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无菌性脓性肉芽肿性皮炎和脂膜炎 Sterile Pyogranulomatous Dermatitis and Panniculitis
作者：Jennifer Schissler, DVM, MS
翻译：关文棉 校对：王帆 关键词 •脓性肉芽肿•皮炎•溃疡性•结节•无菌性•脂膜炎 重点 •诊断包括通过组织病理学、组织培养和辅助诊断排除感染性病因引起的脓性肉芽肿性皮炎和脂膜炎。 •可能发生早期和并发的非特异性临床症状以及血液学炎性指征。 •该综合征的特征是各种大小及程度的结节性、斑块性和溃疡性脓性肉芽肿。 •该综合征是特发性的，尤其对皮质类固醇和非皮质类固醇的免疫调节药有效。 KEYWORDS •Pyogranulomatous •Dermatitis •Ulcerative •Nodular •Sterile •Panniculitis KEY POINTS •The diagnosis involves exclusion of infectious causes of pyogranulomatous dermatitis and panniculitis via histopathology, tissue culture, and ancillary diagnostics. •Prodromal and concurrent nonspecific clinical and hematologic signs of inflammation may occur. •This syndrome is characterized by pyogranulomatous nodules, plaques, and ulcers of variable extent and severity. •This syndrome is idiopathic and typically responds well to corticosteroids and corticosteroid-sparing immunomodulatory drugs 介绍 INTRODUCTION 犬结节性和溃疡性皮炎很难确诊。细菌感染、真菌感染、卵菌病、异物和无菌性炎性疾病，都可表现为相似的单个或多个皮肤结节、斑块、溃疡和瘘道，伴有脓性肉芽肿性炎性反应。进行全面的体格检查和病史调查，有助于判断鉴别诊断的先后顺序。结节和溃疡的病因可以通过细胞学检查得以确定，也可能仍不明确，需要进行组织病理学检查、组织培养和辅助诊断方法。 Canine nodular and ulcerative dermatitis is a diagnostic challenge. Bacterial infection,fungal infection, oomycosis, foreign bodies, and sterile inflammatory conditions may present similarly as solitary or multifocal cutaneous nodules, plaques, ulcers, and draining tracts with pyogranulomatous inflammation. A thorough physical examination and history aid in prioritization of differentials. The cause of the nodules and ulcers may be efficiently identified via cytology or may remain elusive, requiring histopathology,culture, and ancillary diagnostics. 无菌性脓性肉芽肿性皮炎和脂膜炎 (SPDP) 是一种成犬不常见，幼犬罕见的综合征。已证实无自身抗原或外源抗原刺激。SPDP 的特征是表现为各种大小、范围和严重程度的脓性肉芽肿性结节、斑块和溃疡。这种综合症没有正式的命名。用于描述这种综合征的其他术语包括:无菌性肉芽肿/脓性肉芽肿综合征,、无菌性脂膜炎,、无菌性肉芽肿性/脓性肉芽肿性皮炎和脂膜炎。根据不同的命名, 通过整体表现和组织病理学表现，病例可能表现为皮炎、脂膜炎或两者皆有。 Sterile pyogranulomatous dermatitis and panniculitis (SPDP) is an uncommon syndrome of adult and, rarely, juvenile dogs. No autoantigen, or exogenous antigen stimulus has been identified. SPDP is characterized by pyogranulomatous nodules,plaques, and ulcers of variable size, extent, and severity. This syndrome does not have a formalized name. Other terms used to describe this syndrome include: sterile granuloma/pyogranuloma syndrome, sterile panniculitis, sterile granulomatous/pyogranulomatous dermatitis and panniculitis. As indicated by the variation in nomenclature, patients may demonstrate gross and histopathologic manifestations of dermatitis, panniculitis, or both. SPDP需要通过排除法来确诊。治疗SPDP的方法是进行全身免疫调节。因此, 错误诊断SPDP 以及随后进行免疫抑制治疗，最好的情况顶多是无效。最坏的情况, 误诊会带来灾难性的后果。要想成功的治疗脓性肉芽肿性和溃疡性皮炎, 重点是要明确全面的、合理的诊断方法。 SPDP is a diagnosis of exclusion. Treatment of SPDP requires systemic immunomodulation.Therefore, misdiagnosis of SPDP and subsequent immunosuppressive treatment is ineffective, at best. At worst, misdiagnosis is catastrophically counterproductive.To successfully navigate pyogranulomatous and ulcerative dermatitis, a thorough and rational diagnostic approach is paramount. 