key: cord-0690470-zm9f0h27 authors: Simon, Erica; Long, Brit; Koyfman, Alex title: Clinical Mimics: An Emergency Medicine–Focused Review of Influenza Mimics date: 2017-02-16 journal: J Emerg Med DOI: 10.1016/j.jemermed.2016.12.013 sha: bfa186b44bf41d59d7aac68cf65d38b46d1c867a doc_id: 690470 cord_uid: zm9f0h27 BACKGROUND: Influenza viruses are a significant cause of morbidity and mortality in the United States. Given the wide range of symptoms, emergency physicians must maintain a broad differential diagnosis in the evaluation and treatment of patients presenting with influenza-like illnesses. OBJECTIVE: This review addresses objective and subjective symptoms commonly associated with influenza and discusses important mimics of influenza viruses, while offering a practical approach to their clinical evaluation and treatment. DISCUSSION: Influenza-like symptoms are common in the emergency department (ED), and influenza accounts for > 200,000 hospitalizations annually. The three predominant types are A, B, and C, and these viruses are commonly transmitted through aerosolized viral particles with a wide range of symptoms. The most reliable means of identifying influenza in the ED is rapid antigen detection, although consideration of local prevalence is required. High-risk populations include children younger than 4 years, adults older than 50 years, adults with immunosuppression or chronic comorbidities, pregnancy, obesity, residents of long-term care facilities, and several others. The Centers for Disease Control and Prevention recommends treatment with neuraminidase inhibitors in these populations. However, up to 70% of patients with these symptoms may have a mimic. These mimics include infectious and noninfectious sources. The emergency physician must be aware of life-threatening mimics and assess for these conditions while beginning resuscitation and treatment. CONCLUSIONS: The wide range of symptoms associated with influenza overlap with several life-threatening conditions. Emergency physicians must be able to rapidly identify patients at risk for complications and those who require immediate resuscitation. Emergency physicians play a significant role in the evaluation, diagnosis, and treatment of viral respiratory illnesses. Fever, headache, cough, and complaints related to the throat are among the 10 most commonly cited reasons for patient presentation to United States (US) emergency departments (EDs) (1) (2) (3) . From 2007 to 2009, approximately 1.3 million individuals experiencing the symptoms mentioned were assigned a formal diagnosis of influenza by an emergency physician (1) (2) (3) (4) . Each year, nearly 220,000 patients require hospitalization secondary to influenza; an infection with a mortality rate of 1.4 deaths per 100,000 laboratory-confirmed cases (5, 6) . Influenza A, B, and C, named for their respective viral surface proteins, are single-stranded ribonucleic acid viruses belonging to the Orthomyxoviridae family (7) (8) (9) . While all of the influenza viruses possess the capability for human infectivity, influenza types B and C are primarily responsible for the majority of illness observed in the human population (8, 9) . Of the influenza viruses, only influenza A (commonly affecting birds, horses, swine, and dogs) is characterized by subtype based on the composition and morphology of its envelope glycoproteins (7, 8) . Influenza viruses are unique in their ability to generate antigenic variability. Minor (antigenic drift) and major (antigenic shift) genomic changes are responsible for several historical and recent influenza epidemics and pandemics (7) (8) (9) . Given the socioeconomic cost associated with influenza infection (annual direct costs of care estimated as $4.6 billion, with approximately $7 billion lost to sick days/productivity), primary prevention remains a significant public health concern (10). Risk factors predisposing to a severe clinical course include extremes of age, numerous medical comorbidities, and pregnancy; therefore, the Centers for Disease Control and Prevention (CDC) has published recommendations for influenza vaccination, as detailed in Table 1 (11, 12) . Influenza is a respiratory virus primarily transmitted by aerosolized viral particles. Infection by influenza A subtypes can occur through direct contact with an infected animal, exposure to contaminated environment, or ingestion of inadequately prepared food stuffs (7) . Upon failure of host immunologic defenses (immunoglobulin A secretory antibody and mechanical respiratory mucociliary clearance), influenza viruses invade columnar respiratory epithelium, triggering a molecular cascade responsible for the inactivation of host-cell protein synthesis (9, 13, 14) . Local destruction of respiratory epithelium, resulting in the release of pro-inflammatory cytokines, in addition to viral invasion of polymorphonuclear leukocytes, lymphocytes, and monocytes, are responsible