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The Case Files is an anecdotal collection of emergency medicine cases to enable physicians and researchers to find clinically important information on unusual conditions.

Case reports should focus on:

    • Unusual side effects or adverse interactions.
    • Unusual presentations of a disease.
    • Presentations of new and emerging diseases, including new street drugs.
    • Findings that shed new light on a disease or an adverse effect.

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Tuesday, January 22, 2019


A 59-year-old Caucasian man with a past medical history of well-controlled hypertension, hyperlipidemia, and gout presented to the ED with altered mental status. His wife reported that he was found two hours earlier in his home office confused, unable to recall plans made that morning, the current time and date, and his brother's death a year and a half earlier. She stated that the patient was repeating, “I don't know what's happening,” while anxiously pacing around the room. She said he had a history of falls and head injury at age 7, which was accompanied by brief amnesia that had not recurred.

The patient could not remember any of the events from that morning. He was unsure of any falls or trauma that had occurred before. He had no fever, headache, dizziness, lightheadedness, nausea, vomiting, neck pain or stiffness, urinary incontinence, dysuria, weakness, slurred speech, or parasthesias of the extremities. The patient and his wife said he had no history of previous symptoms or seizures. His medications included amlodipine, allopurinol, and atorvastatin. No relevant family history was obtained. The patient did not use tobacco, alcohol, or illicit substances.

His physical examination on admission revealed a temperature of 98.2°F, a blood pressure of 187/101 mm Hg, a heart rate of 99 bpm, a respiration rate of 20 bpm, and oxygen saturation was 98% on room air. No jugular venous distension or carotid bruits were appreciated. His cardiac exam revealed a regular rate and rhythm. A neurologic exam showed the patient was oriented to person and place but not time. Extraocular movements were intact, and his pupils were equal, round, and reactive to light and accommodation. Strabismus of the left eye was noted (present chronically, according to the patient and his wife). Cranial nerves II-XII were grossly intact; no motor or sensory loss was noted in the upper and lower extremities. No abnormalities were observed during the finger-nose and heel-shin tests. Pronator drift was not seen. His NIHSS score was 1. No focal neurological deficits or seizure-like activity was observed.

The patient's comprehensive metabolic panel, complete blood count, coronary risk profile, and coagulation studies were within normal limits. An ECG revealed normal sinus rhythm. A head CT without contrast was performed and found no hemorrhage, acute territorial infarct, midline shift, or space-occupying lesion. A portable chest x-ray was performed and revealed no abnormalities. An MRI without contrast was performed and found no acute intracranial abnormality. An EEG revealed no focal or diffuse abnormalities. No epileptiform discharges were seen.

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Transient Global Amnesia

Transient global amnesia (TGA) is a benign memory disorder of the middle-aged and elderly populations that most commonly presents as temporary, short-term retrograde amnesia. The pathophysiology of this disorder frequently locates the primary site of involvement in the medial temporal lobe and hippocampus via neuroimaging. (J Clin Neurol2009;5[2]:74; Neurol 2005;4[7]:437.) The etiology, however, is unclear, although current hypotheses include migraine, seizure, transient cerebral artery ischemia, or cerebral venous congestion. (Lancet1998;352[9125]:397.)

Despite possible arterial etiology, vascular risk factors (hypertension, hyperlipidemia, diabetes) were shown in many cases to have no link with TGA. Of the many risk factors theorized, the most common finding was increasing age, followed by migraines, epilepsy, and psychogenic disorders. (Brain 2006;129[Pt 7]:1640.) One interesting theory involves venous congestion affecting the cerebral venous system, impeding venous return to the superior vena cava. After the Valsalva maneuver, acute emotional events, and cold water immersion, Doppler ultrasound studies demonstrated increased internal jugular vein reflux prevalence in TGA patients compared with controls. (UpToDate. Dec. 12, 2018;

Patients with TGA frequently present with disorientation and profound anterograde amnesia. They have intact immediate recall, but delayed recall is impaired, which leads to a broken-record phenomenon where the patient asks frequent, repeated questions about his environment and well-being. (Lancet Neurol 2005;4[7]:437.) The mean duration of episodes is approximately six hours and lasts no longer than 24 hours. (Neurology 1987;37[5]:733.) Patients often have no recollection of the event.

