Polymer Fume Fever

Etiology

Polymer fume fever is precipitated by inhaling the thermal decomposition products of fluoropolymers.[2] While PTFE is the most well-recognized cause of polymer fume fever, likely due to its numerous industrial applications, other fluoropolymers, including fluorinated polyethylenepropylene, have also been implicated in this disease process.[4] Similar illnesses have been reported due to the overheating of chloropolymers; in those reports, the specific etiologic compound was not identified.[5]

Although PTFE releases fumes at temperatures as low as 260 °C (500 °F), symptoms in humans generally do not begin until the material is heated to 350 °C (662 °F). Pyrolysis commences at 400 °C (752 °F).[6] 

Perfluoroisobutylene, fluoroethylene, hexafluoroethane, octafluorocyclobutane, and hexafluoropropylene have all been identified as specific pyrolysis or degradation products and are likely the primary xenobiotics that precipitate the clinical effects of polymer fume fever.[7] Pyrolysis of fluoropolymers at even higher temperatures, over 500 °C, releases hydrogen fluoride and carbonyl fluoride, the fluoride analog of phosgene.

Epidemiology

The epidemiology of polymer fume fever is incompletely characterized, and the incidence is likely underreported. 

Polymer fume fever was first reported in the occupational setting among individuals who processed raw PTFE or PTFE-coated products.[2][3] After multiple incidents of flu-like outbreaks among workers, epidemiologists determined these symptoms were most often the result of poor industrial hygiene; individuals who worked with raw PTFE and then touched their cigarettes without adequate hand hygiene were most likely to demonstrate symptoms. Subsequent inhalation of tobacco smoke provided sufficient PTFE exposure to trigger an episode of polymer fume fever, which can be precipitated by exposure to a particle the equivalent of 1 mm in size.[8] Less commonly, breathing the air where coated material has been burned or fused can cause exposure sufficient to precipitate symptoms.[3] 

Most contemporary PTFE exposures occur at home and are the result of inhaling vapors emitted by overheated PTFE-coated pans. The risk of vapor inhalation is increased if the heated cookware is dry, as in circumstances where oil was not added or all added water evaporated.[9] Exposure to particulate PTFE after cooking oils have been applied to the PTFE coating seems less common as the relative smoke points of commonly used cooking oils are all lower than the temperature at which overheated PTFE precipitates symptoms in humans.

More unusual routes of particulate exposure have included inhaling pyrolyzed hair spray formulated with fluorocarbons and contamination of smokable materials after using mold-release spray and dry lubricants.[10][11][12]

Between 2006 and 2012, a yearly average of 9 cases of polymer fume fever were reported to regional poison control centers in the United States. This likely demonstrates underreporting. In a retrospective study of fabrication plant workers, only 10% of workers with symptoms consistent with polymer fume fever sought medical assistance.[13] It can also be surmised that many patients who present to a healthcare facility may not report exposure to PTFE or fluorocarbon-coated materials. Healthcare providers may not inquire into such exposures due to a lack of knowledge of the association between inhalation of fumes and clinical symptoms. And finally, poison center data, in general, suffers from underreporting bias. Even if the connection to fluoropolymer exposure is made, many practitioners do not necessarily need poison control center support or wish to spend the time to report the link.[14] 

Growing evidence also suggests that chronic occupational exposure to unheated PTFE aerosols may place workers at risk for granulomatous lung disease.[15][16]

Pathophysiology

Studies investigating the pathophysiologic mechanisms underlying polymer fume fever are sparse. It is suspected that fluorocarbon degradation products activate neutrophils, leading to a proinflammatory cytokine cascade akin to the processes underlying metal fume fever.[7] When carbonyl fluoride is produced, hydrofluoric acid is generated when the former hydrolyzes after interacting with water. This likely potentiates the inflammatory cascade by precipitating further direct pulmonary injury.

Toxicokinetics

The toxicokinetics and toxicodynamics of the degradation and pyrolytic products that precipitate polymer fume fever are poorly described.

History and Physical

Polymer fume fever generally presents as a mild flu-like illness typified by fever, myalgias, dyspnea, chest tightness, nonproductive cough, and headache.[3]  

Symptoms generally start within 12 hours after exposure, but the presentation may be delayed up to 24 hours.[7] Although pyrexia is occasionally present, overt hypoxia is uncommon. Blood pressure and heart rate are usually normal.

