Idiopathic chylothorax and lymphedema in 2 whippet littermates

Abstract

Idiopathic chylothorax and limb edema was diagnosed in two 2-year-old male whippet siblings. The fact that the 2 related animals developed similar clinical signs at a young age may suggest a congenital or hereditary etiology.

Chylothorax is an uncommon disease characterized by the accumulation of a chylous effusion within the pleural space. Traumatic rupture of the thoracic duct was previously believed to be the main etiology; however, disturbances of the intrathoracic lymph flow and increased right-sided venous pressure, impeding the emptying of the thoracic duct, are currently considered the major causes of chylothorax in small animals (1,2). The condition has been associated with a number of underlying disorders such as cranial mediastinal masses, heart disease, and congenital malformations of the thoracic duct. However, in most animals, no underlying disease can be identified and the chylothorax is termed idiopathic (2). Afghan hounds have a high incidence of lymphatic abnormalities and have a higher relative risk for developing idiopathic chylotho-rax than other breeds (3,4). Even if a congenital or hereditary etiology has been suspected for many years, the underlying mechanism for chylothorax in this breed remains to be determined (4). An abnormal connection between the thoracic duct and the venous angle was described in 1 Afghan hound with chylothorax, but the general anatomy of the thoracic duct in healthy Afghan hounds does not seem to be different from that of other breeds (5,6). This report presents idiopathic chylothorax and lymphedema in 2 young whippet siblings and discusses the possibility of a congenital or hereditary origin of the disorder in this breed.

Case descriptions

Case 1

A 2-year-old entire cryptorchid male whippet, weighing 13.8 kg, was referred with a 3-day history of subcutaneous swelling and purpura extending over both forelimbs, the right thoracic and ventral abdominal walls. According to the owners the dog had yelped shortly before the onset of the clinical signs, but no traumatic event had been observed. Treatment with injectable meloxicam (Metacam; Boehringer, Ingelheim, Germany), enrofloxacin (Baytril; Bayer, Kiel, Germany), and vitamin K₁ (Konakion; Roche, Basel, Switzerland) had been unsuccessful. The dosages of the medications were not reported. On physical examination the dog was bright and alert. The respiratory rate was elevated (40 breaths/min). Thoracic sounds were normal. There was an extensive non-painful pitting edema and purpura extending from the thoracic wall to both forelimbs and the ventral abdomen (Figure 1). The jugular veins were not distended.

Figure 1.

Dog 1 — Extensive non-painful pitting oedema and purpura extending from the thoracic wall to both forelimbs and the ventral abdomen.

Hematology showed lymphopenia [312/mL; reference interval (RI): 1000 to 4800/mL] and monocytopenia (78/mL; RI: 200 to 1000/mL). Serum biochemistry revealed increased activities of alanine aminotransferase (116 IU/L; RI: 11 to 58 IU/L) and alkaline phosphatase (132 IU/L; RI: 14 to 39 IU/L), hypo-proteinemia (51 g/L; RI: 60 to 80 g/L) and hypoalbuminemia (21 g/L; RI: 27 to 38 g/L). Lymphopenia and hypoproteinemia were most likely due to losses into lymph. Hypoalbuminemia was not severe enough to be causing limb edema. Elevations in liver enzyme activities were mild and considered secondary to the overall disease process rather than a sign of primary liver disease. Buccal mucosal bleeding time, platelet count, prothrom-bin time and activated partial thromboplastin time were within reference ranges, excluding primary and secondary hemostatic defects. Urinalysis was unremarkable.

