Thomas M. Roy

Simvastatin-induced lactic acidosis: a rare adverse reaction?

Simvastatin, a hydroxymethylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor, is a commonly used cholesterol‐lowering agent. The long‐term safety profile of simvastatin, established over 10 years of clinical use, is excellent. HMG‐CoA reductase inhibitors block 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, the rate‐limiting enzyme in cholesterol synthesis. However, other important nonsterol compounds, such as coenzyme Q10 (CoQ10), are also derived from the same synthetic pathway. CoQ10 is an essential carrier in the mitochondrial respiratory chain that participates in oxidative phosphorylation. Simvastatin and other HMG‐CoA reductase inhibitors have been documented to lower serum concentrations of CoQ10. It has been suggested that the adverse effect of myopathy caused by HMG‐CoA reductase inhibitors is due to CoQ10 deficiency in the tissue mitochondria. Documentation of this cause‐and‐effect phenomenon, however, has been lacking. We offer evidence that lactic acidosis may develop as a complication of simvastatin therapy. Our patient also manifested the well‐known HMG‐CoA reductase inhibitor drug toxicities of rhabdomyolysis and hepatitis. The occurrence of these known adverse events with lactic acidosis in our patient suggests that interference of the mitochondrial respiratory chain may play a role in the toxicity of this class of drugs.

Pneumomediastinum, pneumopericardium, and epidural pneumatosis in DKA

Pneumomediastinum (PM) is an uncommon condition characterized by the presence of air in the mediastinum. It is associated with alveolar rupture that allows air to traverse along the bronchovascular bundle into the mediastinum. A review of the world medical literature identified 50 additional cases of PM and pneumopericardium (PC) associated with diabetic ketoacidosis (DKA). We report the occurrence of PM, PC, as well as epidural pneumatosis occurring simultaneously in a patient with DKA. Epidural pneumatosis in association with this metabolic derangement has not been previously described.

Axillary artery injuries after proximal fracture of the humerus.

Although axillary artery injury occurs frequently with dislocations of the shoulder and fractures of the clavicle, it is rarely associated with fractures of the proximal humerus. If the axillary artery is damaged, prompt recognition and treatment are necessary to salvage the involved extremity.

False-positive antineutrophil cytoplasmic antibodies in a patient with cavitary pulmonary sporotrichosis

We present a patient with chronic cavitary pulmonary sporotrichosis with elevated antineutrophil cytoplasmic antibody (ANCA) titers. Otolaryngology, pulmonary, and renal evaluations were negative for Wegener’s granulomatosis. Treatment of the pulmonary sporotrichosis with itraconazole resulted in the patient’s clinical improvement and normalization of his ANCA levels. Elevated ANCA levels have been reported with bacterial pneumonias and empyemas as well as Mycobaterium tuberculosis and M bovis. We believe this is the first report of a fungal infection causing a falsepositive ANCA. Antineutrophil cytoplasmic antibodies (ANCA) were first reported in 1964 (1). The cytoplasmic staining pattern for ANCA (cANCA) was initially identified as a highly sensitive and specific marker for Wegener’s granulomatosis. The perinuclear staining pattern for ANCA (pANCA) has been found to occur in a wide range of vasculitic diseases (2,3). As clinical experience with these markers has expanded, the high estimates of sensitivity and specificity reported by specialty centers has been questioned. Pulmonary infections and other disease processes have been reported as causes of false-positive ANCA tests. A false-positive cANCA may contribute to clinical misdiagnosis and inappropriate treatment, resulting in patient morbidity and mortality (4,5). Sporothrix schenckii is a dimorphic saprophytic fungus with a worldwide distribution. It can be isolated from the soil, plants and moss, and thorny bushes. Pulmonary infection with S schenckii is extremely rare (6). We wish to call attention to a patient with localized pulmonary sporotrichosis with elevated ANCA levels.