的慢性抗原刺激。 53 雖然考慮到這些患者特有的牙齦下微生物群，這可能部分成立， 9 但也已經認識到，拔牙對於治療中度至重度牙周炎是有效的，這在高達 93%的受影響貓咪中存在，並且牙齒吸收和保留根部的情況在高達 66%的受影響貓咪中可見。 6,24,53
在 1997 年首次報導了受 FCGS 影響的貓咪進行牙齒拔除的成功率。 53 歷史上，這種治療是基於假設 FCGS 患者存在保護機制的功能障礙或由細菌牙周病原體或病毒引起的有害免疫反應，因此認為拔牙有助於減少這些患者面臨的慢性抗原刺激。 53 雖然考慮到這些患者特有的牙齦下微生物群，這可能部分成立， 9 但也已經認識到，拔牙對於治療中度至重度牙周炎是有效的，這在高達 93%的受影響貓咪中存在，並且牙齒吸收和保留根部的情況在高達 66%的受影響貓咪中可見。 6,24,53
圖 7 總結 FCGS 患者在手術前、手術中和手術後的診斷和治療建議的示意圖。
As discussed in the text, immunosuppressive therapy refers to the use of glucocorticoids to affect the immune response more globally (compared with immunomodulation, which refers to more targeted treatment of specific portions of the immune system via different types of medications).
如文中所述，免疫抑制療法是指使用糖皮質激素更全面地影響免疫反應（與免疫調節相比，免疫調節是指通過不同類型的藥物對免疫系統特定部分進行更具針對性的治療）。
SDAI = Stomatitis Disease Activity Index; CBC = complete blood count; FeLV = feline leukemia virus; FIV = feline immunodeficiency virus; FCV = feline calicivirus; PFFV = puma feline foamy virus; PME = partial mouth extraction; FME = full mouth extraction; IFN = interferon
SDAI = 口腔炎疾病活動指數；CBC = 完整血球計數；FeLV = 貓白血病病毒；FIV = 貓免疫缺陷病毒；FCV = 貓卡利病毒；PFFV = 美洲獅貓泡沫病毒；PME = 部分口腔拔牙；FME = 全口拔牙；IFN = 干擾素
Early studies from 199753 and 20086 reported similar response rates to extraction therapy, with the first of these published works demonstrating that 80% of cats (24/30) were significantly improved or clinically cured at follow-up 11-24 months after treatment.53 In both of these studies, most patients (cumulatively 96.8% [60/62]) were treated with PMEs.
1997 年 53 和 2008 年 6 的早期研究報告了對拔牙療法的相似反應率，其中第一篇發表的作品顯示，80%的貓（24/30）在治療後 11-24 個月的隨訪中顯著改善或臨床治癒。 53 在這兩項研究中，大多數患者（累計 96.8% [60/62]）接受了 PMEs 治療。
Re-evaluating the success rate of extraction therapy after radiographic findings came to light, and with a greater number of patients, a later study, published in 2015, revealed a response rate of 39% (37/95) for substantial clinical improvement and 28% (27/95) for complete resolution of stomatitis.5
在放射學發現浮現後重新評估拔牙療法的成功率，隨著患者數量的增加，2015 年發表的一項後續研究顯示，顯著臨床改善的反應率為 39%（37/95），而口腔炎完全緩解的反應率為 28%（27/95）。
1997 年 53 和 2008 年 6 的早期研究報告了對拔牙療法的相似反應率，其中第一篇發表的作品顯示，80%的貓（24/30）在治療後 11-24 個月的隨訪中顯著改善或臨床治癒。 53 在這兩項研究中，大多數患者（累計 96.8% [60/62]）接受了 PMEs 治療。
Re-evaluating the success rate of extraction therapy after radiographic findings came to light, and with a greater number of patients, a later study, published in 2015, revealed a response rate of 39% (37/95) for substantial clinical improvement and 28% (27/95) for complete resolution of stomatitis.5
在放射學發現浮現後重新評估拔牙療法的成功率，隨著患者數量的增加，2015 年發表的一項後續研究顯示，顯著臨床改善的反應率為 39%（37/95），而口腔炎完全緩解的反應率為 28%（27/95）。
In line with these findings, approximately 33% of cats (31/95) did not respond to extraction therapy in this later study.5 The study also evaluated the role of extended medical management in surgically treated cases and revealed that most (68.8%) of the patients that achieved substantial improvement or complete resolution required medical management with antimicrobial, anti-inflammatory or analgesic medications for a finite amount of time after the 2-week immediate postoperative period.5 In contrast to previous studies, this study was able to evaluate for the first time the effect of the extent of dental extractions on the outcome, concluding that there was no significant difference between cats treated with PMEs vs FMEs in terms of the overall response to treatment.5 This finding supports the notion that dental plaque is a less crucial etiologic factor than previously thought. The possibility that there can be a variation in disease phenotype or that patients treated with PMEs are showing an entirely different disease altogether, such as aggressive periodontitis or contact stomatitis, should also not be discounted.5 Though early intervention could plausibly lead to better outcomes in this inflammatory disease, no studies have evaluated the effect that the duration of clinical signs has on the outcome of surgical treatment. However, in one study, duration of clinical signs was not correlated with severity of the lesions (clinical scores) at the time of treatment.7
根據這些發現，大約 33%的貓（31/95）在這項後續研究中對拔牙療法沒有反應。 5 該研究還評估了在外科治療病例中擴展醫療管理的作用，並顯示大多數（68.8%）獲得顯著改善或完全緩解的患者在兩週的立即術後期間後，需要有限時間的抗微生物、抗炎或止痛藥物進行醫療管理。 5 與之前的研究相比，這項研究首次能夠評估牙齒拔除範圍對結果的影響，得出結論認為接受 PMEs 與 FMEs 治療的貓在整體治療反應方面沒有顯著差異。 5 這一發現支持了牙菌斑是一個不如先前認為的那麼關鍵的病因因素的觀點。還應該考慮到疾病表型可能存在變異，或者接受 PMEs 治療的患者顯示出完全不同的疾病，例如侵襲性牙周炎或接觸性口炎。 5 雖然早期介入可能會導致這種炎症性疾病的更好結果，但尚無研究評估臨床症狀持續時間對手術治療結果的影響。然而，在一項研究中，臨床症狀的持續時間與治療時病變的嚴重程度（臨床評分）並無相關性。 7
