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.
CDC. Follow-up on toxic pneumonia--Spain. MMWR 1981;30:436-8.
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.
Tabuenca JM. Toxic-allergic syndrome caused by ingestion of
rapeseed oil denatured with aniline. Lancet 1981;2:567-8.
Comision Clinica (MTSS). Informe del 13 de Octubre de 1981.
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.
Gordon RS. Oleoanilides and Spanish oil poisoning. Lancet
1981;2:1171-2.
Disclaimer
All MMWR HTML documents published before January 1993 are electronic conversions from ASCII text into HTML. This conversion may have resulted in character translation or format errors in the HTML version. Users should not rely on this HTML document, but are referred to the original MMWR paper copy for the official text, figures, and tables. An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S. Government Printing Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800. Contact GPO for current prices.
**Questions or messages regarding errors in formatting should be addressed to mmwrq@cdc.gov.
