Inflammatory myopathies.

Inflammatory myopathies are the result of infiltration of inflammatory cells into striated muscle, with or without an association with an underlying cause. Two broad classifications are IIMs and secondary inflammatory myopathies associated with other diseases. Standard diagnostic criteria for inflammatory myopathy include the presence of weakness or loss of specific muscle group function, an increase in CK, EMG changes associated with muscle membrane instability, and histologic evidence of inflammation. Not all these criteria, however, must be present. Fresh-frozen biopsy from two proximal muscles is recommended for biopsy confirmation. IIM can either focally affect head or neck muscles or be more diffuse. MMM is an immune-mediated disease characterized by a humoral antibody produced against the unique type IIM and type I variant mvofibers of masticatory muscles of dogs, which causes inflammation and loss of function of the muscles of mastication. Idiopathic polymyositis can affect focal muscle groups (extraocular, laryngeal) or present as multifocal or diffuse involvement of skeletal muscle in the cat and dog. Familial canine DM is an inflammatory disease of the striated muscle, skin, and vasculature in young Collies, Shetland Sheepdogs (Shelties), and, rarely, Collie-crossbred dogs. Immunosuppressive therapy is the key to successful treatment. Protozoal parasitic myopathies are the most common cause of clinically relevant secondary inflammatory myopathies. The degree of systemic involvement is often the limiting factor to successful treatment. Early recognition of the clinical signs for proper diagnostic testing and institution of appropriate therapy can result in a rewarding outcome in treating inflammatory myopathies in the cat and dog.     

Computed tomographic appearance of masticatory myositis in dogs: 7 cases (1999-2006)

OBJECTIVE: To document computed tomography (CT) features in dogs with masticatory myositis. DESIGN: Retrospective case series. ANIMALS: 7 dogs with an immunologic diagnosis of masticatory myositis and an absence of clinical abnormalities of any skeletal muscles other than the masticatory muscles. PROCEDURES: History; clinical, hematologic, biochemical, immunologic, cytologic, and histologic findings; and pre- and postcontrast CT imaging features of masticatory muscles and head and neck lymph nodes were extracted from medical records. RESULTS: On CT images, changes in size (atrophy or swelling) were common for all masticatory muscles except the digastricus muscles, which were involved only in 1 dog. Pre-contrast attenuation changes, most often hypoattenuation with varied distribution patterns, were seen in masticatory muscles of 4 dogs. Contrast enhancement with a predominantly inhomogeneous distribution pattern was seen in the temporalis, masseter, and pterygoid muscles of all dogs. Head and neck lymph nodes were enlarged in all but 1 dog and had contrast enhancement with predominantly central or homogeneous distribution patterns. Muscle biopsy was performed in 6 dogs, with biopsy specimens obtained from areas that had the most obvious contrast enhancement on CT images. For all 6 dogs, biopsy specimens had histologic features indicative of masticatory myositis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that CT may be a useful adjunct in the diagnosis of masticatory myositis in dogs, including selection of sites for diagnostic muscle biopsy.     

Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania infantum)

Twenty-four dogs with a parasitologically and serologically established diagnosis of leishmaniasis were studied to investigate the atrophy of the masticatory muscles which commonly occurs in this disease, and to compare the lesions in the masticatory muscles with those in the cranial tibial muscles. The 24 animals were divided into three groups of eight, group A dogs with no muscular atrophy, group B dogs with different degrees of atrophy in the masticatory and skeletal muscles, and group C dogs with similar degrees of atrophy in the masticatory and skeletal muscles. Increased activities of creatine phosphokinase and lactate dehydrogenase were recorded in only some of the dogs in groups B and C, but there were no significant differences between the mean activities in the three groups. Electromyographic changes indicating myopathy and involving both the temporalis and cranial tibial muscles, were observed in two of the dogs in group A, seven of those in group B, and in all the dogs in group C. Muscle histopathology revealed a variable degree of muscle fibre necrosis and atrophy, mononuclear infiltrates and neutrophilic vasculitis in all the dogs except two in group A. Leishmanial amastigotes were found within macrophages and myofibres in 16 of the dogs, some in each group. IgG immune complexes were detected in muscle samples, and circulating antibodies against myofibres were detected in serum samples from all the 24 dogs.     

