N-methylaniline exposure identified as likely cause of methemoglobinemia during maritime migration
1. In this case series of severe acquired methemoglobinemia among migrants to Italy, prolonged skin exposure to fuel-contaminated seawater was identified as the likely underlying cause.
2. N-methylaniline or its metabolites were detected in nearly all tested patients and in fuel from an implicated vessel.
Evidence Rating Level: 4 (Below Average)
Study Rundown: Acquired methemoglobinemia is an uncommon but potentially life-threatening condition that can be difficult to recognize because conventional pulse oximetry is unreliable and diagnostic CO-oximetry may be unavailable in prehospital or resource-limited settings. Migrants crossing the Central Mediterranean route in overcrowded vessels may have prolonged skin exposure to contaminated seawater accumulating on the vessel floor. Although hydrocarbon inhalation and fuel-related skin injuries had previously been described in this setting, severe methemoglobinemia had not. Clinicians in Lampedusa, Italy identified recurring clusters of affected migrants at disembarkation, prompting a coordinated clinical, toxicologic, and environmental investigation. Overall, the cases were severe, with most patients requiring intravenous methylene blue and many requiring repeated doses. Delayed hemolytic anemia was common, frequently necessitated blood transfusion, and was sometimes accompanied by splenic rupture. Toxicologic testing identified N-methylaniline or related compounds in almost all tested patients, while fuel from a vessel associated with one cluster also contained N-methylaniline; no alternative methemoglobin-inducing agent was identified. Together, the temporal clustering, exposure history, biologic testing, and fuel analysis supported dermal absorption of N-methylaniline from contaminated seawater as the likely cause. The study was limited by incomplete case detection, follow-up, and toxicologic testing. Nonetheless, these findings emphasize the importance of frontline diagnostic testing, access to methylene blue, and continued monitoring for delayed hemolysis in maritime reception settings.
Click to read the study in NEJM
Relevant Reading: Recommendations for diagnosis and treatment of methemoglobinemia
In-Depth [case series]: This coordinated clinical and toxicologic investigation included migrants with an elevated methemoglobin level identified during initial evaluation after disembarkation. Cases were identified primarily through consultation requests to the Pavia Poison Control Center. Of the 82 patients, 90% were male, and the median age was 22.5 years. Patients originated from South Asia (33%), sub-Saharan Africa (18%), the Middle East (11%), and North Africa (10%). Cases occurred in temporal clusters, including a cluster of 41 patients in October 2025. The median methemoglobin level at presentation was 44.6% (IQR, 32.0% to 55.7%), with 83% of patients having a level of at least 25% and 43% having a level of at least 50%. Cutaneous burns, a strong gasoline odor, or other evidence of fuel exposure was documented in 62%. Hemolytic anemia was documented in 38 patients and generally emerged two to four days after disembarkation; all 26 patients with available transfusion data received a blood transfusion. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was identified in 16 of 44 tested patients, 13 of whom developed hemolytic anemia. Splenic rupture occurred in four patients with available complication data, and all underwent splenectomy. Two patients died within 24 hours of disembarkation. Quantitative toxicologic analyses were performed in 39 patients, with N-methylaniline or related compounds detected in 37 patients (95%). N-methylaniline or aniline was detected in the blood of 14 of 38 patients, and the two patients who died had among the highest measured blood concentrations. Environmental testing of fuel obtained from an implicated vessel found an N-methylaniline concentration of 1.1%, and no alternative methemoglobin-inducing agents were identified. In summary, the convergence of clinical, temporal, biologic, and environmental findings identified dermal exposure to N-methylaniline in fuel-contaminated seawater as the likely cause of this outbreak of severe methemoglobinemia.
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