一只犬的钙乳症：一个罕见的钙沉着症的表现

王帆

Milk of Calcium in a Dog: A Rare Presentation of Calcinosis Circumscripta

一只犬的钙乳症：一个罕见的钙沉着症的表现

 

作者;Michela De Lucia | Paola Orlandini | Francesco Godizzi | Arianna Costa | Andrea Pratesi

 

翻译：王帆

 

Keywords: Calcinosis cutis | dog | milk of calcium

关键词：皮肤钙质沉着症|犬|钙乳症

 

ABSTRACT

摘要

This report presents the clinical features, clinicopathological changes, computed tomography images and response- to- treatment of a dog with calcium- laden subcutaneous fluid collections, resembling a rare form of calcinosis in humans termed ‘milk of calcium’.

本报告介绍了一只患有皮下含钙液体积聚（类似人类一种罕见的钙沉积症，即“钙乳症”）的犬的临床特征、临床病理变化、计算机断层扫描图像以及对治疗的反应情况。

 

1 | Introduction

1介绍

In humans, the term ‘milk of calcium’ refers to a rare form of calcinosis characterised by the presence of extensive collection of calcium- rich fluid in various organs (e.g., gallbladder and uri nary tract) or in the subcutaneous and intermuscular regions. The condition has been reported in association with a variety of underlying diseases and it is believed to be caused by several interacting mechanisms including recurrent trauma or tissue damage, chronic inflammation and obstruction.

在人类中，“钙乳症”这一术语指的是罕见的一种钙沉积症，其特征是多种器官（如胆囊和泌尿系统）或皮下和肌肉间区域存在大量富含钙的液体聚集。这种病症曾与多种潜在疾病相关联，并且被认为是由多种相互作用的机制引起的，包括反复的创伤或组织损伤、慢性炎症以及阻塞。

 

Large fluid- filled subcutaneous nodules, resembling milk of calcium in humans, have been reported in dogs with calcinosis circumscripta; yet to the best of the authors' knowledge, no fur ther details on this clinical presentation have been published. We describe the clinical features, clinicopathological changes, computed tomography (CT) images, response to treatment and follow- up of a dog with subcutaneous and intermuscular collec tion of calcium- rich fluid, similar to milk of calcium in humans.

在患有局限性钙化病的犬上，曾有报道称出现过类似人类钙乳症的大量充满液体的皮下结节；但据作者所知，关于这种临床表现的更多细节尚未有相关报道。我们描述了一只患有皮下和肌间富含钙质液体聚集（类似于人类钙乳症）的犬的临床特征、临床病理变化、计算机断层扫描（CT）图像、治疗反应及后续情况。

 

2 | Case Presentation

2病例表现

A 7- month- old, intact male golden retriever was presented for extensive subcutaneous fluid collection that had developed over the previous 2 months.

一只 7 月龄、未去势雄性金毛寻回犬被送来就诊，其在过去两个月内出现了大量皮下积液。

 

At the age of 2 months, the dog was diagnosed with sterile granulomatous dermatitis and lymphadenitis, and treated with prednisolone acetate (Novosterol, MSD Animal Health; 2 mg/ kg once daily) injected subcutaneously on the dorsal neck for 2 weeks, followed by a 6- week course of lower doses (0.3–0.5 mg/ kg every other day) of oral prednisolone. One month after steroid withdrawal, multiple areas of skin induration were noted on the dorsal neck, followed by the appearance of gradually expand ing fluctuant nodules on the left shoulder. Despite the presence of the nodules, a microchip was implanted on the left shoulder because the previously applied one could not be detected. As the nodules on the shoulder and the neck continued to grow, the dog was referred.

该犬在 2 月龄大时被诊断出患有无菌性肉芽肿性皮炎和淋巴结炎，并接受了醋酸泼尼松龙（Novosterol，默沙东动物健康公司；2 毫克/千克，每日一次）的皮下注射治疗，疗程为 2 周，之后又进行了为期 6 周的较低剂量（0.3 - 0.5 毫克/千克，每隔一天一次）的口服泼尼松龙治疗。停用激素一个月后，在颈部背部发现了多个皮肤硬结区域，随后左肩出现了逐渐扩大的有波动感的结节。尽管存在这些结节，但由于之前植入的微芯片无法检测到，所以在左肩植入了一个新的微芯片。由于肩部和颈部的结节继续生长，该犬被转诊治疗。

 

At presentation, the dog had multiple large, fluid- filled masses involving the left shoulder, the left dorsolateral aspect of the neck, the head and the cranial thorax (Figure 1). The masses were not painful, and fluid flowed from one area to another if the dog changed position or after slight compression. The over lying skin was intact yet multifocally erythematous and indu rated. Otherwise, the dog appeared healthy except for stunted growth. No microchip was detected by the scanner.