根據這些發現，大約 33%的貓（31/95）在這項後續研究中對拔牙療法沒有反應。 5 該研究還評估了在外科治療病例中擴展醫療管理的作用，並顯示大多數（68.8%）獲得顯著改善或完全緩解的患者在兩週的立即術後期間後，需要有限時間的抗微生物、抗炎或止痛藥物進行醫療管理。 5 與之前的研究相比，這項研究首次能夠評估牙齒拔除範圍對結果的影響，得出結論認為接受 PMEs 與 FMEs 治療的貓在整體治療反應方面沒有顯著差異。 5 這一發現支持了牙菌斑是一個不如先前認為的那麼關鍵的病因因素的觀點。還應該考慮到疾病表型可能存在變異，或者接受 PMEs 治療的患者顯示出完全不同的疾病，例如侵襲性牙周炎或接觸性口炎。 5 雖然早期介入可能會導致這種炎症性疾病的更好結果，但尚無研究評估臨床症狀持續時間對手術治療結果的影響。然而，在一項研究中，臨床症狀的持續時間與治療時病變的嚴重程度（臨床評分）並無相關性。 7
The impact of concurrent viral infection on the success of extraction therapy has been evaluated in a recent study which showed that FeLV-positive cats had a 7.5-times greater likelihood of no improvement after dental extractions.40 Coinfection with FCV and PFFV has also been found to be significantly more likely in cats with refractory FCGS than in cats with responsive FCGS.10
最近的一項研究評估了同時病毒感染對拔牙療法成功的影響，結果顯示 FeLV 陽性的貓在拔牙後沒有改善的可能性是 7.5 倍。 40 與 FCV 和 PFFV 的共感染在難治性 FCGS 的貓中發現的可能性顯著高於對應性 FCGS 的貓。 10
最近的一項研究評估了同時病毒感染對拔牙療法成功的影響，結果顯示 FeLV 陽性的貓在拔牙後沒有改善的可能性是 7.5 倍。 40 與 FCV 和 PFFV 的共感染在難治性 FCGS 的貓中發現的可能性顯著高於對應性 FCGS 的貓。 10
At this juncture, PMEs (extraction of all premolar and molar teeth) and FMEs have continued to provide the best long-term results.5,7,53 In the light of the existing body of knowledge, the authors have a number of suggestions regarding best practice, as outlined in the box ‘Recommendations for tooth extraction therapy’.
在這個時刻，PMEs（拔除所有前臼齒和臼齒）和 FMEs 仍然提供最佳的長期結果。根據現有的知識體系，作者對最佳實踐有幾項建議，如“牙齒拔除療法建議”框中所述。
在這個時刻，PMEs（拔除所有前臼齒和臼齒）和 FMEs 仍然提供最佳的長期結果。根據現有的知識體系，作者對最佳實踐有幾項建議，如“牙齒拔除療法建議”框中所述。
Medical management 醫療管理
Medical management of FCGS may be challenging to maintain owing to the significant oral pain caused by this disease, but is necessary for both acute and chronic settings.
由於此疾病造成的顯著口腔疼痛，FCGS 的醫療管理可能難以維持，但在急性和慢性情況下都是必要的。
Medical management before tooth extraction has failed to affect the overall response to surgical treatment, and is likely only to temporarily alleviate some of the discomfort associated with stomatitis in cats.5 In short, medical management has no role as a sole treatment entity in place of surgery at this time. However, it is a fundamental consideration, given the often severe pain exhibited by FCGS patients and the concurrent infections that may occur.24 Moreover, approximately a third of cats receiving tooth extraction therapy do not respond to surgical treatment, and appropriate support via medical management becomes essential postoperatively in these refractory cases (see box ‘What denotes “refractory”?’).
在拔牙之前的醫療管理未能影響手術治療的整體反應，並且可能僅能暫時緩解貓咪口腔炎相關的不適。 5 簡而言之，醫療管理目前無法作為手術的唯一治療方式。然而，考慮到 FCGS 患者常表現出的劇烈疼痛以及可能發生的併發感染，這是一個基本的考量。 24 此外，大約三分之一接受拔牙治療的貓咪對手術治療沒有反應，因此在這些難治性病例中，術後通過醫療管理提供適當的支持變得至關重要（見框內“什麼是‘難治性’？”）。
由於此疾病造成的顯著口腔疼痛，FCGS 的醫療管理可能難以維持，但在急性和慢性情況下都是必要的。
Medical management before tooth extraction has failed to affect the overall response to surgical treatment, and is likely only to temporarily alleviate some of the discomfort associated with stomatitis in cats.5 In short, medical management has no role as a sole treatment entity in place of surgery at this time. However, it is a fundamental consideration, given the often severe pain exhibited by FCGS patients and the concurrent infections that may occur.24 Moreover, approximately a third of cats receiving tooth extraction therapy do not respond to surgical treatment, and appropriate support via medical management becomes essential postoperatively in these refractory cases (see box ‘What denotes “refractory”?’).
在拔牙之前的醫療管理未能影響手術治療的整體反應，並且可能僅能暫時緩解貓咪口腔炎相關的不適。 5 簡而言之，醫療管理目前無法作為手術的唯一治療方式。然而，考慮到 FCGS 患者常表現出的劇烈疼痛以及可能發生的併發感染，這是一個基本的考量。 24 此外，大約三分之一接受拔牙治療的貓咪對手術治療沒有反應，因此在這些難治性病例中，術後通過醫療管理提供適當的支持變得至關重要（見框內“什麼是‘難治性’？”）。
The authors institute a personalized medicine (tailored) approach for cats that do not respond to dental extractions. In the absence of systemic disease, refractory cases have been managed with a combination of analgesia and immunosuppressive or immunomodulatory therapy. Current work from the authors’ institution supports the use of biomarkers in stratifying treatment.
作者為不對牙齒拔除手術有反應的貓咪採取個性化醫療（量身定制）的方法。在沒有全身性疾病的情況下，難治性病例已通過鎮痛劑和免疫抑制或免疫調節療法的組合進行管理。作者機構的最新研究支持使用生物標記來分層治療。
Biomarker discovery in patients with FCGS is ongoing work inspired by recent findings that approximately two-thirds of cases that are not responsive to extraction therapy are coinfected with FCV and PFFV,10 and also that there is an effect of FeLV status on the prognosis of these cats.40 Such research suggests that patients that are FeLV, FIV, FCV and/or PFFV positive should undergo medical management in conjunction with surgical management.