for systemic symptoms (9, 15) . Table 2 discusses the affected systems in infection. Signs and symptoms of influenza commonly begin after a 1-to 2-day incubation period and are highly variable (7) (8) (9) (10) . The majority of adolescent and adult patients present with complaints of fever, headache, myalgias, malaise, anorexia, rhinorrhea, pharyngitis, cough, and chest discomfort (9, 10) . Abdominal pain, nausea, and emesis are also commonly reported among the pediatric population (15) . At the extremes of age, influenza can manifest as malaise, lethargy, or altered mental status (9, 13) . While symptoms of influenza may be caused by a number of respiratory viruses (respiratory syncytial virus, parainfluenza virus, adenovirus, rhinovirus, and coronavirus), in the setting of a local outbreak, the accuracy of clinical diagnoses in healthy adolescent and adult patients approximates 80%-90% (9, 23, 24) . It is recommended that confirmatory testing be performed in all populations at high risk for complications secondary to infection (see Table 1 ) and in closed settings in which an influenza outbreak is suspected (e.g., long-term care facilities, inpatient treatment centers) (9, 25) . Methods for influenza detection include antigen detection (rapid influenza diagnostic tests [RIDTs]), direct immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), viral culture, and serology (9, 26) . Ideally, samples should be obtained within 4-5 days after the onset of symptoms, before the decline in viral replication and shedding (9) . Processing time varies according to laboratory and manufacturer. The majority of RIDTs provide results within approximately (27) . Direct immunofluorescence testing, RT-PCR, and viral culture require clinical laboratory handling, with processing time ranging from 1-8 h (direct immunofluorescence and RT-PCR) to 3-10 days (rapid viral culture and traditional viral culture) (9, 26) . While individual sensitivities of the 26 Food and Drug Administrationapproved RT-PCR assays vary, several studies have demonstrated the superiority of RT-PCR in the detection of influenza viruses, making it the gold standard for diagnostic evaluation (28) (29) (30) . Serologic testing allows for the retrospective confirmation of influenza infection, rendering it of little diagnostic utility in the emergency setting (9) . In the majority of immunocompetent individuals, influenza is self-resolving and does not require treatment (9) . In persons who are at high risk for influenza complications, however, initiation of antiviral therapy can significantly reduce morbidity and mortality (9, 30) . Populations in which antiviral treatment is recommended are detailed in Table 1 (31) . Doubleblinded, placebo-controlled studies of influenza antiviral agents reported a mean reduction in febrile influenza Influenza infection can result in direct damage to the thalamus, tegmentum, or cerebellar medulla, resulting in encephalopathy, seizures, or coma. Cellular dysfunction in the setting of viral-associated apoptosis has also been associated with myelitis, Guillain-Barré syndrome, and encephalitis. Reye syndrome can occur in the setting of aspirin administration (9, 17) . Cardiovascular Pericarditis and myocarditis are uncommonly associated with influenza A and B infections (9, 18) . Patients with influenza can experience emesis and diarrhea. Although the pathophysiology of this infectious manifestation is poorly understood, researchers hypothesize a role for the hematogenous spread of infected lymphocytes (19) . Hematologic Leukocytosis is a common cell-mediated immune response to influenza infection. In patients with a white blood cell count >15,000/mm 3 (15 Â 10 9 /L) with or without a left shift, pneumonia, or secondary bacterial infection should be suspected (20, 21) . Myositis and myoglobinuria are frequently observed in the pediatric population and associated with elevated serum creatinine phosphokinase levels (9, 22) . Meningitis and encephalitis may present with fever, neck stiffness (lower sensitivity in the elderly), headache, myalgias, or change in mental status (54) . In the setting of bacterial meningitis, empiric antibiotic therapy should not be delayed for imaging or LP. (Continued ) Dexamethasone should be given to all patients > 1 month of age to reduce neurologic sequelae (0.5 mg/kg, max 10 mg per dose every 6 h). 