Adverse Drug Reaction Probability Scale Research Articles

Liraglutide‐Induced Acute Kidney Injury

Published case reports have documented the relationship between exenatide use and acute kidney injury. However, to our knowledge, no cases of this adverse effect with liraglutide, another glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus, have been reported. We describe a 53-year-old Caucasian woman who came to a community hospital with severe and progressively worsening gastrointestinal symptoms for several weeks, leading to dehydration and development of acute kidney injury. Laboratory results showed an increase in her serum creatinine concentration to 22.8mg/dl and blood urea nitrogen to 150mg/dl; she also had lost 8.9kg in the previous month. One month earlier, the patient had begun liraglutide 1.8mg/day subcutaneously for uncontrolled type 2 diabetes. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 3) between the patient's development of acute kidney injury and liraglutide. Renal biopsy and laboratory testing were helpful in ruling out other potential causes of renal failure and adverse drug reactions due to other drugs such as ciprofloxacin and quinapril. After the reports of the renal biopsy were obtained, liraglutide was determined to be a likely cause of acute tubular necrosis. The patient was successfully treated with discontinuation of liraglutide, volume repletion, and hemodialysis. To our knowledge, this is the first documented case of liraglutide-induced acute tubular necrosis. Clinicians should be aware of this possible complication and closely follow liraglutide's dosage titration recommendations in the package insert. Patients should also be educated about the need to report unusual or prolonged gastrointestinal symptoms.

Neurological Deficits During Treatment With Tumor Necrosis Factor-Alpha Antagonists

IntroductionNeurological deficits that occur during treatment with tumor necrosis factor (TNF)-α antagonists are rare, and their clinical features have not been fully elucidated. MethodsRetrospective review of medical records of 9 patients who were given TNF-α antagonists, subsequently developed neurological deficits and were cared for at the Medical University of South Carolina between January 2002 and May 2010. Adverse drug reaction probability scale was used for the assessment of their causal connection. ResultsThe underlying diseases for which TNF-α antagonists were administered included rheumatologic disorders (4), sarcoidosis (3), psoriasis (1) and Crohn’s disease (1). Etanercept, infliximab or adalimumab was administered to these patients. Neurological complications included central or peripheral demyelination (5), antiphospholipid syndrome/central nervous system lupus (1), Epstein-Barr virus encephalitis (1), axonal sensory polyneuropathy (1) and small fiber polyneuropathy (1). TNF-α antagonists were discontinued in 8 patients and clinical improvement was seen in 3 of them. Additional therapies were given in 4 patients. An adverse drug reaction probability score suggested probable (3/9) and possible (6/9) causal relationships. ConclusionsNeurological deficits that develop during treatment with TNF-α antagonists are relatively rare but important potential complications of these drugs. Determining if the relationship between the neurological deficits and TNF-α antagonist therapy is causal can be challenging and can impact patient care.