在检查时，这只犬身上有多处较大的充满液体的肿块，分布在左肩、颈部的后侧、头部以及颅部胸腔区域（图 1）。这些肿块并不疼痛，而且如果犬改变体位或者受到轻微挤压，液体就会从一处转移到另一处。覆盖在上面的皮肤完好无损，但多处出现发红和炎症。除此之外，这只犬看起来健康，只是生长发育迟缓。扫描仪未检测到微芯片。

 

Ultrasonography showed a subcutaneous collection of fluid containing echogenic particulate material. Two litres of a chalky milky fluid were drained under sedation (see Figure S1). Cytological evaluation of the collected material showed scat tered macrophages and mesenchymal cells admixed with dark brown refractile crystals (Figure 3). No bacterial growth was detected from the fluid, which consisted of pure calcium phos phate (Fourier transform infrared [FT- IR] Nicolet iS5; Thermo Fischer Scientific). Subcutaneous calcinosis in the form of a fluid collection (i.e., milk of calcium) was diagnosed.

超声检查显示，皮下有一个含有强回声颗粒物质的积液囊。在麻醉状态下，抽取了两升乳白色、类似粉笔状的液体（见图 S1）。对收集到的物质进行细胞学评估后发现，其中有散乱分布的巨噬细胞和间充质细胞，混杂着深褐色的不透明晶体（图 3）。从该液体中未检测到细菌生长，其主要成分是纯磷酸钙（傅里叶变换红外光谱 [FT-IR] 尼科莱特 iS5；赛默飞世尔科技）。最终诊断为皮下钙质沉着症，表现为积液囊肿（即钙乳症）。

 

Blood and urine tests showed an elevation of C- reactive protein (0.84 mg/dL [0.01–0.13]) and a slight increase in serum phospho rus (P) concentration (8.6 mg/dL [6.6–8.1]) that was detected at the time of presentation and not on subsequent days. According to the medical history, vitamin D or calcium supplements had not been administered.

血液和尿液检测显示 C 反应蛋白水平升高（0.84 毫克/分升 [0.01 - 0.13]），血清磷（P）浓度略有上升（8.6 毫克/分升 [6.6 - 8.1]），这些指标是在就诊时检测到的，而非在后续几天内出现的。根据病史，患犬未服用维生素 D 或钙剂补充剂。

 

A total body CT scan, performed under general anaesthesia, showed no abnormalities other than the extensive subcutaneous fluid collections, and mineralisation on the left shoulder and the neck, and cutaneous mineralisation on the shoulders, neck and lumbar and perianal areas (Figure 2). Despite a thorough full- body search, the microchip was not detected.

在全身麻醉状态下进行的全身 CT 扫描显示，除了广泛的皮下积液、左肩和颈部的矿物质沉积以及肩部、颈部、腰椎和肛周区域的皮肤矿物质沉积外，没有其他异常情况（图 2）。尽管进行了全面的全身检查，但仍未检测到微芯片。

 

Oral prednisolone (0.5 mg/kg twice daily) was started to con trol the inflammation associated with the calcium deposition. However, a few days after drainage, a larger fluid collection (5 L) appeared. Thus, oral prednisolone was tapered, intravenous zole dronic acid (Acido zoledronico Accord, Accord Healthcare Ltd.; 0.25 mg/kg) was administered, and surgical removal of the masses was planned. Because of the size of the lesions, two surgeries were required, performed 6 weeks apart (Figure 3). Zoledronic acid (0.25 mg/kg) was repeated 1 week before the second surgery.

开始使用口服泼尼松龙（0.5 毫克/千克，每日两次）来控制与钙沉积相关的炎症。然而，在引流几天后，出现了较大的积液（5 升）。因此，口服泼尼松龙的剂量逐渐减少，静脉注射唑来膦酸（阿科迪奥索德罗尼科阿科迪奥，阿科迪奥医疗有限公司；0.25 毫克/千克）被使用，并计划进行肿物切除手术。由于病变的大小，需要进行两次手术，两次手术间隔 6 周（图 3）。在第二次手术前 1 周，重复使用唑来膦酸（0.25 毫克/千克）。

 

Histopathological examination of the removed tissue revealed multiloculated, subcutaneous large pseudocystic cavities lined with fibrous and granulation tissue, macrophages, and multi nucleated giant cells. Interspersed bone metaplasia and granu lomatous foci centred on calcium minerals also were observed (Figure 4, Figure S2).

对切除组织进行的组织病理学检查显示，其中存在多房的、位于皮下的大假性囊肿腔，腔壁由纤维组织、肉芽组织、巨噬细胞和多核巨细胞构成。此外，还观察到散布在其中的骨化变性和肉芽肿性病灶，这些病灶以钙质为中心（图 4、图 S2）。

 

Three months after the second surgery, no recurrence of the lesions was observed, and only small areas of skin induration, consistent with previously documented areas of mineralisation, were still evident on the neck.

