thyroid gland was palpable in the neck region. Fundic examination revealed ... peritonitis), thyroid hormone analysis, and fecal flota- ... that eosinophilia (e.g.parasites, neoplasia, allergic ... tions, multiple small pancreatic nodules, dilation of.
Restrictive cardiomyopathy in a cat with hypereosinophilic syndrome Bill Saxon, Mattie Hendrick, Jerry R. Waddle A12-year-old, 3 kg, spayed female domestic shorthaired cat was presented for examination, having a one month history of progressive weight loss, anorexia, and lethargy. Intermittent vomiting and diarrhea had occurred for two weeks prior to presentation. The vomitus contained bile and was unrelated to eating. The diarrhea contained mucus but no blood. Physical examination revealed a cachectic cat with poor haircoat; rectal temperature was 38°C. Moderate inspiratory dyspnea was present and heart and lung sounds were muffled. The jugular veins were not distended. Mucous membranes were pale and capillary refill time was less than two seconds. Hepatomegaly and bilaterally small kidneys were noted upon abdominal palpation and a slightly enlarged left thyroid gland was palpable in the neck region. Fundic examination revealed bilateral central retinal degeneration. Problems identified by the history and physical examination were related to the gastrointestinal tract, respiratory system, and cardiovascular system. The initial diagnostic plan included chest and abdominal radiographs, complete blood count, serum chemistry panel, urinalysis, viral serological tests (feline leukemia virus, feline immunodeficiency virus, feline infectious peritonitis), thyroid hormone analysis, and fecal flotation for parasites. Based on the inspiratory dyspnea and muffled heart and lung sounds, thoracocentesis was performed. Two hundred mL of cloudy, pale yellow fluid was removed from the pleural space. The fluid had a total nucleated cell count of 5.3 x 109/L. Large numbers of mature eosinophils (greater than 95% of all nucleated cells), occasional monocytes, and few erythrocytes were found on pleural fluid cytology. No cardiac murmurs or arrhythmias were heard by auscultation after thoracocentesis. Chest radiographs and six-lead electrocardiography were normal following thoracocentesis. A slightly enlarged liver, small kidneys, and poor detail (presumably due to loss of intraabdominal fat) were evident on abdominal radiographs. The total white blood cell (WBC) count was 129.50 x 109/L, with 107.48 x 109/L eosinophils. A slight left shift (1.30 x 109/L band neutrophils) and mild anemia (hematocrit 0.23 L/L) were present. Mean corpuscular volume was 61 fL (normal range 39-47 fL). Results of serum chemistry and thyroid hormone analysis were normal, except for mild Can Vet J 1991; 32: 367-369
Department of Clinical Studies (Saxon, Waddle) and Department of Pathobiology (Hendrick), School of Veterinary Medicine, University of Pennsylvania, 3850 Spruce Street, Philadelphia, Pennsylvania, USA 19104-6010. Reprint requests to Dr. B. Saxon: 2005 Hearthstone Lane,
Modesto, California, USA 95355. Can Vet J Volume 32, June 1991
hypoalbuminemia of 2.5 g/dL (normal range = 2.73.6 g/dL). Urinalysis, viral serological results, and fecal flotation were normal or negative. Because a profound peripheral eosinophilia was the predominant abnormality detected by the initial diagnostic workup, the diagnostic plan was expanded to include a platelet count, feline heartworm serology, bone marrow aspiration, and abdominal ultrasound. The platelet count was normal and heartworm serology was negative. Bone marrow aspiration showed hyperplasia of the eosinophil line with normal maturation. No atypical or blast cells were seen. All other cell lines were present and normal. An enlarged liver of normal echogenicity, bilaterally small kidneys with increased echogenicity, and a normal spleen were seen on abdominal ultrasonography. A slight peritoneal effusion was noted and paracentesis revealed strawcolored fluid consisting of predominantly mature eosinophils. A tentative diagnosis of feline hypereosinophilic syndrome (FHES) was made based on the magnitude of the eosinophilia in the peripheral circulation and bone marrow and the absence of any recognizable cause for that eosinophilia (e.g. parasites, neoplasia, allergic lung disease, or connective tissue disorder). Eosinophilic leukemia was considered unlikely because the eosinophils present in this case were of normal maturation and morphology.