Multiple organ failure caused by near-usual doses of colchicine

Multiple organ failure (MOF) due to colchicine treatment is rare, even in the presence of concurrent renal and hepatic failure [1]. Here, we present a case of MOF caused by nearusual doses of colchicine in a patient with risk factors for colchicine intoxication. A 76-year-old male patient with 2 months history of decline in well-being, malaise, and fatigue had been referred to our institution due to elevated alanine aminotransferase (ALT) and aspartate aminotransferase and (AST) levels. His medical history included diabetes mellitus type 2 for 6 months, arterial hypertension for 10 years and gout for 40 years. He had been taking perindoprilhydrochlorothiazide 10/12.5 mg tablet once a day, verapamil sustained-release tablet once a day, and rapeglinid 0.5 mg tablet three times a day. 5 days before the admission, he has been advised to take colchicine tablet 1 mg three times a day by a general practitioner for gout prophylaxis. Physical examination revealed bilateral 3? pretibial oedema and grade 3 holosystolic murmur on the apex. Lungs were clear to auscultation. Left lobe of liver was palpable. On the fifth day of admission, the patient experienced watery diarrhoea four to five times a day lasting for a week. The culture and the microscopic examinations of stool revealed no pathological findings. Oral anti-diabetic drugs were not appropriate for the patient because of hypoglycaemia risk due to chronic liver disease. Angiotensin converting enzyme inhibitors could worsen renal function in a dehydrated diabetic patient. Diarrhoea caused by colchicine overdose resolves by dose reduction, that is why colchicine dose was decreased to 1 mg/day and all the other medications were ceased. On the day 10, the patient became anuric and febrile. Urea and creatinine levels increased. Bicytopenia was observed on his blood count. Arterial blood gas analysis was consistent with metabolic acidosis. He still had diarrhoea. Thus, colchicine was thought to be responsible for this clinical picture and was stopped. Breathing was shallow and laboured. Chest radiography showed bilateral patchy shadowing throughout both the lung fields. Systemic inflammatory response syndrome (SIRS), sepsis and MOF were considered. Piperacilline-tazobactam 2.25 mg four times a day was started. He was intubated due to respiratory failure but unfortunately died on the same day. Use of the Naranjo adverse drug reaction probability scale in our patient indicated a probable relationship (score of 5) between MOF and colchicine therapy. Eighty percent of the patients taking therapeutic doses of colchicine and almost all patients who are exposed to overdose experience GI symptoms. These GI symptoms serve as primary warning signs of colchicine toxicity during treatment for any indicated disease and are usually mild, transient, and reversible by discontinuation or lowering of colchicine dose [1]. Common clinical features of colchicine toxicity along with stages are shown in Table 1. A. Ucgul Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

Cefepime-associated thrombocytopenia in a critically ill patient

Cefepime-induced thrombocytopenia is a rare adverse event (incidence <1.0%), based on data from clinical trials. However, there is limited post-marketing surveillance documentation on thrombocytopenia associated with cefepime. We describe a 45-year-old male who was admitted to the intensive care unit after allegedly being hit by a large metal bar in the right upper chest and shoulder. Rhabdomyolysis secondary to the trauma, pneumothorax, acute renal failure, and nosocomial sepsis were subsequently diagnosed. Four days after intravenous cefepime initiation, the patient developed thrombocytopenia with platelet count dropping from 102 × 10(3)/μL to 15 × 10(3)/μL. Cefepime was discontinued and the platelet count normalized to 140 × 10(3)/μL after 6 days. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between the patient's thrombocytopenia and cefepime therapy. Although cefepime-induced thrombocytopenia is rare, clinicians should be alert to this potential adverse effect among critically ill patients.

Neurotoxicity Associated with Standard Doses of Valacyclovir in Renal Insufficiency

Chronic kidney disease is a growing problem in the United States that increases the risk of medication-related complications. The antiviral medication valacyclovir hydrochloride is indicated for the treatment and/or suppression of herpes labialis, genital herpes, and herpes zoster and requires dosage adjustment for renal impairment. Valacyclovir is generally well tolerated, but serious adverse drug reactions have been reported including neurotoxicity and acute renal failure, especially in the elderly and in those with chronic kidney disease. We present 2 cases of neurotoxicity suspected to be secondary to non-renally dose-adjusted valacyclovir therapy. The first is a female hemodialysis patient who developed neuropsychiatric symptoms within 24 hours of initiating valacyclovir therapy; the second is an elderly gentleman with stage 4 chronic kidney disease and symptoms after 2 days of therapy. Both were prescribed valacyclovir 1 g orally 3 times daily despite renal impairment. Use of the Naranjo adverse drug reaction probability scale suggests probable associations between neuropsychiatric symptoms displayed by the patients and valacyclovir (score of 5 in case 1; score of 7 in case 2). These cases highlight the importance of considering renal status when dosing medications that undergo significant renal elimination.