Our patient's memory gradually returned after six hours, and he was discharged after a 24-hour observation. He was not aware of the preceding events and was not in any distress following his return to baseline. Our patient was seen as an outpatient, and he stated that he had experienced two to three headaches in the week preceding the TGA. He described them as frontal headaches, which were short-lived, resolved without intervention, and did not raise concern at the time. He confirmed that he did not experience a significant stress event preceding the TGA.

The diagnostic workup for TGA should be focused on ruling out differential diagnoses such as seizures, cerebrovascular events, and metabolic encephalopathies. Typically, TGA presents as a focal event compared with other causes producing a more global presentation. (UpToDate. Dec. 12, 2018; An exclusion workup should be performed, including oxygenation, electrolytes, blood glucose, chemistry, and toxicology. Neuroimaging, specifically MRI with diffusion-weighted imaging, is the most accurate test to detect acute ischemic changes and hippocampal lesions. (AJNR Am J Neuroradiol 2012;33[9]:1771; Electroencephalogram can then be performed to exclude an epileptic event.

TGA is a rare neurological syndrome that affects an estimated 5.2 to 10 per 100,000 per year in the general population and an estimated 23.5 to 32 per 100,000 per year among those over 50, with a mean age of 61 at the first episode. (Acta Neurol Scand 1990;81[4]:358; Neurology 1987;37[5]:733.) The annual recurrence rate is estimated to be four to five percent and up to 24 percent for lifetime recurrence depending on the inclusion criteria. (Neurology 1987;37[5]:733.) Despite the chance of recurrence, patients are not at increased risk of developing complications related to TGA compared with the general population. TGA should be included in the differential of altered mental status in the absence of focal neurological deficits with a gradual return to baseline.

Mr. Demchuk is a fourth-year medical student at Spartan Health Sciences University and is currently rotating at Weiss Memorial Hospital in Chicago.

Tuesday, January 22, 2019


A 54-year-old man with a significant past medical history of atrial fibrillation and congestive heart failure presented to the ED with a chief complaint of difficulty walking. He was evaluated at an outside hospital two months earlier, and was found to have methicillin-resistant Staphylococcus aureus bacteremia, lower extremity cellulitis, and acute decompensated congestive heart failure (CHF). He clinically improved over one week, his autoimmune workup was negative, and he was discharged. He failed to follow up with nephrology, cardiology, and dermatology, and stopped taking his medications soon after discharge.

He presented to our ED with worsening lower extremity edema, dyspnea on exertion, worsening skin lesions for six months, and frequent nose bleeds for three days. The patient had no hematemesis, melena, hematochezia, no prior EGD, or colonoscopy. His medications were apixaban, digoxin, and furosemide.

His vitals on arrival were a temperature of 97.7°F, blood pressure of 196/92 mm Hg, heart rate of 97 bpm, respiratory rate of 32 bpm, weight of 487 pounds, and oxygen saturation of was 92% on room air. He had respiratory distress with conversational dyspnea and dried blood in the right nostril. Cardiopulmonary exam revealed an irregularly irregular rhythm and rales in the lung bases. His lower extremities had 3+ pitting edema with associated chronic venous stasis changes. His lymphadenopathy exhibited clear drainage with superficial ulcerations and no evidence of inflammation. His ECG revealed atrial fibrillation at 82 bpm with no acute ischemic changes.

