A 4-year old, male-castrated, mixed breed dog was presented to a primary care veterinarian for a routine wellness examination (day 1). The dog was adopted 7-months prior and the previous medical history was unknown. The owner reported that the dog exercised daily without limitation, lived indoors only, and had no history of trauma. The dog was fed a commercial kibble diet and not administered any medications or supplements. The physical examination, which included thorough neurologic, musculoskeletal, and cardiopulmonary evaluations, was unremarkable. A complete blood count, serum biochemistry, symmetric dimethylarginine (SDMA), and urinalysis were performed. Clinically relevant abnormalities on the serum biochemistry performed at that time included a severe hyperCKemia (15,137 IU/L; reference interval 10-200 IU/L), and moderate increases in alanine transaminase (ALT; [432 IU/L; reference interval 180-121 IU/L]) and aspartate aminotransferase (AST; [404 IU/L; reference interval 16-55 IU/L]) enzyme activities. The complete blood count, SDMA, and urinalysis were unremarkable. A serum biochemical profile was repeated 7-days later, which revealed persistently increased serum CK activity (10,301 IU/L) as well as ALT (409 IU/L) and AST (290 IU/L) enzyme activities (Figure 1). Recommendations for additional diagnostic testing were declined by the owner in favor of empirical treatment for potential toxoplasmosis/neosporosis with clindamycin (22.7 mg/kg, PO, q12 h for 14 days).
The dog was presented for evaluation on day 55. The owner reported no clinical changes in the dog and the physical examination remained unremarkable. A serum biochemistry was repeated and revealed relatively unchanged serum CK, ALT, and AST enzyme activities (Figure 1). A commercial ELISA-based kit (4DX SNAP Plus Test kit, IDEXX Laboratories Inc., Westbrook, ME) was negative for detection of antibodies for Ehrlichia sp., Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi C6 peptide, and Dirofilaria immitis antigen. Differential diagnoses considered by the primary care veterinarian at that time included infectious polymyositis (Toxoplasma gondii or Neospora canis [potentially resistant to clindamycin], Hepatozoon canis or americanum), immune-mediated polymyositis, paraneoplastic polymyositis, congenital myopathy, or a hereditary muscular dystrophic disorder. The following diagnostic tests were recommended; skeletal muscle biopsy, electromyogram (EMG), echocardiogram, serum antinuclear antibodies, and additional infectious disease testing. The owner declined these recommendations because the dog was subclinical and instead opted for an additional course of clindamycin (22.7 mg/kg, PO, q12 h for 30 days). The dog was presented for evaluation on day 97. Again, the owner reported no abnormalities and the dog had an unremarkable physical examination. A serum biochemistry revealed relatively unchanged serum CK, ALT, and AST enzyme activities (Figure 1). All additional diagnostic testing recommendations were declined and the dog was discharged without medications.
The dog was presented to the primary care veterinarian for a wellness examination on day 602. The owner reported no abnormalities since the dog was last evaluated (day 97). The dog continued to exercise daily without limitation. Physical examination was unremarkable. There was no pain elicited with muscle palpation. A complete blood count, serum biochemistry, and urinalysis were performed. The serum biochemistry revealed persistence in severe hyperCKemia and mild to moderate increases in ALT and AST enzyme activities (Figure 1). The complete blood count and urinalysis were unremarkable. The owner declined additional diagnostic tests or empirical therapies at that time because the dog did not demonstrate any clinical abnormalities.
The dog was then presented to the Midwestern University Companion Animal Clinic (MWU-CAC) on day 1,036 for a second opinion regarding the severe hyperCKemia and mild-to-moderate increase in ALT and AST enzyme activities. The dog remained subclinical and exercised daily without limitation. A physical examination performed by a boarded small animal internist (JAJ) was unremarkable. The dog had a normal muscle conditioning score and pain was not elicited with deep palpation of musculature. A neurologic examination performed by a boarded neurologist (JE) revealed the dog was bright, alert and responsive. The dog was ambulatory with no signs of stilted gait, lameness or paresis. There was no overt exercise intolerance after several minutes of walking and trotting. Postural reactions, spinal reflexes and cranial nerves were normal. Serum biochemistry revealed an unchanged severe hyperCKemia and persistent mild-to-moderate derangements in ALT and AST enzyme activities (Figure 1). The dog was negative for detection of antibodies (IgM and IgG) for Toxoplasma gondii or Neospora canis (Protatek Reference Laboratory) and nucleic acids associated with Hepatozoon spp. (Texas A&M Veterinary Medical Diagnostic Laboratory) were not detected. An abdominal ultrasonogram performed by a boarded small animal internist (JAJ) trained in ultrasonography was unremarkable. Differential diagnoses considered at that time in order of likelihood was hereditary muscular dystrophy, and less likely necrotizing myopathy, generalized or focal inflammatory myopathy. Additional diagnostic tests including EMG, echocardiogram, or skeletal muscle biopsies were offered but declined by the owner.
The dog was evaluated on day 1,516 at the MWU-CAC for a pre-anesthetic examination for a dental prophylactic procedure. The owner reported no abnormalities since the dog was last evaluated (day 1,036) and the physical examination remained unremarkable. The dog had no muscle loss and remained active at home. A serum biochemistry revealed an improved, but persistent moderate hyperCKemia and mild-to-moderate increase in ALT and AST enzyme activities (Figure 1). A complete blood count and urinalysis were unremarkable. Next, an echocardiogram and electrocardiogram were performed by a boarded cardiologist (CP) in light of the persistent and unknown cause of severe hyperCKemia to ensure the dog did not have clinically relevant heart disease before undergoing anesthesia. Based on the echocardiographic findings, ACVIM Stage B1 degenerative valvular disease was detected, and demonstrated mild mitral and mild tricuspid regurgitation. The global systolic function appeared preserved. During the echocardiogram, Lead II electrocardiographic monitoring revealed a normal sinus rhythm with no evidence of ectopy.
The last in-hospital recheck examination took place on day 1,807 (5 years from initial evaluation). The owner reported no clinical abnormalities and the physical examination was unremarkable (Supplementary Video). The neurological examination was again normal. A serum biochemistry revealed a moderate hyperCKemia (4,601 IU/L) and mild-to-moderate increases in ALT (225 IU/L) and AST (165 IU/L) enzyme activity (Figure 1). Electrophoretic identification of serum CK isoenzymes (Antech Diagnostics, Irvine, CA, USA) revealed that CK-MM was the predominant electrophoretic fraction (83.7%), followed by CK-MB (10.3%) and CK-BB (6.0%). No injections were administered to the dog at or near the time serum total CK was measured at any of the examination time-points.