Stop and Spot: Everything You Need to Know About Fogo Selvagem
Authors : Alba Vojta, Kourtney Sprague
My MAGIC Experience
Starting my sophomore year in high school, I decided to join MAGIC, a program to help girls explore the field of STEM. I have dreamed of being a doctor since I was a little girl. Growing up, I watched my grandparents in the medical field, which inspired and pushed me to learn more about science. Joining MAGIC allowed me to learn about my interests and unlock different parts of my brain. Specifically, I have been able to learn about Fogo Selvagem (FS), a skin disease extremely prevalent in Brazil. As a Brazilian with half of my family residing in Rio, the disease holds particular significance and personal interest for me. I currently live in New York. Being able to research FS has allowed me to learn about an important medical problem impacting my Brazilian community, making me feel more connected with that side of my identity. Additionally, researching a dermatological disease has allowed me to explore a field I am considering pursuing post-high school. Under the guidance of my MAGIC mentor, Kourtney Sprague, I have learned to dissect and read published research, as well as write a college-level/professional review paper on my knowledge. This experience has made me more confident in my skills as a student and has also deepened my passion for medicine and my hope of becoming a doctor in the future.
“This article is intended for educational purposes and should not be used for diagnosis purposes. Please consult a doctor for proper medical consultation to treat Fogo Selvagem.”
Introduction
Fogo Selvagem (FS), or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease (Hans-Filho et al. 2018). The term pemphigus refers to a group of skin diseases that produce vesicle blisters or erosions on the skin or mucous membranes(Hans-Filho et al. 2018). It is also distinguished through the loss of connection between epidermal cells (acantholysis) (Hans-Filho et al. 2018). There are 4 different forms of pemphigus: pemphigus vulgaris, immunoglobulin pemphigus, paraneoplastic pemphigus, and pemphigus foliaceus. Specifically, pemphigus foliaceus is characterized by the production of autoantibodies targeting desmoglein 1 and the formation of superficial blisters (Hans-Filho et al. 2018). Fogo selvagem and Pemphigus foliaceus share clinical, immunological, and histopathological characteristics, differentiated by Fogo selvagem’s epidemiological aspects. FS is mainly seen in children and young adults located in rural areas. It appears mainly on the trunk and face, with symptoms resembling those of burn injuries (Hans-Filho et al. 2018).
Geographical Aspects
Fogo selvagem means “wildfire” in Portuguese due to the burning sensation it gives to the skin (Hans-Filho et al. 2018). Patients presenting with FS are seen in South American countries but are mainly from Brazil (Figure 1), hence why the translation is Portuguese. Geography is important since Fogo selvagem’s origin is due to genetic, immune, and environmental factors. The first cases of FS were reported in the state of Bahia, Brazil, and later in Minas Gerais and São Paulo (Hans-Filho et al. 2018). The two most important outbreaks of FS were in 1912 in Ouro Preto and Belo Horizonte Brazil (Hans-Filho et al. 2018). Later on in 1914, the first hospital to specifically treat FS was created (Hans-Filho et al. 2018) Cases have been seen in Argentina, Peru, Colombia, and Venezuela starting from the 1940s, with Brazil having the largest caseload with more than 15,000 patients diagnosed since 1989 (Hans-Filho et al. 2018).
Environmental and Genetic Factors
FS affects both sexes of any ethnic group, ranging from children to young adults who possibly have a family history (Hans-Filho et al. 2018). This disease is closely linked with malnutrition and poverty, mainly spotted in rural areas. Inhabitants with brick walls and thatched roofs are at risk of developing FS, the risk increasing if they are exposed to hematophagous insects (Hans-Filho et al. 2018). The salivary protein from a blood-sucking insect may trigger the autoimmune response (Cameron et al. 2017). Genetically, 20% of related family members can develop FS (increasing to 60% in Limao Verde) (Hans-Filho et al. 2018). There are certain major histocompatibility complex (MHC) type II genes related to FS such as DRBI*0404, DRBI*1402, and DRB1*1406, where expression of these genes has shown to be associated with FS (Hans-Filho et al. 2018).
Molecular
In FS, an individual’s immune system reacts against the keratinocytes and desmosomes that make up the skin. FS develops when autoantibodies target the amino-terminal portions of desmoglein where specific epitopes used for pathogenicity are located (Hans-Filho et al. 2018). In reaction, the body produces immunoglobulin G4 antibodies that bind to the desmosomal protein desmoglein-1 (Cameron et al. 2017). When the IgG and Dsg1 bind, the desmosomes in the upper portions of the epidermis detach from the keratinocytes (Hans-Filho et al. 2018). Surface keratinocytes of the epidermis detach from each other and fill with fluid, creating blisters (Figure 2) (Cameron et al. 2017).