55 Consider antibiotic prophylaxis for close contacts. Acyclovir if suspicion for viral encephalitis. Epidural abscess: broad-spectrum antibiotic therapy. Consult neurosurgery as soon as the diagnosis is suspected. Laboratory studies: anemia, thrombocytopenia, transaminitis, elevated lactate. Polymerase chain reaction (PCR) and serology utilized for definitive diagnosis. Yellow fever: Endemic to Africa and Central America, rarely occurring in unvaccinated American travelers (61) . Presentation ranges from subclinical infection to systemic disease (fever, jaundice, hemorrhage, and renal failure). Laboratory studies: anemia, thrombocytopenia, transaminitis. Serology utilized for definitive diagnosis. Transaminitis is proportional to the severity of the disease: peak observed early in the second week of illness in patients who recover (61). Zika virus: Flavivirus closely related to dengue. Unlike other arboviruses, Zika virus may also be transmitted through sexual contact and bodily secretions. Initially isolated to Brazil and Micronesia, local outbreaks have been reported in Florida. Symptomatic patients (only 20% of those infected) may report headache, arthralgias, and fever. A strong association between maternal Zika virus infection and fetal malformations has been identified (61). Diagnosis: PCR and serology. Chikungunya: Prevalent throughout Africa and Asia, the first case identified in the United States was reported in Florida. Patients are most often symptomatic and report high-grade fevers with disabling arthralgias. Migratory polyarthritis with joint effusions (wrists, fingers, ankles) is common. Vesiculobullous eruptions and ulcers may be present (58) . Malaria: Affects 0.6/100,000 population per year in the United States, with nearly all cases occurring in the setting of recent travel (63, 64) . Dengue: initiate treatment based on clinical suspicion and travel history (supportive care, consideration of transfusion as appropriate). Yellow fever: supportive care. Extremes of age associated with increased lethality of the illness. Zika: Most commonly a self-resolving illness. Pregnant patients in whom Zika virus infection is a concern should undergo serial ultrasounds (every 3-4 weeks) to identify potential anatomic abnormalities (62) . Women of child-bearing age who are presumed to be infected with Zika virus should abstain from unprotected intercourse until 8 weeks after resolution of symptoms (62) . Zika virus has been associated with the development of Guillain-Barré syndrome. Chikungunya: Most often self-resolving. The majority of patients do not require admission. Rarely, neurologic complications including seizures, meningo-encephalitis, and encephalopathy may occur (more common in children) (58) . Malaria: If suspected, begin treatment with chloroquine or mefloquine, depending on geographical region of infection, immediately to avoid complications (cerebral malaria, renal failure, pulmonary edema, hemolysis, and splenic rupture) (63). If P. vivax or P. ovale are identified, chloroquine treatment should be followed by primaquine to eradicate the hypnozoite form. (Continued ) Genitourinary infections (73, 74) High fever, abdominal pain, and nausea are the hallmarks of tubo-ovarian abscesses (TOAs) and salpingitis. The majority of TOAs result from salpingitis, both predominately associated with exposure to sexually transmitted infections (STIs) (gonorrhea and chlamydia) (74) . History taking should include queries regarding concern for exposure to STIs, history of STI treatment, and multiple sexual partners, as these are associated with increased risk of salpingitis and subsequent TOA (73, 74) . Parenteral i.v. antibiotic therapy is indicated in patients with suspected salpingitis/TOA and should be continued until the patient is asymptomatic, has been afebrile for 24-48 h, and laboratory studies demonstrate resolution of leukocytosis (73) . (Continued ) illness of 1-1.6 days compared with placebo when therapy was initiated within 48 h of symptom onset (32) (33) (34) (35) . For patients at risk of influenza complications presenting within 48 h of symptom onset, the CDC recommends treatment during the 2016-2017 influenza season as detailed in Table 3 (36) . Two antiviral classes are commonly utilized in the treatment of influenza. The neuraminidase inhibitors oseltamivir (TamifluÓ), zanamivir (RelenzaÓ), and peramivir (RapivabÓ) inhibit viral aggregation and release of infectious nucleic acids to nearby host cells, therefore limiting infection (9, 36) . Amantadine (SymmetrelÓ) and rimantadine (FlumadineÓ), M2 inhibitors, are responsible for halting viral replication by inhibiting the release of infectious viral nucleic acids into host cells (9, 36) . Although amantadine and rimantidine have previously been utilized in the treatment of influenza, the CDC does not recommend their use for the 2016-2017 influenza season because of viral resistance (36) . Individuals to be considered for chemoprophylaxis include family and close contacts of persons with suspected or confirmed cases of influenza at high risk for complications secondary to influenza infection, but have not been vaccinated against influenza strains circulating at the time of exposure (37, 38) . In randomized, placebo-controlled trials, oseltamivir and zanamivir were efficacious in the prevention of influenza among persons administered chemoprophylaxis after exposure to a household member of close contact with laboratory confirmed influenza (oseltamivir 