Pertinent laboratory evaluations revealed a white blood cell count of 8.2, hemoglobin of 11.7 d/dL (baseline of 12 d/dL), mean corpuscular volume of 75, troponin of 0.08 ng/mL (0-0.04), BNP of 1664 pg/mL (0-100), hyponatremia of 128, hypokalemia of 3.5, BUN-to-creatinine ratio of 16:0.8, aspartate aminotransferase of 61 U/L (10-37 U/L), alanine aminotransferase of 56 U/L (9-47 U/L), alkaline phosphatase of 190 U/L (44-140 U/L), INR of 3.2, total bilirubin of 5.3 mg/dL (0.1-1.2 mg/dL), and direct bilirubin of 3.0 mg/dL (<0.3 mg/dL). His thyroid-stimulating hormone was within normal limits.

A chest radiograph demonstrated cardiomegaly, pulmonary vascular congestion, bilateral pleural effusions, and opacification over the right upper lobe, likely representing fluid trapped within the fissure. (Image A.) This constellation of findings was consistent with CHF. Ultrasound of the abdomen revealed mild hepatomegaly with no evidence of hepatic abnormality. CT of the abdomen and pelvis revealed prominent venous vasculature and diffuse anasarca. The patient was placed on BiPAP and given IV furosemide, and a nitroglycerine drip. Echocardiography showed an ejection fraction of 40%, right ventricular dysfunction, dilation, and pulmonary hypertension. His abnormal liver function tests and coagulopathy were suspected secondary to the congestive hepatopathy of CHF. He improved clinically and was admitted for acute decompensated heart failure.

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Image A.

By day five, his lower extremity skin lesions diffused to all extremities and resembled hemorrhagic bullae. He developed periorbital ecchymosis and sinusitis. The patient's erythrocyte sedimentation rate was elevated at 106 mm/hr, his c-reactive protein (CRP) was elevated at 20 mg/L, and he had a positive rheumatoid factor of 37 IU/mL (0-20). His clinical presentation suggested a type of vasculitis, but the serology and tissue evidence was lacking. The patient had a negative ANCA and proteinase 3 antibody at the outside hospital. His vitals remained stable and his congestive hepatopathy and coagulopathy improved.

Continuous Hemorrhage

On day six, his ecchymotic lesions had spread to the eyelids and nose, appearing as violaceous patches with vesicular formation, and a biopsy was done. That evening, his condition acutely worsened with altered mental status and respiratory distress. He appeared diaphoretic, lethargic, and minimally responsive, with coarse breath sounds bilaterally. He was intubated and started on broad-spectrum antibiotics for presumed acute hypoxic and hypercapnic respiratory failure secondary to health care-associated pneumonia.

CT head and brain scans without contrast were negative. (Image B.) We could not rule out underlying airspace disease. He continued to deteriorate and was subsequently placed on vasopressors. His laboratory evaluation was notable for new-onset hematuria. Repeat vasculitis workup revealed a C3 of 69 (79-152), C4 of 10 (16-38), and proteinase 3 (PR3) antibody of 171 (<20). He was started on 1 mg/kg corticosteroids with associated stress ulcer prophylaxis for granulomatosis with polyangiitis.

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Image B.

Blood cultures came back positive for Staphylococcus aureus on day nine. A punch biopsy was notable for leukocytoclastic vasculitis. His c-ANCA antibody was positive with a c-ANCA titer >1:160 (<1:20). Immunosuppressive medication was held in light of underlying septic shock. He was deemed too unstable for a kidney or lung biopsy. On day 10, he began hemorrhaging into his endotracheal tube, raising suspicion for diffuse alveolar hemorrhage or disseminated intravascular coagulation. His INR was now 2.6 from 1.87, lactate dehydrogenase was 411, and fibrinogen was 78 from 175. He was given fresh frozen plasma and cryoprecipitate, began six rounds of plasmapheresis, and underwent emergent bronchoscopy revealing diffuse hemorrhagic and friable mucosa. The next day the patient appeared temporarily stable.