在第二次手术后三个月，未观察到病变复发的情况，但颈部仍可见一些小范围的皮肤硬化区域，这与之前记录的矿化区域相符。

 

3 | Discussion

3讨论

We describe a dog with an extensive subcutaneous collection of calcium- rich fluid resembling milk of calcium in humans. The condition was characterised by the presence of subcu taneous, interconnected, fluctuating masses, covered by in tact, multifocally erythematous and indurated skin. A soft tissue infection was the main clinical differential diagnosis, although unlikely owing to the absence of pain and fever. The chalky, milky appearance of the fluid and its cytologi cal features suggested a calcium- rich fluid. Histopathological findings from the lesions overlapped with those of calcinosis circumscripta. Indeed, in a retrospective pathological study including 77 dogs with calcinosis circumscripta, gross lesions varied from small nodules to large cystic masses containing chalky white material.

我们描述了一只犬与广泛的富含钙的液体皮下收集人钙乳症。该病症的特点是存在皮下，相互联系，波动的肿块，被完整的，多灶性发红和硬化皮肤覆盖。软组织感染是主要的临床鉴别诊断，尽管不太可能，因为没有疼痛和发烧。白垩色，乳白色的外观及其细胞学特征表明这是一种富含钙的液体。组织病理学检查结果与边界钙质沉着症重叠。事实上，在一项包括77只边缘性钙质沉着症犬的回顾性病理研究中，大体病变从小结节到含有白垩白色物质的大囊性肿块不等。

 

The pathogenesis of calcinosis circumscripta is not fully eluci dated, yet involves the calcification of areas of damaged tissue in the setting of normal serum calcium and phosphate concen trations. Because multiple factors, including mechanical and chemical injuries or infectious, inflammatory, and neoplastic diseases, can cause the primary lesion, different clinical scenar ios are possibl. In the present case, tissue damage resulting from multiple subcutaneous injections of prednisolone acetate (the manufacturer recommends a deep intramuscular injection) and the double attempt to apply the microchip seems the most likely cause of the subcutaneous deposition of calcium salts in the neck and the left shoulder. Subsequently, tearing of the calci fied tissue planes could have led to the formation of fluid- filled subcutaneous cavities, as suggested for milk of calcium collec tion in children with juvenile dermatomyositis. Finally, pro longed treatment with systemic glucocorticoids might have been responsible for the cutaneous calcification in multiple areas of the body. Iatrogenic hyperadrenocorticism was the main under lying condition in a series of 46 dogs with calcinosis cutis.

局限性钙化症的发病机制尚未完全阐明，但其发病机制涉及在血清钙和磷浓度正常的情况下，受损组织区域的钙化。由于多种因素，包括机械性损伤、化学损伤或感染、炎症和肿瘤性疾病等，都可能导致原发性病变，因此可能出现不同的临床情况。在本病例中，由于多次皮下注射醋酸泼尼松龙（制造商建议进行深部肌肉注射）以及两次尝试植入微芯片，导致颈部和左肩出现钙盐沉积，这可能是最可能的病因。随后，钙化组织层的撕裂可能导致形成充满液体的皮下腔隙，这类似于患有幼年性皮肌炎的儿童体内的钙收集液囊现象。最后，长期使用全身性糖皮质激素治疗可能是导致身体多个部位皮肤钙化的主要原因。在 46 只患有皮肤钙化症的犬中，医源性肾上腺皮质功能亢进是主要的潜在病因。

 

CT scan was helpful in defining the overall extent of calcium- rich fluid collections and identifying other foci of skin miner alisation. CT scan is effective and sensitive for detecting and characterising the extent of calcinosis cutis in humans.

CT 扫描有助于明确富含钙质的液体积聚的整体范围，并识别其他皮肤矿化病灶。CT 扫描对于检测和描述人类皮肤钙化病的范围具有有效性和敏感性。

 

Surgical removal of the lesions is considered curative in dogs with calcinosis circumscripta. In the present case, we also used zoledronic acid before surgery to try to reduce the size of the lesions that appeared to be enlarging rapidly. Zoledronic acid is an aminobisphosphonate used for the management of pain and hypercalcaemia in dogs.

对于患有局限性钙化病的犬只，手术切除病变被认为是能够治愈的。在本病例中，我们还在手术前使用了唑来膦酸，试图缩小那些似乎在迅速增大的病变区域。唑来膦酸是一种氨基双膦酸盐，用于治疗犬类的疼痛和高钙血症。

 

Bisphosphonates have been proposed to treat milk of calcium in children with juvenile dermatomyositis based on their ability to inhibit bone resorption and calcium accretion to the already formed calcification. However, it is not possible to draw any conclusions about the possible beneficial effect of this drug in this case.

