Brazilian pemphigus, also called pemphigus brasiliensis and fogo selvagem, occurs in some subtropical areas of Brazil, as well as in northern Colombia. Data have been extensively collected in the Limao Verde Amerindian reservation in the state of Mato Grosso do Sul. Most patients affected by fogo selvagem are young adults and children, live in forest areas near rivers and streams and are outdoor workers (farmers or their family members). Most patients live in poor hygiene and housing conditions. The decreased prevalence of fogo selvagem in Sao Paulo and Parana was linked to improved living conditions [28, 29]. A strong relationship has been proven between the occurrence of fogo selvagem and the infestation of the corresponding areas with some insects including Simuliids (also called black fly) with the greatest number of new cases at the end of the rainy season [30]. The same ecological system found in the pemphigus area overlaps with that for vector-borne diseases such as Chagas disease, leishmaniasis and onchocerciasis. Anti-desmoglein 1 antibodies are frequently detectable in normal subjects living in these endemic areas, in which a significant proportion of patients also had onchocerciasis and leishmaniasis. This temporal and geographic clustering suggests that there is an environmental triggering antigen(s) showing molecular mimicry with desmoglein 1 [31]. There is some evidence suggesting that the anti-desmoglein 1 response in fogo selvagem patients living in endemic regions of Brazil is antigen selected [32]. In individuals with the known HLA susceptibility allele and living in endemic areas, the development of fogo selvagem is associated with a subclass switch of the IgG antibody response (from the IgG 1, 2 and 3 subclasses to the IgG 4 subclass) as well as with a change of the antibody reactivity (epitope spreading with development of a reactivity from the EC5 domains of Dsg1 to the EC1 and EC2 domains) [30, 33–35]. A strong association of fogo selvagem with HLA-DRB1*1402 and DRB1*04040 was identified [36].

Interestingly, this endemic type of PF is also associated with poor economic conditions [37]. Some familial cases have been described [38]. Similar to pemphigus brasiliensis, a high prevalence of anti-desmoglein 1 antibodies has been reported in people living in endemic areas, as well as among genetically related or unrelated household members of patients [38–40]. Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in the healthy relatives (up to 22 %) was observed in the rural localities. As observed in Brazil, a high prevalence of anti-desmoglein 1 antibodies in sera from patients with hydatidosis and leishmaniasis (but not affected by pemphigus) has been described [41, 42]. Antibodies against P. papatasi, the main vector of Leishmania major leading to cutaneous leishmaniasis, have also been found in 25 % of PF patients but only in 6 and 3 % of healthy controls and patients with BP [42].

Several triggers have been implicated in bullous pemphigoid (BP) onset including trauma [45, 46], burns [47], radiotherapy [48, 49] and UV radiation including sunlight [50], UVA1 [51], PUVA [52] and photodynamic therapy [53]. Furthermore, about 20 case reports describe the association of vaccination with the onset of BP, most frequently against influenza [46, 54]. Nevertheless, an ecological study over 9 years in Spain did not find a higher incidence of admissions for BP in the 10-week influenza vaccination period compared to the rest of the year [55].

Numerous case reports described the triggering of BP by drugs, most frequently furosemide [56]. In two controlled French studies, however, only a relatively weak association of BP with spironolactone (odds ratio 2.3) and phenothiazines with aliphatic side chains (odds ratio 3.7) was identified [57, 58]. The use of these drugs should thus be carefully evaluated.

Only four epidemiological studies have addressed polymorphisms of HLA genes with BP with divergent results. Studying 21 Caucasian patients, a significant association with DQB1*0301 was detected [59], an observation that was partly confirmed by the demonstration that the primary response of CD4-positive T cells to BP180 in vitro is restricted to DQB1*0301 [60]. Another study with 74 Caucasian patients identified an association with DQB1*0301 only in men [61], whereas in 25 patients from northern China, DRB1*08 and DRB1*08/DQB1*06 were less frequently found compared to controls [62]. Yet other HLA gene polymorphisms, HLA-DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 as well as DRB1*1101 and DQB1*0302, were found in 23 Japanese BP patients [63].