Background

• Fogo Selvagem, also known as Pemphigus Foliaceus, is a rare autoimmune blistering disorder that primarily affects the skin.
• Superficial blisters and skin and mucous membrane erosions characterize it.  

Epidemiology

• The epidemiology of Fogo Selvagem varies across different regions of the world. The disease is more commonly reported in certain geographic areas, including Brazil and other parts of South America. Fogo Selvagem is considered endemic in certain regions of Brazil, particularly in rural areas. 
• The prevalence of Fogo Selvagem in endemic regions can vary significantly. In Brazil, for example, studies have reported prevalence rates ranging from less than 1 case per 10,000 individuals to as high as 15 cases per 10,000 individuals in specific populations. It is important to note that the disease may be underreported or misdiagnosed, leading to potential variations in prevalence estimates. 

Anatomy

Pathophysiology

The pathophysiology of Fogo Selvagem involves an autoimmune response targeting specific skin components. The exact mechanisms underlying the development of the disease have yet to be fully understood, but several key factors have been identified. 

• Autoantibody Production: In Fogo Selvagem, desmoglein 1 (Dsg1) autoantibodies are produced. Desmogleins are proteins that play a crucial role in maintaining the integrity and adhesion of skin cells. In Fogo Selvagem, autoantibodies target and bind to Dsg1, disrupting cell adhesion between keratinocytes, the predominant cell type in the epidermis. 
• Loss of Cell Adhesion: The binding of autoantibodies to Dsg1 triggers a series of events that result in the loss of cell adhesion between keratinocytes. This leads to the separation of skin cells in the superficial layers of the epidermis, forming blisters and erosions. 
• Inflammatory Response: The separation of skin cells and the release of inflammatory mediators contribute to the development of inflammation in the affected areas. Inflammatory cells, such as neutrophils and eosinophils, infiltrate the skin, causing further damage and inflammation. 
• Epidermal Damage: The loss of cell adhesion and inflammation in Fogo Selvagem results in epidermal damage. Blisters, erosions, and crusted lesions can be observed on the skin and mucous membranes, particularly on the face, scalp, chest, and upper back. 

Etiology

The etiology of Fogo Selvagem, or pemphigus foliaceus, has yet to be fully understood. However, it is believed to involve genetic and environmental factors. 

• Genetic Factors: Evidence suggests a genetic predisposition to Fogo Selvagem. Certain genetic variations and polymorphisms have been associated with an increased susceptibility to the disease. Studies have identified specific human leukocyte antigen (HLA) alleles, particularly HLA-DR4 and HLA-DRB1*0404, more commonly found in individuals with Fogo Selvagem. These genetic factors may contribute to the development of an abnormal immune response. 
• Autoantibodies: In Fogo Selvagem, autoantibodies target desmoglein 1 (Dsg1), a protein that plays a crucial role in maintaining the integrity of skin cells. The production of autoantibodies against Dsg1 is a hallmark feature of the disease. However, the trigger for producing these autoantibodies is not yet fully understood. 
• Environmental Triggers: Environmental factors may play a role in triggering or exacerbating Fogo Selvagem. In particular, evidence suggests an association between the disease and exposure to certain environmental factors, such as insect bites. It has been proposed that insect bites, particularly from black flies (Simulium spp.) or mosquitoes, may introduce specific antigens or proteins that trigger an immune response in genetically susceptible individuals. 
• Infectious Agents: Some studies have suggested a potential association between infectious agents and the development of Fogo Selvagem. In particular, an organism called Leishmania braziliensis, which causes leishmaniasis, has been implicated as a potential trigger. Leishmania DNA has been detected in skin lesions of individuals with Fogo Selvagem, suggesting a possible link between the two conditions. However, the exact relationship between the infectious agent and the development of Fogo Selvagem is still under investigation. 