He began hemorrhaging out of his mouth and orogastric tube on day 15, with immediate concern for gastrointestinal hemorrhage. The massive transfusion protocol was activated, and he underwent emergent EGD revealing a large duodenal bulb ulcer with an active bleeding visible vessel. (Image C.) He received 16 mL of epinephrine injection, balloon tamponade, and hemoclip placement x5. He remained on norepinephrine, vasopressin, octreotide, and a pantoprazole infusion. By day 17, he was exhibiting volume overload status post multiple blood products, refractory hyperkalemia, and worsening renal function (creatinine was now 3.7 from 1.2). Decision was made to proceed with modified sustained low-efficiency dialysis, but it was stopped secondary to hypotension. Later that day, he started hemorrhaging again from his orogastric tube. His family elected to terminally wean, and time of death was called minutes later.

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Granulomatosis with polyangiitis (GPA) is a rare multisystemic vasculitis affecting small- to medium-sized vessels. GPA is associated with necrotizing granulomatous inflammation that may affect the lungs, kidneys, skin, and rarely the gastrointestinal tract. This immune-mediated disorder can lead to extensive tissue damage through an initiating inflammatory event and a specific immune response. A group of autoantibodies termed ANCAs help diagnose GPA and similar forms of vasculitis. c-ANCAs, sensitive and highly specific for GPA, are directed against proteinase 3. (The Johns Hopkins Vasculitis Center.

This condition affects roughly three out of 100,000 people, occurring in men and woman equally. (An Bras Dermatol2015;90[3 Suppl 1]:101; Am Board Fam Pract 2003;16[6]:555.) GPA can occur at any age, but it most often occurs between 40 and 65. (J Periodontal Implant Sci 2015;45[6]:247;

GPA can present and progress slowly over months or explosively over days. The respiratory tract and kidney are often involved, though the serious complications can also involve the small and large bowels. The overall 10-year survival rate approaches 75 percent, but the degree of baseline organ damage and existing co-morbidities are markers of poor outcome, as our case demonstrated. (Rheumatology [Oxford] 2002;41[5]:572.)

A Must-Recognize Disease

GPA poses a significant diagnostic challenge given its diverse clinical presentations, from nonspecific constitutional complaints such as fever, weight loss, and fatigue to diffuse hemorrhage. (The Johns Hopkins Vasculitis Center. Common manifestations include conjunctivitis, necrotizing scleritis, chronic sinusitis, rhinitis, epistaxis, saddle nose deformity, petechiae/vesicles/hemorrhagic bullae, pulmonary infiltrates, hemoptysis, hematuria, and diffuse alveolar hemorrhage. (UpToDate. Nov. 26, 2018;

Diagnosing GPA is generally confirmed with a tissue biopsy; renal and lung biopsies are most specific. (Prz Gastroenterol 2016;11[4]:270; Tissue biopsies commonly reveal neutrophilic transmural inflammation of the vessel walls, as noted in our patient, termed leukocytoclastic vasculitis. (J Med Case Rep2014;8:297; Diabetic Foot Complications 2015;7[1]:1; A presumptive diagnosis can also be made if there is a high probability based on clinical findings, including a positive c-ANCA, alveolar hemorrhage, pulmonary nodules, or new-onset destructive rhinosinusitis, in combination with a low likelihood of another etiology. (The Johns Hopkins Vasculitis Center.; UpToDate. Nov. 26, 2018;; UpToDate. Jan. 4, 2017;

ANCA testing sensitivity varies depending on disease progression. c-ANCA has been shown to be most specific and PR3-ANCA most sensitive for GPA, approaching >90% in the setting of clear signs or symptoms. (J Med Case Rep2014;8:297; Diabetic Foot Complications 2015;7[1]:1; Initial ANCA testing for our patient was negative at his prior hospital, but his c-ANCA and PR3-ANCA came back positive later on day seven.

GPA can also present with anything from an ulcer or rash to fulminant multisystem failure. Severe potential complications include diffuse alveolar hemorrhage, gastrointestinal hemorrhage, or rapidly progressive glomerulonephritis, as our patient demonstrated, becoming fatal within days. Poorer survival has been associated with older age and baseline organ damage. Our patient had a significant past medical history and multiple co-morbidities in the setting of septic shock, contributing to his overall extremely high mortality rate.

