Continuing Education Activity

Metal fume fever is a disease most often associated with welders. Welding may cause pulmonary inflammation from the submicron particles of metal oxides in the fumes. Most often, the metal oxide is zinc oxide, but cadmium and manganese and their oxides are also present in some welding processes. Metal fume fever presents as a flu-like syndrome with fever, malaise, bronchospasm, and bi-weekly variations in severity. Symptoms are classically weakest on Sundays and strongest after returning to work on Mondays and Tuesdays. Laboratory evaluation and chest X-rays are normal, except in severe cases. Inter-professional teams are essential in identifying that this is an occupational illness and that welding requires special masking, ventilation, and length of workplace rules.

Objectives:

• Explain the association between metal fumes and their effects on the body.

• Describe the signs and symptoms, including weekly manifestations, of metal fume fever.

• Summarize the pulmonary findings in severe metal fume fever.

• Review the prevention of metal fume fever and how that impacts the entire welding workplace.

Introduction

Metal fume fever is a self-limited febrile illness that occurs in those individuals that fuse metals, such as welders. Welders also are involved in filling indentations and seams in the metal. Metal fume fever presents as a flu-like syndrome occurring shortly after these activities and others where metals are bound together. Improvement occurs over the course of the work week, but re-ex-exposure after return to work results in a return of symptoms, such as fever, malaise, and wheezing. For this reason, it is sometimes called "Monday morning fever." The first reported cases were in the 1830s. The association between metal oxides with symptoms of fever, dyspnea, and muscle aches was proven when Lehmann exposed himself and four volunteers to gaseous products of the welding process, including zinc oxide.[1]

The Bureau of Labor Statistics reports that the syndrome of metal fume fever is seen most often in welders, cutters, brazers, and solderers. Welders use many different techniques. The most common is using electric currents to create heat, slightly melt metals, and bond them together. Arc welding produces currents to create intense heat, which melts metals and facilitates bonding. The process chosen depends on the metals to be bonded. Zinc is the most common metal involved in these bonding procedures.

"Cutters" use an ionized gas called plasma, also of intense heat, to trim metal objects to specific dimensions. Plasma cutters may be involved in dismantling large objects such as ships, railroad cars, and buildings. Solderers and brazers use a third metal to join two or more other metal objects. Solderers typically work with small metal pieces that must be positioned precisely, for example, transistors or computer chips. Brazers connect dissimilar metals through the agency of filler material, thereby producing strong joints between multiple metals. Brazers may also apply coatings to protect against corrosion and wear.

Exposure to metal fumes has caused recognized illness for about 200 years and has been known under several names such as Monday fever, brass founders' ague, welders ague, smelter chills, and zinc shakes.[2] Exposure is from inhaling fumes during the welding process or cutting galvanized metal. Galvanization is a process by which a zinc coating is applied to steel. This process protects the steel from oxidation, corrosion, and weakening.

Etiology

During welding, metals become superhot and let off vapors that condense, oxidize, and are then inhaled. These superheated metals include zinc, iron, cadmium, manganese, chromium, and nickel.[3] About 30% of middle-aged welders had one episode during their careers.[4] The most common cause is zinc oxide, ZnO, generated from molten bronze or galvanized steel.

Epidemiology

Over 420,000 persons were involved in these metal applications in the United States in 2020, according to the Bureau of Labor Statistics, with about 2000 cases estimated for metal fume fever. Many metal workers, even plumbers and pipe fitters, who weld intermittently, are affected.[5] Artists and "do-it-yourselfers" may occasionally use welding and can present with metal fume fever. Ninety-six percent are men, and only about half are occupational. The most characteristic of metal fume fever is the appearance of symptoms on Monday and Tuesday and no symptoms on Sundays. Based on data from Louisiana Poison Control Center, in which 26 cases were reported over two years, 75% only reported and sought no further medical care. Four were evaluated in the emergency department, and only one was admitted to the hospital.[6]

Pathophysiology

Zinc, cadmium, iron, and aluminum oxides are the most common metals involved in metal fume fever. Cadmium may produce a syndrome of pneumonitis, hypoxia, and even death, which in many respects is distinct from metal fume fever.[7] National Institute for Occupational Safety and Health (NIOSH) and other exposure limits exist, but in general, zinc oxide fumes of 75 to 600 mg of zinc per cubic meter for 1 to 3 hours are needed to produce the syndrome. Interestingly, aerosolized zinc oxide powder does not produce the symptoms, whereas fresh zinc oxide does. The difference has been ascribed to the differential in the size of the particles.[8] Zinc oxide powder particles are much larger than freshly produced zinc oxide.[1] Ultrafine particles less than one micron in size drive much of the pathologic effects of metal fumes.[9][8] There may be a type 1 hypersensitivity that may manifest as an angioedema allergic reaction.[10] Pulmonary function testing may show marked bronchospasm.[11]

Bronchoalveolar lavage of zinc oxide exposed volunteers demonstrates elevated interleukin 6, interleukin 8, and tumor necrosis factor in the bronchoalveolar lavage fluid.[12][13][14] The tumor necrosis factor-alpha peaks at 3 hours post-exposure and seems to have a large role in metal fume fever. These cytokine agents may be the pyrogens seen in this syndrome. The lung is the major source of cytokines and is the organ most affected by these inflammatory agents. The interplay of these immune actors promotes inflammation causing neutrophil recruitment and systemic response, such as fever.

Metallothionein-transport proteins, mostly found in the cell's Golgi-apparatus, may modulate the response to metal oxides, and it has been hypothesized that this may impact the clinical response to metal fume fever.[15][16]

History and Physical

Over 90 percent of cases are mild.[1] Typically they manifest with flu-like symptoms of fever, myalgias, arthralgias,  headache, wheezing, an intense thirst, and a metallic taste in the mouth which occur between 4 and 10 hours after stopping exposure to metal binding fumes.[17][4][18] 

Pulse oximetry is generally normal. Affected individuals have symptoms that peak at 18 hours and typically disappear within twenty-four to forty-eight hours. Occasionally cases are more severe with pneumonitis or acute respiratory distress syndrome, or even pneumonitis, pericarditis, and aseptic meningitis.[19][20][21]

Evaluation

The most important aspect of the workup of these patients is to obtain an occupational history of the patient. Smoking, alcoholism, and drug use are standard parts of social history. But how the patient spends the day, either with occupation or avocation, may play a particularly important role in raising the suspicion of the practitioner for the emergency practitioner, occupational physician,  pulmonologist, or other health care provider. The fact that the patient works as a welder in the galvanization process is a common clue for diagnosing metal fume fever. Failure to engage in an occupational and hobby history may result in missing this diagnosis, and the patient may repeatedly expose themselves to unsafe conditions without a mask, adequate ventilation, and prolonged work hours. Chemistry, coagulation parameters, and chest X-ray are all usually normal or unchanged from baseline. There may be a small degree of leukocytosis.[22] 

The patient's C-reactive protein is elevated, but it is non-specific.[23] In general, testing is not indicated unless another process is strongly suspected. Zinc oxide (ZnO) exposure during welding increases the polymorphic nucleated white blood cells in the bronchial lavage fluid but is not associated with changes in bronchospasm or pulmonary function.[18] Occasionally in more severe cases, there may be pneumonitis or even acute respiratory distress syndrome (ARDS).[19]

Treatment / Management

The illness is mostly mild and self-limited. Treatment should be symptom-based with antipyretics for the fever, and fluids may be given if there is dehydration. Occasionally oxygen is needed for the treatment of hypoxemia. If bronchospasm is prominent, inhaled beta-agonists and glucocorticoids may be helpful. A chest X-ray may be helpful in the rare cases of pneumonitis, more typically due to cadmium.[6][1]

Differential Diagnosis

The astute clinician will note the association between occupation, exposure, and symptomatology in metal fume fever. The differential diagnosis includes:  