Clofarabine‐Associated Acute Kidney Injury and Proteinuria

Clofarabine is used as second-line therapy for acute myeloid leukemia. Acute renal impairment is reported with clofarabine; however, it is more likely to occur in patients with confounding factors that may underlie the adverse event. We describe a 65-year-old man treated with clofarabine for relapsed acute myeloid leukemia who experienced severe acute kidney injury and proteinuria temporally related to clofarabine administration. The morning after completion of clofarabine administration, his serum creatinine concentration increased to approximately 1.4-fold above his baseline value, and peaked at 2.8-3.6-fold over baseline within 72 hours. A 24-hour urine collection contained 4100 mg of protein. His serum creatinine concentration gradually returned to within 1.5 times his baseline value. Examination of the patient's clinical course, vital signs, and laboratory results did not yield any compelling evidence of alternative causes for acute kidney injury. The patient's comorbidities included a left ventricular ejection fraction of 35-40% and diabetes mellitus. His drug therapy with potential renal effects-lisinopril, furosemide, tobramycin, allopurinol, and valacyclovir-that preceded clofarabine administration was evaluated, and none was determined to be a major factor in the development of this adverse event. Bone marrow evaluations were negative for residual leukemia after clofarabine therapy. After approximately 11 weeks of hospitalization, the patient and his family made an informed decision to continue supportive care at home. Acute kidney injury in this patient was attributed to clofarabine administration due to the time course of events with respect to potential contributing factors. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of renal effects and clofarabine therapy. To our knowledge, this is the first report of medically significant proteinuria associated with administration of clofarabine. Clinicians should be aware of the potential for acute kidney injury if their patients are administered clofarabine.

Possible Lenalidomide‐Induced Stevens‐Johnson Syndrome During Treatment for Multiple Myeloma

Stevens-Johnson syndrome is a rare, severe cutaneous reaction most often associated with drug therapy. Lenalidomide is a derivative of thalidomide used in the treatment of multiple myeloma. We describe a case of Stevens-Johnson syndrome possibly induced by lenalidomide in a 73-year-old Caucasian female undergoing induction therapy for multiple myeloma. After 13 doses of induction therapy, she was admitted to the hospital directly from her oncologist's office after presenting with a diffuse, bodywide, maculopapular rash with desquamation. She had prominent crusting of her lips, erythematous ulcers on her soft palate that could not be distinguished from petechial hemorrhages, and acute kidney injury (serum creatinine concentration 4.6 mg/dl). She was also febrile and hypotensive. Lenalidomide was discontinued, and the patient was treated with intravenous dexamethasone 10 mg every 6 hours and topical corticosteroids. Over the next week, the patient's condition improved, but she had extensive exfoliation of her rash and pruritus that required antihistamine therapy. By hospital day 9, her rash continued to improve, her pruritus resolved, and she was discharged with a tapering dose of oral prednisone. Lenalidomide was switched to bortezomib for her induction therapy, and the patient did not experience any further cutaneous reactions. The results of a skin biopsy concluded that the findings were consistent with a drug hypersensitivity reaction, suspected to be Stevens-Johnson syndrome. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 3) between the patient's development of Stevens-Johnson syndrome and lenalidomide therapy. To our knowledge, no published case reports of severe dermatologic reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, to lenalidomide have been reported. Thus, we believe this to be the first published case report of a patient who developed Stevens-Johnson syndrome while receiving lenalidomide for induction therapy for multiple myeloma. Clinicians should have a heightened awareness of the signs and symptoms of these severe skin reactions if their patients are receiving lenalidomide.