临床特征和病史调查 SIGNALMENT AND HISTORY 病例可能急性发病，包括单个或多个皮肤病变，以及皮肤疼痛、精神萎靡和组织缺氧。但其他病例表现为病变可自愈和复发，病程时好时坏，对抗生素和全身皮质类固醇的辅助免疫抑制作用效果不一。曾经接受切除活检的病例，都有伤口裂开和/或手术部位病变复发的病史。瘙痒表现并不典型。疼痛在脂膜炎中更为常见。 Patients may present with an acute history involving singular or multiple cutaneous lesions as well as cutaneous pain, malaise, and hyporexia. Yet others present with a waxing and waning course of lesions that spontaneously resolve and recur with a variable response to antimicrobial or subimmunosuppressive courses of systemic corticosteroids. Those having undergone previous excisional biopsies often have a history of dehiscence and/or recurrence of lesions at the surgical site. Pruritus is not a typical feature. Pain occurs more frequently in panniculitis. SPDP病例可以是任何品种或性别。病例通常是成年犬。但是，作者在几只6到12月龄的犬上观察到这种综合征。认为此皮炎的易感品种包括：金毛犬、拳师犬、腊肠犬、牧羊犬、魏玛犬、杜宾犬和英国斗牛犬。认为脂膜炎易感品种包括：贵宾犬、腊肠犬、澳大利亚牧羊犬、布列塔尼猎犬、大麦町、博美犬和吉娃娃。 Patients with SPDP can be of any breed or sexual status. Patients are often adults;however, the author has observed this syndrome in several dogs between 6 and 12 months of age. Suggested breed predispositions for dermatitis include the golden retriever, boxer, dachshund, collie, Weimaraner, Doberman pinscher, and English bulldog. Suggested breed predispositions for panniculitis include poodles, dachshunds, Australian shepherds, Brittany spaniels,dalmatians,Pomeranians,and Chihuahuas. 一些感染性病因引发的结节性、脓性肉芽肿性皮炎具有明显的地理分布差异(表 1)。因此, 有必要了解旅游史和某些地区的真菌、细菌和卵菌病原的相关知识。此外, 如果病例经常在户外生活，那植物异物和与穿刺伤有关的感染(放线菌、 孢子丝菌)，或与淡水游泳有关的感染(链壶菌、腐霉菌)风险将升高。 Some infectious causes of nodular, pyogranulomatous dermatitis/panniculitis have distinct geographic distributions (Table 1). Therefore, travel history and knowledge of regional fungal, bacterial, and oomycotic agents are necessary. Additionally, patients with an active outdoor lifestyle are at higher risk of plant foreign bodies and opportunistic infections associated with puncture wounds (Actinomyces, Sporothrix) or freshwater activities (Lagenidium, Pythium). 病例接受免疫调节剂，如泼尼松龙和环孢菌素(尤其是联合使用)，更容易有机会感染细菌性和真菌性脓性肉芽肿(图1)。 例如，伯克氏菌和双极霉菌（皮肤暗丝孢霉菌）在这种环境下可能是条件致病菌。 Patients receiving immunomodulatory drugs, such as prednisolone and cyclosporine(particularly in combination), are more susceptible to opportunistic bacterial and fungal pyogranulomatous infections (Fig. 1). Burkholderia and bipolaris (phaeohyphomycosis),for example, may be opportunists in such circumstances. 图1。真菌菌丝和脓性肉芽肿性炎性反应。在接受环孢菌素和泼尼松龙治疗 IMHA (免疫介导性溶血性贫血) 的患犬上的条件致病菌感染。(罗曼诺夫斯基染色, 100倍物镜, 1000倍放大). Fig. 1. Fungal hyphae with pyogranulomatous inflammation. Opportunistic infection in dog treated for IMHA (immune mediated hemolytic anemia) with cyclosporine and prednisolone(Romanowsky stain, 100*objective, 1000*total magnification).