在 FCGS 患者中，生物標記的發現仍在進行中，這受到最近發現的啟發，即大約三分之二的對拔牙療法無反應的病例與 FCV 和 PFFV 共同感染， 10 並且 FeLV 狀態對這些貓的預後有影響。 40 這項研究表明，FeLV、FIV、FCV 和/或 PFFV 陽性的患者應該在外科管理的同時進行醫療管理。
作者為不對牙齒拔除手術有反應的貓咪採取個性化醫療（量身定制）的方法。在沒有全身性疾病的情況下，難治性病例已通過鎮痛劑和免疫抑制或免疫調節療法的組合進行管理。作者機構的最新研究支持使用生物標記來分層治療。
Biomarker discovery in patients with FCGS is ongoing work inspired by recent findings that approximately two-thirds of cases that are not responsive to extraction therapy are coinfected with FCV and PFFV,10 and also that there is an effect of FeLV status on the prognosis of these cats.40 Such research suggests that patients that are FeLV, FIV, FCV and/or PFFV positive should undergo medical management in conjunction with surgical management.
在 FCGS 患者中，生物標記的發現仍在進行中，這受到最近發現的啟發，即大約三分之二的對拔牙療法無反應的病例與 FCV 和 PFFV 共同感染， 10 並且 FeLV 狀態對這些貓的預後有影響。 40 這項研究表明，FeLV、FIV、FCV 和/或 PFFV 陽性的患者應該在外科管理的同時進行醫療管理。
The following discussion focuses on analgesic, antimicrobial, immunosuppressive and immunomodulatory therapy, with Figure 7 presenting a summary of key treatment recommendations.
以下討論集中於鎮痛、抗微生物、免疫抑制和免疫調節療法，圖 7 呈現了主要治療建議的摘要。
以下討論集中於鎮痛、抗微生物、免疫抑制和免疫調節療法，圖 7 呈現了主要治療建議的摘要。
Analgesia 鎮痛
Pain management is essential at all stages of FCGS management: in the acute setting, in the post-surgical setting and in those cases refractory to extraction therapy.
疼痛管理在 FCGS 管理的所有階段都是必不可少的：在急性期、在手術後期以及在那些對拔牙療法無反應的病例中。
In a study evaluating the analgesic effects and absorption of buprenorphine after buccal administration in feline oral disease, cats with stomatitis exhibited lower bioavailability and a shorter absorption half-life.55 Despite this, buprenorphine produced an analgesic effect and low inter-individual variability in plasma concentration compared with healthy cats and saline control.55 Other pain management agents that may be beneficial, but where scientific data are still lacking to support their use in FCGS, include N-methyl-D-aspartate (NMDA) receptor antagonists (amantadine), gabapentin, opioids other than buprenorphine, and non-steroidal anti-inflammatory drugs (NSAIDs).
在一項評估布洛芬在貓口腔疾病中經口腔給藥後的鎮痛效果和吸收的研究中，患有口腔炎的貓顯示出較低的生物利用度和較短的吸收半衰期。儘管如此，與健康貓和生理鹽水對照組相比，布洛芬仍產生了鎮痛效果，且血漿濃度的個體間變異性較低。其他可能有益的疼痛管理藥物，但目前仍缺乏科學數據支持其在貓慢性牙齦口腔炎中的使用，包括 N-甲基-D-天冬氨酸（NMDA）受體拮抗劑（阿曼他丁）、加巴噴丁、除布洛芬外的鴉片類藥物以及非類固醇抗炎藥（NSAIDs）。
疼痛管理在 FCGS 管理的所有階段都是必不可少的：在急性期、在手術後期以及在那些對拔牙療法無反應的病例中。
In a study evaluating the analgesic effects and absorption of buprenorphine after buccal administration in feline oral disease, cats with stomatitis exhibited lower bioavailability and a shorter absorption half-life.55 Despite this, buprenorphine produced an analgesic effect and low inter-individual variability in plasma concentration compared with healthy cats and saline control.55 Other pain management agents that may be beneficial, but where scientific data are still lacking to support their use in FCGS, include N-methyl-D-aspartate (NMDA) receptor antagonists (amantadine), gabapentin, opioids other than buprenorphine, and non-steroidal anti-inflammatory drugs (NSAIDs).
在一項評估布洛芬在貓口腔疾病中經口腔給藥後的鎮痛效果和吸收的研究中，患有口腔炎的貓顯示出較低的生物利用度和較短的吸收半衰期。儘管如此，與健康貓和生理鹽水對照組相比，布洛芬仍產生了鎮痛效果，且血漿濃度的個體間變異性較低。其他可能有益的疼痛管理藥物，但目前仍缺乏科學數據支持其在貓慢性牙齦口腔炎中的使用，包括 N-甲基-D-天冬氨酸（NMDA）受體拮抗劑（阿曼他丁）、加巴噴丁、除布洛芬外的鴉片類藥物以及非類固醇抗炎藥（NSAIDs）。
✜ Amantadine has historically been used as an antiviral agent in humans; however, most recently, it has been shown to aid in chronic pain management in cats via antagonism of NMDA receptors.56,57 Sedation can be a side effect observed in cats.56 A dosage of 3–5 mg/kg PO q24h led to a significantly improved quality of life in cats with osteoarthritis.56
✜ 阿曼他丁歷史上被用作人類的抗病毒藥物；然而，最近的研究顯示它可以通過拮抗 NMDA 受體來幫助貓咪的慢性疼痛管理。 56,57 鎮靜可能是貓咪中觀察到的副作用。 56 每公斤 3–5 毫克的口服劑量每 24 小時一次顯著改善了患有骨關節炎的貓咪的生活質量。 56
✜ 阿曼他丁歷史上被用作人類的抗病毒藥物；然而，最近的研究顯示它可以通過拮抗 NMDA 受體來幫助貓咪的慢性疼痛管理。 56,57 鎮靜可能是貓咪中觀察到的副作用。 56 每公斤 3–5 毫克的口服劑量每 24 小時一次顯著改善了患有骨關節炎的貓咪的生活質量。 56
✜ Gabapentin is a structural analog of gamma-aminobutyric acid (GABA) that likely has an inhibitory effect on voltage-gated calcium channels.58 It is the most commonly prescribed medication for management of musculoskeletal and neuropathic pain in cats,59,60 although some studies have reported no significant analgesic effects.61,62 A study evaluating the analgesic effects of gabapentin combined with buprenorphine in cats undergoing ovariohysterectomy found that postoperative pain scores and prevalence of rescue analgesia were not significantly different when compared with use of a meloxicam and buprenorphine combination.63 Both treatment combinations were administered before surgery. Consequently, the authors of this review consider gabapentin to be an adjunct treatment option. The medication has high bioavailability (94.77%) after oral dosing at 5–10 mg/kg.