Dysphagia as the primary clinical abnormality in two dogs with inflammatory myopathy

Two adult Boxers were evaluated because of chronic dysphagia of several years' duration. Serum creatine kinase activity was high in both dogs, but other hematologic or serum biochemical abnormalities were not detected. Esophagraphy revealed abnormalities of the cricopharyngeal phase of swallowing in both dogs, and electromyography of the pharyngeal and laryngeal muscles revealed complex repetitive discharges, positive sharp waves, and fibrillation potentials characteristic of primary myopathy or neuropathy. Because of the severity of their condition, both dogs were euthanatized. Histologically, mixed-cell infiltrates were seen in sections of the masseter and thyropharyngeal muscles. Results of indirect immunofluorescence staining for proteins associated with dystrophic myopathy were unremarkable, except for decreased staining for integrin alpha7. A diagnosis of chronic inflammatory myopathy was made. The clinical importance of reduced staining for integrin alpha7 could not be determined but was considered to be a result of the myopathy.     

Atypical masticatory muscle myositis in three cavalier King Charles spaniel littermates

This case report describes a novel manifestation of the immune-mediated disease, masticatory muscle myositis. Clinical signs, including difficulty in opening the mouth (trismus), were seen in three of four 12-week-old cavalier King Charles spaniel littermates. Diagnosis was established by 2M immunohistochemistry, supported by characteristic histopathological changes in affected temporal muscle. Treatment using corticosteroids at immune-modifying doses resulted in resolution of clinical signs in all the affected animals. Masticatory muscle myositis should be considered as a differential diagnosis in groups of young dogs with clinical signs of myositis localised to the head.     

Locked jaw syndrome in dogs and cats: 37 cases (1998-2005)

A consecutive series of cases of dogs and cats with locked jaw syndrome (inability to open or close the mouth) are reported in this study. Dogs were significantly overrepresented (84.0%) and adult dogs were more frequently affected (81.0%). Temporomandibular joint ankylosis due to fracture was the most common cause (54.0%) of locked jaw syndrome. Additional potential causes of locked jaw syndrome are masticatory muscle myositis, neoplasia, trigeminal nerve paralysis and central neurological lesions, temporomandibular joint luxation and dysplasia, osteoarthritis, retrobulbar abscess, tetanus, and severe ear disease. Treatment of locked jaw is directed towards the primary cause. It is important to treat the tonic spasm in order to minimize periarticular fibrosis. Surgical intervention is recommended for temporomandibular joint ankylosis. Masticatory muscle myositis treatment is initiated by gradually opening the mouth, with medical treatment based on immunosuppressive therapy. Fracture and masticatory muscle myositis are associated with a relatively good prognosis in regard to short-term outcome as compared to animals with central neurologic lesions or osteosarcoma which have a poor prognosis.     

Extraocular muscle myositis and restrictive strabismus in 10 dogs

Ten cases of uni- or bilateral restrictive ventromedial strabismus in young dogs of different breeds are reported. Clinically, abnormalities were restricted to the extraocular muscles with sparing of the masticatory muscles and limb muscles. This was supported in some cases by imaging studies, electrophysiology, and immunocytochemical assay for antibodies against type 2M fibers. Histologically, there was variable lymphocytic plasmacytic mononuclear cell infiltration and fibrosis. This disorder is similar in many aspects to chronic masticatory myositis with focal myositis and subsequent fibrosis. Surgical correction may restore eye position and vision.     

Titin and ryanodine receptor autoantibodies in dogs with thymoma and late-onset myasthenia gravis

Similar to human autoimmune myasthenia gravis (MG), canine MG occurs spontaneously and is associated with autoantibodies against the nicotinic acetylcholine receptor (AChR). In addition to AChR, human MG patients with thymoma or late-onset MG have antibodies against titin and ryanodine receptor (RyR). The objective of this study was to establish if dogs with confirmed MG (AChR antibody titer >0.6 nmol/l) also developed titin and RyR antibodies and identify possible associations with thymoma, late age of onset, or severity of clinical signs. Sera from dogs (n=430) with previously diagnosed autoimmune MG (N=415), other immune-mediated neuromuscular disorders including polymyositis (PM) and masticatory muscle myositis (N=5), and control dogs (N=10) were evaluated for the presence of titin antibodies in ELISA using MGT-30 as antigen, a peptide representing the main immunogenic region (MIR) for human titin antibodies. Titin antibody positive sera were further examined for RyR antibodies in Western blots using a RyR fusion protein (pc2-RyR) as antigen, which covers the MIR for human MG sera. Titin antibodies were found in sera of 80/430 dogs. Thymoma was present in 11/80 and age of onset was after 4 years in 66/80 titin positive dogs. Two of the titin positive dogs had PM. RyR antibodies were found in 13/80 sera (8/13 thymoma, 12/13 age of onset after 4 years, and 1/13 PM). Neither titin nor RyR antibodies were found in sera of healthy control dogs. Acute fulminating MG was described in five dogs with both titin and RyR antibodies. From these studies we conclude that titin and RyR antibodies in canine and human MG have a similar association with thymoma, late-onset MG, and possibly with more severe forms of MG.     