Thoracic radiographs revealed widening of the interlobar fissures, blunting of the costophrenic sulci and retraction of the lung field from the thoracic wall, consistent with a moderate pleural effusion. Thoracic ultrasonography confirmed the presence of anechoic fluid in the pleural space. Echocardiography showed no abnormalities. Thoracocentesis was performed and 600 mL of milky, pinkish fluid were removed. Thoracic radiography was not repeated post-thoracocentesis. Fluid analysis was consistent with a chylous effusion (triglyceride: pleural fluid 10.53 g/L, serum 0.47 g/L; cholesterol: pleural fluid 1 g/L, serum 1.94 g/L; cytology: 40% histiocytes, 40% small lymphocytes and 20% non-degenerate neutrophils). Aerobic and anaerobic bacterial cultures of the effusion were negative. Five punch biopsies of the skin and subcutaneous tissue were taken from the left antebrachial area. The regional lymph nodes were not enlarged and therefore were not sampled. Histopathology of the skin biopsies showed severe edema, mainly within the superficial dermis associated with microhemorhage. The lymphatic vessels were markedly dilated and lined by hyperplastic endothelial cells. There was only a minimal, diffuse, interstitial inflammatory infiltrate, composed of neutrophils, lymphocytes and histiocytes that occasionally contained hemosiderin. There was no evidence of neoplastic infiltration. The histopathology results were consistent with a diagnosis of lymphedema.

Based on these results and in the absence of evidence of an underlying disease, a diagnosis of idiopathic chylothorax and primary lymphedema was made. The dog was discharged on a low fat diet (Hill’s w/d; Hill’s Pet Products, Brussels, Belgium) and hydrotherapy to treat the limb edema. Two weeks later, the purpura had resolved and the subcutaneous edema had improved. Thoracic radiographs and ultrasound revealed persistence of a moderate pleural effusion and mild cranial mediastinal lymphadenomegaly. Approximately 300 mL of chylous effusion were removed via thoracocentesis. The owner declined further investigations and surgical treatment. The dog was managed with repeated thoracocentesis for the next 5 mo until the owner elected surgical management. A right thoracotomy at the 9th intercostal space was performed and the thoracic duct ligated in its more caudal portion as closely as possible to the diaphragm using stainless steel staples. Then a subtotal pericardectomy was performed removing the pericardium to the level of the phrenic nerve. A thoracic drain was placed. The dog continued to produce around 500 mL/day of chylous effusion for the first 4 d after surgery and developed severe hypoalbuminemia (10 g/L; RI: 27 to 38 g/L). The fluid production progressively decreased over the following days (286 mL/d on day 6) and the dog was discharged into the care of the referring veterinarian on day 7 post-surgery with the chest drain in place.

On re-examination 11 days after surgery only 20 mL of chylous effusion could be removed via the drain which was then removed. However, the limb lymphedema had worsened, now also affecting the hind limbs. Serum albumin had increased to 21 g/L (RI: 27 to 38 g/L). The dog’s general demeanor remained good and the body condition was stable. Over the following month the dog continued to produce significant amounts of chylous effusion, requiring intermittent thoracocentesis and developed diarrhea. Thoracic ultrasound performed 17 d after surgery showed presence of a pleural effusion and peripheral consolidation of the right caudal lung lobe. Abdominal ultrasound showed hyperechogenicity of the small intestinal mucosal layer compatible with lymphangiectasia. Due to the lack of improvement, the dog was euthanized. The owner did not allow a postmortem to be performed.

Case 2

A 2-year-old entire male whippet, a littermate of dog 1, weighing 13.4 kg was presented for investigation of progressive exercise intolerance. On presentation the dog was tachypnoeic (72breaths/min), showing a restrictive respiratory pattern. Heart and respiratory sounds were muffled ventrally. No peripheral edema was present. Hematology showed no significant abnormalities. Serum biochemistry revealed increased serum activities of alanine aminotransferase (64 IU/Ll) and alkaline phosphatase (79 IU/L), which were considered secondary to the overall disease process. Thoracic radiographs suggested severe pleural effusion. Repeat radiography after removal of 1000 mL of a milky effusion via thoracocentesis showed no abnormalities other than a mild pneumothorax, which was considered iatrogenic. Pleural fluid analysis was consistent with a chylous effusion (triglyceride: pleural fluid 9.78 g/L, serum: 0.46 g/L; cytology: 20% histiocytes, 55% small lymphocytes and 25% non-degenerate neutrophils). A coagulase-negative Staphylococcus was cultured from the effusion, but was considered to be a contaminant based on the absence of bacteria on cytology of the pleural effusion and the fact that most clinically significant staphylococci are coagulase positive.