• Cadmium pneumonitis[7]
• Covid-19
• Influenza
• Hemophilus influenza
• Parainfluenza
• Polymer fume fever
• Respiratory syncytial virus
• Viral illness
• Viral pneumonia

Pertinent Studies and Ongoing Trials

Based on a six-year longitudinal study, there is an association between hypertension and welding. Neurodegenerative diseases are associated with manganese welders.[24] Manganese welded to steel makes a particularly hard variety of steel, such as used in rock crushers or bars over windows in prisons. Toenail metal concentration has been used as a biomarker of cumulative metal fume exposure.[25]

Prognosis

This illness is typically a benign process resolving in one-half to 2 days. With continued exposure, the symptoms are cyclical, with improvement on Sunday and marked exacerbations on Mondays and Tuesdays. There is an age-related decline in pulmonary function that is greater in metal fume welders than in the typical population.[26]

Complications

In the case of severe hypersensitivity pneumonitis, bilevel-positive airway pressure (BiPAP) and endotracheal intubation may be considered.

Deterrence and Patient Education

Occupational health personnel or industrial hygienists should assess the workplace environment. Workers and artisans should maintain their head and face away from the fumes and avoid breathing them. Also, it is often necessary to increase ventilation in the work zone and provide sufficient exhaust in the area where people are working. Workers should wear appropriate protective masks and work clothing. Safety education must be in place wherever welding is ongoing. In the United States, one may request a Health Hazard Evaluation involving the National Institute of Occupational Safety and Health (NIOSH), including a workplace visit. N95 masks have become standard protection for welders, but are not as effective as elastomeric half-face masks, full-face respirators, and powered air-purifying respirators.[27][28][9] 

The National Institute for Occupational Safety and Health (NIOSH) has recommended 5 mg per cubic meter averaged over a 10-hour shift and 40-hour work week. According to NIOSH, the maximum for short-term 15-minute exposure is 10 mg per cubic meter.

Enhancing Healthcare Team Outcomes

Occupational exposure to toxins, such as metals and metal fume fever, presents a clear opportunity for interprofessional communication and a healthcare team approach. Welding and metal-to-metal bonding are necessary industrial activities, but they must exist in a safe environment. Clinicians (MDs, DOs, NPs, and PAs) and nurses must be astute at picking up the weekly variations in symptoms such as fever and wheezing. Occupational histories are the most crucial element, considering that adults generally spend about one-third of every day involved with their occupation. Often there is a need to maximize safety measures with well-fitting masks and minimize exposures to toxins, such as fresh zinc oxide. In addition, smoking cessation should also be pursued for these workers. 

Patients working in conditions where metal oxides may be generated should have a well-fitted mask, and employers should provide appropriate time limits for exposure while welding. Also, other workers may be exposed at the same workplace, and some may have symptoms but not seek medical attention. A conscientious employer will seek those co-workers who may also be exposed and experiencing symptoms. An astute provider can communicate with the employer. In the USA, the National Institute of Occupational Safety and Health may initiate a Health Hazard Evaluation (HHE) for an entire workplace, as can similar agencies in other parts of the world. These safety processes can be initiated by alert clinicians, nurses, and pharmacists, among others, and can spare an entire workplace from further injury. In addition, advice to the patient about protective gear for a home welder or recreational "do-it-yourselfer" may be crucial in preventing this condition, especially since the hobbyist welder may not reveal their exposure and may not exhibit the weekly cyclical pattern seen in professional welders.

Clinicians and other healthcare providers must remain vigilant for these workplace injuries. The weekly variation in peak expiratory flow rate and the exposure to welding oxides may be all that is necessary to institute precautions and evaluate the workplace. Any interprofessional team member who detects these symptoms or discerns the weekly cyclical nature of this condition should reach out to other medical team members so appropriate interventions can take place in the workplace, leading to improved immediate and long-term health outcomes. [Level 5]