✜ 加巴噴丁是伽馬氨基丁酸（GABA）的結構類似物，可能對電壓依賴性鈣通道具有抑制作用。 58 它是貓咪管理肌肉骨骼和神經性疼痛的最常用藥物， 59,60 雖然一些研究報告顯示其鎮痛效果並不顯著。 61,62 一項評估加巴噴丁與布洛芬聯合使用對接受卵巢子宮切除術貓咪的鎮痛效果的研究發現，術後疼痛評分和救援鎮痛的發生率與使用美洛昔康和布洛芬的組合相比並無顯著差異。 63 這兩種治療組合在手術前給予。因此，本綜述的作者認為加巴噴丁是一種輔助治療選擇。該藥物在口服劑量為 5–10 mg/kg 後具有高生物利用度（94.77%）。
This dose can be repeated every 8–12 h, with pharmacokinetic studies showing the shorter dosing intervals to be more effective than q12h dosing.64
這個劑量可以每 8-12 小時重複，藥物動力學研究顯示較短的給藥間隔比每 12 小時給藥更有效。
✜ 加巴噴丁是伽馬氨基丁酸（GABA）的結構類似物，可能對電壓依賴性鈣通道具有抑制作用。 58 它是貓咪管理肌肉骨骼和神經性疼痛的最常用藥物， 59,60 雖然一些研究報告顯示其鎮痛效果並不顯著。 61,62 一項評估加巴噴丁與布洛芬聯合使用對接受卵巢子宮切除術貓咪的鎮痛效果的研究發現，術後疼痛評分和救援鎮痛的發生率與使用美洛昔康和布洛芬的組合相比並無顯著差異。 63 這兩種治療組合在手術前給予。因此，本綜述的作者認為加巴噴丁是一種輔助治療選擇。該藥物在口服劑量為 5–10 mg/kg 後具有高生物利用度（94.77%）。
This dose can be repeated every 8–12 h, with pharmacokinetic studies showing the shorter dosing intervals to be more effective than q12h dosing.64
這個劑量可以每 8-12 小時重複，藥物動力學研究顯示較短的給藥間隔比每 12 小時給藥更有效。
✜ Steroids can be considered an adjuvant pain control option in patients with FCGS. Glucocorticoids can reduce pain indirectly via anti-inflammatory effects. Evidence suggests that these effects may also be beneficial in neuropathic pain management, and steroid receptors are found in both the central as well as peripheral nervous systems.65 However, chronic antigenic stimulation, as is suspected to occur in FCGS, can lead to T cell dysfunction, termed ‘exhaustion’, possibly negating the effects of these medications (as discussed in the ‘Immunosuppressive therapy’ section).66
✜ 類固醇可以被視為 FCGS 患者的輔助疼痛控制選擇。糖皮質激素可以通過抗炎作用間接減少疼痛。證據表明，這些作用在神經性疼痛管理中也可能是有益的，並且在中樞和周邊神經系統中均發現類固醇受體。 65 然而，慢性抗原刺激，如在 FCGS 中懷疑發生的情況，可能導致 T 細胞功能障礙，稱為“耗竭”，可能抵消這些藥物的效果（如在“免疫抑制療法”部分中討論）。 66
✜ 類固醇可以被視為 FCGS 患者的輔助疼痛控制選擇。糖皮質激素可以通過抗炎作用間接減少疼痛。證據表明，這些作用在神經性疼痛管理中也可能是有益的，並且在中樞和周邊神經系統中均發現類固醇受體。 65 然而，慢性抗原刺激，如在 FCGS 中懷疑發生的情況，可能導致 T 細胞功能障礙，稱為“耗竭”，可能抵消這些藥物的效果（如在“免疫抑制療法”部分中討論）。 66
✜ NSAIDs are often considered in the acute setting but concern over the potential for renal side effects has raised caution with respect to chronic use.
✜ 非類固醇抗發炎藥物（NSAIDs）通常在急性情況下被考慮使用，但對於腎臟副作用的潛在擔憂使得對於長期使用提高了警惕。
Studies evaluating the use of long-term meloxicam (0.01–0.05 mg/kg PO q24h) and robenacoxib (1–2 mg/kg PO q24h) in cats with osteoarthritis and concurrent chronic but stable kidney disease have failed to show detrimental renal effects of these medications in those patients.67-69 It is important to note that follow-up for these cats varied from 28 days to more than 6 months and that their renal disease was categorized as International Renal Interest Society (IRIS) stages 1–2.
研究評估了在患有骨關節炎和同時穩定的慢性腎病的貓中使用長期美洛昔康（0.01–0.05 mg/kg 口服 每 24 小時一次）和羅貝那考昔（1–2 mg/kg 口服 每 24 小時一次），未能顯示這些藥物對這些患者的腎臟有不良影響。 67-69 重要的是要注意，這些貓的隨訪時間從 28 天到超過 6 個月不等，並且他們的腎病被歸類為國際腎臟興趣協會（IRIS）1–2 期。
Additionally, these patients did not necessarily have a medical condition impeding their ability to eat and drink, and thus maintain hydration, as can sometimes happen in FCGS patients.
此外，這些患者不一定有醫療狀況妨礙他們進食和飲水，因此保持水分，這在 FCGS 患者中有時會發生。
✜ 非類固醇抗發炎藥物（NSAIDs）通常在急性情況下被考慮使用，但對於腎臟副作用的潛在擔憂使得對於長期使用提高了警惕。
Studies evaluating the use of long-term meloxicam (0.01–0.05 mg/kg PO q24h) and robenacoxib (1–2 mg/kg PO q24h) in cats with osteoarthritis and concurrent chronic but stable kidney disease have failed to show detrimental renal effects of these medications in those patients.67-69 It is important to note that follow-up for these cats varied from 28 days to more than 6 months and that their renal disease was categorized as International Renal Interest Society (IRIS) stages 1–2.
研究評估了在患有骨關節炎和同時穩定的慢性腎病的貓中使用長期美洛昔康（0.01–0.05 mg/kg 口服 每 24 小時一次）和羅貝那考昔（1–2 mg/kg 口服 每 24 小時一次），未能顯示這些藥物對這些患者的腎臟有不良影響。 67-69 重要的是要注意，這些貓的隨訪時間從 28 天到超過 6 個月不等，並且他們的腎病被歸類為國際腎臟興趣協會（IRIS）1–2 期。
Additionally, these patients did not necessarily have a medical condition impeding their ability to eat and drink, and thus maintain hydration, as can sometimes happen in FCGS patients.
