Severe acute rhabdomyolysis associated with Streptococcus equi infection in four horses

Four Quarter Horses (9 months to 7 years of age) with submandibular lymphadenopathy and firm muscles (palpation of which elicited signs of pain) were evaluated; in general, the horses had a stiff gait, and 3 horses became recumbent. Streptococcus equi was cultured from aspirates of lymph nodes or samples of purulent material collected from the auditory tube diverticula. Once the horses were recumbent, their condition deteriorated rapidly despite aggressive antimicrobial and antiinflammatory treatment, necessitating euthanasia within 24 to 48 hours. One horse did not become recumbent and recovered completely. Among the 4 horses, common clinicopathologic findings included neutrophilia, hyperfibrinogenemia, and high serum activities of creatine kinase and aspartate aminotransferase. Necropsies of the 3 euthanatized horses revealed large, pale areas most prominent in the semimembranosus, semitendinosus, sublumbar, and gluteal muscles that were characterized histologically by severe acute myonecrosis and macrophage infiltration of necrotic myofibers. Streptococcus equi was identified in sections of affected muscle by use of immunofluorescent stains for Lancefield group C carbohydrate and S. equi M protein. In the 4 horses of this report, acute severe rhabdomyolysis without clinical evidence of muscle atrophy or infarction was associated with S. equi infection; rhabdomyolysis was attributed to either an inflammatory cascade resembling streptococcal toxic shock or potentially direct toxic effects of S. equi within muscle tissue.     

Purpura haemorrhagica in 53 horses

The medical records of 53 horses with purpura haemorrhagica were reviewed. Seventeen of them had been exposed to or infected with Streptococcus equi, nine had been infected with Corynebacterium pseudotuberculosis, five had been vaccinated with S. equi M protein, five had had a respiratory infection of unknown aetiology, and two had open wounds; the other 15 cases had no history of recent viral or bacterial infection. The horses were between six months and 19 years of age (mean 8.4 years). The predominant clinical signs were well demarcated subcutaneous oedema of all four limbs and haemorrhages on the visible mucous membranes; other signs included depression, anorexia, fever, tachycardia, tachypnoea, reluctance to move, drainage from lymph nodes, exudation of serum from the skin, colic, epistaxis and weight loss. Haematological and biochemical abnormalities commonly detected were anaemia, neutrophilia, hyperproteinaemia, hyperfibrinogenaemia, hyperglobulinaemia and high activities of muscle enzymes. All of the horses were treated with corticosteroids; 42 also received non-steroidal anti-inflammatory drugs and 26 received antimicrobial drugs. Selected cases received special nursing care, including hydrotherapy and bandaging of the limbs. Most of the horses were treated for more than seven days and none of them relapsed. Forty-nine of the horses survived, one died and three were euthanased, either because their severe clinical disease failed to respond to treatment or because they developed secondary complications. Two of the four non-survivors had been vaccinated against S. equi with a product containing the M protein, one had a S. equi infection and the other had a respiratory infection of undetermined aetiology.     

Masseter myodegeneration as a cause of trismus or dysphagia in adult horses

The medical records of eight horses with histological evidence of myodegeneration of the masseter muscles were examined. While they were alive their most common clinical signs had included difficulty in eating or opening their mouths, weight loss, difficulty in moving, and noticeable atrophy of the masseter muscles. The serum activities of muscle enzymes were abnormally high in all of the horses. Whole blood and/or liver selenium and vitamin E concentrations were less than the reference ranges in some of the horses. The lesions varied with the stage of the disease and consisted of swelling and discoloration, or muscle atrophy and fibrosis. Histologically, the muscle changes ranged from acute to subacute degeneration, with regenerative changes accompanying ongoing degeneration, to chronic degeneration with fibrotic replacement of muscle tissue. There were changes in the masseter muscle of all the horses, but some had widespread lesions in skeletal muscle, and a few also had myocardial lesions.     