Genetics

Prognostic Factors

The prognosis of Fogo Selvagem, or pemphigus foliaceus, can vary among individuals and is influenced by several prognostic factors. These factors can help predict the course of the disease and the likelihood of achieving remission or experiencing disease flares. Some of the important prognostic factors in Fogo Selvagem include: 

• Age at Onset: The age at which Fogo Selvagem develops can impact the prognosis. Studies have suggested that older age at disease onset is associated with a poorer prognosis. Individuals who develop the disease at a younger age tend to respond better to treatment and are more likely to achieve remission. 
• Disease Severity: The severity of Fogo Selvagem at the time of diagnosis is an important prognostic factor. Individuals with widespread skin involvement, extensive blistering, and mucosal involvement (such as in the oral cavity) tend to have a more severe disease course and may experience more treatment-resistant diseases. 
• Autoantibody Profile: The specific autoantibody profile in Fogo Selvagem can influence the prognosis. Some studies have suggested that individuals with high levels of anti-desmoglein 1 (Dsg1) autoantibody tend to have a more severe disease course and a higher risk of relapse. 
• Treatment Response: The response to treatment is a crucial prognostic factor in Fogo Selvagem. Individuals who respond well to treatment, such as corticosteroids and immunosuppressive agents, have a better prognosis. Poor treatment response or resistance to therapy may indicate a more challenging disease course and a higher risk of relapse. 
• Compliance with Treatment: Adherence to treatment and follow-up care is essential for achieving good outcomes in Fogo Selvagem. Individuals who can comply with treatment regimens and receive appropriate medical care consistently have a better prognosis than those with poor treatment adherence. 
• Co-existing Conditions: Other medical conditions or comorbidities can impact the prognosis of Fogo Selvagem. Individuals with underlying health issues, such as diabetes or cardiovascular disease, may have a more complicated disease course and potentially poorer outcomes. 

Clinical History

Non-specific signs & symptoms 

• Fatigue 
• Malaise 
• Fever 
• Itching 
• Pruritis 
• Pain or discomfort 
• Emotional distress 

    Systemic signs & symptoms 

• Generalized weakness 
• Weight loss 
• Lymphadenopathy 
• Joint pain 
• Systemic inflammatory response 

Physical Examination

• Skin examination: 

The healthcare provider will carefully inspect the skin for any characteristic skin lesions associated with pinta disease. These lesions can vary in size, shape, and color. They may appear as discolored patches or areas of the skin with a coppery or bluish hue. The provider will examine the distribution of the lesions and assess their extent and severity. 

• Texture and morphology: 

The texture and morphology of the skin lesions will be evaluated. Pinta lesions can exhibit various features, such as scaling, roughness, or crusting. The provider will observe the texture of the lesions to identify any specific characteristics associated with pinta. 

• Lesion examination:  

The healthcare provider will closely examine individual lesions for specific characteristics. They may assess the borders of the lesions, noting whether they are well-defined or irregular. The provider may also evaluate any secondary changes, such as erosion, ulceration, or scarring. 

• Regional lymph nodes:  

The provider may palpate regional lymph nodes to assess for enlargement or tenderness. Lymphadenopathy is not common in pinta disease, but in rare cases, swelling of lymph nodes near the affected areas may be observed. 

• Systemic examination:

Although pinta primarily affects the skin, a brief systemic examination may be conducted to evaluate overall health. This may involve assessing vital signs and general appearance and conducting an essential physical examination to identify any additional signs or symptoms that could suggest systemic involvement or underlying conditions. Skin Lesions: The skin is carefully examined for blistering, erosions, and crusted or scaly lesions. These lesions are typically located on the face, scalp, chest, upper back, and other areas exposed to friction or trauma. The lesions may vary in size and shape, ranging from small, superficial blisters to more extensive erosions. 

• Distribution and Symmetry:

The distribution pattern of skin lesions is noted during the examination. In Fogo Selvagem, the lesions often have a characteristic distribution known as the seborrheic pattern. This means they are typically concentrated in areas with more sebaceous (oil) glands, such as the central face, upper chest, and upper back. The lesions may also be symmetrical, affecting corresponding areas on both sides of the body. 

• Crusted or Eroded Scalp:

The scalp is examined for crusting, erosions, or scaling. In some cases, Fogo Selvagem can involve the scalp, leading to hair loss and scalp involvement. This can manifest as crusted areas or erosions on the scalp, which may be apparent during the examination. 

• Mucous Membrane Involvement:

The oral mucosa, including the inside of the cheeks, gums, tongue, and throat, is examined for signs of mucous membrane involvement. In Fogo Selvagem, mucosal lesions are less common than other forms of pemphigus, but they can still occur. Erosions or ulcerations on the mucous membranes may indicate Fogo Selvagem. 

• Skin Color and Texture Changes:

Skin color and texture changes are observed during the examination. The affected areas may appear erythematous (red) or have a violaceous hue. The skin texture may be altered, with crusting, scaling, or denuded skin areas. 

