A prospective analysis from the Spanish Registry of pulmonary arterial hypertension (REHAP) examined 59 patients diagnosed with toxic oil syndrome-associated pulmonary arterial hypertension (TOS-PAH) between 1997 and 2025, providing new clinical, pathological and genetic insights into this historically significant form of drug-induced pulmonary arterial hypertension.
Key findings: The patient cohort was 63% female with a median age of 47 years. Remarkably, the median interval between toxic oil exposure and pulmonary arterial hypertension diagnosis was 270.8 months (approximately 22.5 years), with several new cases diagnosed in recent decades, demonstrating the long-lasting effects of the toxic exposure.
Patients diagnosed in earlier periods presented younger with more severe functional impairment and worse hemodynamics, while recent cohorts showed higher prevalence of cardiovascular and respiratory comorbidities.
Overall and transplant-free survival rates remained similar across decades, with median transplantation-free survival of 97.2 months. Three patients achieved complete hemodynamic resolution. Genetic testing was negative in all evaluated patients, and pathological findings were comparable to other pulmonary arterial hypertension forms, though some cases showed significant venous remodeling.
Conclusions: Toxic oil syndrome-associated pulmonary arterial hypertension remains a distinct clinical entity with new cases emerging decades after exposure. Despite evolving presentation patterns over time, its long-term clinical course mirrors that of other Tpulmonary arterial hypertension types.
Citation
Cruz-Utrilla A, Cantero-Acedo Á, Tenes A, Enguita AB, Delgado-Jiménez JF, López-Meseguer M, Martínez-Meñaca A, Lázaro Salvador M, Martín De Miguel I, Gutiérrez-Ortiz E, Tenorio JA, Segovia-Cubero J, Blanco I, Escribano-Subias P. Pulmonary arterial hypertension associated with exposure to toxic rapeseed oil. ERJ Open Res. 2025 Dec 29;11(6):00720-2025. doi: 10.1183/23120541.00720-2025. PMID: 41473551; PMCID: PMC12746113.Copy
Read more at this link on the ERJ Open Research
HISTORICAL CONTEXT
The 1981 Spanish Epidemic: In May 1981, Spain experienced one of the most devastating public health crises in modern European history. The toxic oil syndrome epidemic affected over 20,000 people and caused more than 300 deaths. The outbreak was traced to rapeseed oil that had been illegally imported and fraudulently sold as olive oil for human consumption. The oil had been denatured with aniline for industrial use, then improperly refined for resale as cooking oil.
Clinical manifestations: Victims initially presented with acute respiratory symptoms, eosinophilia, and multi-organ involvement. The syndrome progressed through distinct phases: an acute toxic pneumonitis phase, followed by an intermediate phase with neuromuscular and skin manifestations, and finally a chronic phase where pulmonary arterial hypertension emerged as one of the most serious long-term complications.
Impact on pulmonary hypertension research: The toxic oil syndrome epidemic became a watershed moment in pulmonary hypertension research. However, it’s important to note that international scientific interest in pulmonary hypertension had been catalyzed earlier by another epidemic. In 1967, an outbreak of pulmonary arterial hypertension cases associated with the appetite suppressant aminorex in Europe prompted the World Health Organization to convene the first international meeting of experts on pulmonary hypertension in Geneva in 1973. This landmark gathering established the foundation for systematic study of the condition and international collaboration in pulmonary hypertension research.
See also our infographic on the history of pulmonary hypertension research at this link