If left untreated, GPA is fatal. Prednisone may slow the progression, but it is insufficient by itself and often requires the addition of an immunosuppressant like cyclophosphamide. (The Johns Hopkins Vasculitis Center. Our patient was started on monthly oral cyclophosphamide and daily prednisone given the septic shock and concern for worsening clinical status if daily cyclophosphamide was used.

Recognizing GPA is a true diagnostic challenge given its diverse clinical presentations. As a rapidly progressive and potentially fatal vasculitic process, GPA is a must-recognize disease.

Dr. Taylor is completing his emergency medicine residency at Beaumont Hospital in Farmington Hills, MI, a teaching hospital of Michigan State University, where Dr. Lagerveld is on staff as core faculty for the emergency medicine residency program and serves as the director of ultrasound.

Wednesday, January 16, 2019


An 18-year-old healthy man presented to the ED with a sore throat. He said the pain had started a day earlier when he took three capsules of Molly and drank heavily at a music festival.

The patient reported pain while swallowing, shortness of breath, and pain in his left rib cage after playing basketball a few days earlier. The patient had no jaw or neck pain, coughing, fever, chills, nausea, vomiting, and diarrhea. He had a blood pressure of 126/76 mm Hg, temperature of 98.2°F (orally), heart rate of 70 bpm, respirations of 18 bpm, and oxygen saturation of 100% on room air. The physical exam demonstrated an alert, awake, and oriented patient with evidence of tenderness in the left rib cage. There were no signs of abdominal tenderness, respiratory distress, or asymmetrical breath sounds. The lungs were clear bilaterally, and the heart sounds were normal.

The chest x-ray showed some linear air density streaks in the mediastinum. A CT with and without contrast revealed an extensive pneumomediastinum and considerable subcutaneous emphysema at the base of the neck, posterior right thoracic region, and left axillary area. The results were reviewed with the patient, but he signed out against medical advice after being told of the seriousness of his condition. The patient was advised to return if the condition worsened.

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CT of pneumomediastinum and subcutaneous emphysema.

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CT of pneumomediastinum.

Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative commonly abused by young adults. It is also known as Ecstasy, Molly, Adam, Doves, and Skittles. MDMA promotes social closeness, increases energy, alters sensations, and induces euphoria. The drug has a strong affinity for serotonin receptors and transporters, causing a release of serotonin and a decrease in its uptake at the synaptic clefts. Onset is 30-60 minutes with a duration of action of eight to 24 hours. As a sympathomimetic, the initial onset can produce an elevated heart rate and anxiety. The National Institute of Drug Abuse reported that 11.6 percent of adults 18-25 have taken MDMA at least once. (Sept. 26, 2017;

Ordinarily, the mean pressure in the mediastinum is more negative than the pressure in the pulmonary alveoli. In spontaneous pneumomediastinum, pressure differences rupture the alveoli, allowing free air to travel through the hilum. Air then spreads into the mediastinum by way of loose fascia.

Rare Complications

Pneumomediastinum and subcutaneous emphysema are rare complications of amphetamine use. The pathophysiology of pneumomediastinum after the use of amphetamines is unclear. Pharmacologically the link is yet to be determined between the stimulant and the leakage of air into the mediastinum. It is theorized that initially various mechanisms change the transmural pressure in the alveoli, which can cause rupture of the alveoli, leading to subcutaneous emphysema.

The free air then reaches the mediastinum by dissecting along the bronchovascular layers and fascial planes. Commonly the transmural pressure is changed in cases that involve mechanical ventilation, the Valsalva maneuver, or an extreme straining that occurs during strenuous coughing or vomiting. In this case, an initial increase in alveolar pressure could have arisen from strenuous dancing and vigorous activity and compounded by the surge in activity due to prolonged use of MDMA. A 2011 case report found a previously healthy military trainee developed spontaneous pneumomediastinum after repeatedly yelling “hooah” in a squad competition event. (Mil Med 2011;176[3]:352.)

