Edward F. Bischof

Life-threatening hypocalcemia associated with denosumab in a patient with moderate renal insufficiency

Denosumab, a human monoclonal antibody to the receptor activator of nuclear factor-κB ligand, is a novel therapy to osteoporotic fracture and skeletal-related events in patients with bone metastases. Hypocalcemia is its known adverse effect, although it is generally mild and transient and usually occurs in patients with severe chronic kidney disease or end-stage renal disease. We reported a case 61-year-old woman who received a single dose of denosumab and developed severe symptomatic hypocalcemia associated with prolong QTc interval requiring hospitalization for intravenous calcium.

A case of childhood vasculitis presenting in adulthood

[1] Costantino TG, Parikh AK, Satz WA, et al. Ultrasonography-guided peripheral intravenous access versus traditional approaches in patients with difficult intravenous access. Ann Emerg Med 2005;46:456-61. [2] Keyes LE, Frazee BW, Snoey ER, et al. Ultrasound-guided brachial and basilic vein cannulation in emergency department patients with difficult intravenous access. Ann Emerg Med 1999;34:711-4. [3] Bauman M, Braude D, Crandall C. Ultrasound-guidance vs. standard technique in difficult vascular access patients by ED technicians. Am J Emerg Med 2009;27:135-40. [4] Mills CN, Liebmann O, Stone MB, et al. Ultrasonographically guided insertion of a 15-cm catheter into the deep brachial or basilic vein in patientswith difficult intravenous access. Ann EmergMed 2007;50:68-72. [5] Stein J, George B, River G, et al. Ultrasonographically guided peripheral intravenous cannulation in emergency department patients with difficult intravenous access: a randomized trial. Ann Emerg Med 2009;54:33-40.

Salicylate-induced pulmonary edema--a near-miss diagnosis.

A 43-year-old white woman presented to the emergency department with confusion, agitation, and progressive dyspnea. Chest x-ray revealed pulmonary edema. Initial diagnostic considerations were pneumonia, pulmonary embolism, sepsis, central nervous system infection, substance toxicity, and heart failure. Her salicylate level was 92.6 mg/dL, and an arterial blood gas revealed a respiratory alkalosis and nonanion gap metabolic acidosis, consistent with salicylate poisoning. Noncardiogenic pulmonary edema is an atypical presentation of salicylate toxicity, and this case highlights the importance of an early toxicology screen to make a time-critical diagnosis and provide specific treatment.