A tentative diagnosis of feline hypereosinophilic syndrome was made based on the magnitude of the eosinophilia in the peripheral circulation and bone marrow and the absence of any recognizable cause for that eosinophilia
(e.g. parasites, neoplasia, allergic lung disease, or connective tissue disorder) Treatment was begun with systemic prednisone (TechAmerica, Kansas City, Missouri, USA) 2.2 mg/ kg/day po, furosemide (TechAmerica) 2.2 mg/kg/ day po, fenbendazole (Hoechst-Roussel, Somerville, New Jersey, USA) 50 mg/kg po for three consecutive days, and a bland home-cooked diet of boiled chicken. The cat was examined two weeks later. The owner reported slight improvement in appetite, a decrease in the frequency of vomiting, and persistent diarrhea. Findings on physical examination were unchanged from initial presentation. Only a mild degree of increased inspiratory effort was noted, and thoracocentesis yielded 75 mL of fluid similar to that obtained initially. The total WBC count was 77.20 x 109/L with 29.34 x 109/L eosinophils. A platelet count was again normal. The hematocrit was 0.20 L/L. 367
tion, or death before six months with compatible signs or symptoms; 2) lack of other recognized causes of eosinophilia; and 3) organ system involvement/ dysfunction due to the eosinophilia or unexplained in the given clinical setting (2). Human HES commonly involves the bone marrow, heart, skin, lungs, liver, and central nervous system, and has been reviewed (2,7). Cardiac dysfunction accounts for most of the morbidity and mortality in human HES patients (2,7,8). Feline hypereosinophilic syndrome has been reported infrequently (4-6). Common clinical signs seen in cats with FHES are anorexia, weight loss, and diarrhea. Hematological abnormalities, vomiting, Figure 1. Left atrial wall with thrombus and moderate other than profound hypereosinophilia, are usually endocardial fibrosis. A corrected reticulocyte count was 0.2%. Mean corpuscular volume remained elevated at 63 fL. The cat was sent home and the owner was instructed to continue the medications as directed initially. Two weeks after reexamination (four weeks after initial presentation) the cat was found dead. According to the owner, the cat's appetite and gastrointestinal signs had improved only slightly up to the time of her sudden death. Gross postmortem abnormalities included pleural and peritoneal effusion, pulmonary atelectasis, hepatomegaly, small kidneys with surface indentations, multiple small pancreatic nodules, dilation of the left atrial appendage, left atrial thrombosis, cardiomegaly, and increased weight of the heart (17.8 g) (1). No gross lesions were observed in the gastrointestinal tract or thyroid glands. Histopathological abnormalities were present in the heart, lungs, gastrointestinal tract, bone marrow, and lymph nodes. Cardiac lesions were present both in the endocardium and myocardium. Moderate to severe left ventricular and left atrial endocardial fibrosis was present with intramural arteriosclerosis. A large thrombus containing numerous eosinophils was attached to the wall of the left atrium (Figure 1). There were patchy areas of fibrosis within the myocardium. Mature eosinophils were present within capillaries in the endocardium, as well as within the interstitium where they disrupted normal organization of cardiac muscle fibers. The lungs demonstrated chronic pulmonary arterial thrombosis with some evidence of recanalization. Minimal focal interstitial pneumonia was present. The bone marrow showed eosinophilic hyperplasia. Lymph nodes were infiltrated by mature, lobated eosinophils. Gastrointestinal lesions ranged from eosinophilic enteritis (duodenum) to severe eosinophilic-lymphocytic enteritis with fibrosis (jejunum, ileum, colon). There was chronic passive congestion and chronic interstitial nephritis in the liver and kidneys, respectively. Follicular degeneration of the thyroid glands was present. Hypereosinophilic syndrome (HES) is a rare disease of humans (2), dogs (3), and cats (4-6), associated with prolonged idiopathic peripheral and tissue eosinophilia and organ dysfunction. Diagnostic criteria for human HES are: 1) persistent eosinophilia of six months dura368
absent. The cat in our report had a mild nonregenerative anemia associated with an increased mean corpuscular volume. A nonregenerative anemia with macrocytosis may be seen in FeLV positive cats (9) and in humans with cobalamin deficiency (10), but the cat reported here had a negative ELISA test for FeLV antigen. Macrocytosis secondary to cobalamin deficiency has not been reported in the dog or cat (11). Cobalamin levels were not determined in this cat. Possible explanations for the hypoalbuminemia present in this case include protein loss through the gastrointestinal tract and/or into the pleural and peritoneal cavities. Liver function appeared normal in this cat and proteinuria was absent.