此外，這些患者不一定有醫療狀況妨礙他們進食和飲水，因此保持水分，這在 FCGS 患者中有時會發生。
NSAIDs have been evaluated as an adjunct treatment modality for cats with FCGS. A combination of bovine lactoferrin oral spray (6 mg/cat, q12h) and piroxicam (0.3 mg/kg PO on alternate days) was investigated in a randomized, double-blind clinical trial, and clinical signs were significantly improved in 77% of the cats.70 Oral piroxicam alone decreased clinical signs during the first 2 weeks; however, the combination of bovine lactoferrin oral spray and piroxicam produced an enhanced effect that reduced the severity of the oral lesions and improved clinical signs, quality of life and weight gain over the duration of the 12-week study.70 It is worth mentioning that the authors did not state the success rate for the control group in this study and that control cases were converted to treatment cases after the fourth week.
非類固醇抗發炎藥（NSAIDs）已被評估為貓咪慢性牙齦口炎（FCGS）的輔助治療方式。在一項隨機雙盲臨床試驗中，研究了牛乳鐵蛋白口腔噴霧（每隻貓 6 毫克，每 12 小時一次）和吡羅昔康（每公斤 0.3 毫克，隔天口服）的組合，77%的貓咪臨床症狀顯著改善。 70 單獨使用口服吡羅昔康在前兩週減少了臨床症狀；然而，牛乳鐵蛋白口腔噴霧和吡羅昔康的組合產生了增強效果，減輕了口腔病變的嚴重程度，並改善了臨床症狀、生活品質和在 12 週研究期間的體重增加。 70 值得一提的是，作者在這項研究中並未說明對照組的成功率，且對照案例在第四週後轉為治療案例。
Oral administration of lactoferrin alone had previously been investigated for its effects in inhibiting bacterial growth in cats with stomatitis with and without FIV, and resulted in an improvement in clinical signs as well as a concurrent increase in neutrophil phagocytic activity.71
單獨口服乳鐵蛋白之前已經研究其在抑制患有口腔炎的貓（無論是否感染 FIV）中抑制細菌生長的效果，並導致臨床症狀的改善以及中性粒細胞吞噬活性的同時增加。
非類固醇抗發炎藥（NSAIDs）已被評估為貓咪慢性牙齦口炎（FCGS）的輔助治療方式。在一項隨機雙盲臨床試驗中，研究了牛乳鐵蛋白口腔噴霧（每隻貓 6 毫克，每 12 小時一次）和吡羅昔康（每公斤 0.3 毫克，隔天口服）的組合，77%的貓咪臨床症狀顯著改善。 70 單獨使用口服吡羅昔康在前兩週減少了臨床症狀；然而，牛乳鐵蛋白口腔噴霧和吡羅昔康的組合產生了增強效果，減輕了口腔病變的嚴重程度，並改善了臨床症狀、生活品質和在 12 週研究期間的體重增加。 70 值得一提的是，作者在這項研究中並未說明對照組的成功率，且對照案例在第四週後轉為治療案例。
Oral administration of lactoferrin alone had previously been investigated for its effects in inhibiting bacterial growth in cats with stomatitis with and without FIV, and resulted in an improvement in clinical signs as well as a concurrent increase in neutrophil phagocytic activity.71
單獨口服乳鐵蛋白之前已經研究其在抑制患有口腔炎的貓（無論是否感染 FIV）中抑制細菌生長的效果，並導致臨床症狀的改善以及中性粒細胞吞噬活性的同時增加。
Antimicrobials 抗微生物劑
Scientific data supporting the use of antibiotics in FCGS are limited. One study reporting the effect of different antibiotics documented improvement in 38% of cats treated with amoxicillin and 37% of cats treated with metronidazole.27 Considering these effects are only transient, and that response rates are lower for antibiotics than immuno-suppressive therapy, antibiotic treatment is only recommended in the acute setting and/or if secondary infections are noted.27
支持在貓慢性牙齦口炎（FCGS）中使用抗生素的科學數據有限。一項報告不同抗生素效果的研究顯示，接受阿莫西林治療的貓有 38%改善，接受甲硝唑治療的貓有 37%改善。考慮到這些效果僅是暫時性的，且抗生素的反應率低於免疫抑制療法，因此抗生素治療僅建議在急性情況下和/或如果發現次級感染時使用。
支持在貓慢性牙齦口炎（FCGS）中使用抗生素的科學數據有限。一項報告不同抗生素效果的研究顯示，接受阿莫西林治療的貓有 38%改善，接受甲硝唑治療的貓有 37%改善。考慮到這些效果僅是暫時性的，且抗生素的反應率低於免疫抑制療法，因此抗生素治療僅建議在急性情況下和/或如果發現次級感染時使用。
Research has been performed to investigate the antimicrobial susceptibility of the sub-gingival microbiome of cats.72 However, the patients included in this study had only gingivitis, whereas patients with FCGS show evidence of a more severe form of periodontitis.24 Though studies have described the subgingival microbiome in FCGS patients,9 the antimicrobial resistance patterns of these organisms have yet to be evaluated. An analogous human disease featuring a compromised oral epithelim that would be an indication for complete (or near-complete) tooth extractions is lacking. However, a Cochrane review has investigated the use of antibiotics to prevent complications following tooth extractions in healthy humans.73 Taken together, the studies included in the review found low-certainty evidence that antibiotics may reduce the risk of infection and dry socket compared with placebo in people undergoing extractions of impacted third molars. Furthermore, there was very low-certainty evidence of no increase in the risk of adverse effects in these patients.
已進行研究以調查貓隱龜微生物組的抗微生物敏感性。 72 然而，這項研究中納入的患者僅有牙齦炎，而 FCGS 患者則顯示出更嚴重的牙周炎證據。 24 雖然已有研究描述 FCGS 患者的隱龜微生物組， 9 但這些生物的抗微生物抗藥性模式尚未被評估。缺乏一種類似的人類疾病，其特徵是口腔上皮受損，這將是完全（或接近完全）拔牙的指徵。然而，一項 Cochrane 評估已調查使用抗生素以防止健康人拔牙後的併發症。 73 綜合來看，該評估中納入的研究發現，抗生素可能降低感染和乾槽症的風險，相較於安慰劑，證據確定性較低。此外，這些患者的副作用風險沒有增加的證據確定性非常低。
This may be different in immuno-compromised or immunosuppressed patients, which were not included in this study.73
這在免疫功能低下或免疫抑制的患者中可能有所不同，而這些患者未被納入本研究。
已進行研究以調查貓隱龜微生物組的抗微生物敏感性。 72 然而，這項研究中納入的患者僅有牙齦炎，而 FCGS 患者則顯示出更嚴重的牙周炎證據。 24 雖然已有研究描述 FCGS 患者的隱龜微生物組， 9 但這些生物的抗微生物抗藥性模式尚未被評估。缺乏一種類似的人類疾病，其特徵是口腔上皮受損，這將是完全（或接近完全）拔牙的指徵。然而，一項 Cochrane 評估已調查使用抗生素以防止健康人拔牙後的併發症。 73 綜合來看，該評估中納入的研究發現，抗生素可能降低感染和乾槽症的風險，相較於安慰劑，證據確定性較低。此外，這些患者的副作用風險沒有增加的證據確定性非常低。
This may be different in immuno-compromised or immunosuppressed patients, which were not included in this study.73
這在免疫功能低下或免疫抑制的患者中可能有所不同，而這些患者未被納入本研究。
The authors’ approach is to utilize a short course (5 days) of antimicrobials postoperatively for FCGS cases (amoxicillin clavulanate, 13.75 mg/kg PO q12h; clindamycin 5–11 mg/kg PO q12h) owing to the aggressive nature of surgery and poor condition of the mucogingival tissues. The authors are, however, actively researching if there is a benefit of >24 h antibiotic therapy.