• Secondary Infections:

Secondary infections, such as bacterial or fungal infections, may be noted during the examination. These can occur due to breaks in the skin barrier caused by the blistering and erosions in Fogo Selvagem. 

Age group

Associated comorbidity

• Other autoimmune disease 
• Infections 
• Medications 
• Psychological and emotional factors 

Associated activity

• Other autoimmune disease 
• Infections 
• Medications 
• Psychological and emotional factors 

Acuity of presentation

• The acuity of presentation in Fogo Selvagem, or pemphigus foliaceus, can vary among individuals. Acuity refers to the speed or suddenness with which symptoms develop and progress. Fogo Selvagem’s presentation can range from acute to subacute or chronic. 
• Acute Presentation: In some cases, Fogo Selvagem can have an acute onset, characterized by the rapid development of skin lesions and symptoms. Blisters and erosions may appear suddenly over a short period, often within a few days or weeks. This acute presentation may be associated with a more severe disease course and widespread skin involvement. 
• Subacute Presentation: A subacute presentation in Fogo Selvagem is characterized by a moderately rapid progression of symptoms. The development of blisters and erosions may occur over weeks to months. The disease manifestations may be less severe than the acute presentation but require prompt medical attention and treatment. 
• Chronic Presentation: In some cases, Fogo Selvagem may have a chronic and indolent course. The onset of symptoms and development of skin lesions may be gradual, spanning several months or even years. The disease progression may be slow, with intermittent flares and remissions. The symptoms and skin lesions may be milder in chronic cases, but long-term management and monitoring are still necessary. 

Differential Diagnoses

• Pemphigus Vulgaris: Pemphigus vulgaris is another form of autoimmune blistering disorder. It can share similarities with Fogo Selvagem, but in pemphigus vulgaris, the autoantibodies primarily target desmoglein 3 (Dsg3), whereas Fogo Selvagem targets desmoglein 1 (Dsg1). Skin biopsies and immunofluorescence studies are crucial in differentiating between the two conditions. 
• Bullous Pemphigoid: Bullous pemphigoid is another autoimmune blistering disorder that can present with similar skin manifestations as Fogo Selvagem. However, bullous pemphigoid typically affects older individuals and is characterized by large, tense blisters rather than superficial blisters seen in Fogo Selvagem. Biopsy and immunofluorescence studies aid in distinguishing between the two conditions. 
• Dermatitis Herpetiformis: Dermatitis herpetiformis is a chronic autoimmune skin disorder associated with celiac disease. It is presented with intensely itchy, grouped vesicles and papules, primarily affecting the elbows, knees, buttocks, and back. Biopsy findings, serological tests, and response to a gluten-free diet help differentiate dermatitis herpetiformis from Fogo Selvagem. 
• Epidermolysis Bullosa Acquisita: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder that can resemble Fogo Selvagem clinically. EBA is characterized by the formation of blisters at the dermal-epidermal junction and may have mucosal involvement. Immunofluorescence studies and additional tests, such as direct immunoelectron microscopy, differentiate EBA from Fogo Selvagem. 
• Contact Dermatitis: Contact dermatitis can mimic the blistering and erosions seen in Fogo Selvagem. It occurs due to an allergic or irritant reaction to a specific substance that comes into contact with the skin. Careful history-taking, patch testing, and clinical presentation help differentiate contact dermatitis from Fogo Selvagem. 
• Infectious Conditions: Certain infectious conditions, such as herpes simplex virus infection, varicella-zoster virus infection, or impetigo, can initially present with blistering or erosions on the skin. Evaluating the patient’s history, characteristic clinical features, and appropriate laboratory testing can help distinguish these infections from Fogo Selvagem. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The treatment paradigm for Fogo Selvagem involves a combination of medications to suppress the immune system and reduce inflammation to control the disease. The mainstay of treatment typically includes: 

• Corticosteroids: These are the first-line drugs to control the autoimmune response. Prednisone is a commonly prescribed corticosteroid. 
• Immunosuppressive drugs: In cases where corticosteroids alone are insufficient or cannot be used at high doses for an extended period, other immunosuppressive drugs may be prescribed. These drugs help reduce the immune system’s activity and prevent it from attacking the skin cells. Examples include azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide, and others. 
• Topical treatments: Corticosteroid creams or ointments can treat localized lesions and provide symptomatic relief. 
• Wound care: Proper wound care and hygiene are crucial to prevent secondary infections and aid in healing blisters and erosions. 
• Nutritional support: Adequate nutrition is essential for overall health and wound healing. 
• Regular follow-ups: Monitoring the patient’s progress and adjusting the treatment plan as necessary is essential to manage the condition effectively. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

skin-care-by-altering-the-environment

Temperature and Humidity Control: Maintaining a comfortable and stable environment can help prevent excessive sweating, which can irritate the skin and potentially trigger or exacerbate Fogo Selvagem lesions. Adequate temperature and humidity control can help reduce sweating and provide relief. 