Salinomycin toxicosis in horses

CASE DESCRIPTION: A 4-month-old American Paint filly was evaluated because of sudden onset of ataxia that progressed to recumbency. Five additional horses from the same and neighboring premises developed signs of poor performance, generalized weakness, ataxia, and recumbency; 2 of those horses were also evaluated. A new batch of a commercial feed supplement had been introduced to the horses' diet on each farm within the preceding 3 days. CLINICAL FINDINGS: Other than recumbency, findings of physical and neurologic examinations of the foal were unremarkable. The other 2 horses had generalized weakness and mild ataxia, and 1 horse also had persistent tachycardia. The foal had mild leukocytosis with neutrophilia, hyperglycemia, and mildly high serum creatine kinase activity. Results of cervical radiography, CSF analysis, and assessments of heavy metals and selenium concentrations in blood and vitamin E concentration in serum were within reference limits. Feed analysis revealed high concentrations of the ionophore antimicrobial salinomycin. TREATMENT AND OUTCOME: The 5 affected horses survived, but the foal was euthanized. At necropsy, a major histopathologic finding was severe vacuolation within neurons of the dorsal root ganglia, which was compatible with ionophore toxicosis. The surviving horses developed muscle atrophy, persistent weakness, and ataxia. CLINICAL RELEVANCE: In horses, ionophore toxicosis should be considered as a differential diagnosis for acute weakness, ataxia, recumbency, or sudden death. Furthermore, ionophore toxicosis should be considered as a cause of poor performance, weakness, muscle wasting, and cardiac arrhythmias in horses. Surviving horses may have impaired athletic performance.     

Preparturient hypocalcemia in four cats.

Preparturient hypocalcemia was identified in 4 cats in a specific pathogen-free colony between 1995 and 1996. All cats had an acute onset of clinical signs, 3 to 17 days prior to parturition. Signs of depression, weakness, tachypnea, and mild muscle tremors were the most common clinical signs, following by vomiting and anorexia. Additional abnormalities included hypothermia, third eyelid prolapse, dehydration, pallor, lethargy, flaccid paralysis, and hyperexcitability. Hematologic abnormalities included leukocytosis with neutrophilia and lymphopenia. Hypocalcemia was documented in each queen. Common serum biochemical abnormalities included high aspartate aminotransferase and creatine kinase activities. All cats responded to IV or SC administration of 10% calcium gluconate. Queens were then given calcium orally prior to and following parturition. The queens did not have additional complications for the duration of the gestational or lactational periods.     

Streptococcus equi meningoencephalomyelitis in a foal

CASE DESCRIPTION: A 4-month-old American Paint Horse colt was evaluated because of acute onset of ataxia, left-sided head tilt, and fever and a recently noticed heart murmur. Upper respiratory tract infection caused by Streptococcus equi subsp equi had been diagnosed at 3 months of age. CLINICAL FINDINGS: Hematologic abnormalities included leukocytosis, mature neutrophilia, monocytosis, and mild anemia. Analysis of a CSF sample revealed high total protein concentration and total nucleated cell count; nucleated cells consisted mainly of degenerate neutrophils. Results of a real-time PCR assay were positive for S equi subsp equi, and a diagnosis of S equi subsp equi meningoencephalomyelitis was made. TREATMENT AND OUTCOME: Treatment included administration of potassium penicillin and fluids, but the foal developed uroperitoneum and was subsequently euthanized. Postmortem examination revealed meningoencephalomyelitis, and S equi subsp equi was cultured from a brain aspirate. Additional findings included suppurative cystitis with rupture and neutrophilic myocarditis. CLINICAL RELEVANCE: Findings suggest that S equi subsp equi meningoencephalomyelitis should be considered in the differential diagnosis for foals with neurologic signs that have a history of strangles or exposure to affected horses.     

Adverse Effects of Zilpaterol Administration in Horses: Three Cases

Three healthy horses were fed the beta-adrenergic agonist feed additive zilpaterol at a dosage of 0.17 mg/kg body weight to study zilpaterol elimination kinetics. Soon after ingestion of zilpaterol, the horses developed skeletal muscle tremors and tachycardia. A 75 to 87.5% reduced dose of zilpaterol was fed to the horses 24 hours after the initial dose; administration was discontinued thereafter. The horses exhibited restlessness, muscle tremors, and profuse sweating 20 to 25 minutes after ingestion of zilpaterol. Tachycardia developed within 40 minutes and took up to 2 weeks to resolve. Muscle tremors lasted up to 1 week. The most pronounced derangements in serum biochemistry were increased activities of lactic dehydrogenase, creatine kinase, and aspartate transferase, indicating muscle damage. The most severely affected horse also had transient azotemia, hematuria, and proteinuria, suggesting renal damage. All three horses recovered without treatment and were clinically normal 2 to 3 weeks after the initial dose of zilpaterol. Because of their anabolic properties, beta-adrenergic feed additives are considered a risk for abuse in performance horses, despite the absence of Food and Drug Administration approval for such use. Oral administration of zilpaterol to horses at the dosage indicated for use in cattle may result in prolonged adverse effects, including tachycardia, muscle tremors, and renal damage.     