Probable Quetiapine-Mediated Prolongation of the QT Interval

Purpose: QT prolongation can occur with both first- (FGA) and second-generation antipsychotics (SGA). QT prolongation was identified in an adult patient who presented to the emergency room with schizophrenia, fluid and electrolyte imbalances, and pneumonia. Quetiapine, an SGA, was a component of the pharmacotherapy regimen. Based on the Naranjo adverse drug reaction probability scale rating criteria, a probable causal association was made. Methods: PubMed and Ovid were searched using the terms antipsychotic, psychotropic, QT interval, corrected QT interval (QTc) prolongation, and quetiapine. References were examined for additional articles related to antipsychotic drugs and the QT interval. Discussion: In this patient, the use of quetiapine was identified as a contributing factor in QT prolongation. Prior QT prolongation was experienced with ziprasidone, another SGA. The antidepressant and dose remained consistent throughout the inpatient course of treatment. Other risk factors in this patient included hypokalemia, dehydration, pneumonia, age, gender, and concurrent usage of an antidepressant. Dual psychiatric diagnoses, preexisting cardiovascular disease, and electrolyte disturbances may increase this risk potential. Conclusion: Psychiatric patients may be more at risk of cardiovascular complications, such as QT interval prolongation. The pharmacist can help evaluate risk factors and provide input into the care of all patients, particularly those identified as at risk.

Focal Segmental Glomerulosclerosis with Acute Renal Failure Associated with Eltrombopag Therapy

Eltrombopag, a small‐molecule nonpeptide agonist of the thrombopoietin receptor, is used for treatment of thrombocytopenia of various causes, including chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C‐related liver cirrhosis. During clinical trials, eltrombopag was discontinued in three patients due to ascites, neutropenia, and retinal exudates. Another recently reported major adverse event was reversible acute renal failure in a patient with antiphospholipid syndrome; nephrotoxicity caused by eltrombopag was highly suspected, but a kidney biopsy was not performed. We describe a 46‐year‐old woman with a history of mitral valve prolapse who had an incidental finding of an isolated low platelet count of 22 × 103/mm3. A tentative diagnosis of ITP was made, and oral prednisolone 25 mg twice/day was started. Despite prednisolone dosage adjustments over the next several weeks, her platelet count remained at 15–40 × 103/mm3, and oral eltrombopag 75 mg/day was begun. After seven doses, the patient came to the emergency department with persistent nausea and vomiting. Laboratory work‐up revealed renal failure, and eltrombopag was discontinued. The patient was hospitalized, and on day 2, her renal failure had progressed, and proteinuria was detected. On day 6, emergency hemodialysis was begun. A complete blood count on day 21 revealed progression of anemia and thrombocytopenia. Splenectomy was performed on day 35, which successfully reversed her thrombocytopenia. She was discharged on day 39, and hemodialysis was discontinued on day 44. At follow‐up on day 56, the patient's platelet count was within normal limits. On day 70, kidney biopsy results revealed a typical pattern of focal segmental and diffuse global glomerulosclerosis. By day 210, her ITP had resolved, and her renal function was stable. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of acute renal failure and eltrombopag therapy. To our knowledge, this is the first case report of a patient who experienced acute renal failure and proteinuria concomitant with a pathology of focal segmental glomerulosclerosis after treatment with eltrombopag. This report of a serious case of reversible renal failure after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before commencing with more extensive clinical use in the future.

Bupropion‐Induced Acute Generalized Exanthematous Pustulosis

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous reaction almost always associated with drug therapy. Antimicrobials, anticonvulsants, and nonsteroidal antiinflammatory drugs have the highest association with this adverse reaction, but numerous drugs have been implicated. We describe a 43‐year‐old woman with a history of major depressive disorder who was prescribed bupropion. Approximately 10 days after starting therapy, the patient noticed a rash with small, pustular, erythematous lesions on her arms and thighs. The lesions subsequently coalesced and spread further up her arms and onto her buttocks. Five days after onset of the rash, she came to the emergency department. The patient's symptoms included malaise and fever. She had no mucosal involvement, and laboratory analysis was largely normal except for neutrophilia. Biopsy of the pustules revealed focal, mild hyper‐ and parakeratosis, acanthosis, spongiosis with papillary edema, and exocytosis of neutrophils consistent with AGEP. Discontinuation of bupropion and supportive care resulted in significant improvement in all symptoms during the next 4 days, and the patient was discharged in good condition. This patient had both clinical and histologic findings consistent with AGEP. The European Severe Cutaneous Adverse Reactions (EuroSCAR) study scale suggested that this case was definitely caused by bupropion (score of 11), whereas the Naranjo adverse drug reaction probability scale suggested that this case was probably caused by the drug (score of 6). Treatment for AGEP is largely supportive, and most patients completely recover within 15 days of discontinuing the implicated drug. To our knowledge, this is the first reported case of bupropion‐induced AGEP Clinicians caring for patients taking bupropion should be aware of this rare but serious cutaneous adverse effect.