作者的做法是對 FCGS 病例在手術後使用短期（5 天）的抗微生物藥物（阿莫西林克拉維酸，13.75 mg/kg 口服每 12 小時一次；克林黴素 5–11 mg/kg 口服每 12 小時一次），因為手術的侵襲性和粘膜牙齦組織的狀況不佳。然而，作者正在積極研究超過 24 小時的抗生素治療是否有益。
作者的做法是對 FCGS 病例在手術後使用短期（5 天）的抗微生物藥物（阿莫西林克拉維酸，13.75 mg/kg 口服每 12 小時一次；克林黴素 5–11 mg/kg 口服每 12 小時一次），因為手術的侵襲性和粘膜牙齦組織的狀況不佳。然而，作者正在積極研究超過 24 小時的抗生素治療是否有益。
Immunosuppressive therapy
免疫抑制療法
Glucocorticoids remain the most frequently prescribed medication for the management of stomatitis pre- and postoperatively. In postoperative patients, glucocorticoids have been utilized immediately after surgery and also in refractory cases.
糖皮質激素仍然是術前和術後管理口腔炎最常處方的藥物。在術後患者中，糖皮質激素在手術後立即使用，並且在難治性病例中也有使用。
This approach is in contrast to the use of some novel therapeutics (discussed in the ‘Immunomodulation’ section) that enhance patients’ immune response, rather than immunosuppressing them further.
這種方法與一些新型療法（在「免疫調節」部分討論）形成對比，後者是增強患者的免疫反應，而不是進一步抑制他們的免疫系統。
糖皮質激素仍然是術前和術後管理口腔炎最常處方的藥物。在術後患者中，糖皮質激素在手術後立即使用，並且在難治性病例中也有使用。
This approach is in contrast to the use of some novel therapeutics (discussed in the ‘Immunomodulation’ section) that enhance patients’ immune response, rather than immunosuppressing them further.
這種方法與一些新型療法（在「免疫調節」部分討論）形成對比，後者是增強患者的免疫反應，而不是進一步抑制他們的免疫系統。
Treatment with steroids has been shown to produce complete cure or a marked improvement in about 23% of patients; of those, only 7% achieved clinical remission.47 Considering these facts, along with the potentially harmful side effects of long-term administration, such as diabetes mellitus, the authors recommend that corticosteroids be reserved for patients not responding to pain management protocols, for symptomatic treatment, on a tapering course, or for use as a salvage option.
使用類固醇的治療已顯示約 23%的患者能夠完全治癒或顯著改善；其中只有 7%達到臨床緩解。考慮到這些事實，以及長期使用可能帶來的有害副作用，如糖尿病，作者建議將類固醇保留給對疼痛管理方案無反應的患者，作為症狀治療，採用逐漸減量的方式，或作為救援選擇使用。
If corticosteroids are used, it is recommended that periodic blood work is obtained to assess for potential side effects.
如果使用皮質類固醇，建議定期進行血液檢查以評估潛在的副作用。
使用類固醇的治療已顯示約 23%的患者能夠完全治癒或顯著改善；其中只有 7%達到臨床緩解。考慮到這些事實，以及長期使用可能帶來的有害副作用，如糖尿病，作者建議將類固醇保留給對疼痛管理方案無反應的患者，作為症狀治療，採用逐漸減量的方式，或作為救援選擇使用。
If corticosteroids are used, it is recommended that periodic blood work is obtained to assess for potential side effects.
如果使用皮質類固醇，建議定期進行血液檢查以評估潛在的副作用。
Ciclosporin is also an immunosuppressant that is used in cases of FCGS. Ciclosporin decreases T cell proliferation by reducing IL-2 expression; this, in turn, leads indirectly to decreased B cell function (ie, responsiveness and antibody production) as well as directly decreasing B cell migration.74 A randomized, controlled, double-blind, prospective clinical trial where oral ciclosporin was administered to nine cats that had previously been treated with tooth extractions reported a significant difference in the number of cats experiencing clinical improvement over the 6-week study period between the treatment group (7/9 cats, 77.8%) and the placebo group (1/7 cats, 14.3%).44 Long-term observation of 11 cats, as part of the same study, showed 45.5% (five cats) were clinically cured after receiving ciclosporin for 3 or more months. Furthermore, whole-blood ciclosporin levels >300 ng/ml were associated with significant improvement in oral inflammation in cats with refractory chronic stomatitis.44 Treatment with ciclosporin before dental extractions has also been evaluated in a small number of patients (n = 8), with 50% of the cats reported to achieve clinical remission.75
環孢素也是一種免疫抑制劑，用於 FCGS 的病例。環孢素通過減少 IL-2 的表達來降低 T 細胞增殖；這反過來又間接導致 B 細胞功能（即反應性和抗體產生）的降低，以及直接減少 B 細胞的遷移。 74 一項隨機、對照、雙盲、前瞻性的臨床試驗中，口服環孢素被給予九隻之前接受過拔牙治療的貓，報告顯示在為期 6 週的研究期間，治療組（7/9 隻貓，77.8%）與安慰劑組（1/7 隻貓，14.3%）之間經歷臨床改善的貓數量存在顯著差異。 44 在同一研究中，對 11 隻貓的長期觀察顯示，45.5%（五隻貓）在接受環孢素治療 3 個月或更長時間後臨床治癒。此外，整體血液中環孢素水平>300 ng/ml 與難治性慢性口炎貓的口腔炎症顯著改善相關。 44 在拔牙前使用環孢素的治療也在少數患者（n = 8）中進行評估，報告顯示 50%的貓達到了臨床緩解。 75
環孢素也是一種免疫抑制劑，用於 FCGS 的病例。環孢素通過減少 IL-2 的表達來降低 T 細胞增殖；這反過來又間接導致 B 細胞功能（即反應性和抗體產生）的降低，以及直接減少 B 細胞的遷移。 74 一項隨機、對照、雙盲、前瞻性的臨床試驗中，口服環孢素被給予九隻之前接受過拔牙治療的貓，報告顯示在為期 6 週的研究期間，治療組（7/9 隻貓，77.8%）與安慰劑組（1/7 隻貓，14.3%）之間經歷臨床改善的貓數量存在顯著差異。 44 在同一研究中，對 11 隻貓的長期觀察顯示，45.5%（五隻貓）在接受環孢素治療 3 個月或更長時間後臨床治癒。此外，整體血液中環孢素水平>300 ng/ml 與難治性慢性口炎貓的口腔炎症顯著改善相關。 44 在拔牙前使用環孢素的治療也在少數患者（n = 8）中進行評估，報告顯示 50%的貓達到了臨床緩解。 75
The authors of this review advise against immunosuppression without surgical intervention.