体格检查 PHYSICAL EXAMINATION 为了保护自己和病例, 检查结节性溃疡性皮肤病病例时应该戴手套。在感染性鉴别诊断中,孢子丝菌是最可能的潜在人兽共患病。然而,在下文提到的任何感染中，如果皮肤出现破损, 以及与皮肤直接接触，都有可能发生人兽共患条件致病菌感染，特别是在免疫功能不全的时候。戴手套和适当注意环境卫生，可以降低溃疡性病例在医院内感染条件致病性葡萄球菌的风险。 To protect oneself and patients, wear gloves to examine patients with nodular ulcerative dermatoses. Of the infectious differential diagnoses, Sporothrix likely has the greatest zoonotic potential. However, opportunistic zoonotic infections may occur with any of the infections mentioned in this text if the skin is broken and direct contact is made, particularly if the handler is immunocompromised. Gloves and proper environmental hygiene may reduce the risk of opportunistic nosocomial staphylococcal infection of ulcerated patients. 根据皮炎、脂膜炎或两者都有的不同表现，SPDP的病变表现也各不相同。也会出现局部淋巴结肿大和发热。在胰腺炎、多发性关节炎和全身性红斑狼疮病例中，也有并发无菌性脓性肉芽肿性脂膜炎的报道。因此,腹痛、关节痛或关节积液可能也是鉴别诊断。 SPDP lesions are variable depending on the presence of dermatitis, panniculitis, or both. Regional lymphadenopathy and pyrexia may also be observed. Concurrent sterile pyogranulomatous panniculitis has also been reported in patients with pancreatitis, polyarthritis, and systemic lupus erythematosus; thus, abdominal pain,joint pain, or effusion may also be appreciated. 与无菌性脓性肉芽肿皮炎相关的病变，包括真皮结节、斑块 (图 2A) 和丘疹, 可能有溃疡和瘘道并伴有脓血样渗出。结节大小从1厘米到15厘米不等。病变可能发生在机体的任何部位, 通常位于耳廓、嘴周、眼周和四肢远端。 Lesions associated with sterile pyogranulomatous dermatitis include dermal nodules,plaques (Fig. 2A), and papules that may ulcerate and drain serous to hemopurulent discharge. Nodules range from 1 cm to 15 cm in size. The lesions may occur anywhere on the body and are often located on the pinnae, muzzle, periocular regions,and distal extremities. 与无菌性脓性肉芽肿性脂膜炎相关的病变，包括皮下结节、溃疡和瘘道，可导致溃疡和瘘道伴有油性至脓血样渗出(图3)。溃疡大小可以从针尖大小到非常大面积，也可延伸到肌肉层(图3C和4B)。结节坚实或呈波动感，累及真皮深部和皮下组织。躯干病变最常见。经过治疗或自行恢复后都可能会形成瘢痕。 Lesions associated with sterile pyogranulomatous panniculitis include subcutaneous nodules, ulcers, and draining tracts that may ulcerate and drain oily to hemopurulent discharge (Fig. 3). Ulcers may be pinpoint to very large in size and may extend to the muscular layer (Fig. 3C and 4B). Nodules may be firm or fluctuant and involve the deep dermis as well as the subcutis. Truncal lesions are most common. Scarring may occur following treatment or natural resolution. 虽然没有文献记载, 作者还观察有并发眼睑炎和结膜炎的病例(图 3A和4A)。反应性组织细胞增多症也会有眼粘膜病变。反应性组织细胞增多症的典型表现是鼻黏膜病变。 Although not well documented, the author has also noted patients with concurrent blepharitis and conjunctivitis (Fig. 3A and 4A). Involvement of the ocular mucous membranes may also be observed with reactive histiocytosis. Involvement of the nasal mucous membranes is more typical of reactive histiocytosis. 结节性和溃疡性脓性肉芽肿皮肤病相关的鉴别诊断很多，通过全面的体格检查能提供有价值的线索，有助于鉴别诊断和确诊。(例如，房闪和芽生菌)。 Given the many differential diagnoses associated with nodular and ulcerative pyogranulomatous dermatoses, a thorough physical examination may provide valuable clues to refine differential and diagnostic considerations (eg, aqueous flare and Blastomyces).
图2。杂交贵宾犬斑块样的无菌结节性皮炎 (A) 和治疗后照片(B)。 Fig. 2. Poodle mix with plaque form of sterile nodular dermatitis (A) and after treatment (B).
图3。(A) 无菌性结节性皮炎和脂膜炎的杂交牧羊犬患犬，位于胸部真皮层和皮下结节的结节。(B) 杂交德国牧羊犬的溃疡性结节。(C) 杂交德国牧羊犬前臂严重的溃疡性脂膜炎。 Fig. 3. (A) Dermal and subcutaneous nodule on chest of shepherd cross with sterile nodular dermatitis and panniculitis. (B) Ulcerated nodule in German shepherd cross. (C) Severe ulcerative panniculitis of antebrachium in German shepherd cross. 图4。(A)使用免疫调节剂治疗前，面部多发性结节和溃疡，并发结膜炎和眼睑炎。(B)使用免疫调节剂治疗前，伴有溃疡的大结节。(C)使用免疫调节剂治疗后。(D)使用免疫调节剂治疗后，结节和溃疡已恢复。 Fig. 4. (A) Multiple facial nodules and ulcers with concurrent conjunctivitis and blepharitis,before immunomodulatory treatment. (B) Large nodule with ulcer, before immunomodulatory treatment. (C) After immunomodulatory therapy. (D) Nodule and ulcer resolved after immunomodulatory therapy.