The workup should begin with a chest x-ray to provide a definitive quantification of pneumomediastinum. It does not need to include a CBC, BNP, or CMP. Mild spontaneous pneumomediastinum is self-limiting. Patients can be managed conservatively with analgesia, rest, and by avoiding increased pulmonary pressure. Moderate to severe symptoms are treated with high-concentration oxygen, which will increase the nitrogen washout. A patient with underlying lung disease, however, should receive more aggressive measures to avoid absorptive atelectasis.

It is important to understand the multifaceted presentation, pathophysiology, management, and treatment of MDMA-induced subcutaneous emphysema and pneumomediastinum.

Ms. Bornia is a fourth-year medical student at the Windsor School of Medicine in Saint Kitts and Nevis who is rotating at Weiss Memorial Hospital with Dr. Malik, who is a board-certified emergency and internal medicine physician and the director of the emergency department at Weiss Memorial Hospital, an affiliate of the University of Illinois Hospital. The authors wish to thank Patrick Luft and Gowrishankar Manimaran for their review of this article.

Thursday, December 27, 2018


A 50-year-old man with hypertension presented to the emergency department with an exacerbation of his lower back and perianal pain that he had had for two weeks, with a new onset of active fecal draining and difficulty urinating for four hours. He said he had no headache, nausea, vomiting, weakness, fatigue, fever, and chills, and all other reviews of systems were negative.

His temperature was 98.5°F, blood pressure was 108/57 mm Hg, pulse rate was 113 bpm, respiratory rate was 20 bpm, and oxygen saturation was 97% on room air. His abdomen was soft, mildly distended, and not tender to palpation with normal bowel sounds. His rectum was edematous with indurated perianal tissue. Digital rectal exam was deferred due to draining stool.

Contrast-enhanced CT of the abdomen and pelvis was obtained, which revealed the presence of air within the bilateral ischiorectal fossa with air extending anteriorly into the right scrotum. (Photo.) Fluid was also present along the bilateral levator ani. A diagnosis of Fournier's gangrene was made.

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Contrast-enhanced CT of the abdomen and pelvis showing air extending into the right scrotum (shown in black).

The patient was promptly started on fluid resuscitation and triple antibiotics—piperacillin-tazobactam 3.375 g, metronidazole 500 mg, and vancomycin 1 g. Morphine 4 mg IV push was given for pain, and the patient was hospitalized for surgical debridement. He became stable and was discharged without any complications after six weeks of inpatient care.

A Fatal Infection

Fournier's gangrene is a polymicrobial infection, mainly anaerobic, that arises in the perianal, genital, or abdominal area, followed by the spread of infection in a matter of hours along the epidermis, dermis, subcutaneous tissues, fascia, and muscles, causing necrotizing fasciitis. (Urol Int 2018;101[1]:91; Trauma, impaired immunity as seen in diabetics, the HIV virus, and chemotherapy are possible causes of Fournier's gangrene. (J Emerg Med 2013;44[2]:e247.)

This case is unique because none of the above predisposing factors contributed to the development of Fournier's gangrene. Besides tenderness over the perianal area and new onset of mild fecal drainage, the clinical presentation showed no major evidence of systemic infection, necrotizing tissue, or subcutaneous crepitation. A case series analysis of inpatients with Fournier's gangrene who had a surgical debridement revealed a 20-40 percent mortality rate, with some as high as 88 percent. (Urol Int 2016;97[3]:249; The diagnosis would have been missed had a contrast-enhanced CT scan of the abdomen and pelvis not been performed, which would have led to sepsis and a fatal outcome in hours.

Determining Prognosis

The clinical presentation of Fournier's gangrene varies from anorectal or genital pain with little evidence of cutaneous necrosis to a rapidly spreading necrosis and systemic sepsis without any suspicious source of infection.