Psoriasis Induced by Losartan Therapy: A Case Report and Review of the Literature

Psoriasis is a papulosquamous disease of multifactorial etiology. A combination of genetic and environmental agents is implicated in its pathogenesis. A variety of triggers, including infection, stress, and medications, have been recognized as precipitants of this disease. Nonsteroidal anti-inflammatory drugs, beta-blockers, lithium, synthetic antimalarials, and gold are the most common drugs implicated in precipitating psoriasis. We report a patient with psoriasis induced by initiation of losartan therapy, which resolved with discontinuation of the drug. The Naranjo adverse drug reaction probability scale score indicated that the association between losartan use and psoriasis was probable.

Clarithromycin-induced hypersomnia in children

Two cases of hypersomnia in children caused by therapeutic doses of oral clarithromycin are presented. Clarithromycin-induced hypersomnia in children has not been reported before. A 4-year-old girl and 13-year-old boy received clarithromycin as monotherapy. The girl fell into a deep sleep after every dose of the antibiotic. The boy reported daytime sleepiness and prolongation of night-time sleep during the antibiotic therapy. In both cases the hypersomnia receded after cessation of clarithromycin therapy. The onset of hypersomnia after clarithromycin intake, its remission once the drug was stopped, and the absence of other possible causative factors favored the diagnosis of clarithromycin-induced hypersomnia, further supported by the scores on Naranjo's Adverse Drug Reaction Probability Scale in both cases. Clinicians evaluating children receiving clarithromycin and exhibiting suddenly changed behavior should keep in mind that the antibiotic can produce uncommon adverse reactions.

Montelukast‐Induced Anxiety in Two Pediatric Patients

Montelukast, a leukotriene receptor antagonist, is approved by the United States Food and Drug Administration (FDA) for the prophylaxis and long‐term treatment of asthma, prevention of exercise‐induced broncho‐constriction, and symptomatic relief of allergic rhinitis. In the literature, anxiety has been reported as being related to montelukast only in a retrospective analysis of clinical trial data and in surveillance studies. However, montelukast was associated with anxiety in 421 postmarketing MedWatch adverse event reports received by the FDA between 1998 and 2009. In 2009, a precaution was added to montelukast's package labeling regarding anxiety and other neuropsychiatric adverse events. We describe two pediatric patients with anxiety that manifested during montelukast therapy. The first patient was a 4‐year‐old, 16‐kg boy who experienced anxiety and sleep disturbances within 5 months of starting montelukast 4 mg at bedtime, which subsequently resolved 2 weeks after drug discontinuation. The second patient was a 6‐year‐old, 16.6‐kg girl who developed anxiety 3 weeks after her montelukast dose was increased from 4 mg to 5 mg at bedtime. Her symptoms resolved, without recurrence, within 4 weeks after the dose was reduced to the previously tolerated lower dose. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 3 [first patient]) and probable (score of 8 [second patient]) relationship between these patients' development of anxiety and montelukast therapy. Health care professionals should be aware of the potential for neuropsychiatric adverse effects with montelukast and should assess the need for continued therapy if anxiety is reported.