诊断并发症 CONCURRENT DIAGNOSES 在胰腺肿瘤、多发性关节炎和全身性红斑狼疮病例中，观察到发生了无菌性脓性肉芽肿皮炎和脂膜炎（SPDP）。在犬中，也向人医一样，观察到了无菌性脓性肉芽肿性脂膜炎与胰腺炎的相关性。 Sterile pyogranulomatous dermatitis and panniculitis (SPDP) has been observed with pancreatic neoplasia, polyarthritis, and systemic lupus erythematosis. An association between sterile pyogranulomatous panniculitis and pancreatitis has been noted in dogs, as it has been in humans. 发病机制 ETIOPATHOGENESIS SPDP 的病因尚不明确, 没有已知的微生物制剂或特异性抗原刺激。在北美的流行率、发病率和地理分布并无代表性。 The etiopathogenesis of SPDP is unknown, with no known microbiologic agent or specific antigen stimulus. Prevalence, incidence, and geographic distribution within North America are uncharacterized.
假设通过传统的选择性细菌和真菌培养方法能排除性检测SPDP的病因。对已经确诊为无菌性肉芽肿/脓性肉芽肿皮炎的患犬的20份福尔马林固定的皮肤样本和12份新鲜皮肤样本，以16S rRNA 和ITS-1 区域为目标进行次代序列检查，与正常皮肤样本微生物群没有差异，进一步支持了病因是无菌的。 It has been hypothesized that traditional selective bacterial and fungal culture methods may exclude detection of the etiologic agent of SPDP. Next-generation sequence targeting of 16S rRNA and the ITS-1 region of 20 formalin-fixed skin samples and 12 fresh skin samples from dogs diagnosed with sterile granulomatous/pyogranulomatous dermatitis demonstrated no difference in microbiota compared with normal skin samples supporting a sterile cause.
此前的一项研究表明,46个病例中有21例存在利什曼原虫DNA。然而,值得注意的是,此项研究中调查的犬都在意大利,是利什曼病普遍流行的国家。因此, 不能作为因果关系的有力证据。此外, 这种综合征存在于非利什曼病流行地区 (如美国)。同样的研究也证明了这些病变没有分枝杆菌。 A previous study demonstrated the presence of Leishmania DNA in 21 of 46 cases.However, it should be noted that this study investigated dogs in Italy, where Leishmania is prevalent; therefore, a strong argument for causation cannot be made. Furthermore, this syndrome is present in non–Leishmania-endemic regions (such as the United States). This same study also demonstrated a lack of Mycobacteria DNA in these lesions.
鉴别诊断 DIFFERENTIAL DIAGNOSES 在北美引起犬脓性肉芽肿和肉芽肿性皮炎/脂膜炎的病因见表 1。 Causes of canine pyogranulomatous and granulomatous dermatitis/panniculitis in North America can be seen in Table 1.
诊断 DIAGNOSIS 确诊SPDP的方法是排除其他病因。 The diagnosis of SPDP is established via exclusion of other causes.
细胞学 Cytology 多次抽吸结节进行细胞学准备，避开瘘道。对抽吸物进行仔细检查，评估有无细菌、真菌或卵菌生物存在。在感染性脓性肉芽肿性皮炎/脂膜炎病例中，仅通过细胞学(如：芽生菌)就可以有效地确诊病因。溃疡和瘘道的细胞学检查可能揭示球菌和杆菌的继发性感染，甚至在SPDP或其他无菌操作中。 Perform multiple cytologic preparations of nodule aspirates, avoiding draining tracts.Review aspirates carefully to assess for the presence of bacterial, fungal, or oomycotic organisms. In infectious cases of pyogranulomatous dermatitis/panniculitis, an etiologic diagnosis may be efficiently made via cytology alone (eg, Blastomyces). Cytology of ulcers and draining tracts may reveal secondary infection with cocci and rods, even in SPDP or other sterile processes.