Methods commonly used to diagnose Fournier's gangrene are radiography, ultrasound, computed tomography, and magnetic resonance imaging. A semi-quantitative way of estimating the risk of developing a necrotic infection (the laboratory risk indicator for necrotizing fasciitis, or LRINEC) is based on the assessment of six laboratory considerations, including the number of leukocytes, value of hemoglobin, sodium, glucose, serum creatinine, and C-reactive protein. A score of 6 was recorded in this patient. A LRINEC score of 5 suggests a favorable outcome, compared with a score of 10 pointing to a lethal outcome. (Scand J Trauma Resusc Emerg Med 2017;25[1]:28;

Patients must receive prompt fluid resuscitation, triple antibiotic therapy, and pain control. Cultures should also be obtained to define the causative organism and determination of sensitivity to antibacterial drugs. (Urol Int2018;101[1]:91;

Septic shock is the most common cause of death. Prognostic factors of unfavorable outcomes for Fournier's gangrene include tissue damage beyond the perineum, severe sepsis, pulse over 90 bpm, leukocytes more than 20 × 109/L, and urea level equal to 7 mmoL/L. (Changgeng Yi Xue Za Zhi 1999;22[1]:31.) Management of Fournier's gangrene should be aggressive. Detection of gas in deeper soft tissues is considered an absolute indication for surgical intervention. (Surg Today 2007;37[7]:558.)

Ms. Polat is a fourth-year medical student completing her clinical rotations at Weiss Memorial Hospital in Chicago, IL. Dr. Malik is a board-certified emergency and internal medicine physician and the director of the emergency department at Weiss Memorial Hospital and an affiliate of the University of Illinois Hospital.

Wednesday, December 12, 2018


A 34-year-old man presented with intermittent fever and body aches for 10 days. He had been visiting family in India, and the symptoms began when he returned home. His fever had been as high as 104°F, and he was experiencing nausea, two episodes of bilious emesis, body aches, nonspecific abdominal pain, and multiple episodes of watery, nonbloody diarrhea.

He said he knew of no tuberculosis exposure or ill contacts, and he was current on his routine influenza and hepatitis A vaccines. His temperature was 101.4°F (he had taken acetaminophen three hours earlier), blood pressure was 98/52 mm Hg, heart rate was 125 bpm, respiratory rate was 21 bpm, and oxygen saturation was 100% on room air. The patient appeared pale and ill but in no acute distress. His oral mucosa were dry, and he was tachycardic.

His lungs were clear, and his abdomen was soft and nonperitoneal with tenderness to palpation in the epigastric region and right upper quadrant. Evidence for meningeal signs was negative, and we suspected sepsis given his clinical presentation. Fluid resuscitation was initiated with 30 cc/kg, and blood cultures, a malaria screen, a peripheral smear, parasites, and stool culture were performed. He was empirically started on 2 gm ceftriaxone IV daily for suspected typhoid, deferring malaria treatment until confirmed.

The patient had a leukopenia of 2.6, RBC count of 3.71, hemoglobin of 12.7 d/dL, a mean corpuscular volume of 80, and a platelet level of 79 bil/L (150-400 bil/L) with evidence of pancytopenia. A basic metabolic panel revealed a hyponatremia of 130, hypokalemia of 3.2, bicarbonate of 21, increased blood urea nitrogen of 31 mg/dL, creatinine of 1.1 mg/dL (baseline of 0.8 mg/dL), and blood glucose of 121. The hyponatremia, hypokalemia, and prerenal azotemia were likely secondary to diarrhea and dehydration.

A hepatic function panel revealed a slightly elevated alkaline phosphatase of 111 U/L, aspartate aminotransferase of 143 U/L, alanine aminotransferase of 68 U/L, and a total bilirubin of 1.5 mg/dL. His lactic acid was 2.8. A hemolytic anemia workup was initiated, resulting in an INR of 1.5, PTT of 38.2, fibrinogen of 250, haptoglobin <8, and a lactate dehydrogenase of 1109. The remaining laboratory evaluation, including an acute hepatitis panel, was unremarkable.