Levetiracetam‐Induced Acute Generalized Exanthematous Pustulosis

Antiepileptic drugs have been associated with many adverse effects, including different types of rashes; however, the frequency of rash varies among the drugs. The most common adverse effects associated with levetiracetam include somnolence, asthenia, headache, dizziness, and behavioral abnormalities. Until recently, rash had not been reported as an adverse effect of levetiracetam in adults. We describe a 45‐year‐old, African‐American woman who developed a desquamating rash after starting levetiracetam for a witnessed seizure. The rash improved after the drug was discontinued, but on rechallenge, the desquamating rash reappeared. The patient was hospitalized, levetiracetam was discontinued, and supportive care and treatment with triamcinolone 0.1% cream and oral prednisone were started. Her rash was biopsied, and she was diagnosed with drug‐induced acute generalized exanthematous pustulosis (AGEP). With topical and oral steroid treatment the patient's rash improved, and she was discharged on hospital day 4. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's development of AGEP and levetiracetam exposure. To our knowledge, this is the first case report of levetiracetam‐induced AGEP. Although levetiracetam is usually well tolerated, clinicians should be aware of this potential adverse drug reaction in patients who develop severe skin reactions while receiving this drug.

Antidepressant-Mediated Gastroesophageal Reflux Disease

Anticholinergic effects of medications are factors in autonomic control of the lower esophageal sphincter function. Changes in sphincter control often lead to gastroesophageal reflux disease (GERD), a chronic disease with a prevalence of up to 25% for adults. This effect is a consideration in the treatment of depression, the fourth-leading disease burden. Lower esophageal-sphincter changes are well documented in association with tricyclic antidepressants. The newer medications, selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, are often used as first-line agents. This case report reviews the emergence of GERD in association with the use of newer agents. The patient, a 55-year-old woman, presented to her primary care physician with complaints of low energy, dysphoric mood, and anhedonia of several months' duration. Trials of citalopram and escitalopram were associated with reports of persistent nausea and gastric reflux unresolved by changes in dosing schedule or positioning. Over-the-counter omeprazole on an as-needed basis was added. Ultimately, the patient was successfully managed with desvenlafaxine for dysphoric mood and low energy and scheduled administration of omeprazole for GERD. The adverse drug reaction was evaluated using the Naranjo Adverse Drug Reaction Probability Scale. This methodology indicated a probable relationship (score of 7 out of 12) between initiation of antidepressant therapy and the presentation of GERD symptoms. When evaluating patient response to medication, inquiring about new-onset symptoms may help assess pharmacotherapy, identify potential medication-related effects such as the anticholinergic profile, evaluate the need to add an antisecretory/antispasmodic agent, or consider an alternative treatment strategy.

Topical Podophyllum-induced Toxic Anterior Uveitis

Objective: To report a case of toxic anterior uveitis probably secondary to the use of topical podophyllum.Design: Case report, interventional.Methods: The authors present a 78-year-old male with acute anterior uveitis that developed within a couple of hours of application of topical podophyllum. In vivo confocal microscopy showed unique findings that disappeared following treatment with topical steroids alone. The patient reapplied podophyllum 2 months later and a recurrence of uveitis was noted.Results: A score of 7 was obtained using the adverse drug reaction probability scale, suggesting that the anterior uveitis is a probable adverse reaction to topical podophyllum.Conclusions: Anterior uveitis may occur after topical application of podophyllum.

Azithromycin-Induced Agitation and Choreoathetosis

We report a child who developed agitation and choreoathetoid movements with azithromycin therapy on 2 separate occasions. In both instances, the symptoms resolved when the antibiotic was discontinued. By means of the Naranjo adverse drug reaction probability scale, we classified this event as a probable adverse drug reaction (score of 6 points). To our knowledge, this is the first published case of azithromycin-induced agitation with choreoathetosis. Because this is a widely used medication for many common infectious conditions, including otitis media and pneumonia, this potential serious adverse reaction should be considered.