Echocardiography and thoracic CT showed no morphological abnormalities. Idiopathic chylothorax was diagnosed and the dog was discharged on rutin (Venoruton; Novartis, Brussels, Belgium), 50 mg/kg TID, PO and Hill’s i/d (Hill’s Pet Products, Brussels, Belgium). There was no response to treatment and the dog was admitted 2 wk later for surgery. Ligation of the thoracic duct and subtotal pericardectomy were performed as described. Over the following days, the pleural effusion decreased in quantity and became serosanguineous rather than chylous. The dog was discharged 10 d after surgery. On re-examination 4 and 12 mo after diagnosis, the dog was clinically well. Small amounts of pleural effusion were still present on thoracic radiographs, but did not warrant thoracocentesis. During that period, the dog showed several episodes of front limb edema, which were treated by the referring veterinarian with furosemide (Lasix; Hoechst Marion Roussel SA, Brussels, Belgium) with limited success.

Discussion

The 2 whippets in the present report were siblings and were presented at the age of 2 y within 6 mo of each other showing abnormalities of the lymphatic system. The initial clinical presentation of the 2 dogs varied considerably. The dog in case 1 was presented with a pleural effusion, expansive lymphedema, and purpura. Intestinal lymphangiectasia was suspected based on the presence of gastrointestinal signs and ultrasonographic findings, but was not definitively confirmed via histopathology. The dog in case 2 was presented with a pleural effusion and developed peripheral lymphedema at a later stage. In both cases no underlying abnormalities were identified and a diagnosis of idiopathic chylothorax and primary lymphedema was made. The diagnosis of primary lymphedema in case 1 was complicated by the presence of purpura. While mild extravasation of erythrocytes can be a feature of primary lymphedema, (7) marked purpura associated with edema is more commonly described in association with vasculitis syndromes (8). However, histopathologic examination showed no evidence of vasculitis, and revealed edema in association with severely dilated lymphatic vessels. Primary lymphedema can appear histopathologically either as lymphatic hypoplasia or lymphatic hyperplasia and dilatation (7); thus, in this case a diagnosis of primary lymphedema with lymphatic hyperplasia and dilatation was made. A possible explanation for the initial purpura could be a focal trauma that produced hemorrhage and precipitated the development of lymphedema. Trauma has been reported as a precipitating factor of primary lymphedema in a dog (9) and is supported by the history of the dog crying out shortly before the onset of the clinical signs in this case.

Idiopathic chylothorax associated with primary lymphedema in dogs is only briefly mentioned by 2 sources (3,6) and is also a very rare clinical entity in the human literature (10). In most human cases lymphedema is congenital or hereditary and the association with chylothorax is interpreted as an expression of a more generalized congenital lymphatic malformation (10).

Afghan hounds have a high incidence of lymphatic abnormalities, in particular, chylothorax (3). The underlying mechanism still needs to be determined, but a congenital or hereditary etiology is suspected (4). According to the breeder of the 2 dogs in the present report, neither parents nor other offspring were similarly affected. However, the fact that the 2 dogs developed clinical signs at a similar young age may suggest that the breed predisposition noted in Afghan hounds may extend to other breeds of the sight hound family.

Lymphangiography of both the affected limbs and the thoracic duct may have been helpful in completely defining possible lymphatic abnormalities, but was not performed in the dogs in this report in order to minimize surgical time. High fat cream was fed before surgery. The lipid-loaded and therefore milky chyle helped identify the thoracic duct during surgery.

The 2 related dogs in the present report developed peripheral edema of the front limbs in addition to chylothorax, which may be the consequence of a more generalized abnormality of the lymphatic system. The development of clinical signs in both dogs at a young age may suggest a congenital or hereditary origin.