Immune-based non-erosive inflammatory joint disease of the dog. 2. Polyarthritis/polymyositis syndrome

A connective tissue disorder characterized by non-erosive polyarthritis and polymyositis has been identified in six young adult dogs. The diagnosis was based on the clinical features of stiffness, joint swelling, joint pain, muscle atrophy, muscle pain and contracture and the presence of chronic active inflammation in biopsies of muscle and synovium. A diagnosis of systemic lupus erythematosus was excluded by the absence of circulating antinuclear antibody. Five of the six dogs were of the spaniel breeds. Treatment was with cyclophosphamide and prednisolone. Only two dogs made an apparent recovery.     

Detection of attenuated wavy fibers in the myocardium of Newfoundlands without clinical or echocardiographic evidence of heart disease

OBJECTIVES: To determine whether attenuated wavy fibers may be found in the myocardium of Newfoundlands without clinical or echocardiographic evidence of heart disease. ANIMALS: 15 Newfoundlands from a kennel with a known predisposition to dilated cardiomyopathy (DCM) and 32 dogs of other breeds that died suddenly or were euthanatized for reasons unrelated to heart disease and did not have gross postmortem evidence of heart disease. PROCEDURE: Echocardiography was performed on all Newfoundlands on a yearly basis. Necropsy specimens from all dogs were evaluated for attenuated wavy fibers (i.e., myocardial cells <6 microm in diameter with a wavy appearance). RESULTS: None of the Newfoundlands had clinical signs of heart disease, and results of echocardiographic examinations were within reference ranges. Seven Newfoundlands had histologic evidence of attenuated wavy fibers, whereas attenuated wavy fibers were not found in the remaining 8 Newfoundlands or in any of the 32 dogs of other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that attenuated wavy fibers in dogs with a known predisposition for DCM may indicate an early stage of the disease. However, further studies on a larger number of dogs are needed to confirm this hypothesis.     

Echocardiographic ratio indices in overtly healthy Boxer dogs screened for heart disease

BACKGROUND: Boxer dogs are routinely screened by echocardiography to exclude congenital and acquired heart disease. Individuals of a given breed may span a large range of body sizes, potentially invalidating linear regression of M-mode measurements against body weight. Echocardiographic ratio indices (ERIs) provide a novel method of characterizing echocardiographic differences between Boxers and other dog breeds. HYPOTHESIS: ERIs obtained from overtly healthy Boxer dogs presented for cardiac screening will be different from ERIs established for normal non-Boxer dogs, and those differences will be unrelated to aortic velocity or systolic blood pressure. ANIMALS: Eighty-one Boxers with no outward clinical signs of heart disease were studied. METHODS: All dogs were examined by 2-dimensional, M-mode, and Doppler echocardiography. M-mode measurements were used to perform ERI calculations, and the indices in Boxers were compared between Boxers with varying severity of arrhythmia and those of normal non-Boxer dogs. RESULTS: Differences in weight-based ERIs, which reflect increased thickness of the left ventricular free wall (LVW) and interventricular septum (IVS) and smaller aortic size, were found in overtly healthy Boxer dogs compared with normal non-Boxer dogs. ERIs of left atrial and LV cavity size in overtly healthy Boxers were not significantly different from those of non-Boxer dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Boxer dogs may have an increased relative thickness of the LVW and IVS that is independent of aortic size, aortic velocity, or arterial blood pressure, and this morphology should be taken into consideration when screening Boxers by echocardiography.     

The histological appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease.

