Influenza Like Illness Mimics


Author: Matt Klein, MD (EM Resident Physician, PGY-3, NUEM) // Edited by: Ryan Huebinger, MD (EM Resident Physician, PGY-4, NUEM) // Expert Commentary: Michael Angarone, DO

Citation: [Peer-Reviewed, Web Publication] Klein M, Huebinger R (2016, September 27). Influenza Like Mimics [NUEM Blog. Expert Commentary By Angarone M]. Retrieved from 

Asking The Right Questions

You’ve nearly finished a busy shift, when a 44 year old female with a chief complaint of “not feeling well” gets placed in a room. Per the triage note, she endorses low grade fevers, non-productive cough, and body aches for the past two days. Vital signs are notable for a temperature of 100.4, heart rate of 103, respiratory rate of 18, and oxygen saturation of 96% on room air. Before labeling this patient as the third “influenza like illness” (ILI) you’ve seen today, what other potentially life-threatening flu mimics should be considered?

The Centers for Disease Control and Prevention defines ILI as temperature greater than 100˚F plus either cough or sore throat in the absence of a known cause other than influenza. In many studies, the influenza virus is identified in 25% or fewer patients with ILI. The differential diagnosis for nonspecific viral syndrome is vast. Amid the sea of patients presenting with constitutional symptoms, especially during the peak of flu season, emergency physicians need to efficiently assess for “sick vs not sick” while avoiding the risk of premature closure bias.

A few key elements of the patient’s history can help focus the differential:

Has the patient traveled recently?

A travel history can suggest exposure to a variety of pathogens that mimic influenza. Emerging viral diseases such as MERS or SARS are increasingly common in returning travelers. Travel to tropical or subtropical areas raises the risk of malaria, dengue, yellow fever, and other mosquito borne illnesses. Closer to home, camping or hiking in tick-infested areas can lead to exposure to tick-borne diseases such as Lyme disease and Rocky Mountain Spotted Fever, while contact with rabbits raises the risk of tularemia. West Nile virus, previously only seen in travelers, is now common in the United States. 

Does the patient engage in any high risk behaviors?

The Acute Retroviral Syndrome of early HIV infection can be easily mistaken for a more benign process, and requires a high index of suspicion, especially in patients who engage in unprotected sex or intravenous drug use. Any patient with a fever and history of IVDU should also prompt consideration of epidural abscess and endocarditis.

Are other people around the patient sick as well?

By the peak of flu season, nearly every patient has been exposed to someone with a fever, sore throat, or cough. During colder months, however, statements like “everyone at work has the same thing” or “everyone at home is sick” may raise concern for carbon monoxide toxicity, especially if the patient is also complaining of headache. 

Lice infestation is particularly common among homeless patients and those living in crowded conditions. In one study, 14% of homeless individuals with lice presenting to an ED were also infected with Bartonella quintana, which can lead to trench fever and endocarditis - both of which can mimic the flu.

Does the patient have a headache?

Every emergency physician is going to think of meningitis in a patient complaining of fever and headache, as meningitis can be a particularly lethal viral syndrome mimic. But what about the patient with no other meningeal signs? Early presentations of thrombotic thrombocytopenic purpura (TTP) can mimic a viral syndrome. As with most classic descriptions, the “pentad” of TTP (thrombocytopenia, hemolytic anemia, kidney failure, neurologic symptoms, fever) is rarely completely present, but in a patient with fever, headache, and bruising or petechiae, consider obtaining a CBC and creatinine.

What medications is your patient taking?

Most ILI patients don’t present tachycardic to 140 with spontaneous clonus. But in a febrile patient complaining of myalgias, look for signs of a toxidrome (serotonin syndrome, anticholinergic poisoning, and neuroleptic malignant syndrome). Also, remember the initial presentation of salicylate toxicity can include nonspecific symptoms that can easily be attributed to a viral process, such as fever and GI upset.

Most patients with ILI need nothing more than reassurance and good supportive care, but avoiding premature closure bias during the peak of flu season can help us identify the truly sick person presenting with only vague complaints. 

Expert Commentary

This is an excellent review of the major “other causes” for the presentation of an influenza-like illness (ILI). The initial response to the symptoms of fever, cough and/or sore throat is to make the presumptive diagnosis of influenza or another respiratory viral illness and recommend symptomatic therapy. Many physicians attach the diagnosis of a viral upper respiratory illness (URI) to ILI since these are the most common conditions encountered that lead to these symptoms. It should be noted that the definition of ILI (fever ≥100F plus a cough and/or sore throat) is used by the Centers for Disease Control (CDC) and other health departments to aid in the surveillance of influenza from season to season. A wide differential and suspicion for other causes of ILI should be used, especially when circulating influenza is low or if other symptoms are present. In fact studies have shown that the use of clinical characteristics or using the symptoms of ILI have poor sensitivity for diagnosing influenza. A study from Johns Hopkins conducted during the 2012-2013 influenza season found that using clinical factors had a sensitivity of 36% for the diagnosis of influenza and the use of ILI had a sensitivity of 31% [5]. Even during the influenza season or in an individual who has been vaccinated for influenza it is important to remember that other pathogens can causes these symptoms (adenovirus, respiratory syncytial virus, human metapneumovirus, Mycoplasma pneumoniae, etc.).

Many different infectious and non-infectious conditions can cause ILI (as detailed in the post). The most important factor in the evaluation of a patient with ILI is to identify any other associated symptoms or risk factors that may indicate a specific process other than influenza. The presence of severe sore throat with cervical lymphadenopathy may point more towards HIV, EBV or CMV infection. Photophobia with headaches, neck pain and confusion should alert the physician to a meningitis or encephalitis (bacterial or viral). Presentation in the spring to early fall raises the likelihood of vector born infections such as West Nile virus, Borrelia burgdorferi, Ehrlicia or Rickettsia.  Travel history is very important, especially with the changing ranges of many infections such as Zika virus, Chickungunya virus and Dengue virus.  Non-infectious causes of ILI may present with a myriad of associated symptoms including joint swelling or inflammation, rashes, conjunctivitis, oral ulcers.

It is important to remember that not all influenza-like illnesses are influenza or a viral URI. The thoughtful consideration of infections beyond influenza or upper respiratory viruses for those presenting with ILI is important. The emergency department physician needs to be aware of the many mimics of ILI and those conditions that require further questioning or evaluation to make a diagnosis.  

Michael Angarone, DO

Assistant Professor; Division of Infectious Diseases; Northwestern University Feinberg School of Medicine


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