基于其能够抑制骨质吸收以及促进已形成钙化部位的钙质沉积的特性，双膦酸盐被提议用于治疗患有青少年皮肌炎的儿童的钙质流失问题。然而，目前尚无法就此药物在该病例中的潜在益处得出任何结论。

 

In conclusion, calcinosis circumscripta in the form of milk of calcium must be included in the differential diagnoses of exten sive subcutaneous collections of fluid in dogs.

总之，局限性钙质沉着症（表现为钙乳症）必须纳入犬类大面积皮下积液的鉴别诊断范畴之中。

 

 

FIGURE 1 | Milk of calcium in a 7- month- old golden retriever. (a) Multiple subcutaneous fluid- filled masses are evident in the left dorsolateral region of the head and neck, and on the left shoulder. (b) Fluid collected from the subcutaneous masses has a milky appearance with a pinkish disc olouration resulting from the presence of a minimal amount of blood

图 1 | 一只 7 个月大的金毛猎犬体内的钙质乳状液。（a）头部和颈部的左侧背外侧区域以及左侧肩部可见多个充满液体的皮下肿块。（b）从这些皮下肿块中抽取的液体呈乳白色，带有淡粉色的色泽，这是由于存在少量血液所致。

 

 

 

FIGURE 2 | Computed tomography (CT) of a golden retriever with milk of calcium. (a) Dorsal view. A multilobed mass occupies the left shoulder and the left dorsolateral region of the head, neck and chest to T7. The overlying skin shows multifocal areas of mineralisation (asterisks), also in volving the right shoulder. (b) Transversal view. The masses are bounded by a hyperattenuating capsule and divided into pseudobursae by multiple septa (arrows). Both the capsule and the septa are partially mineralised and richly vascularised. The most sloping part of the lesions is occupied by mineralised material (arrowhead) (Somatom Force; Siemens)

图 2 | 一只金毛猎犬的钙质乳状物质的计算机断层扫描图像。（a）背部视图。一个多叶状肿块占据左肩以及头部、颈部和胸部至 T7 的左后外侧区域。覆盖其上的皮肤显示出多处矿化区域（星号），右侧肩部也有类似情况。（b）横截面视图。肿块被一个高密度的包膜所包围，并由多个隔膜（箭头）分隔成假滑囊。包膜和隔膜部分矿化且血管丰富。病变最倾斜的部分由矿化物质占据（箭头）

 

 

 

FIGURE 3 | Macroscopic pictures of the surgically removed tissue. (a) Masses were carefully debulked and removed intact along with the adher ent skin (asterisks). (b) After opening the excised masses, septa creating pseudobursae (arrows) and foci of semisolid gritty material (arrowhead) are evident.

图 3 | 手术切除组织的宏观图像。（a）将肿块小心地进行减容处理，并完整地连同附着的皮肤一并切除（用星号标出）。（b）在打开切除的肿块后，可以看到形成假滑囊的隔膜（箭头）以及半固体状粗糙物质的聚集（箭头头）。

 

 

 

FIGURE 4 | Histological features of milk of calcium. (a) The lesion is subcutaneous (adipose tissue, arrowhead) and consists of large pseudocystic cavities (asterisk) surrounded by thick fibrous septa (diamond). Smaller foci of granulomatous inflammation centred on calcium minerals (long har row) are present within the fibrous tissue (haematoxylin & eosin, ×20). (b) A fibrous septum with an extended area of osseous metaplasia (asterisk). At the top of the picture is the lumen of a pseudocyst, covered by haemorrhages (arrowheads) (H&E, ×20). (c) Macrophages, multinucleated foreign body and osteoclast- like giant cells (long arrows) mixed with a smaller number of small mature lymphocytes, plasma cells and neutrophils line the pseudocystic cavities that contain amorphous, variably mineralised, proteinaceous material (calcospherites, arrowheads) (H&E, ×400)

图 4 | 钙质乳的组织学特征。（a）病变位于皮下（脂肪组织，箭头所示），由大的假性囊腔（星号）组成，周围环绕着厚实的纤维隔（菱形）。纤维组织内存在围绕钙质矿物质的较小的肉芽肿性炎症病灶（长箭头），呈现在纤维组织中（苏木精-伊红染色，×20）。（b）一个带有扩展的骨化化生区域的纤维隔（星号）。图片顶部是假性囊腔的腔内，覆盖着出血点（箭头）（苏木精-伊红染色，×20）。（c）巨噬细胞、多核异物细胞和类似破骨细胞的巨细胞（长箭头）与少量的小型成熟淋巴细胞、浆细胞和中性粒细胞混合，沿着含有无定形、不同程度矿化的蛋白质样物质（钙质球体，箭头）的假性囊腔排列（苏木精-伊红染色，×400）

 

 

 

 

王明扬

南海

学习

VetF付

学习

杨先生

小卡特鲸鱼

高雪莹

学习