Colonic and rectal forceps and excision biopsies of 355 dogs with clinical signs of large bowel disease were investigated. Five percent of the forceps biopsies were unsuitable for examination; all excision biopsies were of good quality. Forceps biopsies were obtained from one to eight sites, up to 60 cm cranial from the anus, while excision biopsies, mostly from tumors, were from the rectoanal region. Slight to severe colitis and/or proctitis was found in 192 dogs (54%). A single type of colitis was seen in 160 dogs; in 53 cases the lesions were local, in 107 cases multiple. A combination of different types of colitis was found in 32 dogs. Atrophic colitis, diffuse colitis and canine histiocytic ulcerative colitis were the most prominent findings, followed by ulcerative, superficial and eosinophilic colitis. Follicular, hypertrophic and aspecific granulomatous colitis were found in only a few cases. Tumors were diagnosed in 57 dogs (16%). Of these tumors 50 were of epithelial and seven were of mesenchymal origin. A high percentage (61%) of the epithelial tumors consisted of adenomas of the rectoanal region. In ten other dogs (3%) a differential diagnosis of lymphosarcoma or colitis had to be made. Colitis and colorectal tumors were more prevalent in Boxers, German Shepherds, Poodles, Great Danes and Spaniels. In the Boxers simple chronic colitis, as well as canine histiocytic ulcerative colitis were more frequently found, the latter especially in females. Other biopsy findings were edema, crypt cysts, hemorrhages, an increased number of intraepithelial lymphocytes and an increased or decreased number of goblet cells.     

Assessment of heart rate variability in Boxers with arrhythmogenic right ventricular cardiomyopathy

OBJECTIVE: To assess heart rate variability (HRV) in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC), assess the ability of HRV analysis to identify differences in Boxers on the basis of severity of their arrhythmia, and evaluate the use of HRV to determine whether persistently high sympathetic tone is present in these dogs. DESIGN: Prospective study. ANIMALS: 24 Boxers with ARVC and 10 clinically normal non-Boxer dogs. PROCEDURE: Boxers were categorized as dogs with congestive heart failure (CHF), dogs with < or = 2 ventricular premature complexes (VPCs)/24 h (designated unaffected), or dogs with > 1,000 VPCs/24 h (designated affected). Ambulatory electrocardiography (24 hours) was performed in each dog. Recordings were analyzed for HRV variables at a commercial laboratory; differences in HRV variables among groups were compared with 1-way ANOVA. RESULTS: Compared with control non-Boxer dogs and Boxers without CHF (affected and unaffected Boxers), HRV was reduced in Boxers with CHF. No differences in HRV variables were detected between affected and unaffected Boxers. Inconsistent differences were identified between the control dogs and Boxers without CHF that had various degrees of arrhythmias. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that persistently high sympathetic tone is not a consistent feature of ARVC. Differences in some HRV variables between Boxers without CHF and control dogs suggest that Boxers may have different autonomic control of heart rate, compared with that of clinically normal non-Boxer dogs. The usefulness of HRV analysis appears limited to Boxers with ARVC that have systolic dysfunction and CHF.     

MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF CANINE INFLAMMATORY MYOPATHIES IN THREE DOGS

In humans affected with inflammatory myopathies, regions of altered signal intensity are found on magnetic resonance (MR) images of affected muscles. Although electromyography (EMG) is more practical for muscle disease evaluation, and a muscle biopsy is the only manner in which a definitive diagnosis can be made, MR imaging has proven useful if a specific anatomic localization is difficult to achieve. Three dogs with focal inflammatory myopathy diagnosed with the assistance of MR imaging are discussed and the findings are compared with those found in humans. MR images of the affected muscles in each dog were characterized by diffuse and poorly marginated abnormal signal on T1- and T2-weighted images. Marked enhancement was noted in these muscles after contrast medium administration. An inflammatory myopathy was confirmed histologically in all three dogs. A good association existed between the MR images and muscle inflammation identified histopathologically. MR imaging may be a useful adjunctive procedure for canine inflammatory myopathies.     

Assessment of plasma brain natriuretic peptide concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy

OBJECTIVE: To determine whether Boxers with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased plasma concentrations of brain natriuretic peptide (BNP), compared with concentrations in clinically normal dogs. ANIMALS: 13 Boxers with ARVC, 9 clinically normal Boxers, 10 clinically normal non-Boxer dogs, and 5 hound dogs with systolic dysfunction. PROCEDURE: All Boxers were evaluated via 24-hour ambulatory electrocardiography and echocardiography; the number of ventricular premature contractions (VPCs) per 24 hours was assessed. Hound dogs with cardiac pacing-induced systolic dysfunction (positive control dogs) and clinically normal non-Boxer dogs (negative control dogs) were evaluated echocardiographically. Three milliliters of blood was collected from each dog for measurement of plasma BNP concentration by use of a radioimmunoassay. RESULTS: Mean +/- SD plasma BNP concentration for the ARVC-affected Boxers, clinically normal Boxers, negative control dogs, and positive control dogs was 11.0 +/- 4.6 pg/mL, 7.9 +/- 3.2 pg/mL, 11.5 +/- 4.9 pg/mL, and 100.8 +/- 56.8 pg/mL, respectively. Compared with findings in the positive control group, plasma BNP concentration in each of the other 3 groups was significantly different. There was no significant difference in BNP concentration between the 2 groups of Boxers. A significant correlation between plasma BNP concentration and number of VPCs per 24 hours in the ARVC-affected Boxers was not identified. CONCLUSIONS AND CLINICAL RELEVANCE: A significant difference in BNP concentration between Boxers with ARVC and clinically normal Boxers was not identified. Results suggest that BNP concentration may not be an indicator of ARVC in Boxers.     

Muscle disorders and rehabilitation in canine athletes.

Muscle disorders associated with physical exertion in human athletes include delayed-onset muscle soreness, muscle strain, muscle tears, rhabdomyolysis, and acute and chronic compartment syndromes. Given that the structure of muscle is similar among different species, it is reasonable to expect that dogs experience the same phenomena. This article focuses on several of the muscle disorders of bird dogs, namely, coccygeal muscle injury and infraspinatus muscle contracture, and on those of dogs involved in tracking-obedience-protection training, namely, fibrotic myopathy, with an additional discussion of muscle strain. For injury prevention, one important area that can be adapted to canine athletes is the incorporation of warm-up and cool-down into the training program.     

Canine idiopathic dilated cardiomyopathy. Part I: Aetiology, clinical characteristics, epidemiology and pathology

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The aetiology of the myocardial hypokineis is seldom known in the individual case of DCM, although several theories concerning genetic, nutritional, metabolic, inflammatory, infectious, or drug- or toxin-induced myocardial disease have been discussed. DCM is often referred to as being breed-specific for Boxers, Doberman Pinschers, English Cocker Spaniels and other breeds. Review of reports on histopathologic findings in canine DCM reveals two histologically distinct forms of DCM; (1) cardiomyopathy of boxers and of Doberman pinschers, corresponding to the "fatty infiltration-degenerative" type, and (2) the form seen in many giant, large- and medium-sized breeds, including some boxers and Doberman pinschers, which can be classified as the "attenuated wavy fiber" type of DCM. The classification of canine idiopathic DCM according to histologic findigns seems superior to classification suggesting breed-specific syndromes, as some breeds (i.e. boxers and Doberman pinschers) may be affected by both diseases. However, ante mortem aetiological diagnosis of DCM is difficult. DCM carries a poor prognosis in dogs, and few prognostic indicators have been identified.     

Myotonia in related Chow Chow dogs

A myopathy associated with myotonia was observed in three related Chow Chow dogs. The clinical signs were first noticed at 2 to 3 months of age. They included muscle spasm and stiffness of gait which decreased in severity with exercise. Electromyographic findings and the demonstration of a muscle percussion dimple confirmed the presence of myotonia. Dystrophic changes were observed in muscle biopsies but histochemical techniques did not demonstrate fibre type changes. An inherited aetiology was suspected but not confirmed.     

Myopathy associated with hyperadrenocorticism in the dog

Naturally occurring or iatrogenic hyperadrenocorticism was associated with myopathy in six dogs. One dog had muscle weakness and muscle atrophy but normal electromyographic findings. Five dogs had muscle stiffness, proximal appendicular muscle enlargement, and myotonic discharges on electromyography. Histologic, electron microscopic, and histochemical findings in the musculature of dogs that were examined were characteristic of noninflammatory degenerative myopathy. Clinical signs of the myopathy improved to varying degrees in five dogs that were treated for the hyperadrenocorticism.     

Remission of Histiocytic Ulcerative Colitis in Boxer Dogs Correlates with Eradication of Invasive Intramucosal Escherichia coli

Background: Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology.
Hypothesis: Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission.
Animals: Seven Boxer dogs with HUC.
Methods: Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli .
Results: Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7±3.06 mg/kg q24 h, for 9.5±3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17–62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed.
Conclusions and Clinical Relevance: The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli .