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International Notes Follow-Up on Epidemic Pneumonia with Progression to Neuromuscular Illness -- Spain

In May and June 1981, an extensive outbreak of severe respiratory illness occurred in Spain, primarily in Madrid and the northwest regions of the country (1,2). Patients initially had the clinical and radiographic findings of atypical pneumonia, but other common findings were fever, rash, myalgia, and marked eosinophilia. About 1% of patients died. Autopsies showed interstitial pneumonitis and widespread vasculitis (3). Convalescence was prolonged in many cases and was characterized by diffuse myalgia, non-pitting edema of the limbs, liver-enzyme abnormalities, and sustained eosinophilia (4).

Beginning in August, it was recognized that substantial numbers of previously ill patients were developing neuromuscular problems. Clinical manifestations included muscle atrophy, weight loss, weakness, symmetrical sensory loss, and hyporeflexia. Many patients developed keratoconjunctivitis sicca (decreased tearing and salivation) and scleroderma-like changes of the skin. By that time, chest X rays had become normal. Eosinophilia continued, but at somewhat diminished levels. Moderate elevations of liver enzymes persisted (5). Electromyograms showed terminal axonal death, with denervation atrophy on muscle biopsy. Some patients had severe muscle weakness that led to failure of respiratory muscles. Most deaths among patients with neuromuscular illness have largely resulted from complications associated with prolonged maintenance on mechanical ventilation. It is estimated that the epidemic to date has affected about 17,000 persons (about 70% in Madrid). As of December 24, 1981, 13,222 patients had been hospitalized (Figure 1), and 246 had died. Morbidity and case-fatality ratios have been somewhat higher for females than for males, especially among persons between the ages of 10 and 50 years (6).

Thus far, extensive microbiologic testing has failed to implicate any infectious agent known to cause atypical pneumonia, eosinophilia, or neuromuscular disease. However, epidemiologic studies have uniformly shown a strong association between illness and ingestion of an illegally marketed cooking oil. This product contained rapeseed oil, denatured by the addition of 2% aniline and imported into Spain for industrial use. After the oil was processed in Spain to remove the aniline, it was sold from house to house and in itinerant markets, primarily in Madrid and nearby provinces. As marketed, the product appears to have been a variable mixture of rapeseed oil, other seed oils, and liquefied pork fat (2). Small quantities of aniline and fatty acid anilides have been detected in oil samples.

The discovery of an association between illness and consumption of this oil resulted in vigorous efforts by the Spanish government in late June 1981 to remove all implicated oil from the market. At about the time this action was taken, the epidemic occurrence of acute pneumonia fell dramatically (Figure 1). The last reported new case of epidemic illness occurred in September. However, patients with neuromuscular disease, representing about 20% of all cases in the epidemic, constitute a major continuing health problem in Spain. Reported by Ministerio de Sanidad y Consumo, Madrid, Spain; Field Services Div, Epidemiology Program Office, Chronic Diseases Div, Center for Environmental Health, CDC.

Editorial Note

Editorial Note: The unusual collection of clinical features associated with this syndrome (interstitial pneumonitis followed by neuromuscular degeneration and associated with marked eosinophilia and various immunologic abnormalities) clearly represents a new disease. The negative results of extensive testing for known infectious pathogens and the history of chemical denaturation of the implicated oil have suggested that the causative agent may be a chemical toxin.

The search for toxins, however, has been difficult and not yet productive. Because legal action is pending against the distributors of the illicit oil, there is little information regarding the method of processing the oil and the manner in which it might have been contaminated. No known toxic agents have yet been found in any case-associated oils tested thus far, at least not at levels high enough to produce illness. Animal toxicity testing has in general yielded negative results. The clinical picture is not that of toxicity caused by aniline, the chemical denaturant. Much investigative attention has been directed at fatty-acid anilides found in relatively high concentrations in some case-associated oils. The significance of these compounds is uncertain, however, since they are generally considered non-toxic (3,7). Although new cases of the neuromuscular syndrome continued to occur through September, the acute pneumonic phase of the epidemic ended in June. This suggests that exposure to whatever produced the disease may have ceased in early or mid-June, although its delayed sequelae are still being seen in Spanish hospitals.

References

  1. CDC. Atypical pneumonia--Spain. MMWR 1981;30:237-8.

  2. CDC. Follow-up on toxic pneumonia--Spain. MMWR 1981;30:436-8.

  3. Direccion General de Salud Publica, Ministerio de Trabajo, Sanidad y Seguridad Social (MTSS). Informe por la comision de patologos, 6 de Agosto de 1981. Boletin Epidemiologico Semanal 1981: no. 1486:161-2.

  4. Tabuenca JM. Toxic-allergic syndrome caused by ingestion of rapeseed oil denatured with aniline. Lancet 1981;2:567-8.

  5. Comision Clinica (MTSS). Informe del 13 de Octubre de 1981.

  6. Canada-Royo LM. Estudio de afectacion diferencial por sexos y edades en la provincia de Madrid entre el 1 de May y el 5 de Octubre de 1981 como consecuencia del "sindrome toxico." 7 de Octubre de 1981.

  7. Gordon RS. Oleoanilides and Spanish oil poisoning. Lancet 1981;2:1171-2.



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