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The Occupational Medicine Forum is prepared by the ACOEM Occupational and Environmental Medical Practice Committee and does not necessarily represent an official ACOEM position. The Forum is intended for health professionals and is not intended to provide medical or legal advice, including illness prevention, diagnosis or treatment, or regulatory compliance. Such advice should be obtained directly from a physician and/or attorney.Answered by Jonathan Rutchik, MD, MPH, Division of Occupational & Environmental Medicine, University of California San Francisco, San Francisco, CA, USA and Neurology, Environmental and Occupational Medicine Associates, Mill Valley, California; Marcia H. Ratner, PhD, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.Manganese (Mn) is an essential trace element and a ubiquitous metal widely used around the world in everyday products ranging from welding rods to gasoline additives. Because Mn is used in many metal alloys including steel, the risk for occupational and environmental exposures exists in many industrial settings.The initial clinical manifestations of manganese poisoning often include behavioral changes referred to collectively as “manganese psychosis.” The clinical symptoms of manganese psychosis include mood changes, emotional lability, uncontrolled laughter, and hallucinations. Parkinsonism characterized by tremor and gait disturbances emerges with continued exposure to Mn. The diagnosis of Mn-psychosis depends in part on the documentation of exposure based on an accurate and complete occupational or environmental exposure history. The presence of biological markers of exposure in blood or urine samples can aid the clinician in making a diagnosis. Biological markers of effect, such as comorbid symptoms of parkinsonism, combined with abnormal magnetic resonance imaging (MRI) studies revealing hyperintensities in the basal ganglia, facilitate the diagnosis of Mn poisoninig.It is not uncommon for patients and their significant others to seek alternative and toxic explanations for idiopathic neurodegenerative and psychiatric disorders. Therefore, clinicians must diligently explore all explanations for the patient's symptoms before arriving at a diagnosis. Nontoxic etiologies for the patient's symptoms must be ruled out based on the family history, neuroimaging studies, neuropsychological assessment, and results of laboratory tests. Nonoccupational causes of pallidal hyperintensities on an MRI such as hepatic failure must also be ruled out. Progression of symptoms following cessation of exposure is often an indication of an underlying primary idiopathic neurodegenerative or psychiatric process. The differential diagnosis of primary versus secondary psychosis is complex and depends in part on an accurate history of occupational exposure to neurotoxicants that may exacerbate idiopathic disease.This case report demonstrates the inherent difficulties associated with differentiating Mn-psychosis from late-onset schizophrenia when there is a risk for occupational exposure to heavy metals and solvents. It also exemplifies how a single false-positive laboratory result can lead to misdiagnosis and, serves as reminder of the importance of always confirming the results of initial laboratory tests before making a diagnosis. The importance of proper sample timing in relation to tests and procedures that have the potential to confound the results of laboratory tests for biological markers of exposure is discussed in detail.A 42-year-old jewelry maker with no prior psychiatric history presented to an emergency department (ED) with a 3-week history of progressively worsening psychosis. His symptoms included paranoia, delusions, and auditory hallucinations. On admission to the ED, the patient's pupils were equal, round, and reactive to light. He was alert and oriented times three with no evidence of acute distress. He was afebrile and there was no nuchal rigidity. The patient reported that he does not drink or smoke and denied any history of substance abuse.