Update on fogo selvagem, an endemic form of pemphigus foliaceus

Abstract

Pemphigus are organ-specific autoimmune diseases, where autoantibodies (mainly immunoglobulin [Ig]G) directed against epidermal targets (glycoproteins of the desmosomal core) are detected. Endemic pemphigus foliaceus or fogo selvagem (FS) is one of the variants of pemphigus foliaceus pemphigus foliaceus that shares the same clinical and immunopathological features of the classic non-endemic pemphigus foliaceus form, including pathogenic IgG (mainly IgG4) autoantibodies directed against the ectodomain of desmoglein 1 (Dsg1), that lead to acantholysis. Pathogenesis of FS is complex, involving genetic, environmental and immunological factors. Human leukocyte antigen (HLA)-DRB1 alleles DRB1*0404, *1402, *1406 or *0102 have been previously identified as risk factors for FS (relative risk, >14). Individuals exposed to hematophagous insects are more susceptible to develop the disease. Non-pathogenic anti-Dsg1 antibodies of the IgG1 subclass, directed against the extracellular 5 domain of Dsg1, are detected in patients in the preclinical stage of the disease, and also in healthy controls living in endemic areas. In counterpart, patients with FS show pathogenic anti-Dsg1 IgG4 autoantibodies that bind the pathogenic extracellular 1 and 2 domains of Dsg1, emphasizing the intramolecular epitope-spreading hypothesis. A possible explanation for the development of the autoimmune process would be antigenic mimicry, initiated by environmental stimuli in those genetically predisposed individuals. Characterization of the pathogenesis of FS will allow the development of specific therapeutic targets, and the elucidation of other autoimmune processes.

Keywords: autoimmunity; desmoglein; immunofluorescence; immunoglobulin G; pemphigus.

Figure 1

Typical house of a fogo selvagem patient at an endemic region in central Brazil.

Figure 2

Patient with a severe form of Fogo selvagem at the Pemphigus Hospital, São Paulo, Brazil, 1940.(6)

Figure 3

Map of endemic FS sites in Brazil.

Figure 4

Fogo selvagem, localized form.

Figure 5

Fogo selvagem, bullous invasive form.

Figure 6

Fogo selvagem, exfoliative erythroderma.

Figure 7

Fogo selvagem, tinea-imbricata-like: Vesicles or blisters form circinate or annular patterns.

Figure 8

Fogo selvagem and severe herpes simplex infection.

Figure 9

Researchers from the Cooperative Group on Fogo Selvagem Research at the Terena reservation in Limao Verde, MS, Brazil.

Figure 10

Pathogenesis of Fogo Selvagem.