Cotton fever

Cotton fever is a benign, self-limited febrile syndrome typically presenting with fever, rigors, dyspnea, headache, palpitations, back pain, abdominal pain, leukocytosis, myalgias, nausea and vomiting, occurring immediately following drug injection users who filter their drug suspensions through cotton balls before injecting it ¹. Cotton fever is a street term for a febrile reaction that occurs after the injection of a drug, usually heroin, which has been filtered through cotton. While cotton fever syndrome is commonly recognized amongst the injection drug user population, there is a paucity of data in the medical literature and lack of awareness by many physicians ². Blood cultures are normally sterile, and patients recover with only supportive care.

Cotton fever has been theorized to be due to either a hypersensitivity to pyrogenic components in cotton or a reaction to endotoxin from Enterobacter agglomerans (since renamed Pantoea agglomerans), a gram-negative bacterium that frequently colonizes cotton and other plants ³. One report described an intravenous drug user with presumed cotton fever who was found to have a bacteremia due to Enterobacter agglomerans and who required treatment with trimethoprim-sulfamethoxazole ⁴. In general, however, patients with cotton fever have a self-limited disease without an associated bacteremia and only require supportive medical care. Nevertheless, despite the usual low pathogenicity of Enterobacter agglomerans, it has been implicated as the cause of serious infections such as spondylodiscitis ⁵, blood transfusion or infusion-associated sepsis ⁶, septic arthritis ⁷ and osteomyelitis most often because of plant thorn inoculation ⁸, and various eye infections ⁹.

Originally coined in 1975 ¹⁰ cotton fever was described as a benign self-limited febrile syndrome occurring in injection drug users who filtered their drug suspensions through cotton balls. Injection drug use is associated with many infectious and non-infectious complications. The most common associated complications faced by managing physicians are soft-tissue infections, overdose, intoxication, and withdrawal ¹¹. A frequent and challenging triage dilemma in this population is that of fever with active injection drug use. Despite numerous unsuccessful attempts to develop discriminating decision rules to guide ambulatory triage in these cases, clinicians are still unable to reliably exclude occult infections such as endocarditis and osteomyelitis ¹². This often results in short-term hospitalization of these patients, with accrual of health care expenditures.4 An infrequently recognized cause of fever in injection drug users is cotton fever, a poorly characterized systemic febrile inflammatory syndrome seen in this population.

Cotton fever causes

Cotton fever most often associated with injection of heroin ¹³, cotton fever has also been described when injecting hydromophone ¹⁴ or a combination of pentazocine and methylphenidate ¹⁵. The pathophysiology is poorly understood, but three pathogenic theories have been proposed ¹⁵. The pharmacologic theory hypothesizes that the extracts of cotton contain water-soluble, steam-labile substances with pyrogenic activity. The immunologic theory proposes that people may have antibodies to cotton itself. However, no evidence has been found to support the immunologic or pharmacologic theory. Finally, the endotoxin theory suggests that cotton fever may result from the release of endotoxins from Gram negative bacilli such as Enterobacter agglomerans (since renamed Pantoea agglomerans), which has been shown to regularly colonize cotton ¹⁶. Further supporting this endotoxin theory, a case of cotton fever was described in conjunction with Enterobacter agglomerans bacteremia ¹³.

Cotton fever signs and symptoms

Cotton fever is a benign, self-limited febrile syndrome typically presenting with fever, rigors, dyspnea, headache, palpitations, back pain, abdominal pain, leukocytosis, myalgias, nausea and vomiting, occurring immediately following drug injection users who filter their drug suspensions through cotton balls before injecting it ¹. Although cotton fever is self-limited and normally lasts 6 to 12 hours, it can continue for up to 24 to 48 hours.

Cotton fever diagnosis

Cotton fever is a diagnosis of exclusion and is characterized by acute onset of fever and leukocytosis immediately following intravenous drug injection when filtering through cotton. Symptoms begin 15–30 minutes following injection, and are often accompanied by shortness of breath, chills, headache, myalgia, abdominal pain, nausea, vomiting and tachycardia ¹. Although cotton fever is self-limited and normally lasts 6 to 12 hours, it can continue for up to 24 to 48 hours.

The evaluation of a febrile injection drug user continues to present diagnostic challenges for healthcare providers. While the majority of injection drug users will have a readily identifiable source of fever such as pneumonia or cellulitis, there is a subset of patients in which the cause of their fever is not readily identifiable, and about 8–11 % are found to have serious infections such as endocarditis ¹⁷. As the presentation of cotton fever and endocarditis are similar, it is important to consider endocarditis prior to making the diagnosis of cotton fever. The incidence of endocarditis in injection drug users is estimated to be 1.5–3.3 cases per 1000 injection drug users per year ¹⁸. This risk is further increased in the presence of concurrent HIV, which is annually estimated to be present in 6.6 per 1000 injection drug users; this number reflects a dramatic reduction since the advent of highly active anti-retroviral therapies ¹⁹. Another rare complication of injection drug use is osteomyelitis, which should be considered in the appropriate clinical context ²⁰.

Despite the known burden of disease, the evaluation of a febrile injection drug user can be costly and difficult. Attempts at developing triage and diagnosis algorithms for febrile injection drug users have been unsuccessful in accurately predicting who will and who will not have endocarditis ¹². Therefore, doctors still recommend observing febrile injection drug users, who often are unable or unwilling to follow up, until blood cultures are negative ²¹.

Cotton fever treatment

In general, patients with cotton fever have a self-limited disease without an associated bacteremia and only require supportive medical care. However, given the challenges and limitations in the initial triage and management of febrile syndromes in injection drug users, admission for observation is still warranted and recommended, as cotton fever remains a diagnosis of exclusion ¹². Infections such as pneumonia, endocarditis, and osteomyelitis are the most common causes of fever in these patients ²². However, a significant percentage is found not to have any serious infection, and the fever is ascribed to other causes ²³. Quick resolution of fevers and pain symptoms within 24-48 hours in the setting of negative initial blood cultures is suggestive of cotton fever, an under-recognized but possibly common cause of fever in the injection drug users. Further awareness and study are needed to better characterize the epidemiologic and pathogenesis of this syndrome, as there is currently a paucity of information.

References

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