Outbreak of Severe Methemoglobinemia during Maritime Migration

Author(s): Lucia Bernasconi, M.D.¹; Davide Lonati, M.D.¹; Alessandra Teresi, M.D.²; Francesco D’Arca, M.D.³; Nicolò Ricca, M.D.⁴; Daniele Merli, Ph.D.⁵; Martina Pes, M.S.¹; Antonella Rotolo, M.S.¹; Elena Grignani, M.S.⁶; Cristina Agozzino, M.D.⁷; Cristina Carolina Benussi, Pharm.D.¹; Benedetta Brolli, M.D.¹; Eleonora Buscaglia, Pharm.D.¹; Monica Carnovale, M.D.¹; Arianna Centonze, M.D.⁷; Massimo Ciotta, M.D.⁸; Francesco Di Lascio, M.D.⁹; Gerlando Fiorica, M.D.⁹; Tommaso Frigerio, M.D.^1,10; Fabio Genco, M.D.¹¹; Agostino Massimo Geraci, M.D.¹²; Giovanni Ippati, M.D.⁷; Vincenzo Mazzarese, M.D.⁸; Valentina Maria Negrini, M.D.¹; Marco Palmeri, M.D.¹¹; Valeria Margherita Petrolini, M.D.¹; Francesco Petrusa, M.D.¹³; Elisa Roda, Ph.D.¹; Giulia Scaravaggi, Pharm.D.¹; Azzurra Schicchi, M.D., Ph.D.¹; Sara Scotto, M.D.¹; Francesca Zaffino, M.D.¹⁴; Carlo Alessandro Locatelli, M.D.¹;

Source: DOI: 10.1056/NEJMoa2606487

Dr. Anjan Patel's Thoughts

This is a fascinating toxicology detective story with real hematology lessons. Among 82 mostly young male migrants arriving in Lampedusa, median methemoglobin was 45% (43% were at 50% or higher), and the culprit was dermal absorption of N-methylaniline, a gasoline additive, from fuel-contaminated seawater pooling in the boats. Our takeaway is the delayed hemolysis: it hit most patients with available data around days 2 to 4 (up to day 7), every patient with transfusion data needed blood, 4 had splenic rupture, and G6PD deficiency turned up in 16 of 44 tested. It's a good reminder that antidotes only work if they are on the shelf.

BACKGROUND

Migrants crossing the Central Mediterranean sea route travel in overcrowded vessels, where fuel may leak and contaminate seawater accumulating on the vessel floor, resulting in prolonged dermal exposure and fuel-related skin injuries. Since March 2024, clusters of cases of severe acquired methemoglobinemia with no apparent cause have been identified by clinicians in Lampedusa disembarkation among migrants arriving in Italy.

METHODS

We conducted a coordinated clinical and toxicologic investigation to characterize these cases and identify the underlying cause. Biologic samples were obtained from a subset of patients and analyzed for methemoglobin-inducing agents. A fuel sample from a vessel associated with one of the case clusters was also analyzed.

RESULTS

Between March 2024 and December 2025, a total of 82 patients with severe acquired methemoglobinemia were identified, 90% of whom were male; the median age of the patients was 22.5 years (interquartile range, 19.5 to 28.0). The median methemoglobin level presentation was 44.6% (interquartile range, 32.0 to 55.7), with 43% of the patients having a level of 50% or greater. Methylene blue therapy was used in 90% of the patients, often in repeated doses. Hemolytic anemia occurred as a delayed complication in 38 patients, frequently leading to blood transfusion. Two patients died. Toxicologic analysis identified N-methylaniline (a gasoline additive) or its metabolites in 37 of 39 tested patients (95%) and N-methylaniline a concentration of 1.1% in the fuel sample from the vessel.

CONCLUSIONS

This investigation identified dermal absorption of the gasoline additive N-methylaniline from fuel-contaminated seawater as the likely cause of recurrent, life-threatening methemoglobinemia associated with maritime migration. These findings underscore the importance of methylene blue availability and frontline diagnostic capacity in settings where similar exposure conditions may occur.

Author Affiliations

¹Pavia Poison Control Center, National Toxicology Information Center, Laboratory of Clinical and Experimental Toxicology, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; ²Emergency Medical Services 118, Lampedusa Base, Azienda di Rilievo Nazionale e di Alta Specializzazione (ARNAS) Civico Di Cristina Benfratelli Hospital, Palermo, Italy; ³Emergency Health Care Facility (Punto Territoriale di Emergenza), Azienda Sanitaria Provinciale (ASP) di Palermo, Lampedusa, Italy; ⁴Italian Red Cross, Lampedusa Migrant Reception Hotspot, Lampedusa, Italy; ⁵Department of Chemistry, University of Pavia, Pavia, Italy; ⁶Environmental Research Center, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; ⁷Anesthesia and Intensive Care Unit with Hyperbaric Chamber, Sant’Antonio Abate Hospital, ASP Trapani, Erice, Italy; ⁸Anesthesia and Intensive Care Unit, ARNAS Civico Di Cristina Benfratelli Hospital, Palermo, Italy; ⁹Anesthesia and Intensive Care Unit, San Giovanni di Dio Hospital, ASP Agrigento, Agrigento, Italy; ¹⁰Emergency Medicine Unit and Emergency Medicine Postgraduate Training Program, IRCCS Policlinico San Matteo University Hospital, University of Pavia, Pavia, Italy; ¹¹Emergency Medical Services 118, ARNAS Civico Di Cristina Benfratelli Hospital, Palermo, Italy; ¹²Emergency Department, ARNAS Civico Di Cristina Benfratelli Hospital, Palermo, Italy; ¹³Anesthesia and Intensive Care Unit, Hyperbaric Medicine and Pain Therapy Unit, ASP Agrigento, Sciacca–Ribera Hospitals, Sciacca, Italy; ¹⁴Office of the Directorate General for Health Emergencies and National Antidote Stockpile, Department of Prevention, Research, and Health Emergencies, Ministry of Health, Rome

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