Annabelle, an 18-year-old white woman, was referred by her primary care provider to our gastroenterology practice for markedly elevated serum transaminase levels. Her mother and grandmother accompanied her.
The patient had no complaints at presentation. Her only sibling, a 20-year-old sister, had recently been given a diagnosis of hereditary hemochromatosis; she was not undergoing phlebotomy at that time. Annabelle had come in for screening and was found to have markedly elevated serum transaminase levels: aspartate aminotransferase (AST) 539 U/L and alanine aminotransferase (ALT) 361 U/L. The remaining levels were within normal limits: alkaline phosphatase 31 U/L, total bilirubin 0.5 mg/dL, direct bilirubin 0.1 mg/dL, albumin 3.9 g/dL, and total protein 6.8 g/dL. Her hepatitis panel was nonreactive. Her hepatitis B surface antibody was reactive, and this suggested immunity. An ultrasound of her abdomen was unremarkable. At 2 years prior, her AST and ALT levels had been normal: 23 and 16 U/L, respectively.
Two months earlier, under the direction of a local allergist, Annabelle had begun treatment with allergy serum for Raynaud phenomenon. A friend of the family, who is an oncologist, remarked that the histamine in the allergy serum could cause elevated transaminase levels. However, the allergist maintained that he had never encountered this type of reaction in his 20-plus years of practice.
In addition, Annabelle had had a tattoo placed on her right lower abdomen 3 months earlier and had undergone umbilical piercing 1 year earlier. She denied past and present use of illegal drugs and promiscuous behaviors. She was not using acetaminophen or alcohol in excess.
She was planning to enter a nearby university as a freshman in the coming fall.
Laboratory tests and imaging
The immediate plan was to rule out conditions that can cause hepatocyte injury, such as autoimmune hepatitis, Wilson disease, hemochromatosis, cytomegalovirus infection, Epstein-Barr virus infection, and celiac sprue. Therefore, the following laboratory tests and measurements were ordered: serum immunoglobulin A (IgA), IgG, and IgM; protein electrophoresis; anti-mitochondrial antibody; antinuclear antibody; gamma-glutamyl transpeptidase (GGT); ceruloplasmin; serum iron, ferritin, and fasting transferrin; vitamin B12; cytomegalovirus antibody titer; monospot with reflex Epstein-Barr virus antibody panel; IgA tissue transglutaminase; hemoglobin A1C; and thyroid-stimulating hormone (TSH). All values were within normal limits. Annabelle’s vitamin B12 level was low normal at 197 pg/mL. Her AST and ALT levels had risen to 670 and 487 U/L, respectively. Magnetic resonance imaging of the liver was ordered, and it showed mild hepatomegaly, a homogeneous liver parenchyma, no enhancing lesions or biliary duct dilation, and no evidence of cholelithiasis or choledocholithiasis. The utility of a liver biopsy was discussed, and the patient was advised to follow up with the supervising gastroenterologist, Dr. S.F.M.
After 9 days, Annabelle returned for a visit with Dr. S.F.M., who, because of the AST>ALT pattern and the recent history of Raynaud phenomenon, suspected a mixed connective tissue disease or perhaps scleroderma. Additional laboratory measurements were ordered: anti-double-stranded DNA antibody, complement C3 and C4, liver/kidney microsomal antibody, and other autoimmune antibodies. All values were within normal limits. Dr. S.F.M. then referred Annabelle to a rheumatologist at a nearby tertiary center.
In the meantime, Annabelle experienced the rapid onset of progressively worsening proximal muscle weakness, with marked weakness of her limbs. She had obvious difficulty standing up from a sitting position. She went to see the rheumatologist, who, because of the AST>ALT pattern and her new complaint of muscle weakness, suspected a muscular etiology. Serum creatine kinase (CK) and aldolase levels were ordered. An evaluation by a neurologist was considered to rule out the possibility of Guillain-Barré syndrome, as she had received the meningococcal vaccine 4 to 6 weeks earlier. A vascular pathology was also considered.
Interestingly, her laboratory test results included a markedly elevated CK level at 23,822 U/L, and the aldolase level was also high at 226 mg/dL (range 88-174). A provisional diagnosis of myositis with proximal myopathy was made.
Annabelle was admitted to the hospital for further testing and intravenous hydration, as a CK level above 16,000 U/L is associated with acute renal failure. Computed tomography of the abdomen and pelvis with contrast showed bilateral anterior thigh compartment-predominant myositis and mild third spacing. A left deltoid muscle biopsy was performed under monitored anesthesia care (MAC) with local anesthesia. The pathology report indicated that (1) the exact subtype of autoimmune inflammatory myopathy was not clear, with some features favoring dermatomyositis and some consistent with a synthetase syndrome (a rare medical condition associated with interstitial lung disease, dermatomyositis, polymyositis, and autoimmune diseases), and that (2) substantial perimysial pathology and substantial necrosis were present.
Electromyography showed electrodiagnostic evidence of myopathy with irritable muscle membrane and evidence of active denervation and myopathic motor unit action potentials (MUAPs), with recruitment seen predominantly in the proximal limb muscles. In acute myopathic disorders with active inflammation and/or necrosis, denervation activity can be prominent, MUAPs will be small and polyphasic, and recruitment patterns will be full with decreased amplitudes.