Idiopathic myositis presenting as cervical myalgia in a Petite Basset Griffon Vendeen

Clinical History

A 10 year old female spayed Petite Basset Griffon Vendeen was evaluated for a history of decreased appetite, lethargy, and left thoracic limb lameness. The dog had been treated 3 weeks earlier for back pain. It was treated with a tapering course of prednisone over 2 weeks beginning at 20mg per day and cage rest for presumed intervertebral disc disease. Clinical signs improved with treatment. Three weeks later the dog developed a lameness in the left thoracic limb and was febrile (103°F). At that point the patient was referred to the Veterinary Specialty Hospital of San Diego.

Physical and Neurological Examination

At presentation the patient was febrile (103.3°F). Physical and neurological examination was unremarkable with the exception of apparent cervical pain.

Diagnostic Tests

CBC - mature neutrophilia (67,773 cells/uL), mild lymphocytosis (4,674 cells/uL), mild monocytosis (4,674 cells/uL)
Chemistry analysis - Elevated alkaline phosphatase (AP, 1272U/L), elevated alanine aminotransferase (ALT, 114 U/L), elevated gamma-glutamyl transpeptidase (GGT, 21 U/L), elevated total bilirubin (0.9 mg/dL), elevated cholesterol (255 mg/dL, reference range 114-250 mg/dL), and normal creatine kinase activity (CK, 121 U/L, reference range 54-380 U/L)
Arthrocentesis of the left tarsus and carpus were performed to rule out polyarthritis. Both samples were normal.
Orthogonal radiographs of the cervical vertebral column were unremarkable. The patient was discharged with amoxicillin/clavulaunic acid (250 mg PO BID) and enrofloxacin (68 mg PO q24hr), as well as tramadol (50mg PO q8hr).
At the one-week recheck the patient's appetite had decreased and it was having trouble rising in the thoracic limbs. The client had been monitoring the rectal temperature at home, and it had fluctuated between 103.3 and 103.9°F. The apparent cervical pain had worsened. Complete bloodwork revealed a decrease in all liver values (AP, ALT, GGT, total bilirubin, and cholesterol) but no change in the leukocytosis except for a mild increase of the neutrophilia (69,468 cells/uL). The CK activity remained normal(46 U/L). An MRI of the patient's cervical vertebral column and adjacent structures revealed no disc degeneration or compression of the spinal cord. On T2-weighted images there was diffuse hyperintensity within the longus colli muscles (Fig. 1). The hyperintensity was also seen extending into the adjacent muscles.

Figure 1. MR images from a dog with myositis of the paraspinal musculature. Sagittal T2-weighted (A) and transverse T1-weighted (B), T2-weighted (C), and T1-weighted post-contrast (D) images are shown at the level of C3. Note the increased signal intensity within the longus colli and longus capitus muscles (arrowheads in figures A,C,D) and extending into the longissimus cervicis and spinalis cervicis muscles (asterisks in figures C and D) which is evident on the T2-weighted and post-contrast images. There were also two focal areas of T2-weighted hyperintensity which were hypointense on T1-weighted pre- and post-contrast images with ring enhancement on the post-contrast image (arrows in figures C and D).

A focal myopathy was identified as the possible cause of the patient's apparent cervical pain. Due to the focal nature of the lesion as well as the historical neutrophilia and fever, an infectious process such as an abscess or foreign body was considered most likely. An immune-mediated polymyositis or nonspecific myonecrosis was considered less probable due to the focal nature of the clinical signs. No foreign body could be identified on either MRI or ultrasound exam. Electrodiagnostics were not pursued as a generalized polymyopathy was not considered a likely rule-out and it was felt that surgical exploration of the cervical muscles was the next diagnostic step to identify a causative agent for the focal muscle lesion. Surgical exploration of the ventral cervical muscles was performed. A standard approach to the ventral vertebral column for a ventral slot procedure was used. The longus colli and longus capitus muscles were identified and muscle biopsies obtained. There was excessive variability in myofiber size with scattered atrophic fibers having a round shape and endomysial and perimysial fibrosis (Fig. 2). Mixed mononuclear cell infiltrations were present having an endomysial and perimysial distribution. Immunofluorescent staining was performed on muscle cryosections using previously characterized monoclonal antibodies against canine leukocytea and major histocompatibility complex (MHC) antigens (Fig 3.

Figure 2.A biopsy from the longus coli muscle was evaluated in frozen sections (8µm). Excessive variability in myofiber size was noted with scattered atrophic fibers having a round shape. Mononuclear cell infiltrates were evident having an endomysial and perimysial distribution. Endomysial and perimysial fibrosis were also observed. H&E stain, bar = 50 µ

Figure 3. Fresh frozen biopsy sections (8µm) from the longus coli muscle were incubated with monoclonal antibodies against T-cell antigens (CD4, CD8), against B cell antigen CD21, against major histocompatibility antigens (MHC-I,MHC-II),, against collagen VI (COL-VI) for identification of fibrosis and against developmental myosin heavy chain (dMHC) for identification of regenerating myofibers. CD8+ cells were present in greater numbers than CD4+ T cells or CD21+ B cells. Increased expression of MHC-I was noted on the muscle sarcolemma (arrow). Infiltrating cells expressed MHC-II. Excessive localization of COL-VI was noted in areas of fibrosis and extensive fiber loss. Regenerating fibers were not evident using the antibody against developmental myosin heavy chain (dMHC). Control sections omitted the primary antibody (No). Fluorescein isothiocyanate, bar = 50µm.

Treatment and Outcome

Before muscle biopsy results became available, the patient was discharged with instructions to continue the enrofloxacin, amoxicillin/clavulanate, and tramadol as previously prescribed. The patient was also treated with an additional antibiotic (trimethoprim sulfa 480mg PO q12hr) and prednisone (7.5mg PO q12hr). The results of the muscle biopsies were received two days after discharge. Based on the results of the biopsies all antibiotics were discontinued and the prednisone dose increased to 10mg q12hr. Two weeks after starting treatment with prednisone the patient's apparent cervical pain had resolved and appetite had improved. The dog continued to have a mature neutrophilia (29,348 cells/uL) but it was dramatically lower than at the time of diagnosis. Chemistry profiles were not repeated. Azathioprine (50mg PO q24hr) therapy was initiated 2 weeks into prednisone therapy. After 2 weeks the azathioprine was tapered to 50mg every other day, and the prednisone to 10mg once per day. Five weeks after initiation of prednisone treatment the patient's leukocytosis had resolved. Initial attempt at tapering to every other day prednisone therapy resulted in a relapse of clinical signs. The patient is currently maintained with azathioprine (50mg PO every other day) and prednisone (5mg PO every third day).