Antipsychotics-induced ischemic colitis

Ischemic colitis (IC) is a rare adverse effect of antipsychotic drugs, most commonly with phenothiazine and the atypical antipsychotic medications. Taking thesemedications with drugs with anticholinergic effects can increase the risk of developing IC. A 34-year-old man presented with 2 days of left lowerquadrantabdominalpainandrectal bleeding.Hismedicalhistory included psychosis under long-term compliancewith oxcarbazepine and quetiapine administration. Three days before the onset of symptoms, he received amitriptyline10mgatnight for insomnia.Hisphysicalexaminationshoweddiffuseabdominal tenderness with guarding, and a blood test revealed leukocytosis. A sigmoidoscopy revealed IC involving the splenicflexure to sigmoid colon, confirmed by a biopsy. According to the association between the medications and onset of symptoms, the patient’s IC was likely caused bys quetiapine or the combination of quetiapine, oxcarbazepine, and amitriptyline, secondary to the anticholinergic effect. Therefore, any patients starting antipsychotic medications, particularly those with anticholinergic properties, should be counseled regarding the risk of complications. Although IC is a rare adverse effect of antipsychotic drugs, it is still very important to consider because of the potentially fatal outcome. Ischemic colitis (IC) is the most common form of intestinal ischemia, accounting for more than half of cases [1,2]. It often presents as mild and transient episodes,without the need to seekmedical attention, and some cases are misdiagnosed as inflammatory bowel disease or infectious colitis [2]. It is most common in the elderly with multiple comorbidities. The incidence rate varies from 1.1 per 100,000 in those younger than 40 years to 107 per 100,000 among those aged 80 and older [3]. Several medications have evidence of causing IC including antihypertensive, antibiotics, opioids, and female hormones [4]. Phenothiazine and clozapine are the most reported antipsychotics thought to cause IC [5-7]. Quetiapine is one of the atypical antipsychotic drugs with less anticholinergic effects and has little evidence of associationwith IC [8]. We presented the case of a 34-year-oldmanwithmultiple episodes of IC, long-term use of quetiapine and oxcarbazepine, and recently prescribed amitriptyline. A 34-year-old man with a past medical history of hypertension and psychosis presentedwith a 2-dayhistory of left lower quadrant abdominal pain and bright red blood per rectum. The pain was sudden and severe. Three days before the onset of symptoms, hewas prescribed amitriptyline 10 mg nightly for insomnia. The patient was compliant with taking his prescribed oxcarbazepine (300 mg twice a day) and quetiapine (400 mg daily) for psychosis for 20 years. Relevant past medical history includes 2 previous episodes of IC in 2005 and 2013 documented by colonoscopy. Onexamination, thepatienthad abody temperatureof 37.2°C, heart rate of 114beats perminute, respiratory rate of 16breathsperminute, andblood pressure of 150/100mmHg. Hewas in acute distress because of abdominal pain.Abdomenwasmildlydistendedwith tenderness topalpation, guarding but no rigidity, and normoactive bowel sound. Laboratory work revealed 0735-6757/© 2015 Elsevier Inc. All rights reserved. white blood cell count 15.3 x 10/mm, aspartate aminotransferase 15 IU/L, alanine aminotransferase 30 IU/L, alkaline phosphatase 136 IU/L. Hemoglobin level, platelets, bloodureanitrogen, creatinine, electrolytes, amylase, and lipasewerenormal. Anabdominalfilmrevealedno freeair. TheCT scan abdomen revealed some thickening and pericolonic stranding of the junction of the sigmoid and descending colon possibly because of focal colitis. Bloodandstool cultureswerenegative for growth.Clostridiumdifficile test was negative. Patient underwent a sigmoidoscopy, which showedmild erythemamostly around the splenic flexure. Tissue biopsy revealed IC. The patient was initially treated with intravenous fluids and received levofloxacin 750 mg daily and metronidazole 500mg every 8 hours intravenously for 3 days and switched to orally for another 5 days. With treatment, his fever, abdominal pain, and blood per rectum resolved. His white blood cell count trendeddown to10.0. Itwas recommendedbygastroenterology forpsychiatry to reevaluate his antipsychotic regimen given the associationwith IC. Many drugs have been shown to cause IC. Antipsychotic medications, especially atypical antipsychotic drugs, nonsteroidal anti-inflammatory drugs, digitalis, dopamine, epinephrine or norepinephrine, methysergide, vasopressin, pseudoephedrine, cyclosporine, danazol, diuretics, flutamide, glycerin enema, phospho soda solution, tricyclic antidepressants (TCAs) have been considered to increase the risk of causing IC [5,9-11]. Our patient is relatively young compared with most IC cases. He did not have any predisposing factors for atherosclerosis such as diabetes, dyslipidemia, or tobacco use, except for hypertension. Moreover, the investigation ruled out coagulation disorders and viral or bacterial infection. Thus, no factors for IC were detected in the patient by appropriate workup other than the long-timeuse of quetiapine, oxcarbazepine, and anewdrug, TCAs (amitriptyline). Our patient experienced 2 previous episodes of IC confirmed by colonoscopy raising the concern that these episodes could have been caused by atypical antipsychotic medication (quetiapine) and oxcarbazepine. According to previous reports, several atypical antipsychotics including clozapine and olanzapine have been associatedwith IC because of their anticholinergic effects. A lesser extent of evidence indicates that quetiapine, aripiprazole, paliperidone, risperidone, and ziprazidone may be associated with IC [12]. From their antagonizing acetylcholine properties, intestinal smooth muscle contraction is inhibited, which results in functional bowel obstruction and leads to abdominal distension, which was found in this patient. Consequently, untreated bowel obstruction can lead to IC by impairing the colonic arterial supply, increasing the intraluminal pressure, andcausing shuntingofblood frommucosa to serosa [13-15]. For the recent episode of IC, the combination of quetiapine, oxcarbazepine, and TCAs (amitriptyline) administrationwould be themost appropriate explanation. Tricyclic antidepressants have anticholinergic activity that can cause colonic hypomotility, paralytic ileus rarely complicated with cecal perforation because of intestinal pseudo-obstruction, and gangrenous left-sided IC from decreased colonic perfusion [16]. In our patient, although a normal dose of TCAwas administered, IC likely developeddue to an additivemechanism along with the long-term use of quetiapine and oxcarbazepine. 1716.e6 S. Upala et al. / American Journal of Emergency Medicine 33 (2015) 1716.e5–1716.e6 Our case supports that TCAs can promote transient nongangrenous IC in patients who take antipsychotic medications. Clinicians should raise awareness for patients with long-term antipsychotic drug use to prevent this rare lethal event. Sikarin Upala, MD, MS Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown NY Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Karn Wijarnpreecha, MD Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY Cardiac Electrophysiology Research and Training Center, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Veeravich Jaruvongvanich, MD Department of Internal Medicine, University of Hawaii, Honolulu, HI Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Significance of halo, reversed halo and air crescent signs in lymphomatoid granulomatosis and pulmonary fungal infections