The DRESS Syndrome: The Great Clinical Mimicker

The life-threatening DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is characterized by the presence of at least three of the following findings: fever, exanthema, eosinophilia, atypical circulating lymphocytes, lymphadenopathy, and hepatitis. This syndrome is difficult to diagnose, as many of its clinical features mimic those found with other serious systemic disorders. This idiosyncratic reaction occurs most commonly after exposure to drugs such as allopurinol, sulfonamides, and aromatic anticonvulsants such as phenytoin, phenobarbital, and carbamazepine. We describe a 44-year-old woman who was brought to the emergency department with new-onset hemorrhagic stroke. She was admitted to the intensive care unit where she received supportive care that included clonidine and hydralazine for blood pressure control and phenytoin for seizure prophylaxis. On hospital day 21, the patient developed signs and symptoms of severe sepsis. Despite receipt of broad-spectrum antibiotics (vancomycin and piperacillin-tazobactam) and supportive care, the patient's clinical condition worsened with progressive jaundice, severe oliguria, and labile blood pressures. All cultures revealed no growth, and her chest radiograph remained clear. Several days after the onset of her fever, the patient developed several hematologic abnormalities including thrombocytopenia, with schistocytes present on a peripheral smear. She also had an elevated lactate dehydrogenase level. A provisional diagnosis of thrombotic thrombocytopenic purpura was made; however, the patient then developed severe facial edema, nearly global erythroderma, and severe exfoliative dermatitis. A punch biopsy of the skin was compatible with the DRESS syndrome. Phenytoin, vancomycin, and piperacillin-tazobactam were discontinued, and the patient was started on systemic corticosteroids, with rapid resolution of her fever and eosinophilia and progressive improvement in her skin rash and multiorgan system dysfunction. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of DRESS syndrome and treatment with phenytoin. Clinicians should have a high index of suspicion for the DRESS syndrome in patients being treated with aromatic anticonvulsants who develop a sepsis-like syndrome. Furthermore, considering the potential severe effects associated with phenytoin, the risks and benefits should be carefully evaluated before using this agent for seizure prophylaxis.

Citalopram-Induced Parkinsonian Syndrome

To draw attention on citalopram as a possible cause of movement disorders. Case report of a patient with sudden-onset bilateral parkinsonian syndrome after administration of citalopram. We describe a 67-year-old woman who developed sudden-onset bilateral rigidity, bradykinesia, resting and postural tremor, and typical parkinsonian gait 2 weeks after citalopram was administered. After discontinuation of citalopram, full recovery was observed, with a 4/108 score on the motor subscale of the Unified Parkinson Disease Rating Scale. Use of the Naranjo Adverse Drug Reactions Probability Scale indicated a probable (score of 8) adverse reaction of sudden-onset parkinsonism associated with citalopram consumption. Physicians should be aware of possible parkinsonism as adverse reaction in patient taking citalopram because recognition and appropriate management can enable proper treatment and prevent serious adverse outcomes.

Intraoperative anaphylaxis associated with bacitracin irrigation

Three cases of severe anaphylactic reactions associated with prophylactic bacitracin irrigation during cardiac procedures are describe. In all three cases, bacitracin irrigation was concentrated at 50,000 units per 10 mL and applied directly to the pacemaker pocket. The first case described involved an 88-year-old woman undergoing pacemaker insertion to correct bradycardia. Within 10 minutes of bacitracin irrigation, she lost consciousness and developed apnea, diffuse erythema, and hypotension. In the second case, a 69-year-old man receiving a cardiac resynchronization defibrillator implant developed apnea, hypotension, decreased pulse, erythema of the extremities, and a maculopapular rash within 15 minutes of bacitracin administration. The third case involved an 83-year-old woman undergoing a dual pacemaker battery change; she became agitated and was noted to have hypotension, anxiety, and other symptoms 8 minutes after bacitracin irrigation. Two of the three cases involved apnea and loss of consciousness, and all three patients developed erythema or rash. Application of the adverse drug reaction probability scale developed by Naranjo et al. yielded a score of 3 (indicating a possible adverse reaction to bacitracin) in all three cases. As in other published reports of anaphylactic reactions associated with bacitracin irrigation, development of hypotension within 15 minutes of bacitracin administration was the first sign of an adverse reaction in these cases. Three patients developed severe adverse reactions after prophylactic bacitracin irrigation, two during pacemaker insertions and one during a cardiac resynchronization defibrillator implantation.