1. Skin care by altering the contact 

Specialty: Dermatology, Family Medicine, Public Health 

• Soft Clothing and Avoidance of Friction: Wearing loose-fitting, soft clothing made of natural fibers (such as cotton) can help minimize friction and irritation on the skin. Avoiding tight or rough-textured clothing can reduce discomfort and potential trauma to the affected areas. 
• Gentle Skin Care: Adopting a gentle skincare routine is essential in managing Fogo Selvagem. Use mild, fragrance-free cleansers and avoid harsh soaps or irritants that can further compromise the skin barrier. Pat-drying the skin gently after washing and avoiding excessive rubbing can help prevent additional damage or irritation. 
• Moisturization: Regular and adequate skin moisturization is essential in managing Fogo Selvagem. Applying moisturizers or emollients after bathing or as needed helps to keep the skin hydrated, reduce dryness, and minimize the risk of skin cracking or further damage. 
• Protection from Sun Exposure: Sun exposure can potentially trigger or worsen Fogo Selvagem lesions. Protecting the skin from excessive sun exposure is advisable by wearing protective clothing, using a broad-spectrum sunscreen with a high sun protection factor (SPF), and seeking shade during peak sun hours. 
• Allergen Avoidance: Identifying and avoiding potential allergens or irritants that can exacerbate Fogo Selvagem is essential. This may involve evaluating personal care products, detergents, or other environmental triggers contributing to skin irritation. Choosing hypoallergenic products or avoiding known irritants can be beneficial. 

Topical immunosuppressive agents for the treatment of Fogo Selvagem

In treating Fogo Selvagem, or pemphigus foliaceus, pharmaceutical agents are commonly used alongside systemic drugs to control disease and reduce inflammation. 

• Tacrolimus 

Tacrolimus works by inhibiting the activity of calcineurin, a protein involved in the immune response. By blocking calcineurin, tacrolimus suppresses the production of inflammatory mediators and helps to reduce inflammation. 

Tacrolimus is available in topical ointment or cream formulations. It is applied directly to the affected areas of the skin, usually once or twice daily. 

Topical antihistamines for the treatment of Fogo Selvagem

• Pimecrolimus 

Pimecrolimus works by inhibiting the activity of calcineurin, a protein involved in the immune response. By blocking calcineurin, pimecrolimus helps to suppress the production of inflammatory mediators and reduce inflammation.  

Pimecrolimus is not explicitly approved for treating Fogo Selvagem, but it has been investigated as an off-label treatment option in some cases. Research studies and case reports have suggested its potential effectiveness in reducing inflammation and improving the condition. 

Administration of systemic glucocorticosteroids

• Prednisone 

In managing Fogo Selvagem, prednisone is often prescribed as the initial treatment to control disease activity and alleviate symptoms. The dosage of prednisone and treatment duration varies depending on the severity of the disease, individual patient factors, and response to therapy. High-dose prednisone is usually initiated to control disease, gradually tapering the dose to the lowest effective maintenance dose. 

The potential side effects may include weight gain, increased risk of infections, osteoporosis, high blood pressure, elevated blood sugar levels, and mood changes. 

Prednisone is often used with other medications, such as immunosuppressive agents, to achieve optimal disease control and minimize the long-term use of corticosteroids. 

Administration of nonsteroidal adjunctive therapy

If disease control is inadequate or to minimize the long-term use of corticosteroids, adjunctive immunosuppressive medications are added. The choice of medication depends on factors such as disease severity, patient characteristics, and potential side effects. 

Close monitoring of medication response, laboratory parameters, and side effects is necessary during this phase. 

• Azathioprine 

Azathioprine is an immunosuppressive medication commonly used as adjunctive therapy in treating Fogo Selvagem, or pemphigus foliaceus. Azathioprine works by suppressing the immune system and reducing the production of immune cells that play a role in the autoimmune response. It inhibits the synthesis of DNA and RNA, leading to a decrease in the proliferation of immune cells. 

