ToxCard: Cotton Fever

Authors: Victoria Serven, MD (Emergency Medicine Resident, Carolinas Medical Center, Charlotte, NC), Kathryn T Kopec, DO (Emergency Medicine Attending; Medical Toxicologist, Carolinas Medical Center, Charlotte, NC) // Reviewed by: Cynthia Santos, MD (@Cynthia Santos, MD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)


A 17-year-old female presents to the emergency department (ED) complaining of fever, chills, vomiting, and myalgias. She admits to using heroin two times earlier that day. Vital signs on arrival are: 101.7C, BP 112/70mmHg, HR 115 bpm, RR 22 breaths/minute, SpO2 98% on RA. 


  • What is Cotton Fever and its mechanism of action?
  • How should a provider manage a patient they suspect is suffering from Cotton Fever?


Cotton Fever is a benign, self-limited febrile syndrome commonly seen in intravenous (IV) drug users who filter their drugs through cotton balls. Cotton balls are used to filter out large particles and help ensure all of the liquid is drawn up into the syringe (1). Another common practice for IV drug users who have run out of drug or are trying to conserve drug is taking several used cotton balls and drawing up the remnants of left-over heroin (1). Medical literature on these practices or the resulting symptoms that contribute to cotton fever is limited; however, they are easily recognized amongst members of the IV drug community (2). 

Mechanism of Action:

The exact mechanism of action regarding the pathophysiology of Cotton Fever is unknown, however, there are three prevailing theories (3).

  • Pharmacologic Theory: 
    • Substances within the cotton material have pyrogenic activity
  • Immunologic Theory: 
    • Some patients have performed antibodies to cotton
  • Endotoxin Theory: 
    • Gram negative bacilli are taken up in the cotton and release endotoxins 
    • Enterobacter agglomerans (recently renamed to Pantoea agglomerans) has been implicated with Cotton Fever.
      • It is the only bacteria to have been cultured from a patient suffering from cotton fever; however, this identification occurred in a single case report (4). 
      • Interestingly though E. agglomerans has been shown to colonize cotton plants (3).

Clinical Presentation:

  • Symptoms include nausea, vomiting, fever, chills, headache, myalgias, abdominal pain, and tachycardia.
  • Onset is usually 15-30 minutes following IVDU with the use of cotton.
  • Symptoms usually persists for 6-12 hours but can extend as long as 24-48 hours.


These patients should be approached as a fever of unknown origin in an IVDU. The differential diagnosis includes several life-threatening conditions including osteomyelitis, endocarditis, HIV, meningitis, pneumonia, cellulitis, abscess, and bacteremia (5). Patients should undergo a complete physical exam including a thorough skin exam as well as the laboratory studies and imaging listed below. Cotton fever should ultimately be considered a diagnosis of exclusion (5). 


    • CBC, BMP, LFTs, UA
    • ECG
    • CXR 
    • Blood cultures


  • Standard of care is supportive care including IVF, antipyretics, antiemetics, and empiric antibiotics. 
  • These patients should undergo admission and observation until a 24-hour negative blood culture result has been achieved.
  • Often patients who are familiar with this illness will request to be discharged once they are feeling better (6). 
    • Given the severity of other illnesses on the differential that are associated with fever in IVDU it is recommended that patients who have reliable, close follow up be discharged before completing their workup (2). 

Key Points: 

  • Cotton Fever is a transient flu-like illness following injection of drugs filtered through cotton.
  • Cotton filter removes large particles & allows for efficient liquid extraction. 
  • May be secondary to endotoxin release from gram negative bacilli in cotton 
  • Diagnosis of exclusion. 
  • Work includes labs, blood cultures, CXR, and ECG.
  • Management is aimed at symptomatic treatment and empiric antibiotics. 
  • Can discharge after 24 hours of negative blood cultures OR after symptom resolution if patient has excellent, reliable follow up. 



  1. A Safety Manual for Injection Drug Users. Harm Reduction Colition. NY. US. 2011. Accessed on July 12, 2020. Online. Available:
  2. Harrison D.W., Walls R.M. Cotton fever”: a benign febrile syndrome in intravenous drug abusers. J Emerg Med. 1990;8(2):135–139. 
  3. Torka P., Gill S. Cotton fever: an evanescent process mimicking sepsis in an intravenous drug abuser. J Emerg Med. 2013;44(6):e385–7. 
  4. Francis MJ, Chin J, Lomiguen CM, Glaser A. Cotton fever resulting in Enterobacter asburiae endocarditis. IDCases. 2019;19:e00688. Published 2019 Dec 20. doi:10.1016/j.idcr.2019.e00688
  5. Ramik D., Mishriki Y. The other “Cotton fever” Infect Dis Clin Pract. 2008;16(3):192–193. 
  6. Xie Y., Pope B.A., Hunter A.J. Cotton fever: does the patient know best? J Gen Intern Med. 2016;31(4):442–444.


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