SPDP细胞学检查提示脓性肉芽肿性渗出。可能同时有少量嗜酸性粒细胞、浆细胞和淋巴细胞。在脂膜炎抽吸物中可观察到含脂滴的巨噬细胞和游离脂滴。由于严重的炎性反应，可能看到反应性纤维细胞，导致误诊为肉瘤。 SPDP cytology demonstrates a pyogranulomatous exudate; eosinophils, plasma cells, and lymphocytes may be concurrently present in smaller numbers. Lipidladen macrophages and free lipid may be observed in panniculitis aspirates. Given severe inflammation, reactive fibrocytes may be seen, leading to misdiagnosis of sarcoma.
怀疑有分支杆菌时，建议使用抗酸染色。在某些病例中，可看到巨噬细胞中出现染色不良的杆菌，可通过抗酸染色证实它们存在。 Acid-fast stain of aspirates is recommended when Mycobacterium is suspected; in some cases poorly staining rods may be visualized in macrophages, and their presence is confirmed via acid-fast stain.
组织病理学 Histopathology 如果细胞学不能确定病因，建议进行组织病理学检查。最好对新病变进行活检采样。避开瘘道和溃疡，因为这些病变没有诊断价值。进行多处活检采样，直径至少6毫米。推荐进行楔形切除活检，因为应包括表皮、真皮和深层皮下组织。需要进行特殊染色，以便诊断分枝杆菌和真菌微生物。 If an etiologic agent is not confirmed via cytology, histopathology is recommended. Biopsy of new lesions is preferable. Avoid draining tracts and ulcers, as they are of poor diagnostic value. Perform multiple biopsies of at least 6 mm in diameter. An excisional wedge is recommended, as the epidermis, dermis, and deep subcutaneous tissues should be included. Request special stains to facilitate the diagnosis of mycobacterial and fungal organisms.
预期的SPDP组织病理学表现包括结节性至弥漫性真皮和/或皮下肉芽肿性或脓性肉芽肿性皮炎。在无菌性脓性肉芽肿性皮炎中，最严重的炎性反应往往是在附件周围和血管周围区域。由于附件周围严重的炎性反应，也可能发展出现疖病。淋巴细胞、浆细胞和嗜酸性粒细胞可能少量出现。脂膜炎可为叶状或隔状。纤维化常见于慢性病变。 Expected histopathologic findings for SPDP include nodular to diffuse dermal and/or subcutaneous granulomatous or pyogranulomatous dermatitis. In sterile pyogranulomatous dermatitis, the inflammation is often most severe in the peri-adnexal and perivascular areas. Furunculosis as an extension of severe peri-adnexal inflammation may also be present. Lymphocytes, plasma cells, and eosinophils may be present in smaller numbers. Panniculitis may be lobar or septal. Fibrosis is noted in chronic lesions.
感染性脓性肉芽肿性皮炎和脂膜炎的组织病理学变化也相同。因此，可通过组织病理学的特殊染色(六胺银染色、PAS染色、革兰氏染色、抗酸染色)，以及细菌和真菌培养得出明确诊断。 Identical histopathologic changes are expected in infectious pyogranulomatous dermatitis and panniculitis. Therefore, histopathologic special stains (Gomori methenamine silver, periodic acid–Schiff, gram, acid fast) and bacterial and fungal cultures are indicated for a definitive diagnosis.
在真皮层深部和脂膜炎表现中，以少量中性粒细胞为主，并缺乏空泡样巨噬细胞时，病理学家很难将SPDP(巨噬细胞)与组织细胞增多症(树突状细胞)和罕见的非趋上皮样淋巴瘤(低分化淋巴细胞)进行区分。因此,诊断方法可能需要选择免疫组化染色或组织抽吸液流式细胞术。 In deep dermal and panniculitis presentations, when neutrophils are less predominant and foamy macrophages are absent, the pathologist may be challenged to distinguish SPDP (macrophages) from histiocytosis (dendritic cells) and rarely nonepitheliotropic lymphoma (poorly differentiated lymphoblasts). Thus, selective immunohistochemical stains, or flow cytometry of tissue aspirates, may be required for diagnosis. 培养 Culture 使用无菌外科操作采集皮肤和皮下组织样本，达到最大程度采集病原体，避免培养污染菌。将采集的组织进行需氧菌和厌氧菌、分枝杆菌和真菌培养。如果怀疑分枝杆菌感染，可进行聚合酶链反应(PCR)检查加快诊断，因为分枝杆菌生长缓慢，可能需要数周时间才能培养出来。为保证实验室人员的安全，通过地区性病史调查，并结合细胞学检查、组织病理学检查或辅助诊断测试，彻底排除芽生菌病、球虫病和组织胞浆菌病以后，再进行真菌培养。 Collect dermal and subcutaneous tissue samples with an aseptic surgical technique to maximize the yield of the etiologic agent and avoid culture of contaminants. Submit tissue for aerobic and anaerobic bacterial, mycobacterial, and fungal culture. If Mycobacterium is suspected, polymerase chain reaction (PCR) may be performed to expedite a definitive diagnosis, as slow-growing Mycobacterium species may take several weeks to recover from culture. For the safety of laboratory personnel, fungal culture should be withheld until blastomycosis, coccidioidomycosis, and histoplasmosis have been satisfactorily ruled out via geographic history or a combination of cytology, histopathology, or ancillary diagnostic tests.