Serum creatine kinase response to exercise during dexamethasone-induced insulin resistance in Quarter Horses with polysaccharide storage myopathy

OBJECTIVE: To determine effects of dexamethasone on insulin sensitivity, serum creatine kinase (CK) activity 4 hours after exercise, and muscle glycogen concentration in Quarter Horses with polysaccharide storage myopathy (PSSM). ANIMALS: 4 adult Quarter Horses with PSSM. PROCEDURE: A 2 x 2 crossover design was used with dexamethasone (0.08 mg/kg) or saline (0.9% NaCl) solution administered IV every 48 hours. Horses were exercised on a treadmill daily for 3 wk/treatment with a 2-week washout period between treatments. Serum CK activity was measured daily 4 hours after exercise. At the end of each treatment period, serum cortisol concentrations were measured, a hyperinsulinemic euglycemic clamp (HEC) technique was performed, and muscle glycogen content was determined. RESULTS: Mean +/- SEM serum cortisol concentration was significantly lower after 48 hours for the dexamethasone treatment (0.38 +/- 0.08 mg/dL), compared with the saline treatment (4.15 +/- 0.40 mg/dL). Dexamethasone significantly decreased the rate of glucose infusion necessary to maintain euglycemia during the HEC technique, compared with the saline treatment. Muscle glycogen concentrations and mean CK activity after exercise were not altered by dexamethasone treatment, compared with the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone significantly reduced whole-body insulin-stimulated glucose uptake in Quarter Horses with PSSM after a 3-week period but did not diminish serum CK response to exercise or muscle glycogen concentrations in these 4 horses. Therefore, a decrease in glucose uptake for 3 weeks did not appear to alleviate exertional rhabdomyolysis in these horses. It is possible that long-term treatment may yield other results.     

Hypoadrenocorticism in a cat

Primary hypoadrenocorticism was diagnosed in an eight-year-old neutered male cat. The predominant presenting complaint was dysphagia. Other historical signs included lethargy, weight loss, polydipsia, polyuria, muscle weakness and occasional vomiting. The signs had waxed and waned over the two months before presentation and had improved when the cat was treated with enrofloxacin and prednisolone by the referring veterinarian. On referral, dehydration, depression and poor bodily condition were found on physical examination. Results of initial laboratory tests revealed mild anaemia, hyperkalaemia, hyponatraemia, hypochloraemia and elevations in serum creatinine and creatine kinase. The diagnosis of primary adrenocortical insufficiency was established on the basis of results of an adrenocorticotropic hormone (ACTH) stimulation test and endogenous plasma ACTH determination. Initial therapy for hypoadrenocorticism included intravenous administration of 0.9 per cent saline and dexamethasone, and oral fludrocortisone acetate. Within one week the cat was clinically normal and two years later was still alive and well on fludrocortisone acetate treatment only.     

Unusual Patterns of Serum Antibodies to Streptococcus Equi in Two Horses with Purpura Hemorrhagica

An enzyme-linked immunosorbent assay (ELISA) was developed for use in horses to determine serum titers of antibodies of the immunoglobulin classes IgA, IgG, and IgM to Streptococcus equi M-like protein and culture supernatant protein antigens. Serum antibodies were determined in 28 adult horses, including 9 horses with recent S. equi infections, 17 horses without known exposure to S. equi, but without a history of respiratory disease in the preceding 4 months, and 2 horses with clinical purpura hemorrhagica. Serum IgA titers to culture supernatant protein antigen were highest in recently infected horses (P less than 0.001). Serial determinations of antibody titers in the horses with purpura showed that IgG antibodies to both S. equi M-like protein and culture supernatant protein antigens were undetectable initially, but later rose coincidental with clinical recovery from the disease. Possible mechanisms for these findings are discussed.     

Decreased erythrocyte potassium concentration associated with exercise-related myopathy in horses

To investigate the possibility that a disorder of potassium balance may have a role in the development of equine rhabdomyolysis, the potassium concentration within erythrocytes (RBC [K+]) and plasma (P [K+]) was measured in 3 groups of horses: group 1, eight 2-year-old fillies that had postexercise muscle soreness within 48 hours of sample collection; group 2, ten 2-year-old fillies subjected to identical management and training conditions (as fillies of group 1) and that did not have signs of myopathy; and group 3, 32 yearlings of both sexes on the farm of origin of groups 1 and 2 that were pastured and not in training. Creatine kinase activity in serum from horses of groups 1 and 2 was also measured. The mean P [K+] was not significantly different between groups, whereas the mean RBC [K+] was significantly (P less than 0.01) lower in group-1 fillies vs group-2 fillies and group-3 horses. Group-1 fillies also had markedly high serum creatine kinase activity. Results of the study revealed significantly lower RBC [K+] in horses that had had signs of myopathy within the preceding 48 hours. This does not prove a causal relationship between RBC potassium depletion and myopathy, but does suggest that decreased RBC [K+] may be observed in horses with exercise-related myopathy.     