• Mycophenolate mofetil 

Mycophenolate mofetil works by inhibiting the proliferation of immune cells, particularly lymphocytes, which play a role in the autoimmune response seen in Fogo Selvagem. It specifically targets the de novo synthesis of purine nucleotides required for lymphocyte proliferation. Mycophenolate mofetil is typically used as an adjunctive therapy alongside systemic glucocorticosteroids in Fogo Selvagem. The combination of mycophenolate mofetil with glucocorticosteroids helps to achieve better disease control and allows for a reduction in the dosage of glucocorticosteroids. 

• Methotrexate 

Methotrexate works by inhibiting the production of DNA and RNA, leading to suppression of cell proliferation, including immune cells involved in the autoimmune response seen in Fogo Selvagem. Methotrexate is often used as an adjunctive therapy alongside systemic glucocorticosteroids or other immunosuppressive medications in Fogo Selvagem. It helps to achieve better disease control and reduces the reliance on higher doses of corticosteroids. 

• Cyclosporine 

Cyclosporine suppresses the immune response, explicitly targeting T-cell activation and function. It inhibits the production and release of inflammatory mediators involved in the autoimmune response seen in Fogo Selvagem. 

Cyclosporine is often used as an adjunctive therapy alongside systemic glucocorticosteroids or other immunosuppressive medications in Fogo Selvagem. It helps to achieve better disease control and reduces the reliance on higher doses of corticosteroids. 

• Rituximab 

Rituximab targets a specific protein on B-cells called CD20, leading to the depletion of these cells from circulation. B-cells play a role in the production of autoantibodies involved in the autoimmune response seen in Fogo Selvagem. By targeting and reducing B-cells, rituximab helps to suppress the autoimmune response. 

• Dapsone 

Dapsone is thought to exert its therapeutic effects in Fogo Selvagem by suppressing the autoimmune response and reducing inflammation. It inhibits neutrophil chemotaxis and the production of reactive oxygen species, which are involved in the inflammatory process seen in Fogo Selvagem. 

Dapsone is often used as an adjunctive therapy alongside systemic glucocorticosteroids or other immunosuppressive medications in Fogo Selvagem. It helps to achieve better disease control and reduces the reliance on higher doses of corticosteroids. 

Long-Term Management and Monitoring

• Long-term management involves continued monitoring of disease activity, treatment response, and potential side effects of medications. 
• Regular follow-up visits with healthcare professionals, such as dermatologists or rheumatologists, are necessary to evaluate disease status and adjust treatment accordingly. 
• Patients should be educated about medication adherence, self-monitoring for disease flares, and promptly report any new or worsening symptoms. 

In managing Fogo Selvagem, or pemphigus foliaceus, procedures are not typically the primary form of intervention. The mainstay of treatment involves medical therapies aimed at suppressing the autoimmune response and reducing inflammation. However, in some instances, procedures may be utilized to support overall disease management. Here are some scenarios where procedures may be considered: 

• Skin Biopsy: A skin biopsy is commonly used to diagnose Fogo Selvagem. It involves removing a small sample of affected skin for microscopic examination. The biopsy helps confirm the presence of acantholysis (the separation of skin cells) and can differentiate Fogo Selvagem from other blistering disorders. 
• Immunofluorescence Studies: Immunofluorescence studies involve taking a small sample of skin tissue and testing it using specific antibodies. This procedure helps identify the deposition of immunoglobulins and complement proteins within the skin, confirming the autoimmune nature of Fogo Selvagem. Immunofluorescence studies can be performed on fresh or frozen skin biopsy samples. 
• Wound Care Procedures: In cases of extensive or non-healing erosions or ulcers, wound care procedures may promote healing and prevent secondary infection. These procedures can include the application of specialized dressings, such as hydrocolloids or advanced wound dressings, to create a moist wound environment and protect the skin. 
• Biopsy of Mucous Membranes: When mucous membrane involvement is suspected, a biopsy of the affected area may be performed. This can help confirm the diagnosis and differentiate Fogo Selvagem from other conditions affecting mucous membranes. 

Treatment and management of Fogo Selvagem typically involve several phases, each with specific goals and interventions. They include: 

• Acute Phase  
• Induction Phase 
• Maintenance Phase 
• Long-term Management Phase 

Medication

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References

• Fogo Selvagem 
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106655/