Post-fluid resuscitation, the patient's tachycardia resolved, he was normotensive, and a two-hour repeat lactic acid was normal at 0.8. A urinalysis revealed cloudy urine, positive for ketones, and 1+ blood. An ultrasound of the right upper quadrant revealed gallbladder sludge with mild wall thickening but no evidence of infectious or inflammatory process, with an overall unremarkable ultrasound.

The patient was admitted, and he remained intermittently febrile up to 102.7°F with rigors and chills. His fibrinogen decreased to 213 from 250, and laboratory evaluation showed disseminated intravascular coagulation. Blood cultures were positive for gram-negative bacilli, and stool culture was positive for Salmonella typhi.

The patient had improved by day six, and his leukopenia and thrombocytopenia had resolved. A day later, he was discharged on levofloxacin 500 mg daily for seven days, antiemetics, antacids, and diphenoxylate-atropine. A month later, he had resumed daily activities and had no symptoms.

Starting Treatment

Enteric fever, also called typhoid fever, can be a severe life-threatening illness with most cases acquired through international travel. This multisystem disease has many clinical manifestations and hematologic abnormalities, ranging from abdominal pain and fever to anemia, eosinopenia, leukopenia, thrombocytopenia, and disseminated intravascular coagulation.

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Typhoid and paratyphoid fevers are acquired by ingestion of fecal-contaminated food or water. These organisms survive the gastric acid of the stomach, enter the small intestine, penetrate the epithelial layer, and ultimately disseminate through a hematogenous route or lymphatic route. (UpToDate, July 7, 2017;; UpToDate, Nov. 27, 2017; Infection results in septicemia with blood cultures being the mainstay for the diagnosis. Stool cultures are often negative the first week of the illness.

Enteric fever has an incubation period of six to 30 days, and present with increasing fever, fatigue, malaise, headache, and a temperature as high as 104°F by the fourth day of the illness. Abdominal pain develops the second week, with symptoms including nausea, vomiting, and diarrhea. Hepatosplenomegaly is evident the third week, along with possible intestinal hemorrhage and perforation secondary to necrosis of the Peyer's patches. The majority of patients will have an anemia with leukopenia and a left shift.

Intestinal perforation with peritonitis should be considered the third week if leukocytosis is noted. Abnormal liver function studies are also typically seen, but it can be a diagnostic challenge to distinguish Salmonella hepatitis from viral hepatitis. One study of 27 patients with Salmonella-associated hepatitis and 27 patients with viral hepatitis found that serum aminotransferases tended to be lower with a peak of 296 for Salmonella hepatitis compared with a peak of 3234 with viral hepatitis. (UpToDate, Nov. 27, 2017;

Another study of 20 patients with positive blood cultures for Salmonella typhi found DIC in a subclinical form in eight patients, defined as a lower normal fibrinogen in the absence of liver disease and a low platelet count with prolonged PT/PTT but without bleeding diathesis. (Trop Doct 1995;25[4]:156.) The anemia typically does not need to be treated because it is related to endotoxemia and will improve during recovery. Overall, the most common clinical findings are leukopenia and eosinopenia, compared with the leukocytosis often exhibited in malaria.

Dengue fever can mimic typhoid fever in the early stages with leukopenia, and it tends to have eosinophilia. A relative bradycardia, rose-colored macules on the trunk and abdomen, and a pulse-temperature dissociation also raise suspicion for typhoid fever. Patients with severe enteric fever may develop altered mental status, delirium, and confusion, termed typhoid encephalopathy, that has a mortality rate of 10-55 percent. (UpToDate, Nov. 27, 2017;

Fluoroquinolones are recommended, though resistance is up to 80 percent in travelers returning from Southeast Asia. Third-generation cephalosporins are recommended when resistance is suspected. (CDC, May 31, 2017;

Dr. Taylor, top left, and Dr. Taecker are emergency medicine residents at Beaumont Hospital in Farmington Hills, MI, a teaching hospital of Michigan State University. Dr. Zelenka-Joshowitz is an emergency physician and core faculty for the emergency medicine residency at Beaumont Hospital, Farmington Hills, MI, and a clinical instructor at Michigan State University.