這篇評論的作者建議在沒有手術介入的情況下不要進行免疫抑制。
這篇評論的作者建議在沒有手術介入的情況下不要進行免疫抑制。
Immunomodulation 免疫調節
Immunomodulation is often reserved for refractory cases (ie, those that have not responded to surgery). Note that, as referred to earlier, the time at which a patient is defined as refractory varies. Moreover, the use of biomarkers has significant potential in this context to reduce waiting times for medical therapy and improve patient quality of life.
免疫調節通常保留給難治性病例（即那些對手術未有反應的病例）。請注意，如前所述，患者被定義為難治性的時間有所不同。此外，在這種情況下，生物標記的使用具有顯著潛力，可以縮短醫療治療的等待時間並改善患者的生活質量。
免疫調節通常保留給難治性病例（即那些對手術未有反應的病例）。請注意，如前所述，患者被定義為難治性的時間有所不同。此外，在這種情況下，生物標記的使用具有顯著潛力，可以縮短醫療治療的等待時間並改善患者的生活質量。
In refractory cases, treatment with recombinant feline interferon-omega (rFeIFN-ω) and mesenchymal stromal cell (MSC) therapy has shown promise. A controlled, randomized, double-blind study found that oromucosal rFeIFN-ω resulted in moderate improvement to clinical cure in 55% of treated cats and marked improvement to clinical cure in 45%.47 Results of a study investigating subcutaneous administration of rFeIFN-ω in FCV-positive cats with FCGS found that stomatitis was improved through inhibition of FCV proliferation.38 Subcutaneous rFeIFN-ω has also shown clinical efficacy in cats that are naturally infected with FeLV or coinfected with FeLV and FIV.76 Additionally, oral rFeIFN-ω has been shown to be an effective alternative therapy for FIV-infected cats.77
在難治性病例中，重組貓干擾素-omega (rFeIFN-ω) 和間充質基質細胞 (MSC) 治療顯示出希望。一項受控、隨機、雙盲研究發現，口腔黏膜給藥的 rFeIFN-ω 在 55%的治療貓中導致臨床治癒的中度改善，而在 45%的治療貓中導致臨床治癒的顯著改善。 47 一項研究的結果顯示，在 FCV 陽性的貓中皮下給藥 rFeIFN-ω 可通過抑制 FCV 增殖來改善口腔炎症。 38 皮下 rFeIFN-ω 在自然感染 FeLV 或同時感染 FeLV 和 FIV 的貓中也顯示出臨床療效。 76 此外，口服 rFeIFN-ω 已被證明是 FIV 感染貓的一種有效替代療法。 77
在難治性病例中，重組貓干擾素-omega (rFeIFN-ω) 和間充質基質細胞 (MSC) 治療顯示出希望。一項受控、隨機、雙盲研究發現，口腔黏膜給藥的 rFeIFN-ω 在 55%的治療貓中導致臨床治癒的中度改善，而在 45%的治療貓中導致臨床治癒的顯著改善。 47 一項研究的結果顯示，在 FCV 陽性的貓中皮下給藥 rFeIFN-ω 可通過抑制 FCV 增殖來改善口腔炎症。 38 皮下 rFeIFN-ω 在自然感染 FeLV 或同時感染 FeLV 和 FIV 的貓中也顯示出臨床療效。 76 此外，口服 rFeIFN-ω 已被證明是 FIV 感染貓的一種有效替代療法。 77
In a study evaluating the efficacy of rFeIFN-ω for clinical improvement and reduction of concurrent viral excretion in retrovirus-infected cats from a rescue shelter, caudal stomatitis was a common finding (6/16 cats), particularly among FIV-positive cats.78 In this study, FIV-infected and FIV/FeLV coinfected cats improved during therapy. Interestingly, all of the FIV cats that tested positive for FCV (4/7) had gingivo-stomatitis; and, of the 11 FCV-positive cats, nine had reduced viral loads post-rFeIFN-ω treatment.78 Taken together, these studies confirm the role of rFeIFN-ω therapy in patients with FCGS and confirmed retroviral (FIV/FeLV) or FCV infection. rFeIFN-ω is approved for use in Europe, but is currently not approved in the USA.