考虑到环境中普遍存在条件致病性真菌和细菌微生物(如链洛孢霉、伯克氏菌)，能在培养基中单独获得，特别是在进行表面培养代替组织培养时，是不足以确诊的。对组织进行细胞学检查和/或组织病理学检查时发现的条件致病菌感染，可作为确诊依据。 Given that opportunistic fungal and bacterial organisms are environmentally ubiquitous(eg, Alternaria, Burkholderia), recovery from culture alone,particularly when surface culture is performed instead of tissue culture, is not sufficient for a definitive diagnosis. Cytologic and/or histopathologic evidence for tissue involvement of opportunistic infections is required for a definitive diagnosis.
SPDP病例有阴性培养结果，或溃疡病变继发细菌感染，会在培养基上发现微生物，通常是葡萄球菌属。因此，建议采集非溃疡组织进行培养。 Patients with SPDP will have negative cultures or culture will yield organisms reflective of secondary bacterial infection of ulcers, frequently Staphylococcus sp. Thus, tissue cultures of nonulcerated lesions are recommended. 其他测试 Additional Tests 有全身性临床症状, 如精神沉郁、发热、低体温、腹痛或关节痛的病例，建议进行全血细胞计数、血清生化检查和尿分析,以评估有无胰腺疾病或全身性红斑狼疮。单纯SPDP的病例可能有轻度、非再生障碍性贫血、高球蛋白血症和白细胞增多症。 Consider complete blood count, serum biochemistry, and urinalysis in patients with systemic clinical signs, such as malaise, pyrexia, hyporexia, abdominal pain, or joint involvement, to assess for pancreatic involvement or evidence for systemic lupus erythematosus.Patients with SPDP alone may have mild, nonregenerative anemia, hyperglobulinemia, and leukocytosis.
有地域性或旅行史的病例，症状表现也支持芽生菌病、球孢子菌病或组织胞浆菌病，同时细胞学没有发现微生物，可以通过血清学辅助检查和尿液测试确诊，不需要进行真菌培养。 Patients with geographic or travel history and signs supportive of blastomycosis, coccidioidomycosis, or histoplasmosis with no organisms found on cytology may be diagnosed via ancillary serologic and urine tests sans fungal culture.
针对分枝杆菌的PCR检测能确诊或加快诊断。PCR可用于鉴别腐霉菌和链壶菌,并有助于诊断这些难以培养的微生物。 PCR for Mycobacterium may confirm or expedite the diagnosis. PCR can be used to distinguish Pythium from Lagenidium and aid in the diagnosis of these fastidious organisms. 持久病因和诱发因素 PERPETUATING AND TRIGGERING FACTORS 根据作者的经验，除非接受免疫调节剂治疗能很好的控制住SPDP病例，否则一旦引起免疫刺激或发生创伤后可能会复发。有意思的是，作者曾注意到接种疫苗会引起全身复发，以及在撕裂伤/穿刺伤局部会复发脓性肉芽肿性结节性皮炎。据作者所知，这些现象并无其他资料记载。 In the experience of the author, otherwise well-controlled patients receiving immunomodulatory therapy with SPDP may relapse following a triggering immunostimulatory or traumatic event. The author has anecdotally noted generalized relapses associated with vaccination and focal relapses of pyogranulomatous nodular dermatitis in areas of laceration/puncture. These phenomena are not otherwise documented to the author’s knowledge.
治疗 TREATMENT SPDP的治疗包括免疫调节。当全身应用免疫抑制剂量的皮质类固醇时，治疗效果明显且迅速。严重的深层溃疡可能需要常规伤口护理和辅助疼痛管理。 Treatment of SPDP involves immunomodulation. A response to systemic corticosteroids is typically rapid when immunosuppressive doses are used. General wound care and ancillary pain management may be required for severe, deep ulcers.
