RCMI International Symposium on Health Disparities
November 12-15, 2000
San Juan, Puerto Rico

Invited Speakers

FOGO SELVAGEM: AN ENVIRONMENTALLY-TRIGGERED
HUMAN AUTOIMMUNE DISEASE



Luis A. Díaz, M.D.
University of North Carolina at Chapel Hill
Chapel Hill, NC

Pemphigus foliaceus is an autoimmune disease characterized by superficial subcorneal blisters and pathogenic autoantibodies that are specific for the ectodomain of the desmosomal glycoprotein, desmoglein 1. There are two forms of pemphigus foliaceus -- the non-endemic form of worldwide distribution first described by Cazenave in Paris in 1844 and the endemic form, known as fogo selvagem, seen in certain rural areas of Brazil and first reported in 1903. Although most frequently seen in Brazil there are reports of other foci of endemic pemphigus foliaceus in Colombia and Tunisia. The endemic and non-endemic forms of this disease are quite similar to one another at the clinical, histological and immunological levels; however, there are several remarkable features that are unique to the endemic form, such as the geographic, temporal and familial clustering of cases, the increased frequency of cases among young adults and children, and an association with certain HLA-DR alleles.

Several epidemiological features of fogo selvagem have strongly suggested that sensitization and production of pathogenic autoantibodies in this disease are linked to exposure to an environmental antigen(s). Fogo selvagem is highly restricted to endemic foci that are almost exclusively located in rural areas of Brazil. All races and ethnic groups are affected including Brazilians of Portuguese, Spanish, German, African and Japanese descent living in endemic areas. The incidence of fogo selvagem decreases dramatically as a region develops from a rural to an urban environment. Significantly, there are no reported cases of person-to-person transmission, and no microbe has been successfully cultured or identified.

We have recently identified an Amerindian settlement in Brazil that exhibits a 3.4% prevalence of fogo selvagem -- the Terena Reservation of Limao Verde. Among this population of 916, we have documented 1-4 new cases per year. Interestingly, within other neighboring Terena reservations there are very few, or no, cases of fogo selvagem (only 2 documented cases within these other populations which have been monitored by our research group for the past five years). We have demonstrated recently that the prevalence of anti-desmoglein autoantibodies in this reservation is high among normal inhabitants and fogo selvagem patients. In five patients we detected anti-desmoglein autoantibodies 1-5 years previous to the onset of the clinical skin disease. In summary, the results of our sero-epidemiological studies reveal an overlap between a foci of active fogo selvagem, a high prevalence of anti-desmoglein autoantibodies in a population at risk and a geographic area in Brazil. This human settlement and neighboring communities may provide us with unique opportunities for identifying and characterizing the environmental factors involved in triggering a human autoimmune disease.