The physical examination is usually unremarkable except for occasional abnormal pulmonary findings, including nonproductive cough and bronchospasm. Crackles or rales may be present in instances where the patient is experiencing noncardiogenic pulmonary edema induced by the fluoropolymer degradation products.[17]

A known exposure to fluorocarbon degradation products is required to diagnose polymer fume fever. These precipitating exposures most commonly include accidentally overheating nonstick cookware or smoking after occupational work with granular PTFE particles or substrate. Although occupational exposure is less common with stricter controls, inquiring if the patient failed to wash their hands before smoking may be illuminating.[2][3]

Evaluation

Although the diagnosis of polymer fume fever is clinical, obtaining a complete blood count with differential and chest radiography is reasonable. Leukocytosis with a left shift may be present. Chest radiography findings are often normal but, after significant exposures, may reveal bilateral infiltrates consistent with pulmonary edema.[18]

Pulmonary function tests or spirometry, including FEV₁ and FEV₁/FVC, have limited utility when diagnosing or treating polymer fume fever. While many patients with polymer fume fever have normal pulmonary function, some exhibit a mild obstructive pattern exacerbated from their baseline. However, it is important to note that an underlying smoking history frequently confounds these results.[3][7]

Treatment / Management

The typical course of polymer fume fever is mild and self-limited. Treatment should be directed toward the presenting symptoms. Fever can be effectively managed with antipyretics such as acetaminophen or nonsteroidal anti-inflammatory drugs. Bronchospasm is effectively treated with inhaled beta-agonists or glucocorticoids. Hypoxic patients should be placed on supplemental oxygen.

In cases of acute respiratory distress syndrome (ARDS) or severe non-cardiogenic pulmonary edema, bilevel-positive airway pressure (BiPAP) or endotracheal intubation with ventilator support may be required.[18](B3)

Decisions surrounding inpatient admission should be tailored to the timing and severity of the clinical presentation and exposure. It is reasonable to observe patients with significant and prolonged exposures, such as overheated PTFE-coated cookware, as there may be a latency of many hours until symptoms peak.

Differential Diagnosis

A clinical history specifically identifying an appropriate fluoropolymer exposure, as well as the exclusion of other potential causes, is required to establish a diagnosis of polymer fume fever.

The differential diagnosis of polymer fume fever comprises noninfectious and infectious etiologies. Noninfectious etiologies of the clinical constellation of symptoms seen in polymer fume fever include metal fume fever, trimellitic flu, farmer's lung, and many other causes of hypersensitivity pneumonitis.[7][19][20] 

Infectious diagnoses that may mimic polymer fume fever include typical and atypical bacterial respiratory illnesses and viral infections with influenza, Sars-cov-2, parainfluenza, or respiratory syncytial virus. However, polymer fume fever does not usually present with the typical viral upper respiratory symptoms of congestion, rhinorrhea, and otalgia. Additionally, the concomitant presence of diarrhea, in particular, should suggest another etiology.[7]

Toxicity and Adverse Effect Management

There currently does not appear to be any longstanding harm after a single episode of polymer fume fever or persistent toxicity from a single exposure to fluorocarbon polymer degradation products. Nevertheless, the lack of evidence in this realm should not be assumed to indicate evidence of a lack of harm. There is a burgeoning field of research exploring the long-term effects of fluorocarbon toxicology on human health, and further insights in the coming years should be expected.

Prognosis

Polymer fume fever typically follows a benign course, and most affected patients make a full and brisk recovery. Symptoms generally peak within 24 hours of exposure and gradually improve over 24 to 48 hours.[7] Even when patients present with more significant symptoms, such as pulmonary edema, a full recovery is expected over the following 5 to 10 days.[18] Death from polymer fume fever is exceedingly rare.[21] Unlike metal fume fever, tachyphylaxis is not described.

Complications

Most patients will make a complete recovery. Permanent impairment in lung function and physiology, such as pulmonary fibrosis, is rarely described and appears to be restricted to those with recurrent exposures.[7][22]