Proline-glutamic acid-proline-lysine repetition peptide as an antigen for the serological diagnosis of strangles

The reactivity of the proline-glutamic acid-proline-lysine (PEPK) repetition peptide antigen in 3176 serum samples was investigated to evaluate its utility as an antigen for the serological diagnosis of strangles. The reactivity of the sera of horses infected with Streptococcus equi subspecies equi was high when the peptide had several PEPK repetitions. However, as the number of PEPK repetitions increased, the reactivity of the antigen with the sera of horses infected with Streptococcus equi subspecies zooepidemicus also increased. In horses infected experimentally with S equi, the reactivity of the PEPK antigen with five repetitions increased one week after inoculation and continued to increase during the following four weeks. The optical density (OD) values of test sera from horses infected experimentally with S equi and sera from horses that had recovered from strangles were high. The od values of sera from horses that had recovered from an experimental infection with S zooepidemicus and of sera from healthy horses were comparatively low.     

Myonecrosis in three horses with colic: evidence for endotoxic injury

Three horses with colic, clinical evidence of endotoxaemia and high serum activities of creatine kinase and aspartate aminotransferase were examined postmortem. The horses were diagnosed with severe ulcerative colitis, pyloric ulceration and stenosis with colonic sand impaction, and colonic obstruction due to faecaliths. There was no gross or histological evidence of muscle trauma. Their semimembranosus muscles had scattered acute to subacute segmental necrosis of the myofibres, suggestive of endotoxin-induced muscle injury.     

Prevalences and clinical signs of polysaccharide storage myopathy and shivers in Belgian draft horses

OBJECTIVE: To determine prevalences of polysaccharide storage myopathy (PSSM) and shivers in Belgian Draft Horses (BDHs) and determine whether there was an association between these 2 conditions. DESIGN: Prospective cohort study. ANIMALS: 103 BDHs > 1 year old. PROCEDURE: Owners were questioned regarding clinical signs of PSSM, shivers, and hindquarter weakness, defined as poor hindquarter muscling and lack of propulsion. Blood samples were collected for determination of serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations. A biopsy sample from the gluteus medius muscle was submitted for histologic, histochemical, and biochemical analysis. A diagnosis of PSSM was made if abnormal amylase-resistant polysaccharide inclusions were seen histologically. RESULTS: 37 (36%) horses had PSSM and 19 (18%) had shivers, but only 6 (6%) had both PSSM and shivers, whereas 31 (30%) had PSSM alone, 13 (13%) had shivers alone, and 53 (51%) had neither, and a significant association between PSSM and shivers was not detected. Hindquarter weakness was found in 30 horses. Only 13 of 37 (35%) horses with PSSM and 11 of 19 (58%) horses with shivers had hindquarter weakness. Serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations were not significantly different between horses with and without PSSM or between horses with and without shivers. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PSSM and shivers are common but unrelated disorders in BDHs.     

Proglycogen, macroglycogen, glucose, and glucose-6-phosphate concentrations in skeletal muscles of horses with polysaccharide storage myopathy performing light exercise

OBJECTIVE: To determine concentrations of proglycogen (PG), macroglycogen (MG), glucose, and glucose-6-phosphate (G-6-P) in skeletal muscle of horses with polysaccharide storage myopathy (PSSM) before and after performing light submaximal exercise. ANIMALS: 6 horses with PSSM and 4 control horses. PROCEDURES: Horses with PSSM completed repeated intervals of 2 minutes of walking followed by 2 minutes of trotting on a treadmill until muscle cramping developed. Four untrained control horses performed a similar exercise test for up to 20 minutes. Serum creatine kinase (CK) activity was measured before and 4 hours after exercise. Concentrations of total glycogen (G(t)), PG, MG, G-6-P, free glucose, and lactate were measured in biopsy specimens of gluteal muscle obtained before and after exercise. RESULTS: Mean serum CK activity was 26 times higher in PSSM horses than in control horses after exercise. Before exercise, muscle glycogen concentrations were 1.5, 2.2, and 1.7 times higher for PG, MG, and G(t), respectively, in PSSM horses, compared with concentrations in control horses. No significant changes in G(t), PG, MG, G-6-P, and lactate concentrations were detected after exercise. However, free glucose concentrations in skeletal muscle increased significantly in PSSM horses after exercise. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results suggests that glucose uptake in skeletal muscle is augmented in horses with PSSM after light exercise. There is excessive storage of PG and MG in horses with PSSM, and high concentrations of the 2 glycogen fractions may affect functional interactions between glycogenolytic and glycogen synthetic enzymes and glycosomes.     

Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle

ObjecTIVE: To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC). ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3alpha/beta protein abundance and phosphorylation state (PKB Ser(473) and GSK-3alpha/beta Ser(21/9)), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration. RESULTS: Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3alpha Ser(21) and GSK-3B Ser(9) were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.     

Changes in serum muscle enzyme levels associated with training schedules and stage of the oestrous cycle in Thoroughbred racehorses

Blood samples were collected twice weekly over a nine month period from 24 Thoroughbred racehorses in training at Newmarket to study the effects of daily training schedules and stage of oestrous cycle on serum enzyme levels and clinical signs of equine exertional myopathy. The sampling period extended from November to July and was performed between 16:00 h and 18:00 h so as to be at least 6 h after exercise. Serum creatine kinase, aspartate aminotransferase and plasma progestogen concentrations were measured. All horses were subjected to a similar traditional training programme. The study demonstrated marked fluctuations in serum muscle enzyme concentrations which were more pronounced in two-year-old fillies than three-year-old fillies and colts. There was no correlation, however, with the stage of oestrous cycle. It was concluded that some degree of muscle cell damage, which results in a variable increase in serum creatine kinase levels, occurs in all horses following light exercise after a rest day. Traditional flat race training may not be ideal in this respect and it is suggested that, for horses with an observed tendency towards exertional myopathy, more consistent and longer periods of less strenuous exercise may be advantageous.     

A nutritional myopathy enzootic in a group of yearling beef cattle

Steers and bulls under feedlot conditions and on an apparently adequate ration developed transitory signs of diarrhea and unthriftiness. One animal became recumbent. Sick and clinically normal animals in the group had elevated serum creatine kinase and aspartate aminotransferase enzyme values and degenerative changes in muscle fibers on biopsy. Feed analysis was carried out and the animals were monitored over several weeks by means of muscle biopsy and serum enzyme analysis as well as by postmortem examination at slaughter. Subclinical myopathy was found in several animals and was thought to be related to low vitamin E content in the high moisture corn ration.     

Complications associated with Streptococcus equi infection on a horse farm

Complications associated with Streptococcus equi infection developed in 15 (20.3%) of 74 horses on one farm included death, guttural pouch empyema, purpura hemorrhagica, upper respiratory tract obstruction, pneumonia, pleuropneumonia, agalactia, mesenteric lymph node abscessation, and periorbital abscessation. Death was attributed to pneumonia in 3 horses and to upper respiratory tract obstruction in 2 horses. One horse was euthanatized because of severe purpura hemorrhagica.     

Enzyme-linked immunosorbent assay for diagnosis of Corynebacterium (Rhodococcus) equi infection in foals

An enzyme-linked immunosorbent assay (ELISA) was used to diagnose Corynebacterium (Rhodococcus) equi infection in foals. In tests done with different antigen-extraction procedures (sodium dodecyl sulfate, sodium deoxycholate, polyoxy-ethylene [9] p-tert-octylphenol, polyoxy-ethylene [9-10] p-tert-octylphenol, sonification, homogenization, and heat treatment at 121 C), Tween 20 was a satisfactory reactive antigen. Using hyperimmune rabbit sera or infected foal sera, we investigated the specificity and the sensitivity of the ELISA with the Tween 20 antigen of the different serotypes or of the isolates. Corynebacterium equi strain ATCC 6939 antigen had the best activity for detecting antibodies to C equi in foals. Sera from 218 healthy horses, 11 healthy foals, 17 healthy newborn foals, a foal with suspected C equi infection, and 5 infected foals were evaluated for antibodies to C equi, using ELISA. The optical density values of 206 healthy horses, 17 healthy newborn foals, and 9 healthy foals were less than 0.1. Infected foal sera, except from foal 3, and serum from a foal with suspected C equi infection had higher optical density values. Using ELISA, specific antibodies against C equi were detected in a naturally infected 6-week-old foal after the foal had a rapid increase in the number of bacteria in the feces and after the initial development of clinical signs of illness at 5 weeks of age. Therefore, ELISA was useful for the early diagnosis of C equi infection in foals.