68%-89%, zanamivir 72%-82%) (37) (38) (39) (40) (41) . Chemoprophylaxis should continue for no longer than 10 days after the most recent exposure (see Table 3 for chemoprophylaxis recommendations) (42) . Current studies indicate that up to 70% of patients presenting with influenza-like illnesses are not infected with the influenza virus (37) . Tables 4 and 5 address clinical conditions that commonly present as an influenza-like illness, along with diagnostic and treatment pearls and pitfalls. Identifying individuals infected with the influenza viruses, specifically those at risk for adverse outcomes secondary to infection, is paramount in limiting the morbidity and mortality associated with influenza. Due to the extensive variability of influenza symptoms, and Laboratory studies often reveal a leukocytosis > 20,000/mm 3 . Imaging: Ultrasound or CT with i.v. contrast are both highly sensitive for the diagnosis of TOA and salpingitis (73). (75, 76) Characterized by fever, tachydysrhythmias, diaphoresis, nausea, vomiting, confusion, and delirium. In patients with known thyroid disease, thyroid storm may occur in the setting of trauma, infection, pulmonary embolism, myocardial infarction, and diabetes ketoacidosis. Even when promptly recognized, mortality is estimated as 20%-30% (75) . Burch & Wartofsky Diagnostic Criteria may be utilized for diagnosis (76) . Evaluation: Obtain thyroid-stimulating hormone and free thyroxine levels. Treatment includes: b-blockade, systemic corticosteroid therapy, administration of thionamides, and iodine. Supportive care with fluid resuscitation, external cooling methods as indicated. Consider antibiotic therapy, as sepsis or infection (pulmonary source most common) is the most likely underlying trigger. Pulmonary embolism (PE) (77, 78) Dyspnea is reported as the earliest symptom of PE, and tachypnea the earliest sign. Patients may report pleuritic chest pain, fever, and hemoptysis. Evaluation: Perform a thorough history and examination utilizing the Wells Criteria or Revised Geneva score for risk stratification (78) . Chest x-ray study and electrocardiogram (ECG) are commonly nonspecific. Echocardiography may be used for rapid triage in the unstable patient (evidence of right ventricular strain), as well as risk stratification. Utilize D-dimer and PERC (Pulmonary Embolism Ruleout Criteria) as appropriate. computed tomography (CT) pulmonary angiography remains the gold standard for diagnosis (sensitive and specific for emboli localized to the main, lobar, and segmental pulmonary arteries) (78) . Anticoagulate as indicated. (86) . CVST: Heparin often administered. An extended-spectrum penicillin and third-generation cephalosporin should be utilized if concern for infectious etiology (88) . VST: anticoagulation is the primary treatment. Thrombolectomy or thrombolysis may be required (90) . Intestinal ischemia (92) (93) (94) Abdominal pain out of proportion to examination in addition to nausea, emesis, and diarrhea may be presenting signs. Risk factors: hypotension, afib, severe cardiovascular disease, and recent MI. Mesenteric ischemia may occur secondary to: acute arterial embolus, acute arterial thrombosis, venous thrombosis, and nonocclusive mesenteric ischemia. Mortality is estimated as ranging from 63% to 100% (93) . Evaluation: No laboratory study is sensitive or specific to exclude the diagnosis of bowel ischemia (92) . Leukocytosis and elevated lactate often noted on laboratory analysis (92) . Imaging: CT angiography is sensitive (74%-100%) and specific (100%) for the diagnosis of mesenteric ischemia (94) . Initiate fluid resuscitation and oxygen supplementation as necessary. Administer broad-spectrum antibiotics. Anticoagulation often required. Consult surgery as soon as the diagnosis is suspected (early angiography and surgical intervention improve mortality). that the influenza virus circulates concurrently with other respiratory viruses, the emergency physician must be acutely aware of influenza mimics and their evaluation and treatment (97,98). 1. The assessment of a patient presenting with fever, headache, chills, myalgias, sore throat, and influenza-like symptoms (or in the case of the pediatric patient: decreased appetite, decreased per os tolerance, or decreased urinary output) begins with evaluation of airway, breathing, and circulation (3). A definitive airway should be obtained in all toxicappearing patients with signs of impending airway compromise including stridor, ''hot potato voice,'' trismus, seated in the tripod position, or in those presenting with an inability to protect their airway (altered mental status) (70) . An assessment of systemic inflammatory response syndrome criteria should be performed, and diagnostic testing ordered as appropriate, given the physician's clinical suspicion regarding the etiology of the systemic illness. Potential studies include a complete blood count, serum electrolytes, urinalysis, chest x-ray study, blood cultures, and lactate. If sepsis is suspected, the provider should initiate fluid resuscitation to improve peripheral perfusion and administer broad-spectrum antimicrobials (44-46,98). 