在一項評估 rFeIFN-ω對於臨床改善和減少救助收容所中逆轉錄病毒感染貓隻的病毒排泄的療效的研究中，尾部口炎是一個常見的發現（16 隻貓中有 6 隻），特別是在 FIV 陽性貓中。在這項研究中，FIV 感染和 FIV/FeLV 共感染的貓在治療期間有所改善。有趣的是，所有檢測出 FCV 陽性的 FIV 貓（7 隻中有 4 隻）都有牙齦口炎；而在 11 隻 FCV 陽性的貓中，有 9 隻在 rFeIFN-ω治療後病毒載量減少。綜合來看，這些研究確認了 rFeIFN-ω療法在 FCGS 患者以及確認的逆轉錄病毒（FIV/FeLV）或 FCV 感染中的作用。rFeIFN-ω在歐洲獲得批准使用，但目前在美國尚未獲得批准。
在一項評估 rFeIFN-ω對於臨床改善和減少救助收容所中逆轉錄病毒感染貓隻的病毒排泄的療效的研究中，尾部口炎是一個常見的發現（16 隻貓中有 6 隻），特別是在 FIV 陽性貓中。在這項研究中，FIV 感染和 FIV/FeLV 共感染的貓在治療期間有所改善。有趣的是，所有檢測出 FCV 陽性的 FIV 貓（7 隻中有 4 隻）都有牙齦口炎；而在 11 隻 FCV 陽性的貓中，有 9 隻在 rFeIFN-ω治療後病毒載量減少。綜合來看，這些研究確認了 rFeIFN-ω療法在 FCGS 患者以及確認的逆轉錄病毒（FIV/FeLV）或 FCV 感染中的作用。rFeIFN-ω在歐洲獲得批准使用，但目前在美國尚未獲得批准。
The efficacy of both autologous and allogeneic, fresh, adipose-derived MSCs administered intravenously has been studied in cats with refractory FCGS,29,45,46 and is reported in a recently published paper from the authors’ group at the University of California, Davis (see ‘Companion paper on FCGS’ highlight circle).79 The immunomodulatory action of MSCs has shown promise for treating cats with refractory FCGS, with up to 57% and 71% of FCGS patients exhibiting clinical improvement or remission after allogeneic and autologous treatments, respectively.29,46 No response was seen when treating with MSCs before extraction therapy in a pilot study.80
自體和異體新鮮脂肪來源的間充質幹細胞（MSCs）靜脈注射的療效已在患有難治性貓咪慢性牙齦口腔炎（FCGS）的貓中進行研究，並在加州大學戴維斯分校的作者團隊最近發表的論文中報導（見「FCGS 的伴隨論文」重點圈）。MSCs 的免疫調節作用對於治療難治性 FCGS 的貓咪顯示出希望，分別有高達 57%和 71%的 FCGS 患者在接受異體和自體治療後出現臨床改善或緩解。在一項初步研究中，在提取療法之前使用 MSCs 治療未見反應。
自體和異體新鮮脂肪來源的間充質幹細胞（MSCs）靜脈注射的療效已在患有難治性貓咪慢性牙齦口腔炎（FCGS）的貓中進行研究，並在加州大學戴維斯分校的作者團隊最近發表的論文中報導（見「FCGS 的伴隨論文」重點圈）。MSCs 的免疫調節作用對於治療難治性 FCGS 的貓咪顯示出希望，分別有高達 57%和 71%的 FCGS 患者在接受異體和自體治療後出現臨床改善或緩解。在一項初步研究中，在提取療法之前使用 MSCs 治療未見反應。
Key Points 要點
✜ Current evidence regarding the etiology of FCGS points toward an immune-mediated disease process with both local and systemic ramifications in response to a chronic antigenic stimulant.
✜ 目前有關 FCGS 病因的證據指向一種免疫介導的疾病過程，對於慢性抗原刺激的反應具有局部和全身的影響。
✜ 目前有關 FCGS 病因的證據指向一種免疫介導的疾病過程，對於慢性抗原刺激的反應具有局部和全身的影響。
✜ There is increasing scientific support for a role for FCV as a part of the etiology of FCGS - at least as a disease-modulating agent.
✜ 越來越多的科學證據支持貓皰疹病毒（FCV）在貓慢性牙齦口炎（FCGS）病因中的角色——至少作為一種疾病調節因子。
✜ 越來越多的科學證據支持貓皰疹病毒（FCV）在貓慢性牙齦口炎（FCGS）病因中的角色——至少作為一種疾病調節因子。
✜ All cats with FCGS are affected by periodontitis to varying extents.
✜ 所有患有 FCGS 的貓咪在不同程度上都受到牙周炎的影響。
✜ 所有患有 FCGS 的貓咪在不同程度上都受到牙周炎的影響。
✜ Surgical treatment continues to be the gold standard therapy, with extraction of all teeth for patients where the inflammation extends to the rostral oral cavity. Partial (premolar and molar) dental extractions may be considered for patients where inflammation is confined to the regions of the premolar and molar teeth.
✜ 手術治療仍然是黃金標準療法，對於炎症擴展至前口腔的患者，需拔除所有牙齒。對於炎症僅限於前臼齒和臼齒區域的患者，可以考慮部分（前臼齒和臼齒）牙齒拔除。
✜ 手術治療仍然是黃金標準療法，對於炎症擴展至前口腔的患者，需拔除所有牙齒。對於炎症僅限於前臼齒和臼齒區域的患者，可以考慮部分（前臼齒和臼齒）牙齒拔除。
✜ Given the complexity of this disease, and until a tooth-sparing treatment option is found, a personalized medicine approach is recommended. The aim should be to optimize patient care, allowing for more timely medical treatment for those patients that are predicted to have a poor response to surgical treatment.
✜ 鑑於這種疾病的複雜性，在找到保留牙齒的治療選擇之前，建議採用個性化醫療方法。目標應該是優化病人護理，讓那些預測對手術治療反應不佳的病人能夠及時接受醫療治療。
✜ 鑑於這種疾病的複雜性，在找到保留牙齒的治療選擇之前，建議採用個性化醫療方法。目標應該是優化病人護理，讓那些預測對手術治療反應不佳的病人能夠及時接受醫療治療。
✜ The value of medical management in the acute setting before extractions are performed, in the immediate postoperative period and for treatment of refractory cases, is recognized.
✜ 在進行拔牙之前的急性情況下、立即術後期間以及對難治性病例的治療中，醫療管理的價值是被認可的。
✜ 在進行拔牙之前的急性情況下、立即術後期間以及對難治性病例的治療中，醫療管理的價值是被認可的。
Ethical approval 倫理批准
This work did not involve the use of animals and therefore ethical approval was not specifically required for publication in JFMS.
本研究未涉及動物的使用，因此在 JFMS 發表時不需要特別的倫理審批。
本研究未涉及動物的使用，因此在 JFMS 發表時不需要特別的倫理審批。
Informed consent 知情同意
This work did not involve the use of animals (including cadavers) and therefore informed consent was not required. No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.
本研究未涉及動物（包括屍體）的使用，因此不需要知情同意。此出版物中沒有可識別的動物或人，因此不需要額外的出版知情同意。
本研究未涉及動物（包括屍體）的使用，因此不需要知情同意。此出版物中沒有可識別的動物或人，因此不需要額外的出版知情同意。
Conflict of interest 利益衝突
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
作者聲明在本研究、作者身份和/或本文章的出版方面沒有潛在的利益衝突。
作者聲明在本研究、作者身份和/或本文章的出版方面沒有潛在的利益衝突。
Funding 資助
The authors received no financial support for the research, authorship, and/or publication of this article.
作者在本研究、著作及/或本文章的出版上未獲得任何財務支持。
作者在本研究、著作及/或本文章的出版上未獲得任何財務支持。
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