We read with interest the article by Lota et al .1 The authors report a case of lymphomatoid granulomatosis (LG) with an atypical CT finding of crescent sign for LG. Typically, LG patients with lung involvement can present with pulmonary …

Reported Cases of Recurrent Takotsubo Cardiomyopathy with Variant Forms of Left Ventricular Dysfunction

We read with great interest the article by Aggarwal and Krantz, entitled “Migratory takotsubo cardiomyopathy in the setting of cholecystitis.” This was a very interesting case presentation regarding stress-related cardiomyopathy involving variable myocardial segments at different time points. The author mentioned that this was the first reported case. After careful review, however, we found several reports in the literature of recurrent takotsubo cardiomyopathy with variable patterns of left ventricular dysfunction. In 2007, Blessing et al reported a 70-year-old man with recurrent takotsubo cardiomyopathy demonstrating basal area akinesis initially and apical ballooning on the second episode. In 2009, Izumo et al reported a 78-year-old male with recurrent takotsubo cardiomyopathy. At the first episode, the patient was found to have apical akinesis and basal hyperkinesis while at the second episode; 2 years later, he was found to have mid-ventricular akinesis combined with normal apical wall motion. In 2011, From et al presented a clinical image of a 65-year-old female with recurrent takotsubo cardiomyopathy manifesting as typical apical ballooning at the first episode and mid-ventricular variant at

Purple urine bag syndrome.

A 44-year-old man with Downs syndrome and neurogenic bladder which required a suprapubic catheter presented with fever and change in his urine color for one day. Physical examination revealed a temperature of 38.3°C, blood pressure of 60/30 mmHg, pulse rate of 120/min and urine with purple discoloration in the urine catheter and bag (Figure 1). A urine dipstick test indicated the presence of leukocytes, positive nitrate and a pH value of 8.5. The patient was resuscitated with intravenous crystalloid fluid and empiric antibiotics (vancomycin and piperacillin/tazobactam) were started. The patients urine culture subsequently grew Enterococcus faecalis. His antibiotic was changed to levofloxacin as per sensitivity analysis. The patient responded well to treatment as his fever subsided and improved and his urine color gradually returned to yellow. Fig. 1. Purple discoloration of urine in the urine catheter and bag. Purple urine bag syndrome (PUBS) is a rare condition characterized by purple discoloration of urine in a urine catheter and bag typically seen in patients with chronic debilitation with a history of long-term indwelling urinary catheter [1]. The pathogenesis of this discoloration is associated with tryptophans metabolism as intestinal bacteria metabolize tryptophan to indole and later converted to indican by the liver. Indican, in turn, is excreted and broken down in the urine into indirubin (red) and indigo (blue) in an alkaline environment by sufatase or phosphatase-containing bacteria, such as Providencia stuartii, Providencia rettgeri, Proteus mirabilis, Klebsiella pneumoniae, Escherichia coli, Enterococcus spp., etc. [2] PUBS is generally a benign process but it provides a clue to the presence of an underlying urinary tract infection. The discoloration usually gradually disappears after antibiotic treatment and good urologic sanitation, as seen in our patient [1, 3].

Association between takotsubo syndrome and thrombocytopenia

We thank Katoh et al [1] for their interesting article. The authors reported takotsubo syndrome associated with hypoglycemia. We are also interested in takotsubo syndrome and recently reviewed this condition and its association. We found an interesting topic regarding association between takotsubo cardiomyopathy and thrombocytopenia. Wewould like to discuss the possible causes of thrombocytopenia in patients with takotsubo syndrome. Although there is no clear explanation for why patients with takotsubo syndrome can present with thrombocytopenia, there have been reports of this acute cardiomyopathy and thrombocytopenia related to thrombotic thrombocytopenic purpura [2] and seizure [3] in the literature. Renal insufficiency, fever, hemolytic anemia, or seizure in patients with takotsubo cardiomyopathy should raise the suspicion of thrombotic thrombocytopenic purpura.

Syncope in Brugada syndrome type 3: an electrocardiographic lesson

We thank Grossman et al. [1] for their wonderful article on the incidence of critical interventions or adverse outcomes associated with near syncope comparing these outcomes with the ones of patients with true syncope. In addition, we would like to emphasize that physicians should further evaluate for arrhythmias in patients with either near syncope or true syncope based on electrocardiographic (ECG) findings. American Journal of Emergency Medicine 31 (2013) 621–630