全身治疗初期阶段临床症状得以缓解(图2B和4C, D)和，尝试用非甾体类免疫调节剂维持治疗。免疫调节剂的选择取决于临床严重程度。 The general treatment strategy involves initiation of clinical remission (Figs. 2B and 4C, D) and attempted maintenance with a nonsteroidal immunomodulatory protocol. The choice of immunomodulator is based on the degree of clinical severity.
对于临床表现中度至重度的病例，推荐使用泼尼松龙，其次是免疫调节剂，考虑到这些治疗的疗效有延迟，通常在治疗早期一起使用，因为能减少或停止糖皮质激素的用量。后者免疫调节剂需要与糖皮质激素联用以缓解症状的治疗方法不常见。 For moderate to severe presentations, prednisolone is recommended and a secondary immunomodulator is often added early in therapy as a corticosteroid-sparing or eliminating drug given the delayed time of efficacy for these therapies. Less commonly a secondary immunomodulator is required in conjunction with corticosteroid therapy to induce remission.
伴有发热、精神沉郁、疼痛或病情持续发展，而细胞学检查、体格检查或病史调查又不支持感染性病因的病例，作者会使用泼尼松，以0.5至1.0 mg/kg剂量每24小时口服一次进行治疗，直到通过阴性培养结果和组织病理学结果支持确诊SPDP。这种剂量往往能使SPDP快速达到临床舒适，进而等待检查结果，但对大多数病例来说，是不足以缓解症状的。当然，如果确实存在感染原因，则要权衡临床舒适度和潜在的感染恶化风险。 In patients with fever, malaise, pain, or advancing disease with no compelling cytologic, physical, or historical evidence of infectious cause, the author will treat patients with prednisone at 0.5 to 1.0 mg/kg by mouth every 24 hours pending confirmation of SPDP via negative culture and supportive histopathology results. Such dosages often provide rapid clinical comfort in SPDP as results await but are insufficient to induce remission in most patients. This relief, of course, must be weighed with the potential risk of worsening infection if an infectious cause is indeed present.
泼尼松/泼尼松龙 Prednisone/Prednisolone 对于中度至重度临床表现，首次剂量以总量为2 mg/kg，每24小时口服一次。病变通常在2至6周内明显消退。此后，可以在4到8周内逐渐减少剂量，至每隔一天，将所需剂量控制在每48小时0.25 mg/kg，或用非激素类免疫调节剂维持。 A total of 2 mg/kg is administered by mouth every 24 hours for initial control for moderate to severe presentations. Lesions typically resolve in 2 to 6 weeks. After this time the dosage can be tapered over a period of 4 to 8 weeks to the lowest every-other-day dosage needed for control with a goal dosage of 0.25 mg/kg every 48 hours, discontinuation, or maintenance with a nonsteroid immunomodulatory.
强力霉素和烟酰胺 Doxycycline and Niacinamide 对于较轻病例，强力霉素和烟酰胺是耐受性良好的免疫调节剂，可单独使用，或对于轻度至中度病例，可降低类固醇用量。这种联合用药可能需要8周才能完全发挥作用。值得注意的是，在目前有多重耐药性葡萄球菌感染的情况下，不赞成使用慢性抗菌治疗(强力霉素)。 Doxycycline and niacinamide provide well-tolerated immunomodulation for mild cases as a sole therapy or for mild to moderate presentations as a steroid-sparing therapy. This combination may take up to 8 weeks for full effect. Of note, the use of chronic antimicrobial therapy (doxycycline) is considered less favorable in the current era of multidrug-resistant staphylococcal infections.
烟酰胺每8至12小时口服一次。对于体重不足10公斤的犬，每次剂量为250mg。对于体重超过10公斤的犬，每次剂量为500mg。 Niacinamide is administered by mouth every 8 to 12 hours. For dogs less than 10 kg,250 mg is administered at each dose. For dogs greater than 10 kg, 500 mg is administered at each dose.
强力霉素每天口服两次，每次5.0 - 7.5 mg/kg。 Doxycycline is administered at 5.0 to 7.5 mg/kg by mouth twice a day.