2. After initial resuscitation and stabilization of the toxic-appearing patient, a focused history and examination allows for the development of a differential diagnosis based on targeted questioning regarding immunization status, medical comorbidities, daily medication use, sexual practices, and recent travel (e.g., high-risk areas for mosquitoborne illness, such as Southeast Asia, Africa, South/Central America). A determination regarding the requirement for adjunct testing and advanced imaging (point-of-care blood glucose, respiratory viral panel, serology, peripheral smear, head noncontrast computed tomography [CT], abdomen/pelvis CT) can then be made. 3. In the nontoxic, immunocompetent adolescent or adult patient, the clinical diagnosis of influenza is accurate in up to 90% of cases (23, 24, 97) . Patients, or caregivers of patients older than 1 month of age, presenting for evaluation and treatment within 48 h of symptoms onset should be counseled about the benefits (reduced duration of illness up to 1.6 days), and common side effects (gastrointestinal upset) of antiviral therapy (31) (32) (33) 35 Table 3 ), confirmatory testing for influenza should be performed. RIDT has a sensitivity of 50%-70% and specificity > 90%, and testing should be interpreted in terms of the community prevalence of influenza infection (9, 26) . The utility of performing direct immunofluorescence and RT-PCR testing in the ED may be limited by required laboratory processing times (1-8 h) (9, 26) . RT-PCR is recognized as the gold standard for the definitive diagnosis of influenza (28) (29) (30) 97) . In approaching the patient with influenza-like symptoms, the emergency physician must make a determination regarding the severity of illness. Identification of the need for immediate airway management and resuscitation is paramount. Any concern for an infection other than influenza, such as pneumonia, warrants antimicrobials and fluid resuscitation. Ultimately, a thorough history and physical examination allow for the directed performance of evaluation and treatment. Fever, headache, cough, and sore throat-a myriad of chief complaints associated with influenza and influenza-like illnesses-represent the most common reasons for presentation to US EDs (3) . Given the significant overlap in the presenting signs and symptoms of influenza and influenza mimics, and the plethora of infectious and noninfectious influenza mimics, the emergency physician must be able to quickly identify patients as toxicappearing or non-toxic-appearing, perform initial resuscitation as appropriate, and collect an adequate history and perform a physical examination to determine necessary methods for patient evaluation and treatment. Deaths: final data for 2014 Emergency department visits. National Center for Health Statistics A national study of the impact of rapid influenza testing on clinical care in the emergency department Influenza-associated hospitalizations in the United States First Consult Henry's Clinical Diagnosis and Management by Laboratory Methods Influenza (including avian influenza and swine influenza) The National Institute for Occupational Safety and Health. Seasonal influenza (flu) in the workplace Vaccination: who should do it, who should not and who should take precautions. National Center for Health Statistics People at high risk for flu related complications Individual expression of the influenza virus PA protein induces degradation of coexpressed proteins Apoptosis: a mechanism of cell killing by influenza A and B viruses The pathology of influenza virus infections Vaccination: clinical signs and symptoms of influenza Influenza virus associated encephalopathy Myocarditis with influenza B infection Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance and pathophysiology of human influenza fecal samples: what do we know Harrison's Principles of Internal Medicine An office-based approach to influenza: clinical diagnosis and laboratory testing Bacterial, fungal, parasitic, and viral myositis Predicting influenza infections during epidemics with use of a clinical case definition Clinical signs and symptoms predicting influenza infection Rapid identification of nine microorganisms causing acute respiratory tract infections by single-tube reverse transcription-PCR: feasibility study Guidance for clinicians on the use of RT-PCR and other molecular assays for the diagnosis of influenza virus infection Rapid diagnostic testing for influenza: information for clinical laboratory directors FDA-cleared RT-PCR assays and other molecular assays for influenza viruses Comparison study of real-time reverse transcription polymerase chain reaction assay with an enzyme immunoassay and shell vial culture for influenza