Cotton Fever

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When a patient with a history of recent IVDU presents with a complaint of fever, the mind of the provider should immediately focus on the numerous possible infectious complications that can arise.  Infectious endocarditis can lead to septic emboli spread to any organ system.  Pneumonia can result from aspiration or septic embolization. Cellulitis/abscess can obviously result from local injection.  But what about when a source of fever is not readily identifiable? When cultures are negative and the patient’s symptoms have resolved, what could have been the cause of their febrile illness?

Cotton fever is an uncommon, diagnosis of exclusion in patient’s with a history of recent IVDU presenting with a complaint of fever.  Numerous published case reports detail a clinical presentation mimicking sepsis with patients commonly having tachycardia (up to the 130’s), fever (up to 103), and physical complaints of myalgias, arthralgias, and occasional abdominal pain.  The symptoms are, however, fleeting in nature, resolving sometimes within hours of their presentation to an Emergency Department.  Leukocytosis can be found on laboratory testing (up to 22K in published case reports). (1) Other labs are typically normal assuming the absence of other ongoing medical issues (e.g. hepatitis C, dehydration, acute kidney injury).  Needless to say, blood cultures obtained during their presentation are negative (with one notable exception detailed below).

If not an infection, what causes “cotton fever” and why is it termed “cotton fever”?  

Heroin and other injected street drugs are sold in a powders.  Users of these drugs will dissolve the powder in water and use a filter (often cotton balls) when aspirating the now solved drug into a syringe.  Users are also known to heat the previously used cotton ball filters in water in an attempt to extract small amounts of drug that may have been adherent to the filter - a process known as “shooting the cottons.” (2)

There are 3 possible explanations for the transient febrile process in the published literature. (3)

Explanation #1 - It’s an antibody mediated response.  The idea underlying this theory is that individuals form antibodies in response to repeated exposure to cotton proteins.  This theory is the least favored as attempts to isolate antibodies have been unsuccessful.

Explanation #2 - It’s the cotton fibers themselves. Cotton fibers contain water soluble polypeptides with pyrogenic activity and cotton fibers are used in animal models to induce fever and study anti-pyretics

Explanation #3 - It’s from endotoxins stemming from bacteria that adhere to the cotton fibers.  Cotton is known to be colonized with a number of gram negative rods including Enterobacter agglomerans.  In one published case of fever in a patient with IVDU, blood cultures were able to isolate E. agglomerans. Cultures of the cotton ball used by the patient also grew E. agglomerans along with Leclercia adecarboxylata and Acinetobacter Iwoffi. (1).  As the cultures in these patients are usually negative, it is thought that the febrile response actually occurs as a result of exposure to endotoxin as opposed to transient bacteremia.

What to Do?

“Cotton fever” is truly a diagnosis of exclusion.  A patient who has a history of IVDU who presents with a febrile illness needs a thorough history and physical exam and diagnostic evaluation to identify a source of their fever.  The patient with persistent fever or significant vital sign abnormalities should be admitted to await the results of blood cultures. (3, 4)  For patient’s with a normal diagnostic evaluation and who’s symptoms have resolved in the ED, the decision making may be more fraught.  Admission for observation and monitoring of symptoms is appropriate and prudent in these patients.  Discharge from the ED would hinge on arranging rock solid outpatient follow up and/or a sure way to contact the patient, something that may be particularly challenging in this patient population.

References

  1. Zerr AM, Ku K, Kara A. Cotton Fever: A Condition Self-Diagnosed by IV Drug Users. The Journal of the American Board of Family Medicine 2016;29(2):276–9. 
  2. Shragg T. ‘‘Cotton fever’’ in narcotic addicts. JACEP 1978;7:279–80. 
  3. Torka, P., Gill, S. Cotton Fever: An Evanescent Process Mimicking Sepsis in an Intravenous Drug Abuser. JEM 2013;44(6):e385–7. 
  4. Harrison D, Walls R. “Cotton Fever”: A Benign Febrile Syndrome in Intravenous Drug Abusers. The Journal of Emergency Medicine 1990;8:135–9.