Clinical Features
The clinical features of FS appear similar to classical pemphigus foliaceus (Schwartz et al. 2021). There is the presence of cutaneous lesions and blisters that rupture easily (Figure 3). The blisters are spread across the skin, multiplying and generalizing (Schwartz et al. 2021). Sun exposure causes the lesions to worsen which prolongs the healing process. These lesions can be localized, where they have limited systemic spread (Rolinson, n.d.), or generalized where they spread throughout the host. Generalized forms have hyperpigmentation, and verrucous (wart-like) lesions, and can lead to death (Schwartz et al. 2021). These lesions form along the central trunk and face, resulting in changes in the hair and nails, and can also. cause burning pain (Schwartz et al. 2021).
Treatment
Systemic corticosteroid therapy has been the preferred treatment for patients with severe FS (Schwartz et al. 2021). 1 mg/kg of Prednisone is administered daily as a single dose, administered until the formation of blisters ends. If symptoms do not resolve, more aggressive treatments are utilized such as rituximab, IVIg, or immunoadsorption. The initial steroid dose is then reduced to 0.5 mg/kg once FS becomes moderate, followed by slowly reducing it until it is at the minimal effective maintenance dose (image from ppt). For mild FS, topical or Intralesional corticosteroids or 0.25 mg/kg prednisone is used, later being reduced once there is a positive response to treatment. If there are complications, the dosage can be doubled (image from ppt). Another form of therapy is using immunosuppressants. 1–2 mg/kg of azathioprine is administered until lesions clear, then slow diminishing of dose. Another immunosuppressant used is cyclophosphamide with a starting dose of 100–200 mg qd which is later reduced to 50–100 mg qd with a positive response (Schwartz et al. 2021). Plasmapheresis is another form of therapy used with patients with poorly controlled disease or with high circulating autoantibody concentrations (Schwartz et al. 2021). Plasmapheresis allows removal of plasma from patients through separation of plasma from blood cells and then the blood cells can be returned to the patient. To avoid rebound of autoantibody concentrations, plasmapheresis is paired with a daily dose of \ cyclophosphamide. Photoprotection is also helpful due to UV-B lights triggering acantholysis and flaring (Schwartz et al. 2021). FS therapy is less aggressive than other forms of pemphigus hence there are lower mortality rates.
Complications
There are many complications, not only in the development of FS but also in the therapy needed to treat it. Impetigo is a main complication of FS treatment causing highly contagious sores to develop around the mouth (Schwartz et al. 2021). This infection is often seen in children due to their immature immune system, but due to immuno-suppression from FS treatment, these patients become susceptible to impetigo (Mayo Clinic Staff, 2023). Due to their suppressed immune system, FS patients are also more susceptible to fungal infections (Schwartz et al. 2021). Dwarfism, dermatophytosis, warts, azoospermia, and scabies also have the possibility of occurring (Schwartz et al. 2021). Geographical location can also impact FS treatment complications. In Peru, there has been the presence of bacterial skin infection (pyodermitis) and urinary tract infection (pyelonephritis) during treatment (Schwartz et al. 2021).
Post-Treatment and Prevention
Following treatment of FS, patients should meet regularly with clinics to monitor the disease. It is important to look out for disease advancement, infections, complications, and agreement with medicine. Monitoring of therapy is vital to see if there has been progression with treatment (Schwartz et al. 2021). The more extensive the treatment, the more important it is to follow up and monitor. It is necessary to minimize exposure to hematophagous insects in endemic areas. This includes using insecticides, insect screens, and protective clothing. Photoprotection is also helpful to prevent the triggering of acantholysis (Schwartz et al. 2021).
References
1. Hans-Filho, G., Aoki, V., Bittner, N. R. H., & Bittner, G. C. (2018). Fogo selvagem: endemic pemphigus foliaceus. Anais brasileiros de dermatologia, 93(5), 638–650.
2. Abréu-Vélez A, Reason M, Howard S & Roselino A. Endemic pemphigus foliaceus over a century: part I. NAJ Med Sci 2010; 2(2): 51–9.
3. Aoki V, Rivitti A, Diaz L, Cooperative Group on Fogo Selvagem Research. Update on fogo selvagem, an endemic form of pemphigus foliaceus. Dermatol 2015; 42: 18–26.
4. Bastuji-Garin S, Suissi R, Blum L, et al. Comparative epidemiology of pemphigus in Tunisia and France: unusual incidence of pemphigus foliaceus in young Tunisian women. J Invest Dermatol 1995; 104: 302–5.
5. Millikan R, Rivitti E, Hans-Filho G, et al. Environmental risk factors of endemic pemphigus foliaceus (fogo selvagem). Journal Investig Dermatol Symp Proc 2004; 9:34–40.
6. Mayo Clinic Staff (2023, April 19), “Impetigo.” Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/impetigo/symptoms-causes/syc-20352352
7. William D James, MD (2021, April16), “Fogo Selvagem Clinical Presentation.” Medscape Dermatology. https://emedicine.medscape.com/article/1063347-clinical?form=fpf