virus detection in adult patients Utility of reverse transcriptase PCR for rapid diagnosis of influenza a virus infection and detection of amantadine-resistant influenza a virus isolates Influenza antiviral medications: summary for physicians The treatment of influenza with antiviral drugs Evaluation of therapeutic efficacy of amantadine in patients with naturally occurring A2 influenza Therapeutic effect of amantadine HCl and rimantadine HCl in naturally occurring influenza A2 respiratory illness in man Recovery of drug-resistant influenza A during therapeutic use of rimantadine Centers for Disease Control and Prevention. Guidance on the use of influenza antiviral agents Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season Centers for Disease Control and Prevention. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). Available at Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. GG167 Study Group Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial Prolonged viral shedding in pandemic influenza A H1N1: clinical significance and viral load analysis in hospitalized patients American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis The third international consensus definitions for sepsis and septic shock (Sepsis-3) Emergency management of severe sepsis and septic shock s Principles and Practice of Infectious Diseases Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes-proceedings of the HCAP summit s Principles and Practice of Infectious Diseases Bacterial pericarditis in infancy and childhood Infective endocarditis Endocarditis and Intravascular Infections Recommendations for the practice of echocardiography in infective endocarditis Key points: meningitis, encephalitis, and brain abscess Clinical features suggestive of meningitis in children: a systematic review of prospective data Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis Spinal epidural abscess Zika and Chikungunya: emerging arboviruses in the new world The global distribution and burden of dengue World Health Organization. Dengue and severe dengue fact sheet Yellow fever: epidemiology and prevention Update: interim guidance for health care providers caring for women of reproductive age with possible zika virus exposure-United States Acute human immunodeficiency virus infection Evaluation of the performance characteristics of 6 rapid HIV antibody tests Management of newly diagnosed HIV infection s Principles and Practice of Infectious Diseases Deep neck infections The digestive system s Principles and Practice of Infectious Diseases s Principles and Practice of Infectious Diseases Tubo-ovarian abscess: pathogenesis and management Thyroid and adrenal disorders Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys Pulmonary embolism Comparison of the Wells and Revised Geneva Scores for the diagnosis of pulmonary embolism: an Austrialian experience Acute respiratory distress syndrome: diagnosis and management The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination ARDS clinical network mechanical ventilation protocol summary Acute myocardial infarction ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary Subarachnoid hemorrhage CTA of the brain is a reasonable option to consider to help rule out subarachnoid hemorrhage in select patients Guidelines for the management of aneurysmal subarachnoid hemorrhage Acute subarachnoid hemorrhage: using 64-slice multidetector CT angiography to ''triage'' patients' treatment Stroke and transient ischemic attack overview Cavernous sinus thrombosis Headache disorders Do normal d-dimer levels reliably exclude cerebral sinus thrombosis? A solution of problems? Emergency Medicine: Diagnosis and Management. 7 th ed History of mesenteric ischemia: the evolution of a diagnosis and management Intestinal ischemia General approach to the poisoned patient Monoamine oxidase inhibitor overdose Influenza testing, diagnosis Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012 Influenza and upper respiratory infections account for a large amount of emergency department (ED) presentations. However, many critical conditions can present with similar symptoms. This review evaluates influenza symptoms and diagnosis, while discussing mimics and an approach to evaluation and management. Influenza can present with a variety of symptoms, and providers demonstrate a diagnostic accuracy approaching 90% in the correct setting. Rapid antigen detection can be useful in the ED, and treatment is warranted for several populations within 48 h of symptom onset. Approximately 70% of patients with influenza-like symptoms are experiencing a mimic. Several of these conditions that mimic the presentation of influenza require rapid management. This evaluation of influenza and its mimics discusses the presentation, diagnosis, and management of influenza, while detailing the presentation and diagnosis of several deadly conditions requiring rapid diagnosis and treatment.