一旦病变得到改善，剂量可以逐渐减少到每天一次，持续一个月，如果有效，可以尝试隔日一次治疗。 Once lesions are resolved, the dosage may be tapered to once daily over a period of a month and, if effective, every-other-day treatment may be attempted. 环孢菌素 (礼来公司的阿托皮卡) Cyclosporine (Atopica, Elanco) 每24小时口服总量为5-10mg/kg。对于中度至重度SPDP病例,环孢菌素可降低类固醇用量，对于轻度至中度病例，单独使用环孢菌素治疗有效。值得注意的是, 可能需要长达8周的时间才能见效。一旦有效, 剂量可以会减少到每48至72小时一次, 以维持症状。 A total of 5 to 10 mg/kg is administered by mouth every 24 hours. Cyclosporine provides reliable steroid-sparing control for moderate to severe cases of SPDP and is a reliable sole therapy for mild to moderate presentations. It is important to note that it can take up to 8 weeks for full clinical effect. Once resolution is achieved, the dosage may be reduced to every 48 to 72 hours to maintain resolution.
根据作者的经验, 环孢菌素是治疗SPDP最确实有效的非类固醇类免疫调节剂。 In the author’s experience, cyclosporine is the most reliably effective nonsteroidal immunomodulatory drug for SPDP. 霉酚酸酯 Mycophenolate Mofetil 口服总剂量为20-40mg/kg，每日2-3次。病变得以缓解可能需要长达8周的时间。尚未记录此药可用于治疗SPDP。这种药物的耐受性比硫唑嘌呤更好，在中度到重度的病例中，可作为一种能降低类固醇剂量的药物，特别是对环孢菌素不耐受的情况下。 A total of 20 to 40 mg/kg is administered by mouth divided into 2 or 3 daily dosages. Remission may take up to 8 weeks. This medication has not been well documented as a treatment of SPDP. This medication is better tolerated than azathioprine and is used in moderate to severe cases as a steroid-sparing drug, particularly if cyclosporine is not tolerated. 硫唑嘌呤 Azathioprine 每24小时口服总量为1-2 mg/kg，可用于治疗顽固性病例或降低类固醇用量。临床完全见效可能需要8周。一旦症状缓解，剂量可减少到每48小时1-2 mg/kg，并逐渐降至能维持症状的最低剂量。 A total of 1 to 2 mg/kg by mouth every 24 hours is used for refractory cases or as a steroid-sparing drug. Full clinical effect may take up to 8 weeks. Once remission is achieved, the dosage is reduced to 1 to 2 mg/kg every 48 hours and slowly tapered to the lowest dosage required to maintain remission.
考虑到骨髓毒性、胰腺毒性和肝毒性副作用，硫唑嘌呤最好保留用于治疗类固醇、环孢菌素和霉酚酸酯控制不住的顽固性病例。在首次治疗的前8周，建议每两周进行一次全血细胞计数和血清生化检查。 Given the myelotoxic, pancreatic, and hepatotoxic side effects, azathioprine is best reserved for steroid, cyclosporine, and mycophenolate refractory cases. A complete blood count is recommended every 2 weeks as well as serum chemistries for the first 8 weeks of therapy.
维生素E Vitamin E 总剂量为400IU，每12小时一次，是一种有效的辅助抗氧化治疗方案，已成功用于无菌性脓性肉芽肿性脂膜炎的病例。 A total of 400 IU every 12 hours is a helpful adjunct antioxidative treatment that has shown to be successful in cases of sterile pyogranulomatous panniculitis.
对于单个病灶，可以手术切除，但是，也可能会形成新的病变。作者治疗过手术切除肉芽肿后裂开的病例。手术部位有脓性肉芽肿性炎症浸润。 For solitary lesions, surgical removal may be curative; however, it is possible that new lesions may form. The author has treated cases that have dehisced after surgical removal of the granuloma. The surgery site was infiltrated with pyogranulomatous inflammation.
预后 PROGNOSIS
免疫调节治疗对 SPDP 的生存和缓解有较好的预测作用。面部可能会出现瘢痕,并可能会导致瘢痕性眼睑外翻，需要手术矫正(图5)。大多数病例需要持续免疫调节治疗, 以防止复发。 Prognosis for survival and remission of SPDP is good with immunomodulatory therapy. Scarring may occur and, in the facial area, may result in cicatricial ectropion requiring surgical correction (Fig. 5). Most cases require maintenance immunomodulatory therapy to prevent relapse.
Fig. 5. Cicatricial ectropion in a mixed-breed dog following untreated SPDP. 图5所示。未治疗的SPDP杂交患犬的瘢痕性眼睑外翻。
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发表于 2019-7-2 23:47:58
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