Hypereosinophilic syndrome is a rare disease of humans, dogs, and cats, associated with prolonged idiopathic peripheral and tissue eosinophilia and organ dysfunction Histopathological examination in cats affected with FHES has demonstrated the presence of eosinophils in multiple organs including the gastrointestinal tract, lymph nodes, bone marrow, liver, spleen, heart, adrenal glands, kidneys, skin, lungs, and thyroid gland (4-6). Response to therapy has been uniformly poor with survival times ranging most often from one week to several months. Therapy most often consists of immunosuppressive doses of corticosteroids. Hydroxyurea, cytotoxic agents (e.g. cyclophosphamide) and leukopheresis have been used in refractory human cases (2). Hydroxyurea was used in one previously reported case of FHES (6). No treatment has been shown consistently to prolong survival. The cat in the present report shares some clinical, hematological, and histopathological features with previously reported cases of FHES. This cat also fulfilled the criteria for establishing a diagnosis of HES as described for humans. The histopathological abnormalities in the heart and pulmonary arteries in the present case have not been reported previously in cats with FHES. As stated above, cardiac dysfunction is the leading cause of death in human HES patients. Though the precise mechanism(s) by which eosinophils damage the heart are unknown, it is thought that eosinophil Can Vet J Volume 32, June 1991
products, e.g. major basic protein (MBP), damage The cause of pulmonary arterial thrombosis in this endothelial cells within the endocardium and micro- case is unknown. Thromboembolism is a known cause vasculature (2). This is believed to initiate platelet of organ dysfunction in human HES patients, though aggregation and activation resulting in mural throm- arterial thrombosis is uncommon (13). The hyperbosis. Subsequently, the mural thrombi undergo orga- coagulable state associated with high numbers of nization and are replaced by dense fibrous connective eosinophils is thought to be multifactorial (14). Major tissue. Histological lesions in affected human hearts basic protein causes endothelial damage and results in include fibrotic thickening of the endocardium by platelet aggregation and activation, as stated previcollagen-rich connective tissue, mural thrombosis, ously (13). Eosinophilic cationic protein (ECP) is fibrinoid change, inflammation, and thrombosis of thought to activate the Hageman factor (factor XII) small intramural coronary vessels (2). Eosinophilic of the intrinsic pathway of the coagulation cascade infiltration of the myocardium and endocardium is a (2,13). Coagulation abnormalities in HES patients variable finding and present in about 30(! of cases (2). that may render them hypercoagulable and prone The changes seen in such hearts are believed to to thromboembolism include decreased fibrinolytic represent a continuum beginning with early infiltra- activity and increased levels of monocyte-derived tion of the heart with high numbers of eosinophils and procoagulants (14). minimal organ dysfunction and culminating in end stage fibrosis in the absence of eosinophils. Clinically, Acknowledgments the terminal fibrosis is manifested as congestive heart The authors wish to thank Mrs. Marie Marino for her failure (CHF) due to restrictive cardiomyopathy. The cvi presence of CHF in human HES patients is a poor assistance. prognostic sign (2,8). Previously, there have been no reports of cardiac References dysfunction associated with FHES. However, four of 1. Liu SK. Acquired cardiac lesions leading up to congestive heart failure in the cat. Am J Vet Res 1970; 31: 2085. the previously reported cats had histological cardiac 2. Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, abnormalities. One cat had a focal accumulation of Bjornson BH. The idiopathic hypereosinophilic syndrome: mononuclear cells in the myocardium (6), one cat had clinical, pathophysiologic, and therapeutic considerations. Ann invasion of pericardium, epicardium, and endocarIntern Med 1982; 97: 78-92. dium, including the aortic valve, by mature eosinophils 3. Goto N, Kawamura M, Inoue M, Sato A. Pathology of two cases of canine disseminated hypereosinophilic disease. Jpn J and lymphocytes (4), and two cats had subendocardial Vet Sci 1983; 45: 305-312. infiltration of eosinophils without fibrosis (5). 4. Hendrick M. A spectrum of hypereosinophilic syndromes The cat reported herein was dyspneic on initial preexemplified by six cats with eosinophilic enteritis. Vet Pathol 1981; 18: 188-200. sentation, had a persistent pleural effusion, passive McEwen SA, Valli VEO, Hulland TJ. Hypereosinophilic synhepatic congestion, and developed ascites. These find- 5. drome in cats: A report of three cases. Can J Comp Med 1985; ings are compatible with right sided CHF. Thoracic 49: 248-253. auscultation, chest radiographs, and electrocar- 6. Scott DW, Randolph JF, Walsh KM. Hypereosinophilic syndiography were normal in this cat. These findings do drome in a cat. Feline Pract 1985; 15: 22-30. not support, nor do they rule out, cardiac disease, and 7. Jameson MD, Segraves SD. Idiopathic hypereosinophilic synPostgrad Med 1988; 84: 93-101. echocardiography was not done. Cardiac evaluation 8. drome. Presti C, Ryan T, Armstrong WF. Two-dimensional and doppler may be indicated in cats with FHES; echocardiography echocardiographic findings in hypereosinophilic syndrome. is a sensitive indicator of involvement of the heart in Am Heart J 1987; 114: 172-175. human HES patients and should be considered in cats 9. Kociba GJ. Hematologic consequences of feline leukemia virus infection. In: Kirk RW, ed. Current Veterinary Therapy IX with FHES. (Small Animal Practice). Philadelphia: WB Saunders, 1986: Histopathological findings in the heart of this cat 488-490. are similar to those seen in the hearts of human HES 10. Guyton AC. Textbook of Medical Physiology. 7th ed. patients and are compatible with feline restrictive Philadelphia: WB Saunders, 1986: 45. cardiomyopathy (12). Such findings include cardio- 11. Weises ME. Erythrocytes and associated disorders. In: Ettinger SJ, ed. Textbook of Veterinary Internal Medicine. 3rd ed. megaly, disorganization of muscle fibers, patchy 2. Philadelphia: WB Saunders, 1989: 2156. fibrosis, endocardial fibrosis, and thrombosis. In addi- 12. Vol. Liu SK. Cardiovascular pathology. In: Fox PR, ed. Canine and tion, it is plausible that the four cats previously Feline Cardiology. New York: Churchill Livingstone, 1988: 653. reported to have FHES-associated histological cardiac 13. Vazquez JJ, Pavon AF, Arnalich F, et al. Coagulation abnormalities in patients with eosinophilia. Postgrad Med J 1987; 63: abnormalities and the cat presented here represent a spectrum of changes that may be seen in the hearts of 14. 943-945. Passerini CG, Cortellaro M, Cofrancesco E. Possible mechahypereosinophilic cats, analogous to the spectrum of nisms of fibrin deposition in the hypereosinophilic syndrome. cardiac lesions seen in humans with HES. Haemostasis 1989; 1: 32-37.
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